bluuebunny/crossref_metadata_2025 huggingface dataset:
The Welfare of Cattle, Sheep, Goats and Pigs from the Perspective of Traumatic Injuries Detected at Slaughterhouse Postmortem Inspection
Authors: Valkova Lenka , Vecerek Vladimir , Voslarova Eva , Kaluza Michal , Takacova Daniela
Published: May 2021

The welfare of cattle, pigs, sheep and goats was assessed by measuring trauma detected during veterinary postmortem inspection at slaughterhouses. The subject of this evaluation were all bovine, porcine, ovine and caprine animals slaughtered at Czech slaughterhouses in the monitored period, i.e., a total of 1,136,754 cows, 257,912 heifers, 1,015,541 bulls, 104,459 calves, 586,245 sows, 25,027,303 finisher pigs, 123,191 piglets, 22,815 ewes, 114,264 lambs, 1348 does and 5778 kids. The data on the numbers of traumatic findings were obtained retrospectively from a national veterinary database collecting data from slaughterhouse postmortem examinations. The results showed that findings of trauma were observed at a low frequency in the studied species. Injuries were detected most frequently in cows (1.71%). In contrast, no findings associated with the presence of trauma were recorded in does and kids. From the viewpoint of trauma localization, findings on the limbs were more frequent than findings on the body (p < 0.01). The only exceptions to this were lambs, does and kids, for which there was no statistically significant difference between findings on the limbs and the body (p = 1.00). The results show that housing system (bedding, the presence of slats, floor hardness), transport of animals to the slaughterhouse (moving animals to the vehicle, loading ramps, floors in transport vehicles and the transport of animals itself) and design of the slaughterhouse (unloading ramps, passageways and slaughterhouse floors) have a greater impact on the limbs than the bodies of animals in the majority of species. A difference was also demonstrated in the occurrence of findings of trauma in the limbs and body (p < 0.01) between culled adult animals and fattened animals, namely in cattle and pigs. A difference (p < 0.01) between ewes and lambs was found only in the occurrence of traumatic injury to the limbs. The results showed that fattened animals are affected by the risk of trauma to a lesser extent than both culled adult animals and young animals. Statistically significant differences (p < 0.01) were also found between the studied species and categories of animals. The category most affected from the viewpoint of injury both to the limbs and body was cows. In contrast to cows that are typically reared indoors, the low frequency of traumatic findings was found in small ruminants and in bulls, i.e., animals typically reared outdoors. Assumedly, access to pasture may be beneficial considering the risk of traumatic injury.
Australian Livestock Export Industry Workers’ Attitudes toward Animal Welfare
Authors: Willis Renee S. , Dunston-Clarke Emma J. , Keating Leah R. , Fleming Patricia A. , Collins Teresa
Published: May 2021

Understanding live export industry workers’ attitudes and beliefs toward animal welfare can provide insight into their decision-making processes and likely behavior. Industry workers (n = 265) with various roles within the supply chain were surveyed from different global regions. Participants were divided into ten categories according to their industry roles and compared using ordinal regression. Respondents were highly likely to have a positive attitude toward animal welfare; the majority of workers enjoyed working with livestock (95.8%) and agreed that livestock should be treated with respect (97.7%). Workers demonstrated a strong understanding of animal welfare concepts, 168 respondents (63.4%) provided examples of ways they had improved animal welfare in their workplace, and 164 workers (61.9%) suggested ways that animal welfare could be improved further. Most workers (95.8%) agreed that animal welfare was satisfactory in their workplace. Five out of the 24 multiple-choice responses differed significantly by the participant’s industry role, but no particular group displayed consistently divergent beliefs or attitudes. Given the community concern regarding animals in the livestock export supply chain, it is imperative to understand the attitudes of industry personnel who are responsible for the daily management of the animals. This knowledge assists in the development of animal welfare policy and can inform strategies to manage public perception.
Computed Tomography Osteodensitometry for Assessment of Bone Mineral Density of the Canine Head—Preliminary Results
Authors: Woods Glynn , Israeliantz Gunz Nicolas , Handel Ian , Liuti Tiziana , Mellanby Richard J. , Schwarz Tobias
Published: May 2021

Despite bone mineral density (BMD) being regularly measured in human patients, BMD studies in clinical cohorts of dogs is lacking. In order to facilitate BMD assessment and in turn better identify dogs suffering from metabolic bone disease, rapid, easy and precise computed tomography (qCT) techniques are required. In this study we aimed to assess the utility of quantitative computed tomography (qCT) bone mineral density (BMD) measurement of the canine calvarium using a semiautomated osteodensitometry software and define host factors associated with canine bone mineral density in a skeletally healthy population. Calvarial qCT at the level of the temporomandibular joints was performed on 323 dogs using a dedicated osteodensitometry calibration phantom during a clinically indicated head computed tomography (CT). Calvarial BMD was analyzed using a dedicated semiautomatic osteodensitometry software for contouring of the calvarial lamellar bone margins and BMD calculation. The mean duration of the calvarial qCT scanning was 64.6 s, and the mean duration of BMD analysis was 34 s, with a mean of two manual adjustments required for the bone margin tracing. The median BMD of all dogs in our study was 659 mg Calcium hydroxyapatite/mL. There was a negative linear correlation between BMD and body weight, but no correlation with age, sex or neutered status. Canine BMD assessment using qCT of the calvarium is a practical and fast technique that can be added to a clinical CT examination with minimal extra time requirements. Canine BMD host-dependent factors exhibit different relationships from that of humans; however, further investigation is warranted.
Dynamic Maneuverability Analysis: A Preliminary Application on an Autonomous Underwater Reconfigurable Vehicle
Authors: Topini Edoardo , Pagliai Marco , Allotta Benedetto
Published: May 2021

Since the development of the first autonomous underwater vehicles, the demanded tasks for subsea operations have become more and more challenging as, for instance, intervention, maintenance and repair of seabed installations, in addition to surveys. As a result, the development of autonomous underwater reconfigurable vehicles (AURVs) with the capability of interacting with the surrounding environment and autonomously changing the configuration, according to the task at hand, can represent a real breakthrough in underwater system technologies. Driven by these considerations, an innovative AURV has been designed by the Department of Industrial Engineering of the University of Florence (named as UNIFI DIEF AURV), capable of efficiently reconfiguring its shape according to the task at hand. In particular, the UNIFI DIEF AURV has been provided with two extreme configurations: a slender (“survey”) configuration for long navigation tasks, and a stocky (“hovering”) configuration designed for challenging goals as intervention operations. In order to observe the several dynamic features for the two different configurations, a novel formulation for the dynamic maneuverability analysis (DMA) of an AURV, adapting Yoshikawa’s well-known manipulability theory for robotic arms, is proposed in this work. More specifically, we introduce a novel analysis which relates the vehicle body-fixed accelerations with the rotational speed of each thruster, taking into account also the AURV dynamic model for each configuration and the propulsion system.
Application of Collision Warning Algorithm Alarm in Fishing Vessel’s Waterway
Authors: Lee Myoung-Ki , Park Young-Soo , Park Sangwon , Lee Eunkyu , Park Minjeong , Kim Ni-Eun
Published: May 2021

The aim of this study is to apply a collision warning algorithm for a small fishing vessel in a fishing waterway to verify its alarm operation and to validate its feasibility. For this purpose, a scenario-based real ship test was conducted, and cases extracted from real sea data (Vpass data) were applied. Moreover, zones with frequent alarms and high-risk waters were compared. First, we installed millimeter-wave communication terminals in three small fishing vessels and applied our algorithm based on two scenarios. Furthermore, we applied the collision warning algorithm by extracting two cases encountered by multiple ships from the Vpass data. The results show that the algorithm triggered alarms continuously under risky situations. This study also compares waterway risk levels as assessed by maritime risk-assessment tools (potential assessment of risk model, environment stress model, and International Association of Marine Aids to Navigation and Lighthouse Authorities Waterway Risk Assessment Program MkII) and the locations having frequent alarms based on Vpass data collected for 7 days. Not only did the eastern sea of Yeongheung Island indicate that more alarms were triggered, but we found high-risk results from the risk-level assessment, indicating that the risky zones and the frequent alarm zones were identical. Additional research is necessary to develop an algorithm based on qualitative evaluation by actual ship operators. In addition, since fishing vessels navigate differently from general navigation methods during fishing, it is necessary to develop additional algorithms for this.
Geoarchaeology: Where Geosciences Meet the Humanities to Reconstruct Past Human–Environment Interactions. An Application to the Coastal Areas of the Largest Mediterranean Islands
Authors: Ghilardi Matthieu
Published: May 2021

The study of past Human–Environment interactions has long been seen at a very local scale, that of sites of human occupation. Geoarchaeology differs from the traditional concepts of Environmental Archaeology and Landscape Archaeology in this respect since it adopts a different spatial resolution based on the development of multidisciplinary research at the scale of geographical, geological or geomorphological features. In this paper, we aim to contribute to the definition of coastal geoarchaeology where environmental holistic studies can be developed, thus integrating both continental and marine dynamics. A specific application is realized here for the largest Mediterranean islands where heterogeneity can be observed in research over the last decades. For this reason, we divide the Mediterranean Basin into four areas in order to review the main works conducted. In general, investigating coastal environments represents an exciting opportunity to reconstruct past landscapes and to evidence the long-term history of human occupation and land use by employing a wide range of proxies. We focus in particular on the coastal wetlands of Corsica, where a large number of lagoons have been cored since the early 2010s. Multiproxy laboratory analyses reveal a history of the complex relationships between past human societies and their environments which is complementary to existing archaeological studies.
A Mobile Robot Position Adjustment as a Fusion of Vision System and Wheels Odometry in Autonomous Track Driving
Authors: Zwierzchowski Jarosław , Pietrala Dawid , Napieralski Jan , Napieralski Andrzej
Published: May 2021

Autonomous mobile vehicles need advanced systems to determine their exact position in a certain coordinate system. For this purpose, the GPS and the vision system are the most often used. These systems have some disadvantages, for example, the GPS signal is unavailable in rooms and may be inaccurate, while the vision system is strongly dependent on the intensity of the recorded light. This paper assumes that the primary system for determining the position of the vehicle is wheel odometry joined with an IMU (Internal Measurement Unit) sensor, which task is to calculate all changes in the robot orientations, such as yaw rate. However, using only the results coming from the wheels system provides additive measurement error, which is most often the result of the wheels slippage and the IMU sensor drift. In the presented work, this error is reduced by using a vision system that constantly measures vehicle distances to markers located in its space. Additionally, the paper describes the fusion of signals from the vision system and the wheels odometry. Studies related to the positioning accuracy of the vehicle with both the vision system turned on and off are presented. The laboratory averaged positioning accuracy result was reduced from 0.32 m to 0.13 m, with ensuring that the vehicle wheels did not experience slippage. The paper also describes the performance of the system during a real track driven, where the assumption was not to use the GPS geolocation system. In this case, the vision system assisted in the vehicle positioning and an accuracy of 0.2 m was achieved at the control points.
Community Detection Based on Graph Representation Learning in Evolutionary Networks
Authors: Chen Dongming , Nie Mingshuo , Wang Jie , Kong Yun , Wang Dongqi , Huang Xinyu
Published: May 2021

Aiming at analyzing the temporal structures in evolutionary networks, we propose a community detection algorithm based on graph representation learning. The proposed algorithm employs a Laplacian matrix to obtain the node relationship information of the directly connected edges of the network structure at the previous time slice, the deep sparse autoencoder learns to represent the network structure under the current time slice, and the K-means clustering algorithm is used to partition the low-dimensional feature matrix of the network structure under the current time slice into communities. Experiments on three real datasets show that the proposed algorithm outperformed the baselines regarding effectiveness and feasibility.
Brilliant Red HE-3B Dye Biosorption by Immobilized Residual Consortium Bacillus sp. Biomass: Fixed-Bed Column Studies
Authors: Horciu Luiza , Zaharia Carmen , Blaga Alexandra , Rusu Lacramioara , Suteu Daniela
Published: May 2021

Residual biomass from various industries represents an important source of valuable compounds, used as raw materials for the production of a wide range of new products and also in various treatment and valorization processes or/and sanitation services, thus responding to the principles of sustainable development, waste recovery, and a green and circular economy. The aim of this work is to make use of residual Bacillus sp. biomass (resulting from a process of removing fatty acids from municipal wastewater) immobilized in alginate that, although it results in large quantities from biotechnological processes, is not reported to be valorized in dye biosorption processes, except in few specific applications. The biosorption potential of residual Bacillus sp. biomass in the reactive Brilliant Red HE-3B textile dye removal from aqueous systems was studied in a fixed-bed column. The effects of various experimental operating parameters, such as bed depth (h), flow rate (Fv), were investigated, and the modeling of experimental data based on Thomas and Yoon–Nelson kinetic models was satisfactorily achieved. The obtained results reconfirm that the studied residual biomass can be also considered as a good biosorbent in dynamic operating system, and can be beneficially used in the treatment of wastewater containing small quantities of organic dyes.
Study of Image Classification Accuracy with Fourier Ptychography
Authors: Zhang Hongbo , Zhang Yaping , Wang Lin , Hu Zhijuan , Zhou Wenjing , Tsang Peter W. M. , Cao Deng , Poon Ting-Chung
Published: May 2021

In this research, the accuracy of image classification with Fourier Ptychography Microscopy (FPM) has been systematically investigated. Multiple linear regression shows a strong linear relationship between the results of image classification accuracy and image visual appearance quality based on PSNR and SSIM with multiple training datasets including MINST, Fashion MNIST, Cifar, Caltech 101, and customized training datasets. It is, therefore, feasible to predict the image classification accuracy only based on PSNR and SSIM. It is also found that the image classification accuracy of FPM reconstructed with higher resolution images is significantly different from using the lower resolution images under the lower numerical aperture (NA) condition. The difference is yet less pronounced under the higher NA condition.
Development of a Drawing Application for Communication Support during Endoscopic Surgery and Its Evaluation Using Steering Law
Authors: Asao Takafumi , Kobayashi Takeru , Kotani Kentaro , Suzuki Satoshi , Obama Kazutaka , Sumii Atsuhiko , Nishigori Tatsuto
Published: May 2021

The purpose of this study is to construct a hands-free endoscopic surgical communication support system that can draw lines in space corresponding to head movements using AR technology and evaluate the applicability of the drawing motion by the head movement to the steering law, one of the HCI models, for the potential use during endoscopic surgery. In the experiment, the participants manipulated the cursor by using head movements through the pathway and movement time (MT); the number of errors and subjective evaluation of the difficulty of the task was obtained. The results showed that the head-movement-based line drawing manipulation was significantly affected by the tracking direction and by the task difficulty, shown as the Index of Difficulty (ID). There was high linearity between ID and MT, with a coefficient of determination R2 of 0.9991. The Index of Performance was higher in the horizontal and vertical directions compared to diagonal directions. Although the weight and biocompatibility of the AR glasses must be overcome to make the current prototype a viable tool for supporting communication in the operating room environment, the prototype has the potential to promote the development of a computer-supported collaborative work environment for endoscopic surgery purposes.
Enhancing Surface Fault Detection Using Machine Learning for 3D Printed Products
Authors: Kadam Vaibhav , Kumar Satish , Bongale Arunkumar , Wazarkar Seema , Kamat Pooja , Patil Shruti
Published: May 2021

In the era of Industry 4.0, the idea of 3D printed products has gained momentum and is also proving to be beneficial in terms of financial and time efforts. These products are physically built layer-by-layer based on the digital Computer Aided Design (CAD) inputs. Nonetheless, 3D printed products are still subjected to defects due to variation in properties and structure, which leads to deterioration in the quality of printed products. Detection of these errors at each layer level of the product is of prime importance. This paper provides the methodology for layer-wise anomaly detection using an ensemble of machine learning algorithms and pre-trained models. The proposed combination is trained offline and implemented online for fault detection. The current work provides an experimental comparative study of different pre-trained models with machine learning algorithms for monitoring and fault detection in Fused Deposition Modelling (FDM). The results showed that the combination of the Alexnet and SVM algorithm has given the maximum accuracy. The proposed fault detection approach has low experimental and computing costs, which can easily be implemented for real-time fault detection.
Comparative Assessment of Medicinal Plant Utilization among Balti and Shina Communities in the Periphery of Deosai National Park, Pakistan
Authors: Abbas Zaheer , Kousar Shazia , Aziz Muhammad Abdul , Pieroni Andrea , Aldosari Ali Abdullah , Bussmann Rainer W. , Raza Ghulam , Abbasi Arshad Mehmood
Published: May 2021

Traditional ecological knowledge, linguistic, and sociocultural perspectives are key contributors to environmental sustainability. Therefore, it is essential to identify and preserve this biocultural heritage, especially that of indigenous communities and minorities. We conducted an ethnobotanical survey to document the plant species used by the Balti and Shina communities living in the buffer zone of Deosai National Park (DNP), western Himalayas, Pakistan. A combination of random and purposive sampling techniques was adapted, targeting middle- and old-aged informants. A total of 46 semi-structured interviews were conducted and the gathered data were evaluated using relative frequency of citation (RFC) and through comparison with the ethnomedicinal literature. In total, 47 medicinal plant species belonging to 42 genera and 23 families were recorded. Baltis and Shinas cited 42 and 38 plant species, respectively, that were used to treat various diseases. About 60% of species were common among both communities, but 27.7% and 12.8% were exclusive to Baltis and Shinas, respectively. Considerable heterogeneity was noted in vernacular names, plant part(s) used, preparation, and administration. Ribes alpestre, Aconitum violaceum, Delphinium brunonianum, Thymus linearis, and Swertia petiolata were highly utilized species having RFCs > 50. In addition, 46% of medicinal uses, specifically that of Allardia tomentosa, A. tridactylites, Jurinea dolomiaea, and Gallium boreale, were reported for the first time from the region. Cross-cultural analysis revealed sociocultural gaps between both groups. Relatively, Baltis retained more ethnomedicinal knowledge and their traditional medicinal system is more closely associated with traditional Tibetan medicine. Generally, Balti and Shina communities retain substantial biocultural and ethnological diversity, which has been reflected in the present study. Our findings underline the importance and need for sustainable utilization of natural resources, specifically the plant species of this region. However, an in-depth ethnobotanical investigation may underpin the holistic comparative medical ethnobotany of the entire region.
Virulence Determinants of Colistin-Resistant K. pneumoniae High-Risk Clones
Authors: Dogan Ozlem , Vatansever Cansel , Atac Nazli , Albayrak Ozgur , Karahuseyinoglu Sercin , Sahin Ozgun Ekin , Kilicoglu Bilge Kaan , Demiray Atalay , Ergonul Onder , Gönen Mehmet , Can Fusun
Published: May 2021

We proposed the hypothesis that high-risk clones of colistin-resistant K. pneumoniae (ColR-Kp) possesses a high number of virulence factors and has enhanced survival capacity against the neutrophil activity. We studied virulence genes of ColR-Kp isolates and neutrophil response in 142 patients with invasive ColR-Kp infections. The ST101 and ST395 ColR-Kp infections had higher 30-day mortality (58%, p = 0.005 and 75%, p = 0.003). The presence of yersiniabactin biosynthesis gene (ybtS) and ferric uptake operon associated gene (kfu) were significantly higher in ST101 (99%, p ≤ 0.001) and ST395 (94%, p < 0.012). Being in ICU (OR: 7.9; CI: 1.43–55.98; p = 0.024), kfu (OR:27.0; CI: 5.67–179.65; p < 0.001) and ST101 (OR: 17.2; CI: 2.45–350.40; p = 0.01) were found to be predictors of 30-day mortality. Even the neutrophil uptake of kfu+-ybtS+ ColR-Kp was significantly higher than kfu--ybtS- ColR-Kp (phagocytosis rate: 78% vs. 65%, p < 0.001), and the kfu+-ybtS+ ColR-Kp survived more than kfu--ybtS- ColR-Kp (median survival index: 7.90 vs. 4.22; p = 0.001). The kfu+-ybtS+ ColR-Kp stimulated excessive NET formation. Iron uptake systems in high-risk clones of colistin-resistant K. pneumoniae enhance the success of survival against the neutrophil phagocytic defense and stimulate excessive NET formation. The drugs targeted to iron uptake systems would be a promising approach for the treatment of colistin-resistant high-risk clones of K. pneumoniae infections.
A Comparison of Craniofacial Characteristics between Two Different Adult Populations with Class II Malocclusion—A Cross-Sectional Retrospective Study
Authors: Sivakumar Arvind , Nalabothu Prasad , Thanh Huyen Nguyen , Antonarakis Gregory S.
Published: May 2021

The dental, skeletal, and soft-tissue characteristics of a particular malocclusion can differ based on ethnicity, race, age, sex and geographical location with Class II malocclusion being one of the most prevalent malocclusions encountered in orthodontic clinical practice. The broad understanding of the characteristics of vertical skeletal and dental parameters in patients with Class II malocclusion can help clinicians to identify patterns and variations in the expression of this phenotype for better treatment outcomes. Hence, we compared the craniofacial characteristics of skeletal and dental Class II malocclusion traits from Indian and Vietnamese individuals to analyze the vertical skeletal and dental patterns in both population groups. The sample comprised of lateral cephalograms from 100 young adults with Class II malocclusion, of which fifty (25 males and 25 females) were from South India and the other 50 age- and sex-matched adults from Vietnam. The lateral cephalometric radiographs were digitized into anonymous image files and were traced and assessed for 16 vertical skeletal and dental parameters. The ANB angle was greater in males (+1.4 deg; p < 0.001) and females (+1.9 deg; p < 0.001) in the South Indian population. The Vietnamese males had a larger mandibular plane angle, articular angle, anterior facial height and lower anterior facial height compared to the Indian males. The Vietnamese females had larger mandibular plane and articular angles compared to the Indian females. The skeletal class II malocclusion was more severe in the South Indian compared to the Vietnamese adults. The Vietnamese sample showed a generalized tendency towards a more vertical skeletal growth pattern and in males this pattern seemed to be due to the dentoalveolar component. The Vietnamese females showed a tendency towards a vertical growth pattern, but without apparent contribution by the dentoalveolar component.
Cas12a and Lateral Flow Strip-Based Test for Rapid and Ultrasensitive Detection of Spinal Muscular Atrophy
Authors: Zhang Chunhua , Li Zhuo , Chen Miaomiao , Hu Zhiqing , Wu Lingqian , Zhou Miaojin , Liang Desheng
Published: May 2021

Spinal muscular atrophy (SMA) is characterized by severe lethality and irreversible progression. Early diagnosis of SMA is of more practical significance with the emergence of effective therapy. However, existing techniques to identify SMA patients rely on cumbersome instruments, hindering their accessibility and application. An SMA-Cas12a-strip assay was developed with the integration of Cas12a-based nucleic acid detection, isothermal amplification, and lateral flow strip. The analytical performance of the assay was assessed with clinical samples. To explore its extensible utility, various specimens were tested. Validated with 168 clinical samples, the sensitivity and specificity of the SMA-Cas12a-strip assay were both 100%. The minimum detectable concentration of genomic DNA containing the target gene achieved 526 aM. The assay was compatible with specimens from several sources, and the turnaround time could be within 1.5 h. We developed a simple, cost-effective, and highly sensitive and specific assay to detect SMA patients. With little and field-portable equipment, the assay holds great promise in the detection of SMA patients, particularly in low-resource regions.
Pre-Operative Decitabine in Colon Cancer Patients: Analyses on WNT Target Methylation and Expression
Authors: Linnekamp Janneke F. , Kandimalla Raju , Fessler Evelyn , de Jong Joan H. , Rodermond Hans M. , van Bochove Gregor G. W. , The Frans O. , Punt Cornelis J. A. , Bemelman Willem A. , van de Ven Anthony W. H. , Tanis Pieter J. , Kemper Elles M. , Koens Lianne , Dekker Evelien , Vermeulen Louis , van Laarhoven Hanneke W. M. , Medema Jan Paul
Published: May 2021

DNA hypermethylation is common in colon cancer. Previously, we have shown that methylation of WNT target genes predicts poor prognosis in stage II colon cancer. The primary objective of this study was to assess whether pre-operative treatment with decitabine can decrease methylation and increase the expression of WNT target genes APCDD1, AXIN2 and DKK1 in colon cancer patients. A clinical study was conducted, investigating these potential effects of decitabine in colon cancer patients (DECO). Patients were treated two times with 25 mg/m2 decitabine before surgery. Methylation and expression of LINE1 and WNT target genes (primary outcome) and expression of endogenous retroviral genes (secondary outcome) were analysed in pre- and post-treatment tumour samples using pyrosequencing and rt-PCR. Ten patients were treated with decitabine and eighteen patients were used as controls. Decitabine treatment only marginally decreased LINE1 methylation. More importantly, no differences in methylation or expression of WNT target or endogenous retroviral genes were observed. Due to the lack of an effect on primary and secondary outcomes, the study was prematurely closed. In conclusion, pre-operative treatment with decitabine is safe, but with the current dosing, the primary objective, increased WNT target gene expression, cannot be achieved.
Primary Aneurysmal Bone Cyst and Its Recent Treatment Options: A Comparative Review of 74 Cases
Authors: Deventer Nils , Schulze Martin , Gosheger Georg , de Vaal Marieke , Deventer Niklas
Published: May 2021

(1) Background: An aneurysmal bone cyst (ABC) is a benign, locally aggressive tumor. Different treatment modalities are described in the literature i.e., en bloc resection, intralesional curettage and percutaneous sclerotherapy. (2) Methods: This single-center study is a review of 74 patients with primary ABCs who underwent a surgical treatment or polidocanol instillation. Cyst volume measurements using MRI and conventional radiographs are compared. (3) Results: The mean pre-interventional MRI-based cyst volume was 44.07 cm3 and the mean radiographic volume was 27.27 cm3. The recurrence rate after intralesional curettage with the need for further treatment was 38.2% (13/34). The instillation of polidocanol showed a significant reduction of the initial cyst volume (p < 0.001) but a persistent disease occurred in 29/32 cases (90.6%). In 10 of these 29 cases (34.5%) further treatment was necessary. After en bloc resection (eight cases) a local recurrence occurred in two cases (25%), in one case with the need for further treatment. (4) Conclusions: MRI scans are superior to biplanar radiographs in the examination of ABCs. Sequential percutaneous instillations of polidocanol are equally effective in the therapy of primary ABCs compared to intralesional curettage. However, several instillations have to be expected. In a considerable number of cases, a conversion to intralesional curettage or en bloc resection may be necessary.
Data-Driven Mathematical Model of Osteosarcoma
Authors: Le Trang , Su Sumeyye , Kirshtein Arkadz , Shahriyari Leili
Published: May 2021

As the immune system has a significant role in tumor progression, in this paper, we develop a data-driven mathematical model to study the interactions between immune cells and the osteosarcoma microenvironment. Osteosarcoma tumors are divided into three clusters based on their relative abundance of immune cells as estimated from their gene expression profiles. We then analyze the tumor progression and effects of the immune system on cancer growth in each cluster. Cluster 3, which had approximately the same number of naive and M2 macrophages, had the slowest tumor growth, and cluster 2, with the highest population of naive macrophages, had the highest cancer population at the steady states. We also found that the fastest growth of cancer occurred when the anti-tumor immune cells and cytokines, including dendritic cells, helper T cells, cytotoxic cells, and IFN-γ, switched from increasing to decreasing, while the dynamics of regulatory T cells switched from decreasing to increasing. Importantly, the most impactful immune parameters on the number of cancer and total cells were the activation and decay rates of the macrophages and regulatory T cells for all clusters. This work presents the first osteosarcoma progression model, which can be later extended to investigate the effectiveness of various osteosarcoma treatments.
Prediction of Microvascular Invasion in Hepatocellular Carcinoma via Deep Learning: A Multi-Center and Prospective Validation Study
Authors: Wei Jingwei , Jiang Hanyu , Zeng Mengsu , Wang Meiyun , Niu Meng , Gu Dongsheng , Chong Huanhuan , Zhang Yanyan , Fu Fangfang , Zhou Mu , Chen Jie , Lyv Fudong , Wei Hong , Bashir Mustafa R. , Song Bin , Li Hongjun , Tian Jie
Published: May 2021

Microvascular invasion (MVI) is a critical risk factor for postoperative recurrence of hepatocellular carcinoma (HCC). Preknowledge of MVI would assist tailored surgery planning in HCC management. In this multicenter study, we aimed to explore the validity of deep learning (DL) in MVI prediction using two imaging modalities—contrast-enhanced computed tomography (CE-CT) and gadoxetic acid-enhanced magnetic resonance imaging (EOB-MRI). A total of 750 HCCs were enrolled from five Chinese tertiary hospitals. Retrospective CE-CT (n = 306, collected between March, 2013 and July, 2019) and EOB-MRI (n = 329, collected between March, 2012 and March, 2019) data were used to train two DL models, respectively. Prospective external validation (n = 115, collected between July, 2015 and February, 2018) was performed to assess the developed models. Furthermore, DL-based attention maps were utilized to visualize high-risk MVI regions. Our findings revealed that the EOB-MRI-based DL model achieved superior prediction outcome to the CE-CT-based DL model (area under receiver operating characteristics curve (AUC): 0.812 vs. 0.736, p = 0.038; sensitivity: 70.4% vs. 57.4%, p = 0.015; specificity: 80.3% vs. 86.9%, p = 0.052). DL attention maps could visualize peritumoral high-risk areas with genuine histopathologic confirmation. Both DL models could stratify high and low-risk groups regarding progression free survival and overall survival (p < 0.05). Thus, DL can be an efficient tool for MVI prediction, and EOB-MRI was proven to be the modality with advantage for MVI assessment than CE-CT.
MicroRNAs Deregulated in Intraductal Papillary Mucinous Neoplasm Converge on Actin Cytoskeleton-Related Pathways That Are Maintained in Pancreatic Ductal Adenocarcinoma
Authors: Fernandez-Castañer Elena , Vila-Casadesus Maria , Vila-Navarro Elena , Parra Carolina , Lozano Juan Jose , Castells Antoni , Gironella Meritxell
Published: May 2021

Intraductal papillary mucinous neoplasms (IPMN) are pancreatic cystic lesions that can develop into pancreatic ductal adenocarcinoma (PDAC). Although there is an increasing incidence of IPMN diagnosis, the mechanisms of formation and progression into invasive cancer remain unclear. MicroRNAs (miRNAs) are small non-coding RNAs, repressors of mRNA translation, and promising diagnostic biomarkers for IPMN and PDAC. Functional information on the role of early-altered miRNAs in this setting would offer novel strategies for tracking the IPMN-to-PDAC progression. In order to detect mRNAs that are likely to be under miRNA regulation in IPMNs, whole transcriptome and miRNome data from normal pancreatic tissue (n = 3) and IPMN lesions (n = 4) were combined and filtered according to negative correlation and miRNA-target prediction databases by using miRComb R package. Further comparison analysis with PDAC data allowed us to obtain a subset of miRNA-mRNA pairs shared in IPMN and PDAC. Functional enrichment analysis unravelled processes that are mainly related with cell structure, actin cytoskeleton, and metabolism. MiR-181a appeared as a master regulator of these processes. The expression of selected miRNA-mRNA pairs was validated by qRT-PCR in an independent cohort of patients (n = 40), and then analysed in different pancreatic cell lines. Finally, we generated a cellular model of HPDE cells stably overexpressing miR-181a, which showed a significant alteration of actin cytoskeleton structures accompanied by a significant downregulation of EPB41L4B and SEL1L expression. In situ hybridization of miR-181a and immunohistochemistry of EPB41L4B and SEL1L in pancreatic tissues (n = 4 Healthy; n = 3 IPMN; n = 4 PDAC) were also carried out. In this study, we offer insights on the potential implication of miRNA alteration in the regulation of structural and metabolic changes that pancreatic cells experience during IPMN establishment and that are maintained in PDAC.
Afucosylated IgG Targets FcγRIV for Enhanced Tumor Therapy in Mice
Authors: Braster Rens , Bögels Marijn , Benonisson Hreinn , Wuhrer Manfred , Plomp Rosina , Bentlage Arthur E. H. , Korthouwer Rianne , Visser Remco , Verbeek J. Sjef , van Egmond Marjolein , Vidarsson Gestur
Published: May 2021

Promising strategies for maximizing IgG effector functions rely on the introduction of natural and non-immunogenic modifications. The Fc domain of IgG antibodies contains an N-linked oligosaccharide at position 297. Human IgG antibodies lacking the core fucose in this glycan have enhanced binding to human (FcγR) IIIa/b, resulting in enhanced antibody dependent cell cytotoxicity and phagocytosis through these receptors. However, it is not yet clear if glycan-enhancing modifications of human IgG translate into more effective treatment in mouse models. We generated humanized hIgG1-TA99 antibodies with and without core-fucose. C57Bl/6 mice that were injected intraperitoneally with B16F10-gp75 mouse melanoma developed significantly less metastasis outgrowth after treatment with afucosylated hIgG1-TA99 compared to mice treated with wildtype hhIgG1-TA99. Afucosylated human IgG1 showed stronger interaction with the murine FcγRIV, the mouse orthologue of human FcγRIIIa, indicating that this glycan change is functionally conserved between the species. In agreement with this, no significant differences were observed in tumor outgrowth in FcγRIV-/- mice treated with human hIgG1-TA99 with or without the core fucose. These results confirm the potential of using afucosylated therapeutic IgG to increase their efficacy. Moreover, we show that afucosylated human IgG1 antibodies act across species, supporting that mouse models can be suitable to test afucosylated antibodies.
Lesion-Function Analysis from Multimodal Imaging and Normative Brain Atlases for Prediction of Cognitive Deficits in Glioma Patients
Authors: Kocher Martin , Jockwitz Christiane , Lohmann Philipp , Stoffels Gabriele , Filss Christian , Mottaghy Felix M. , Ruge Maximilian I. , Weiss Lucas Carolin , Goldbrunner Roland , Shah Nadim J. , Fink Gereon R. , Galldiks Norbert , Langen Karl-Josef , Caspers Svenja
Published: May 2021

Cognitive deficits are common in glioma patients following multimodality therapy, but the relative impact of different types and locations of treatment-related brain damage and recurrent tumors on cognition is not well understood. In 121 WHO Grade III/IV glioma patients, structural MRI, O-(2-[18F]fluoroethyl)-L-tyrosine FET-PET, and neuropsychological testing were performed at a median interval of 14 months (range, 1–214 months) after therapy initiation. Resection cavities, T1-enhancing lesions, T2/FLAIR hyperintensities, and FET-PET positive tumor sites were semi-automatically segmented and elastically registered to a normative, resting state (RS) fMRI-based functional cortical network atlas and to the JHU atlas of white matter (WM) tracts, and their influence on cognitive test scores relative to a cohort of matched healthy subjects was assessed. T2/FLAIR hyperintensities presumably caused by radiation therapy covered more extensive brain areas than the other lesion types and significantly impaired cognitive performance in many domains when affecting left-hemispheric RS-nodes and WM-tracts as opposed to brain tissue damage caused by resection or recurrent tumors. Verbal episodic memory proved to be especially vulnerable to T2/FLAIR abnormalities affecting the nodes and tracts of the left temporal lobe. In order to improve radiotherapy planning, publicly available brain atlases, in conjunction with elastic registration techniques, should be used, similar to neuronavigation in neurosurgery.
Development of a Multi-Institutional Prediction Model for Three-Year Survival Status in Patients with Uterine Leiomyosarcoma (AGOG11-022/QCGC1302 Study)
Authors: Tse Ka-Yu , Wong Richard Wing-Cheuk , Chao Angel , Ueng Shir-Hwa , Yang Lan-Yan , Cummings Margaret , Smith Deborah , Lai Chiung-Ru , Lau Hei-Yu , Yen Ming-Shyen , Cheung Annie Nga-Yin , Leung Charlotte Ka-Lun , Chan Kit-Sheung , Chan Alice Ngot-Htain , Li Wai-Hon , Choi Carmen Ka-Man , Pong Wai-Mei , Hui Hoi-Fong , Yuk Judy Ying-Wah , Yao Hung , Yuen Nancy Wah-Fun , Obermair Andreas , Lai Chyong-Huey , Ip Philip Pun-Ching , Ngan Hextan Yuen-Sheung
Published: May 2021

Background: The existing staging systems of uterine leiomyosarcoma (uLMS) cannot classify the patients into four non-overlapping prognostic groups. This study aimed to develop a prediction model to predict the three-year survival status of uLMS. Methods: In total, 201 patients with uLMS who had been treated between June 1993 and January 2014, were analyzed. Potential prognostic indicators were identified by univariate models followed by multivariate analyses. Prediction models were constructed by binomial regression with 3-year survival status as a binary outcome, and the final model was validated by internal cross-validation. Results: Nine potential parameters, including age, log tumor diameter, log mitotic count, cervical involvement, parametrial involvement, lymph node metastasis, distant metastasis, tumor circumscription and lymphovascular space invasion were identified. 110 patients had complete data to build the prediction models. Age, log tumor diameter, log mitotic count, distant metastasis, and circumscription were significantly correlated with the 3-year survival status. The final model with the lowest Akaike’s Information Criterion (117.56) was chosen and the cross validation estimated prediction accuracy was 0.745. Conclusion: We developed a prediction model for uLMS based on five readily available clinicopathologic parameters. This might provide a personalized prediction of the 3-year survival status and guide the use of adjuvant therapy, a cancer surveillance program, and future studies.
Reduced Lamin A/C Does Not Facilitate Cancer Cell Transendothelial Migration but Compromises Lung Metastasis
Authors: Roncato Francesco , Regev Ofer , Feigelson Sara W. , Yadav Sandeep Kumar , Kaczmarczyk Lukasz , Levi Nehora , Drago-Garcia Diana , Ovadia Samuel , Kizner Marina , Addadi Yoseph , Sabino João C. , Ovadya Yossi , de Almeida Sérgio F. , Feldmesser Ester , Gerlitz Gabi , Alon Ronen
Published: May 2021

The mechanisms by which the nuclear lamina of tumor cells influences tumor growth and migration are highly disputed. Lamin A and its variant lamin C are key lamina proteins that control nucleus stiffness and chromatin conformation. Downregulation of lamin A/C in two prototypic metastatic lines, B16F10 melanoma and E0771 breast carcinoma, facilitated cell squeezing through rigid pores, and reduced heterochromatin content. Surprisingly, both lamin A/C knockdown cells grew poorly in 3D spheroids within soft agar, and lamin A/C deficient cells derived from spheroids transcribed lower levels of the growth regulator Yap1. Unexpectedly, the transendothelial migration of both cancer cells in vitro and in vivo, through lung capillaries, was not elevated by lamin A/C knockdown and their metastasis in lungs was even dramatically reduced. Our results are the first indication that reduced lamin A/C content in distinct types of highly metastatic cancer cells does not elevate their transendothelial migration (TEM) capacity and diapedesis through lung vessels but can compromise lung metastasis at a post extravasation level.
Validation of Selected Head and Neck Cancer Prognostic Markers from the Pathology Atlas in an Oral Tongue Cancer Cohort
Authors: Wirsing Anna Maria , Bjerkli Inger-Heidi , Steigen Sonja Eriksson , Rikardsen Oddveig , Magnussen Synnøve Norvoll , Hegge Beate , Seppola Marit , Uhlin-Hansen Lars , Hadler-Olsen Elin
Published: May 2021

The Pathology Atlas is an open-access database that reports the prognostic value of protein-coding transcripts in 17 cancers, including head and neck cancer. However, cancers of the various head and neck anatomical sites are specific biological entities. Thus, the aim of the present study was to validate promising prognostic markers for head and neck cancer reported in the Pathology Atlas in oral tongue squamous cell carcinoma (OTSCC). We selected three promising markers from the Pathology Atlas (CALML5, CD59, LIMA1), and analyzed their prognostic value in a Norwegian OTSCC cohort comprising 121 patients. We correlated target protein and mRNA expression in formalin-fixed, paraffin-embedded cancer tissue to five-year disease-specific survival (DSS) in univariate and multivariate analyses. Protein expression of CALML5 and LIMA1 were significantly associated with five-year DSS in the OTSCC cohort in univariate analyses (p = 0.016 and p = 0.043, respectively). In multivariate analyses, lymph node metastases, tumor differentiation, and CALML5 were independent prognosticators. The prognostic role of the other selected markers for head and neck cancer patients identified through unbiased approaches could not be validated in our OTSCC cohort. This underlines the need for subsite-specific analyses for head and neck cancer.
Modulation of Endocannabinoid Tone in Osteoblastic Differentiation of MC3T3-E1 Cells and in Mouse Bone Tissue over Time
Authors: Kostrzewa Magdalena , Mahmoud Ali Mokhtar , Verde Roberta , Scotto di Carlo Federica , Gianfrancesco Fernando , Piscitelli Fabiana , Ligresti Alessia
Published: May 2021

Bone is a highly complex and metabolically active tissue undergoing a continuous remodeling process, which endures throughout life. A complex cell-signaling system that plays role in regulating different physiological processes, including bone remodeling, is the endocannabinoid system (ECS). Bone mass expresses CB1 and CB2 cannabinoid receptors and enzymatic machinery responsible for the metabolism of their endogenous ligands, endocannabinoids (AEA and 2-AG). Exogenous AEA is reported to increase the early phase of human osteoblast differentiation in vitro. However, regarding this cell context little is known about how endocannabinoids and endocannabinoid-related N-acylethanolamines like PEA and OEA are modulated, in vitro, during cell differentiation and, in vivo, over time up to adulthood. Here we characterized the endocannabinoid tone during the different phases of the osteoblast differentiation process in MC3T3-E1 cells, and we measured endocannabinoid levels in mouse femurs at life cycle stages characterized by highly active bone growth (i.e., of juvenile, young adult, and mature adult bone). Endocannabinoid tone was significantly altered during osteoblast differentiation, with substantial OEA increment, decline in 2-AG and AEA, and consistent modulation of their metabolic enzymes in maturing and mineralized MC3T3-E1 cells. Similarly, in femurs, we found substantial, age-related, decline in 2-AG, OEA, and PEA. These findings can expand existing knowledge underlying physiological bone cell function and contribute to therapeutic strategies for preventing bone-related metabolic changes accruing through lifespan.