bluuebunny/crossref_metadata_2025 huggingface dataset:
Hydrogeophysical Characterization of Fractured Aquifers for Groundwater Exploration in the Federal District of Brazil
Authors: Hussain Yawar , Campos José Eloi Guimarães , Borges Welitom Rodrigues , Uagoda Rogério Elias Soares , Hamza Omar , Havenith Hans-Balder
Published: March 2022

The present study applies a geophysical approach to the Federal district of Brazil, a challenging hydrogeologic setting that requires improved investigation to enhance groundwater prospecting to meet the rising water demand. The geophysical characterization of a complex hard-rock aquifer sub-system was conducted using direct current (DC) electrical resistivity tomography (ERT) integrated with surface geological information. With a total of twenty-seven ERT profiles, the resistivity acquisition was carried out using a dipole-dipole array of electrodes with an inter-electrode spacing of 10 m. Based on resistivity ranges, the interpretation of the inverted resistivity values indicated a ground profile consisting of upper dry soil, saprolite, weathered, and fresh bedrock. Along with this layered subsurface stratigraphy, the approach allowed us to map the presence of significant hydrogeological features sharp contrasting anomalies that may suggest structural controls separating high-resistivity (≥7000 Ω m) and low-resistivity (<7000 Ω m) conducting zones in the uppermost 10 m of the ground. The assumed impacts of these features on groundwater development are discussed in light of the Brasilia aquifer settings.
Explicit Solution to Large Deformation of Cantilever Beam by Improved Homotopy Analysis Method II: Vertical and Horizontal Displacements
Authors: Li Yinshan , Li Xinye , Xie Chen , Huo Shuhao
Published: March 2022

Explicit solutions to vertical and horizontal displacements are derived for large deformation of a cantilever beam under point load at the free end by an improved homotopy analysis method (IHAM). Quadratic and cubic nonlinear differential equations are adopted to construct more proficient nonlinear equations for vertical and horizontal displacements respectively combined with their currently available nonlinear displacement equations. Higher-order nonlinear iterative homotopy equations are established to solve the vertical and horizontal displacements by combining simultaneous equations of the constructed nonlinear equations and the auxiliary linear equations. The convergence range of vertical displacement is extended by the homotopy-Páde approximation. The explicit solutions to the vertical and horizontal displacements are in favorable agreements with the respective exact solutions. The convergence ranges for a relative error of 1% by the improved homotopy analysis method for vertical and horizontal displacements increases by 60% and 7%, respectively. These explicit formulas are helpful in practical engineering design for very slender structures, such as high-rise buildings and long bridges.
Effect of MetaFoundation on the Seismic Responses of Liquid Storage Tanks
Authors: Farajian Mostafa , Khodakarami Mohammad Iman , Sharafi Pejman
Published: March 2022

Cylindrical liquid storage tanks are vital lifeline structures, playing a critical role in industry and human life. Damages to these structures during previous earthquakes indicate their vulnerability against seismic events. A novel strategy to reduce the seismic demands in the structures is the use of metamaterials, being periodically placed in the foundation, called MetaFoundation (MF). The periodic configuration of metamaterials can create a stop band, leading to a decrease in wave propagation in the foundation. The aim of this paper is to study the effect of MF on the dynamic behaviour of liquid storage tanks. To that end, the governing equations of motion of the liquid storage tank equipped with MF are derived and solved in the time domain to obtain the time history of the responses under a set of ground motions. Then, the peak responses of tanks, mounted on MF, are compared with the corresponding responses in the fixed base condition. Besides, a parametric study is performed to assess the effect of the predominant frequency of earthquakes, the number of layers of metamaterials, the thickness of soft material, and the damping ratios of soft material on the performance of the MF. The obtained results indicate that the MF improves the dynamic behaviour of the squat tank, in which the mean ratio of responses using MF to the ones in the fixed base conditions equals 0.551 for impulsive displacement, overturning moment, and base shear.
Design of an Origami Crawling Robot with Reconfigurable Sliding Feet
Authors: Fei Fei , Leng Ying , Xian Sifan , Dong Wende , Yin Kuiying , Zhang Guanglie
Published: March 2022

This paper presents a novel reconfigurable crawling robot based on an origami twisted tower structure. Compared with other origami structures, the twisted tower can achieve extension, contraction, and bending motions as the flexible body parts in robotic designs. The kinematics of a one-layer twisted tower were analyzed with rotation and bending angles. The mechanical properties of the one-layer, two-layer, and four-layer twisted towers were compared with compression experiments. A rope-motor-driven crawling robot was designed to realize forward, backward, left-turning, and right-turning motions. Two types of crawling robot with specific sliding feet were developed to adapt to different ground conditions: one made of rubber, and the other embedded with an electromagnet. The experimental results show that the proposed robots can move at an average forward speed of 0.48 cm/s on a wooden desk, and at 0.52 cm/s forward speed or 0.65 cm/s backward speed on an iron platform.
Digitalizing Maritime Containers Shipping Companies: Impacts on Their Processes
Authors: Sanchez-Gonzalez Pedro-Luis , Díaz-Gutiérrez David , Núñez-Rivas Luis R.
Published: March 2022

Key analysts are emphasizing the importance of the digitalization especially of the supply chain. This work aims to improve maritime shipping companies by introducing digitalization in their operations. This objective is achieved analyzing the impact of maritime container shipping companies’ digitalization. This analysis requires as input the Business Process Model (BPMo) and an inventory of digital applications to verify how the BPMo changes when deploying the applications, define the prerequisites necessary for this deployment, and identify the key performance indicators (KPIs) to track it. The impact of the deployment of the applications has been quantified by using four performance dimensions: Costs, Time, Quality, and Flexibility. The results show that the impacts are different per application, with changes in the processes, the addition of new ones, and the decommissioning of others. The impact of digitalization is high when trying to deploy all the applications at the same time. Companies can leverage this work, which requires reviewing the documented impacts in their processes and the applications’ prerequisites as well as updating their existing balanced scorecard, incorporating the application’s KPIs. A list of 10 applications has been identified as “quick wins”; then, applications can be the starting point for digitalizing a company.
Assessment of Visual Representation Methods of Linear Discontinuous Deformation Zones in the Right-of-Way
Authors: Wróblewska Magdalena , Grygierek Marcin
Published: March 2022

Mining impacts on the ground surface may manifest themselves, inter alia, in the form of continuous and discontinuous deformations. Discontinuous deformations significantly deteriorate the condition of the road surface, posing a threat to the safety of use. Therefore, in mining areas, it is necessary to carry out an ongoing inspection of the condition of objects and thus determine the need and scope of their repair. The key method of assessing the scope of the surface repair needed is to observe the road surface. This article presents the results of selected measurement methods carried out near discontinuous deformation zones in the right-of-way. The use of measurements with the use of a laser profilograph allowed determining the evenness of the tested pavement. Additionally, geodetic methods were used: leveling and GPS satellite positioning, to determine the displacement of points forming the observation lines along the right-of-way. In order to identify, in detail, linear discontinuous deformations, non-ceiling photogrammetry was used with the use of an unmanned aerial vehicle. The comparison of selected methods and their advantages and disadvantages allowed for the assessment of their usefulness in visual representation zones of linear discontinuous deformations. The results of this research show the usefulness of laser profilographs, while the greatest detail of the measurement was obtained by low-ceiling photogrammetry with the use of an unmanned aerial vehicle.
Geology and Petrogeochemistry of Lijiapuzi Nb-Ta Granitic Pegmatite Deposit: Implications for Ore Genesis and Prospecting
Authors: Fu Jianfei , Yao Yuzeng , Liu Jing , Li Zining , Jia Sanshi , Pang Yemao
Published: March 2022

Most of the rare metal pegmatite deposits in China lie in West, Central and South China, and the Lijiapuzi Nb-Ta deposit is the only pegmatite-type Nb-Ta deposit in Northeast China, therefore a detailed study of the Lijiapuzi deposit is of great importance to the metallogeny and exploration of rare metal deposits in Northeast China. The Nb-Ta bearing pegmatites in Lijiapuzi district are composed of a microcline wall zone, a muscovite (lepidolite)-albite intermediate zone and a quartz core, and the rare metal mineralization mainly occurs in the intermediate zone and is intimately related to the albitization. The lithogeochemical features indicate that Lijiapuzi pegmatoids are rich in silicon and alkaline, poor in calcium, magnesium, titanium and phosphorus, and belong to peraluminous granitoid rocks. The enrichment of large ion lithophile elements (LILEs) and depletion of high field-strength elements (HFSEs), the distinct right-inclined REE pattern with obvious Eu negative anomaly, lower ratio of Nb/Ta and higher ratio of La/Nb and Rb/Sr indicate that the pegmatite was of a crustal origin and formed in relatively extensional tectonic setting of post-orogenesis. The pegmatites in Lijiapuzi area can be divided into two categories, i.e., the NW-trending pegmatites are shorter and thicker, with obvious zoning and localized in the upper part of the near-surface, while the NE-trending pegmatites are longer, thinner, devoid of zoning and localized in the lower part of the district. This probably means that excellent ore prospecting potential exists in the lower part of the Lijiapuzi district.
On the Applicability of Approximate Rolling and Sliding Contact Algorithms in Anisothermal Problems with Thermal Softening
Authors: Wölfle Christoph Hubertus , Krempaszky Christian , Werner Ewald
Published: March 2022

The residual stress approximation methods formulated by McDowell and Moyar, Jiang and Sehitoglu, and McDowell for rolling and sliding contact problems are reconsidered in the context of single anisothermal loading cycles and isotropic hardening. A consistent extention to incorporate thermal softening is developed and the generalized thermoelastoplastic algorithms are cast into a proper predictor–corrector formulation. Detailed explicit and implicit numerical integration strategies are presented and validated using specifically designed finite element models that conform to the underlying mechanical assumptions. Then, the applicability of the approximate algorithms to anisothermal problems with isotropic hardening and thermal softening is analyzed by assuming a rate-independent Johnson–Cook-type yield stress model and by comparing the obtained transient and residual stresses to results from full-scale finite element half-space models under varying loading and strain-hardening intensities. An in-depth, comparative discussion on the adequacy of the algorithms in conjunction with the justification of their respective mechanical simplifications follows. Sufficiently strong strain hardening is found to be a prerequisite for accurate predictions, and Jiang and Sehitoglu’s approach is deemed to be preferable for the considered type of problem. The conclusions drawn from the investigations are discussed in the context of common applications with particular emphasis on manufacturing process modeling and the corresponding guidelines are proposed for such use cases.
Potential of Time-Resolved Serial Femtosecond Crystallography Using High Repetition Rate XFEL Sources
Authors: de Wijn Raphaël , Melo Diogo V. M. , Koua Faisal H. M. , Mancuso Adrian P.
Published: March 2022

This perspective review describes emerging techniques and future opportunities for time-resolved serial femtosecond crystallography (TR-SFX) experiments using high repetition rate XFEL sources. High repetition rate sources are becoming more available with the European XFEL in operation and the recently upgraded LCLS-II will be available in the near future. One efficient use of these facilities for TR-SFX relies on pump–probe experiments using a laser to trigger a reaction of light-responsive proteins or mix-and-inject experiments for light-unresponsive proteins. With the view to widen the application of TR-SFX, the promising field of photocaged compounds is under development, which allows the very fast laser triggering of reactions that is no longer limited to naturally light-responsive samples. In addition to reaction triggering, a key concern when performing an SFX experiment is efficient sample usage, which is a main focus of new high repetition rate-compatible sample delivery methods.
Joule-Heating Annealing to Increase Organic Solar Cells Performance: A Comparative Study
Authors: Méndez Maria , Fernández Daniel , Viterisi Aurelien , Martínez-Ferrero Eugenia , Palomares Emilio
Published: March 2022

In this work, we present our results on the influence of post-deposition treatments on the morphology and optical properties of photoactive films made of small molecules and their subsequent effect on the performance of photovoltaic (PV) devices. We have chosen DPP(TBFu)2:PC61BM as a benchmark model system and compared a novel joule-heating annealing (JHA) treatment with the widely used temperature annealing (TA) and solvent annealing (SVA) treatments. Detailed characterization of the morphology of the active layer and the performance of the devices suggests that JHA is a valuable post-treatment technique that provides fast information about the development of domains in the photoactive layer. Finally, in this context, solar cells on flexible indium tin oxide (ITO) substrates, made of polyethylene terephthalate (PET), were fabricated and analyzed.
Numerical Study of Wave Effect on Aircraft Water-Landing Performance
Authors: Chen Jichang , Xiao Tianhang , Wang Mingzhen , Lu Yujin , Tong Mingbo
Published: March 2022

Aircraft, such as amphibious planes, airliners, helicopters and re-entry capsules, are frequently subject to impacting loads from water-landing/ditching on various free surfaces, especially under wave conditions. Understanding and quantifying the water-landing/ditching performance on wave surfaces are of fundamental important for the design and certification of crashworthiness in the field of aerospace engineering. This study aims to numerically assess the effect of wave surface on water-landing process of an amphibious aircraft. The numerical implementation is realized in Reynolds-averaged Navier–Stokes (RANS) framework by combining finite volume method (FVM), volume of fluid (VOF) approach and velocity-inlet wavemaker. The temporal-spatial characteristic of numerical wave and the accuracy of presented model are, respectively, validated by analytical wave and convergence studies. The aircraft landing simulations with different free surface conditions, i.e., calm water, regular wave with different wave heights are then performed and quantitatively compared through several physical parameters, including acceleration, velocity, pressure, pitch angle and free surface deformation. It was found that the aircraft regular wave-landing process experiences several unique stages comparing with the calm-water-landing case. The results clearly confirm that wave surface can influence the aircraft landing performance to a great extent. The fundamental mechanism is found to be that the wave surface slope and wave particle velocity remarkably change the impacting position and effective impacting velocity of the aircraft.
Aesthetic Quality Properties of Carbonate Breccias Associated with Textural and Compositional Factors: Marrón Emperador Ornamental Stone (Upper Cretaceous, Southeast Spain)
Authors: Muñoz-Cervera Maria Concepción , Rodriguez-Garcia Miguel Ángel , Cañaveras Juan Carlos
Published: March 2022

The aesthetic properties of ornamental stones, including colour, texture, and the presence or absence of discontinuities, are influential in their use and marketing. This is particularly critical in brecciated rocks such as the Marrón Emperador (ME) ornamental stone, a dark brown breccia dolostone (Upper Cretaceous, southeast Spain). ME shows a high chromatic and textural variability, which is one of its most appreciated commercial features. Through a petrographic, mineralogical, geochemical and colourimetric study of samples obtained from quarries, outcrops and/or drilling cores, several quality categories have been established, as well as the relationship between the aesthetic properties of ME ornamental stone with its compositional and textural factors. Three main types of breccia constitute the ME exploitable lithotect: crackle and mosaic packbreccias, and rubble floatbreccias. Breccia clasts are mainly composed of hypidiotopic-idiotopic medium- to coarsely-crystalline dolosparites, microcrystalline dolosparites and dolomicrites. Results show that diagenetic processes are mainly responsible for the colour of ME dolostones, revealing that the Sr content is a key factor. The darker brown dolomites always show a higher Sr content, where other typical chromophore elements in dolomites, such as Fe and Mn, do not present this correlation. This study provides evidence for the complexity of processes and factors that are responsible for aesthetic quality features in ornamental stones.
Channelling the Unknown: Noise in Art Ecosystems
Authors: Goodfellow Paul
Published: March 2022

At both the individual and societal levels, we are entangled within environmental, social, and technological systems that shape our material and emotional states. Contemporary art needs to integrate and challenge the information circulating within these interacting systems to address our increasingly complex lifeworld. This systemic understanding emerged in the 1960s as part of a broader growth in relational thinking within the natural and social sciences, which extended the conceptual boundaries of the artwork. The ecosystem, a model originally developed within ecology, is an example of a systems model as it describes the flow of matter, energy, and information through the physical world. This model has evolved into a powerful analogical tool to describe contemporary culture’s entanglement with nature and technology. The ecosystem model is invoked here to describe how information flows through the artwork. The paper suggests that art is a vital form of communication as it can channel noise or unknown information. This channelling is demonstrated with the artwork, The Creation Myth (1998), by Jason Rhoades. This work anticipated the convergence of natural and technological systems, and it demonstrates the ability of the arts to channel unknown messages or noise, thereby disrupting the dominant signals of contemporary culture.
Stationary Battery Thermal Management: Analysis of Active Cooling Designs
Authors: Hailu Getu , Henke Martin , Petersen Todd
Published: March 2022

Stationary battery systems are becoming more prevalent around the world, with both the quantity and capacity of installations growing at the same time. Large battery installations and uninterruptible power supply can generate a significant amount of heat during operation; while this is widely understood, current thermal management methods have not kept up with the increase of stationary battery installations. Active cooling has long been the default approach of thermal management for stationary batteries; however, there is no academic research or comparative studies available for this technology. The present work presents assessment of different active cooling methods through an experimentally validated computational fluid dynamics simulation. Following model validation, several cooling system configurations were analyzed, including effects from implementing either a perforated vent plate or vortex generators. The vent plate was observed to greatly increase cooling performance while simultaneously promoting temperature uniformity between batteries. Vortex generators were shown to marginally increase cooling performance, yet, future research is recommended to study the effects and improvement of the design. The average battery temperature for the vented model is reduced by approximately 5.2 °C, while the average temperature differential among the batteries was only 2.7 °C, less than the recommend value (3 °C) by ASHRAE/IEEE Standards.
A Combined System Metrics Approach to Cloud Service Reliability Using Artificial Intelligence
Authors: Chhetri Tek Raj , Dehury Chinmaya Kumar , Lind Artjom , Srirama Satish Narayana , Fensel Anna
Published: March 2022

Identifying and anticipating potential failures in the cloud is an effective method for increasing cloud reliability and proactive failure management. Many studies have been conducted to predict potential failure, but none have combined SMART (self-monitoring, analysis, and reporting technology) hard drive metrics with other system metrics, such as central processing unit (CPU) utilisation. Therefore, we propose a combined system metrics approach for failure prediction based on artificial intelligence to improve reliability. We tested over 100 cloud servers’ data and four artificial intelligence algorithms: random forest, gradient boosting, long short-term memory, and gated recurrent unit, and also performed correlation analysis. Our correlation analysis sheds light on the relationships that exist between system metrics and failure, and the experimental results demonstrate the advantages of combining system metrics, outperforming the state-of-the-art.
Microbial Diversity and Safety in Fermented Beverages
Authors: Chaves-López Clemencia , Cordero-Bueso Gustavo
Published: March 2022

For thousands of years, humans have exploited the natural process of fermentation of various foods to preserve them, and to enjoy the changes in the sensory characteristics that could be produced [...]
Correlation between Lymphocyte-to-Monocyte Ratio (LMR), Neutrophil-to-Lymphocyte Ratio (NLR), Platelet-to-Lymphocyte Ratio (PLR) and Tumor-Infiltrating Lymphocytes (TILs) in Left-Sided Colorectal Cancer Patients
Authors: Gawiński Cieszymierz , Michalski Wojciech , Mróz Andrzej , Wyrwicz Lucjan
Published: March 2022

Colorectal cancer (CRC) is one of the leading causes of cancer-related mortality worldwide. Novel markers are required in order to select high-risk patients and better adjust the treatment. Both peripheral and local markers of cancer-related inflammation (CRI) such as lymphocyte-to-monocyte ratio (LMR), neutrophil-to-lymphocyte ratio (NLR) or platelet-to-lymphocyte ratio (PLR) and tumor-infiltrating lymphocytes (TILs) have been thoroughly investigated in recent years and deemed to be highly prognostic. We hypothesized that there is an association between local and peripheral CRI indices and that blood-based biomarkers may serve as a surrogate of TILs. We retrospectively analyzed 87 patients with locally advanced left-sided CRC treated with radical-intent surgery in the Maria Skłodowska-Curie National Research Institute of Oncology in Warsaw, Poland, between January 2014 and December 2015. Fifty patients were found eligible for the study. The patients were divided in terms of pre-treatment values of systemic inflammatory response (SIR) markers into LMR/NLR/PLR-high and low groups. We evaluated the resected specimens by immunohistochemistry in order to assess the densities of CD3+ and CD8+ lymphocytes in the center of the tumor and in the invasive margin. We found that the level of CD3+ lymphocytes in the center of the tumor was statistically significantly higher in patients with low pre-treatment NLR (p = 0.044); however, no correlation between any of the SIR markers and CD3+ or CD8+ TILs was observed. Five-year overall survival (OS) was longer in patients with high LMR (p < 0.001), low NLR (p = 0.001) and low PLR (p = 0.095). No correlation between the density of TILs and OS was demonstrated. In conclusion, based on our study, peripheral blood-based markers and CD3+ and CD8+ TILs are not interrelated.
The Proteome of Antibody-Mediated Rejection: From Glomerulitis to Transplant Glomerulopathy
Authors: Chauveau Bertrand , Raymond Anne-Aurélie , Di Tommaso Sylvaine , Visentin Jonathan , Vermorel Agathe , Dugot-Senant Nathalie , Dourthe Cyril , Dupuy Jean-William , Déchanet-Merville Julie , Duong Van Huyen Jean-Paul , Rabant Marion , Couzi Lionel , Saltel Frédéric , Merville Pierre
Published: March 2022

Antibody-mediated rejection (ABMR) is the leading cause of allograft failure in kidney transplantation. Its histological hallmark is represented by lesions of glomerulitis i.e., inflammatory cells within glomeruli. Current therapies for ABMR fail to prevent chronic allograft damage i.e., transplant glomerulopathy, leading to allograft loss. We used laser microdissection of glomeruli from formalin-fixed allograft biopsies combined with mass spectrometry-based proteomics to describe the proteome modification of 11 active and 10 chronic active ABMR cases compared to 8 stable graft controls. Of 1335 detected proteins, 77 were deregulated in glomerulitis compared to stable grafts, particularly involved in cellular stress mediated by interferons type I and II, leukocyte activation and microcirculation remodeling. Three proteins extracted from this protein profile, TYMP, WARS1 and GBP1, showed a consistent overexpression by immunohistochemistry in glomerular endothelial cells that may represent relevant markers of endothelial stress during active ABMR. In transplant glomerulopathy, 137 proteins were deregulated, which favor a complement-mediated mechanism, wound healing processes through coagulation activation and ultimately a remodeling of the glomerular extracellular matrix, as observed by light microscopy. This study brings novel information on glomerular proteomics of ABMR in kidney transplantation, and highlights potential targets of diagnostic and therapeutic interest.
A Framework for Prefabricated Component Hoisting Management Systems Based on Digital Twin Technology
Authors: Zhao Yuhong , Cao Cunfa , Liu Zhansheng
Published: March 2022

The hoisting of prefabricated components (PCs) is a key step during the construction of prefabricated buildings. Aiming at the problems existing in the control of PC hoisting, an innovative hoisting management system framework based on the digital twin (DT) is established in this paper. The system framework comprehensively utilizes the building information model (BIM) and Internet of Things (IoT) to establish a digital twin model (DTm) for PC hoisting control and uses Dijkstra’s algorithm to conduct hoisting route planning according to the BIM data in the model. Meanwhile, long-range radio (LoRa) technology was used for data acquisition and transmission to monitor the movement state of the PCs in the hoisting process. By testing it in a prefabricated building project, the DT control method was conducted to realize the functions of real-time information collection, hoisting path planning and PC positioning, which proved the feasibility and effectiveness of the method. As a key technology to realize intelligent manufacturing, DT has been widely studied in academia. The DTm of the hoisting process of PCs is established in this study; it improves the level of intelligent management of prefabricated building construction and provides a new idea for intelligent building construction.
Functional Ex Vivo Tissue-Based Chemotherapy Sensitivity Testing for Breast Cancer
Authors: Ladan Marjolijn M. , Meijer Titia G. , Verkaik Nicole S. , Komar Zofia M. , van Deurzen Carolien H. M. , den Bakker Michael A. , Kanaar Roland , van Gent Dik C. , Jager Agnes
Published: March 2022

Background chemotherapy is part of most breast cancer (BC) treatment schedules. However, a substantial fraction of BC tumors does not respond to the treatment. Unfortunately, no standard biomarkers exist for response prediction. Therefore, we aim to develop ex vivo sensitivity assays for two types of commonly used cytostatics (i.e., platinum derivates and taxanes) on organotypic BC tissue slices. Methods: Ex vivo cisplatin sensitivity assays were established using organotypic tissue slices derived from the surgical resection material of 13 primary BCs and 20 fresh histological biopsies obtained from various metastatic sites. Furthermore, tissue slices of 10 primary BCs were used to establish a docetaxel ex vivo sensitivity assay. Results: Cisplatin sensitivity was assessed by tissue morphology, proliferation and apoptosis, while the relative increase in the mitotic index was discriminative for docetaxel sensitivity. Based on these read-outs, a scoring system was proposed to discriminate sensitive from resistant tumors for each cytostatic. We successful completed the cisplatin sensitivity assay on 12/16 (75%) biopsies as well. Conclusions: We developed an ex vivo cisplatin and docetaxel assay on BC slices. We also adapted the assay for biopsy-sized specimens as the next step towards the correlation of ex vivo test results and in vivo responses.
Innate and Adaptive Immunopathogeneses in Viral Hepatitis; Crucial Determinants of Hepatocellular Carcinoma
Authors: Zaki Marco Y. W. , Fathi Ahmed M. , Samir Samara , Eldafashi Nardeen , William Kerolis Y. , Nazmy Maiiada Hassan , Fathy Moustafa , Gill Upkar S. , Shetty Shishir
Published: March 2022

Viral hepatitis B (HBV) and hepatitis C (HCV) infections remain the most common risk factors for the development of hepatocellular carcinoma (HCC), and their heterogeneous distribution influences the global prevalence of this common type of liver cancer. Typical hepatitis infection elicits various immune responses within the liver microenvironment, and viral persistence induces chronic liver inflammation and carcinogenesis. HBV is directly mutagenic but can also cause low-grade liver inflammation characterized by episodes of intermittent high-grade liver inflammation, liver fibrosis, and cirrhosis, which can progress to decompensated liver disease and HCC. Equally, the absence of key innate and adaptive immune responses in chronic HCV infection dampens viral eradication and induces an exhausted and immunosuppressive liver niche that favors HCC development and progression. The objectives of this review are to (i) discuss the epidemiological pattern of HBV and HCV infections, (ii) understand the host immune response to acute and chronic viral hepatitis, and (iii) explore the link between this diseased immune environment and the development and progression of HCC in preclinical models and HCC patients.
Minerals and Cancer: Overview of the Possible Diagnostic Value
Authors: Venturelli Sascha , Leischner Christian , Helling Thomas , Renner Olga , Burkard Markus , Marongiu Luigi
Published: March 2022

Cancer is the second leading cause of death worldwide and is expected to increase by one-third over the next two decades, in parallel with the growing proportion of the elderly population. Treatment and control of cancer incidence is a global issue. Since there is no clear way to prevent or cure this deadly malignancy, diagnostic, predictive, and prognostic markers for oncological diseases are of great therapeutic value. Minerals and trace elements are important micronutrients for normal physiological function of the body. They are abundant in natural food sources and are regularly included in dietary supplements whereas highly processed industrial food often contains reduced or altered amounts of them. In modern society, the daily intake, storage pools, and homeostasis of these micronutrients are dependent on certain dietary habits and can be thrown out of balance by malignancies. The current work summarizes the data on minerals and trace elements associated with abnormal accumulation or depletion states in tumor patients and discusses their value as potential tumor-associated biomarkers that could be introduced into cancer therapy.
3D-Image-Guided Multi-Catheter Interstitial Brachytherapy for Bulky and High-Risk Stage IIB–IVB Cervical Cancer
Authors: Kokabu Tetsuya , Masui Koji , Tarumi Yosuke , Noguchi Naoki , Aoyama Kohei , Kataoka Hisashi , Matsushima Hiroshi , Yoriki Kaori , Shimizu Daisuke , Yamazaki Hideya , Yamada Kei , Mori Taisuke
Published: March 2022

This study aimed to evaluate the efficacy and safety of computed tomography-magnetic resonance imaging (CT-MRI)-guided multi-catheter interstitial brachytherapy for patients with bulky (≥4 cm) and high-risk, stage IIB–IVB advanced cervical cancer. Eighteen patients who underwent concurrent chemoradiotherapy with multi-catheter interstitial brachytherapy between September 2014 and August 2020 were enrolled. The prescribed dose of external beam radiotherapy was 45–50.4 Gy, and the brachytherapy high-dose-rate aim was 25–30 Gy per 5 fractions. The endpoints were four-year local and pelvic control rates, four-year disease-free and overall survival rates, and the adverse events rate. The median follow-up period was 48.4 months (9.1–87.5 months). Fifteen patients received concurrent cisplatin therapy (40 mg/m2, q1week). Four (22.2%), seven (38.9%), and seven (38.9%) patients had stage II, III, and IV cervical cancer, respectively. Pelvic and para-aortic lymph node metastases were observed in 11 (61.1%) and 2 (11.1%) patients, respectively. The median pre-treatment volume was 87.5 cm3. The four-year local control, pelvic control, disease-free survival, and overall survival rates were 100%, 100%, 81.6%, and 87.8%, respectively. Three (16.7%) patients experienced grade 3 adverse events, and none experienced grade 4–5 adverse events. CT-MRI-guided multi-catheter interstitial brachytherapy could be a promising treatment strategy for locally advanced cervical cancer.
PITX1 Is a Regulator of TERT Expression in Prostate Cancer with Prognostic Power
Authors: Poos Alexandra , Schroeder Cornelia , Jaishankar Neeraja , Röll Daniela , Oswald Marcus , Meiners Jan , Braun Delia , Knotz Caroline , Frank Lukas , Gunkel Manuel , Spilger Roman , Wollmann Thomas , Polonski Adam , Makrypidi-Fraune Georgia , Fraune Christoph , Graefen Markus , Chung Inn , Stenzel Alexander , Erfle Holger , Rohr Karl , Baniahmad Aria , Sauter Guido , Rippe Karsten , Simon Ronald , Koenig Rainer
Published: March 2022

The current risk stratification in prostate cancer (PCa) is frequently insufficient to adequately predict disease development and outcome. One hallmark of cancer is telomere maintenance. For telomere maintenance, PCa cells exclusively employ telomerase, making it essential for this cancer entity. However, TERT, the catalytic protein component of the reverse transcriptase telomerase, itself does not suit as a prognostic marker for prostate cancer as it is rather low expressed. We investigated if, instead of TERT, transcription factors regulating TERT may suit as prognostic markers. To identify transcription factors regulating TERT, we developed and applied a new gene regulatory modeling strategy to a comprehensive transcriptome dataset of 445 primary PCa. Six transcription factors were predicted as TERT regulators, and most prominently, the developmental morphogenic factor PITX1. PITX1 expression positively correlated with telomere staining intensity in PCa tumor samples. Functional assays and chromatin immune-precipitation showed that PITX1 activates TERT expression in PCa cells. Clinically, we observed that PITX1 is an excellent prognostic marker, as concluded from an analysis of more than 15,000 PCa samples. PITX1 expression in tumor samples associated with (i) increased Ki67 expression indicating increased tumor growth, (ii) a worse prognosis, and (iii) correlated with telomere length.
Delivering Glioblastoma a Kick—DGKα Inhibition as a Promising Therapeutic Strategy for GBM
Authors: Purow Benjamin
Published: March 2022

Diacylglycerol kinase α (DGKα) inhibition may be particularly relevant for the treatment of glioblastoma (GBM), a relatively common brain malignancy incurable with current therapies. Prior reports have shown that DGKα inhibition has multiple direct activities against GBM cells, including suppressing the oncogenic pathways mTOR and HIF-1α. It also inhibits pathways associated with the normally treatment-resistant mesenchymal phenotype, yielding preferential activity against mesenchymal GBM; this suggests possible utility in combining DGKα inhibition with radiation and other therapies for which the mesenchymal phenotype promotes resistance. The potential for DGKα inhibition to block or reverse T cell anergy also suggests the potential of DGKα inhibition to boost immunotherapy against GBM, which is generally considered an immunologically “cold” tumor. A recent report indicates that DGKα deficiency increases responsiveness of macrophages, indicating that DGKα inhibition could also have the potential to boost macrophage and microglia activity against GBM—which could be a particularly promising approach given the heavy infiltration of these cells in GBM. DGKα inhibition may therefore offer a promising multi-pronged attack on GBM, with multiple direct anti-GBM activities and also the ability to boost both adaptive and innate immune responses against GBM. However, both the direct and indirect benefits of DGKα inhibition for GBM will likely require combinations with other therapies to achieve meaningful efficacy. Furthermore, GBM offers other challenges for the application of DGKα inhibitors, including decreased accessibility from the blood-brain barrier (BBB). The ideal DGKα inhibitor for GBM will combine potency, specificity, and BBB penetrability. No existing inhibitor is known to meet all these criteria, but the strong potential of DGKα inhibition against this lethal brain cancer should help drive development and testing of agents to bring this promising strategy to the clinic for patients with GBM.
Long-Term Feasibility of 13.56 MHz Modulated Electro-Hyperthermia-Based Preoperative Thermoradiochemotherapy in Locally Advanced Rectal Cancer
Authors: Lee Yohan , Kim Sunghyun , Cha Hyejung , Han Jae Hun , Choi Hyun Joon , Go Eun , You Sei Hwan
Published: March 2022

We evaluated the effect of 13.56 MHz modulated electro-hyperthermia (mEHT) boost in neoadjuvant treatment for cT3-4- or cN-positive rectal cancer. Sixty patients who completed the mEHT feasibility trial (ClinicalTrials.gov Identifier: NCT02546596) were analyzed. Whole pelvis radiotherapy of 40 Gy, mEHT boost twice a week during radiotherapy, and surgical resection 6–8 weeks following radiotherapy were performed. The median age was 59. The median follow-up period was 58 (6–85) months. Total/near total tumor regression was observed in 20 patients (33.3%), including nine cases of complete response. T- and N-downstaging was identified in 40 (66.6%) and 53 (88.3%) patients, respectively. The 5-year overall and disease-free survival were 94.0% and 77.1%, respectively. mEHT energy of ≥3800 kJ potentially increased the overall survival (p = 0.039). The ypN-stage and perineural invasion were possible significant factors in disease-free (p = 0.003 and p = 0.005, respectively) and distant metastasis-free (p = 0.011 and p = 0.034, respectively) survival. Tumor regression, resection margin status, and other molecular genetic factors showed no correlation with survival. Although a limited analysis of a small number of patients, mEHT was feasible considering long-term survival. A relatively low dose irradiation (40 Gy) plus mEHT setting could ensure comparable clinical outcomes with possible mEHT-related prognostic features.
Molecular Imaging and Theragnostics of Thyroid Cancers
Authors: Giovanella Luca , Deandreis Desiree’ , Vrachimis Alexis , Campenni Alfredo , Petranovic Ovcaricek Petra
Published: March 2022

Molecular imaging plays an important role in the evaluation and management of different thyroid cancer histotypes. The existing risk stratification models can be refined, by incorporation of tumor-specific molecular markers that have theranostic power, to optimize patient-specific (individualized) treatment decisions. Molecular imaging with varying radioisotopes of iodine (i.e., 131I, 123I, 124I) is an indispensable component of dynamic and theragnostic risk stratification of differentiated carcinoma (DTC) while [18F]F-fluorodeoxyglucose ([18F]FDG) positron emission tomography/computed tomography (PET/CT) helps in addressing disease aggressiveness, detects distant metastases, and risk-stratifies patients with radioiodine-refractory DTC, poorly differentiated and anaplastic thyroid cancers. For medullary thyroid cancer (MTC), a neuroendocrine tumor derived from thyroid C-cells, [18F]F-dihydroxyphenylalanine (6-[18F]FDOPA) PET/CT and/or [18F]FDG PET/CT can be used dependent on serum markers levels and kinetics. In addition to radioiodine therapy for DTC, some theragnostic approaches are promising for metastatic MTC as well. Moreover, new redifferentiation strategies are now available to restore uptake in radioiodine-refractory DTC while new theragnostic approaches showed promising preliminary results for advanced and aggressive forms of follicular-cell derived thyroid cancers (i.e., peptide receptor radiotherapy). In order to help clinicians put the role of molecular imaging into perspective, the appropriate role and emerging opportunities for molecular imaging and theragnostics in thyroid cancer are discussed in our present review.
The Spermidine Synthase Gene SPD1: A Novel Auxotrophic Marker for Chlamydomonas reinhardtii Designed by Enhanced CRISPR/Cas9 Gene Editing
Authors: Freudenberg Robert A. , Wittemeier Luisa , Einhaus Alexander , Baier Thomas , Kruse Olaf
Published: March 2022

Biotechnological application of the green microalga Chlamydomonas reinhardtii hinges on the availability of selectable markers for effective expression of multiple transgenes. However, biological safety concerns limit the establishment of new antibiotic resistance genes and until today, only a few auxotrophic markers exist for C. reinhardtii. The recent improvements in gene editing via CRISPR/Cas allow directed exploration of new endogenous selectable markers. Since editing frequencies remain comparably low, a Cas9-sgRNA ribonucleoprotein (RNP) delivery protocol was strategically optimized by applying nitrogen starvation to the pre-culture, which improved successful gene edits from 10% to 66% after pre-selection. Probing the essential polyamine biosynthesis pathway, the spermidine synthase gene (SPD1) is shown to be a potent selectable marker with versatile biotechnological applicability. Very low levels of spermidine (0.75 mg/L) were required to maintain normal mixotrophic and phototrophic growth in newly designed spermidine auxotrophic strains. Complementation of these strains with a synthetic SPD1 gene was achieved when the mature protein was expressed in the cytosol or targeted to the chloroplast. This work highlights the potential of new selectable markers for biotechnology as well as basic research and proposes an effective pipeline for the identification of new auxotrophies in C. reinhardtii.
A Human In Vitro Model to Study Adenoviral Receptors and Virus Cell Interactions
Authors: Tsoukas Raphael L. , Volkwein Wolfram , Gao Jian , Schiwon Maren , Bahlmann Nora , Dittmar Thomas , Hagedorn Claudia , Ehrke-Schulz Eric , Zhang Wenli , Baiker Armin , Ehrhardt Anja
Published: March 2022

To develop adenoviral cell- or tissue-specific gene delivery, understanding of the infection mechanisms of adenoviruses is crucial. Several adenoviral attachment proteins such as CD46, CAR and sialic acid have been identified and studied. However, most receptor studies were performed on non-human cells. Combining our reporter gene-tagged adenovirus library with an in vitro human gene knockout model, we performed a systematic analysis of receptor usage comparing different adenoviruses side-by-side. The CRISPR/Cas9 system was used to knockout CD46 and CAR in the human lung epithelial carcinoma cell line A549. Knockout cells were infected with 22 luciferase-expressing adenoviruses derived from adenovirus species B, C, D and E. HAdV-B16, -B21 and -B50 from species B1 as well as HAdV-B34 and -B35 were found to be CD46-dependent. HAdV-C5 and HAdV-E4 from species E were found to be CAR-dependent. Regarding cell entry of HAdV-B3 and -B14 and all species D viruses, both CAR and CD46 play a role, and here, other receptors or attachment structures may also be important since transductions were reduced but not completely inhibited. The established human knockout cell model enables the identification of the most applicable adenovirus types for gene therapy and to further understand adenovirus infection biology.
The Neurotoxicity of Vesicles Secreted by ALS Patient Myotubes Is Specific to Exosome-Like and Not Larger Subtypes
Authors: Anakor Ekene , Milla Vanessa , Connolly Owen , Martinat Cecile , Pradat Pierre Francois , Dumonceaux Julie , Duddy William , Duguez Stephanie
Published: March 2022

Extracellular vesicles can mediate communication between tissues, affecting the physiological conditions of recipient cells. They are increasingly investigated in Amyotrophic Lateral Sclerosis, the most common form of Motor Neurone Disease, as transporters of misfolded proteins including SOD1, FUS, TDP43, or other neurotoxic elements, such as the dipeptide repeats resulting from C9orf72 expansions. EVs are classified based on their biogenesis and size and can be separated by differential centrifugation. They include exosomes, released by the fusion of multivesicular bodies with the plasma membrane, and ectosomes, also known as microvesicles or microparticles, resulting from budding or pinching of the plasma membrane. In the current study, EVs were obtained from the myotube cell culture medium of ALS patients or healthy controls. EVs of two different sizes, separating at 20,000 or 100,000 g, were then compared in terms of their effects on recipient motor neurons, astrocytes, and myotubes. Compared to untreated cells, the smaller, exosome-like vesicles of ALS patients reduced the survival of motor neurons by 31% and of myotubes by 18%, decreased neurite length and branching, and increased the proportion of stellate astrocytes, whereas neither those of healthy subjects, nor larger EVs of ALS or healthy subjects, had such effects.