bluuebunny/crossref_metadata_2025 huggingface dataset:
Artificial Intelligence Is Stupid and Causal Reasoning Will Not Fix It
Authors: Bishop J. Mark
Published: January 2021

Artificial Neural Networks have reached “grandmaster” and even “super-human” performance across a variety of games, from those involving perfect information, such as Go, to those involving imperfect information, such as “Starcraft”. Such technological developments from artificial intelligence (AI) labs have ushered concomitant applications across the world of business, where an “AI” brand-tag is quickly becoming ubiquitous. A corollary of such widespread commercial deployment is that when AI gets things wrong—an autonomous vehicle crashes, a chatbot exhibits “racist” behavior, automated credit-scoring processes “discriminate” on gender, etc.—there are often significant financial, legal, and brand consequences, and the incident becomes major news. As Judea Pearl sees it, the underlying reason for such mistakes is that “... all the impressive achievements of deep learning amount to just curve fitting.” The key, as Pearl suggests, is to replace “reasoning by association” with “causal reasoning” —the ability to infer causes from observed phenomena. It is a point that was echoed by Gary Marcus and Ernest Davis in a recent piece for theNew York Times: “we need to stop building computer systems that merely get better and better at detecting statistical patterns in data sets—often using an approach known as ‘Deep Learning’—and start building computer systems that from the moment of their assembly innately grasp three basic concepts: time, space, and causality.” In this paper, foregrounding what in 1949 Gilbert Ryle termed “a category mistake”, I will offer an alternative explanation for AI errors; it is not so much that AI machinery cannot “grasp” causality, but that AI machinery (qua computation) cannot understand anything at all.
Effects of NGF Addition on Llama (Lama glama) Sperm Traits After Cooling
Authors: Sari Luciana M. , Zampini Renato , Gonzalez del Pino Francisco , Argañaraz Martin E. , Ratto Marcelo H. , Apichela Silvana A.
Published: January 2021

To provide new insights into the mechanisms through which seminal plasma proteins can protect sperm from damage caused during refrigeration, we evaluate the possibility that β-NGF can contribute to the improvement of sperm quality after cooling. First, β-NGF was detected in refrigerated sperm and compared with unrefrigerated sperm by western blotting of the proteins adsorbed by sperm, showing that native β-NGF is still present even 24 h after cooling only as an active form. Then, the effect of exogenous β-NGF on sperm quality after cooling was evaluated. A total of 12 ejaculates from male llamas (three ejaculates per male), were obtained by electro-ejaculation, diluted 4:1 with buffer Hepes-balanced salt solution and centrifuged at 800 × g for 8 min to remove the seminal plasma. Sperm were suspended in Tris-citrate-fructose-egg yolk diluent for a final concentration of 30 ×106/ml and cooled at 5°C for 24 h. After refrigeration, the extended sperm were equilibrated for 5 min at 37°C and divided into the following subgroups: sperm samples without treatment (control) and sperm samples supplemented with exogenous human β-NGF (10, 100, and 500 ng/ml). At 5, 30, and 60 min of incubation sperm were evaluated for sperm viability (using eosin/nigrosin stain), sperm motility and vigor (observed under light microscopy), and mitochondrial activity (using the JC-1 fluorescent marker). Vigor data were analyzed with the nonparametric Kruskal-Wallis test. The rest of the variables were analyzed with a mixed models approach. Mean comparisons were performed using Fisher's LSD test with a confidence level of 95%. A principal components analysis was performed to analyze the relationships between variables. Treatment of 24 h cooled sperm with 10 or 100 ng/ml of human β-NGF increased the percentage of total motility and vigor (p < 0.05). Besides, an incubation time of 60 min would be adequate to improve sperm quality, since all variables are positively related. The significant improvement observed in the motility and vigor of post-refrigerated sperm suggests that supplementation with exogenous β-NGF may be profitable for the improvement of cooled llama sperm.
Neuroendocrine Carcinomas of the Canine Mammary Gland: Histopathological and Immunohistochemical Characteristics
Authors: Nakagaki Karen Yumi Ribeiro , Nunes Maíra Meira , Garcia Ana Paula Vargas , De Brot Marina , Cassali Geovanni Dantas
Published: January 2021

Invasive mammary carcinomas with neuroendocrine differentiation are rare in women and were reported only once in female dogs. For the present study, ten cases of solid mammary carcinoma positive for chromogramin A in immunohistochemistry were selected. Histopathological characteristics of these tumors were described and immunohistochemical evaluation was performed with chromogranin A, synaptophysin, CD56, NSE, PGP 9.5, pancitokeratin, Ki67, estrogen receptor (ER), and progesterone receptor (PR). The average animal age was 13.2 years old and the average tumor size was 4.8 cm. In total, 70% of the neoplasms were classified as grade III and 30% as grade II by the Nottingham histological grade system. High mitotic index was observed with a mean of 27.5 mitoses in 10 high magnification fields. Only one case showed typical carcinoid tumor characteristics. In addition, vascular invasion was shown in 3 tumors. All carcinomas were positive for chromogran A, while only two cases were reactive to synaptophysin. For PGP 9.2, NSE and CD56, we observed positivity of 100, 90, and 70%, respectively, in the samples, being that no tumor was positive for all the neuroendocrine markers. All neoplasms showed ER and PR in at least 10% of neoplastic cells, while Ki67 varied from 29 to 95%, with mean mitotic index of 67%. Four of the ten animals died within 1 year of the tumor diagnosis. Neuroendocrine neoplasms occur in the canine mammary gland and are propably underdiagnosed. This is due to their non-specific morphological characteristics and the low use of neuroendocrine immunohistochemistric markers the diagnostic routine. More studies are necessary to determine the prognosis of this new histological type.
Evaluation of Processing Tomato Pomace after Composting on Soil Properties, Yield, and Quality of Processing Tomato in Greece
Authors: Kakabouki Ioanna , Folina Antigolena , Efthimiadou Aspasia , Karydogianni Stella , Zisi Charikleia , Kouneli Varvara , Kapsalis Nikolaos C. , Katsenios Nikolaos , Travlos Ilias
Published: January 2021

While processing tomato cultivation (Solanum lycopersicum L.) is considered one of the most important industrial crops in Greece, a waste known as tomato pomace is growing significantly high. Notably, the tomato pomace presents enormous opportunities for the creations of organic fertilizers. The aim of this study was to investigate the use of tomato pomace as a fertilizer in the same crop. A field experiment was established at the Agricultural University of Athens during 2018 and 2019 in a randomized complete design with five treatments (control, inorganic NPK (NPK), Tomato pomace and Biocycle Humus Soil (Tp and BHS), Tomato pomace and Farmyard manure (Tp and FYM), and Tomato pomace and Compost (Tp and CM). Physical soil properties such as soil porosity and penetration resistance were improved by the application of organic blends. Additionally, soil nitrogen content ranged from 0.10% (control and NPK) to 0.13% (Tp and FYM). A significant increase of yield was noticed under organic fertilization where the highest yield of 8.00 tn ha−1 was recorded in Tp and BHS (2018). Lycopene content was significantly affected by fertilization and its highest values were 87.25 (Tp and BHS; 2018), and 88.82 mg kg−1 fresh (Tp and FYM; 2019). Regarding fruit firmness, the three organic blends did not have statistically significant difference. In addition, the Total Soluble Solids (TSS) was significantly affected by the fertilization and the maximum value was 4.80 ◦Brix (Tp and CM; 2018). In brief, tomato pomace blended with organic fertilizers was yielded considerable since it improved soil quality and increased yield.
Insights into the Mechanism of Bovine Spermiogenesis Based on Comparative Transcriptomic Studies
Authors: Li Xin , Duan Chenying , Li Ruyi , Wang Dong
Published: January 2021

To reduce subfertility caused by low semen quality and provide theoretical guidance for the eradication of human male infertility, we sequenced the bovine transcriptomes of round, elongated spermatids and epididymal sperms. The differential analysis was carried out with the reference of the mouse transcriptome, and the homology trends of gene expression to the mouse were also analysed. First, to explore the physiological mechanism of spermiogenesis that profoundly affects semen quality, homological trends of differential genes were compared during spermiogenesis in dairy cattle and mice. Next, Gene Ontology (GO), Kyoto Encyclopaedia of Genes and Genomes (KEGG) pathway enrichment, protein–protein interaction network (PPI network), and bioinformatics analyses were performed to uncover the regulation network of acrosome formation during the transition from round to elongated spermatids. In addition, processes that regulate gene expression during spermiogenesis from elongated spermatid to epididymal sperm, such as ubiquitination, acetylation, deacetylation, and glycosylation, and the functional ART3 gene may play important roles during spermiogenesis. Therefore, its localisation in the seminiferous tubules and epididymal sperm were investigated using immunofluorescent analysis, and its structure and function were also predicted. Our findings provide a deeper understanding of the process of spermiogenesis, which involves acrosome formation, histone replacement, and the fine regulation of gene expression.
Effect of Feeding Wet Feed or Wet Feed Fermented by Bacillus licheniformis on Growth Performance, Histopathology and Growth and Lipid Metabolism Marker Genes in Broiler Chickens
Authors: Saleh Ahmed A. , Shukry Mustafa , Farrag Foad , Soliman Mohamed M. , Abdel-Moneim Abdel-Moneim Eid
Published: January 2021

The present study evaluated the effect of three feeding methods (dry feed, wet feed or wet feed fermented with Bacillus licheniformis) on the growth performance, intestinal histomorphometry and gene expression of the lipid metabolism- and growth-related genes of broiler chickens. A total of 360 one-day-old Cobb-500 broiler chicks were randomly allotted into three groups containing four replicates with 30 birds each. The first group (control) was fed a dry mash basal diet. The second and third groups were fed wet feed and fermented wet feed. The final body weight and weight gain were reduced (p < 0.01) in the wet feed group, while they did not differ between the fermented wet feed and dry feed groups. Feed intake was not altered, and feeding on wet feed significantly (p < 0.01) increased the feed-to-gain ratio compared to the remaining groups. No differences between the three feeding methods in carcass characteristics, blood biochemistry and nutrient digestibility were observed except for crude protein digestibility, which was increased (p < 0.01) in the fermented wet feed group. Duodenal and ileal villi heights were elevated in birds fed fermented wet feeds, while crypt depth was not altered. The expression fold of IGF-1, GH and m-TOR genes in the pectoral muscle of birds fed wet feed was decreased (p < 0.05), while myostatin gene expression was elevated. Feeding on wet feed reduced the hepatic gene expression of PPARγ and increased that of FAS. In conclusion, wet feed negatively affected the broiler chickens’ efficiency under heat stress; however, fermenting the wet feed with Bacillus licheniformis improved feed utilization and birds’ performance compared to the dry feed group.
A Single Dose of Synbiotics and Vitamins at Birth Affects Piglet Microbiota before Weaning and Modifies Post-Weaning Performance
Authors: Girard Marion , Tretola Marco , Bee Giuseppe
Published: January 2021

Early-life microbial colonization is an important driver for the development and maturation of the gut. The present study aimed to determine whether a single-dose supplement given only at birth would improve piglet performance and modify their fecal microbiota during the suckling and post-weaning periods. At birth, piglets from eight litters received a supplement (SUP+) while piglets from six other litters received water (SUP−). All piglets were monitored until two weeks post-weaning, and fecal samples were collected on Day 16 of age and two weeks post-weaning (Day 39 ± 1). The supplementation resulted in an improvement of average daily gain during the whole experimental period, mainly due to a better growth and a reduction in the incidence of diarrhea in the post-weaning period. There were no differences in the abundance and diversity of the main taxa, although the supplementation increased the relative abundance of rare taxa, such as bacteria from the Saccharibacteria and Cyanobacteria phyla, and the Lentisphaeria class in the suckling period. In addition, at 16 days of age, SUP+ piglets had a more diverse core microbiota, with bacteria from the Lactobacillus genus being present in the core microbiota of SUP+ piglets and absent from SUP− piglets. Therefore, the enhanced growth performance and reduction in diarrhea seem to be related to changes in fecal microbiota during the suckling period rather than at two weeks post-weaning.
Evaluation of Chemical Composition, Radical Scavenging and Antitumor Activities of Satureja hortensis L. Herb Extracts
Authors: Bimbiraitė-Survilienė Kristina , Stankevičius Mantas , Šuštauskaitė Simona , Gęgotek Agnieszka , Maruška Audrius , Skrzydlewska Elżbieta , Barsteigienė Zita , Akuņeca Ieva , Ragažinskienė Ona , Lukošius Audronis
Published: January 2021

Satureja hortensis L. is an annual herbaceous plant of the Lamiaceae Lindl. family. S. hortensis L., related to thyme and rosemary, is used as spice and traditional medicinal herb in Europe. Mainly due to the polyphenols contained in S. hortensis L., this plant exhibits multiple biological effects. However, therapeutic effects on cells, including skin tumors, have not yet been studied. Therefore, the aim of this study was to compare the composition and the resulting antioxidant as well as biological properties [on melanocytes and melanoma cells] of summer, savory growing in botanical garden of Vytautas Magnus University in middle Lithuania climatic conditions, collected during various phases of vegetation. It has been shown that the budding phase alcohol extract of this plant contains the largest amounts of polyphenols, including rutin and rosemary acid, which promote the radical scavenging activity and antioxidant properties. In contrast, the extract from the massive flowering phase already at a concentration of 12.5 µg/mL reduces the survival of melanoma cells to 60% with 90% melanocytes survival. In addition, extracts from beginning of flowering and end of flowering at a concentration of 25 µg/mL, containing significantly less rutin and rosmarinic acid, in combination with irradiation of cells with UVB, significantly increased the lipid peroxidation process, particularly in melanoma cells. These data indicate the possibility of using extracts from S. hortensis L. to modulate/differentiate the metabolism of normal and tumor skin cells.
Influence of Ammonia Stripping Parameters on the Efficiency and Mass Transfer Rate of Ammonia Removal
Authors: Kim Eun Ju , Kim Ho , Lee Eunsil
Published: January 2021

This study analyzed the influence of different ammonia stripping parameters on ammonia removal efficiency and mass transfer rate. Ammonia stripping was performed on two devices, a column and a packed tower, with artificial ammonium hydroxide wastewater. First, ammonia concentration and pH were varied in a column without liquid circulation. At the same pH, the removal efficiency and mass transfer rate were constant, irrespective of initial ammonia concentration. When pH was increased, the ammonia fraction also increased, resulting in higher removal efficiency and mass transfer rate. Second, the effects of stripping were assessed using a packed tower with fluid circulation. The ammonium hydroxide concentration did not affect the removal efficiency or mass transfer rate. Furthermore, at apparatus liquid-gas ratios of 26.8–107.2 L/m3, a lower liquid-gas ratio led to increased ammonia removal efficiency and mass transfer rate. Conversely, the lower the liquid-gas ratio, the greater the air consumption. In conclusion, considering the removal rate and volume of air supply, the range of optimal liquid-gas ratio was determined as 26.8–53.6 L/m3. In particular, the 26.8 L/m3 condition achieved the best ammonia removal rate of 63.0% through only 6 h of stripping at 70 °C and pH 8.5.
Study on Wear Resistance of Ti-6Al-4V Alloy Composite Coating Prepared by Laser Alloying
Authors: Chen Quan , Zhang Jiajia , Huang Anguo , Wei Pengyu
Published: January 2021

Titanium alloy has extensive applications in numerous fields, such as in aerospace, shipbuilding, petrochemical, and bio-medical. However, under the condition of high temperature (above 700 °C), it is difficult to meet the requirements of the performance of the turbine blades, piston rings, valves, etc. In this paper, the alloy powder is composed of Ni60A, TiN, Al, and Si in accordance with the proportion of 1:3:4:2 (mass ratio), and the composite coating, such as TiN, TiB, Ti5Si3, and Al3Ti were synthesized on Ti-6Al-4V alloy by Yttrium Aluminium Garnet(YAG) laser. The friction and wear experiments were carried out on Ti-6Al-4V alloy and alloyed coatings at different loads (3N, 6N, 9N), and different temperatures (25 °C, 350 °C, 700 °C). The impact of load and temperature on wear performance were analyzed by analyzing the friction traces. The results showed that the abrasion loss, wear width, and depth, wear volume, and wear ratio of the alloyed coatings were less than Ti-6Al-4V alloy, and the surface of furrow was shallow and the wear was less. However, under high temperature conditions, the alloy coating wears worse than Ti-6Al-4V alloy, and the high temperature wear resistance is not ideal.
Hair Removal Combining Saliency, Shape and Color
Authors: Ramella Giuliana
Published: January 2021

In a computer-aided system for skin cancer diagnosis, hair removal is one of the main challenges to face before applying a process of automatic skin lesion segmentation and classification. In this paper, we propose a straightforward method to detect and remove hair from dermoscopic images. Preliminarily, the regions to consider as candidate hair regions and the border/corner components located on the image frame are automatically detected. Then, the hair regions are determined using information regarding the saliency, shape and image colors. Finally, the detected hair regions are restored by a simple inpainting method. The method is evaluated on a publicly available dataset, comprising 340 images in total, extracted from two commonly used public databases, and on an available specific dataset including 13 images already used by other authors for evaluation and comparison purposes. We propose also a method for qualitative and quantitative evaluation of a hair removal method. The results of the evaluation are promising as the detection of the hair regions is accurate, and the performance results are satisfactory in comparison to other existing hair removal methods.
Changes in Muscle Hardness from Resting to Mid-Range Lengthened Positions Detected by Shear Wave Elastography (SWE) with a Novel Protocol of Ultrasound Probe Placement
Authors: Ren Long-Jun , Cheng Connie Lok-Kan , Ma Christina Zong-Hao , Zheng Yong-Ping
Published: January 2021

Muscle hardness and its relationship with different muscle lengths/positions are important for understanding its underlying physiological status, and yet remained unclear. This study aimed to detect the local muscle hardness at different muscle lengths and identify the influence of muscle position on muscle hardness in healthy adults. A total of 26 healthy adults participated in this study. Shear wave elastography (SWE) was used to measure the muscle hardness of the Rectus Femoris (RF), Tibialis Anterior (TA) and Gastrocnemius Medialis (GM). Each muscle was tested at both resting (RST) and mid-range lengthened (MRL) positions. A novel ultrasound probe placing method was introduced, applied, and evaluated in this study. Moderate to excellent intra-/inter-rater reliability (Intraclass Correlation Coefficient, ICC ≥ 0.70) was found for muscle hardness measurements. The muscle hardness significantly increased from the RST to MRL position for all three muscles (p < 0.001). This study found that the muscle hardness increased at its mid-range lengthened position from the resting position. The mid-range lengthened muscle position of TA and GM could also be sensitive enough to reflect the age-related changes in local muscle hardness. This study also highlights the importance of placing the assessed extremities in an appropriate and consistent position when assessing muscle qualities by ultrasonics in clinical practice.
Individual Differences in Hemodynamic Responses Measured on the Head Due to a Long-Term Stimulation Involving Colored Light Exposure and a Cognitive Task: A SPA-fNIRS Study
Authors: Zohdi Hamoon , Scholkmann Felix , Wolf Ursula
Published: January 2021

When brain activity is measured by neuroimaging, the canonical hemodynamic response (increase in oxygenated hemoglobin ([O2Hb]) and decrease in deoxygenated hemoglobin ([HHb]) is not always seen in every subject. The reason for this intersubject-variability of the responses is still not completely understood. This study is performed with 32 healthy subjects, using the systemic physiology augmented functional near-infrared spectroscopy (SPA-fNIRS) approach. We investigate the intersubject variability of hemodynamic and systemic physiological responses, due to a verbal fluency task (VFT) under colored light exposure (CLE; blue and red). Five and seven different hemodynamic response patterns were detected in the subgroup analysis of the blue and red light exposure, respectively. We also found that arterial oxygen saturation and mean arterial pressure were positively correlated with [O2Hb] at the prefrontal cortex during the CLE-VFT independent of the color of light and classification of the subjects. Our study finds that there is substantial intersubject-variability of cerebral hemodynamic responses, which is partially explained by subject-specific systemic physiological changes induced by the CLE-VFT. This means that both subgroup analyses and the additional assessment of systemic physiology are of crucial importance to achieve a comprehensive understanding of the effects of a CLE-VFT on human subjects.
Functionalized Graphene Quantum Dots Modulate Malignancy of Glioblastoma Multiforme by Downregulating Neurospheres Formation
Authors: Perini Giordano , Palmieri Valentina , Ciasca Gabriele , Primiano Aniello , Gervasoni Jacopo , De Spirito Marco , Papi Massimiliano
Published: January 2021

Glioblastoma multiforme (GBM) is the most aggressive brain cancer. We previously demonstrated the effect of biocompatible surface functionalized graphene quantum dots (GQDs) on GBM cells as chemotherapy enhancers in combination with the antitumor drug doxorubicin (Dox). However, traditional two-dimensional cultures could not represent a reliable model of tumor behavior. In this work, we investigated the effect of carboxylated (COOH-GQDs), aminated (NH2-GQDs) and unfunctionalized GQDs on a three-dimensional model of neurospheres. Neurospheres are clusters of GBM cells, which formation is driven by the presence of a stem subpopulation involved in cancer malignancy. Tumor recurrence after surgical resection, chemotherapy and radiotherapy indeed depends on the presence of cancer cells with stem properties. We measured a significant reduction in number and size of neurospheres after two weeks of monitoring in the presence of COOH-GQDs and GQDs. Previous works pointed out how variations of membrane fluidity could affect membrane stability and cell-to-cell interactions, thus influencing cell clustering. Therefore, we measured changes in membrane fluidity after administration of GQDs. We found that COOH-GQDs and GQDs significantly increased membrane fluidity with respect to the treatment with NH2-GQDs or compared to untreated cells. Shifts in the phase of phospholipid bilayer were in accordance with the negative surface net charge of GQDs. We depicted a strong correlation between negatively charged GQDs-induced increase in membrane fluidity and the downregulation of neurospheres formation. Our results indicate that COOH-GQDs and GQDs significantly modulate tumor malignancy by increasing fluidity of cell membrane, with a consequent inhibition of cell-to-cell interaction.
Relation of Metal-Binding Property and Selective Toxicity of 8-Hydroxyquinoline Derived Mannich Bases Targeting Multidrug Resistant Cancer Cells
Authors: Pape Veronika F.S. , Gaál Anikó , Szatmári István , Kucsma Nóra , Szoboszlai Norbert , Streli Christina , Fülöp Ferenc , Enyedy Éva A. , Szakács Gergely
Published: January 2021

Resistance to chemotherapeutic agents is a major obstacle in cancer treatment. A recently proposed strategy is to target the collateral sensitivity of multidrug resistant (MDR) cancer. Paradoxically, the toxicity of certain metal chelating agents is increased, rather than decreased, by the function of P-glycoprotein (Pgp), which is known to confer resistance by effluxing chemotherapeutic compounds from cancer cells. We have recently characterized and compared the solution’s chemical properties including ligand protonation and the metal binding properties of a set of structurally related 8-hydroxyquinoline derived Mannich bases. Here we characterize the impact of the solution stability and redox activity of their iron(III) and copper(II) complexes on MDR-selective toxicity. Our results show that the MDR-selective anticancer activity of the studied 8-hydroxyquinoline derived Mannich bases is associated with the iron deprivation of MDR cells and the preferential formation of redox-active copper(II) complexes, which undergo intracellular redox-cycling to induce oxidative stress.
Immunogenomic Gene Signature of Cell-Death Associated Genes with Prognostic Implications in Lung Cancer
Authors: Ahluwalia Pankaj , Ahluwalia Meenakshi , Mondal Ashis K. , Sahajpal Nikhil , Kota Vamsi , Rojiani Mumtaz V. , Rojiani Amyn M. , Kolhe Ravindra
Published: January 2021

Lung cancer is one of the leading causes of death worldwide. Cell death pathways such as autophagy, apoptosis, and necrosis can provide useful clinical and immunological insights that can assist in the design of personalized therapeutics. In this study, variations in the expression of genes involved in cell death pathways and resulting infiltration of immune cells were explored in lung adenocarcinoma (The Cancer Genome Atlas: TCGA, lung adenocarcinoma (LUAD), 510 patients). Firstly, genes involved in autophagy (n = 34 genes), apoptosis (n = 66 genes), and necrosis (n = 32 genes) were analyzed to assess the prognostic significance in lung cancer. The significant genes were used to develop the cell death index (CDI) of 21 genes which clustered patients based on high risk (high CDI) and low risk (low CDI). The survival analysis using the Kaplan–Meier curve differentiated patients based on overall survival (40.4 months vs. 76.2 months), progression-free survival (26.2 months vs. 48.6 months), and disease-free survival (62.2 months vs. 158.2 months) (Log-rank test, p < 0.01). Cox proportional hazard model significantly associated patients in high CDI group with a higher risk of mortality (Hazard Ratio: H.R 1.75, 95% CI: 1.28–2.45, p < 0.001). Differential gene expression analysis using principal component analysis (PCA) identified genes with the highest fold change forming distinct clusters. To analyze the immune parameters in two risk groups, cytokines expression (n = 265 genes) analysis revealed the highest association of IL-15RA and IL 15 (> 1.5-fold, p < 0.01) with the high-risk group. The microenvironment cell-population (MCP)-counter algorithm identified the higher infiltration of CD8+ T cells, macrophages, and lower infiltration of neutrophils with the high-risk group. Interestingly, this group also showed a higher expression of immune checkpoint molecules CD-274 (PD-L1), CTLA-4, and T cell exhaustion genes (HAVCR2, TIGIT, LAG3, PDCD1, CXCL13, and LYN) (p < 0.01). Furthermore, functional enrichment analysis identified significant perturbations in immune pathways in the higher risk group. This study highlights the presence of an immunocompromised microenvironment indicated by the higher infiltration of cytotoxic T cells along with the presence of checkpoint molecules and T cell exhaustion genes. These patients at higher risk might be more suitable to benefit from PD-L1 blockade or other checkpoint blockade immunotherapies.
The Role of Cannabinoids as Anticancer Agents in Pediatric Oncology
Authors: Andradas Clara , Truong Alexandra , Byrne Jacob , Endersby Raelene
Published: January 2021

Cannabinoids are a group of chemicals that bind to receptors in the human body and, in turn, modulate the endocannabinoid system (ECS). They can be endogenously produced, synthetic, or derived from the plant Cannabis sativa L. Research over the past several decades has shown that the ECS is a cellular communication network essential to maintain multiple biological functions and the homeostasis of the body. Indeed, cannabinoids have been shown to influence a wide variety of biological effects, including memory, pain, reproduction, bone remodeling or immunity, to name a few. Unsurprisingly, given these broad physiological effects, alterations of the ECS have been found in different diseases, including cancer. In recent years, the medical use of cannabis has been approved in different countries for a variety of human conditions. However, the use of these compounds, specifically as anticancer agents, remains controversial. Studies have shown that cannabinoids do have anticancer activity in different tumor types such as breast cancer, melanoma, lymphoma and adult brain cancer. Specifically, phytocannabinoids Δ9-tetrahydrocannabinol (THC) and cannabidiol (CBD) has been shown to induce apoptosis and inhibit proliferation of adult cancer cells, as well as modulate angiogenesis and metastasis. Despite increasing evidence that cannabinoids elicit antitumor effects in adult cancers, there is minimal data available on their effects in children or in pediatric cancers despite public and clinical demand for information. Here we describe a comprehensive and critical review of what is known about the effects of cannabinoids on pediatric cancers, highlight current gaps in knowledge and identify the critical issues that need addressing before considering these promising but controversial drugs for use in pediatric oncology.
Novel Epigenetic Eight-Gene Signature Predictive of Poor Prognosis and MSI-Like Phenotype in Human Metastatic Colorectal Carcinomas
Authors: Condelli Valentina , Calice Giovanni , Cassano Alessandra , Basso Michele , Rodriquenz Maria Grazia , Zupa Angela , Maddalena Francesca , Crispo Fabiana , Pietrafesa Michele , Aieta Michele , Sgambato Alessandro , Tortora Giampaolo , Zoppoli Pietro , Landriscina Matteo
Published: January 2021

Epigenetics is involved in tumor progression and drug resistance in human colorectal carcinoma (CRC). This study addressed the hypothesis that the DNA methylation profiling may predict the clinical behavior of metastatic CRCs (mCRCs). The global methylation profile of two human mCRC subgroups with significantly different outcome was analyzed and compared with gene expression and methylation data from The Cancer Genome Atlas COlon ADenocarcinoma (TCGA COAD) and the NCBI GENE expression Omnibus repository (GEO) GSE48684 mCRCs datasets to identify a prognostic signature of functionally methylated genes. A novel epigenetic signature of eight hypermethylated genes was characterized that was able to identify mCRCs with poor prognosis, which had a CpG-island methylator phenotype (CIMP)-high and microsatellite instability (MSI)-like phenotype. Interestingly, methylation events were enriched in genes located on the q-arm of chromosomes 13 and 20, two chromosomal regions with gain/loss alterations associated with adenoma-to-carcinoma progression. Finally, the expression of the eight-genes signature and MSI-enriching genes was confirmed in oxaliplatin- and irinotecan-resistant CRC cell lines. These data reveal that the hypermethylation of specific genes may provide prognostic information that is able to identify a subgroup of mCRCs with poor prognosis.
Reducing the Photodegradation of Perovskite Quantum Dots to Enhance Photocatalysis in CO2 Reduction
Authors: Lee Hanleem , Kim Meeree , Lee Hyoyoung
Published: January 2021

Solution-processed perovskite quantum dots (QDs) have been intensively researched as next-generation photocatalysts owing to their outstanding optical properties. Even though the intrinsic physical properties of perovskite QDs have been significantly improved, the chemical stability of these materials remains questionable. Their low long-term chemical stability limits their commercial applicability in photocatalysis. In this study, we investigated the photodegradation mechanisms of perovskite QDs and their hybrids via photoluminescence (PL) by varying the excitation power and the ultraviolet (UV) exposure power. Defects in perovskite QDs and the interface between the perovskite QD and the co-catalyst influence the photo-stability of perovskite QDs. Consequently, we designed a stable perovskite QD film via an in-situ cross-linking reaction with amine-based silane materials. The surface ligand comprising 2,6-bis(N-pyrazolyl)pyridine nickel(II) bromide (Ni(ppy)) and 5-hexynoic acid improved the interface between the Ni co-catalyst and the perovskite QD. Then, ultrathin SiO2 was fabricated using 3-aminopropyltriethoxy silane (APTES) to harness the strong surface binding energy of the amine functional group of APTES with the perovskite QDs. The Ni co-catalyst content was further increased through Ni doping during purification using a short surface ligand (3-butynoic acid). As a result, stable perovskite QDs with rapid charge separation were successfully fabricated. Time-correlated single photon counting (TCSPC) PL study demonstrated that the modified perovskite QD film exhibited slow photodegradation owing to defect passivation and the enhanced interface between the Ni co-catalyst and the perovskite QD. This interface impeded the generation of hot carriers, which are a critical factor in photodegradation. Finally, a stable red perovskite QD was synthesized by applying the same strategy and the mixture between red and green QD/Ni(ppy)/SiO2 displayed an CO2 reduction capacity for CO (0.56 µmol/(g∙h)).
Association between Inflammation and Function of Cell Adhesion Molecules Influence on Gastrointestinal Cancer Development
Authors: Huang Hsiang-Wei , Chang Cheng-Chih , Wang Chia-Siu , Lin Kwang-Huei
Published: January 2021

Gastrointestinal cancer is highly associated with inflammatory processes inducing the release of cytokines from cancer or immune cells, including interferons, interleukins, chemokines, colony-stimulating factors, and growth factors, which promote or suppress tumor progression. Inflammatory cytokines within the tumor microenvironment promote immune cell infiltration. Infiltrating immune, and tumor-surrounding stromal cells support tumor growth, angiogenesis, metastasis, and immunosuppression through communication with inflammatory cytokines and cell adhesion molecules. Notably, infiltrating immune and tumor cells present immunosuppressive molecules, such as programmed death-ligand 1 (PD-L1) and CD80/CD86. Suppression of cytotoxic T cells promotes tumor avoidance of immune surveillance and greater malignancy. Moreover, glycosylation and sialylation of proteins hyperexpressed on the cancer cell surface have been shown to enhance immune escape and metastasis. Cytokine treatments and immune checkpoint inhibitors are widely used in clinical practice. However, the tumor microenvironment is a rapidly changing milieu involving several factors. In this review, we have provided a summary of the interactions of inflammation and cell adhesion molecules between cancer and other cell types, to improve understanding of the tumor microenvironment.
Limited Proteolysis-Coupled Mass Spectrometry Identifies Phosphatidylinositol 4,5-Bisphosphate Effectors in Human Nuclear Proteome
Authors: Sztacho Martin , Šalovská Barbora , Červenka Jakub , Balaban Can , Hoboth Peter , Hozák Pavel
Published: January 2021

Specific nuclear sub-compartments that are regions of fundamental processes such as gene expression or DNA repair, contain phosphoinositides (PIPs). PIPs thus potentially represent signals for the localization of specific proteins into different nuclear functional domains. We performed limited proteolysis followed by label-free quantitative mass spectrometry and identified nuclear protein effectors of the most abundant PIP—phosphatidylinositol 4,5-bisphosphate (PIP2). We identified 515 proteins with PIP2-binding capacity of which 191 ‘exposed’ proteins represent a direct PIP2 interactors and 324 ‘hidden’ proteins, where PIP2 binding was increased upon trypsin treatment. Gene ontology analysis revealed that ‘exposed’ proteins are involved in the gene expression as regulators of Pol II, mRNA splicing, and cell cycle. They localize mainly to non-membrane bound organelles—nuclear speckles and nucleolus and are connected to the actin nucleoskeleton. ‘Hidden’ proteins are linked to the gene expression, RNA splicing and transport, cell cycle regulation, and response to heat or viral infection. These proteins localize to the nuclear envelope, nuclear pore complex, or chromatin. Bioinformatic analysis of peptides bound in both groups revealed that PIP2-binding motifs are in general hydrophilic. Our data provide an insight into the molecular mechanism of nuclear PIP2 protein interaction and advance the methodology applicable for further studies of PIPs or other protein ligands.
Linking the Endocannabinoidome with Specific Metabolic Parameters in an Overweight and Insulin-Resistant Population: From Multivariate Exploratory Analysis to Univariate Analysis and Construction of Predictive Models
Authors: Depommier Clara , Flamand Nicolas , Pelicaen Rudy , Maiter Dominique , Thissen Jean-Paul , Loumaye Audrey , Hermans Michel P. , Everard Amandine , Delzenne Nathalie M. , Di Marzo Vincenzo , Cani Patrice D.
Published: January 2021

The global obesity epidemic continues to rise worldwide. In this context, unraveling new interconnections between biological systems involved in obesity etiology is highly relevant. Dysregulation of the endocannabinoidome (eCBome) is associated with metabolic complications in obesity. This study aims at deciphering new associations between circulating endogenous bioactive lipids belonging to the eCBome and metabolic parameters in a population of overweight or obese individuals with metabolic syndrome. To this aim, we combined different multivariate exploratory analysis methods: canonical correlation analysis and principal component analysis, revealed associations between eCBome subsets, and metabolic parameters such as leptin, lipopolysaccharide-binding protein, and non-esterified fatty acids (NEFA). Subsequent construction of predictive regression models according to the linear combination of selected endocannabinoids demonstrates good prediction performance for NEFA. Descriptive approaches reveal the importance of specific circulating endocannabinoids and key related congeners to explain variance in the metabolic parameters in our cohort. Analysis of quartiles confirmed that these bioactive lipids were significantly higher in individuals characterized by important levels for aforementioned metabolic variables. In conclusion, by proposing a methodology for the exploration of large-scale data, our study offers additional evidence of the existence of an interplay between eCBome related-entities and metabolic parameters known to be altered in obesity.
Identification of Targets from LRRK2 Rescue Phenotypes
Authors: Toh Joanne , Chua Ling Ling , Ho Patrick , Sandanaraj Edwin , Tang Carol , Wang Hongyan , Tan Eng King
Published: January 2021

Parkinson’s disease (PD) is an age-dependent neurodegenerative condition. Leucine-rich repeat kinase 2 (LRRK2) mutations are the most frequent cause of sporadic and autosomal dominant PD. The exact role of LRRK2 protective variants (R1398H, N551K) together with a pathogenic mutant (G2019S) in aging and neurodegeneration is unknown. We generated the following myc-tagged UAS-LRRK2 transgenic Drosophila: LRRK2 (WT), N551K, R1398H, G2019S single allele, and double-mutants (N551K/G2019S or R1398H/G2019S). The protective variants alone were able to suppress the phenotypic effects caused by the pathogenic LRRK2 mutation. Next, we conducted RNA-sequencing using mRNA isolated from dopaminergic neurons of these different groups of transgenic Drosophila. Using pathway enrichment analysis, we identified the top 10 modules (p < 0.05), with “LRRK2 in neurons in Parkinson’s disease” among the candidates. Further dissection of this pathway identified the most significantly modulated gene nodes such as eEF1A2, ACTB, eEF1A, and actin cytoskeleton reorganization. The induction of the pathway was successfully restored by the R1398H protective variant and R1398H-G2019S or N551K-G2019S rescue experiments. The oxidoreductase family of genes was also active in the pathogenic mutant and restored in protective and rescue variants. In summary, we provide in vivo evidence supporting the neuroprotective effects of LRRK2 variants. RNA sequencing of dopaminergic neurons identified upregulation of specific gene pathways in the Drosophila carrying the pathogenic variant, and this was restored in the rescue phenotypes. Using protective gene variants, our study identifies potential new targets and provides proof of principle of a new therapeutic approach that will further our understanding of aging and neurodegeneration in PD.
Comparing Surface Plasmon-Optical and Electronic Immuno-Sensing of Affinity Interactions—A Case Study
Authors: Knoll Wolfgang , Liu Jing , Yu Fang , Niu Lifang , Reiner-Rozman Ciril , Köper Ingo
Published: January 2021

In this case study, we provide a few examples for affinity-sensors based on optical detection concepts and compare them with electronic read-out schemes. We concentrate and briefly summarize two of the most advanced versions in each category: one is a surface-plasmon field-enhanced fluorescence spectroscopic approach, while in the electronic sensing domain we concentrate on graphene-based field-effect transistors as the read-out platform. Both transduction principles are surface-sensitive and-selective, however, with penetration lengths into the analyte solution (e.g., into a flow cell attached) that are very different and that depend on totally different physical principles: while for surface-plasmons the evanescent character of the plasmon mode, propagating along the noble metal-solution interface with a penetration length in the order of 100 nm (for Au/water and a laser wavelength of = 632.8 nm), the “penetration depth” in electronic transistor-based sensing is governed by the Debye length which, for a physiological salt environment, amounts to less than 1 nm. Taking these differences into account, one can optimize the sensor read-out by the appropriate interfacial architecture used to functionalize the transducers by immobilizing one of the affinity interaction partners. We will discuss this for both concepts by giving a few examples of the achievable limit of detection for both methods. The examples discussed include a classical system, i.e., the binding of human chorionic gonadotropin (hCG) to its surface-immobilized antibodies or Fab fragments, the detection of lipopolysaccharides in a tethered bimolecular lipid membrane, and, as an example for small analyte detection by antibodies, the monitoring of aflatoxin B1, a member of the food toxin family of mycotoxins.
Proposal of Methodology for Evaluation of a Vertical Shanty Building in Beira, Mozambique
Authors: Santos Michael M. , Lanzinha João C. G. , Vaz Ferreira Ana
Published: January 2021

Emerging economies are in an almost winless situation: they would benefit from improving the extremely poor economic situation, making them self-reliant and economically productive. However, the poor fight for daily survival and, therefore, cannot afford to improve themselves. This article describes the state of the “Grande Hotel” in the city of Beira, Mozambique, built-in Portuguese colonial times, a real vertical shanty building that is occupied by approximately 1000 inhabitants trapped in poverty. To carry out any constructive intervention in a building or an urban complex, it is necessary to carry out a rehabilitation project that is developed based on a diagnosis of the building understudy, its main deteriorations, the causes, mechanisms of action, evolution, and possible treatments to be used for its repair. Analysis methods are necessary for the conservation of buildings since trying to stop, or correct buildings’ deterioration without a diagnosis of their problems or a prognosis on their evolution is a risky procedure with a high percentage of failure chances. The use of an appropriate methodology for diagnosing the damage present in the “Grande Hotel” and its prediction of evolution and development should directly impact a better quality of rehabilitation projects in the neighborhood where the building is located.
Engineering Copper Adhesion on Poly-Epoxy Surfaces Allows One-Pot Metallization of Polymer Composite Telecommunication Waveguides
Authors: Addou Fouzi , Duguet Thomas , Ledru Yohann , Mesnier Didier , Vahlas Constantin
Published: January 2021

Mass gain in the aerospace sector is highly demandable for energy savings and operational efficiency. Replacement of metal parts by polymer composites meets this prerequisite, provided the targeted functional properties are recovered. In the present contribution, we propose two innovative and scalable processes for the metallization of the internal faces of carbon fiber reinforced polymer radiofrequency waveguides foreseen for implementation in telecommunications satellites. They involve sequential direct liquid injection metalorganic chemical vapor deposition of copper and cobalt. The use of ozone pretreatment of the polymer surface prior deposition, or of cost effective anhydrous dimethoxyethane as solvent for the injection of the copper precursor, yield strongly adherent, 5 µm Cu films on the polymer composite. Their electrical resistivity is in the 4.1–5.0 μΩ·cm range, and they sustain thermal cycling between −175 °C and +170 °C. Such homogeneous and conformal films can be obtained at temperatures as low as 115 °C. Demonstration is achieved on a polymer composite waveguide, composed of metallized 60-mm long straight sections and of E-plane and H-plane elbows, that paves the way towards the metallization of scale one devices.