bluuebunny/crossref_metadata_2025 huggingface dataset:
MRI-Based Radiomics Input for Prediction of 2-Year Disease Recurrence in Anal Squamous Cell Carcinoma
Authors: Giraud Nicolas , Saut Olivier , Aparicio Thomas , Ronchin Philippe , Bazire Louis-Arnaud , Barbier Emilie , Lemanski Claire , Mirabel Xavier , Etienne Pierre-Luc , Lièvre Astrid , Cacheux Wulfran , Darut-Jouve Ariane , De la Fouchardière Christelle , Hocquelet Arnaud , Trillaud Hervé , Charleux Thomas , Breysacher Gilles , Argo-Leignel Delphine , Tessier Alexandre , Magné Nicolas , Ben Abdelghani Meher , Lepage Côme , Vendrely Véronique
Published: January 2021

Purpose: Chemo-radiotherapy (CRT) is the standard treatment for non-metastatic anal squamous cell carcinomas (ASCC). Despite excellent results for T1-2 stages, relapses still occur in around 35% of locally advanced tumors. Recent strategies focus on treatment intensification, but could benefit from a better patient selection. Our goal was to assess the prognostic value of pre-therapeutic MRI radiomics on 2-year disease control (DC). Methods: We retrospectively selected patients with non-metastatic ASCC treated at the CHU Bordeaux and in the French FFCD0904 multicentric trial. Radiomic features were extracted from T2-weighted pre-therapeutic MRI delineated sequences. After random division between training and testing sets on a 2:1 ratio, univariate and multivariate analysis were performed on the training cohort to select optimal features. The correlation with 2-year DC was assessed using logistic regression models, with AUC and accuracy as performance gauges, and the prediction of disease-free survival using Cox regression and Kaplan-Meier analysis. Results: A total of 82 patients were randomized in the training (n = 54) and testing sets (n = 28). At 2 years, 24 patients (29%) presented relapse. In the training set, two clinical (tumor size and CRT length) and two radiomic features (FirstOrder_Entropy and GLCM_JointEnergy) were associated with disease control in univariate analysis and included in the model. The clinical model was outperformed by the mixed (clinical and radiomic) model in both the training (AUC 0.758 versus 0.825, accuracy of 75.9% versus 87%) and testing (AUC 0.714 versus 0.898, accuracy of 78.6% versus 85.7%) sets, which led to distinctive high and low risk of disease relapse groups (HR 8.60, p = 0.005). Conclusion: A mixed model with two clinical and two radiomic features was predictive of 2-year disease control after CRT and could contribute to identify high risk patients amenable to treatment intensification with view of personalized medicine.
Effects of In-Hospital Exercise on Frailty in Patients with Hepatocellular Carcinoma
Authors: Tsuchihashi Jin , Koya Shunji , Hirota Keisuke , Koga Noboru , Narao Hayato , Tomita Manabu , Kawaguchi Takumi , Hashida Ryuki , Nakano Dan , Tsutsumi Tsubasa , Yoshio Sachiyo , Matsuse Hiroo , Sanada Taku , Notsumata Kazuo , Torimura Takuji
Published: January 2021

Frailty including physical inactivity is associated with the survival of patients with hepatocellular carcinoma (HCC). We aimed to investigate the effects of in-hospital exercise on frailty in patients with HCC. This was a multi-center observational study. Patients with HCC were classified into exercise (n = 114) and non-exercise (n = 67) groups. The exercise group was treated with a mixture of aerobic and resistance exercises (20–40 min/day, median four days). Frailty was assessed using the liver frailty index (LFI). Factors for changes in LFI were examined by multivariate and decision-tree analyses. The factors were also examined after propensity score matching. During hospitalization, LFI was significantly improved in the exercise group compared to the non-exercise group (ΔLFI −0.17 vs. −0.02, p = 0.0119). In multivariate analysis, exercise (odds ratio (OR) 2.38, 95% confidence interval (CI) 1.240–4.570, p = 0.0091) and females (OR 2.09; 95%CI, 1.062–4.109; p = 0.0328) were identified as independent factors for the improvement of LFI. In the decision-tree analysis, exercise was identified as an initial classifier associated with the improvement of LFI. Similar findings were also seen in the propensity score matching analyses. We demonstrated that in-hospital exercise improved frailty in patients with HCC. Thus, in-hospital exercise may be beneficial for improving physical function in patients with HCC.
Serum Response Factor (SRF) Drives the Transcriptional Upregulation of the MDM4 Oncogene in HCC
Authors: Pellegrino Rossella , Thavamani Abhishek , Calvisi Diego F. , Budczies Jan , Neumann Ariane , Geffers Robert , Kroemer Jasmin , Greule Damaris , Schirmacher Peter , Nordheim Alfred , Longerich Thomas
Published: January 2021

Different molecular mechanisms support the overexpression of the mouse double minute homolog 4 (MDM4), a functional p53 inhibitor, in human hepatocellular carcinoma (HCC). However, the transcription factors (TFs) leading to its transcriptional upregulation remain unknown. Following promoter and gene expression analyses, putative TFs were investigated using gene-specific siRNAs, cDNAs, luciferase reporter assays, chromatin immunoprecipitation, and XI-011 drug treatment in vitro. Additionally, MDM4 expression was investigated in SRF-VP16iHep transgenic mice. We observed a copy-number-independent upregulation of MDM4 in human HCCs. Serum response factor (SRF), ELK1 and ELK4 were identified as TFs activating MDM4 transcription. While SRF was constitutively detected in TF complexes at the MDM4 promoter, presence of ELK1 and ELK4 was cell-type dependent. Furthermore, MDM4 was upregulated in SRF-VP16-driven murine liver tumors. The pharmacological inhibitor XI-011 exhibited anti-MDM4 activity by downregulating the TFs driving MDM4 transcription, which decreased HCC cell viability and increased apoptosis. In conclusion, SRF drives transcriptional MDM4 upregulation in HCC, acting in concert with either ELK1 or ELK4. The transcriptional regulation of MDM4 may be a promising target for precision oncology of human HCC, as XI-011 treatment exerts anti-MDM4 activity independent from the MDM4 copy number and the p53 status.
Oncological Outcomes after Liver Venous Deprivation for Colorectal Liver Metastases: A Single Center Experience
Authors: Khayat Salah , Cassese Gianluca , Quenet François , Cassinotto Christophe , Assenat Eric , Navarro Francis , Guiu Boris , Panaro Fabrizio
Published: January 2021

Colorectal liver metastases (CRLM) are the major cause of death in patients with colorectal cancer (CRC). The cornerstone treatment of CRLM is surgical resection. Post-operative morbidity and mortality are mainly linked to an inadequate future liver remnant (FLR). Nowadays preoperative portal vein embolization (PVE) is the most widely performed technique to increase the size of the future liver remnant (FLR) before major hepatectomies. One method recently proposed to increase the FLR is liver venous deprivation (LVD), but its oncological impact is still unknown. The aim of this study is to report first short- and long-term oncological outcomes after LVD in patients undergoing right (or extended right) hepatectomy for CRLM. Seventeen consecutive patients undergoing LVD between July 2015 and May 2020 before an (extended) right hepatectomy were retrospectively analyzed from an institutional database. Post-operative and follow-up data were analyzed and reported. Primary outcomes were 1-year and 3-year overall survival (OS) and hepatic recurrence (HR). Postoperative complications occurred in 8 patients (47%). No deaths occurred after surgery. HR occurred in 9 patients (52.9%). 1-year and 3-year OS were 87% (95% confidence interval [CI]: ±16%) and 60.3%, respectively (95% CI: ±23%). Median Disease-Free Survival (DFS) was 6 months (CI 95%: 4.7–7.2). With all the limitations of a retrospective study with a small sample size, LVD showed similar oncological outcomes compared to literature reports for Portal Vein Embolization (PVE).
ASCT2 and LAT1 Contribution to the Hallmarks of Cancer: From a Molecular Perspective to Clinical Translation
Authors: Lopes Catarina , Pereira Carina , Medeiros Rui
Published: January 2021

The role of the amino acid transporters ASCT2 and LAT1 in cancer has been explored throughout the years. In this review, we report their impact on the hallmarks of cancer, as well as their clinical significance. Overall, both proteins have been associated with cell death resistance through dysregulation of caspases and sustainment of proliferative signaling through mTOR activation. Furthermore, ASCT2 appears to play an important role in cellular energetics regulation, whereas LAT1 expression is associated with angiogenesis and invasion and metastasis activation. The molecular impact of these proteins on the hallmarks of cancer translates into various clinical applications and both transporters have been identified as prognostic factors in many types of cancer. Concerning their role as therapeutic targets, efforts have been undertaken to synthesize competitive or irreversible ASCT2 and LAT1 inhibitors. However, JHP203, a selective inhibitor of the latter, is, to the best of our knowledge, the only compound included in a Phase 1 clinical trial. In conclusion, considering the usefulness of ASCT2 and LAT1 in a variety of cancer-related pathways and cancer therapy/diagnosis, the development and testing of novel inhibitors for these transporters that could be evaluated in clinical trials represents a promising approach to cancer prognosis improvement.
The Role of the Eph Receptor Family in Tumorigenesis
Authors: Anderton Meg , van der Meulen Emma , Blumenthal Melissa J. , Schäfer Georgia
Published: January 2021

The Eph receptor tyrosine kinase family, activated by binding to their cognate ephrin ligands, are important components of signalling pathways involved in animal development. More recently, they have received significant interest due to their involvement in oncogenesis. In most cases, their expression is altered, affecting the likes of cell proliferation and migration. Depending on the context, Eph receptors have the potential to act as both tumour promoters and suppressors in a number of cancers, such as breast cancer, colorectal cancer, lung cancer, prostate cancer, brain cancer and Kaposi’s sarcoma (KS), the latter being intrinsically linked to EphA2 as this is the receptor used for endothelial cell entry by the Kaposi’s sarcoma-associated herpesvirus (KSHV). In addition, EphA2 deregulation is associated with KS, indicating that it has a dual role in this case. Associations between EphA2 sequence variation and KSHV infection/KS progression have been detected, but further work is required to formally establish the links between EphA2 signalling and KS oncogenesis. This review consolidates the available literature of the role of the Eph receptor family, and particularly EphA2, in tumorigenesis, with the aim to develop a better understanding of Eph signalling pathways for potential targeting in novel cancer therapies.
The Functional Crosstalk between Myeloid-Derived Suppressor Cells and Regulatory T Cells within the Immunosuppressive Tumor Microenvironment
Authors: Haist Maximilian , Stege Henner , Grabbe Stephan , Bros Matthias
Published: January 2021

Immune checkpoint inhibitors (ICI) have led to profound and durable tumor regression in some patients with metastatic cancer diseases. However, many patients still do not derive benefit from immunotherapy. Here, the accumulation of immunosuppressive cell populations within the tumor microenvironment (TME), such as myeloid-derived suppressor cells (MDSC), tumor-associated macrophages (TAM), and regulatory T cells (Treg), contributes to the development of immune resistance. MDSC and Treg expand systematically in tumor patients and inhibit T cell activation and T effector cell function. Numerous studies have shown that the immunosuppressive mechanisms exerted by those inhibitory cell populations comprise soluble immunomodulatory mediators and receptor interactions. The latter are also required for the crosstalk of MDSC and Treg, raising questions about the relevance of cell–cell contacts for the establishment of their inhibitory properties. This review aims to outline the current knowledge on the crosstalk between these two cell populations, issuing particularly the potential role of cell adhesion molecules. In this regard, we further discuss the relevance of β2 integrins, which are essential for the differentiation and function of leukocytes as well as for MDSC–Treg interaction. Lastly, we aim to describe the impact of such bidirectional crosstalk for basic and applied cancer research and discuss how the targeting of these pathways might pave the way for future approaches in immunotherapy.
Remodeling of the Lymph Node High Endothelial Venules Reflects Tumor Invasiveness in Breast Cancer and is Associated with Dysregulation of Perivascular Stromal Cells
Authors: Bekkhus Tove , Martikainen Teemu , Olofsson Anna , Franzén Boger Mathias , Vasiliu Bacovia Daniel , Wärnberg Fredrik , Ulvmar Maria H.
Published: January 2021

The tumor-draining lymph nodes (TDLNs) are primary sites for induction of tumor immunity. They are also common sites of metastasis, suggesting that tumor-induced mechanisms can subvert anti-tumor immune responses and promote metastatic seeding. The high endothelial venules (HEVs) together with CCL21-expressing fibroblastic reticular cells (FRCs) are essential for lymphocyte recruitment into the LNs. We established multicolor antibody panels for evaluation of HEVs and FRCs in TDLNs from breast cancer (BC) patients. Our data show that patients with invasive BC display extensive structural and molecular remodeling of the HEVs, including vessel dilation, thinning of the endothelium and discontinuous expression of the HEV-marker PNAd. Remodeling of the HEVs was associated with dysregulation of CCL21 in perivascular FRCs and with accumulation of CCL21-saturated lymphocytes, which we link to loss of CCL21-binding heparan sulfate in FRCs. These changes were rare or absent in LNs from patients with non-invasive BC and cancer-free organ donors and were observed independent of nodal metastasis. Thus, pre-metastatic dysregulation of core stromal and vascular functions within TDLNs reflect the primary tumor invasiveness in BC. This adds to the understanding of cancer-induced perturbation of the immune response and opens for prospects of vascular and stromal changes in TDLNs as potential biomarkers.
Nuclear Localization of PTTG1 Promotes Migration and Invasion of Seminoma Tumor through Activation of MMP-2
Authors: Teveroni Emanuela , Di Nicuolo Fiorella , Bianchetti Giada , Epstein Alan L. , Grande Giuseppe , Maulucci Giuseppe , De Spirito Marco , Pontecorvi Alfredo , Milardi Domenico , Mancini Francesca
Published: January 2021

(1) Background: PTTG1 sustains the invasiveness of several cancer types. We previously reported that in seminomas, PTTG1 was detected in the peripheral area of the tumor and in the leading infiltrative edge. Here, we investigate the PTTG1 role on the invasive properties of seminoma. (2) Methods: three seminoma cell lines were used as in vitro model. PTTG1 levels and localization were investigated by biochemical and immunofluorescence analyses. Wound-healing, Matrigel invasion assays, and zymography were applied to study migratory and invasive capability of the cell lines. RNA interference and overexpression experiments were performed to address the PTTG1 role in seminoma invasiveness. PTTG1 and its target MMP-2 were analyzed in human testicular tumors using the Atlas database. (3) Results: PTTG1 was highly and differentially expressed in the seminoma cell lines. Nuclear PTTG1 was positively correlated to the aggressive phenotype. Its modulation confirms these results. Atlas database analysis revealed that PTTG1 was localized in the nucleus in seminoma compared with non-seminoma tumors, and that MMP-2 levels were significantly higher in seminomas. (4) Conclusions: nuclear PTTG1 promotes invasiveness of seminoma cell lines. Atlas database supported these results. These data lead to the hypothesis that nuclear PTTG1 is an eligible prognostic factor in seminomas.
New Bromo- and Iodo-Hydroxylactones with Two Methyl Groups Obtained by Biotransformation of Bicyclic Halolactones
Authors: Grabarczyk Małgorzata , Mączka Wanda , Maciejewska Gabriela , Wińska Katarzyna
Published: January 2021

The subject of the research was to determine the ability of the filamentous fungi to biotransform bicyclic halolactones containing two methyl groups in their structure. By chemical synthesis three bicyclic halolactones with two methyl groups, one in the cyclohexane ring and one in the lactone ring, were obtained: 2-chloro-4,7-dimethyl-9-oxabicyclo[4.3.0]nonan-8-one, 2-bromo-4,7-dimethyl-9-oxabicyclo[4.3.0]nonan-8-one, and 2-iodo-4,7-dimethyl-9-oxabicyclo[4.3.0]nonan-8-one. These compounds were formed as mixtures of two diastereoisomers. The obtained halolactones (as mixture of two diastereoisomers) were subjected to screening biotransformation with the use of eight strains of filamentous fungi: Fusarium culmorum AM10, F. avenaceum AM12, F. semitectum AM20, F. solani AM203, Absidia coerulea AM93, A. cylindrospora AM336, Penicillium chermesinum AM113, P. frequentans AM351. Two of the substrates, 2-bromo-4,7-dimethyl-9-oxabicyclo[4.3.0]nonan-8-one and 2-iodo-4,7-dimethyl-9-oxabicyclo[4.3.0]nonan-8-one, were hydroxylated without removing the halogen atom from the molecule, giving 2-bromo-7-hydroxy-4,7-dimethyl-9-oxabicyclo[4.3.0]nonan-8-one, 2-bromo-5-hydroxy-4,7-dimethyl-9-oxabicyclo[4.3.0]nonan-8-one, and 2-iodo-7-hydroxy-4,7-dimethyl-9-oxabicyclo[4.3.0]nonan-8-one as products. The hydroxylation capacity was demonstrated by strains of Absidia cylindrospora AM336, Fusarium avenaceum AM12, and F. solani AM203. The structures of all lactones were determined on the basis spectroscopic data.
Wastewater Contaminated with Hydrazine as Scavenger Agent for Hydrogen Production by Cu/Ti Nanostructures
Authors: Hinojosa Reyes Mariana , Camposeco Roberto , Rodríguez González Vicente
Published: January 2021

Cu/Ti photocatalysts were prepared by the sol-gel process with different copper loadings (1.0, 2.5, and 5.0 wt.%) and then thermally treated at several calcination temperatures from 400 to 600 °C. The materials were characterized by X-ray diffraction (XRD), N2 physisorption, Scanning Electronic Microscopy with Energy Dispersive X-ray Spectroscopy (SEM-EDS), Ultraviolet-visible-Diffuse Reflection Spectroscopy, Ultraviolet-visible spectroscopy as a function of the temperature, (Temperature Programmed Reduction) TPR-chemisorption, XPS (X-ray Photoelectron Spectroscopy) and OH determination through DRIFTS (Diffuse reflectance infrared Fourier transform spectroscopy). The Cu/Ti photocatalysts were evaluated for the photocatalytic production of hydrogen using hydrazine as scavenging agent. Moreover, a detailed study of the Cu1+/Cu2+ ratio and the corresponding formation of copper oxide was carried out to understand the correlation between the copper species and the photocatalytic activity. Simultaneously, the OH groups on the TiO2 surface also show insights into the behavior of these materials during the photocatalytic reaction. Despite the low hydrazine concentration (20 mM), the 1.0 (wt.%) Cu/Ti 500 photocatalyst enhanced the hydrogen production three and two times more than photolysis and bare TiO2, respectively. The 1.0 Cu/Ti 500 photocatalyst displayed outstanding stability for at least three continuous cycles of 8 h each, preserving the hydrogen production. The novel ability shown in this work represents an alternative to reduce the hydrazine residues in wastewater to transform it into a hydrogen-producing energy source and must be extended to other reductive pollutants found in wastewater.
Top 10 Cited Papers in the Section “Environmental Catalysis”
Authors: Lamonier Jean-François
Published: January 2021

This editorial examines the 10 most cited articles of 2018–2019 published in the “Environmental Catalysis” section of the Catalysts journal [...]
Regulation of Osteoclast Differentiation and Activity by Lipid Metabolism
Authors: Kim Haemin , Oh Brian , Park-Min Kyung-Hyun
Published: January 2021

Bone is a dynamic tissue and is constantly being remodeled by bone cells. Metabolic reprogramming plays a critical role in the activation of these bone cells and skeletal metabolism, which fulfills the energy demand for bone remodeling. Among various metabolic pathways, the importance of lipid metabolism in bone cells has long been appreciated. More recent studies also establish the link between bone loss and lipid-altering conditions—such as atherosclerotic vascular disease, hyperlipidemia, and obesity—and uncover the detrimental effect of fat accumulation on skeletal homeostasis and increased risk of fracture. Targeting lipid metabolism with statin, a lipid-lowering drug, has been shown to improve bone density and quality in metabolic bone diseases. However, the molecular mechanisms of lipid-mediated regulation in osteoclasts are not completely understood. Thus, a better understanding of lipid metabolism in osteoclasts can be used to harness bone cell activity to treat pathological bone disorders. This review summarizes the recent developments of the contribution of lipid metabolism to the function and phenotype of osteoclasts.
MiR-26a-5p as a Reference to Normalize MicroRNA qRT-PCR Levels in Plasma Exosomes of Pediatric Hematological Malignancies
Authors: Damanti Carlotta C. , Gaffo Enrico , Lovisa Federica , Garbin Anna , Di Battista Piero , Gallingani Ilaria , Tosato Anna , Pillon Marta , Carraro Elisa , Mascarin Maurizio , Elia Caterina , Biffi Alessandra , Bortoluzzi Stefania , Mussolin Lara
Published: January 2021

Plasma exosomal microRNAs (miRNAs) are considered as valid circulating biomarkers for cancer diagnosis and prognosis. Quantitative real-time polymerase chain reaction (qRT-PCR), the most commonly used technique to assess circulating miRNA levels, requires a normalization step involving uniformly expressed endogenous miRNAs. However, there is still no consensus on reference miRNAs for plasma exosomal miRNA abundance normalization. In this study, we identified a panel of miRNAs with stable abundance by analyzing public plasma exosome RNA-seq data and selected miR-486-5p, miR-26a-5p, miR-423-5p and miR191-5p as candidate normalizers. Next, we tested the abundance variation of these miRNAs by qRT-PCR in plasma exosomes of healthy donors and pediatric patients with anaplastic large cell lymphoma, Burkitt lymphoma, Hodgkin lymphoma and mature B-cell acute lymphoblastic leukemia. MiR-486-5p and miR-26a-5p showed the most stable levels, both between healthy controls and patients and among the malignancies analyzed. In light of previous reports on miRNA stability in different exosome isolation methods, our data indicated that miR-26a-5p is a bona fide reference miRNA for qRT-PCR normalization to evaluate miRNA abundance from circulating plasma exosomes in studies of hematological malignancies.
The Effect of Abiotic Factors on Abundance and Photosynthetic Performance of Airborne Cyanobacteria and Microalgae Isolated from the Southern Baltic Sea Region
Authors: Wiśniewska Kinga , Śliwińska-Wilczewska Sylwia , Lewandowska Anita , Konik Marta
Published: January 2021

Cyanobacteria and microalgae present in the aquatic or terrestrial environment may be emitted into the air and transported along with air masses over long distances. As a result of staying in the atmosphere, these organisms may develop a greater tolerance to stressful factors, but this topic is still relatively unknown. The main aim was to show an autecological characteristic of some airborne microalgae and cyanobacteria strains by a factorial laboratory experiment approach, including changes in irradiance, temperature, and salinity conditions. The additional purpose of this work was also to present part of the Culture Collection of Baltic Algae (CCBA) collection, which consists of airborne algae (AA) isolated from the atmospheric air of the southern Baltic Sea region. Altogether, 61 strains of airborne cyanobacteria and microalgae from the southern Baltic Sea region were isolated from May 2018 to August 2020. Selected microorganisms were tested in controlled laboratory conditions to identify their response to different irradiance (10–190 µmol photons m−2 s−1), temperature (13–23 °C), and salinity conditions (0–36 PSU). The highest numbers of cells (above 30 × 105 cell mL−1) were recorded for cyanobacterium Nostoc sp., and for diatoms Nitzschia sp., Amphora sp., and Halamphora sp. We found that for cyanobacterium Nostoc sp. as well as for green alga Coccomyxa sp. the maximum cell concentrations were recorded at the salinity of 0 PSU. Moreover, cyanobacteria Planktolyngbya contorta, Pseudanabaena catenata, Leptolyngbya foveolarum, Gloeocapsa sp., and Rivularia sp. were able to grow only at a salinity of 0 PSU. On the other hand, in the range of 16–24 PSU, the highest cell numbers of examined diatoms have been identified. Our research provided that deposited airborne microalgae and cyanobacteria showed full colonization potential. The present experiment suggests that the adaptive abilities of microorganisms, in particular those producing toxins, may contribute to the spread in the future. Thus, it may increase human exposure to their negative health effects. Any distinctive adaptations of the genera give them an additional competitive advantage and a greater chance for territorial expansion.
Cellular and Molecular Mechanisms of R/S-Roscovitine and CDKs Related Inhibition under Both Focal and Global Cerebral Ischemia: A Focus on Neurovascular Unit and Immune Cells
Authors: Le Roy Lucas , Letondor Anne , Le Roux Cloé , Amara Ahmed , Timsit Serge
Published: January 2021

Ischemic stroke is the second leading cause of death worldwide. Following ischemic stroke, Neurovascular Unit (NVU) inflammation and peripheral leucocytes infiltration are major contributors to the extension of brain lesions. For a long time restricted to neurons, the 10 past years have shown the emergence of an increasing number of studies focusing on the role of Cyclin-Dependent Kinases (CDKs) on the other cells of NVU, as well as on the leucocytes. The most widely used CDKs inhibitor, (R)-roscovitine, and its (S) isomer both decreased brain lesions in models of global and focal cerebral ischemia. We previously showed that (S)-roscovitine acted, at least, by modulating NVU response to ischemia. Interestingly, roscovitine was shown to decrease leucocytes-mediated inflammation in several inflammatory models. Specific inhibition of roscovitine majors target CDK 1, 2, 5, 7, and 9 showed that these CDKs played key roles in inflammatory processes of NVU cells and leucocytes after brain lesions, including ischemic stroke. The data summarized here support the investigation of roscovitine as a potential therapeutic agent for the treatment of ischemic stroke, and provide an overview of CDK 1, 2, 5, 7, and 9 functions in brain cells and leucocytes during cerebral ischemia.
Ionizing Radiation-Induced Extracellular Vesicle Release Promotes AKT-Associated Survival Response in SH-SY5Y Neuroblastoma Cells
Authors: Tortolici Flavia , Vumbaca Simone , Incocciati Bernadette , Dayal Renu , Aquilano Katia , Giovanetti Anna , Rufini Stefano
Published: January 2021

Radiation therapy is one of the most effective methods of tumor eradication; however, in some forms of neuroblastoma, radiation can increase the risk of secondary neoplasms, due to the ability of irradiated cells to transmit pro-survival signals to non-irradiated cells through vesicle secretion. The aims of this study were to characterize the vesicles released by the human neuroblastoma cell line SH-SY5Y following X-ray radiations and their ability to increase invasiveness in non-irradiated SH-SY5Y cells. We first purified the extracellular vesicles released by the SH-SY5Y cells following X-rays, and then determined their total amount, dimensions, membrane protein composition, and cellular uptake. We also examined the effects of these extracellular vesicles on viability, migration, and DNA damage in recipient SH-SY5Y cells. We found that exposure to X-rays increased the release of extracellular vesicles and altered their protein composition. These vesicles were readily uptaken by non-irradiated cells, inducing an increase in viability, migration, and radio-resistance. The same results were obtained in an MYCN-amplified SK-N-BE cell line. Our study demonstrates that vesicles released from irradiated neuroblastoma cells stimulate proliferation and invasiveness that correlate with the epithelial to mesenchymal transition in non-irradiated cells. Moreover, our results suggest that, at least in neuroblastomas, targeting the extracellular vesicles may represent a novel therapeutic approach to counteract the side effects associated with radiotherapy.
Tumor-Associated Antigen xCT and Mutant-p53 as Molecular Targets for New Combinatorial Antitumor Strategies
Authors: Magri Jolanda , Gasparetto Alessandro , Conti Laura , Calautti Enzo , Cossu Chiara , Ruiu Roberto , Barutello Giuseppina , Cavallo Federica
Published: January 2021

The cystine/glutamate antiporter xCT is a tumor-associated antigen that has been newly identified in many cancer types. By participating in glutathione biosynthesis, xCT protects cancer cells from oxidative stress conditions and ferroptosis, and contributes to metabolic reprogramming, thus promoting tumor progression and chemoresistance. Moreover, xCT is overexpressed in cancer stem cells. These features render xCT a promising target for cancer therapy, as has been widely reported in the literature and in our work on its immunotargeting. Interestingly, studies on the TP53 gene have revealed that both wild-type and mutant p53 induce the post-transcriptional down modulation of xCT, contributing to ferroptosis. Moreover, APR-246, a small molecule drug that can restore wild-type p53 function in cancer cells, has been described as an indirect modulator of xCT expression in tumors with mutant p53 accumulation, and is thus a promising drug to use in combination with xCT inhibition. This review summarizes the current knowledge of xCT and its regulation by p53, with a focus on the crosstalk of these two molecules in ferroptosis, and also considers some possible combinatorial strategies that can make use of APR-246 treatment in combination with anti-xCT immunotargeting.
Safety and Effects of the Rapid Maxillary Expander on Temporomandibular Joint in Subjects Affected by Juvenile Idiopathic Arthritis: A Retrospective Study
Authors: Abate Andrea , Cavagnetto Davide , Rusconi Francesca Maria Emilia , Cressoni Paolo , Esposito Luca
Published: January 2021

Background: In Juvenile Idiopathic Arthritis (JIA) temporo-mandibular joints are often affected causing skeletal and dental malocclusions. The most frequent condition is mandibular hypoplasia, that may be associated with maxillary hypoplasia. The aim of this retrospective case control study is to investigate the effects and the safety of rapid maxillary expansion (RME) in growing patients affected by JIA. It was evaluated whether RME could be performed without complications on TMJs of JIA patients using DC/TMD protocol, and naso-maxillary transversal parameters were compared with the ones obtained on healthy patients. Methods: Twenty-five patients affected by JIA that ceased to manifest TMJ (Temporo-Mandibular Joint) symptoms in the previous year were treated with RME to solve the maxillary transverse hypoplasia. Postero-anterior cephalometric tracings were collected before and after treatment; linear measurements were obtained to study maxillary and nasal cavity modifications. Data were compared to those of a similar group of twenty-five healthy patients. Paired t-test and Independent t-test were used to evaluate changes before and after treatment in each group and to perform a comparison between the groups. Results: All patients demonstrated a statistically significant increase in nasal cavity width, maxillary width and upper and lower intermolar width. No patients presented a worsening of their TMJs condition. Intragroup comparisons revealed significant changes of cephalometric measurements, but no difference was found when comparing JIA and healthy patients. Conclusions: Growing patients with JIA that ceased to show signs of active TMJ involvement for at least one year could be safely treated with RME, expecting similar benefits to those of healthy patients. Dentists and rheumatologists should be informed of safety and potential benefits of palatal expansion in JIA patients in order to improve the outcome of orthodontic treatment and reduce the indication for more invasive procedures (i.e., Surgical Assisted Rapid Maxillary Expansion).
Study of the Adhesion of Silicate-Based Coating Formulations on a Wood Substrate
Authors: Cheumani Yona Arnaud Maxime , Žigon Jure , Dahle Sebastian , Petrič Marko
Published: January 2021

Silicate coatings are environmentally friendly inorganic-based products that have long been used for mineral substrates and protection of steel against corrosion. The development and acceptance of these coatings in the wood sector require some adjustments in formulations or special preparation of the surface to be coated to obtain durable finishes. In this work, the adhesion of various silicate-based formulations to a beech wood substrate (Fagus sylvatica L.), was assessed with the main objective to study relevant parameters and potential improvements. Adhesion strength was determined by pull-off and cross-cut tests. Other coating properties such as scratch, impact, and water resistance were also determined. Surface roughness and interface were analyzed using confocal laser scanning microscopy (CLSM) and scanning electron microscopy (SEM), and coating curing was studied by attenuated total reflection-infrared spectroscopy (ATR FTIR). The results showed that adhesion was highly dependent on formulation, penetration of the coatings into wood, and mechanical anchoring. Increasing the content of solid particles in the coating formulations or adding a polyol (glycerol, xylose), which probably acted as a coalescent, considerably decreased the adhesion strength, probably by blocking penetration into the wood by forming aggregates. Adhesion was improved by pre-mineralization of the surface, and substitution of a part of the potassium silicate binder with potassium methyl siliconate reduced the formation of cracks caused by dimensional instability of the wood.
Meso-Simulation and Experimental Research on the Mechanical Behavior of an Energetic Explosive
Authors: Pan Qinxue , Li Shuangyang , Liu Yang , Xu Xiaoyu , Chang Meile , Zhang Yunmiao
Published: January 2021

This study establishes a model for polymer-bonded explosives (PBX) using Digimat-FE. The model identifies the relationship between the material’s effective elastic modulus and the explosive particle volume fraction, shape and gradation, and porosity, as well as other factors. Further, finite element analysis of the stress distribution of the PBX composite material is performed, and the mathematical models between the ultrasonic attenuation coefficient, particle volume fraction, and ultrasonic frequency are established. Finally, an efficient ultrasonic nondestructive testing system is designed to determine the stress distribution and fine crack groups in the material. Experimental results indicate that the relative error of stress detection is within 15%, which meets the requirements of engineering applications.
Dual-Band Plasmonic Perfect Absorber Based on the Hybrid Halide Perovskite in the Communication Regime
Authors: Xu Liang , Zeng Jian , Luo Xin , Xia Libin , Ma Zongle , Peng Bojun , Li Zhengquan , Zhai Xiang , Wang Lingling
Published: January 2021

Due to the weak absorption of (CH3NH3)PbI3 in the communication regime, which restricts its optoelectronic applications, we design a adjustable dual-band perfect absorber based on the (CH3NH3)PbI3 to significantly enhance its absorption capability. Since the localized plasmon (LP) mode and surface plasmon (SP) mode are excited in the structure, which can both greatly enhance light absorption of the (CH3NH3)PbI3 layer, dual-band perfect absorption peaks are formed in the communication regime, and the absorption of (CH3NH3)PbI3 layer is increased to 43.1% and 64.2% at the dual-band absorption peaks by using finite-difference time-domain (FDTD) methods, respectively. By varying some key structural parameters, the dual-band absorption peaks of (CH3NH3)PbI3 can be separately shifted in a wide wavelength region. Moreover, the designed absorber can keep good performance under wide angles of incidence and manifested polarization correlation. Furthermore, not just for (CH3NH3)PbI3, the physical mechanism in this absorber can also be utilized to strengthen the absorption of other halide perovskites.
Antimicrobial Peptides Grafted onto a Plasma Polymer Interlayer Platform: Performance upon Extended Bacterial Challenge
Authors: Griesser Stefani S. , Jasieniak Marek , Vasilev Krasimir , Griesser Hans J.
Published: January 2021

To combat infections on biomedical devices, antimicrobial coatings have attracted considerable attention, including coatings comprising naturally occurring antimicrobial peptides (AMPs). In this study the aim was to explore performance upon extended challenge by bacteria growing in media above samples. The AMPs LL37, Magainin 2, and Parasin 1 were selected on the basis of well-known membrane disruption activity in solution and were covalently grafted onto a plasma polymer platform, which enables application of this multilayer coating strategy to a wide range of biomaterials. Detailed surface analyses were performed to verify the intended outcomes of the coating sequence. Samples were challenged by incubation in bacterial growth media for 5 and 20 h. Compared with the control plasma polymer surface, all three grafted AMP coatings showed considerable reductions in bacterial colonization even at the high bacterial challenge of initial seeding at 1 × 107 CFU, but there were increasing numbers of dead bacteria attached to the surface. All three grafted AMP coatings were found to be non-toxic to primary fibroblasts. These coatings thus could be useful to produce antibacterial surface coatings for biomaterials, though possible consequences arising from the presence of dead bacteria need to be studied further, and compared to non-fouling coatings that avoid attachment of dead bacteria.
Energy-Efficient Task Partitioning for Real-Time Scheduling on Multi-Core Platforms
Authors: El Sayed Manal A. , Saad El Sayed M. , Aly Rasha F. , Habashy Shahira M.
Published: January 2021

Multi-core processors have become widespread computing engines for recent embedded real-time systems. Efficient task partitioning plays a significant role in real-time computing for achieving higher performance alongside sustaining system correctness and predictability and meeting all hard deadlines. This paper deals with the problem of energy-aware static partitioning of periodic, dependent real-time tasks on a homogenous multi-core platform. Concurrent access of the tasks to shared resources by multiple tasks running on different cores induced a higher blocking time, which increases the worst-case execution time (WCET) of tasks and can cause missing the hard deadlines, consequently resulting in system failure. The proposed blocking-aware-based partitioning (BABP) algorithm aims to reduce the overall energy consumption while avoiding deadline violations. Compared to existing partitioning strategies, the proposed technique achieves more energy-saving. A series of experiments test the capabilities of the suggested algorithm compared to popular heuristics partitioning algorithms. A comparison was made between the most used bin-packing algorithms and the proposed algorithm in terms of energy consumption and system schedulability. Experimental results demonstrate that the designed algorithm outperforms the Worst Fit Decreasing (WFD), Best Fit Decreasing (BFD), and Similarity-Based Partitioning (SBP) algorithms of bin-packing algorithms, reduces the energy consumption of the overall system, and improves schedulability.
Diagnostic and Therapeutic Applications of Extracellular Vesicles in Interstitial Lung Diseases
Authors: Ibrahim Abdulrahman , Ibrahim Ahmed , Parimon Tanyalak
Published: January 2021

Interstitial lung diseases (ILDs) are chronic irreversible pulmonary conditions with significant morbidity and mortality. Diagnostic approaches to ILDs are complex and multifactorial. Effective therapeutic interventions are continuously investigated and explored with substantial progress, thanks to advances in basic understanding and translational efforts. Extracellular vesicles (EVs) offer a new paradigm in diagnosis and treatment. This leads to two significant implications: new disease biomarker discovery that enables reliable diagnosis and disease assessment and the development of regenerative medicine therapeutics that target fibroproliferative processes in diseased lung tissue. In this review, we discuss the current understanding of the role of diseased tissue-derived EVs in the development of interstitial lung diseases, the utility of these EVs as diagnostic and prognostic tools, and the existing therapeutic utility of EVs. Furthermore, we review the potential therapeutic application of EVs derived from various cellular sources.
Pelvic Lymphadenectomy in Gynecologic Oncology—Significance of Anatomical Variations
Authors: Kostov Stoyan , Kornovski Yavor , Slavchev Stanislav , Ivanova Yonka , Dzhenkov Deyan , Dimitrov Nikolay , Yordanov Angel
Published: January 2021

Pelvic lymphadenectomy is a common surgical procedure in gynecologic oncology. Pelvic lymph node dissection is performed for all types of gynecological malignancies to evaluate the extent of a disease and facilitate further treatment planning. Most studies examine the lymphatic spread, the prognostic, and therapeutic significance of the lymph nodes. However, there are very few studies describing the possible surgical approaches and the anatomical variations. Moreover, a correlation between anatomical variations and lymphadenectomy in the pelvic region has never been discussed in medical literature. The present article aims to expand the limited knowledge of the anatomical variations in the pelvis. Anatomical variations of the ureters, pelvic vessels, and nerves and their significance to pelvic lymphadenectomy are summarized, explained, and illustrated. Surgeons should be familiar with pelvic anatomy and its variations to safely perform a pelvic lymphadenectomy. Learning the proper lymphadenectomy technique relating to anatomical landmarks and variations may decrease morbidity and mortality. Furthermore, accurate description and analysis of the majority of pelvic anatomical variations may impact not only gynecological surgery, but also spinal surgery, urology, and orthopedics.
Review of Dermoscopy and Reflectance Confocal Microscopy Features of the Mucosal Melanoma
Authors: De Pascalis Andrea , Perrot Jean Luc , Tognetti Linda , Rubegni Pietro , Cinotti Elisa
Published: January 2021

Mucosal melanoma is a rare tumor with aggressive biological behavior and poor prognosis. Diagnosis is often performed at an advanced stage when the lesions become symptomatic. Although dermoscopy and reflectance confocal microscopy (RCM) are widely used techniques for the diagnosis of cutaneous tumors, their use for mucosal lesions is not well established, probably because the latter are rarer. The objective of this study was to evaluate current literature on these imaging techniques for mucosal melanoma. We searched in PubMed and Cochrane databases all studies up to October 2020 dealing with dermoscopy, RCM, and mucosal melanoma. We found that the most relevant dermoscopic features were structureless pattern and/or the presence of multiple colors. RCM examination mainly showed numerous basal hyper-reflective dendritic cells and loss of normal architecture of the papillae of the lamina propria. Although diagnostic algorithms have been proposed for both techniques, the limit of these methods is the absence of large studies and of standardized and shared diagnostic criteria.
Time-Rescaling of Dirac Dynamics: Shortcuts to Adiabaticity in Ion Traps and Weyl Semimetals
Authors: Roychowdhury Agniva , Deffner Sebastian
Published: January 2021

Only very recently, rescaling time has been recognized as a way to achieve adiabatic dynamics in fast processes. The advantage of time-rescaling over other shortcuts to adiabaticity is that it does not depend on the eigenspectrum and eigenstates of the Hamiltonian. However, time-rescaling requires that the original dynamics are adiabatic, and in the rescaled time frame, the Hamiltonian exhibits non-trivial time-dependence. In this work, we show how time-rescaling can be applied to Dirac dynamics, and we show that all time-dependence can be absorbed into the effective potentials through a judiciously chosen unitary transformation. This is demonstrated for two experimentally relevant scenarios, namely for ion traps and adiabatic creation of Weyl points.
Emergency Online Learning in Low-Resource Settings: Effective Student Engagement Strategies
Authors: Abou-Khalil Victoria , Helou Samar , Khalifé Eliane , Chen MeiRong Alice , Majumdar Rwitajit , Ogata Hiroaki
Published: January 2021

We aim to identify the engagement strategies that higher education students, engaging in emergency online learning in low-resource settings, perceive to be effective. We conducted a sequential mixed-methods study based on Moore’s interaction framework for distance education. We administered a questionnaire to 313 students engaging in emergency online learning in low-resource settings to examine their perceptions of different engagement strategies. Our results showed that student–content engagement strategies, e.g., screen sharing, summaries, and class recordings, are perceived as the most effective, closely followed by student–teacher strategies, e.g., Q and A sessions and reminders. Student–student strategies, e.g., group chat and collaborative work, are perceived as the least effective. The perceived effectiveness of engagement strategies varies based on the students’ gender and technology access. To support instructors, instructional designers, and researchers, we propose a 10-level guide for engaging students during emergency online classes in low-resource settings.
Linear Ultrasound Transmitter Based on Transformer with Improved Saturation Performance
Authors: Ricci Stefano , Russo Dario
Published: January 2021

Ultrasound methods are currently employed in a wide range of applications. They are integrated in complex electronics systems, like clinical echographs, but also in small and compact boards, like industrial sensors, embedded systems, and portable devices. Ultrasound waves are typically generated by energizing a piezoelectric transducer through a high-voltage sequence of small sinusoidal bursts. Moreover, in several applications, the ultrasound board should work in a wide frequency range. This makes the transmitter, i.e., the electronics that drives the transducer, a key part of the circuit. The use of a small transformer simplifies the electronics and reduces the need of high-voltage power sources. Unfortunately, the transformer magnetic core, when subjected to the sequence of bursts employed in ultrasound, is particularly prone to saturation. This phenomenon limits the maximum voltage and/or the minimum frequency the transformer can be employed for. In this work, a transmitter based on a transformer is proposed. Inspired by the technique currently employed in the power network transformers, we added a prefluxing circuit, which improves the saturation performance 2-fold. The proposed transmitter was implemented in a test board and experimented with two commercial transformers at 80 Vpp. Measurements show that the proposed prefluxing circuit moves down the minimum usable frequency 2-fold: from 400 to 200 kHz for one of the two transformers, and from 2.4 to 1.2 MHz for the other.