bluuebunny/crossref_metadata_2025 huggingface dataset:
Nonlinear Vibration Isolation via a NiTiNOL Wire Rope
Authors: Niu Mu-Qing , Chen Li-Qun
Published: October 2021

Vibration isolators with both stiffness and damping nonlinearities show promise for exhibiting compound advantages for broadband vibration isolation. A nonlinear isolator with a NiTiNOL wire rope is proposed with cubic stiffness, hysteretic damping, and pinching effects induced by geometric constraints, inner frictions, and phase transitions, respectively. A combined method of a beam constraint model and a Bouc-Wen model is presented to characterize the restoring force of the NiTiNOL wire rope. The frequency responses of the nonlinear isolator were analyzed through a harmonic balance method with an alternating frequency/time domain technique. The generalized equivalent stiffness and the generalized equivalent damping ratio were defined for a comprehensive understanding of the nonlinear characteristics. The isolator exhibited a stiffness-softening-hardening characteristic. The pinching effect, the Bouc-Wen hysteresis, and the cubic stiffness mainly influenced the equivalent stiffness at the initial value, the small displacements, and the large displacements, respectively. The rate-independent damping ratio increased and then decreased with increasing displacement, and the parameters influenced the damping ratio change in different ways. Compared to an isolator with a steel wire rope, the isolator with a NiTiNOL wire rope exhibited less initial stiffness and a stronger damping effect, and thus, better vibration isolation performance. The relationships of the peak displacement transmissibility and the resonant frequency with the excitation amplitude were both non-monotonic due to the non-monotonic changes of the stiffness and the damping ratio. The minimum peak transmissibility, the lowest resonant frequency, and their corresponding excitation amplitudes depended on the isolator parameters. The isolator demonstrated stiffness–softening and stiffness–hardening types of jump phenomena with different parameters.
Hoek-Brown Failure Criterion-Based Creep Constitutive Model and BP Neural Network Parameter Inversion for Soft Surrounding Rock Mass of Tunnels
Authors: Chen Chao , Li Tianbin , Ma Chunchi , Zhang Hang , Tang Jieling , Zhang Yin
Published: October 2021

This paper summarizes the main factors affecting the large deformation of soft rock tunnels, including the lithology combination, weathering effect, and underground water status, by reviewing the typical cases of largely-deformed soft rock tunnels. The engineering geological properties of the rock mass were quantified using the rock mass block index (RBI) and the absolute weathering index (AWI) to calculate the geological strength index (GSI). Then, the long-term strength σr and the elastic modulus E0 of the rock mass were calculated according to the Hoek–Brown failure criterion and substituted into the creep constitutive model based on the Nashihara model. Finally, the creep parameters of the surrounding rock mass of the Ganbao tunnel were inverted and validated by integrating the on-site monitoring and BP neural network. The inversion results were consistent with the measured convergence during monitoring and satisfied the engineering requirements of accuracy. The method proposed in this paper can be used to invert the geological parameters of the surrounding rock mass for a certain point, which can provide important mechanical parameters for the design and construction of tunnels, and ensure the stability of the surrounding rock mass during the period of construction and the safety of the lining structure during operation.
Semantic Fusion with Deep Learning and Formal Ontologies for Evaluation of Policies and Initiatives in the Smart City Domain
Authors: Kilicay-Ergin Nil , Barb Adrian S.
Published: October 2021

Decision makers and policy analysts at different administrative levels often lack a holistic view of the problem as there are semantic variations in policy documents due to domain-specific content. For example, smart city initiatives are derived from national and international initiatives which may influence the incentives for local participants, but local initiatives reflect the local contextual elements of the city. Balanced assessment of smart city initiatives should include a systemic evaluation of the initiatives at multiple levels including the city, the country in which the city resides as well as at international level. In this paper, a knowledge elicitation methodology is presented for multi-granularity evaluation of policies and initiatives. The methodology is demonstrated on the evaluation of smart city initiatives generated at different administrative levels. Semantic networks are constructed using formal ontologies and deep learning methods for automatic semantic evaluation of initiatives to abstract knowledge found in text. Three smart city initiatives published by different administrative levels including international, national, and city level are evaluated in terms of relevance, coherence, and alignment of multi-level smart city initiatives. Experiments and analysis ultimately provide a holistic view of the problem which is necessary for decision makers and policy analysts of smart cities.
Home Gardens as a Source of Medicinal, Herbal and Food Preparations: Modern and Historical Approaches in Lithuania
Authors: Pranskuniene Zivile , Bajoraite Roberta , Simaitiene Zenona , Bernatoniene Jurga
Published: October 2021

The culture of home gardens in Lithuania comes from the deep traditions of agriculture. The purpose of this study was to collect and evaluate the ethnobotanical knowledge of medicinal plants grown in Tauragė District home gardens and to compare it with archival sources. A field survey was conducted from July 2019 to October 2020 in the Tauragė District, and the target group consisted of 27 respondents. The data obtained during the research were compared with the unpublished work of E. Šimkūnaitė, dated 1948. During the research, 100 cultivated plant species were recorded and assigned to 36 plant families (76 plant species and 38 plant families in the archival source, respectively). Many of the species grown earlier/at present in home gardens were used without EMA approved medical indications and were based solely on folk knowledge and experience in medicine. Despite the wide network of pharmacies and well-available primary health care in Lithuania, the residents of Tauragė District still grow medicinal plants in their home gardens for various purposes—from homemade medicines to food–herbal preparations. This food–medicine connection is as tight as it was in the archival study of 1948, which shows the surviving Lithuanian tradition of growing both food and medicine in home gardens. Those cultivated plants most suitable for Lithuanian climatic conditions and with ethnic heritage-based medical applications can be a source of ideas for further research.
Knee Exoskeletons Design Approaches to Boost Strength Capability: A Review
Authors: Meda-Gutiérrez Juan R. , Zúñiga-Avilés Luis Adrián , Vilchis-González Adriana H. , Ávila-Vilchis Juan Carlos
Published: October 2021

There are different devices to increase the strength capacity of people with walking problems. These devices can be classified into exoskeletons, orthotics, and braces. This review aims to identify the state of the art in the design of these medical devices, based on an analysis of patents and literature. However, there are some difficulties in processing the records due to the lack of filters and standardization in the names, generating discrepancies between the search engines, among others. Concerning the patents, 74 patents were analyzed using search engines such as Google Patents, Derwent, The Lens, Patentscope, and Espacenet over the past ten years. A bibliometric analysis was performed using 63 scientific reports from Web of Science and The Lens in the same period for scientific communications. The results show a trend to use the mechanical design of exoskeletons based on articulated rigid structures and elements that provide force to move the structure. These are generally two types: (a) elastic elements and (b) electromechanical elements. The United States accounts for 32% of the technological patents reviewed. The results suggest that the use of exoskeletons or orthoses customized to the users’ needs will continue to increase over the years due to the worldwide growth in disability, particularly related to mobility difficulties and technologies related to the combined use of springs and actuators.
Moringa oleifera Leaf Powder as Functional Additive in Cookies to Protect SH-SY5Y Cells
Authors: Nuzzo Domenico , Picone Pasquale , Lozano Sanchez Jesus , Borras-Linares Isabel , Guiducci Alessandro , Muscolino Emanuela , San Biagio Pier Luigi , Dispenza Clelia , Bulone Donatella , Giacomazza Daniela , Lapasin Romano
Published: October 2021

The aim of this work is the evaluation of the addition of Moringa leaf powder (MLP) in cookies in terms of antioxidant properties, dough processability and sensorial properties of the cookies. The total content of biophenols and flavonoids in MLP was detected and the identification of the bioactive molecules was performed by HPLC-ESI-TOF-MS measurements, before and after oven treatment at 180 °C for 20 min. After a preliminary evaluation of the MLP water soluble fraction (MLPsf) cytotoxicity, its protective effect against an oxidative injury induced in the SH-SY5Y cells was assessed. Data evidence that the bioactive molecules present in MLPsf are effective in preventing ROS production and in protecting neuronal cells against oxidative stress. Prototypes of cookies containing MLP in different concentrations were then produced and evaluated by a consumer panel. Selected doughs containing MLP were analysed to determine the total content of biophenols in the cookies after baking and their enrichment in terms of valuable chemical elements. The influence of MLP on the viscoelastic behaviour and morphology of the doughs was also assessed. Finally, the potential role in counteracting the insurgence of not treatable neurodegenerative pathologies of two main MLP components, glucomoringin and kaempferol derivatives, present also after the thermal treatment, was discussed.
Classification of Problem and Solution Strings in Scientific Texts: Evaluation of the Effectiveness of Machine Learning Classifiers and Deep Neural Networks
Authors: Mishra Rohit Bhuvaneshwar , Jiang Hongbing
Published: October 2021

One of the central aspects of science is systematic problem-solving. Therefore, problem and solution statements are an integral component of the scientific discourse. The scientific analysis would be more successful if the problem–solution claims in scientific texts were automatically classified. It would help in knowledge mining, idea generation, and information classification from scientific texts. It would also help to compare scientific papers and automatically generate review articles in a given field. However, computational research on problem–solution patterns has been scarce. The linguistic analysis, instructional-design research, theory, and empirical methods have not paid enough attention to the study of problem–solution patterns. This paper tries to solve this issue by applying the computational techniques of machine learning classifiers and neural networks to a set of features to intelligently classify a problem phrase from a non-problem phrase and a solution phrase from a non-solution phrase. Our analysis shows that deep learning networks outperform machine learning classifiers. Our best model was able to classify a problem phrase from a non-problem phrase with an accuracy of 90.0% and a solution phrase from a non-solution phrase with an accuracy of 86.0%.
Automated Breast Lesion Detection and Characterization with the Wavelia Microwave Breast Imaging System: Methodological Proof-of-Concept on First-in-Human Patient Data
Authors: Fasoula Angie , Duchesne Luc , Gil Cano Julio Daniel , Moloney Brian M. , Abd Elwahab Sami M. , Kerin Michael J.
Published: October 2021

Microwave Breast Imaging (MBI) is an emerging non-ionizing imaging modality, with the potential to support breast diagnosis and management. Wavelia is an MBI system prototype, of 1st generation, which has recently completed a First-In-Human (FiH) clinical investigation on a 25-symptomatic patient cohort, to explore the capacity of the technology to detect and characterize malignant (invasive carcinoma) and benign (fibroadenoma, cyst) breast disease. Two recent publications presented promising results demonstrated by the device in this FiH study in detecting and localizing, as well as delineating size and malignancy risk, of malignant and benign palpable breast lesions. In this paper, the methodology that has been employed in the Wavelia semi-automated Quantitative Imaging Function (QIF), to support breast lesion detection and characterization in the FiH clinical investigation of the device, is presented and the critical design parameters are highlighted.
Spatiotemporal Analysis of Haze in Beijing Based on the Multi-Convolution Model
Authors: Yin Lirong , Wang Lei , Huang Weizheng , Liu Shan , Yang Bo , Zheng Wenfeng
Published: October 2021

As a kind of air pollution, haze has complex temporal and spatial characteristics. From the perspective of time, haze has different causes and levels of pollution in different seasons. From the perspective of space, the concentration of haze in adjacent areas will affect each other, showing some correlation. In this paper, we construct a multi-convolution haze-level prediction model for predicting haze levels in different areas of Beijing, which uses the remote sensing satellite image of the Beijing divided into nine regions as input and the haze pollution level as output. We categorize the predictions into four seasons in chronological order and use frequency histograms to analyze haze levels in different regions in different seasons. The results show that the haze pollution in the southern regions is significantly different from that in the northern regions. In addition, the haze tends to be clustered in adjacent areas. We use Global Moran’s I to analyze the predictions and find that haze is related to the geographical location in summer and autumn. We also use Local Moran’s I, Moran scatter plot, and Local Indicators of Spatial Association (LISA) to study the spatial characteristics of haze in adjacent areas. The results show, for the spatial distribution of haze in Beijing, that the southern regions present a high-high agglomeration, while the northern regions exhibit a ‘low-low agglomeration. The temporal evolution of haze on the seasonal scale, according to the chronological order of winter, spring, and summer to autumn, shows that the haze gradually becomes agglomerated. The main finding is that the haze pollution in southern Beijing is significantly different from that of northern regions, and haze tends to be clustered in adjacent areas.
Is Football/Soccer Purely Stochastic, Made Out of Luck, or Maybe Predictable? How Does Bayesian Reasoning Assess Sports?
Authors: Blanco Leonardo Barrios , Ferreira Paulo Henrique , Louzada Francisco , Nascimento Diego Carvalho do
Published: October 2021

Predicting the game score is a well-explored duty, using mathematical/statistical models. Nonetheless, by adopting a Bayesian methodology, this study aimed to estimate probabilistically the Chilean Premier League teams’ position, considering them a hierarchical structure. This approach enabled the evaluation of the main Chilean championship that provides the major soccer players for the national team. Thus, a countable (Poisson) regression structure was considered to explain each match as a combination of home advantage, added to the power of attack and defense of each team and considering their performance in the championship as an independent game. We were able to quantify the relationship across the defense and attack of each team and, in addition, were able to group/verify the performance of the entirety of the 2020 Chilean Premier League. For the model validation, we saved the last five games for the model prediction and we found that, in this league, the teams presented a statistical significance in the attack factors, which influences the scores (goals); however, all the teams showed low defense power and we have also found that playing at home or away did not present a game advantage. Our model was able to predict the Chilean league position table, with precision on the top five positions, and from the 6–11 positions there was a small shift (close performance in the championship) caused by the similarity of the expected number of goals, which implied the same position on the rank. This type of model has been shown to be very competitive for the soccer championship prediction.
Systematic Characterization of TCP Gene Family in Four Cotton Species Revealed That GhTCP62 Regulates Branching in Arabidopsis
Authors: Liu Zhao , Yang Jingyu , Li Shengdong , Liu Le , Qanmber Ghulam , Chen Guoquan , Duan Zhenyu , Zhao Na , Wang Gang
Published: October 2021

TEOSINTE-BRANCHED1/CYCLOIDEA/PCF (TCP) transcription factors play an essential role in regulating various physiological and biochemical functions during plant growth. However, the function of TCP transcription factors in G. hirsutum has not yet been studied. In this study, we performed genome-wide identification and correlation analysis of the TCP transcription factor family in G. hirsutum. We identified 72 non-redundant GhTCP genes and divided them into seven subfamilies, based on phylogenetic analysis. Most GhTCP genes in the same subfamily displayed similar exon and intron structures and featured highly conserved motif structures in their subfamily. Additionally, the pattern of chromosomal distribution demonstrated that GhTCP genes were unevenly distributed on 24 out of 26 chromosomes, and that fragment replication was the main replication event of GhTCP genes. In TB1 sub-family genes, GhTCP62 was highly expressed in the axillary buds, suggesting that GhTCP62 significantly affected cotton branching. Additionally, subcellular localization results indicated that GhTCP62 is located in the nucleus and possesses typical transcription factor characteristics. The overexpression of GhTCP62 in Arabidopsis resulted in fewer rosette-leaf branches and cauline-leaf branches. Furthermore, the increased expression of HB21 and HB40 genes in Arabidopsis plants overexpressing GhTCP62 suggests that GhTCP62 may regulate branching by positively regulating HB21 and HB40.
Long-Lasting Effect after Single Hyaluronate Injection for Unilateral Vocal Fold Paralysis: Does Concentration Matter?
Authors: Lee Yi-Chieh , Pei Yu-Cheng , Lu Yi-An , Chung Hsiu-Feng , Li Hsueh-Yu , Lee Li-Ang , Fang Tuan-Jen
Published: October 2021

Background: Early injection laryngoplasty (EIL) using hyaluronic acid (HA) is an effective treatment for glottic insufficiency in patients with acute unilateral vocal fold paralysis (UVFP). Most patients benefit by showing improvement in voice and quality of life and implied reduced need for permanent laryngoplasty. However, injected HA might resolve within a short period, so its long-term outcomes and the need for secondary procedures need to be clarified. Methods: Patients who underwent EIL with HA for acute UVFP from January 2015 to December 2018 were included. The factors that may associate with the prognosis including voice performance and laryngeal configuration at presentation, the cause of UVFP, and the type of HA for EIL were analyzed. Results: Ninety-four patients were included for analysis, with a mean follow-up period of 25.1 months (95% CI: 22.8–27.4 months). After primary HA injection, 22 patients (23.4%) underwent secondary procedures (rate: 13.1% per person-year), and most (63.6%) of the events occurred after one year from the first injection. The rate of secondary procedures within the first 12 months was 9.0% (14.1% and 4.3% for low-concentrated HA (LHA) and high-concentrated HA (HHA), respectively). The incidence of the secondary procedures was higher in the LHA group (18.2%) (p = 0.026) than in the HHA group (7.5%). Conclusions: The rate of secondary procedures was lower than the prediction based on the resorption time of HA, a finding that could be partly accounted for by both natural nerve recovery and a long-lasting effect of EIL. EIL with HHA had a lower rate of re-treatment than that with LHA, suggesting a better clinical utility for acute UVFP.
Variances in the Expression of mRNAs and miRNAs Related to the Histaminergic System in Endometrioid Endometrial Cancer
Authors: Czerwiński Michał , Bednarska-Czerwińska Anna , Ordon Paweł , Gradzik Magdalena , Oplawski Marcin , Boroń Dariusz , Zientek Hanna , Ogloszka Oskar , Grabarek Beniamin Oskar
Published: October 2021

Research has indicated higher concentrations of histamine and polyamine in endometrioid tissue in comparison with healthy tissue. The aim of this study was to evaluate changes in the expression patterns of messenger RNA (mRNAs) and microRNA (miRNAs) related to the histaminergic system in endometrial samples and whole blood in women with endometrioid endometrial cancer. The study group consisted of 30 women with endometrioid endometrial cancer qualified for hysterectomy (G1 well-differentiated, 15 cases; G2 moderately differentiated, 8 cases; and G3 poorly differentiated, 7 cases). The control group included 30 women with no neoplastic changes during routine gynecological examinations. The molecular analysis consisted of the microarray analysis of mRNAs and miRNAs related to the histaminergic system, reverse-transcription quantitative polymerase chain reaction (RTqPCR), and enzyme-linked immunosorbent assay (ELISA). Out of 65 mRNAs connected with the histaminergic system, 10 differentiate the samples of tissue and blood obtained from patients with endometrioid endometrial cancer in comparison with the control group (p < 0.05). mRNA histamine receptor 1,3 (HRH1, HRH3), and solute carrier family 22 member 3 (SLC23A2) differentiating samples of endometrioid endometrial cancer independent of either G or control. The highest probability of interaction, based on the target score miRDB, between the selected miRNAs and mRNAs was found for the hybrids hsa-miR-1-3p and endothelin 1 (END1), hsa-miR-27a-5β and SLC23A2. The selected mRNA and miRNA transcripts seem to be promising for molecularly targeted therapies in the context of endometrioid endometrial cancer.
Tenofovir Hampers the Efficacy of Sorafenib in Prolonging Overall Survival in Hepatocellular Carcinoma
Authors: Liang Kung-Hao , Chen Sung-Fang , Lin Yu-Hua , Chu Yu-De , Lin Yang-Hsiang , Lai Ming-Wei , Lin Chih-Lang , Yeh Chau-Ting
Published: October 2021

Sorafenib is a first-line treatment for patients with advanced hepatocellular carcinoma (HCC). These patients may simultaneously receive anti-hepatitis B treatment if they are viremic. The N-Acetylgalactosaminyltransferase 14 (GALNT14) gene can serve as a biomarker to guide HCC treatments. However, the enzyme substrates of its gene product, GalNAc-T14 (a glycosyltransferase), remained uncharacterized. Here, we conducted a glycoproteome-wide search for GalNAc-T14 substrates using lectin affinity chromatography followed by tandem mass spectrometry. Seventeen novel GalNAc-T14 substrates were identified. A connective map analysis showed that an antiviral drug, tenofovir, was the leading medicinal compound to down-regulate the expression of these substrates. In vitro assays showed that HCC cells were resistant to sorafenib if pretreated by tenofovir but not entecavir. Clinical analysis showed that the concomitant use of tenofovir and sorafenib was a previously unrecognized predictive factor for unfavorable overall survival (hazard ratio = 2.060, 95% confidence interval = [1.256, 3.381], p = 0.004) in a cohort of 181 hepatitis-B-related, sorafenib-treated HCC patients (concomitant tenofovir versus entecavir treatment; p = 0.003). In conclusion, by conducting a glycoproteome-wide search for GalNAc-T14 substrates, we unexpectedly found that tenofovir was a major negative regulator of GalNAc-T14 substrates and an unfavorable anti-hepatitis B drug in HCC patients receiving sorafenib.
Self-Processing and Self-Face Reaction Time Latencies: A Review
Authors: Gallup Gordon G. , Platek Steven M.
Published: October 2021

In this article, we detail the advantages of self-face identification latencies over more traditional tests of mirror self-recognition. Using reaction time latencies (measured in milliseconds) to identify different dimensions of the self, instead of relying on a simple dichotomous pass/fail mirror mark-test outcome, enables investigators to examine individual differences in self-processing time. This is a significant methodological step forward with important implications. The point of departure for our article is to detail research we and others have conducted on latencies for self-face identification, to show how self-processing occurs in the right side of the brain, how schizophrenia is a self-processing disorder, how self-face reaction time latencies implicate the existence of an underlying multiple modal self-processing system, and to explore ideas for future research.
Cold-Blooded and on Purpose: A Review of the Biology of Proactive Aggression
Authors: Belfry Kimberly D. , Kolla Nathan J.
Published: October 2021

Proactive aggression (PA) is a planned and unprovoked form of aggression that is most often enacted for personal gain or in anticipation of a reward. Frequently described as “cold-blooded” or goal oriented, PA is thought to be associated with low autonomic arousal. With this view in mind, we performed a scoping review of the biological correlates of PA and identified 74 relevant articles. Physiological findings indicated a robust association between PA and reduced resting heart rate, and to a lesser extent a relationship between PA and decreased heart rate and skin conductance reactivity, perhaps indicating dampened sympathetic function. The twin literature identified PA as a heritable trait, but little evidence implicates specific genes in the pathogenesis of PA. Neuroimaging studies of PA pinpoint impaired amygdala function in the assessment and conditioning of aversive stimuli, which may influence the establishment of behavioral patterns. Nodes of the default mode network were identified as possible neural correlates of PA, suggesting that altered function of this network may be involved in the genesis of PA. Given the overlap of PA with reactive aggression and the overall behavioral complexity of PA, it is clear that multiple endophenotypes of PA exist. This comprehensive review surveys the most salient neurobiologically informed research on PA.
HBIM for the Characteristics of Korean Traditional Wooden Architecture: Bracket Set Modelling Based on 3D Scanning
Authors: Youn Hyun-Chul , Yoon Jun-Seop , Ryoo Seong-Lyong
Published: October 2021

Historic building information modelling (HBIM) is a technology that documents and analyses 3D model information for reverse engineering using laser scan and image survey data of buildings having heritage value. In the case of traditional Korean wooden architectures, especially the bracket-sets of buildings, there is a limit to accuracy, owing to non-visible seams. Thus, in this study, mesh modelling is conducted using point-cloud data of the entire Seoikheon building of Jeonju Pungpajigwan, which is a national cultural property of Korea. After dismantling the building, scanning the members and cross-checking the cloud data, it was possible to create a realistic Rhino 3D model that includes joints of the bracket set. Hence, it is possible to implement a 3D model in Revit that reflects the unique shapes and characteristics of traditional wooden architectures. The resultant model not only provides a platform of various historic building information, but it can also be used as a digital twin to understand deformation and damage to wooden joints.
A Tissue Section-Based Near-Infrared Spectroscopical Analysis of Salivary Gland Tumors
Authors: Coopman Renaat , De Bruyne Sander , Speeckaert Marijn , Vermassen Tijl , Vermeersch Hubert , Creytens David , Delanghe Joris
Published: October 2021

SGTs vary in histological behavior. Mucins, a major component in salivary glands, consist of a glycosylated and sialylated protein core. Rapid evolutions in glycobiology have demonstrated the important role of glycoproteins in cancer development. NIR spectroscopy is a method for the biochemical analysis of substrates. NIR spectra can be analyzed using specific chemometrics. Our aim was to explore the diagnostic possibilities of NIR spectroscopy in SGTs. 238 Hematoxylin and Eosine stained (H&E) SGT tissue sections were examined using NIR spectroscopy. 45 deparaffinized tissue sections were treated with neuraminidase to identify wavelengths in the NIR spectrum related to sialylation. NIR spectra were analyzed with chemometrics. NIR spectra could distinguish malignant SGTs from controls and benign SGTs. Prediction models based on the entire spectral range resulted in a 73.1% accurate classification of malignant SGTs and controls, while, based on neuraminidase experimental spectral peak differences (1436 nm; 1713 nm; 1783 nm; 1924 nm; 2032 nm; 2064 nm; 2178 nm; 2216 nm), an improved overall correct classification rate of 91.9% was obtained between healthy subjects and malignant tumors. H&E tissue section-based NIR spectroscopy can identify malignant SGTs from controls, promising an alternative method in the diagnosis of SGTs.
Sarcopenia Predicts Cancer Mortality in Male but Not in Female Patients Undergoing Surgery for Cholangiocellular Carcinoma
Authors: Jördens Markus Sebastian , Heinrichs Lisa , Loosen Sven H. , Wittig Linda , Keitel Verena , Schöler David , Schulze-Hagen Maximilian , Loberg Christina , Antoch Gerald , Knoefel Wolfram Trudo , Luedde Tom , Fluegen Georg , Roderburg Christoph
Published: October 2021

Introduction: Surgery represents the only curative treatment option for patients with cholangiocarcinoma. However, complete tumor resection requires extensive surgery in many patients, and it is still debated which patients represent the ideal candidates for such therapy in terms of overall survival. Sarcopenia has been associated with an adverse outcome for various malignancies, but its role in the context of patients undergoing tumor resection for cholangiocellular adenocarcinoma (CCA) is only poorly understood. Here, we evaluated the role of sarcopenia in the outcome of CCA patients undergoing radical tumor resection. Methods: Pre-operative CT scans were used to assess the skeletal muscle index (L3SMI) as well as the psoas muscle index (L3PMI) in n = 76 patients receiving curative intended surgery for CCA. L3SMI and L3PMI were correlated with clinical and laboratory markers. Results: Patients with a skeletal muscle index or psoas muscle index above an established ideal cut-off (54.26 and 1.685 cm2/m2) showed a significantly better overall survival in Kaplan–Meier Curve analyses (L3SMI: 1814 days (95% CI: 520–3108) vs. 467 days (95% CI: 225–709) days; log rank X2(1) = 7.18, p = 0.007; L3PMI: 608 days (95% CI: 297–919) vs. 87 days (95% CI: 33–141), log rank X2(1) = 18.71; p < 0.001). Notably, these findings, especially for L3PMI, were confirmed in univariate (L3SMI: HR 0.962 (0.936–0.989); p = 0.006; L3PMI: HR 0.529 (0.366–0.766); p ≤ 0.001) and multivariate Cox regression analyses. Further analyses revealed that the prognostic value of both L3SMI and L3PMI was restricted to male patients, while in female patients survival was independent of the individual muscle mass. Conclusion: Measurement of muscle mass from preoperative CT scans represents an easily obtainable tool to estimate patient prognosis following curative surgery. The prognostic value was restricted to male patients, while in female patients these parameters did not reflect the patient outcome.
The C-Circle Biomarker Is Secreted by Alternative-Lengthening-of-Telomeres Positive Cancer Cells inside Exosomes and Provides a Blood-Based Diagnostic for ALT Activity
Authors: Chen Yuan-Yin , Dagg Rebecca , Zhang Yuchen , Lee Joyce H. Y. , Lu Robert , Martin La Rotta Nancy , Sampl Sandra , Korkut-Demirbaş Medina , Holzmann Klaus , Lau Loretta M. S. , Reddel Roger R. , Henson Jeremy D.
Published: October 2021

C-Circles, self-primed telomeric C-strand templates for rolling circle amplification, are the only known alternative-lengthening-of-telomeres (ALT)-specific molecule. However, little is known about the biology of C-Circles and if they may be clinically useful. Here we show that C-Circles are secreted by ALT+ cancer cells inside exosomes, and that a blood-based C-Circle Assay (CCA) can provide an accurate diagnostic for ALT activity. Extracellular vesicles were isolated by differential centrifugation from the growth media of lung adenocarcinoma, glioblastoma, neuroblastoma, osteosarcoma, and soft tissue sarcoma cell lines, and C-Circles were detected in the exosome fraction from all eleven ALT+ cancer cell lines and not in any extracellular fraction from the eight matching telomerase positive cancer cell lines or the normal fibroblast strain. The existence of C-Circles in ALT+ exosomes was confirmed with exosomes isolated by iodixanol gradient separation and CD81-immunoprecipitation, and C-Circles in the exosomes were protected from nucleases. On average, 0.4% of the total ALT+ intracellular C-Circles were secreted in the exosomes every 24 h. Comparing the serum-based and tumor-based CCAs in 35 high risk neuroblastoma patients divided randomly into ALT+ threshold derivation and validation groups, we found the serum-based CCA to have 100% sensitivity (6/6), 70% specificity (7/10), and 81% concordance (13/16). We conclude that the secretion of C-Circles by ALT+ cancer cells in the exosomes provides a stable blood-based biomarker and a potential clinical diagnostic for ALT activity.
Improved Brønsted to Lewis (B/L) Ratio of Co- and Mo-Impregnated ZSM-5 Catalysts for Palm Oil Conversion to Hydrocarbon-Rich Biofuels
Authors: Riyanto Teguh , Istadi Istadi , Jongsomjit Bunjerd , Anggoro Didi D. , Pratama Aryadita Ayu , Faris Muhammad Aviv Al
Published: October 2021

The purposes of this study are to investigate the effect of metal (Co and Mo) impregnation to ZSM-5 catalysts on the Brønsted to Lewis (B/L) ratio as the active sites of cracking reaction, and the catalysts’ performance testing for palm oil cracking to produce hydrocarbon-rich biofuels. Both metals were impregnated on the ZSM-5 catalyst using a wet-impregnation method. The catalysts were characterized using X-ray diffraction (XRD), X-ray Fluorescence (XRF), Scanning Electron Microscopy (SEM), Brunauer–Emmett–Teller (BET), and Pyridine-probed Fourier-Transform Infrared (Py-FTIR) spectroscopy methods. The catalysts were tested on the cracking process of palm oil to biofuels in a continuous fixed-bed catalytic reactor. In order to determine the composition of the organic liquid product (OLP, biofuels), the product was analyzed using a gas chromatography-mass spectrometry (GC-MS) method. The results showed that the co-impregnation of Co and Mo to ZSM-5 highly increased the Brønsted to Lewis acid site (B/L) ratio, although the total number of acid sites decreased. However, the impregnation of Co and Mo on the ZSM-5 decreased the surface area of catalysts due to pore blocking by metals, while the B/L ratio of the catalysts increased. It was obtained that by utilizing Co- and Mo-impregnated ZSM-5 catalysts, the hydrocarbons product selectivity increased from 84.32% to 95.26%; however, the yield of biofuels decreased from 67.57% to 41.35%. The increase in hydrocarbons product selectivity was caused by the improvement of the Brønsted to Lewis (B/L) acid sites ratio.
Gordonia hydrophobica Nitrile Hydratase for Amide Preparation from Nitriles
Authors: Grill Birgit , Horvat Melissa , Schwab Helmut , Gross Ralf , Donsbach Kai , Winkler Margit
Published: October 2021

The active pharmaceutical ingredient levetiracetam has anticonvulsant properties and is used to treat epilepsies. Herein, we describe the enantioselective preparation of the levetiracetam precursor 2-(pyrrolidine-1-yl)butanamide by enzymatic dynamic kinetic resolution with a nitrile hydratase enzyme. A rare representative of the family of iron-dependent nitrile hydratases from Gordonia hydrophobica (GhNHase) was evaluated for its potential to form 2-(pyrrolidine-1-yl)butanamide in enantioenriched form from the three small, simple molecules, namely, propanal, pyrrolidine and cyanide. The yield and the enantiomeric excess (ee) of the product are determined most significantly by the substrate concentrations, the reaction pH and the biocatalyst amount. GhNHase is also active for the hydration of other nitriles, in particular for the formation of N-heterocyclic amides such as nicotinamide, and may therefore be a tool for the preparation of various APIs.
Advances in Nonprecious Metal Homogeneously Catalyzed Formic Acid Dehydrogenation
Authors: Iglesias Manuel , Fernández-Alvarez Francisco J.
Published: October 2021

Formic acid (FA) possesses a high volumetric concentration of H2 (53 g L−1). Moreover, it can be easily prepared, stored, and transported. Therefore, FA stands out as a potential liquid organic hydrogen carrier (LOHC), which allows storage and transportation of hydrogen in a safe way. The dehydrogenation to produce H2 and CO2 competes with its dehydration to give CO and H2O. For this reason, research on selective catalytic FA dehydrogenation has gained attention in recent years. Several examples of highly active homogenous catalysts based on precious metals effective for the selective dehydrogenation of FA have been reported. Among them are the binuclear iridium-bipyridine catalysts described by Fujita and Himeda et al. (TOF = 228,000 h−1) and the cationic species [IrClCp*(2,2′-bi-2-imidazoline)]Cl (TOF = 487,500 h−1). However, examples of catalytic systems effective for the solventless dehydrogenation of FA, which is of great interest since it allows to reduce the reaction volume and avoids the use of organic solvents that could damage the fuel cell, are scarce. In this context, the development of transition metal catalysts based on cheap and easily available nonprecious metals is a subject of great interest. This work contains a summary on the state of the art of catalytic dehydrogenation of FA in homogeneous phase, together with an account of the catalytic systems based on non-precious metals so far reported.
Boron Neutron Capture Therapy (BNCT) for Cutaneous Malignant Melanoma Using 10B-p-Boronophenylalanine (BPA) with Special Reference to the Radiobiological Basis and Clinical Results
Authors: Fukuda Hiroshi
Published: October 2021

BNCT is a radiotherapeutic method for cancer treatment that uses tumor-targeting 10B-compounds. BNCT for cutaneous melanoma using BPA, a phenylalanine derivative, was first initiated by Mishima et al. in 1987. This article reviews the radiobiological basis of melanoma control and damage to normal tissues as well as the results of clinical studies. Experimental studies showed that the compound biological effectiveness (CBE) values of the 10B (n, α)7Li reaction for melanoma control ranged from 2.5 to 3.3. The CBE values of the 10B (n, α)7Li reaction for skin damage ranged from 2.4 to 3.7 with moist desquamation as the endpoint. The required single radiation dose for controlling human melanoma was estimated to be 25 Gy-Eq or more by analyzing the 50% tumor control dose data of conventional fractionated radiotherapy. From the literature, the maximum permissible dose to human skin by single irradiation was estimated to be 18 Gy-Eq. With respect to the pharmacokinetics of BPA in patients with melanoma treated with 85–350 mg/kg BPA, the melanoma-to-blood ratio ranged from 2.1–3.8 and the skin-to-blood ratio was 1.31 ± 0.22. Good local tumor control and long-term survival of the patients were achieved in two clinical trials of BNCT conducted in Japan.
DNA Methylation and Schizophrenia: Current Literature and Future Perspective
Authors: Magwai Thabo , Shangase Khanyiso Bright , Oginga Fredrick Otieno , Chiliza Bonginkosi , Mpofana Thabisile , Xulu Khethelo Richman
Published: October 2021

Schizophrenia is a neuropsychiatric disorder characterized by dissociation of thoughts, idea, identity, and emotions. It has no central pathophysiological mechanism and precise diagnostic markers. Despite its high heritability, there are also environmental factors implicated in the development of schizophrenia. Epigenetic factors are thought to mediate the effects of environmental factors in the development of the disorder. Epigenetic modifications like DNA methylation are a risk factor for schizophrenia. Targeted gene approach studies attempted to find candidate gene methylation, but the results are contradictory. Genome-wide methylation studies are insufficient in literature and the available data do not cover different populations like the African populations. The current genome-wide studies have limitations related to the sample and methods used. Studies are required to control for these limitations. Integration of DNA methylation, gene expression, and their effects are important in the understanding of the development of schizophrenia and search for biomarkers. There are currently no precise and functional biomarkers for the disorder. Several epigenetic markers have been reported to be common in functional and peripheral tissue. This makes the peripheral tissue epigenetic changes a surrogate of functional tissue, suggesting common epigenetic alteration can be used as biomarkers of schizophrenia in peripheral tissue.
EphA2 Expression in Bone Sarcomas: Bioinformatic Analyses and Preclinical Characterization in Patient-Derived Models of Osteosarcoma, Ewing’s Sarcoma and Chondrosarcoma
Authors: Giordano Giorgia , Merlini Alessandra , Ferrero Giulio , Mesiano Giulia , Fiorino Erika , Brusco Silvia , Centomo Maria Laura , Leuci Valeria , D’Ambrosio Lorenzo , Aglietta Massimo , Sangiolo Dario , Grignani Giovanni , Pignochino Ymera
Published: October 2021

Bone sarcomas are a group of heterogeneous malignant mesenchymal tumors. Complete surgical resection is still the cornerstone of treatment, but, in the advanced/unresectable setting, their management remains challenging and not significantly improved by target- and immuno-therapies. We focused on the tyrosine kinase Eph type-A receptor-2 (EphA2), a key oncoprotein implicated in self-renewal, angiogenesis, and metastasis, in several solid tumors and thus representing a novel potential therapeutic target. Aiming at better characterizing its expression throughout the main bone sarcoma histotypes, we investigated EPHA2 expression in the Cancer Cell Lines Encyclopedia and in public datasets with clinical annotations. looking for correlations with molecular, histopathological and patients’ features and clinical outcomes in a total of 232 osteosarcomas, 197 Ewing’s sarcomas, and 102 chondrosarcomas. We observed EPHA2 expression in bone sarcoma cell lines. We demonstrated higher EPHA2 expression in tumor tissues when compared to normal counterparts. A significant correlation was found between EPHA2 expression and Huvos grade (osteosarcoma) and with worse overall survival (dedifferentiated chondrosarcoma). Next, we characterized EPHA2 expression and activation in bone sarcoma primary tissues and in patient-derived xenografts generated in our laboratory to verify their reliability as in vivo models of osteosarcoma, Ewing’s sarcoma and chondrosarcoma. Furthermore, for the first time, we demonstrated EPHA2 expression in chondrosarcoma, suggesting its potential key role in this histotype. Indeed, we observed a significant dose-dependent antitumor effect of the EphA2-inhibitor ALW-II-41-27 in patient-derived in vitro models. In conclusion, EphA2 targeting represents a promising novel therapeutic strategy against bone sarcomas.
Development of Functional Thyroid C Cell-like Cells from Human Pluripotent Cells in 2D and in 3D Scaffolds
Authors: Abu-Bonsrah Kwaku Dad , Newgreen Donald F. , Dottori Mirella
Published: October 2021

Medullary thyroid carcinoma contributes to about 3–4% of thyroid cancers and affects C cells rather than follicular cells. Thyroid C cell differentiation from human pluripotent stem cells has not been reported. We report the stepwise differentiation of human embryonic stem cells into thyroid C cell-like cells through definitive endoderm and anterior foregut endoderm and ultimobranchial body-like intermediates in monolayer and 3D Matrigel culture conditions. The protocol involved sequential treatment with interferon/transferrin/selenium/pyruvate, foetal bovine serum, and activin A, then IGF-1 (Insulin-like growth factor 1), on the basis of embryonic thyroid developmental sequence. As well as expressing C cell lineage relative to follicular-lineage markers by qPCR (quantitative polymerase chain reaction) and immunolabelling, these cells by ELISA (enzyme-linked immunoassay) exhibited functional properties in vitro of calcitonin storage and release of calcitonin on calcium challenge. This method will contribute to developmental studies of the human thyroid gland and facilitate in vitro modelling of medullary thyroid carcinoma and provide a valuable platform for drug screening.
Opsoclonus-Myoclonus Syndrome in Children and Adolescents: A Therapeutic Challenge
Authors: Auconi Marina , Papetti Laura , Ruscitto Claudia , Ferilli Michela Ada Noris , Ursitti Fabiana , Sforza Giorgia , Vigevano Federico , Valeriani Massimiliano
Published: October 2021

Opsoclonus-myoclonus syndrome (OMS) is a neurological non-fatal disease that usually responds to immunotherapies. However, the real challenge is to counteract the high frequency of relapses and long-term developmental sequelae. Since the OMS is extremely rare, a common consensus regarding therapeutic guidelines is still lacking. The goals of this study were to test whether ACTH was superior to other immunotherapies and to investigate whether an early treatment could improve the outcome. Sixteen children affected by OMS were retrospectively reviewed. Eight children had a neuroblastic tumor. The other eight patients were affected by non-paraneoplastic OMS. Overall, the most commonly used treatment was corticotherapy (n = 11). However, ACTH (n = 10), rituximab (n = 7), immunoglobulins (n = 4), cyclophosphamide (n = 3), and mycophenolate (n = 2) were also administered. ACTH was associated with a high percentage of patients who healed (80%) and, as a first-line therapy, was associated with a lower incidence of relapses. An early treatment was associated with a favorable long-term outcome. Long-term sequelae occurred in 42% of patients who were treated early and in all of those who were treated late. It is advisable for the affected children to be identified at an early time, as they may benefit from an early treatment. ACTH represents an effective treatment with a high probability of recovery and low rate of relapses.
Significant Leukocytosis with Hypereosinophilia Secondary to Trichuris trichiura in Adult: A Case Report
Authors: Abdullah Nasturah , Baharudin Noorhida , Mohd Rustam Farah Roslinda , Khalid Zalizah
Published: October 2021

Eosinophilic leukocytosis can be attributed to a number of clinical conditions such as parasitic infection, allergies, and neoplasms. Parasitic infection is the main cause of eosinophilia; however, a marked leukocytosis with hypereosinophilia secondary to Trichuris trichiura in adults has not been previously reported. We describe a case of a 39-year-old man who presented with fever and diarrhea. The investigation revealed a white blood cell (WBC) count of 20.69 × 109/L with an absolute eosinophil count of 12.44 × 109/L. Fecal microscopic examination demonstrated T. trichuria eggs. The WBC count returned to normal following treatment with albendazole. The literature pertaining to hematological findings associated with Trichuris trichiura is explored in this report. This case highlights that a significant elevation of leukocyte count with hypereosinophilia can be one of the manifestations of trichuriasis infection in adults. Empirical treatment with anti-helminthic agents may play a role in suspected cases to avoid severe complications, such as Trichuris dysentery syndrome.