bluuebunny/crossref_metadata_2025 huggingface dataset:
An Automatic Approach for Individual HU-Based Characterization of Lungs in COVID-19 Patients
Authors: Mazzilli Aldo , Fiorino Claudio , Loria Alessandro , Mori Martina , Esposito Pier Giorgio , Palumbo Diego , de Cobelli Francesco , del Vecchio Antonella
Published: January 2021

The ongoing COVID-19 pandemic currently involves millions of people worldwide. Radiology plays an important role in the diagnosis and management of patients, and chest computed tomography (CT) is the most widely used imaging modality. An automatic method to characterize the lungs of COVID-19 patients based on individually optimized Hounsfield unit (HU) thresholds was developed and implemented. Lungs were considered as composed of three components—aerated, intermediate, and consolidated. Three methods based on analytic fit (Gaussian) and maximum gradient search (using polynomial and original data fits) were implemented. The methods were applied to a population of 166 patients scanned during the first wave of the pandemic. Preliminarily, the impact of the inter-scanner variability of the HU-density calibration curve was investigated. Results showed that inter-scanner variability was negligible. The median values of individual thresholds th1 (between aerated and intermediate components) were −768, −780, and −798 HU for the three methods, respectively. A significantly lower median value for th2 (between intermediate and consolidated components) was found for the maximum gradient on the data (−34 HU) compared to the other two methods (−114 and −87 HU). The maximum gradient on the data method was applied to quantify the three components in our population—the aerated, intermediate, and consolidation components showed median values of 793 ± 499 cc, 914 ± 291 cc, and 126 ± 111 cc, respectively, while the median value of the first peak was −853 ± 56 HU.
Attention-Based Transfer Learning for Efficient Pneumonia Detection in Chest X-ray Images
Authors: Cha So-Mi , Lee Seung-Seok , Ko Bonggyun
Published: January 2021

Pneumonia is a form of acute respiratory infection commonly caused by germs, viruses, and fungi, and can prove fatal at any age. Chest X-rays is the most common technique for diagnosing pneumonia. There have been several attempts to apply transfer learning based on a Convolutional Neural Network to build a stable model in computer-aided diagnosis. Recently, with the appearance of an attention mechanism that automatically focuses on the critical part of the image that is crucial for the diagnosis of disease, it is possible to increase the performance of previous models. The goal of this study is to improve the accuracy of a computer-aided diagnostic approach that medical professionals can easily use as an auxiliary tool. In this paper, we proposed the attention-based transfer learning framework for efficient pneumonia detection in chest X-ray images. We collected features from three-types of pre-trained models, ResNet152, DenseNet121, ResNet18 as a role of feature extractor. We redefined the classifier for a new task and applied the attention mechanism as a feature selector. As a result, the proposed approach achieved accuracy, F-score, Area Under the Curve(AUC), precision and recall of 96.63%, 0.973, 96.03%, 96.23% and 98.46%, respectively.
Estimation of the Noise Source Level of a Commercial Ship Using On-Board Pressure Sensors
Authors: Jeong Hongseok , Lee Jeung-Hoon , Kim Yong-Hyun , Seol Hanshin
Published: January 2021

The dominant underwater noise source of a ship is known to be propeller cavitation. Recently, attempts have been made to quantify the source strength using on-board pressure sensors near the propeller, as this has advantages over conventional noise measurement. In this study, a beamforming method was used to estimate the source strength of a cavitating propeller. The method was validated against a model-scale measurement in a cavitation tunnel, which showed good agreement between the measured and estimated source levels. The method was also applied to a full-scale measurement, in which the source level was measured using an external hydrophone array. The estimated source level using the hull pressure sensors showed good agreement with the measured one above 400 Hz, which shows potential for noise monitoring using on-board sensors. A parametric study was carried out to check the practicality of the method. From the results, it was shown that a sufficient recording time is required to obtain a consistent level at high frequencies. Changing the frequency resolution had little effect on the result, as long as enough data were provided for the one-third octave band conversion. The number of sensors affected the mid- to low-frequency data.
Mechanical Design of a Bioinspired Compliant Robotic Wrist Rehabilitation Equipment
Authors: Filip Ovidiu , Deaconescu Andrea , Deaconescu Tudor
Published: January 2021

Early social reintegration of patients with disabilities of the wrist is possible with the help of dedicated rehabilitation equipment. Using such equipment reduces the duration of recovery and reduces significantly rehabilitation costs. Based on these considerations the paper puts forward a novel constructive solution of rehabilitation equipment that ensures the simultaneous passive mobilization of the radiocarpal, metacarpophalangeal, and interphalangeal joints. The novelty of this equipment consists in the bioinspired concept of the hand support based on the Fin-Ray effect and in driving it by means of a pneumatic muscle, an inherently compliant actuator. The paper places an emphasis on the compliant character of the rehabilitation equipment that is responsible for its adaptability to the concrete conditions of patient pain tolerability.
A Review of Experimental and Numerical Studies of Lithium Ion Battery Fires
Authors: Ghiji Matt , Edmonds Shane , Moinuddin Khalid
Published: January 2021

Lithium-ion batteries (LIBs) are used extensively worldwide in a varied range of applications. However, LIBs present a considerable fire risk due to their flammable and frequently unstable components. This paper reviews experimental and numerical studies to understand parametric factors that have the greatest influence on the fire risks associated with LIBs. The LIB chemistry and the state of charge (SOC) are shown to have the greatest influence on the likelihood of a LIB transitioning into thermal runaway (TR) and releasing heats which can be cascaded to cause TR in adjacent cells. The magnitude of the heat release rate (HRR) is quantified to be used as a numerical model input parameter (source term). LIB chemistry, the SOC, and incident heat flux are proven to influence the magnitude of the HRR in all studies reviewed. Therefore, it may be conjectured that the most critical variables in addressing the overall fire safety and mitigating the probability of TR of LIBs are the chemistry and the SOC. The review of numerical modeling shows that it is quite challenging to reproduce experimental results with numerical simulations. Appropriate boundary conditions and fire properties as input parameters are required to model the onset of TR and heat transfer from thereon.
Variational Mode Decomposition Based Time-Varying Force Identification of Stay Cables
Authors: Hou Shitong , Dong Bin , Fan Jianhua , Wu Gang , Wang Haochen , Han Yitian , Zhao Xiaojin
Published: January 2021

Stay cables are important structural members of cable-stayed bridges, which play a significant role in the health monitoring and assessment of cable-stayed bridges. The in-service cable force, which varies from the effects of vehicle load, wind load and other environmental factors, may cause fatigue damage in stay cables. Traditional force identification methods can only calculate the time-average cable force instead of the instantaneous force. A novel method has been proposed in this paper for identifying time-varying cable tension based on the variational mode decomposition (VMD) method. This recent method decomposes signals and adaptively estimates instantaneous frequency combined with the Hilbert–Huang transform method. In the proposed study, the time-varying modal frequencies were identified from stay cable acceleration data, and then the time-varying cable tension was identified by the relationship between cable tension and identified fundamental frequency. Scaled and full-scale models of stay cables were implemented successively to illustrate the validity of the proposed method. The results showed that the variational mode decomposition (VMD) method has a good effect on identifying the time-varying cable forces, even the sudden changes in cable force. According to the cable force identification results, the maximum error was 8.4%, which meets the actual application of time-varying cable force measurements. An on-site test was also implemented to monitor the cable force during a construction period, and the results showed that the proposed method can provide accurate real-time results for evaluation and decision-making.
Adaptive Automation Assembly Systems in the Industry 4.0 Era: A Reference Framework and Full–Scale Prototype
Authors: Bortolini Marco , Faccio Maurizio , Galizia Francesco Gabriele , Gamberi Mauro , Pilati Francesco
Published: January 2021

Industry 4.0 emerged in the last decade as the fourth industrial revolution aiming at reaching greater productivity, digitalization and operational efficiency standard. In this new era, if compared to automated assembly systems, manual assembly systems (MASs) are still characterized by wide flexibility but poor productivity levels. To reach acceptable performances in terms of both productivity and flexibility, higher automation levels are required to increase the skills and capabilities of the human operators with the aim to design next-generation assembly systems having higher levels of adaptivity and collaboration between people and automation/information technology. In the current literature, such systems are called adaptive automation assembly systems (A3Ss). For A3Ss, few design approaches and industrial prototypes are available. This paper, extending a previous contribution by the Authors, expands the lacking research in the field and proposes a general framework guiding toward A3S effective design and validation. The framework is applied to a full-scale prototype, highlighting its features together with the technical- and human-oriented improvements arising from its adoption. Specifically, evidence from this study show a set of benefits from adopting innovative A3Ss in terms of reduction of the assembly cycle time (about 30%) with a consequent increase of the system productivity (about 45%) as well as relevant improvements of ergonomic posture indicators (about 15%). The definition of a general framework for A3S design and validation and the integration of the productivity and ergonomic analysis of such systems are missing in the current literature, representing an element of innovation. Globally, this research paper provides advanced knowledge to guide research, industrial companies and practitioners in switching from traditional to advanced assembly systems in the emerging Industry 4.0 era matching current industrial and market features.
Phytochemicals Block Glucose Utilization and Lipid Synthesis to Counteract Metabolic Reprogramming in Cancer Cells
Authors: Wu Qiong , Zhao Bo , Sui Guangchao , Shi Jinming
Published: January 2021

Aberrant metabolism is one of the hallmarks of cancers. The contributions of dysregulated metabolism to cancer development, such as tumor cell survival, metastasis and drug resistance, have been extensively characterized. “Reprogrammed” metabolic pathways in cancer cells are mainly represented by excessive glucose consumption and hyperactive de novo lipogenesis. Natural compounds with anticancer activities are constantly being demonstrated to target metabolic processes, such as glucose transport, aerobic glycolysis, fatty acid synthesis and desaturation. However, their molecular targets and underlying anticancer mechanisms remain largely unclear or controversial. Mounting evidence indicated that these natural compounds could modulate the expression of key regulatory enzymes in various metabolic pathways at transcriptional and translational levels. Meanwhile, natural compounds could also inhibit the activities of these enzymes by acting as substrate analogs or altering their protein conformations. The actions of natural compounds in the crosstalk between metabolism modulation and cancer cell destiny have become increasingly attractive. In this review, we summarize the activities of natural small molecules in inhibiting key enzymes of metabolic pathways. We illustrate the structural characteristics of these compounds at the molecular level as either inhibitor of various enzymes or regulators of metabolic pathways in cancer cells. Our ultimate goal is to both facilitate the clinical application of natural compounds in cancer therapies and promote the development of novel anticancer therapeutics.
A Possible Linkage between Dust Frequency and the Siberian High in March over Northeast Asia
Authors: Park Sung-Bin , Cho Jeong-A , Park Sang Seo , Koo Ja-Ho , Lee Yun Gon
Published: January 2021

Spring dust frequency in northeast Asia has been investigated using various approaches to understand the mechanisms of dust emission and transport. However, little attention has been paid to the linkage between dust activity and the Siberian High (SH), particularly when the SH pressure system is highly variable. In this study, we characterize the possible physical mechanisms of dust emission and transport associated with the Siberian High Intensity (SHI) and Siberian High Position Index (SHPI) in March using 18 years of ground-based observations and reanalysis data. We found that when the SHI was strong and the SH’s center was farther east (“Strong–East period”), surface and atmospheric temperatures were cooler than when the SHI was weak and the SH’s center was farther west (“Weak-West period”), due to anomalous anticyclonic pressure and strong easterlies. As a result, a reduction in the meridional temperature gradient in the lower atmosphere suppressed dust emission and transport, due to stagnant atmospheric conditions. This anomalous anticyclonic pressure in the Strong-East case seems to reduce the development of extratropical cyclones (ETC) in northeast Asia, leading to a less effective dust transport. A case study with composite analysis also showed a similar physical mechanism: stagnant air accompanying weakened westerlies in the Strong-East period suppressed dust transport to South Korea. Our findings reveal that the intensity and position of the SH can be utilized to identify spring transboundary air pollutants in northeast Asia.
Understanding Spatial Variability of NO2 in Urban Areas Using Spatial Modelling and Data Fusion Approaches
Authors: Munir Said , Mayfield Martin , Coca Daniel
Published: January 2021

Small-scale spatial variability in NO2 concentrations is analysed with the help of pollution maps. Maps of NO2 estimated by the Airviro dispersion model and land use regression (LUR) model are fused with measured NO2 concentrations from low-cost sensors (LCS), reference sensors and diffusion tubes. In this study, geostatistical universal kriging was employed for fusing (integrating) model estimations with measured NO2 concentrations. The results showed that the data fusion approach was capable of estimating realistic NO2 concentration maps that inherited spatial patterns of the pollutant from the model estimations and adjusted the modelled values using the measured concentrations. Maps produced by the fusion of NO2-LCS with NO2-LUR produced better results, with r-value 0.96 and RMSE 9.09. Data fusion adds value to both measured and estimated concentrations: the measured data are improved by predicting spatiotemporal gaps, whereas the modelled data are improved by constraining them with observed data. Hotspots of NO2 were shown in the city centre, eastern parts of the city towards the motorway (M1) and on some major roads. Air quality standards were exceeded at several locations in Sheffield, where annual mean NO2 levels were higher than 40 µg/m3. Road traffic was considered to be the dominant emission source of NO2 in Sheffield.
The Influence of Ocean Acidification and Warming on DMSP & DMS in New Zealand Coastal Water
Authors: Saint-Macary Alexia D. , Barr Neill , Armstrong Evelyn , Safi Karl , Marriner Andrew , Gall Mark , McComb Kiri , Dillingham Peter W. , Law Cliff S.
Published: January 2021

The cycling of the trace gas dimethyl sulfide (DMS) and its precursor dimethylsulfoniopropionate (DMSP) may be affected by future ocean acidification and warming. DMSP and DMS concentrations were monitored over 20-days in four mesocosm experiments in which the temperature and pH of coastal water were manipulated to projected values for the year 2100 and 2150. This had no effect on DMSP in the two-initial nutrient-depleted experiments; however, in the two nutrient-amended experiments, warmer temperature combined with lower pH had a more significant effect on DMSP & DMS concentrations than lower pH alone. Overall, this indicates that future warming may have greater influence on DMS production than ocean acidification. The observed reduction in DMSP at warmer temperatures was associated with changes in phytoplankton community and in particular with small flagellate biomass. A small decrease in DMS concentration was measured in the treatments relative to other studies, from −2% in the nutrient-amended low pH treatment to −16% in the year 2150 pH and temperature conditions. Temporal variation was also observed with DMS concentration increasing earlier in the higher temperature treatment. Nutrient availability and community composition should be considered in models of future DMS.
Optimization of Lutein Recovery from Tetraselmis suecica by Response Surface Methodology
Authors: Lee Kang Hyun , Jang Ye Won , Kim Hansol , Ki Jang-Seu , Yoo Hah Young
Published: January 2021

Microalgae have been attracting attention as feedstock for biorefinery because they have various advantages, such as carbon fixation, high growth rate and high energy yield. The bioactive compounds and lutein contained in microalgae are known to be beneficial for human health, especially eye and brain health. In this study, in order to improve the recovery of bioactive extracts including lutein from Tetraselmis suecica with higher efficiency, an effective solvent was selected, and the extraction parameters such as temperature, time and solid loading were optimized by response surface methodology. The most effective solvent for lutein recovery was identified as 100% methanol, and the optimum condition was determined (42.4 °C, 4.0 h and 125 g/L biomass loading) by calculation of the multiple regression model. The maximum content of recovered lutein was found to be 2.79 mg/mL, and the ABTS radical scavenging activity (IC50) and ferric reducing antioxidant power (FRAP) value were about 3.36 mg/mL and 561.9 μmol/L, respectively. Finally, the maximum lutein recovery from T. suecica through statistical optimization was estimated to be 22.3 mg/g biomass, which was 3.1-fold improved compared to the control group.
Phytogenic Synthesis of Pd-Ag/rGO Nanostructures Using Stevia Leaf Extract for Photocatalytic H2 Production and Antibacterial Studies
Authors: Mallikarjuna Koduru , Nasif Omaima , Ali Alharbi Sulaiman , Chinni Suresh V. , Reddy Lebaka Veeranjaneya , Reddy Minnam Reddy Vasudeva , Sreeramanan Subramaniam
Published: January 2021

Continuously increasing energy demand and growing concern about energy resources has attracted much research in the field of clean and sustainable energy sources. In this context, zero-emission fuels are required for energy production to reduce the usage of fossil fuel resources. Here, we present the synthesis of Pd-Ag-decorated reduced graphene oxide (rGO) nanostructures using a green chemical approach with stevia extract for hydrogen production and antibacterial studies under light irradiation. Moreover, bimetallic nanostructures are potentially lime lighted due to their synergetic effect in both scientific and technical aspects. Structural characteristics such as crystal structure and morphological features of the synthesized nanostructures were analyzed using X-ray diffraction and transmission electron microscopy. Analysis of elemental composition and oxidation states was carried out by X-ray photoelectron spectroscopy. Optical characteristics of the biosynthesized nanostructures were obtained by UV-Vis absorption spectroscopy, and Fourier transform infrared spectroscopy was used to investigate possible functional groups that act as reducing and capping agents. The antimicrobial activity of the biosynthesized Pd-Ag-decorated rGO nanostructures was excellent, inactivating 96% of Escherichia coli cells during experiments over 150 min under visible light irradiation. Hence, these biosynthesized Pd-Ag-decorated rGO nanostructures can be utilized for alternative nanomaterial-based drug development in the future.
Development of Smart-Ring-Based Chest Compression Depth Feedback Device for High Quality Chest Compressions: A Proof-of-Concept Study
Authors: Lee Seungjae , Song Yeongtak , Lee Jongshill , Oh Jaehoon , Lim Tae Ho , Ahn Chiwon , Kim In Young
Published: January 2021

Recently, a smart-device-based chest compression depth (CCD) feedback system that helps ensure that chest compressions have adequate depth during cardiopulmonary resuscitation (CPR) was developed. However, no CCD feedback device has been developed for infants, and many feedback systems are inconvenient to use. In this paper, we report the development of a smart-ring-based CCD feedback device for CPR based on an inertial measurement unit, and propose a high-quality chest compression depth estimation algorithm that considers the orientation of the device. The performance of the proposed feedback system was evaluated by comparing it with a linear variable differential transformer in three CPR situations. The experimental results showed compression depth errors of 2.0 ± 1.1, 2.2 ± 0.9, and 1.4 ± 1.1 mm in the three situations. In addition, we conducted a pilot test with an adult/infant mannequin. The results of the experiments show that the proposed smart-ring-based CCD feedback system is applicable to various chest compression methods based on real CPR situations.
Vibrational Spectra of Nucleotides in the Presence of the Au Cluster Enhancer in MD Simulation of a SERS Sensor
Authors: Zolotoukhina Tatiana , Yamada Momoko , Iwakura Shingo
Published: January 2021

Surface-enhanced Raman scattering (SERS) nanoprobes have shown tremendous potential in in vivo imaging. The development of single oligomer resolution in the SERS promotes experiments on DNA and protein identification using SERS as a nanobiosensor. As Raman scanners rely on a multiple spectrum acquisition, faster imaging in real-time is required. SERS weak signal requires averaging of the acquired spectra that erases information on conformation and interaction. To build spectral libraries, the simulation of measurement conditions and conformational variations for the nucleotides relative to enhancer nanostructures would be desirable. In the molecular dynamic (MD) model of a sensing system, we simulate vibrational spectra of the cytosine nucleotide in FF2/FF3 potential in the dynamic interaction with the Au20 nanoparticles (NP) (EAM potential). Fourier transfer of the density of states (DOS) was performed to obtain the spectra of bonds in reaction coordinates for nucleotides at a resolution of 20 to 40 cm−1. The Au20 was optimized by ab initio density functional theory with generalized gradient approximation (DFT GGA) and relaxed by MD. The optimal localization of nucleotide vs. NP was defined and the spectral modes of both components vs. interaction studied. Bond-dependent spectral maps of nucleotide and NP have shown response to interaction. The marker frequencies of the Au20—nucleotide interaction have been evaluated.
Integrating Multi–Omics Data for Gene-Environment Interactions
Authors: Du Yinhao , Fan Kun , Lu Xi , Wu Cen
Published: January 2021

Gene-environment (G×E) interaction is critical for understanding the genetic basis of complex disease beyond genetic and environment main effects. In addition to existing tools for interaction studies, penalized variable selection emerges as a promising alternative for dissecting G×E interactions. Despite the success, variable selection is limited in terms of accounting for multidimensional measurements. Published variable selection methods cannot accommodate structured sparsity in the framework of integrating multiomics data for disease outcomes. In this paper, we have developed a novel variable selection method in order to integrate multi-omics measurements in G×E interaction studies. Extensive studies have already revealed that analyzing omics data across multi-platforms is not only sensible biologically, but also resulting in improved identification and prediction performance. Our integrative model can efficiently pinpoint important regulators of gene expressions through sparse dimensionality reduction, and link the disease outcomes to multiple effects in the integrative G×E studies through accommodating a sparse bi-level structure. The simulation studies show the integrative model leads to better identification of G×E interactions and regulators than alternative methods. In two G×E lung cancer studies with high dimensional multi-omics data, the integrative model leads to an improved prediction and findings with important biological implications.
Recognition Memory in Noonan Syndrome
Authors: Costanzo Floriana , Alfieri Paolo , Caciolo Cristina , Bergonzini Paola , Perrino Francesca , Zampino Giuseppe , Leoni Chiara , Menghini Deny , Digilio Maria Cristina , Tartaglia Marco , Vicari Stefano , Carlesimo Giovanni Augusto
Published: January 2021

Noonan syndrome (NS) and the clinically related NS with multiple lentiginous (NMLS) are genetic conditions characterized by upregulated RAS mitogen activated protein kinase (RAS–MAPK) signaling, which is known to impact hippocampus-dependent memory formation and consolidation. The aim of the present study was to provide a detailed characterization of the recognition memory of children and adolescents with NS/NMLS. We compared 18 children and adolescents affected by NS and NMLS with 22 typically developing (TD) children, matched for chronological age and non-verbal Intelligence Quotient (IQ), in two different experimental paradigms, to assess familiarity and recollection: a Process Dissociation Procedure (PDP) and a Task Dissociation Procedure (TDP). Differences in verbal skills between groups, as well as chronological age, were considered in the analysis. Participants with NS and NSML showed reduced recollection in the PDP and impaired associative recognition in the TDP, compared to controls. These results indicate poor recollection in the recognition memory of participants with NS and NSML, which cannot be explained by intellectual disability or language deficits. These results provide evidence of the role of mutations impacting RAS–MAPK signaling in the disruption of hippocampal memory formation and consolidation.
Problems and Needs Persist for Oklahoma City Bombing Survivors Many Years Later
Authors: Tucker Phebe , Pfefferbaum Betty , Watson Kevin , Hester Landon , Czapla Christopher
Published: January 2021

Background: This study assesses long-term physical and emotional symptoms and unmet needs in direct survivors of the 1995 Oklahoma City terrorist bombing 18 ½ years after the event. Methods: A telephone questionnaire assessed psychiatric symptoms, health problems and coping strategies in 138 terrorism survivors (of whom 80% were physically injured) from a state registry of directly exposed persons, and 171 non-exposed community controls. Structured survey questions measured psychiatric symptoms, posttraumatic growth, general health problems and health care utilization. Open-ended questions explored survivors’ most important terrorism-related problems and needs. Quantitative and qualitative data analysis methods were undertaken. Results: Survivors reported similar rates of major health problems and general health care utilization, more anxiety and depression symptoms, and more ancillary health care use than controls on structured assessments. Survivors also reported posttraumatic growth, using several positive coping skills. Open-ended questions identified survivors’ specific continuing bombing-related problems, and needs which were not disclosed on the questionnaire; these included many lasting physical injuries, health problems (especially hearing difficulties), specific posttraumatic stress disorder (PTSD) symptoms, other emotional symptoms, work and financial problems, interpersonal issues, and desires to help others. Conclusions: Results suggest that extended recovery services are needed long after terrorism exposure, and that open-ended assessment is useful to identify those requiring services.
The Cartis Form for the Seismic Vulnerability Assessment of Timber Large-Span Structures
Authors: Faggiano Beatrice , Iovane Giacomo , Gaspari Andrea , Fournely Eric , Bouchair AbdelHamid , Landolfo Raffaele , Piazza Maurizio
Published: January 2021

Italy is located in a very active seismic zone, and many earthquakes have marked the country, some of them in the recent past. In order to take adequate measures of seismic prevention and protection, in the last decades, the Italian Civil Protection Department (DPC) initiated a survey and introduced a specific form for the quick and/or post-seismic assessment of buildings. This is useful to obtain statistics on the types of structures and their vulnerability and a judgement on the damage, leading to a decision about the possibility of reuse and/or the level of retrofitting to be applied. Those activities have been developed since the beginning of 2000. This task is currently carried out by the Italian DPC-ReLUIS project research, line WP2 on the inventory of building structures, setting up the CARTIS form for any structural type, like masonry, reinforced concrete, precast concrete, steel, and timber structures, the latter being mainly related to large span buildings, extensively used in Italy. In this context, the paper presents the first draft of the CARTIS form for large span timber structures that provides a general description for typical structural schemes, through the singular points commonly considered as seismic structural vulnerabilities. Moreover, the statistics on timber large span structures based on a sample of 10 buildings is presented.
MicroRNAs in the Pathogenesis of Hepatocellular Carcinoma: A Review
Authors: Morishita Asahiro , Oura Kyoko , Tadokoro Tomoko , Fujita Koji , Tani Joji , Masaki Tsutomu
Published: January 2021

Hepatocellular carcinoma (HCC) is the seventh most frequent cancer and the fourth leading cause of cancer mortality worldwide. Despite substantial advances in therapeutic strategies, the prognosis of late-stage HCC remains dismal because of the high recurrence rate. A better understanding of the etiology of HCC is therefore necessary to improve outcomes. MicroRNAs (miRNAs) are small, endogenous, noncoding, single-stranded RNAs that modulate the expression of their target genes at the posttranscriptional and translational levels. Aberrant expression of miRNAs has frequently been detected in cancer-associated genomic regions or fragile sites in various human cancers and has been observed in both HCC cells and tissues. The precise patterns of aberrant miRNA expression differ depending on disease etiology, including various causes of hepatocarcinogenesis, such as viral hepatitis, alcoholic liver disease, or nonalcoholic steatohepatitis. However, little is known about the underlying mechanisms and the association of miRNAs with the pathogenesis of HCC of various etiologies. In the present review, we summarize the key mechanisms of miRNAs in the pathogenesis of HCC and emphasize their potential utility as valuable diagnostic and prognostic biomarkers, as well as innovative therapeutic targets, in HCC diagnosis and treatment.
The Potential of T Cell Factor 1 in Sustaining CD8+ T Lymphocyte-Directed Anti-Tumor Immunity
Authors: Jung Sungmin , Baek Jea-Hyun
Published: January 2021

T cell factor 1 (TCF1) is a transcription factor that has been highlighted to play a critical role in the promotion of T cell proliferation and maintenance of cell stemness in the embryonic and CD8+ T cell populations. The regulatory nature of TCF1 in CD8+ T cells is of great significance, especially within the context of T cell exhaustion, which is linked to the tumor and viral escape in pathological contexts. Indeed, inhibitory signals, such as programmed cell death 1 (PD-1) and cytotoxic-T-lymphocyte-associated protein 4 (CTLA-4), expressed on exhausted T lymphocytes (TEX), have become major therapeutic targets in immune checkpoint blockade (ICB) therapy. The significance of TCF1 in the sustenance of CTL-mediated immunity against pathogens and tumors, as well as its recently observed necessity for an effective anti-tumor immune response in ICB therapy, presents TCF1 as a potentially significant biomarker and/or therapeutic target for overcoming CD8+ T cell exhaustion and resistance to ICB therapy. In this review, we aim to outline the recent findings on the role of TCF1 in T cell development and discuss its implications in anti-tumor immunity.
Brain Metastases from Uterine Cervical and Endometrial Cancer
Authors: Kato Mayumi Kobayashi , Tanase Yasuhito , Uno Masaya , Ishikawa Mitsuya , Kato Tomoyasu
Published: January 2021

Reports on brain metastases (BMs) from uterine cervical carcinoma (CC) and uterine endometrial carcinoma (EC) have recently increased due to the development of massive databases and improvements in diagnostic procedures. This review separately investigates the prevalence, clinical characteristics, clinical presentation, diagnosis, treatment, and prognosis of BMs from CC and uterine endometrial carcinoma EC. For patients with CC, early-stage disease and poorly differentiated carcinoma lead to BMs, and elderly age, poor performance status, and multiple BMs are listed as poor prognostic factors. Advanced-stage disease and high-grade carcinoma are high-risk factors for BMs from EC, and multiple metastases and extracranial metastases, or unimodal therapies, are possibly factors indicating poor prognosis. There is no “most effective” therapy that has gained consensus for the treatment of BMs. Treatment decisions are based on clinical status, number of the metastases, tumor size, and metastases at distant organs. Surgical resection followed by adjuvant radiotherapy appears to be the best treatment approach to date. Stereotactic ablative radiation therapy has been increasingly associated with good outcomes in preserving cognitive functions. Despite treatment, patients died within 1 year after the BM diagnosis. BMs from uterine cancer remain quite rare, and the current evidence is limited; thus, further studies are needed.
Exploiting Gangliosides for the Therapy of Ewing’s Sarcoma and H3K27M-Mutant Diffuse Midline Glioma
Authors: Wingerter Arthur , El Malki Khalifa , Sandhoff Roger , Seidmann Larissa , Wagner Daniel-Christoph , Lehmann Nadine , Vewinger Nadine , Frauenknecht Katrin B. M. , Sommer Clemens J. , Traub Frank , Kindler Thomas , Russo Alexandra , Otto Henrike , Lollert André , Staatz Gundula , Roth Lea , Paret Claudia , Faber Jörg
Published: January 2021

The ganglioside GD2 is an important target in childhood cancer. Nevertheless, the only therapy targeting GD2 that is approved to date is the monoclonal antibody dinutuximab, which is used in the therapy of neuroblastoma. The relevance of GD2 as a target in other tumor entities remains to be elucidated. Here, we analyzed the expression of GD2 in different pediatric tumor entities by flow cytometry and tested two approaches for targeting GD2. H3K27M-mutant diffuse midline glioma (H3K27M-mutant DMG) samples showed the highest expression of GD2 with all cells strongly positive for the antigen. Ewing’s sarcoma (ES) samples also showed high expression, but displayed intra- and intertumor heterogeneity. Osteosarcoma had low to intermediate expression with a high percentage of GD2-negative cells. Dinutuximab beta in combination with irinotecan and temozolomide was used to treat a five-year-old girl with refractory ES. Disease control lasted over 12 months until a single partially GD2-negative intracranial metastasis was detected. In order to target GD2 in H3K27M-mutant DMG, we blocked ganglioside synthesis via eliglustat, since dinutuximab cannot cross the blood–brain barrier. Eliglustat is an inhibitor of glucosylceramide synthase, and it is used for treating children with Gaucher’s disease. Eliglustat completely inhibited the proliferation of primary H3K27M-mutant DMG cells in vitro. In summary, our data provide evidence that dinutuximab might be effective in tumors with high GD2 expression. Moreover, disrupting the ganglioside metabolism in H3K27M-mutant DMG could open up a new therapeutic option for this highly fatal cancer.
Cytoreductive Surgery with Hyperthermic Intraperitoneal Chemotherapy for Peritoneal Carcinomatosis from Epithelial Ovarian Cancer: A 20-Year Single-Center Experience
Authors: Carboni Fabio , Federici Orietta , Sperduti Isabella , Zazza Settimio , Sergi Domenico , Corona Francesco , Valle Mario
Published: January 2021

Despite improvement in treatments, the peritoneum remains the primary site of relapse in most ovarian cancer cases. Patients who underwent cytoreductive surgery with hyperthermic intraperitoneal chemotherapy for peritoneal carcinomatosis from epithelial ovarian cancer were reviewed. Kaplan–Meier curves and multivariate Cox analyses were used to identify survival rates and prognostic factors. This study included 158 patients. The procedure was mostly performed for recurrent disease (46.8%) and high-grade serous carcinoma (58.2%). The median peritoneal cancer index was 14, and complete cytoreduction was obtained in 87.9% of cases. Grade IV morbidity occurred in 15.2% of patients, mostly requiring surgical reoperation, and one patient (0.6%) died within 90 days. The median follow-up was 63.5 months. The Kaplan–Meier 5-year overall survival (OS) and disease-free survival (DFS) rates were 42.1% and 24.3%, respectively. Multiple regression logistic analyses demonstrated that the completeness of cytoreduction (CC) score (p ≤ 0.0001), pancreatic resection (p ≤ 0.0001) and number of resections (p = 0.001) were significant factors influencing OS; whereas the CC score (p ≤ 0.0001) and diaphragmatic procedures (p = 0.01) were significant for DFS. The addition of hyperthermic intraperitoneal chemotherapy to standard multimodality therapy may improve outcomes in both primary and recurrent epithelial ovarian cancer without impairing early postoperative results, but the exact timing has not yet been established. Prospective randomized studies will clarify the role and indications of this approach.
Comparison of Three Catalytic Processes in Degradation of HPAM by tBu-TPyzPzCo
Authors: Wang Dejun , Li Hui , Jiang Xiren , Zhao Chaocheng , Zhao Yuhui
Published: January 2021

The present study describes a two-step synthesis process for the cobalt complex of tetra-2,3-(5,6-di-tert-butyl-pyrazino) porphyrazine (tBu-TPyzPzCo). The product was ultrasonically impregnated onto carbon black (CB) to prepare a supported catalyst (tBu-TPyzPzCo/CB). We built a split photoelectric catalytic device to test the performance of photocatalytic, electrocatalytic and photoelectrocatalytic degradation of partially hydrolyzed polyacrylamide (HPAM). The results confirm that HPAM exhibited more efficient degradation in the presence of a supporting catalyst using the photoelectrocatalytic process than by photocatalytic or electrocatalytic oxidation—or even the sum of the two in saline water. The photoelectrocatalytic reaction confirmed that the process conforms to quasi-first order reaction kinetics, while the reaction rate constants were 6.03 times that of photocatalysis and 3.97 times that of electrocatalysis. We also compared the energy consumption of the three processes and found that the photoelectrocatalytic process has the highest energy efficiency.
Sialic Acids and Their Influence on Human NK Cell Function
Authors: Rosenstock Philip , Kaufmann Thomas
Published: January 2021

Sialic acids are sugars with a nine-carbon backbone, present on the surface of all cells in humans, including immune cells and their target cells, with various functions. Natural Killer (NK) cells are cells of the innate immune system, capable of killing virus-infected and tumor cells. Sialic acids can influence the interaction of NK cells with potential targets in several ways. Different NK cell receptors can bind sialic acids, leading to NK cell inhibition or activation. Moreover, NK cells have sialic acids on their surface, which can regulate receptor abundance and activity. This review is focused on how sialic acids on NK cells and their target cells are involved in NK cell function.
Immunotherapy of Glioblastoma: Current Strategies and Challenges in Tumor Model Development
Authors: Majc Bernarda , Novak Metka , Kopitar-Jerala Nataša , Jewett Anahid , Breznik Barbara
Published: January 2021

Glioblastoma is the most common brain malignant tumor in the adult population, and immunotherapy is playing an increasingly central role in the treatment of many cancers. Nevertheless, the search for effective immunotherapeutic approaches for glioblastoma patients continues. The goal of immunotherapy is to promote tumor eradication, boost the patient’s innate and adaptive immune responses, and overcome tumor immune resistance. A range of new, promising immunotherapeutic strategies has been applied for glioblastoma, including vaccines, oncolytic viruses, immune checkpoint inhibitors, and adoptive cell transfer. However, the main challenges of immunotherapy for glioblastoma are the intracranial location and heterogeneity of the tumor as well as the unique, immunosuppressive tumor microenvironment. Owing to the lack of appropriate tumor models, there are discrepancies in the efficiency of various immunotherapeutic strategies between preclinical studies (with in vitro and animal models) on the one hand and clinical studies (on humans) on the other hand. In this review, we summarize the glioblastoma characteristics that drive tolerance to immunotherapy, the currently used immunotherapeutic approaches against glioblastoma, and the most suitable tumor models to mimic conditions in glioblastoma patients. These models are improving and can more precisely predict patients’ responses to immunotherapeutic treatments, either alone or in combination with standard treatment.
Functional Restoration of Pituitary after Pituitary Allotransplantation into Hypophysectomized Rats
Authors: Choi Jai Ho , Lee Jung Eun , Kim Hong-Lim , Ko Seung Hyun , Kim Se Hoon , Yang Seung Ho
Published: January 2021

Long-term hormone replacement therapy due to panhypopituitarism can lead to serious complications and thus, pituitary transplantation is considered a more desirable. We investigated functional restoration after allotransplatation of the pituitary gland. We transplanted extracted pituitary gland into the omentum of an hypophysectomized rat. Two experiments were performed: (1) to confirm the hypophysectomy was successful and (2) to assess functional restoration after pituitary transplantation. Pituitary hormone level and weight change were consecutively assessed. Electron microscopic (EM) examinations were performed to identify morphological changes at 3 days after transplantation. We confirmed that pituitary gland was properly extracted from 6 rats after sacrifice. The findings showed (1) a weight loss of more than 3% or (2) a weight change of less than 2% along with a decreased growth hormone (GH) level by more than 80% at 2 weeks post-hypophysectomy. A further four rats underwent pituitary transplantation after hypophysectomy and were compared with the previously hypophysectomized rats. All showed rapid weight gain during the two weeks after transplantation. The thyroid-stimulating hormone, prolactin, and GH levels were restored at one week post-transplantation and maintained for 10 weeks. Hypophyseal tissue architecture was maintained at 3 days after transplantation, as indicated by EM. These data suggest that a transplanted pituitary gland can survive in the omentum with concomitant partial restoration of anterior pituitary hormones.
Experimental Type 2 Diabetes Differently Impacts on the Select Functions of Bone Marrow-Derived Multipotent Stromal Cells
Authors: Ribot Jonathan , Denoeud Cyprien , Frescaline Guilhem , Landon Rebecca , Petite Hervé , Pavon-Djavid Graciela , Bensidhoum Morad , Anagnostou Fani
Published: January 2021

Bone marrow-derived multipotent stromal cells (BMMSCs) represent an attractive therapeutic modality for cell therapy in type 2 diabetes mellitus (T2DM)-associated complications. T2DM changes the bone marrow environment; however, its effects on BMMSC properties remain unclear. The present study aimed at investigating select functions and differentiation of BMMSCs harvested from the T2DM microenvironment as potential candidates for regenerative medicine. BMMSCs were obtained from Zucker diabetic fatty (ZDF; an obese-T2DM model) rats and their lean littermates (ZL; controls), and cultured under normoglycemic conditions. The BMMSCs derived from ZDF animals were fewer in number, with limited clonogenicity (by 2-fold), adhesion (by 2.9-fold), proliferation (by 50%), migration capability (by 25%), and increased apoptosis rate (by 2.5-fold) compared to their ZL counterparts. Compared to the cultured ZL-BMMSCs, the ZDF-BMMSCs exhibited (i) enhanced adipogenic differentiation (increased number of lipid droplets by 2-fold; upregulation of the Pparg, AdipoQ, and Fabp genes), possibly due to having been primed to undergo such differentiation in vivo prior to cell isolation, and (ii) different angiogenesis-related gene expression in vitro and decreased proangiogenic potential after transplantation in nude mice. These results provided evidence that the T2DM environment impairs BMMSC expansion and select functions pertinent to their efficacy when used in autologous cell therapies.