bluuebunny/crossref_metadata_2025 huggingface dataset:
Analysis and Mapping of Detailed Inner Information of Crystalline Grain by Wavelength-Resolved Neutron Transmission Imaging with Individual Bragg-Dip Profile-Fitting Analysis
Authors: Sakurai Yosuke , Sato Hirotaka , Adachi Nozomu , Morooka Satoshi , Todaka Yoshikazu , Kamiyama Takashi
Published: June 2021

As a new method for evaluating single crystals and oligocrystals, pulsed neutron Bragg-dip transmission analysis/imaging method is being developed. In this study, a single Bragg-dip profile-fitting analysis method was newly developed, and applied for analyzing detailed inner information in a crystalline grain position-dependently. In the method, the spectrum profile of a single Bragg-dip is analyzed at each position over a grain. As a result, it is expected that changes in crystal orientation, mosaic spread angle and thickness of a perfect crystal can be evaluated from the wavelength, the width and the integrated intensity of the Bragg-dip, respectively. For confirming this effectiveness, the method was applied to experimental data of position-dependent Bragg-dip transmission spectra of a Si-steel plate consisting of oligocrystals. As a result, inner information of multiple crystalline grains could be visualized and evaluated. The small change in crystal orientation in a grain, about 0.4°, could be observed by imaging the Bragg-dip wavelengths. By imaging the Bragg-dip widths, both another grain and mosaic block in a grain were detected. Furthermore, imaging results of the integrated intensities of Bragg-dips were consistent with the results of Bragg-dip width imaging. These small crystallographic changes have not been observed and visualized by previous Bragg-dip analysis methods.
A Dual-Gas Sensor Using Photoacoustic Spectroscopy Based on a Single Acoustic Resonator
Authors: Jiang Yiming , Zhang Tie , Wang Gaoxuan , He Sailing
Published: June 2021

A dual-gas photoacoustic spectroscopy (PAS) sensor based on wavelength modulation spectroscopy (WMS) was developed and experimentally demonstrated. Distributed feedback (DFB) laser diodes, emitting at 1512 and 1653 nm, were utilized as the excitation sources for the simultaneous measurement of NH3 and CH4, respectively. The PAS signal was excited by modulating the DFB laser at the first longitudinal resonant frequency of a cylindrical acoustic resonator. Absorption lines for NH3 and CH4 were simultaneously recorded during one frequency scan of the DFB lasers without using any optical switch. The interference of NH3 and CH4 on each other was investigated for accurate detection. The limits of detection (LoDs) of the PAS sensor for NH3 and CH4 for an integration time of 100 s were determined to be 0.1 and 0.3 ppm, respectively. The present PAS sensor provides a new scheme for multi-gas analysis with the advantages of cost-effectiveness, a simple structure and multi-wavelength operation.
Classification of Daily Irradiance Profiles and the Behaviour of Photovoltaic Plant Elements: The Effects of Cloud Enhancement
Authors: Santiago Isabel , Esquivel-Martin Jorge Luis , Trillo-Montero David , Real-Calvo Rafael Jesús , Pallarés-López Víctor
Published: June 2021

In this work, the automatic classification of daily irradiance profiles registered in a photovoltaic installation located in the south of Spain was carried out for a period of nine years, with a sampling frequency of 5 min, and the subsequent analysis of the operation of the elements of the installation on each type of day was also performed. The classification was based on the total daily irradiance values and the fluctuations of this parameter throughout the day. The irradiance profiles were grouped into nine different categories using unsupervised machine learning algorithms for clustering, implemented in Python. It was found that the behaviour of the modules and the inverter of the installation was influenced by the type of day obtained, such that the latter worked with a better average efficiency on days with higher irradiance and lower fluctuations. However, the modules worked with better average efficiency on days with irradiance fluctuations than on clear sky days. This behaviour of the modules may be due to the presence, on days with passing clouds, of the phenomenon known as cloud enhancement, in which, due to reflections of radiation on the edges of the clouds, irradiance values can be higher at certain moments than those that occur on clear sky days, without passing clouds. This is due to the higher energy generated during these irradiance peaks and to the lower temperatures that the module reaches due to the shaded areas created by the clouds, resulting in a reduction in its temperature losses.
Evaluation of the Water Shielding Performance of a Capillary Barrier System through a Small-Scale Model Test
Authors: Kim Byeong-Su
Published: June 2021

Capillary barrier (CB) systems consisting of a fine-grained soil layer placed over a coarse-grained soil layer can generally provide a water-shielding effect, increasing the slope stability of soil structures during rainfall. In order to improve the water-shielding performance of CB systems, laboratory model tests have been previously conducted under various conditions; notably, large-scale model tests are especially required. The inefficiency in increasing the production time of CB models until now explains their high cost. In this paper, we propose a laboratory small-scale CB (SSCB) model test for a quick and efficient evaluation of the function of a CB system. In this model test, differently from previous studies, a side drainage flow in the direction of the inclined sand layer was set as the no-flow condition; moreover, the laboratory SSCB model tests were performed by considering three rainfall intensities (i.e., 20, 50, and 100 mm/h) under the lateral no-flow condition. The results showed that the larger the rainfall intensity, the shorter the diversion length was of the CB system. To evaluate the effectiveness of the SSCB model test proposed in this study, the diversion length was estimated by an empirical equation under the lateral flow condition based on hydraulic conductivity functions and the soil water characteristic curves of sand and gravel and then compared to the results of the SSCB model tests. It was hence demonstrated that the water-shielding performance of the CB system can be efficiently evaluated through SSCB model tests under the lateral no-flow condition, rather than through large-scale model tests.
Calibration of Acoustic Emission Parameters in Relation to the Equilibrium Moisture Content Variations in a Pinus sylvestris Beam
Authors: Bartolucci Beatrice , Frasca Francesca , Siani Anna Maria , Bertolin Chiara
Published: June 2021

Under constant temperature conditions, air relative humidity variations affect hygroscopic objects, such as wood, modifying their moisture content and provoking, at low values, damages and fractures. The parameters (amplitude, counts, and energy) derived from the acoustic emission non-destructive technique are calibrated with respect to equilibrium moisture content values using 14 samplings of Pinus sylvestris. The experimental procedure uses multi-technique approaches involving a universal testing machine, digital image correlation, and acoustic emissions, and notes that the three parameters of acoustic emission strictly depend on the equilibrium moisture content. For a better interpretation, a statistical approach is applied to model the equilibrium moisture content variations radially and longitudinally. Amplitude, counts, and energy are calibrated as a function of the equilibrium moisture content, indicating that all three parameters are necessary to have an integral vision of the conservation of a wooden material. Moreover, the shape of the macro-fractures that occur at the surface can be associated with the level of moisture or dryness of the sample. Finally, the proposed method can be used in situ because, through acoustic emission monitoring, it is possible to quantify the fingerprint of the state of conservation of a material.
Wheat Bread Fortification: The Supplement of Teff Flour and Chia Seeds
Authors: Zięć Gabriela , Gambuś Halina , Lukasiewicz Marcin , Gambuś Florian
Published: June 2021

The evaluation of the quality and contents of nutritionally important chemical components in wheat bread fortified with teff flour and chia seed was shown. In the work, the quality was determined by means of the volume, total baking loss and yield and also by performing organoleptic evaluation. Moreover, the staling process in bread was also investigated. The research covers wheat bread (standard) and bread supplemented with 5, 10 and 15% of teff flour as well as bread with 5 and 10% of chia seed. It was found that the addition of teff flour or chia seeds significantly influenced all the quality characteristics. In the organoleptic evaluation, all the bread obtained was of the best quality. Moreover, in both teff flour and chia seed fortified bread it was established that they contained a higher content of protein, fat, ash and dietary fibre compared to pure wheat products. Therefore, the described fortifying raw materials can be considered a wholesome raw material in bakery production.
Evaluation of Classical Mathematical Models of Tumor Growth Using an On-Lattice Agent-Based Monte Carlo Model
Authors: Ruiz-Arrebola Samuel , Guirado Damián , Villalobos Mercedes , Lallena Antonio M.
Published: June 2021

Purpose: To analyze the capabilities of different classical mathematical models to describe the growth of multicellular spheroids simulated with an on-lattice agent-based Monte Carlo model that has already been validated. Methods: The exponential, Gompertz, logistic, potential, and Bertalanffy models have been fitted in different situations to volume data generated with a Monte Carlo agent-based model that simulates the spheroid growth. Two samples of pseudo-data, obtained by assuming different variability in the simulation parameters, were considered. The mathematical models were fitted to the whole growth curves and also to parts of them, thus permitting to analyze the predictive power (both prospective and retrospective) of the models. Results: The consideration of the data obtained with a larger variability of the simulation parameters increases the width of the χ2 distributions obtained in the fits. The Gompertz model provided the best fits to the whole growth curves, yielding an average value of the χ2 per degree of freedom of 3.2, an order of magnitude smaller than those found for the other models. Gompertz and Bertalanffy models gave a similar retrospective prediction capability. In what refers to prospective prediction power, the Gompertz model showed by far the best performance. Conclusions: The classical mathematical models that have been analyzed show poor prediction capabilities to reproduce the MTS growth data not used to fit them. Within these poor results, the Gompertz model proves to be the one that better describes the growth data simulated. The simulation of the growth of tumors or multicellular spheroids permits to have follow-up periods longer than in the usual experimental studies and with a much larger number of samples: this has permitted performing the type of analysis presented here.
Experimental and Numerical Investigation of an Innovative Method for Strengthening Cold-Formed Steel Profiles in Bending throughout Finite Element Modeling and Application of Neural Network Based on Feature Selection Method
Authors: Taheri Ehsan , Esgandarzadeh Fard Saeid , Zandi Yousef , Samali Bijan
Published: June 2021

This study evaluates an innovative reinforcement method for cold-formed steel (CFS) upright sections through finite element assessment as well as prediction of the normalized ultimate load and deflection of the profiles by artificial intelligence (AI) and machine learning (ML) techniques. Following the previous experimental studies, several CFS upright profiles with different lengths, thicknesses and reinforcement spacings are modeled and analyzed under flexural loading. The finite element method (FEM) is employed to evaluate the proposed reinforcement method in different upright sections and to provide a valid database for the analytical study. To detect the most influential factor on flexural strength, the “feature selection” method is performed on the FEM results. Then, by using the feature selection method, a hybrid neural network (a combination of multi-layer perceptron algorithm and particle swarm optimization method) is developed for the prediction of normalized ultimate load. The correlation coefficient (R), root mean square error (RMSE), Nash–Sutcliffe efficiency (NSE), mean absolute error (MAE) and Wilmot’s index of agreement (WI) are used as the measure of precision. The results show that the geometrical parameters have almost the same contribution in the flexural capacity and deflection of the specimens. According to the performance evaluation indexes, the best model is detected and optimized by tuning other algorithm parameters. The results indicate that the hybrid neural network can successfully predict the normalized ultimate load and deflection.
Elaiophylin Is a Potent Hsp90/ Cdc37 Protein Interface Inhibitor with K-Ras Nanocluster Selectivity
Authors: Siddiqui Farid A. , Vukic Vladimir , Salminen Tiina A. , Abankwa Daniel
Published: June 2021

The natural product elaiophylin is a macrodiolide with a broad range of biological activities. However, no direct target of elaiophylin in eukaryotes has been described so far, which hinders a systematic explanation of its astonishing activity range. We recently showed that the related conglobatin A, a protein–protein interface inhibitor of the interaction between the N-terminus of Hsp90 and its cochaperone Cdc37, blocks cancer stem cell properties by selectively inhibiting K-Ras4B but not H-Ras. Here, we elaborated that elaiophylin likewise disrupts the Hsp90/ Cdc37 interaction, without affecting the ATP-pocket of Hsp90. Similarly to conglobatin A, elaiophylin decreased expression levels of the Hsp90 client HIF1α, a transcription factor with various downstream targets, including galectin-3. Galectin-3 is a nanocluster scaffold of K-Ras, which explains the K-Ras selectivity of Hsp90 inhibitors. In agreement with this K-Ras targeting and the potent effect on other Hsp90 clients, we observed with elaiophylin treatment a submicromolar IC50 for MDA-MB-231 and MIA-PaCa-2 3D spheroid formation. Finally, a strong inhibition of MDA-MB-231 cells grown in the chorioallantoic membrane (CAM) microtumor model was determined. These results suggest that several other macrodiolides may have the Hsp90/ Cdc37 interface as a target site.
Macrophage Plasticity and Polarization Are Altered in the Experimental Model of Multiple Sclerosis
Authors: Leuti Alessandro , Talamonti Emanuela , Gentile Antonietta , Tiberi Marta , Matteocci Alessandro , Fresegna Diego , Centonze Diego , Chiurchiù Valerio
Published: June 2021

Multiple sclerosis (MS) is an immune-mediated demyelinating disease of the central nervous system. MS is characterized by infiltrations of leukocytes such as T and B lymphocytes and macrophages. Macrophages have been identified as major effectors of inflammation and demyelination in both MS and its animal model, experimental autoimmune encephalomyelitis (EAE). However, the activation and heterogeneity of macrophages in MS has been poorly investigated. Thus, in this study, we evaluated M1 and M2 macrophages immunophenotype from EAE and control mice by analyzing over 30 surface and intracellular markers through polychromatic flow cytometry, qRT-PCR, and ELISA assay. We showed that M1 macrophages possessed a higher proinflammatory profile in EAE compared to control mice, since they expressed higher levels of activation/co-stimulatory markers (iNOS, CD40, and CD80) and cytokines/chemokines (IL-6, IL-12, CCL2, and CXCL10), whereas M2 lost their M2-like phenotype by showing a decreased expression of their signature markers CD206 and CCL22, as well as a concomitant upregulation of several M1 makers. Furthermore, immunization of M1 and M2 macrophages with MOG35-55 led to a significant hyperactivation of M1 and a concomitant shift of anti-inflammatory M2 to pro-inflammatory M1 macrophages. Overall, we provide evidence for a phenotypic alteration of M1/M2 balance during MS, which can be of crucial importance not only for a better understanding of the immunopathology of this neurodegenerative disease but also to potentially develop new macrophage-centered therapeutic strategies.
Three-Dimensional X-ray Imaging of β-Galactosidase Reporter Activity by Micro-CT: Implication for Quantitative Analysis of Gene Expression
Authors: Ermakova Olga , Orsini Tiziana , Fruscoloni Paolo , Chiani Francesco , Gambadoro Alessia , Putti Sabrina , Cirilli Maurizio , Mezzi Alessio , Kaciulis Saulius , Pasquini Miriam , Raspa Marcello , Scavizzi Ferdinando , Tocchini-Valentini Glauco P.
Published: June 2021

Acquisition of detailed anatomical and molecular knowledge from intact biological samples while preserving their native three-dimensional structure is still a challenging issue for imaging studies aiming to unravel a system’s functions. Three-dimensional micro-CT X-ray imaging with a high spatial resolution in minimally perturbed naive non-transparent samples has recently gained increased popularity and broad application in biomedical research. Here, we describe a novel X-ray-based methodology for analysis of β-galactosidase (lacZ) reporter-driven gene expression in an intact murine brain ex vivo by micro-CT. The method relies on detection of bromine molecules in the product of the enzymatic β-galactosidase reaction. Enhancement of the X-ray signal is observed specifically in the regions of the murine brain where expression of the lacZ reporter gene is also detected histologically. We performed quantitative analysis of the expression levels of lacZ reporter activity by relative radiodensity estimation of the β-galactosidase/X-gal precipitate in situ. To demonstrate the feasibility of the method, we performed expression analysis of the Tsen54-lacZ reporter gene in the murine brain in a semi-quantitative manner. Human mutations in the Tsen54 gene cause pontocerebellar hypoplasia (PCH), a group of severe neurodegenerative disorders with both mental and motor deficits. Comparing relative levels of Tsen54 gene expression, we demonstrate that the highest Tsen54 expression is observed in anatomical brain substructures important for the normal motor and memory functions in mice.
Estimation of the Age of Architectural Heritage Objects by Microstructural Changes of Calcite in Lime Mortars of Ancient Brickwork and Masonry
Authors: Kotlyar Vladimir , Pishchulina Victoria , Beskopylny Alexey , Meskhi Besarion , Popov Yury , Efremenko Innessa
Published: June 2021

Determining the age of ancient architectural and cultural monuments is a significant scientific problem. An approach based on the transformation of portlandite into calcite and subsequent recrystallization of calcite is considered, which allows for estimating the relative age of ancient brickworks for local groups of historic buildings based on the results of diffraction studies of powder samples of carbonate mortars and measurements of samples with a known age. This article presents the results of the study of lime mortars of ancient brickwork. Under natural conditions, the process of transformation of portlandite into calcite takes from 100 to 200 years. The rate of this process is influenced by temperature, humidity, peculiarities of interaction with carbon dioxide contained in the air, etc. Examples show that portlandite is completely transformed into calcite in masonry mortars of the 18th century and that portlandite is not found in older mortars. It was determined that after the transformation of portlandite into calcite, an increase in the degree of recrystallization of calcite is observed, which manifests itself in powder diffraction patterns in the relative broadening of the diffraction peak of calcite hkl 104. In a detailed study, an estimate of the peak width at half maximum (FWHM) associated with the degree of crystallinity is effective. The actual data are given, which show that in older lime mortars the degree of recrystallization of calcite is higher than in younger ones. This fact makes it possible to indirectly determine the relative age of brickwork and masonry of various buildings of architectural heritage, which is especially relevant for the objects with the use of lime mortars of the northern provinces of the Byzantine Oecumene and other periods of various cultures.
Immunotherapeutic Approaches in Malignant Pleural Mesothelioma
Authors: Terenziani Rita , Zoppi Silvia , Fumarola Claudia , Alfieri Roberta , Bonelli Mara
Published: June 2021

Malignant pleural mesothelioma (MPM) is a rare and aggressive malignant disease affecting the mesothelium, commonly associated to asbestos exposure. The current therapeutic actions, based on cisplatin/pemetrexed treatment, are limited due to the late stage at which most patients are diagnosed and to the intrinsic chemo-resistance of the tumor. Another relevant point is the absence of approved therapies in the second line setting following progression of MPM after chemotherapy. Considering the poor prognosis of the disease and the fact that the incidence of this tumor is expected to increase in the next decade, novel therapeutic approaches are urgently needed. In the last few years, several studies have investigated the efficacy and safety of immune-checkpoint inhibitors (ICIs) in the treatment of unresectable advanced MPM, and a number of trials with immunotherapeutic agents are ongoing in both first line and second line settings. In this review, we describe the most promising emerging immunotherapy treatments for MPM (ICIs, engineered T cells to express chimeric antigen receptors (CARs), dendritic cells (DCs) vaccines), focusing on the biological and immunological features of this tumor as well as on the issues surrounding clinical trial design.
Cell Plasticity and Prostate Cancer: The Role of Epithelial–Mesenchymal Transition in Tumor Progression, Invasion, Metastasis and Cancer Therapy Resistance
Authors: Papanikolaou Sofia , Vourda Aikaterini , Syggelos Spyros , Gyftopoulos Kostis
Published: June 2021

Prostate cancer, the second most common malignancy in men, is characterized by high heterogeneity that poses several therapeutic challenges. Epithelial–mesenchymal transition (EMT) is a dynamic, reversible cellular process which is essential in normal embryonic morphogenesis and wound healing. However, the cellular changes that are induced by EMT suggest that it may also play a central role in tumor progression, invasion, metastasis, and resistance to current therapeutic options. These changes include enhanced motility and loss of cell–cell adhesion that form a more aggressive cellular phenotype. Moreover, the reverse process (MET) is a necessary element of the metastatic tumor process. It is highly probable that this cell plasticity reflects a hybrid state between epithelial and mesenchymal status. In this review, we describe the underlying key mechanisms of the EMT-induced phenotype modulation that contribute to prostate tumor aggressiveness and cancer therapy resistance, in an effort to provide a framework of this complex cellular process.
Gemcitabine/Nab-Paclitaxel versus FOLFIRINOX in Locally Advanced Pancreatic Cancer: A European Multicenter Study
Authors: Williet Nicolas , Petrillo Angelica , Roth Gaël , Ghidini Michele , Petrova Mila , Forestier Julien , Lopez Anthony , Thoor Audrey , Weislinger Lucie , De Vita Ferdinando , Taieb Julien , Phelip Jean Marc
Published: June 2021

Background: Gemcitabine/nab-paclitaxel (GN) and FOLFIRINOX (FFX) are two standard first-line therapies for metastatic pancreatic cancer (PC) but have rarely been compared, especially in patients with locally advanced PC (LAPC). Methods: This is a retrospective European multicenter study including patients with LAPC treated with either GN or FFX as the first-line therapy between 2010 and 2019. Coprimary objectives were progression-free survival (PFS) and overall survival (OS), both estimated using the Kaplan–Meier method. Results: A total of 147 patients (GN: n = 60; FFX: n = 87) were included. Tumor resection rates were similar between the two groups (16.7% vs. 16.1%; p = 1), with similar R0 resection rates (88.9%). Median PFS rates were not statistically different: 9 months (95% CI: 8–13.5) vs. 12.1 months (95% CI: 10.1–14.6; p = 0.8), respectively. Median OS rates were 15.7 months (95% CI: 12.6–20.2) and 16.7 months (95% CI: 14.8–20.4; p = 0.7), respectively. Abdominal pain at the baseline (HR = 2.03, p = 0.03), tumors located in the tail of the pancreas (HR = 4.35, p = 0.01), CA19-9 > 200 UI/L (HR = 2.03, p = 0.004) and tumor resection (HR = 0.37, p = 0.007) were independent prognostic factors for PFS, similarly to OS. CA19-9 ≤ 200 UI/L (OR = 2.6, p = 0.047) was predictive of the tumor response. Consolidation chemoradiotherapy, more often used in the FFX group (11.7% vs. 50.6%; p < 0.001), was not predictive. Conclusion: This retrospective study did not show any difference between GN and FFX as the first-line treatment in patients with LAPC.
Diving into the Pleural Fluid: Liquid Biopsy for Metastatic Malignant Pleural Effusions
Authors: Sorolla Maria Alba , Sorolla Anabel , Parisi Eva , Salud Antonieta , Porcel José M.
Published: June 2021

Liquid biopsy is emerging as a promising non-invasive diagnostic tool for malignant pleural effusions (MPE) due to the low sensitivity of conventional pleural fluid (PF) cytological examination and the difficulty to obtain tissue biopsies, which are invasive and require procedural skills. Currently, liquid biopsy is increasingly being used for the detection of driver mutations in circulating tumor DNA (ctDNA) from plasma specimens to guide therapeutic interventions. Notably, malignant PF are richer than plasma in tumor-derived products with potential clinical usefulness, such as ctDNA, micro RNAs (miRNAs) and long non-coding RNAs (lncRNAs), and circulating tumor cells (CTC). Tumor-educated cell types, such as platelets and macrophages, have also been added to this diagnostic armamentarium. Herein, we will present an overview of the role of the preceding biomarkers, collectively known as liquid biopsy, in PF samples, as well as the main technical approaches used for their detection and quantitation, including a proper sample processing. Technical limitations of current platforms and future perspectives in the field will also be addressed. Using PF as liquid biopsy shows promise for use in current practice to facilitate the diagnosis and management of metastatic MPE.
Real-World Analysis of the Impact of Radiotherapy on Immunotherapy Efficacy in Non-Small Cell Lung Cancer
Authors: Onn Amir , Gottfried Teodor , Stemmer Amos , Appel Sarit , Lawrence Yaacov R. , Urban Damien , Beller Tamar , Daher Sameh , Bar Jair
Published: June 2021

Background: Immunotherapy (IO) provides a significant benefit for a subgroup of non-small cell lung cancer (NSCLC) patients. Radiotherapy (XRT) might enhance the efficacy of IO. We evaluated the impact of the specifics of XRT treatments on the OS of IO-treated NSCLC patients. Methods: Metastatic NSCLC patients treated with IO were retrospectively identified. Parameters included demographics, tumor characteristics, IO and XRT details. Correlation between the parameters and OS was tested with Cox regression. Results: 453 patients were included. No XRT was given to 167 (36.9%) patients, whereas XRT prior and after IO had 182 (40.2%) and 104 (22.9%) patients, respectively. XRT total doses between 30 and 40 Gy had better overall survival (OS) compared to non-irradiated patients (hazard ratio (HR) 0.5, 95% CI 0.25–1.0, p = 0.049). Worse outcome was seen with total doses ≤ 10 Gy (HR 1.67, 95% 1.13–2.5, p = 0.01), XRT fractions of 4.1–8 Gy (HR 1.48, 95% CI 1.05–2.1, p = 0.027) and XRT to the bone (HR 1.36, 95% CI 1.01–1.8, p = 0.04). Several clinical parameters correlated with OS in the univariate analysis of the IO-treated patients. While, in the multivariate analysis, only ECOG-PS, treatment line, type of IO, albumin and NLR remained statistically significant. Conclusion: Specific doses, fractions and sites of XRT correlated with the OS of IO-treated NSCLC patients in the univariate analysis, although not in the multivariate analysis.
Interfractional Geometric Variations and Dosimetric Benefits of Stereotactic MRI Guided Online Adaptive Radiotherapy (SMART) of Prostate Bed after Radical Prostatectomy: Post-Hoc Analysis of a Phase II Trial
Authors: Cao Minsong , Gao Yu , Yoon Stephanie M. , Yang Yingli , Sheng Ke , Ballas Leslie K. , Basehart Vincent , Sachdeva Ankush , Felix Carol , Low Daniel A. , Steinberg Michael L. , Kishan Amar U.
Published: June 2021

Purpose: To evaluate geometric variations of patients receiving stereotactic body radiotherapy (SBRT) after radical prostatectomy and the dosimetric benefits of stereotactic MRI guided adaptive radiotherapy (SMART) to compensate for these variations. Materials/Methods: The CTV and OAR were contoured on 55 MRI setup scans of 11 patients treated with an MR-LINAC and enrolled in a phase II trial of post-prostatectomy SBRT. All patients followed institutional bladder and rectum preparation protocols and received five fractions of 6−6.8 Gy to the prostate bed. Interfractional changes in volume were calculated and shape deformation was quantified by the Dice similar coefficient (DSC). Changes in CTV-V95%, bladder and rectum maximum dose, V32.5Gy and V27.5Gy were predicted by recalculating the initial plan on daily MRI. SMART was retrospectively simulated if the predicted dose exceeded pre-set criteria. Results: The CTV volume and shape remained stable with a median volumetric change of 3.0% (IQR −3.0% to 11.5%) and DSC of 0.83 (IQR 0.79 to 0.88). Relatively large volumetric changes in bladder (median −24.5%, IQR −34.6% to 14.5%) and rectum (median 5.4%, IQR − 9.7% to 20.7%) were observed while shape changes were moderate (median DSC of 0.79 and 0.73, respectively). The median CTV-V95% was 98.4% (IQR 94.9% to 99.6%) for the predicted doses. However, SMART would have been deemed beneficial for 78.2% of the 55 fractions based on target undercoverage (16.4%), exceeding OAR constraints (50.9%), or both (10.9%). Simulated SMART improved the dosimetry and met dosimetric criteria in all fractions. Moderate correlations were observed between the CTV-V95% and target DSC (R2 = 0.73) and bladder mean dose versus volumetric changes (R2 = 0.61). Conclusions: Interfractional dosimetric variations resulting from anatomic deformation are commonly encountered with post-prostatectomy RT and can be mitigated with SMART.
Expression of X-Linked Inhibitor of Apoptosis Protein (XIAP) in Breast Cancer Is Associated with Shorter Survival and Resistance to Chemotherapy
Authors: Devi Gayathri R. , Finetti Pascal , Morse Michael A. , Lee Seayoung , de Nonneville Alexandre , Van Laere Steven , Troy Jesse , Geradts Joseph , McCall Shannon , Bertucci Francois
Published: June 2021

XIAP, the most potent inhibitor of cell death pathways, is linked to chemotherapy resistance and tumor aggressiveness. Currently, multiple XIAP-targeting agents are in clinical trials. However, the characterization of XIAP expression in relation to clinicopathological variables in large clinical series of breast cancer is lacking. We retrospectively analyzed non-metastatic, non-inflammatory, primary, invasive breast cancer samples for XIAP mRNA (n = 2341) and protein (n = 367) expression. XIAP expression was analyzed as a continuous value and correlated with clinicopathological variables. XIAP mRNA expression was heterogeneous across samples and significantly associated with younger patients’ age (≤50 years), pathological ductal type, lower tumor grade, node-positive status, HR+/HER2− status, and PAM50 luminal B subtype. Higher XIAP expression was associated with shorter DFS in uni- and multivariate analyses in 909 informative patients. Very similar correlations were observed at the protein level. This prognostic impact was significant in the HR+/HER2− but not in the TN subtype. Finally, XIAP mRNA expression was associated with lower pCR rate to anthracycline-based neoadjuvant chemotherapy in both uni- and multivariate analyses in 1203 informative patients. Higher XIAP expression in invasive breast cancer is independently associated with poorer prognosis and resistance to chemotherapy, suggesting the potential therapeutic benefit of targeting XIAP.
Neuro-Signals from Gut Microbiota: Perspectives for Brain Glioma
Authors: D’Alessandro Giuseppina , Lauro Clotilde , Quaglio Deborah , Ghirga Francesca , Botta Bruno , Trettel Flavia , Limatola Cristina
Published: June 2021

Glioblastoma (GBM) is the most aggressive form of glioma tumor in adult brain. Among the numerous factors responsible for GBM cell proliferation and invasion, neurotransmitters such as dopamine, serotonin and glutamate can play key roles. Studies performed in mice housed in germ-free (GF) conditions demonstrated the relevance of the gut-brain axis in a number of physiological and pathological conditions. The gut–brain communication is made possible by vagal/nervous and blood/lymphatic routes and pave the way for reciprocal modulation of functions. The gut microbiota produces and consumes a wide range of molecules, including neurotransmitters (dopamine, norepinephrine, serotonin, gamma-aminobutyric acid [GABA], and glutamate) that reach their cellular targets through the bloodstream. Growing evidence in animals suggests that modulation of these neurotransmitters by the microbiota impacts host neurophysiology and behavior, and affects neural cell progenitors and glial cells, along with having effects on tumor cell growth. In this review we propose a new perspective connecting neurotransmitter modulation by gut microbiota to glioma progression.
CT-Detected Subsolid Nodules: A Predictor of Lung Cancer Development at Another Location?
Authors: Schreuder Anton , Prokop Mathias , Scholten Ernst T. , Mets Onno M. , Chung Kaman , Mohamed Hoesein Firdaus A. A. , Jacobs Colin , Schaefer-Prokop Cornelia M.
Published: June 2021

The purpose of this case–cohort study was to investigate whether the frequency and computed tomography (CT) features of pulmonary nodules posed a risk for the future development of lung cancer (LC) at a different location. Patients scanned between 2004 and 2012 at two Dutch academic hospitals were cross-linked with the Dutch Cancer Registry. All patients who were diagnosed with LC by 2014 and a random selection of LC-free patients were considered. LC patients who were determined to be LC-free at the time of the scan and all LC-free patients with an adequate scan were included. The nodule count and types (solid, part-solid, ground-glass, and perifissural) were recorded per scan. Age, sex, and other CT measures were included to control for confounding factors. The cohort included 163 LC patients and 1178 LC-free patients. Cox regression revealed that the number of ground-glass nodules and part-solid nodules present were positively correlated to future LC risk. The area under the receiver operating curve of parsimonious models with and without nodule type information were 0.827 and 0.802, respectively. The presence of subsolid nodules in a clinical setting may be a risk factor for future LC development in another pulmonary location in a dose-dependent manner. Replication of the results in screening cohorts is required for maximum utility of these findings.
An Overview of the Recent Development of Anticancer Agents Targeting the HIF-1 Transcription Factor
Authors: Shirai Yukari , Chow Christalle C. T. , Kambe Gouki , Suwa Tatsuya , Kobayashi Minoru , Takahashi Itsuki , Harada Hiroshi , Nam Jin-Min
Published: June 2021

Hypoxia, a characteristic feature of solid tumors, is associated with the malignant phenotype and therapy resistance of cancers. Hypoxia-inducible factor 1 (HIF-1), which is responsible for the metazoan adaptive response to hypoxia, has been recognized as a rational target for cancer therapy due to its critical functions in hypoxic regions. In order to efficiently inhibit its activity, extensive efforts have been made to elucidate the molecular mechanism underlying the activation of HIF-1. Here, we provide an overview of relevant research, particularly on a series of HIF-1 activators identified so far and the development of anticancer drugs targeting them.
Cross-Coupling as a Key Step in the Synthesis and Structure Revision of the Natural Products Selagibenzophenones A and B
Authors: Lapinskaite Ringaile , Malatinec Štefan , Mateus Miguel , Rycek Lukas
Published: June 2021

Selagibenzophenone A (1) and its isomer selagibenzophenone B (2) were recently described as natural products from Selaginella genus plants with PDE4 inhibitory activity. Herein, we report the first total syntheses of both compounds. By comparing spectroscopic data of the synthetic compounds with reported data for the isolated material, we demonstrate that the structure of one of the two natural products was incorrectly assigned, and that in fact isolated selagibenzophenone A and selagibenzophenone B are identical compounds. The synthetic strategy for both 1 and 2 is based on a cross-coupling reaction and on the addition of organometallic species to assemble the framework of the molecules. Identifying a suitable starting material with the correct substitution pattern is crucial because its pattern is reflected in that of the targeted compounds. These syntheses are finalized via global deprotection. Protecting the phenols as methoxy groups provides the possibility for partial control over the selectivity in the demethylation thanks to differences in the reactivity of the various methoxy groups. Our findings may help in future syntheses of derivatives of the biologically active natural product and in understanding the structure–activity relationship.
Interference of LPS H. pylori with IL-33-Driven Regeneration of Caviae porcellus Primary Gastric Epithelial Cells and Fibroblasts
Authors: Gonciarz Weronika , Krupa Agnieszka , Moran Anthony P. , Tomaszewska Agata , Chmiela Magdalena
Published: June 2021

Background: Lipopolysaccharide (LPS) of Helicobacter pylori (Hp) bacteria causes disintegration of gastric tissue cells in vitro. It has been suggested that interleukin (IL)-33 is involved in healing gastric injury. Aim: To elucidate whether Hp LPS affects regeneration of gastric barrier initiated by IL-33. Methods: Primary gastric epithelial cells or fibroblasts from Caviae porcellus were transfected with siRNA IL-33. Such cells, not exposed or treated with LPS Hp, were sub-cultured in the medium with or without exogenous IL-33. Then cell migration was assessed in conjunction with oxidative stress and apoptosis, activation of extracellular signal-regulated kinase (Erk), production of collagen I and soluble ST2 (IL-33 decoy). Results: Control cells not treated with LPS Hp migrated in the presence of IL-33. The pro-regenerative activity of IL-33 was related to stimulation of cells to collagen I production. Wound healing by cells exposed to LPS Hp was inhibited even in the presence of IL-33. This could be due to increased oxidative stress and apoptosis in conjunction with Erk activation, sST2 elevation and modulation of collagen I production. Conclusions: The recovery of gastric barrier cells during Hp infection potentially can be affected due to downregulation of pro-regenerative activity of IL-33 by LPS Hp.
The Origin of the Cyathea delgadii Sternb. Somatic Embryos Is Determined by the Developmental State of Donor Tissue and Mutual Balance of Selected Metabolites
Authors: Mikuła Anna , Tomaszewicz Wojciech , Dziurka Michał , Kaźmierczak Andrzej , Grzyb Małgorzata , Sobczak Mirosław , Zdańkowski Piotr , Rybczyński Jan
Published: June 2021

Somatic embryogenesis is the formation of a plant embryo from a cell other than the product of gametic fusion. The need to recognize the determinants of somatic cell fate has prompted investigations on how endogenous factors of donor tissues can determine the pattern of somatic embryo origin. The undertaking of this study was enabled by the newly developed experimental system of somatic embryogenesis of the tree fern Cyathea delgadii Sternb., in which the embryos are produced in hormone-free medium. The contents of 89 endogenous compounds (such as sugars, auxins, cytokinins, gibberellins, stress-related hormones, phenolic acids, polyamines, and amino acids) and cytomorphological features were compared between two types of explants giving rise to somatic embryos of unicellular or multicellular origin. We found that a large content of maltose, 1-kestose, abscisic acid, biologically active gibberellins, and phenolic acids was characteristic for single-cell somatic embryo formation pattern. In contrast, high levels of starch, callose, kinetin riboside, arginine, and ethylene promoted their multicellular origin. Networks for visualization of the relations between studied compounds were constructed based on the data obtained from analyses of a Pearson correlation coefficient heatmap. Our findings present for the first time detailed features of donor tissue that can play an important role in the somatic-to-embryogenic transition and the somatic embryo origin.
Current Insights into Immunology and Novel Therapeutics of Atopic Dermatitis
Authors: Kader Hidaya A. , Azeem Muhammad , Jwayed Suhib A. , Al-Shehhi Aaesha , Tabassum Attia , Ayoub Mohammed Akli , Hetta Helal F. , Waheed Yasir , Iratni Rabah , Al-Dhaheri Ahmed , Muhammad Khalid
Published: June 2021

Atopic dermatitis (AD) is one of the most prevalent inflammatory disease among non-fatal skin diseases, affecting up to one fifth of the population in developed countries. AD is characterized by recurrent pruritic and localized eczema with seasonal fluctuations. AD initializes the phenomenon of atopic march, during which infant AD patients are predisposed to progressive secondary allergies such as allergic rhinitis, asthma, and food allergies. The pathophysiology of AD is complex; onset of the disease is caused by several factors, including strong genetic predisposition, disrupted epidermal barrier, and immune dysregulation. AD was initially characterized by defects in the innate immune system and a vigorous skewed adaptive Th2 response to environmental agents; there are compelling evidences that the disorder involves multiple immune pathways. Symptomatic palliative treatment is the only strategy to manage the disease and restore skin integrity. Researchers are trying to more precisely define the contribution of different AD genotypes and elucidate the role of various immune axes. In this review, we have summarized the current knowledge about the roles of innate and adaptive immune responsive cells in AD. In addition, current and novel treatment strategies for the management of AD are comprehensively described, including some ongoing clinical trials and promising therapeutic agents. This information will provide an asset towards identifying personalized targets for better therapeutic outcomes.
Pomological Descriptors, Phenolic Compounds, and Chemical Monitoring in Olive Fruits Irrigated with Dairy Treated Wastewater
Authors: Sdiri Wiem , Dabbou Samia , Nava Vincenzo , Di Bella Giuseppa , Ben Mansour Hedi
Published: June 2021

In this work, the pomological characteristics, phenolic composition, and chemical contents modification in response to treated wastewater (TWW) irrigation was studied on olive fruits. The experiment was carried out during two successive years (2016/2017) on olive trees (cv. Chemlali). Three irrigation treatments were adopted and two TWW irrigation levels were applied (T1: 20% ETc; T2: 40% ETc; CT: Control Treatment (rainfed condition)). Results show that TWW irrigation leads to increased fruit fresh weight and water content, whatever the level applied. In addition, fruit oil content remained unaffected by TWW irrigation. Moreover, this agronomic practice preserves some phenolic compound contents like verbascoside, therefore fruits nutritional value. A positive feature was then observed following TWW irrigation. In fact, oleuropein, tyrosol, luteolin-7-glucoside, and pinoresinol amounts were enhanced in treated olive fruits. On the other hand, TWW irrigated trees with a level of 40% ETc (T2) produced olive fruits richer in Mg and K than those cultivated in rainfed conditions (CT). Fruits Zn, Mn, and Pb contents decreased as a result of olive trees TWW irrigation.
Ecosystem-Based Adaptation to Protect Avian Species in Coastal Communities in the Greater Niagara Region, Canada
Authors: Gauthier Samantha , May Bradley , Vasseur Liette
Published: June 2021

Coastal communities are increasingly vulnerable to climate change and its effects may push coastal ecosystems to undergo irreversible changes. This is especially true for shorebirds with the loss of biodiversity and resource-rich habitats to rest, refuel, and breed. To protect these species, it is critical to conduct research related to nature-based Solutions (NbS). Through a scoping review of scientific literature, this paper initially identified 85 articles with various ecosystem-based adaptation (EbA) strategies that could help conserve shorebird populations and promote ecotourism. Of these 85 articles, 28 articles had EbA strategies that were examined, with some like coral reefs and mangroves eliminated as they were inappropriate for this region. The scoping review identified four major EbA strategies for the Greater Niagara Region with living shorelines and beach nourishment being the most suitable, especially when combined. These strategies were then evaluated against the eight core principles of nature-based solutions protecting shorebird as well as human wellbeing. Living shoreline strategy was the only one that met all eight NbS principles. As the coastline of the region greatly varies in substrate and development, further research will be needed to decide which EbA strategies would be appropriate for each specific area to ensure their efficacy.
Trait Interindividual Differences in the Magnitude of Subjective Sleepiness from Sleep Inertia
Authors: Lundholm Kirsie R. , Honn Kimberly A. , Skeiky Lillian , Muck Rachael A. , Van Dongen Hans P. A.
Published: June 2021

In shift work settings and on-call operations, workers may be at risk of sleep inertia when called to action immediately after awakening from sleep. However, individuals may differ substantially in their susceptibility to sleep inertia. We investigated this using data from a laboratory study in which 20 healthy young adults were each exposed to 36 h of total sleep deprivation, preceded by a baseline sleep period and followed by a recovery sleep period, on three separate occasions. In the week prior to each laboratory session and on the corresponding baseline night in the laboratory, participants either extended their sleep period to 12 h/day or restricted it to 6 h/day. During periods of wakefulness in the laboratory, starting right after scheduled awakening, participants completed neurobehavioral tests every 2 h. Testing included the Karolinska Sleepiness Scale to measure subjective sleepiness, for which the data were analyzed with nonlinear mixed-effects regression to quantify sleep inertia. This revealed considerable interindividual differences in the magnitude of sleep inertia, which were highly stable within individuals after both baseline and recovery sleep periods, regardless of study condition. Our results demonstrate that interindividual differences in subjective sleepiness due to sleep inertia are substantial and constitute a trait.