bluuebunny/crossref_metadata_2025 huggingface dataset:
Crop Management with the IoT: An Interdisciplinary Survey
Authors: Vitali Giuliano , Francia Matteo , Golfarelli Matteo , Canavari Maurizio
Published: January 2021

In this study, we analyze how crop management will benefit from the Internet of Things (IoT) by providing an overview of its architecture and components from agronomic and technological perspectives. The present analysis highlights that IoT is a mature enabling technology with articulated hardware and software components. Cheap networked devices can sense crop fields at a finer grain to give timeliness warnings on the presence of stress conditions and diseases to a wider range of farmers. Cloud computing allows reliable storage, access to heterogeneous data, and machine-learning techniques for developing and deploying farm services. From this study, it emerges that the Internet of Things will draw attention to sensor quality and placement protocols, while machine learning should be oriented to produce understandable knowledge, which is also useful to enhance cropping system simulation systems.
Initial Crown Diameter Influences on the Fruit Yield and Quality of Strawberry Pircinque
Authors: Fagherazzi Antonio Felippe , Suek Zanin Daniel , Soares dos Santos Marllon Fernando , Martins de Lima Juliana , Welter Paola Daiane , Francis Richter Adrik , Regianini Nerbass Francine , Anneliese Kretzschmar Aike , Rufato Leo , Baruzzi Gianluca
Published: January 2021

In strawberry production, the combination of a high productive performance and fruits with desirable physicochemical characteristics requires the use of plants with a good quality and high initial vigor. This study aimed to evaluate the effect of plants with different crown diameters on the productive performance and fruit quality of strawberry plants of the cultivar ‘Pircinque’ (Short Day). The study was conducted in two evaluation cycles (2016/2017 and 2017/2018). The experimental design was divided into randomized blocks, with four repetitions, and plots consisting of 20 plants. This study evaluated the crown diameters of plants of 5, 7, 9, 11, 13, 15, 17, and 19 mm. The productivity and number of fruit values increased significantly by 57% with larger caliber plants, which also provided precocity of productivity. The use of more vigorous plants also favored the production of fruits with higher soluble solids/titratable acidity ratios (+28%) and with epidermis coloration closer to intense red (−4.3%). For the cultivar ‘Pircinque’, plant crown diameters between 15 and 17 mm are the most favorable because they condition the best productive performances in combination with precocity and a good fruit quality.
Early-Stage Phenotyping of Root Traits Provides Insights into the Drought Tolerance Level of Soybean Cultivars
Authors: Dayoub Elana , Lamichhane Jay Ram , Schoving Céline , Debaeke Philippe , Maury Pierre
Published: January 2021

Soybean (Glycine max (L.) Merr.) may contribute to the agro-ecological transition of cropping systems in Europe, but its productivity is severely affected by summer drought. New drought-avoidance cropping strategies, such as early sowing, require cultivars with high early plant growth under suboptimal conditions. This study aims at phenotyping early-stage root and shoot traits of 10 cultivars commonly grown in Europe. Cultivars were grown in minirhizotrons under two soil moisture status in controlled conditions. Root and shoot traits were evaluated at 10 days after sowing. Field early growth of two cultivars was also analyzed under early and conventional sowing dates. A significant intraspecific variability (p < 0.05) was found for most investigated shoot and root morpho-physiological traits regardless of the soil moisture status under controlled conditions. However, no significant difference among cultivars (p > 0.05) was found in terms of root architectural traits that were mainly affected by water stress. Total root length was positively correlated with shoot length and shoot dry matter (p < 0.05). Under field conditions, the differences between cultivars were expressed by the canopy cover at emergence, which determines the subsequent canopy cover dynamics. The significant early growth difference among cultivars was not related to the maturity group. Cultivars characterized by high root depth and length, high root density and narrow root angle could be considered as good candidates to cope with water stress via better soil exploration. New agronomic strategies mobilizing the diversity of cultivars could thus be tested to improve soybean water use efficiency in response to climate change.
MicroRNA-210 Regulates Endoplasmic Reticulum Stress and Apoptosis in Porcine Embryos
Authors: Ridlo Muhammad Rosyid , Kim Eui Hyun , Kim Geon A.
Published: January 2021

Endoplasmic reticulum (ER) stress can be triggered during in vitro embryo production and is a major obstacle to embryo survival. MicroRNA (miR)-210 is associated with cellular adaptation to cellular stress and inflammation. An experiment was conducted to understand the effects of miR-210 on in vitro embryo development, ER stress, and apoptosis; to achieve this, miR-210 was microinjected into parthenogenetically activated embryos. Our results revealed that miR-210 inhibition significantly enhanced the cleavage rate, blastocyst formation rate, and total cell number (TCN) of blastocysts, and reduced expression levels of XBP1 (p < 0.05). miR-210 inhibition greatly reduced the expression of ER stress-related genes (uXBP1, sXBP1, ATF4, and PTPN1) and Caspase 3 and increased the levels of NANOG and SOX2 (p < 0.05). A miR-210-mimic significantly decreased the cleavage, blastocyst rate, TCN, and expression levels of XBP1 compared with other groups (p < 0.05). The miR-210-mimic impaired the expression levels of uXBP1, sXBP1, ATF4, PTPN1, and Caspase 3 and decreased the expression of NANOG and SOX2 (p < 0.05). In conclusion, miR-210 plays an essential role in porcine in vitro embryo development. Therefore, we suggest that miR-210 inhibition could alleviate ER stress and reduce apoptosis to support the enhancement of in vitro embryo production.
Prediction of Calving to Conception Interval Length Using Algorithmic Analysis of Endometrial mRNA Expression in Bovine
Authors: Tobolski Dawid , Łukasik Karolina , Bacławska Agnieszka , Skarżyński Dariusz Jan , Hostens Miel , Barański Wojciech
Published: January 2021

After parturition, the uterus undergoes significant reconstruction, allows the endometrium to create an environment for subsequent embryo development. Here, we used an unsupervised algorithmic approach to select characteristic endometrial mRNA expression patterns of proposed markers and investigate each marker’s role as an individual indicator of reproductive success. Clinically healthy cows at a sixth week postpartum were examined, the percentage of neutrophils (PMNs%) in the cytological smear was calculated, and an endometrial biopsy was taken for qPCR. Based on pregnancy examination, cows were divided into three groups: Pregnant before 100 days postpartum (P100, n = 11), pregnant between 100–200-day (P200, n = 14), and culled (C, n = 10). Animals were also classified based on two PMNs% thresholds > 5% PMNs and > 10% PMNs. The expression of IL1B, IL6, CXCL8, and IL17A was higher in >10%PMNs. The expression of PTGS1 was higher in the P200 compared to P100. Upregulation of inhibin A subunit (INHA) and downregulation of inhibin β A subunit (INHBA) were observed in the P100. INHBA/INHA ratio was the most accurate linear predictor of the calving-to-conception interval. The application of the k-means algorithm allowed the identification of five unique expression patterns. The sensitivity and specificity of predicting allocation to P100 were 81% and 79%. We also documented the low efficiency of genes associated with subclinical endometritis and PMNs% in determining reproductive capability. These results suggested the presence of distinctive expression patterns in 6 weeks postpartum, correlated with cows’ reproductive capacity. Furthermore, we proposed the INHBA/INHA ratio as an indicator of calving-to-conception interval length.
Mineral Element Deposition and Gene Expression across Different Tissues of Cherry Valley Ducks
Authors: Song Qianqian , Zhang Yi , Bai Hao , Zhong Li , Li Xiaofan , Zhao Wenming , Chang Guobin , Chen Guohong
Published: January 2021

This study was conducted to investigate the deposition of several mineral elements and the mRNA levels of mineral-related genes across different tissues of cherry valley ducks. The contents of magnesium (Mg), potassium (K), zinc (Zn), and selenium (Se) in ducks’ breast muscle, thigh muscle, liver, skin, and tibia at the age of 0, 21, 35, 49, and 63 days, respectively, were measured using an atomic fluorescence spectrophotometer, while the mRNA levels of mineral-related genes were detected by qRT-PCR. The results revealed that the dynamics of Mg and K were generally similar in each tissue, with a significant positive correlation (p < 0.05). In the breast muscle, thigh muscle, and liver, the contents of almost all mineral elements reached their peak values (p < 0.05) at the age of 49 to 63 days. Interestingly, the expression of most mineral-related genes was the highest at birth (p < 0.05). In addition, there was a significant negative correlation between the expression of ATP1A1 and the deposition of K (r = −0.957, p < 0.05), and a similar result was found for the expression of ATP8 and the deposition of Zn (r = −0.905, p < 0.05). Taken together, Mg and K could be used as joint indicators for the precise breeding of the high-quality strain of cherry valley ducks, while the age of 49 to 63 days could be used as the reference for the best marketing age. In addition, ATP1A1 and ATP8 could be used as the key genes to detect K and Zn, respectively. Hence, the findings of this study can be used to improve the production and breeding efficiency of high-quality meat ducks.
Genome-Based Analyses of Fitness Effects and Compensatory Changes Associated with Acquisition of blaCMY-, blaCTX-M-, and blaOXA-48/VIM-1-Containing Plasmids in Escherichia coli
Authors: Pietsch Michael , Pfeifer Yvonne , Fuchs Stephan , Werner Guido
Published: January 2021

(1) Background: Resistance plasmids are under selective conditions beneficial for the bacterial host, but in the absence of selective pressure, this carriage may cause fitness costs. Compensation of this fitness burden is important to obtain competitive ability under antibiotic-free conditions. In this study, we investigated fitness effects after a conjugative transfer of plasmids containing various beta-lactamase genes transferred into Escherichia coli. (2) Methods: Fourteen beta-lactamase-encoding plasmids were transferred from clinical donor strains to E. coli J53. Growth rates were compared for all transconjugants and the recipient. Selected transconjugants were challenged in long-term growth experiments. Growth rates were assessed at different time points during growth for 500 generations. Whole-genome sequencing (WGS) of initial and evolved transconjugants was determined. Results: Most plasmid acquisitions resulted in growth differences, ranging from −4.5% to 7.2%. Transfer of a single blaCMY-16-carrying plasmid resulted in a growth burden and a growth benefit in independent mating. Long-term growth led to a compensation of fitness burdens and benefits. Analyzing WGS revealed genomic changes caused by Single Nucleotide Polymorphisms (SNPs) and insertion sequences over time. Conclusions: Fitness effects associated with plasmid acquisitions were variable. Potential compensatory mutations identified in transconjugants’ genomes after 500 generations give interesting insights into aspects of plasmid–host adaptations.
Multidrug-Resistant Bacterial Infections in Geriatric Hospitalized Patients before and after the COVID-19 Outbreak: Results from a Retrospective Observational Study in Two Geriatric Wards
Authors: Gasperini Beatrice , Cherubini Antonio , Lucarelli Moira , Espinosa Emma , Prospero Emilia
Published: January 2021

The impact of the COVID-19 pandemic on multidrug-resistant (MDR) bacteria is unknown. The purpose of this study was to assess prevalence, etiology, and association with mortality of MDR bacteria in older adult patients before and after the first peak of the COVID-19 pandemic in Italy. An observational retrospective study was conducted in two geriatric wards of the Azienda Ospedaliera Ospedali Riuniti Marche Nord, Fano, and of the INRCA, IRCCS, Ancona, in the Marche Region, Italy, from December 2019 to February 2020 and from May to July 2020. A total of 73 patients (mean age 87.4 ± 5.9, 27.4% men) and 83 cultures (36 pre-COVID-19 and 47 post-COVID-19) were considered. Overall, 46 cultures (55.4%) reported MDR bacteria (50% in pre- and 59.6% in post-COVID-19 period, p = 0.384). MDR bacteria in bloodstream significantly increased in post-COVID-19 period (68.8% vs. 40.0% p = 0.038) and MDR bacteria in urine did not change (51.6 vs. 54.8%, p = 0.799). Escherichia coli was the main MDR bacterium in pre-COVID-19, p = 0.082 and post-COVID-19, p = 0.026. Among patients with MDR infection, in-hospital mortality was 37.5% and 68.8% in pre- and post-COVID-19, respectively (p = 0.104), and mortality at 30 days was higher in post-COVID-19 period (78.9% vs. 27.3%, p = 0.012). An increased number of MDR bacteria in bloodstream and mortality after MDR infection have been observed in the post-COVID-19 period.
Buckling Test of Composite Cylindrical Shells with Large Radius Thickness Ratio
Authors: Takano Atsushi , Kitamura Ryuta , Masai Takuma , Bao Jingxuan
Published: January 2021

A buckling test of composite cylindrical shells with a radius–thickness ratio (r/t) = 893 under axial compression was conducted to investigate the effects of the radius–thickness ratio (r/t). It is known that the buckling load of cylinders shows large differences and scatter between theory and experiment. The ratio of the experimental buckling load and theoretical buckling load is called the knockdown factor (KDF). Many investigations have been conducted to find the cause of the degradation and scatter in the KDF, but as yet, no cause has been found. In 1968, NASA’s buckling design criterion, NASA SP-8007, gave an empirical KDF curve that decreased with the increasing r/t (up to 2000) for metal cylinders. The same curve has been applied to composite cylinders. Recently, Takano derived a flat lower-bound KDF in terms of A- and B-basis values (99% and 90% probability with a 95% confidence level) through a statistical analysis of experimental buckling loads. The result, however, based on experimental results up to r/t = 500 and, thus, the dependency on a large range of r/t, is not clear. Thus, the authors focused on a larger range of r/t. Cylindrical shells made from carbon fiber-reinforced plastic (CFRP) were tested. The nominal radius, thickness, and length were r = 100.118 mm, t = 0.118 mm, and L = 200 mm and, thus, the r/t = 848 and length-to-radius ratio (L/r) = 2.0. Shape imperfections were also measured by using in-house laser displacement equipment. The buckling load was slightly affected by the r/t, but the reduction in the KDF was insignificant.
Atmospheric Dynamics and Numerical Simulations of Six Frontal Dust Storms in the Middle East Region
Authors: Hamzeh Nasim Hossein , Karami Sara , Kaskaoutis Dimitris G. , Tegen Ina , Moradi Mohamad , Opp Christian
Published: January 2021

This study analyzes six frontal dust storms in the Middle East during the cold period (October–March), aiming to examine the atmospheric circulation patterns and force dynamics that triggered the fronts and the associated (pre- or post-frontal) dust storms. Cold troughs mostly located over Turkey, Syria and north Iraq played a major role in the front propagation at the surface, while cyclonic conditions and strong winds facilitated the dust storms. The presence of an upper-atmosphere (300 hPa) sub-tropical jet stream traversing from Egypt to Iran constitutes also a dynamic force accompanying the frontal dust storms. Moderate-Resolution Imaging Spectroradiometer (MODIS) and Cloud-Aerosol Lidar and Infrared Pathfinder Satellite Observation (CALIPSO) observations are used to monitor the spatial and vertical extent of the dust storms, while model (Weather Research and Forecasting model coupled with Chemistry (WRF-Chem), Copernicus Atmospheric Monitoring Service (CAMS), Regional Climate Model-4 (RegCM4)) simulations are also analyzed. The WRF-Chem outputs were in better agreement with the MODIS observations compared to those of CAMS and RegCM4. The fronts were identified by WRF-Chem simulations via gradients in the potential temperature and sudden changes of wind direction in vertical cross-sections. Overall, the uncertainties in the simulations and the remarkable differences between the model outputs indicate that modelling of dust storms in the Middle East is really challenging due to the complex terrain, incorrect representation of the dust sources and soil/surface characteristics, and uncertainties in simulating the wind speed/direction and meteorological dynamics. Given the potential threat by dust storms, more attention should be directed to the dust model development in this region.
Biochemical Characterization and Functional Analysis of Heat Stable High Potential Protease of Bacillus amyloliquefaciens Strain HM48 from Soils of Dachigam National Park in Kashmir Himalaya
Authors: Mushtaq Hina , Jehangir Arshid , Ganai Shabir Ahmad , Farooq Saleem , Ganai Bashir Ahmad , Nazir Ruqeya
Published: January 2021

A novel temperature stable alkaline protease yielding bacteria was isolated from the soils of Dachigam National Park, which is known to be inhabited by a wide variety of endemic plant and animal species of Western Himalaya. This high-potential protease producing isolate was characterized and identified as Bacillus amyloliquefaciens strain HM48 by morphological, Gram’s staining and biochemical techniques followed by molecular characterization using 16S rRNA approach. The extracellular protease of B. amyloliquefaciens HM48 was purified by precipitating with ammonium sulfate (80%), followed by dialysis and Gel filtration chromatography increasing its purity by 5.8-fold. The SDS–PAGE analysis of the purified enzyme confirmed a molecular weight of about ≈25 kDa. The enzyme displayed exceptional activity in a broad temperature range (10–90 °C) at pH 8.0, retaining its maximum at 70 °C, being the highest reported for this proteolytic Bacillus sp., with KM and Vmax of 11.71 mg/mL and 357.14 µmol/mL/min, respectively. The enzyme exhibited remarkable activity and stability against various metal ions, surfactants, oxidizing agent (H2O2), organic solvents and displayed outstanding compatibility with widely used detergents. This protease showed effective wash performance by exemplifying complete blood and egg-yolk stains removal at 70 °C and efficiently disintegrated chicken feathers making it of vital importance for laundry purpose and waste management. For functional analysis, protease gene amplification of strain HM48 yielded a nucleotide sequence of about 700 bp, which, when checked against the available sequences in NCBI, displayed similarity with subtilisin-like serine protease of B. amyloliquefaciens. The structure of this protease and its highest-priority substrate β-casein was generated through protein modeling. These protein models were validated through futuristic algorithms following which protein–protein (protease from HM48 and β-casein) docking was performed. The interaction profile of these proteins in the docked state with each other was also generated, shedding light on their finer details. Such attributes make this thermally stable protease novel and suitable for high-temperature industrial and environmental applications.
Insulin/IGF Axis in Breast Cancer: Clinical Evidence and Translational Insights
Authors: Biello Federica , Platini Francesca , D’Avanzo Francesca , Cattrini Carlo , Mennitto Alessia , Genestroni Silvia , Martini Veronica , Marzullo Paolo , Aimaretti Gianluca , Gennari Alessandra
Published: January 2021

Background: Breast cancer (BC) is the most common neoplasm in women. Many clinical and preclinical studies investigated the possible relationship between host metabolism and BC. Significant differences among BC subtypes have been reported for glucose metabolism. Insulin can promote tumorigenesis through a direct effect on epithelial tissues or indirectly by affecting the levels of other modulators, such as the insulin-like growth factor (IGF) family of receptors, sex hormones, and adipokines. The potential anti-cancer activity of metformin is based on two principal effects: first, its capacity for lowering circulating insulin levels with indirect endocrine effects that may impact on tumor cell proliferation; second, its direct influence on many pro-cancer signaling pathways that are key drivers of BC aggressiveness. Methods: In the present review, the interaction between BC, host metabolism, and patients’ prognosis has been reviewed across available literature evidence. Conclusions: Obesity, metabolic syndrome, and insulin resistance are all involved in BC growth and could have a relevant impact on prognosis. All these factors act through a pro-inflammatory state, mediated by cytokines originated in fat tissue, and seem to be related to a higher risk of BC development and worse prognosis.
Immunotherapy and Immunotherapy Combinations in Metastatic Castration-Resistant Prostate Cancer
Authors: Bansal Dhruv , Reimers Melissa A. , Knoche Eric M. , Pachynski Russell K.
Published: January 2021

Although most prostate cancers are localized, and the majority are curable, recurrences occur in approximately 35% of men. Among patients with prostate-specific antigen (PSA) recurrence and PSA doubling time (PSADT) less than 15 months after radical prostatectomy, prostate cancer accounted for approximately 90% of the deaths by 15 years after recurrence. An immunosuppressive tumor microenvironment (TME) and impaired cellular immunity are likely largely responsible for the limited utility of checkpoint inhibitors (CPIs) in advanced prostate cancer compared with other tumor types. Thus, for immunologically “cold” malignancies such as prostate cancer, clinical trial development has pivoted towards novel approaches to enhance immune responses. Numerous clinical trials are currently evaluating combination immunomodulatory strategies incorporating vaccine-based therapies, checkpoint inhibitors, and chimeric antigen receptor (CAR) T cells. Other trials evaluate the efficacy and safety of these immunomodulatory agents’ combinations with standard approaches such as androgen deprivation therapy (ADT), taxane-based chemotherapy, radiotherapy, and targeted therapies such as tyrosine kinase inhibitors (TKI) and poly ADP ribose polymerase (PARP) inhibitors. Here, we will review promising immunotherapies in development and ongoing trials for metastatic castration-resistant prostate cancer (mCRPC). These novel trials will build on past experiences and promise to usher a new era to treat patients with mCRPC.
Treatment of Advanced Gastro-Entero-Pancreatic Neuro-Endocrine Tumors: A Systematic Review and Network Meta-Analysis of Phase III Randomized Controlled Trials
Authors: Ricci Claudio , Lamberti Giuseppe , Ingaldi Carlo , Mosconi Cristina , Pagano Nico , Alberici Laura , Ambrosini Valentina , Manuzzi Lisa , Monari Fabio , Malvi Deborah , Rosini Francesca , Minni Francesco , Campana Davide , Casadei Riccardo
Published: January 2021

Several new therapies have been approved to treat advanced gastro-entero-pancreatic neuroendocrine neoplasms (GEP–NENs) in the last twenty years. In this systematic review and meta-analysis, we searched MEDLINE, ISI Web of Science, and Scopus phase III randomized controlled trials (RCTs) comparing two or more therapies for unresectable GEP–NENs. Network metanalysis was used to overcome the multiarm problem. For each arm, we described the surface under the cumulative ranking (SUCRA) curves. The primary endpoints were progression-free survival and grade 3–4 of toxicity. We included nine studies involving a total of 2362 patients and 5 intervention arms: SSA alone, two IFN-α plus SSA, two Everolimus alone, one Everolimus plus SSA, one Sunitinib alone, one 177Lu-Dotatate plus SSA, and one Bevacizumab plus SSA. 177Lu-Dotatate plus SSA had the highest probability (99.6%) of being associated with the longest PFS. This approach was followed by Sunitinib use (64.5%), IFN-α plus SSA one (53.0%), SSA alone (46.6%), Bevacizumab plus SSA one (45.0%), and Everolimus ± SSA one (33.6%). The placebo administration had the lowest probability of being associated with the longest PFS (7.6%). Placebo or Bevacizumab use had the highest probability of being the safest (73.7% and 76.7%), followed by SSA alone (65.0%), IFN-α plus SSA (52.4%), 177Lu-Dotatate plus SSA (49.4%), and Sunitinib alone (28.8%). The Everolimus-based approach had the lowest probability of being the safest (3.9%). The best approaches were SSA alone or combined with 177Lu-Dotatate.
Immune Checkpoint Inhibitory Therapy in Sarcomas: Is There Light at the End of the Tunnel?
Authors: Siozopoulou Vasiliki , Domen Andreas , Zwaenepoel Karen , Van Beeck Annelies , Smits Evelien , Pauwels Patrick , Marcq Elly
Published: January 2021

Soft tissue and bone sarcomas are a very heterogeneous group of tumors with many subtypes for which diagnosis and treatment remains a very challenging task. On top of that, the treatment choices are limited, and the prognosis of aggressive sarcomas remains poor. Immune checkpoint inhibitors (ICIs) have drawn a lot of attention last years because of their promising response rates and their durable effects. ICIs are currently widely used in the daily routine practice for the treatment of a different malignancies, such as melanoma, Hodgkin lymphoma, and non-small cell lung carcinoma. Still, ICIs are not included in the standard treatment protocols of the different sarcoma types. However, a plethora of clinical trials investigates the clinical benefit of ICIs in sarcomas. There is clear need to develop predictive biomarkers to determine which sarcoma patients are most likely to benefit from immune checkpoint blockade. This review will focus on (i) the clinical trial results on the use of ICIs in different sarcoma types; and on (ii) possible biomarkers predictive for the effectiveness of these drugs in sarcomas.
Identification of a Dexamethasone Mediated Radioprotection Mechanism Reveals New Therapeutic Vulnerabilities in Glioblastoma
Authors: Aldaz Paula , Auzmendi-Iriarte Jaione , Durántez Maika , Lasheras-Otero Irene , Carrasco-Garcia Estefania , Zelaya M. Victoria , Bragado Laura , Olías-Arjona Ana , Egaña Larraitz , Samprón Nicolás , Morilla Idoia , Redondo-Muñoz Marta , Rico Mikel , Squatrito Massimo , Maria-Alonso Marta , Fernández-Irigoyen Joaquín , Santamaria Enrique , Larráyoz Iñaki M. , Wellbrock Claudia , Matheu Ander , Arozarena Imanol
Published: January 2021

(1) Background: Despite the indisputable effectiveness of dexamethasone (DEXA) to reduce inflammation in glioblastoma (GBM) patients, its influence on tumour progression and radiotherapy response remains controversial. (2) Methods: We analysed patient data and used expression and cell biological analyses to assess effects of DEXA on GBM cells. We tested the efficacy of tyrosine kinase inhibitors in vitro and in vivo. (3) Results: We confirm in our patient cohort that administration of DEXA correlates with worse overall survival and shorter time to relapse. In GBM cells and glioma stem-like cells (GSCs) DEXA down-regulates genes controlling G2/M and mitotic-spindle checkpoints, and it enables cells to override the spindle assembly checkpoint (SAC). Concurrently, DEXA up-regulates Platelet Derived Growth Factor Receptor (PDGFR) signalling, which stimulates expression of anti-apoptotic regulators BCL2L1 and MCL1, required for survival during extended mitosis. Importantly, the protective potential of DEXA is dependent on intact tyrosine kinase signalling and ponatinib, sunitinib and dasatinib, all effectively overcome the radio-protective and pro-proliferative activity of DEXA. Moreover, we discovered that DEXA-induced signalling creates a therapeutic vulnerability for sunitinib in GSCs and GBM cells in vitro and in vivo. (4) Conclusions: Our results reveal a novel DEXA-induced mechanism in GBM cells and provide a rationale for revisiting the use of tyrosine kinase inhibitors for the treatment of GBM.
A Splice Variant in SLC16A8 Gene Leads to Lactate Transport Deficit in Human iPS Cell-Derived Retinal Pigment Epithelial Cells
Authors: Klipfel Laurence , Cordonnier Marie , Thiébault Léa , Clérin Emmanuelle , Blond Frédéric , Millet-Puel Géraldine , Mohand-Saïd Saddek , Goureau Olivier , Sahel José-Alain , Nandrot Emeline F. , Léveillard Thierry
Published: January 2021

Age-related macular degeneration (AMD) is a blinding disease for which most of the patients remain untreatable. Since the disease affects the macula at the center of the retina, a structure specific to the primate lineage, rodent models to study the pathophysiology of AMD and to develop therapies are very limited. Consequently, our understanding relies mostly on genetic studies highlighting risk alleles at many loci. We are studying the possible implication of a metabolic imbalance associated with risk alleles within the SLC16A8 gene that encodes for a retinal pigment epithelium (RPE)-specific lactate transporter MCT3 and its consequences for vision. As a first approach, we report here the deficit in transepithelial lactate transport of a rare SLC16A8 allele identified during a genome-wide association study. We produced induced pluripotent stem cells (iPSCs) from the unique patient in our cohort that carries two copies of this allele. After in vitro differentiation of the iPSCs into RPE cells and their characterization, we demonstrate that the rare allele results in the retention of intron 2 of the SLC16A8 gene leading to the absence of MCT3 protein. We show using a biochemical assay that these cells have a deficit in transepithelial lactate transport.
Contribution of the CK2 Catalytic Isoforms α and α’ to the Glycolytic Phenotype of Tumor Cells
Authors: Zonta Francesca , Borgo Christian , Quezada Meza Camila Paz , Masgras Ionica , Rasola Andrea , Salvi Mauro , Pinna Lorenzo A. , Ruzzene Maria
Published: January 2021

CK2 is a Ser/Thr protein kinase overexpressed in many cancers. It is usually present in cells as a tetrameric enzyme, composed of two catalytic (α or α’) and two regulatory (β) subunits, but it is active also in its monomeric form, and the specific role of the different isoforms is largely unknown. CK2 phosphorylates several substrates related to the uncontrolled proliferation, motility, and survival of cancer cells. As a consequence, tumor cells are addicted to CK2, relying on its activity more than healthy cells for their life, and exploiting it for developing multiple oncological hallmarks. However, little is known about CK2 contribution to the metabolic rewiring of cancer cells. With this study we aimed at shedding some light on it, especially focusing on the CK2 role in the glycolytic onco-phenotype. By analyzing neuroblastoma and osteosarcoma cell lines depleted of either one (α) or the other (α’) CK2 catalytic subunit, we also aimed at disclosing possible pro-tumor functions which are specific of a CK2 isoform. Our results suggest that both CK2 α and α’ contribute to cell proliferation, survival and tumorigenicity. The analyzed metabolic features disclosed a role of CK2 in tumor metabolism, and suggest prominent functions for CK2 α isoform. Results were also confirmed by CK2 pharmacological inhibition. Overall, our study provides new information on the mechanism of cancer cells addiction to CK2 and on its isoform-specific functions, with fundamental implications for improving future therapeutic strategies based on CK2 targeting.
Unlike its Paralog LEDGF/p75, HRP-2 Is Dispensable for MLL-R Leukemogenesis but Important for Leukemic Cell Survival
Authors: Van Belle Siska , El Ashkar Sara , Čermáková Kateřina , Matthijssens Filip , Goossens Steven , Canella Alessandro , Hodges Courtney H. , Christ Frauke , De Rijck Jan , Van Vlierberghe Pieter , Veverka Václav , Debyser Zeger
Published: January 2021

HDGF-related protein 2 (HRP-2) is a member of the Hepatoma-Derived Growth Factor-related protein family that harbors the structured PWWP and Integrase Binding Domain, known to associate with methylated histone tails or cellular and viral proteins, respectively. Interestingly, HRP-2 is a paralog of Lens Epithelium Derived Growth Factor p75 (LEDGF/p75), which is essential for MLL-rearranged (MLL-r) leukemia but dispensable for hematopoiesis. Sequel to these findings, we investigated the role of HRP-2 in hematopoiesis and MLL-r leukemia. Protein interactions were investigated by co-immunoprecipitation and validated using recombinant proteins in NMR. A systemic knockout mouse model was used to study normal hematopoiesis and MLL-ENL transformation upon the different HRP-2 genotypes. The role of HRP-2 in MLL-r and other leukemic, human cell lines was evaluated by lentiviral-mediated miRNA targeting HRP-2. We demonstrate that MLL and HRP-2 interact through a conserved interface, although this interaction proved less dependent on menin than the MLL-LEDGF/p75 interaction. The systemic HRP-2 knockout mice only revealed an increase in neutrophils in the peripheral blood, whereas the depletion of HRP-2 in leukemic cell lines and transformed primary murine cells resulted in reduced colony formation independently of MLL-rearrangements. In contrast, primary murine HRP-2 knockout cells were efficiently transformed by the MLL-ENL fusion, indicating that HRP-2, unlike LEDGF/p75, is dispensable for the transformation of MLL-ENL leukemogenesis but important for leukemic cell survival.
Neglected Fractures of the Lateral Humeral Condyle in Children; Which Treatment for Which Condition?
Authors: Trisolino Giovanni , Antonioli Diego , Gallone Giovanni , Stallone Stefano , Zarantonello Paola , Tanzi Piergiuseppe , Olivotto Eleonora , Stilli Luca , Di Gennaro Giovanni Luigi , Stilli Stefano
Published: January 2021

Background: Neglected fractures of the lateral humeral condyle (LHC) are misdiagnosed or insufficiently treated fractures, presenting later than 3 weeks after injury. The management of neglected LHC fractures in children remains controversial. Methods: Twenty-seven children were included in this retrospective study. Charts and medical records were investigated for demographics, time interval between injury and treatment, and type of treatment. Baseline radiographs were assessed for fracture grading and displacement. Final radiographs were investigated for bone healing, avascular necrosis, elbow deformities and growth disturbances. Complications were classified by the Clavien–Dindo–Sink (CDS) system. Outcomes were assessed according to the Dhillon Score (DhiS) and Mayo Elbow Performance Score (MEPS). Results: The mean time from injury to presentation was 27 months. Treatments included nonoperative management (6 patients), “in-situ” fixation (7 patients), open reduction and internal fixation (11 patients) and corrective osteotomy (3 patients). The mean follow-up was 7 years (range: 2–16). Overall, we observed complications in 16 patients (59%); six complications were considered major (22%) and occurred in Weiss Grade 3 fractures, with lateral displacement ≥5 mm. At the latest follow-up, pain and functional scores improved in 23 of 27 patients (85%). Mean MEPS increased from an average of 62 points preoperatively to 98 points postoperatively, while mean DhiS improved on average from 5 to 8 points. CDS score and time interval between injury and treatment were independent predictors of MEPS and DhiS. Conclusion: Our study describes outcomes from a cohort of children undergoing different treatments for neglected LHC fractures. Prolonged time interval between injury and treatment and perioperative major complications negatively impacted the treatment outcomes. Our findings strengthen the requirement for widely agreed guidelines of surgical management in neglected LHC fractures.
Study on Eccentric Uncoupled Blasting Effect of Cutting Seam Pipe
Authors: Wang Wei , Zhang Jiaqi , Liu Ao
Published: January 2021

In order to study the blasting effect and the damage to the rock mass when the cutting seam cartridge is eccentrically and uncoupled. The ANSYS/LS-DYNA® nonlinear dynamic platform was used to simulate the blasting effect of five eccentric uncoupled coefficients on the cutting seam cartridge, and the crack growth process under the condition of complete eccentricity was simulated. By comparing and analyzing the stress of measuring points in the direction of cutting seam, vertical cutting seam direction, and circumferential cutting seam pipe under different working conditions. It is concluded that the effect of detonation products is affected by the wrapping property of the cutting seam pipe and the eccentric uncoupled coefficient. With the increase of the eccentric uncoupled coefficient, the load distribution presents obvious non-uniformity. The pressure on the uncoupled side of the blasthole is smaller than that on the coupled side, and the peak time of the uncoupled side also lags behind that on the coupled side. When the eccentric uncoupled coefficient is 1, the peak pressure on the coupled side is 5.78 times that of the uncoupled side, and the explosive stress field is biased toward the coupled side. The existence of the cutting seam pipe causes stress concentration at the opening, which enhances the guiding effect of the initial crack, and the stress in the non-cutting seam direction is buffered. Therefore, the eccentric arrangement of the cutting seam pipe determines the formation of the initial crack and the subsequent blasting effect. When the cutting seam cartridge is arranged eccentrically and uncoupled, it will cause under-excavation at the connection direction of blasthole, which will cause less disturbance to the rock mass on the uncoupled side. If the retaining side rock mass is on the coupled side in actual blasting, the eccentric uncoupled arrangement will cause greater over-excavation and damage. Therefore, it is necessary to avoid this situation as far as possible and provide better guidance for the actual construction.
Surface Analysis of Chamber Coating Materials Exposed to CF4/O2 Plasma
Authors: Park Seung Hyun , Kim Kyung Eon , Hong Sang Jeen
Published: January 2021

Coating the inner surfaces of high-powered plasma processing equipment has become crucial for reducing maintenance costs, process drift, and contaminants. The conventionally preferred alumina (Al2O3) coating has been replaced with yttria (Y2O3) due to the long-standing endurance achieved by fluorine-based etching; however, the continuous increase in radio frequency (RF) power necessitates the use of alternative coating materials to reduce process shift in a series of high-powered semiconductor manufacturing environments. In this study, we investigated the fluorine-based etching resistance of atmospheric pressure-sprayed alumina, yttria, yttrium aluminum garnet (YAG), and yttrium oxyfluoride (YOF). The prepared ceramic-coated samples were directly exposed to silicon oxide etching, and the surfaces of the plasma-exposed samples were characterized by scanning electron microscopy, energy-dispersive X-ray spectroscopy, and X-ray photoelectron spectroscopy. We found that an ideal coating material must demonstrate high plasma-induced structure distortion by the fluorine atom from the radical. For endurance to fluorine-based plasma exposure, the bonding structure with fluoride was shown to be more effective than oxide-based ceramics. Thus, fluoride-based ceramic materials can be promising candidates for chamber coating materials.
Hf-Based UiO-66 as Adsorptive Compound and Oxidative Catalyst for Denitrogenation Processes
Authors: Faria Rui G. , Julião Diana , Balula Salete S. , Cunha-Silva Luís
Published: January 2021

A series of porous metal–organic frameworks (MOFs) of the UiO-66 family, namely UiO-66(Zr), UiO-66(Hf) and UiO-66(Hf)-NH2, prepared by solvothermal procedures were characterized, and their catalytic efficiency for oxidative denitrification (ODN) was investigated for the first time. Sustainable denitrogenation systems combining adsorption and oxidative catalytic capacity were designed using a model diesel containing two distinct nitrogen compounds (NCs) in a solvent-free medium and using an environment-friendly oxidant (H2O2). An efficient adsorptive denitrogenation process was only achieved after long reaction times (24 h): using the Hf-based MOFs, the adsorptive denitrogenation increased from 19% to 79% at 5 to 24 h, while the UiO-66(Zr) reached 76% after 24 h, although the absence of adsorption capacity after 5 h. UiO-66(Hf) and UiO-66(Hf)-NH2 also revealed superior oxidative catalytic denitrogenation than UiO-66(Zr), attaining 97% of efficiency instead of 80%. ODN processes demonstrated to be more effective than the adsorptive denitrogenation, mainly during the first hours of the process. In addition, the metal center in the MOF structure had a larger influence than the presence of the amine-functional groups. Hf-based compounds revealed higher denitrogenation efficiency than the UiO-66(Zr) for a shorter reaction time (5 h).
Spectroscopic Investigations, Computational Analysis and Molecular Docking to SAR-Cov-2 Targets Studies of 5,8-Quinolinedione Attached to Betulin Derivatives
Authors: Kadela-Tomanek Monika , Jastrzębska Maria , Marciniec Krzysztof , Bębenek Ewa , Chrobak Elwira , Boryczka Stanisław
Published: January 2021

The 5,8-quinolinedione-betulin hybrids were investigated using spectroscopic methods as well as a variety of quantum chemical calculations in order to characterize their molecular structure. We used FT-IR and NMR spectroscopy supplemented by the density functional theory (DFT) calculations, molecular electrostatic potential (MEP) and molecular orbital (HOMO, LUMO) analyses. The experimental and calculated FT-IR spectra showed a good correlation for all compounds. Analysis of carbonyl band showed that the compounds are the 7-mono substituted. The calculated 1H NMR and 13C NMR spectra of hybrids reproduced well the experimental ones. Identification of C-6 and C-7 carbon atoms of 5,8-quinolinedione revealed the position of betulin moiety at the C-7 of 5,8-quinolinedione. Molecular electrostatic potential maps of hybrids allowed to recognize the electrophilic and nucleophilic regions within the molecules. The molecular docking study was used to examine the interaction between the 5,8-quinolinedione-betulin hybrids and the SARS-CoV-2 protein, like: Mpro and PLpro. The obtained results showed that compounds with the highest Dock Score are good anti-SARS-CoV-2 potential drug candidates.
Publisher’s Note: Continued Publication of Current Oncology by MDPI
Authors: Mihaila Delia
Published: January 2021

Current Oncology was launched in 1994 and has published international and multidisciplinary research in the field of cancer therapy, to report on and review progress made in managing this disease over the last 26 years [...]
Current Oncology: A Multidisciplinary Medium for Clinical Oncology
Authors: Gill Sharlene
Published: January 2021

In recent years, the field of oncology has witnessed the unprecedented pace of genomics discovery, knowledge translation, and clinical research validation, which has led to novel systemic and locoregional therapeutics, an evolving role of immunotherapy, and a broader application of precision oncology [...]
Research Productivity of Canadian Radiation Oncology Residents: A Time-Trend Analysis
Authors: Mutsaers Adam , Jia Sangyang , Warner Andrew , Nguyen Timothy K. , Laba Joanna M. , Palma David A.
Published: January 2021

(1) Background: Research productivity is a mandatory component of Canadian radiation oncology (RO) resident training. To our knowledge, Canadian RO resident research publication productivity has not previously been analysed. (2) Methods: We compiled a 12-year database of RO residents in Canadian training programs who completed residency between June 2005 and June 2016. Resident names and dates of training were abstracted from provincial databases and department websites and were used to abstract data from PubMed, including training program, publication year, journal, type of research, topic and authorship position. Residents were divided into four time periods and the linear trend test evaluated publication rates over time. Univariable and multivariable logistic regression analyses were performed to identify authorship predictors. (3) Results: 227 RO residents representing 363 publications were identified. The majority were first-author publications (56%) and original research (77%). Overall, 82% of first-author, and 80% of any-author articles were published in resident year 4 or higher. Mean number of publications for first-author and any-author positions increased significantly over time (p = 0.016 and p = 0.039, respectively). After adjusting for gender and time period, large institutions (> 3 residents per year) trended toward associations with more first-author publications (odds ratio (OR): 2.44; p = 0.066) and more any-author publications (OR: 2.49; p = 0.052). No significant differences were observed by gender. (4) Conclusions: Canadian RO resident publication productivity nearly doubled over a 12-year period. The majority of publications are released in the last 2 years of residency, and larger residency programs may be associated with more publications. These findings serve as a baseline as programs transition to Competency Based Medical Education (CBME).
Evolution of Systemic Treatment Uptake and Survival in Advanced Non-Small Cell Lung Cancer
Authors: Stock-Martineau Sophie , Laurie Katie , McKinnon Mathieu , Zhang Tinghua , Wheatley-Price Paul
Published: January 2021

Background: Non-small cell lung cancer (NSCLC) commonly presents at advanced stage. We previously reported systemic treatment uptake in stage IV NSCLC climbing from 55% (2009–2012) to 62% (2015–2017). Since then, first-line immunotherapy and 2nd/3rd generation tyrosine kinase inhibitors (TKIs) have emerged as standards of care. We explored whether treatment rates continued to rise and studied outcomes. Methods: We reviewed all cases of de novo stage IIIB/IIIC/IV NSCLC seen in out-patient medical oncology consultation at our institution between 2009–2012 (cohort A), 2015–2017 (cohort B), and June–December 2018 (cohort C). We compared rates of systemic treatment, molecular testing, targeted therapy, and immune checkpoint inhibitor (ICI) use. We compared survival in the overall, treated/untreated, younger and elderly population in cohort A vs. cohort B + C (=cohort D). Results: Cohorts A, B, and C included 528, 463, and 93 patients, respectively. Overall, 66% received any systemic therapy in cohort C, compared to 62% in cohort B and 55% in cohort A. Across three time periods, first-line chemotherapy rates fell (93, 76, 46%) while rates of first-line targeted therapy (5, 16, 15%) and ICI (0, 2, 36%) rose. Among molecular subtypes, first-line targeted treatment in EGFR-positive patients (63, 94, 100%) and anaplastic lymphoma kinase (ALK)-positive patients (0, 91, 100%) rose. Survival improved in all subgroups in cohort D vs. cohort A, except for patients ≥ 70 years and the untreated population. Conclusions: Systemic treatment rose across three time periods, reflecting the introduction of rapid diagnostic pathways, reflex molecular testing, ICI, and targeted therapies. Survival outcomes of advanced NSCLC patients have significantly improved.