bluuebunny/crossref_metadata_2025 huggingface dataset:
A Comparative Study of Sheep Breeds: Fattening Performance, Carcass Characteristics, Meat Chemical Composition and Quality Attributes
Authors: Suliman G. M. , Al-Owaimer A. N. , El-Waziry A. M. , Hussein E. O. S. , Abuelfatah K. , Swelum A. A.
Published: March 2021

Fattening performance, Carcass characteristics, chemical composition, and meat quality were evaluated in three sheep breeds: Awassi, Harri, and Najdi. Forty-five lambs of similar weight and age were raised for 90 days under similar conditions. The Harri and Najdi breeds had higher dressing-out percentages than Awassi sheep. The Awassi and Harri breeds had thicker backfat than the Najdi breed. No significant difference was found in moisture, protein, and intramuscular fat among the breeds. However, the Harri breed had a higher ash content than the Awassi and Najdi breeds. The Najdi breed had higher ultimate pH and lower cooking loss than the Awassi and Harri breeds. Awassi and Harri sheep had a higher myofibril fragmentation index, longer sarcomere length, and lower hardness and chewiness than Najdi sheep. Subjectively, no significant differences were detected between the breeds, except for flavor intensity while the Awassi sheep were rated in between and not significantly different. In conclusion, breed affected carcass characteristics, meat composition, and the quality of sheep. The dressing yield was higher in Harri and Najdi than Awassi sheep. Awassi sheep showed superior meat quality characteristics followed by Harri sheep. However, Najdi sheep had the best cooking loss percentage and flavor intensity score.
An Integrated Neural Network and SEIR Model to Predict COVID-19
Authors: Zisad Sharif Noor , Hossain Mohammad Shahadat , Hossain Mohammed Sazzad , Andersson Karl
Published: March 2021

A novel coronavirus (COVID-19), which has become a great concern for the world, was identified first in Wuhan city in China. The rapid spread throughout the world was accompanied by an alarming number of infected patients and increasing number of deaths gradually. If the number of infected cases can be predicted in advance, it would have a large contribution to controlling this pandemic in any area. Therefore, this study introduces an integrated model for predicting the number of confirmed cases from the perspective of Bangladesh. Moreover, the number of quarantined patients and the change in basic reproduction rate (the R0-value) can also be evaluated using this model. This integrated model combines the SEIR (Susceptible, Exposed, Infected, Removed) epidemiological model and neural networks. The model was trained using available data from 250 days. The accuracy of the prediction of confirmed cases is almost between 90% and 99%. The performance of this integrated model was evaluated by showing the difference in accuracy between the integrated model and the general SEIR model. The result shows that the integrated model is more accurate than the general SEIR model while predicting the number of confirmed cases in Bangladesh.
Tibetan Macaques with Higher Social Centrality and More Relatives Emit More Frequent Visual Communication in Collective Decision-Making
Authors: Tang Zifei , Wang Xi , Wu Mingyang , Chen Shiwang , Li Jinhua
Published: March 2021

Animals on the move often communicate with each other through some specific postures. Previous studies have shown that social interaction plays a role in communication process. However, it is not clear whether the affinity of group members can affect visual communication. We studied a group of free-ranging Tibetan macaques (Macaca thibetana) at Huangshan Mountain, China, and answered whether and how social centrality or relatives matter in visual signals during group movement using Tobit regression modeling. All individuals emitted the signals of back-glances and pauses in collective movement. The emission of two signals decreased with the number of participants increased. The back-glance and pause signals emitted by the participating individuals were stronger as the position moved backward in the group. Sex, age, and rank had no significant influence on back-glance and pause signals. Individuals with higher social centrality would emit more pause signals, but social centrality had no effect on the back-glance signal. Individuals with more relatives in the group had more back-glance signals, but this had no effect on the pause signal. This study verifies that social centrality and the number of relatives have effects on visual signals in Tibetan macaques. We provide insights into the relationship between communication behaviors and group cooperation in social animals.
A New, Practical Animal Welfare Assessment for Dairy Farmers
Authors: van Eerdenburg Frank J. C. M. , Di Giacinto Alice M. , Hulsen Jan , Snel Bert , Stegeman J. Arjan
Published: March 2021

The Welfare Quality® assessment protocol (WQ) is the most extensive way to measure animal welfare. This study was set up to determine if resource-based welfare indicators, that are easier and faster to measure, could replace the more time consuming, animal-based measurements of the WQ. The WQ was applied on 60 dairy farms in the Netherlands, with good, moderate and poor welfare. The WQ protocol classified most farms (87%) as ‘acceptable’. Several of the animal-based measures of WQ correlated well with measures in the environment. Using these correlations, an alternative welfare assessment protocol (new Welfare Monitor) was designed, which takes approximately 1.5 h for a farm with 100 dairy cows. Because the opinion of farmers about welfare assessment is important if one wants to improve conditions for the cows at a farm, another objective of this study was to evaluate the usefulness of the new Welfare Monitor for the farmer. Over two years, the farms were visited, and advice was given to improve the conditions at the farm. After the first welfare assessment and advice, farmers improved the conditions for their cows substantially. Farms where the category score had increased made more improvements on average than those that did not upgrade.
Parking Space Recognition Method Based on Parking Space Feature Construction in the Scene of Autonomous Valet Parking
Authors: Ma Shidian , Fang Weifeng , Jiang Haobin , Han Mu , Li Chenxu
Published: March 2021

At present, the realization of autonomous valet parking (AVP) technology does not achieve information interaction between the parking spaces and vehicles, and accurate parking spaces information perception cannot be obtained when the accuracy of the search is not precise. In addition, when using the camera vision to identify the parking spaces, traditional parking space features such as parking lines and parking angles recognition are susceptible to light and environment. Especially when the vehicle nearby partially occupies the parking space to be parked, it is not easy to determine whether it is a valid empty parking space. This paper proposes a parking space recognition method based on parking space features in the scene of AVP. By constructing the multi-dimensional features containing the parking space information, the cameras are used to extract features’ contour, locate features’ position and recognize features. In this paper, a new similarity calculation formula is proposed to recognize the stained features through template matching algorithm. According to the relative position relationship between the feature and parking space, the identification of effective empty parking spaces and their boundaries is realized. The experimental results show that compared with the recognition of traditional parking lines and parking angles, this method can identify effective empty parking spaces even when the light conditions are complex and the parking spaces are partially occupied by adjacent vehicles, which simplifies the recognition algorithm and improves the reliability of the parking spaces identification.
Prediction of Solar Irradiance and Photovoltaic Solar Energy Product Based on Cloud Coverage Estimation Using Machine Learning Methods
Authors: Park Seongha , Kim Yongho , Ferrier Nicola J. , Collis Scott M. , Sankaran Rajesh , Beckman Pete H.
Published: March 2021

Cloud cover estimation from images taken by sky-facing cameras can be an important input for analyzing current weather conditions and estimating photovoltaic power generation. The constant change in position, shape, and density of clouds, however, makes the development of a robust computational method for cloud cover estimation challenging. Accurately determining the edge of clouds and hence the separation between clouds and clear sky is difficult and often impossible. Toward determining cloud cover for estimating photovoltaic output, we propose using machine learning methods for cloud segmentation. We compare several methods including a classical regression model, deep learning methods, and boosting methods that combine results from the other machine learning models. To train each of the machine learning models with various sky conditions, we supplemented the existing Singapore whole sky imaging segmentation database with hazy and overcast images collected by a camera-equipped Waggle sensor node. We found that the U-Net architecture, one of the deep neural networks we utilized, segmented cloud pixels most accurately. However, the accuracy of segmenting cloud pixels did not guarantee high accuracy of estimating solar irradiance. We confirmed that the cloud cover ratio is directly related to solar irradiance. Additionally, we confirmed that solar irradiance and solar power output are closely related; hence, by predicting solar irradiance, we can estimate solar power output. This study demonstrates that sky-facing cameras with machine learning methods can be used to estimate solar power output. This ground-based approach provides an inexpensive way to understand solar irradiance and estimate production from photovoltaic solar facilities.
Label-Free and Highly-Sensitive Detection of Ochratoxin A Using One-Pot Synthesized Reduced Graphene Oxide/Gold Nanoparticles-Based Impedimetric Aptasensor
Authors: Alhamoud Yasmin , Li Yingying , Zhou Haibo , Al-Wazer Ragwa , Gong Yiying , Zhi Shuai , Yang Danting
Published: March 2021

Ochratoxin A (OTA) primarily obtained by the genera aspergillus and penicillium, is one of the toxic substances for different organs and systems of the human body such as the kidney, liver, neurons and the immune system. Moreover, it is considered to cause tumors and fetal malformation even at a very low concentration. Fast and sensitive assay for detection of OTA at ultralow levels in foods and agricultural products has been an increasing demand. In this study, a new label-free electrochemical biosensor based on three-dimensional reduced graphene oxide/gold nanoparticles/aptamer for OTA detection was constructed. The 3D-rGO/Au NPs nanocomposites were firstly synthesized using a one-pot hydrothermal process under optimized experimental conditions. The 3D-rGO/Au NPs with considerable particular surface area and outstanding electrical conductivity was then coated on a glass carbon electrode to provide tremendous binding sites for -SH modified aptamer via the distinctive Au–S linkage. The presence of OTA was specifically captured by aptamer and resulted in electrochemical impedance spectroscopy (EIS) signal response accordingly. The constructed impedimetric aptasensor obtained a broad linear response from 1 pg/mL to 10 ng/mL with an LOD of 0.34 pg/mL toward OTA detection, highlighting the excellent sensitivity. Satisfactory reproducibility was also achieved with the relative standard deviation (RSD) of 1.393%. Moreover, the proposed aptasensor obtained a good recovery of OTA detection in red wine samples within the range of 93.14 to 112.75% along with a low LOD of 0.023 ng/mL, indicating its applicability for OTA detection in real samples along with economical, specific, susceptible, fast, easy, and transportable merits.
Single-Nucleotide Polymorphisms in Oxidative Stress-Related Genes and the Risk of a Stroke in a Polish Population—A Preliminary Study
Authors: Synowiec Ewelina , Wigner Paulina , Cichon Natalia , Watala Cezary , Czarny Piotr , Saluk-Bijak Joanna , Miller Elzbieta , Sliwinski Tomasz , Zielinska-Nowak Ewa , Bijak Michal
Published: March 2021

The present preliminary case-control study was undertaken to detect the potential association of six single nucleotide polymorphisms (SNPs) in oxidative stress-related genes: SOD2 (c.47T > C; rs4880), CAT (c.-89A > T; rs7943316), GPX4 (c.660T > A; rs713041), NOS1 (g.117803515C > T; rs1879417) and NOS2 (c.1823C > T; rs2297518 and c.-227G > C; rs10459953) and the occurrence of a stroke. The SNPs were determined using the TaqMan® Allelic Discrimination Assay in 107 patients with strokes and 107 age- and sex-matched individuals who had not experienced cerebrovascular accidents. The T alleles of the rs4880 were positively correlated with a stroke (bootstrap OR 1.31; 1.07–1.59 95% CI). In the case of the rs713041, an association with the T allele was found (bootstrap OR 1.36; 1.12–1.67). In addition, the occurrence of a stroke was associated with the presence of the C allele of the rs1879417 (bootstrap OR 1.32; 1.09–1.61). We also found that the C/C genotype and C allele of the rs2297518 increased the risk of a stroke (bootstrap ORs 7.00; 4.34–11.29 and 4.96; 3.88–6.34, respectively). Moreover, the C allele of the rs10459953 was associated with an increased occurrence of this disease (bootstrap OR 1.31; 1.08–1.60). These results indicated that genetics variants in the SOD2, GPX4, NOS1 and NOS2 might be associated with susceptibility to strokes in the Polish population.
Numerical Analysis on Global Serviceability Behaviours of Tall CLT Buildings to the Eurocodes and UK National Annexes
Authors: Zhao Xuan , Zhang Binsheng , Kilpatrick Tony , Sanderson Iain
Published: March 2021

Cross-laminated timber (CLT) is an innovative engineered timber product and has been widely used for constructing tall timber buildings due to its excellent structural performance and good strength with its multi-layers of boards in both perpendicular directions. However, the global serviceability performance of tall timber buildings constructed from CLT products for the lift core, walls, and floors under wind load is not well known yet, even though it is crucial in a design. In this study, the finite element software SAP2000 is used to numerically simulate the global static and dynamic serviceability behaviours of a 30-storey tall CLT building assumed in Glasgow, Scotland, UK. The maximum horizontal storey displacement due to wind is only 16.6% of the design limit and the maximum global horizontal displacement is only 13.8% of the limit set to the Eurocodes. The first three lowest vibrational frequencies, modes and shapes were obtained, with the fundamental frequency being 19.9% larger than the code-recommended value. Accordingly, the peak acceleration of the building due to wind was determined as per the Eurocodes and ISO standard. The results show that the global serviceability behaviours of the building satisfy the requirements of the Eurocodes and other design standards. Parametric studies on the peak accelerations of the tall CLT building were also conducted by varying the timber material properties and building masses. By increasing the timber grade for CLT members, the generalised building mass and the generalised building stiffness can all be adopted to lower the peak accelerations at the top level of the building, so as to reduce human perceptions of the wind-induced vibrations with respect to the peak acceleration.
Biophysical Analysis of Acute and Late Toxicity of Radiotherapy in Gastric Marginal Zone Lymphoma—Impact of Radiation Dose and Planning Target Volume
Authors: Reinartz Gabriele , Baehr Andrea , Kittel Christopher , Oertel Michael , Haverkamp Uwe , Eich Hans Th.
Published: March 2021

Successful studies on radiation therapy for gastric lymphoma led to a decrease in planning target volume (PTV) and radiation dose with low toxicities, maintaining excellent survival rates. It remains unclear as to which effects are to be expected concerning dose burden on organs at risk (OAR) by decrease in PTV vs. dose and whether a direct impact on toxicity might be expected. We evaluated 72 radiation plans, generated prospectively for a cohort of 18 patients who were treated for indolent gastric lymphoma in our department. As a prospective work, four radiation plans with different radiation doses and target volumes (40 Gy-involved field, 40 Gy-involved site, 30 Gy-involved field, 30 Gy-involved site) were generated for each patient. Mean dose burden on adjacent organs was compared between the planning groups. Cohort toxicity data served to estimate parameters for the Lyman–Kutcher–Burman (LKB) model for normal tissue complication probability (NTCP). These were used to anticipate adverse events for OAR. Literature parameters were used to estimate high-grade toxicities of OAR. Decrease of dose and/or PTV led to median dose reductions between 0.13 and 5.2 Gy, with a significant dose reduction on neighboring organs. Estimated model parameters for liver, spleen, and bowel toxicity were feasible to predict cohort toxicities. NTCP for the endpoints elevated liver enzymes, low platelet count, and diarrhea ranged between 15.9 and 22.8%, 27.6 and 32.4%, and 21.8 and 26.4% for the respective four plan variations. Field and dose reduction highly impact dose burden and NTCP for OAR during stomach radiation. Our estimated LKB model parameters offer a good approximation for low-grade toxicities in abdominal organs with modern radiation techniques.
Relative Sensitivity of Core-Needle Biopsy and Incisional Biopsy in the Diagnosis of Musculoskeletal Sarcomas
Authors: Klein Alexander , Fell Theresa , Birkenmaier Christof , Fromm Julian , Jansson Volkmar , Knösel Thomas , Dürr Hans Roland
Published: March 2021

Background: There is no evidence as to the diagnostic value of the two most frequently used methods of biopsies in sarcomas: Incisional or core needle biopsy. The aim of our study was to evaluate the diagnostic sensitivity of the incisional and the core needle biopsy techniques in the diagnosis of bone and soft tissue sarcomas. Methods: We included 417 patients with a definitive diagnosis of bone or soft tissue sarcoma in whom a total of 472 biopsies had been performed. We correlated the results of the biopsies with the result of the definitive histopathological examination of the resected tumor. Dignity, entity, and grading (whenever possible) of the tissue samples were evaluated. Results: A total of 258 biopsies (55%) were performed in order to diagnose a soft tissue tumor and 351 biopsies (74.4%) were core needle biopsies. The number of repeat core needle biopsies, necessitated because of inconclusive histopathological results, was significantly higher (50 vs. 5; p = 0.003). We observed no significant difference regarding dignity, entity, and grading between the 2 different types of biopsies. Only with regards to the determination of dignity and entity of chondroid tumors, incisional biopsy was superior with statistical significance (p = 0.024). Conclusions: This study represents the largest study on biopsies for bone and soft tissue sarcomas. Based only on our results, we are unable to favor one method of biopsy and found high accuracy with both methods. Considering the potential complications, the added oncological risks of incisional biopsies and the ready availability of core needle biopsies, the latter, in our assessment, represents a valid and favourable method for bone and soft tissue sarcomas.
Myxoma Virus Expressing LIGHT (TNFSF14) Pre-Loaded into Adipose-Derived Mesenchymal Stem Cells Is Effective Treatment for Murine Pancreatic Adenocarcinoma
Authors: Jazowiecka-Rakus Joanna , Hadrys Agata , Rahman Masmudur M. , McFadden Grant , Fidyk Wojciech , Chmielik Ewa , Pazdzior Marlena , Grajek Maciej , Kozik Violetta , Sochanik Aleksander
Published: March 2021

Pancreatic ductal adenocarcinoma (PDAC) is a weakly immunogenic fatal neoplasm. Oncolytic viruses with dual anti-cancer properties—oncolytic and immune response-boosting effects—have great potential for PDAC management. Adipose-derived stem cells (ADSCs) of mesenchymal origin were infected ex vivo with recombinant myxoma virus (MYXV), which encodes murine LIGHT, also called tumor necrosis factor ligand superfamily member 14 (TNFSF14). The viability and proliferation of ADSCs were not remarkably decreased (1–2 days) following MYXV infection, in sharp contrast to cells of pancreatic carcinoma lines studied, which were rapidly killed by the infection. Comparison of the intraperitoneal (IP) vs. the intravenous (IV) route of ADSC/MYXV administration revealed more pancreas-targeted distribution of the virus when ADSCs were delivered IP to mice bearing orthotopically injected PDAC. The biodistribution, tumor burden reduction and anti-tumor adaptive immune response were examined. Bioluminescence data, used to assess the presence of the luciferase-tagged virus after IP injection, indicated enhanced trafficking into the pancreata of mice bearing orthotopically-induced PDAC, as compared to tumor-free animals, resulting in extended survival of the treated PDAC-seeded animals and in the boosted expression of key adaptive immune response markers. We conclude that ADSCs pre-loaded with transgene-armed MYXV and administered IP allow for the effective ferrying of the oncolytic virus to sites of PDAC and mediate improved tumor regression.
Large Scale Molecular Studies of Pituitary Neuroendocrine Tumors: Novel Markers, Mechanisms and Translational Perspectives
Authors: Peculis Raitis , Niedra Helvijs , Rovite Vita
Published: March 2021

Pituitary neuroendocrine tumors (PitNETs) are non-metastatic neoplasms of the pituitary, which overproduce hormones leading to systemic disorders, or tumor mass effects causing headaches, vertigo or visual impairment. Recently, PitNETs have been investigated in large scale (exome and genome) molecular analyses (transcriptome microarrays and sequencing), to uncover novel markers. We performed a literature analysis on these studies to summarize the research data and extrapolate overlapping gene candidates, biomarkers, and molecular mechanisms. We observed a tendency in samples with driver mutations (GNAS, USP8) to have a smaller overall mutational rate, suggesting driver-promoted tumorigenesis, potentially changing transcriptome profiles in tumors. However, direct links from drivers to signaling pathways altered in PitNETs (Notch, Wnt, TGF-β, and cell cycle regulators) require further investigation. Modern technologies have also identified circulating nucleic acids, and pinpointed these as novel PitNET markers, i.e., miR-143-3p, miR-16-5p, miR-145-5p, and let-7g-5p, therefore these molecules must be investigated in the future translational studies. Overall, large-scale molecular studies have provided key insight into the molecular mechanisms behind PitNET pathogenesis, highlighting previously reported molecular markers, bringing new candidates into the research field, and reapplying traditional perspectives to newly discovered molecular mechanisms.
The Role of Cancer-Associated Fibroblasts in Tumor Progression
Authors: Joshi Rushikesh S. , Kanugula Samanvi S. , Sudhir Sweta , Pereira Matheus P. , Jain Saket , Aghi Manish K.
Published: March 2021

In the era of genomic medicine, cancer treatment has become more personalized as novel therapeutic targets and pathways are identified. Research over the past decade has shown the increasing importance of how the tumor microenvironment (TME) and the extracellular matrix (ECM), which is a major structural component of the TME, regulate oncogenic functions including tumor progression, metastasis, angiogenesis, therapy resistance, and immune cell modulation, amongst others. Within the TME, cancer-associated fibroblasts (CAFs) have been identified in several systemic cancers as critical regulators of the malignant cancer phenotype. This review of the literature comprehensively profiles the roles of CAFs implicated in gastrointestinal, endocrine, head and neck, skin, genitourinary, lung, and breast cancers. The ubiquitous presence of CAFs highlights their significance as modulators of cancer progression and has led to the subsequent characterization of potential therapeutic targets, which may help advance the cancer treatment paradigm to determine the next generation of cancer therapy. The aim of this review is to provide a detailed overview of the key roles that CAFs play in the scope of systemic disease, the mechanisms by which they enhance protumoral effects, and the primary CAF-related markers that may offer potential targets for novel therapeutics.
CD19 Chimeric Antigen Receptor-Exosome Targets CD19 Positive B-lineage Acute Lymphocytic Leukemia and Induces Cytotoxicity
Authors: Haque Shabirul , Vaiselbuh Sarah R.
Published: March 2021

CAR-T cell therapy is not without some clinical adverse effects, namely cytokine storms, due to a massive release of cytokines when CAR-T cells multiply in the body. Our goal was to develop exosomes expressing CD19 CAR to treat CD19-positive B-cell malignancies, instead of using whole CD19 CAR-T cells, thereby reducing the clinical risk of uncontrolled cytokine storms. Exosomes are extracellular nanovesicles (30–150 nm), composed of lipids, proteins, and nucleic acids, that carry the fingerprint of their parent cells. Exosomes are a preferred delivery system in nano-immunotherapy. Here, HEK293T parent cells were transduced with CD19 CAR plasmids and cellular CD19 CAR expression was confirmed. Exosomes (Exo-CD19 CAR) were isolated from the conditioned medium of non-transduced (WT) and CD19 CAR plasmid transduced HEK293T cells. Consequently, CD19 B-lineage leukemia cell lines were co-cultured with Exo-CD19 CAR and cell death was measured. Our data show that Exo-CD19 CAR treatment induced cytotoxicity and elevated pro-apoptotic genes in CD19-positive leukemia B-cells without inducing cell death in CD19-negative cells. Overall, the novel CD19 CAR exosomes target the CD19 surface antigens of leukemic B-cells and can induce contact-dependent cytotoxicity.
Deciphering the Risk of Developing Second Primary Thyroid Cancer Following a Primary Malignancy—Who Is at the Greatest Risk?
Authors: Trinh Lily N. , Crawford Andrew R. , Hussein Mohammad H. , Zerfaoui Mourad , Toraih Eman A. , Randolph Gregory W. , Kandil Emad
Published: March 2021

Background: It is critical to understand factors that may contribute to an increased risk of SPTC in order to develop surveillance protocols in high-risk individuals. This systematic review and meta-analysis will assess the association between primary malignancy and SPTC. Methods: A search of PubMed and Embase databases was completed in April 2020. Inclusion criteria included studies that reported the incidence or standardized incidence ratio of any primary malignancy and SPTC, published between 1980–2020. The PRISMA guidelines were followed and the Newcastle–Ottawa Scale was used to assess quality of studies. Results: 40 studies were included, which were comprised of 1,613,945 patients and 15 distinct types of primary cancers. In addition, 4196 (0.26%) patients developed SPTC following a mean duration of 8.07 ± 4.39 years. Greater risk of developing SPTC was found following primary breast (56.6%, 95%CI, 44.3–68.9, p < 0.001), renal cell (12.2%, 95%CI, 7.68–16.8, p < 0.001), basal cell (7.79%, 95%CI, 1.79–13.7, p = 0.011), and ovarian cancer (11.4%, 95%CI, 3.4–19.5, p = 0.005). SPTC patients were more likely to be females (RR = 1.58, 95%CI, 1.2–2.01, p < 0.001) and Caucasians (p < 0.001). Conclusions: Surveillance protocols should be considered for patients at a higher risk of SPTC, including those with primary breast, renal cell, basal cell and ovarian cancers who are female and/or Caucasian.
Dynamic Contrast-Enhanced MRI of Prostate Lesions of Simultaneous [68Ga]Ga-PSMA-11 PET/MRI: Comparison between Intraprostatic Lesions and Correlation between Perfusion Parameters
Authors: Zhao Jing , Kader Avan , Mangarova Dilyana B. , Brangsch Julia , Brenner Winfried , Hamm Bernd , Makowski Marcus R.
Published: March 2021

We aimed to retrospectively compare the perfusion parameters measured from dynamic contrast-enhanced (DCE) magnetic resonance imaging (MRI) of prostate benign lesions and malignant lesions to determine the relationship between perfusion parameters. DCE-MRI was performed in patients with PCa who underwent simultaneous [68Ga]Ga-prostate-specific membrane antigen (PSMA)-11 positron emission tomography (PET)/MRI. Six perfusion parameters (arrival time (AT), time to peak (TTP), wash-in slope (W-in), wash-out slope (W-out), peak enhancement intensity (PEI), and initial area under the 60-s curve (iAUC)), and a semi-quantitative parameter, standardized uptake values maximum (SUVmax) were calculated by placing regions of interest in the largest area of the lesions. The DCE-MRI parameters between prostate benign and malignant lesions were compared. The DCE-MRI parameters in both the benign and malignant lesions subgroup with SUVmax ≤ 3.0 and SUVmax > 3.0 were compared. The correlation of DCE-MRI parameters was investigated. Malignant lesions demonstrated significantly shorter TTP and higher SUVmax than did benign lesions. In the benign and malignant lesions subgroup, perfusion parameters of lesions with SUVmax ≤ 3.0 show no significant difference to those with SUVmax > 3.0. DCE-MRI perfusion parameters show a close correlation with each other. DCE-MRI parameters reflect the perfusion characteristics of intraprostatic lesions with malignant lesions, demonstrating significantly shorter TTP. There is a moderate to strong correlation between DCE-MRI parameters. Semi-quantitative analysis reflects that malignant lesions show a significantly higher SUVmax than benign lesions.
Computer-Aided Segmentation and Machine Learning of Integrated Clinical and Diffusion-Weighted Imaging Parameters for Predicting Lymph Node Metastasis in Endometrial Cancer
Authors: Yang Lan-Yan , Siow Tiing Yee , Lin Yu-Chun , Wu Ren-Chin , Lu Hsin-Ying , Chiang Hsin-Ju , Ho Chih-Yi , Huang Yu-Ting , Huang Yen-Ling , Pan Yu-Bin , Chao Angel , Lai Chyong-Huey , Lin Gigin
Published: March 2021

Precise risk stratification in lymphadenectomy is important for patients with endometrial cancer (EC), to balance the therapeutic benefit against the operation-related morbidity and mortality. We aimed to investigate added values of computer-aided segmentation and machine learning based on clinical parameters and diffusion-weighted imaging radiomics for predicting lymph node (LN) metastasis in EC. This prospective observational study included 236 women with EC (mean age ± standard deviation, 51.2 ± 11.6 years) who underwent magnetic resonance (MR) imaging before surgery during July 2010–July 2018, randomly split into training (n = 165) and test sets (n = 71). A decision-tree model was constructed based on mean apparent diffusion coefficient (ADC) value of the tumor (cutoff, 1.1 × 10−3 mm2/s), skewness of the relative ADC value (cutoff, 1.2), short-axis diameter of LN (cutoff, 1.7 mm) and skewness ADC value of the LN (cutoff, 7.2 × 10−2), as well as tumor grade (1 vs. 2 and 3), and clinical tumor size (cutoff, 20 mm). The sensitivity and specificity of the model were 94% and 80% for the training set and 86%, 78% for the independent testing set, respectively. The areas under the receiver operating characteristics curve (AUCs) of the decision-tree was 0.85—significantly higher than the mean ADC model (AUC = 0.54) and LN short-axis diameter criteria (AUC = 0.62) (both p < 0.0001). We concluded that a combination of clinical and MR radiomics generates a prediction model for LN metastasis in EC, with diagnostic performance surpassing the conventional ADC and size criteria.
Raman Spectral Signatures of Serum-Derived Extracellular Vesicle-Enriched Isolates May Support the Diagnosis of CNS Tumors
Authors: Bukva Matyas , Dobra Gabriella , Gomez-Perez Juan , Koos Krisztian , Harmati Maria , Gyukity-Sebestyen Edina , Biro Tamas , Jenei Adrienn , Kormondi Sandor , Horvath Peter , Konya Zoltan , Klekner Almos , Buzas Krisztina
Published: March 2021

Investigating the molecular composition of small extracellular vesicles (sEVs) for tumor diagnostic purposes is becoming increasingly popular, especially for diseases for which diagnosis is challenging, such as central nervous system (CNS) malignancies. Thorough examination of the molecular content of sEVs by Raman spectroscopy is a promising but hitherto barely explored approach for these tumor types. We attempt to reveal the potential role of serum-derived sEVs in diagnosing CNS tumors through Raman spectroscopic analyses using a relevant number of clinical samples. A total of 138 serum samples were obtained from four patient groups (glioblastoma multiforme, non-small-cell lung cancer brain metastasis, meningioma and lumbar disc herniation as control). After isolation, characterization and Raman spectroscopic assessment of sEVs, the Principal Component Analysis–Support Vector Machine (PCA–SVM) algorithm was performed on the Raman spectra for pairwise classifications. Classification accuracy (CA), sensitivity, specificity and the Area Under the Curve (AUC) value derived from Receiver Operating Characteristic (ROC) analyses were used to evaluate the performance of classification. The groups compared were distinguishable with 82.9–92.5% CA, 80–95% sensitivity and 80–90% specificity. AUC scores in the range of 0.82–0.9 suggest excellent and outstanding classification performance. Our results support that Raman spectroscopic analysis of sEV-enriched isolates from serum is a promising method that could be further developed in order to be applicable in the diagnosis of CNS tumors.
Attribution of NF-κB Activity to CHUK/IKKα-Involved Carcinogenesis
Authors: Li Xin , Hu Yinling
Published: March 2021

Studies analyzing human cancer genome sequences and genetically modified mouse models have extensively expanded our understanding of human tumorigenesis, even challenging or reversing the dogma of certain genes as originally characterized by in vitro studies. Inhibitor-κB kinase α (IKKα), which is encoded by the conserved helix-loop-helix ubiquitous kinase (CHUK) gene, is first identified as a serine/threonine protein kinase in the inhibitor-κB kinase complex (IKK), which is composed of IKKα, IKKβ, and IKKγ (NEMO). IKK phosphorylates serine residues 32 and 36 of IκBα, a nuclear factor-κB (NF-κB) inhibitor, to induce IκBα protein degradation, resulting in the nuclear translocation of NF-κB dimers that function as transcriptional factors to regulate immunity, infection, lymphoid organ/cell development, cell death/growth, and tumorigenesis. NF-κB and IKK are broadly and differentially expressed in the cells of our body. For a long time, the idea that the IKK complex acts as a direct upstream activator of NF-κB in carcinogenesis has been predominately accepted in the field. Surprisingly, IKKα has emerged as a novel suppressor for skin, lung, esophageal, and nasopharyngeal squamous cell carcinoma, as well as lung and pancreatic adenocarcinoma (ADC). Thus, Ikkα loss is a tumor driver in mice. On the other hand, lacking the RANKL/RANK/IKKα pathway impairs mammary gland development and attenuates oncogene- and chemical carcinogen-induced breast and prostate tumorigenesis and metastasis. In general, NF-κB activation leads one of the major inflammatory pathways and stimulates tumorigenesis. Since IKKα and NF-κB play significant roles in human health, revealing the interplay between them greatly benefits the diagnosis, treatment, and prevention of human cancer. In this review, we discuss the intriguing attribution of NF-κB to CHUK/IKKα-involved carcinogenesis.
Safety and Treatment Outcomes of Nivolumab for the Treatment of Recurrent or Metastatic Head and Neck Squamous Cell Carcinoma: Retrospective Multicenter Cohort Study
Authors: Vasiliadou Ifigenia , Breik Omar , Baker Holly , Leslie Isla , Sim Van Ren , Hegarty Gemma , Michaelidou Andriana , Nathan Kannon , Hartley Andrew , Good James , Sanghera Paul , Fong Charles , Urbano Teresa Guerrero , Lei Mary , Petkar Imran , Ferreira Miguel Reis , Nutting Chris , Wong Kee Howe , Newbold Kate , Harrington Kevin , Bhide Shree , Kong Anthony
Published: March 2021

Nivolumab is an anti-PD-1 monoclonal antibody currently used as immunotherapy for patients with recurrent/metastatic head and neck squamous cell carcinoma (HNSCC) with evidence of disease progression after platinum-based chemotherapy. This study evaluates real-world safety and treatment outcomes of non-trial nivolumab use. A retrospective multicenter cohort study of patients with recurrent/metastatic HNSCC treated with nivolumab between January 2017 and March 2020 was performed. Overall, 123 patients were included. The median age was 64 years, the majority of patients were male (80.5%) and had a smoking history (69.9%). Primary outcomes included overall response rate (ORR) of 19.3%, median progression-free survival (PFS) of 3.9 months, 1-year PFS rate of 16.8%, a median overall survival (OS) of 6.5 months and 1-year OS rate of 28.6%. These results are comparable to the CHECKMATE-141 study. Of 27 patients who had PD-L1 status tested, positive PD-L1 status did not significantly affect PFS (p = 0.86) or OS (p = 0.84). Nivolumab was well tolerated with only 15.1% experiencing immune-related toxicities (IRT) and only 6.7% of patients stopping due to toxicity. The occurrence of IRT appeared to significantly affect PFS (p = 0.01) but not OS (p = 0.07). Nivolumab in recurrent/metastatic HNSCC is well tolerated and may be more efficacious in patients who develop IRT.
EBV and the Pathogenesis of NK/T Cell Lymphoma
Authors: Montes-Mojarro Ivonne A. , Fend Falko , Quintanilla-Martinez Leticia
Published: March 2021

Epstein-Barr virus (EBV) is a ubiquitous gamma herpes virus with tropism for B cells. EBV is linked to the pathogenesis of B cell, T cell and NK cell lymphoproliferations, with extranodal NK/T cell lymphoma, nasal type (ENKTCL) being the prototype of an EBV-driven lymphoma. ENKTCL is an aggressive neoplasm, particularly widespread in East Asia and the native population of Latin America, which suggests a strong genetic predisposition. The link between ENKTCL and different populations has been partially explored. EBV genome sequencing analysis recognized two types of strains and identified variants of the latent membrane protein 1 (LMP1), which revealed different oncogenic potential. In general, most ENKTCL patients carry EBV type A with LMP1 wild type, although the LMP1 variant with a 30 base pair deletion is also common, especially in the EBV type B, where it is necessary for oncogenic transformation. Contemporary high-throughput mutational analyses have discovered recurrent gene mutations leading to activation of the JAK-STAT pathway, and mutations in other genes such as BCOR, DDX3X and TP53. The genomic landscape in ENKTCL highlights mechanisms of lymphomagenesis, such as immune response evasion, secondary to alterations in signaling pathways or epigenetics that directly or indirectly interfere with oncogenes or tumor suppressor genes. This overview discusses the most important findings of EBV pathogenesis and genetics in ENKTCL.
Fine-Tuning Approach for Segmentation of Gliomas in Brain Magnetic Resonance Images with a Machine Learning Method to Normalize Image Differences among Facilities
Authors: Takahashi Satoshi , Takahashi Masamichi , Kinoshita Manabu , Miyake Mototaka , Kawaguchi Risa , Shinojima Naoki , Mukasa Akitake , Saito Kuniaki , Nagane Motoo , Otani Ryohei , Higuchi Fumi , Tanaka Shota , Hata Nobuhiro , Tamura Kaoru , Tateishi Kensuke , Nishikawa Ryo , Arita Hideyuki , Nonaka Masahiro , Uda Takehiro , Fukai Junya , Okita Yoshiko , Tsuyuguchi Naohiro , Kanemura Yonehiro , Kobayashi Kazuma , Sese Jun , Ichimura Koichi , Narita Yoshitaka , Hamamoto Ryuji
Published: March 2021

Machine learning models for automated magnetic resonance image segmentation may be useful in aiding glioma detection. However, the image differences among facilities cause performance degradation and impede detection. This study proposes a method to solve this issue. We used the data from the Multimodal Brain Tumor Image Segmentation Benchmark (BraTS) and the Japanese cohort (JC) datasets. Three models for tumor segmentation are developed. In our methodology, the BraTS and JC models are trained on the BraTS and JC datasets, respectively, whereas the fine-tuning models are developed from the BraTS model and fine-tuned using the JC dataset. Our results show that the Dice coefficient score of the JC model for the test portion of the JC dataset was 0.779 ± 0.137, whereas that of the BraTS model was lower (0.717 ± 0.207). The mean Dice coefficient score of the fine-tuning model was 0.769 ± 0.138. There was a significant difference between the BraTS and JC models (p < 0.0001) and the BraTS and fine-tuning models (p = 0.002); however, no significant difference between the JC and fine-tuning models (p = 0.673). As our fine-tuning method requires fewer than 20 cases, this method is useful even in a facility where the number of glioma cases is small.
Liver Transplantation for T2 Hepatocellular Carcinoma during the COVID-19 Pandemic: A Novel Model Balancing Individual Benefit against Healthcare Resources
Authors: Cillo Umberto , Vitale Alessandro , Volk Michael L. , Frigo Anna Chiara , Feltracco Paolo , Cattelan Annamaria , Brancaccio Giuseppina , Feltrin Giuseppe , Angeli Paolo , Burra Patrizia , Lonardi Sara , Trapani Silvia , Cardillo Massimo
Published: March 2021

The COVID-19 pandemic caused temporary drops in the supply of organs for transplantation, leading to renewed debate about whether T2 hepatocellular carcinoma (HCC) patients should receive priority during these times. The aim of this study was to provide a quantitative model to aid decision-making in liver transplantation for T2 HCC. We proposed a novel ethical framework where the individual transplant benefit for a T2 HCC patient should outweigh the harm to others on the waiting list, determining a “net benefit”, to define appropriate organ allocation. This ethical framework was then translated into a quantitative Markov model including Italian averages for waiting list characteristics, donor resources, mortality, and transplant rates obtained from a national prospective database (n = 8567 patients). The net benefit of transplantation in a T2 HCC patient in a usual situation varied from 0 life months with a model for end-stage liver disease (MELD) score of 15, to 34 life months with a MELD score of 40, while it progressively decreased with acute organ shortage during a pandemic (i.e., with a 50% decrease in organs, the net benefit varied from 0 life months with MELD 30, to 12 life months with MELD 40). Our study supports the continuation of transplantation for T2 HCC patients during crises such as COVID-19; however, the focus needs to be on those T2 HCC patients with the highest net survival benefit.
Metformin Attenuates Monosodium-Iodoacetate-Induced Osteoarthritis via Regulation of Pain Mediators and the Autophagy–Lysosomal Pathway
Authors: Na Hyun Sik , Kwon Ji Ye , Lee Seon-Yeong , Lee Seung Hoon , Lee A Ram , Woo Jin Seok , Jung KyungAh , Cho Keun-Hyung , Choi Jeong-Won , Lee Dong Hwan , Min Hong-Ki , Park Sung-Hwan , Kim Seok Jung , Cho Mi-La
Published: March 2021

Osteoarthritis (OA) is the most common degenerative arthritis associated with pain and cartilage destruction in the elderly; it is known to be involved in inflammation as well. A drug called celecoxib is commonly used in patients with osteoarthritis to control pain. Metformin is used to treat type 2 diabetes but also exhibits regulation of the autophagy pathway. The purpose of this study is to investigate whether metformin can treat monosodium iodoacetate (MIA)-induced OA in rats. Metformin was administered orally every day to rats with OA. Paw-withdrawal latency and threshold were used to assess pain severity. Cartilage damage and pain mediators in dorsal root ganglia were evaluated by histological analysis and a scoring system. Relative mRNA expression was measured by real-time PCR. Metformin reduced the progression of experimental OA and showed both antinociceptive properties and cartilage protection. The combined administration of metformin and celecoxib controlled cartilage damage more effectively than metformin alone. In chondrocytes from OA patients, metformin reduced catabolic factor gene expression and inflammatory cell death factor expression, increased LC3Ⅱb, p62, and LAMP1 expression, and induced an autophagy–lysosome fusion phenotype. We investigated if metformin treatment reduces cartilage damage and inflammatory cell death of chondrocytes. The results suggest the potential for the therapeutic use of metformin in OA patients based on its ability to suppress pain and protect cartilage.
Metabolomic Variation Aligns with Two Geographically Distinct Subpopulations of Brachypodium Distachyon before and after Drought Stress
Authors: Skalska Aleksandra , Beckmann Manfred , Corke Fiona , Savas Tuna Gulsemin , Tuna Metin , Doonan John H. , Hasterok Robert , Mur Luis A. J.
Published: March 2021

Brachypodium distachyon (Brachypodium) is a non-domesticated model grass that has been used to assess population level genomic variation. We have previously established a collection of 55 Brachypodium accessions that were sampled to reflect five different climatic regions of Turkey; designated 1a, 1c, 2, 3 and 4. Genomic and methylomic variation differentiated the collection into two subpopulations designated as coastal and central (respectively from regions 1a, 1c and the other from 2, 3 and 4) which were linked to environmental variables such as relative precipitation. Here, we assessed how far genomic variation would be reflected in the metabolomes and if this could be linked to an adaptive trait. Metabolites were extracted from eight-week-old seedlings from each accession and assessed using flow infusion high-resolution mass spectrometry (FIE-HRMS). Principal Component Analysis (PCA) of the derived metabolomes differentiated between samples from coastal and central subpopulations. The major sources of variation between seedling from the coastal and central subpopulations were identified. The central subpopulation was typified by significant increases in alanine, aspartate and glutamate metabolism and the tricarboxylic acid (TCA) cycle. Coastal subpopulation exhibited elevated levels of the auxin, indolacetic acid and rhamnose. The metabolomes of the seedling were also determined following the imposition of drought stress for seven days. The central subpopulation exhibited a metabolomic shift in response to drought, but no significant changes were seen in the coastal one. The drought responses in the central subpopulation were typified by changes in amino acids, increasing the glutamine that could be functioning as a stress signal. There were also changes in sugars that were likely to be an osmotic counter to drought, and changes in bioenergetic metabolism. These data indicate that genomic variation in our Turkish Brachypodium collection is largely reflected as distinctive metabolomes (“metabolotypes”) through which drought tolerance might be mediated.
Still Digging: Advances and Perspectives in the Study of the Diversity of Several Sedentarian Annelid Families
Authors: Grosse Maël , Zhadan Anna , Langeneck Joachim , Fiege Dieter , Martínez Alejandro
Published: March 2021

Sedentarian annelids are a diverse and heterogeneous group of marine worms representing more than 8600 species gathered in ca. 43 families. The attention brought to these organisms is unevenly distributed among these families, and the knowledge about them sometimes scarce. We review here the current knowledge about the families Acrocirridae, Cirratulidae (including Ctenodrilidae), Cossuridae, Longosomatidae, Paraonidae, and Sternaspidae in terms of biodiversity as well as the evolution of the taxonomy and systematics of each group. We present the challenges faced when studying these organisms and compare methodologies across groups and perspectives in future research.