bluuebunny/crossref_metadata_2025 huggingface dataset:
Human–robot creative interactions: Exploring creativity in artificial agents using a storytelling game
Authors: Sandoval Eduardo Benítez , Sosa Ricardo , Cappuccio Massimiliano , Bednarz Tomasz
Published: August 2022

Creativity in social robots requires further attention in the interdisciplinary field of human–robot interaction (HRI). This study investigates the hypothesized connection between the perceived creative agency and the animacy of social robots. The goal of this work is to assess the relevance of robot movements in the attribution of creativity to robots. The results of this work inform the design of future human–robot creative interactions (HRCI). The study uses a storytelling game based on visual imagery inspired by the game “Story Cubes” to explore the perceived creative agency of social robots. This game is used to tell a classic story for children with an alternative ending. A 2 × 2 experiment was designed to compare two conditions: the robot telling the original version of the story and the robot plot twisting the end of the story. A Robotis Mini humanoid robot was used for the experiment, and we adapted the Short Scale of Creative Self (SSCS) to measure perceived creative agency in robots. We also used the Godspeed scale to explore different attributes of social robots in this setting. We did not obtain significant main effects of the robot movements or the story in the participants’ scores. However, we identified significant main effects of the robot movements in features of animacy, likeability, and perceived safety. This initial work encourages further studies experimenting with different robot embodiment and movements to evaluate the perceived creative agency in robots and inform the design of future robots that participate in creative interactions.
A novel encoding element for robust pose estimation using planar fiducials
Authors: Rijlaarsdam David D. W. , Zwick Martin , Kuiper J.M. (Hans)
Published: August 2022

Pose estimation in robotics is often achieved using images from known and purposefully applied markers or fiducials taken by a monocular camera. This low-cost system architecture can provide accurate and precise pose estimation measurements. However, to prevent the restriction of robotic movement and occlusions of features, the fiducial markers are often planar. While numerous planar fiducials exist, the performance of these markers suffers from pose ambiguities and loss of precision under frontal observations. These issues are most prevalent in systems with less-than-ideal specifications such as low-resolution detectors, low field of view optics, far-range measurements etc. To mitigate these issues, encoding markers have been proposed in literature. These markers encode an extra dimension of information in the signal between marker and sensor, thus increasing the robustness of the pose solution. In this work, we provide a survey of these encoding markers and show that existing solutions are complex, require optical elements and are not scalable. Therefore, we present a novel encoding element based on the compound eye of insects such as the Mantis. The encoding element encodes a virtual point in space in its signal without the use of optical elements. The features provided by the encoding element are mathematically equivalent to those of a protrusion. Where existing encoding fiducials require custom software, the projected virtual point can be used with standard pose solving algorithms. The encoding element is simple, can be produced using a consumer 3D printer and is fully scalable. The end-to-end implementation of the encoding element proposed in this work significantly increases the pose estimation performance of existing planar fiducials, enabling robust pose estimation for robotic systems.
Data protection as privilege—Factors to increase meaning of GDPR in vulnerable groups
Authors: Breuer Jonas , Heyman Rob , Brakel Rosamunde van
Published: August 2022

The General Data Protection Regulation in the EU has the potential to empower citizens towards data-based innovation and datafication. Realising this potential in practise is challenging, mainly because not everyone has the capabilities, seemingly expected by the lawmakers, to make use of relevant legal provisions. This empirical study sets out to investigate what can increase capabilities of citizens in datafied societies to understand and exercise their rights to data protection, as means to increase participation in socio-technical systems. We concentrate on vulnerable groups and criticise the GDPR as regarding data literacies as intrinsic life goals instead of instrumental means. We expand vulnerability to capability deprivation, based on a dynamic understanding of layered vulnerabilities. This overcomes solely negative associations of vulnerability and provides a more constructive framing in support of literacies of everyone, including less literate or more vulnerable. Based on this approach, we consider what is lacking to achieve GDPR literacy. We conducted interviews with representatives of civil society organisations supporting different groups in Flanders, Belgium. Based on these insights, we argue that a layered approach to vulnerability leads to a layered approach to capabilities, and to a layered approach of support based on the most appropriate conversion factors for different groups: (a) at the right place and time, (b) broader support structures from authorities, and (c) a focus on clear communication with the reader in mind.
Klebsiella pneumoniae liver abscess with purulent meningitis and endogenous endophthalmitis: A case report
Authors: Li Fang , Zheng Wenfei , Yu Jian , Zhao Linyan
Published: August 2022

This is a rare but typical case of a Klebsiella pneumoniae liver abscess with migratory infections including purulent meningitis and endogenous endophthalmitis. The patient had a chief complaint of 7 days of fever, 4 days of blurry vision, and 4 h of glossolalia. Ultrasound scan and computed tomography (CT) suggested a liver abscess. Both blood and drainage fluid cultures grew K. pneumoniae with a high mucosal phenotype. The patient was finally diagnosed with a K. pneumoniae liver abscess, purulent meningitis, and endogenous K. pneumoniae endophthalmitis in the right eye. Ultrasound-guided percutaneous catheter drainage (PCD) of the liver abscess was performed, and meropenem was used to control infection. The patient was given 0.1 ml of vancomycin (10 g/L) and 0.1 ml of ceftazidime (20 g/L) were by intravitreal injection for the treatment of endophthalmitis. The infection was gradually controlled after such treatments. The patient was discharged from our hospital with an improved condition. However, during the time of follow-up, she developed complications due to severe pneumonia and eventually died in a local hospital. This case revealed that a rapid diagnosis followed by appropriate treatment would improve prognosis and prevent severe metastatic complications.
Postoperative paralytic ileus following debulking surgery in ovarian cancer patients
Authors: Egger Eva K. , Merker Freya , Ralser Damian J. , Marinova Milka , Vilz Tim O. , Matthaei Hanno , Hilbert Tobias , Mustea Alexander
Published: August 2022

Aim

This study aims to evaluate the incidence of postoperative ileus (POI) following cytoreductive surgery in epithelial ovarian cancer (EOC) patients and its impact on anastomotic leakage occurrence and postoperative complications.

Methods

A total of 357 surgeries were performed on 346 ovarian cancer patients between 1/2010 and 12/2020 at our institution. The postoperative course regarding paralytic ileus, anastomotic leakage, and postoperative complications was analyzed by Fisher's exact test and through ordinal logistic regression.

Results

A total of 233 patients (65.3%) returned to normal gastrointestinal functions within 3 days after surgery. A total of 123 patients (34.5%) developed POI. There were 199 anastomoses in 165 patients and 24 leakages (12.1%). Postoperative antibiotics (p 0.001), stoma creation (p 0.0001), and early start of laxatives (p 0.0048) significantly decreased POI, while anastomoses in general (p 0.0465) and especially low anastomoses (p 0.0143) showed increased POI rates. Intraoperative positive fluid excess >5,000 cc was associated with a higher risk for POI (p 0.0063), anastomotic leakage (p 0.0254), and severe complications (p 0.0012).

Conclusion

Postoperative antibiotics, an early start with laxatives, and stoma creation were associated with reduced POI rates. Patients with anastomoses showed an increased risk for POI. Severe complications, anastomotic leakages, and POI were more common in the case of intraoperative fluid balance exceeding 5,000 cc.
Dietary Vitamin K Intake and HPV-Infection Status Among American Women: A Secondary Analysis From National Health and Nutrition Examination Survey Data From 2003 to 2016
Authors: Jiang Yinhui , Xu Shu , Lan Jinzhi , Zhang Jinjuan , Chen Tengxiang
Published: August 2022

Objective: Cervical cancer is a serious potential risk to women’s health, and is closely related to persistent HPV infection. Vitamin K mainly existed in green vegetables, fruit, and dairy products. This research aims to observe the association between vitamin K and HPV-infection.

Methods: 13,447 participants from the NHANES were selected. Dietary vitamin K intake was used as the objective independent variable and continuous variable, HPV-infection status was used as the outcome variable, and characteristics of selected participants were used as the covariates.

Results: There was a nonlinearity between vitamin K intake and HPV-infection, and the inflection point is 3.81 of log2 vitamin K intake. In a range of 0–3.81, Each one-unit increase in log2 vitamin K intake was associated with a 43% reduction in the risk of HPV infection. When log2 vitamin K intake excess of 3.81, the risk of HPV infection did not continue to decline. The HPV-subtype was not associated with vitamin K intake.

Conclusion: There is a nonlinearity between vitamin K intake and HPV-infection status. But HPV-subtype was not associated with vitamin K intake.
Loneliness and Depression Among Female University Students During the COVID-19 Pandemic: A Cross-Sectional Study in Riyadh, Saudi Arabia, 2020
Authors: Alateeq Deemah , Aljabri Alhanouf , Aldogiam Ghada , Alajmi Haya , Alsoqaih Hussah , Alfadhly Rawan , Alshahrani Raneem
Published: August 2022

Objectives: Quarantine-related loneliness has impacted university students during the coronavirus disease 2019 (COVID-19) pandemic. This study aims to evaluate loneliness among female university students in Riyadh, Saudi Arabia during the pandemic and to investigate its correlation with depression.

Methods: A sample of 753 female students was collected during the first COVID-19 summer vacation outbreak through a cross-sectional survey that consisted of two parts: 1) Sociodemographic characteristics and COVID-19 related questions; 2) The eight-item UCLA Loneliness Scale (ULS-8) and the Patient Health Questionnaire-9 (PHQ-9).

Results: Most participants were between 18 and 22 years old (75.2%) and were studying at humanities college (61.50%). Loneliness and depression were reported among 63.3% and 41.1% of female students, respectively, and the correlation between them was significantly positive (beta = 0.419, p < 0.001). Having a previous history of a psychiatric condition and families with insufficient monthly income were the main associated factors with high levels of loneliness and depression.

Conclusion: Female university students experienced loneliness and depression under quarantine during the first COVID-19 summer vacation outbreak. Psychosocial intervention for the vulnerable groups is essential, as are longitudinal studies.
Strategies to Improve the Safety of iPSC-Derived β Cells for β Cell Replacement in Diabetes
Authors: Pellegrini Silvia , Zamarian Valentina , Sordi Valeria
Published: August 2022

Allogeneic islet transplantation allows for the re-establishment of glycemic control with the possibility of insulin independence, but is severely limited by the scarcity of organ donors. However, a new source of insulin-producing cells could enable the widespread use of cell therapy for diabetes treatment. Recent breakthroughs in stem cell biology, particularly pluripotent stem cell (PSC) techniques, have highlighted the therapeutic potential of stem cells in regenerative medicine. An understanding of the stages that regulate β cell development has led to the establishment of protocols for PSC differentiation into β cells, and PSC-derived β cells are appearing in the first pioneering clinical trials. However, the safety of the final product prior to implantation remains crucial. Although PSC differentiate into functional β cells in vitro, not all cells complete differentiation, and a fraction remain undifferentiated and at risk of teratoma formation upon transplantation. A single case of stem cell-derived tumors may set the field back years. Thus, this review discusses four approaches to increase the safety of PSC-derived β cells: reprogramming of somatic cells into induced PSC, selection of pure differentiated pancreatic cells, depletion of contaminant PSC in the final cell product, and control or destruction of tumorigenic cells with engineered suicide genes.
Increased Sulphur Amino Acids Consumption as OH-Methionine or DL-Methionine Improves Growth Performance and Carcass Traits of Growing-Finishing Pigs Fed under Hot Conditions
Authors: da Silva Caio Abércio , Dias Cleandro Pazinato , Callegari Marco Aurélio , de Souza Kelly Lais , Barbi José Henrique , Fagundes Naiara Simarro , Batonon-Alavo Dolores I. , Foppa Luciana
Published: August 2022

This study aimed to evaluate the impact of DL-Methionine (DL-Met) or OH-Methionine (OH-Met) when supplemented beyond the usually accepted requirements in sulfur amino acids (SAA) on the performance and carcass traits of growing-finishing pigs. Two hundred mixed sex pigs were distributed in a randomized block (body weight and sex), under a 2 × 2 factorial design with two methionine sources, DL-methionine, or OH-Methionine and two methionine doses (100% SAA or 120% of the SAA level present in the control). Diets were formulated to meet amino acids recommendations of the Brazilian Tables for Poultry and Swine (2017), except for SAA, which varied with the methionine doses. Daily feed intake, daily weight gain, and feed conversion were evaluated. Moreover, the carcasses were measured electronically for fat thickness (FT), longissimus dorsi muscle depth (LD), and lean meat (%). During the growing phase II (92 till 122 days of age), daily feed intake (p < 0.001) and daily weight gain (p < 0.05) increased with the high SAA levels. High SAA levels also provided greater daily weight gain during the entire period of the trial (0.90 versus 0.86 kg; p < 0.05) No significant interaction was observed between the methionine source and the SAA level for any carcass traits. However, animals that received OH-Met had greater (p < 0.05) loin depth (58.37 versus 55.21 mm) and those that received higher doses of methionine presented heavier (p < 0.05) carcass weight (78.16 versus 74.70 kg), and more (p < 0.05) lean meat weight (43.69 versus 41.90 kg). Taken together, these results demonstrated that supplementation of high sulfur amino acids levels under hot conditions provided heavier carcasses and more lean meat.
Flexible DEM Model Development and Parameter Calibration for Rape Stem
Authors: Guan Zhuohuai , Mu Senlin , Li Haitong , Jiang Tao , Zhang Min , Wu Chongyou
Published: August 2022

The discrete element method (DEM) is an effective technical tool for simulating the dynamic behavior of granular materials in agricultural engineering. However, most of the agricultural materials, such as rape stems, are flexible bodies, and it is difficult to simulate their elastic-plastic characteristics such as bending and failure using the rigid discrete element model. In this research, a flexible DEM model for rape stems was developed and the related parameters were calibrated. The proposed model consists of sequentially arranged rigid units, which were bonded together by the Hertz–Mindlin bonding contact model in the EDEM. The range of the contact parameters of a rape stem was first determined by bench test. The rape stem repose angle test was carried out as an evaluation indicator for the calibration of the DEM contact parameters. The significant factors affecting the repose angle in the contact parameters were discovered using the Plackett–Burman simulation test, and the optimal combination of these parameters was determined based on the response surface simulation test. The rape stem repose angle simulation result was 26.55° with a relative error of 2.2% for the physical tests. The rape-stem flexible DEM model’s bonding parameters were calibrated based on a three-point bending physical test and a Box–Behnken simulation test. The test results show that a rape stem’s maximum damage force obtained from the constructed model was 16.76 N, and the relative error of the measured values from the physical tests was 3.5%. The flexible DEM model could demonstrate the deformation and fracture of rape stems under an external force and can be used for the simulation of harvesting processes such as cutting, conveying, and threshing.
Development of an Intelligent Solution for the Optimization of Hybrid Energy Systems
Authors: Saba Djamel , Hajjej Fahima , Cheikhrouhou Omar , Sahli Youcef , Hadidi Abdelkader , Hamam Habib
Published: August 2022

This paper presents a proposal for the development of a new intelligent solution for the optimization of hybrid energy systems. This solution is of great importance for installers of hybrid energy systems, as it helps them obtain the best configuration of the hybrid energy system (efficient and less expensive). In this solution, it is sufficient to enter the name of the location of the hybrid energy system that we want to install; after that, the solution will show the name of the best technology from which the optimal configuration of this system can be obtained. To accomplish this goal, the study relied on the ontology approach for two reasons, one of which is related to the nature of hybrid systems, because it is characterized by a large amount of information that requires good structuring, and the second reason is the interaction of hybrid energy systems with the external environment (climate, site characteristics). Afterward, to develop the knowledge base of the ontology, many steps were followed, the first of which is related to a detailed study of the existing one and the extraction of the basic elements, such as the concepts and the relations between them, followed by the development of the rules of intelligent reasoning, which is an interaction between the elements of the ontology through which all possible cases are treated. The “Protégé” software was used to edit these elements and perform the simulation process to show the results of the developed solution. Finally, the paper includes a case study, and the results show the importance of the developed solution, and it is open to future developments.
MULTI-NETVIS: Visual Analytics for Multivariate Network
Authors: Wang Song , Chen Shijie , Cai Ting , Wu Yadong
Published: August 2022

In the process of multivariate network exploration and analysis, it is important to consider network topology and attribute correlation analysis. In order to consider both in presentation and analysis, existing research focuses on visual design and multiple-view visualization. However, this multitudinous visual design makes network cognition and analysis difficult. In multi-view visualization, the associated information among attributes is rarely retained and is often accompanied by tedious interaction processes. In this paper, a layout scheme is proposed to balance attribute and topology analysis in multivariate network visual analysis and a multivariate network visual analytics system is implemented based on the layout scheme. The analysis scenarios of overall, community, and local multi-granularity are provided by the layout scheme, which combines 3D, 2.5D, and 2D layouts. According to the layout scheme, we propose a layout transformation method to maintain the relative position of the topological context layouts in three dimensions. Furthermore, we propose a Louvain-3D FDA layout algorithm for the 3D layout, and introduce an edge bundling algorithm in the 2.5D layout to achieve an attribute-oriented topology layout. Combining the principle of interaction from global to detail, we design a novel system, Multi-NetVis, which supports users in drilling exploration and analysis and takes both the network attribute correlations and topological structure into consideration. Finally, two datasets are selected to demonstrate the usage scenarios and an evaluation experiment is designed to verify the effectiveness of the layout scheme.
Development of Damage Type Viscoelastic Ontological Model for Soft and Hard Materials under High-Strain-Rate Conditions
Authors: Liu Wei , Xu Xiangyun , Mu Chaomin
Published: August 2022

By improving the ZWT model, a principal structure model applicable to both soft and hard materials under dynamic loading conditions was obtained. Dynamic mechanical experiments were conducted using SHPB to obtain stress–strain curves for coal rock and foam concrete. The ZWT intrinsic model was simplified according to the dynamic impact characteristics of concrete, and the intrinsic model was established by introducing macroscopic damage quantity D and correction factor δ. The stress–strain curves of coal rock, foamed concrete, steel fiber concrete, granite, lightweight foamed concrete, and EPS concrete at different strain rates were used to validate the present constitutive model and prove the correctness of the model.
Defeat Magic with Magic: A Novel Ransomware Attack Method to Dynamically Generate Malicious Payloads Based on PLC Control Logic
Authors: Zhang Yipeng , Li Min , Zhang Xiaoming , He Yueying , Li Zhoujun
Published: August 2022

The Industrial Control System (ICS) is a public facility that provides services to lots of users; thus, its security has always been a critical factor in measuring its availability. Recently, a new type of attack on ICS has occurred frequently, which realizes the extortion of users by invading the information domain and destroying the physical domain. However, due to the diversity and unavailability of an ICS control logic, the targets of such attacks are usually limited to PCs and servers, leaving more disruptive attack methods unexplored. To contribute more possible attack methods to strengthen the immunity of ICS, in this paper, we propose a novel ransomware attack method named Industrial Control System Automatic Ransomware Constructor (ICS-ARC). Compared to existing ICS ransomware, ICS-ARC can automatically generate an International Electrotechnical Commission (IEC) compliant payload to compromise the Programmable Logic Controller (PLC) without a pre-known control logic, dramatically reducing adversary requirements and leaving room for error. To evaluate the attack capability of ICS-ARC, we built a tap water treatment system as the simulation experiment target for verification. The experimental results determine that ICS-ARC can automatically generate malicious code without the control logic and complete the attack against target PLCs. In addition, to assist the related research on future attacks and defenses, we present the statistical results and corresponding analysis of PLC based on Shodan.
Data Augmentation in 2D Feature Space for Intelligent Weak Fault Diagnosis of Planetary Gearbox Bearing
Authors: Yang Rui , An Zenghui , Huang Weiling , Wang Rijun
Published: August 2022

Quickly detecting and accurately diagnosing early bearing faults is the key to ensuring the stable operation of high-precision equipment. In actual industrial applications, it is common to face the issues of big data and poor fault identification accuracy. To accurately and automatically realize the diagnostics of rolling bearings, a convolutional neural network algorithm and fault feature enhancement method is proposed. A two-dimensional space feature extraction method based on the Cyclostationary theory and wavelet transform shows good results in noise suppression. Firstly, the cyclic demodulation of wavelet transform coefficients is performed on bearing vibration signals to convert one-dimensional vibration data into a two-dimensional spectrogram for enhancing the weak fault feature. Secondly, the image segmentation theory is introduced, which can obtain more data and improve the calculation accuracy and efficiency on the basis of data dimension reduction. Finally, the augmented 2D spectrograms are inputted into a convolutional neural network. Through the analysis of the actual planetary gearbox bearing data, and compared with other mainstream intelligence algorithms, the effectiveness and superiority of this method are verified.
Fully Dynamic High–Resolution Model for Dispersion of Icelandic Airborne Mineral Dust
Authors: Cvetkovic Bojan , Dagsson-Waldhauserová Pavla , Petkovic Slavko , Arnalds Ólafur , Madonna Fabio , Proestakis Emmanouil , Gkikas Antonis , Vukovic Vimic Ana , Pejanovic Goran , Rosoldi Marco , Ceburnis Darius , Amiridis Vassilis , Lisá Lenka , Nickovic Slobodan , Nikolic Jugoslav
Published: August 2022

Icelandic topsoil sediments, as confirmed by numerous scientific studies, represent the largest and the most important European source of mineral dust. Strong winds, connected with the intensive cyclonic circulation in the North Atlantic, induce intense emissions of mineral dust from local sources all year and carry away these fine aerosol particles for thousands of kilometers. Various impacts of airborne mineral dust particles on local air quality, human health, transportation, climate and marine ecosystems motivated us to design a fully dynamic coupled atmosphere–dust numerical modelling system in order to simulate, predict and quantify the Icelandic mineral dust process including: local measurements and source specification over Iceland. In this study, we used the Dust Regional Atmospheric Model (DREAM) with improved Icelandic high resolution dust source specification and implemented spatially variable particle size distribution, variable snow cover and soil wetness. Three case studies of intense short- and long-range transport were selected to evaluate the model performance. Results demonstrated the model’s capability to forecast major transport features, such as timing, and horizontal and vertical distribution of the processes. This modelling system can be used as an operational forecasting system, but also as a reliable tool for assessing climate and environmental Icelandic dust impacts.
Dose-Related Reduction in Hippocampal Neuronal Populations in Fetal Alcohol Exposed Vervet Monkeys
Authors: Burke Mark W. , Slimani Hocine , Ptito Maurice , Ervin Frank R. , Palmour Roberta M.
Published: August 2022

Fetal alcohol spectrum disorder (FASD) is a chronic debilitating condition resulting in behavioral and intellectual impairments and is considered the most prevalent form of preventable mental retardation in the industrialized world. We previously reported that 2-year-old offspring of vervet monkey (Chlorocebus sabeus) dams drinking, on average, 2.3 ± 0.49 g ethanol per Kg maternal body weight 4 days per week during the last third of pregnancy had significantly lower numbers of CA1 (−51.6%), CA2 (−51.2%) and CA3 (−42.8%) hippocampal neurons, as compared to age-matched sucrose controls. Fetal alcohol-exposed (FAE) offspring also showed significantly lower volumes for these structures at 2 years of age. In the present study, we examined these same parameters in 12 FAE offspring with a similar average but a larger range of ethanol exposures (1.01–2.98 g/Kg/day; total ethanol exposure 24–158 g/Kg). Design-based stereology was performed on cresyl violet-stained and doublecortin (DCX)-immunostained sections of the hippocampus. We report here significant neuronal deficits in the hippocampus with a significant negative correlation between daily dose and neuronal population in CA1 (r2 = 0.486), CA2 (r2 = 0.492), and CA3 (r2 = 0.469). There were also significant correlations between DCX population in the dentate gyrus and daily dose (r2 = 0.560). Both correlations were consistent with linear dose-response models. This study illustrates that neuroanatomical sequelae of fetal ethanol exposure are dose-responsive and suggests that there may be a threshold for this effect.
Deformation Characteristics and Optimization Design for Large-Scale Deep and Circular Foundation Pit Partitioned Excavation in a Complex Environment
Authors: Shi Hai , Jia Zhilei , Wang Tao , Cheng Zhiqiang , Zhang De , Bai Mingzhou , Yu Kun
Published: August 2022

With the rapid development of urban rail transit, the impact of the construction of large-scale deep and circular foundation pits (LDCFPs) on the surrounding environment has become increasingly prominent; however, there is no definite standard for the design theory and construction method of the retaining structure of LDCFPs; therefore, the such standard needs further research and exploration. The paper is based on the LDCFP engineering of a subway station in Wuhan, China. Two partitioned excavation methods (step-by-step and synchronous excavation) of LDCFP were discussed by numerical simulation; the deformation characteristics of the soil around the foundation pit, the lateral deformation of the retaining structure in each partitioned district, and the distribution of the supporting axial force were analyzed; the deformation law of LDCFP was revealed; and the safe and economic excavation method was determined. The field monitoring test was carried out to reveal the deformation characteristics and stress evolution behavior for the supporting structure of the LDCFP in the subway station. It was concluded that the construction method of synchronous partitioned excavation in the same layer is more conducive to controlling the overall deformation, with the deformation of the circular retaining structure being uniform and the “vault effect” of the circular retaining structure having a certain constraint on the deformation of the foundation pit. The research results can provide guidance for the design and construction of supporting engineering and similar engineering.
Research-Integrated Pedagogy with Climate-Responsive Strategies: Vernacular Building Renovation Design
Authors: Lin Hankun , Yin Shi , Xie Chao , Lin Yaoguang
Published: August 2022

Following the rapid development and urbanization in China over recent decades, sustainable renovation of urban residences has become an important issue. This study aimed to develop an architectural teaching program integrating the study of local climate, vernacular buildings, climate-responsive design strategies, and simulation tools. A local house in a high-density neighborhood in Guangzhou, China, in a hot-humid climate area was selected for renovation in this teaching program. Investigations of the urban neighborhood development, the construction and climate-responsive characteristics of the vernacular houses, long-term thermal environment characteristics, and sustainable design strategies were conducted before the design project began. The guidelines of Active House combining passive strategies and active technologies were incorporated into the concept design. The students’ works represented their understanding of the characteristics of a hot-humid climate, responsive strategies for the local buildings, preliminary methodologies of micro-climate analysis, and technologies supporting sustainable building design. Thus, this program provided a valuable approach to the appropriate pedagogy for a research-integrated design studio within the context of sustainable architectural education development.
Updated Neoadjuvant Treatment Landscape for Early Triple Negative Breast Cancer: Immunotherapy, Potential Predictive Biomarkers, and Novel Agents
Authors: Garufi Giovanna , Carbognin Luisa , Schettini Francesco , Seguí Elia , Di Leone Alba , Franco Antonio , Paris Ida , Scambia Giovanni , Tortora Giampaolo , Fabi Alessandra
Published: August 2022

Triple-negative breast cancer (TNBC) is characterized by the absence of hormone receptor and HER2 expression, and therefore a lack of therapeutic targets. Anthracyclines and taxane-based neoadjuvant chemotherapy have historically been the cornerstone of treatment of early TNBC. However, genomic and transcriptomic analyses have suggested that TNBCs include various subtypes, characterized by peculiar genomic drivers and potential therapeutic targets. Therefore, several efforts have been made to expand the therapeutic landscape of early TNBC, leading to the introduction of platinum and immunomodulatory agents into the neoadjuvant setting. This review provides a comprehensive overview of the currently available evidence regarding platinum agents and immune-checkpoint-inhibitors for the neoadjuvant treatment of TNBC, as well as the novel target therapies that are currently being evaluated in this setting. Taking into account the economic issues and the side effects of the expanding therapeutic options, we focus on the potential efficacy biomarkers of the emerging therapies, in order to select the best therapeutic strategy for each specific patient.
BRPF1-KAT6A/KAT6B Complex: Molecular Structure, Biological Function and Human Disease
Authors: Zu Gaoyu , Liu Ying , Cao Jingli , Zhao Baicheng , Zhang Hang , You Linya
Published: August 2022

The bromodomain and PHD finger–containing protein1 (BRPF1) is a member of family IV of the bromodomain-containing proteins that participate in the post-translational modification of histones. It functions in the form of a tetrameric complex with a monocytic leukemia zinc finger protein (MOZ or KAT6A), MOZ-related factor (MORF or KAT6B) or HAT bound to ORC1 (HBO1 or KAT7) and two small non-catalytic proteins, the inhibitor of growth 5 (ING5) or the paralog ING4 and MYST/Esa1-associated factor 6 (MEAF6). Mounting studies have demonstrated that all the four core subunits play crucial roles in different biological processes across diverse species, such as embryonic development, forebrain development, skeletal patterning and hematopoiesis. BRPF1, KAT6A and KAT6B mutations were identified as the cause of neurodevelopmental disorders, leukemia, medulloblastoma and other types of cancer, with germline mutations associated with neurodevelopmental disorders displaying intellectual disability, and somatic variants associated with leukemia, medulloblastoma and other cancers. In this paper, we depict the molecular structures and biological functions of the BRPF1-KAT6A/KAT6B complex, summarize the variants of the complex related to neurodevelopmental disorders and cancers and discuss future research directions and therapeutic potentials.
Efficacy of Large Use of Combined Hypofractionated Radiotherapy in a Cohort of Anti-PD-1 Monotherapy-Treated Melanoma Patients
Authors: Saiag Philippe , Molinier Rafaele , Roger Anissa , Boru Blandine , Otmezguine Yves , Otz Joelle , Valery Charles-Ambroise , Blom Astrid , Longvert Christine , Beauchet Alain , Funck-Brentano Elisa
Published: August 2022

To assess the role of radiotherapy in anti-PD-1-treated melanoma patients, we studied retrospectively a cohort of 206 consecutive anti-PD-1 monotherapy-treated advanced melanoma patients (59% M1c/d, 50% ≥ 3 metastasis sites, 33% ECOG PS ≥ 1, 33% > 1st line, 32% elevated serum LDH) having widely (49%) received concurrent radiotherapy, with RECIST 1.1 evaluation of radiated and non-radiated lesions. Overall (OS) and progression-free (PFS) survivals were calculated using Kaplan–Meier. Radiotherapy was performed early (39 patients) or after 3 months (61 patients with confirmed anti-PD-1 failure). The first radiotherapy was hypofractionated extracranial radiotherapy to 1–2 targets (26 Gy-4 weekly sessions, 68 patients), intracranial radiosurgery (25 patients), or palliative. Globally, 67 (32.5% [95% CI: 26.1–38.9]) patients achieved complete response (CR), with 25 CR patients having been radiated. In patients failing anti-PD-1, PFS and OS from anti-PD-1 initiation were 16.8 [13.4–26.6] and 37.0 months [24.6–NA], respectively, in radiated patients, and 2.2 [1.5–2.6] and 4.3 months [2.6–7.1], respectively, in non-radiated patients (p < 0.001). Abscopal response was observed in 31.5% of evaluable patients who radiated late. No factors associated with response in radiated patients were found. No unusual adverse event was seen. High-dose radiotherapy may enhance CR rate above the 6–25% reported in anti-PD-1 monotherapy or ipilimumab + nivolumab combo studies in melanoma patients.
Serum Levels of CXCL13 Are an Independent Predictor of Survival Following Resection of Biliary Tract Cancer
Authors: Loosen Sven H. , Ulmer Tom F. , Labuhn Simon , Bednarsch Jan , Lang Sven A. , Alizai Patrick H. , Schneider Anne T. , Vucur Mihael , Neumann Ulf P. , Luedde Tom , Roderburg Christoph
Published: August 2022

Background: The prognosis of biliary tract cancer (BTC) has remained very poor. Although tumor resection represents a potentially curative therapy for selected patients, tumor recurrence is common, and 5-year survival rates have remained below 50%. As stratification algorithms comprising the parameters of individual tumor biology are missing, the identification of ideal patients for extensive tumor surgery is often challenging. The CXC chemokine family exerts decisive functions in cell–cell interactions and has only recently been associated with cancer, but little is known about their function in BTC. Here, we aim to evaluate a potential role of circulating CXCL1, CXCL10 and CXCL13 in patients with resectable BTC. Methods: Serum levels of CXCL1, CXCL10 and CXCL13 were measured by multiplex immunoassay in a cohort of 119 BTC patients undergoing tumor resection and 50 control samples. Results: Circulating levels of CXCL1, CXCL10 and CXCL13 were all significantly elevated in BTC patients compared to healthy controls and increased the diagnostic power of established tumor markers such as CA19-9 when used in combination. Importantly, elevated levels of CXCL13 both before and after tumor resection identified a subgroup of patients with significantly impaired outcomes following tumor resection. As such, BTC patients with initial CXCL13 levels above the ideal prognostic cut-off value (25.01 pg/mL) had a median overall survival (OS) of 290 days compared to 969 days for patients with low initial CXCL13 levels. The prognostic value of circulating CXCL13 was further confirmed by uni- and multivariate Cox regression analyses. Finally, the individual kinetics of CXCL13 before and after tumor resection were also indicative of patient outcomes. Conclusion: Our data support a fundamental role of the CXC chemokine family in BTC and identified circulating levels of CXCL13 as a previously unrecognized marker for predicting outcomes following the resection of BTC.
Expression of SARS-CoV-2-Related Surface Proteins in Non-Small-Cell Lung Cancer Patients and the Influence of Standard of Care Therapy
Authors: Deben Christophe , Le Compte Maxim , Siozopoulou Vasiliki , Lambrechts Hilde , Hermans Christophe , Lau Ho Wa , Huizing Manon , Lamote Kevin , Hendriks Jeroen M. H. , Van Dam Peter , Pauwels Patrick , Smits Evelien L. J. , Peeters Marc , Lardon Filip
Published: August 2022

In this study, we aimed to study the expression of SARS-CoV-2-related surface proteins in non-small-cell lung cancer (NSCLC) cells and identify clinicopathological characteristics that are related to increased membranous (m)ACE2 protein expression and soluble (s)ACE2 levels, with a particular focus on standard of care (SOC) therapies. ACE2 (n = 107), TMPRSS2, and FURIN (n = 38) protein expression was determined by immunohistochemical (IHC) analysis in NSCLC patients. sACE2 levels (n = 64) were determined in the serum of lung cancer patients collected before, during, or after treatment with SOC therapies. Finally, the TCGA lung adenocarcinoma (LUAD) database was consulted to study the expression of ACE2 in EGFR- and KRAS-mutant samples and ACE2 expression was correlated with EGFR/HER, RAS, BRAF, ROS1, ALK, and MET mRNA expression. Membranous (m)ACE2 was found to be co-expressed with mFURIN and/or mTMPRSS2 in 16% of the NSCLC samples and limited to the adenocarcinoma subtype. TMPRSS2 showed predominantly atypical cytoplasmic expression. mACE2 and sACE2 were more frequently expressed in mutant EGFR patients, but not mutant-KRAS patients. A significant difference was observed in sACE2 for patients treated with targeted therapies, but not for chemo- and immunotherapy. In the TCGA LUAD cohort, ACE2 expression was significantly higher in EGFR-mutant patients and significantly lower in KRAS-mutant patients. Finally, ACE2 expression was positively correlated with ERBB2-4 and ROS1 expression and inversely correlated with KRAS, NRAS, HRAS, and MET mRNA expression. We identified a role for EGFR pathway activation in the expression of mACE2 in NSCLC cells, associated with increased sACE2 levels in patients. Therefore, it is of great interest to study SARS-CoV-2-infected EGFR-mutated NSCLC patients in greater depth in order to obtain a better understanding of how mACE2, sACE2, and SOC TKIs can affect the course of COVID-19.
Live Biotherapeutic Lactococcus lactis GEN3013 Enhances Antitumor Efficacy of Cancer Treatment via Modulation of Cancer Progression and Immune System
Authors: Kim Sujeong , Kim Yunjae , Lee Suro , Kim Yulha , Jeon Byungkwan , Kim Hyerim , Park Hansoo
Published: August 2022

The gut microbiota is responsible for differential anticancer drug efficacies by modulating the host immune system and the tumor microenvironment. Interestingly, this differential effect is highly strain-specific. For example, certain strains can directly suppress tumor growth and enhance antitumor immunity; however, others do not have such an effect or even promote tumor growth. Identifying effective strains that possess antitumor effects is key for developing live biotherapeutic anticancer products. Here, we found that Lactococcus lactis GEN3013 inhibits tumor growth by regulating tumor angiogenesis and directly inducing cancer cell death. Moreover, L. lactis GEN3013 enhanced the therapeutic effects of oxaliplatin and the PD-1 blockade. Comprehensive immune profiling showed that L. lactis GEN3013 augmented cytotoxic immune cell populations, such as CD4+ T cells, CD8+ effector T cells, and NK cells in the tumor microenvironment. Our results indicate that L. lactis GEN3013 is a promising candidate for potentiating cancer treatment in combination with current standard therapy.
A Real-World Multicentre Retrospective Study of Low-Dose Apatinib for Human Epidermal Growth Factor Receptor 2-Negative Metastatic Breast Cancer
Authors: Zeng Tianyu , Sun Chunxiao , Liang Yan , Yang Fan , Yan Xueqi , Bao Shengnan , Zhang Yucheng , Huang Xiang , Fu Ziyi , Li Wei , Yin Yongmei
Published: August 2022

Treatment options for human epidermal growth factor receptor (HER2)-negative breast cancer patients are limited in comparison to the HER2-positive patients, particularly for metastatic breast cancer patients. Apatinib is a small-molecule tyrosine kinase inhibitor that targets the vascular endothelial growth factor receptor 2 (VEGFR-2). Here, we reported the apatinib-based therapy data in HER2-negative metastatic breast cancer. Apatinib was taken at a dose of 250 mg orally once per day and combined with standard chemotherapy regimens. The PFS and OS of 128 patients were 4.7 months and 15.3 months, respectively. The objective response rate (ORR) and the disease control rate (DCR) were 22.7% and 80.5%, respectively. Patients with breast cancer susceptibility gene (BRCA) mutations were found to have a longer PFS and OS. Moreover, combination immunotherapy or paclitaxel-platinum regimens shared an improved response to other regimens. Most of the adverse effects (hypertension, anaemia, and hand-foot syndrome) were grade 1 to 2. Metastatic breast cancer patients could benefit from apatinib therapy at a low dosage, and the adverse effects are mild in real-world clinical practice. Furthermore, BRCA may be a putative biomarker for apatinib in HER2-negative breast cancer. Immunotherapy or paclitaxel-platinum regimens may be recommended to combine with apatinib therapy.
Embryonated Chicken Tumor Xenografts Derived from Circulating Tumor Cells as a Relevant Model to Study Metastatic Dissemination: A Proof of Concept
Authors: Rousset Xavier , Maillet Denis , Grolleau Emmanuel , Barthelemy David , Calattini Sara , Brevet Marie , Balandier Julie , Raffin Margaux , Geiguer Florence , Garcia Jessica , Decaussin-Petrucci Myriam , Peron Julien , Benzerdjeb Nazim , Couraud Sébastien , Viallet Jean , Payen Léa
Published: August 2022

Patient-Derived Xenografts (PDXs) in the Chorioallantoic Membrane (CAM) are a representative model for studying human tumors. Circulating Tumor Cells (CTCs) are involved in cancer dissemination and treatment resistance mechanisms. To facilitate research and deep analysis of these few cells, significant efforts were made to expand them. We evaluated here whether the isolation of fresh CTCs from patients with metastatic cancers could provide a reliable tumor model after a CAM xenograft. We enrolled 35 patients, with breast, prostate, or lung metastatic cancers. We performed microfluidic-based CTC enrichment. After 48–72 h of culture, the CTCs were engrafted onto the CAM of embryonated chicken eggs at day 9 of embryonic development (EDD9). The tumors were resected 9 days after engraftment and histopathological, immunochemical, and genomic analyses were performed. We obtained in ovo tumors for 61% of the patients. Dedifferentiated small tumors with spindle-shaped cells were observed. The epithelial-to-mesenchymal transition of CTCs could explain this phenotype. Beyond the feasibility of NGS in this model, we have highlighted a genomic concordance between the in ovo tumor and the original patient’s tumor for constitutional polymorphism and somatic alteration in one patient. Alu DNA sequences were detected in the chicken embryo’s distant organs, supporting the idea of dedifferentiated cells with aggressive behavior. To our knowledge, we performed the first chicken CAM CTC-derived xenografts with NGS analysis and evidence of CTC dissemination in the chicken embryo.
Adverse Renal Effects of Anticancer Immunotherapy: A Review
Authors: Borówka Maciej , Łącki-Zynzeling Stanisław , Nicze Michał , Kozak Sylwia , Chudek Jerzy
Published: August 2022

Modern oncological therapy utilizes various types of immunotherapy. Immune checkpoint inhibitors (ICIs), chimeric antigen receptor T cells (CAR-T) therapy, cancer vaccines, tumor-targeting monoclonal antibodies (TT-mAbs), bispecific antibodies and cytokine therapy improve patients’ outcomes. However, stimulation of the immune system, beneficial in terms of fighting against cancer, generates the risk of harm to other cells in a patient’s body. Kidney damage belongs to the relatively rare adverse events (AEs). Best described, but still, superficially, are renal AEs in patients treated with ICIs. International guidelines issued by the European Society for Medical Oncology (ESMO) and the American Society of Clinical Oncology (ASCO) cover the management of immune-related adverse events (irAEs) during ICI therapy. There are fewer data concerning real occurrence and possible presentations of renal adverse drug reactions of other immunotherapeutic methods. This implies the need for the collection of safety data during ongoing clinical trials and in the real-life world to characterize the hazard related to the use of new immunotherapies and management of irAEs.