bluuebunny/crossref_metadata_2025 huggingface dataset:
Molecular Bases of Fruit Quality in Prunus Species: An Integrated Genomic, Transcriptomic, and Metabolic Review with a Breeding Perspective
Authors: García-Gómez Beatriz E. , Salazar Juan A. , Nicolás-Almansa María , Razi Mitra , Rubio Manuel , Ruiz David , Martínez-Gómez Pedro
Published: December 2020

In plants, fruit ripening is a coordinated developmental process that requires the change in expression of hundreds to thousands of genes to modify many biochemical and physiological signal cascades such as carbohydrate and organic acid metabolism, cell wall restructuring, ethylene production, stress response, and organoleptic compound formation. In Prunus species (including peaches, apricots, plums, and cherries), fruit ripening leads to the breakdown of complex carbohydrates into sugars, fruit firmness reductions (softening by cell wall degradation and cuticle properties alteration), color changes (loss of green color by chlorophylls degradation and increase in non-photosynthetic pigments like anthocyanins and carotenoids), acidity decreases, and aroma increases (the production and release of organic volatile compounds). Actually, the level of information of molecular events at the transcriptional, biochemical, hormonal, and metabolite levels underlying ripening in Prunus fruits has increased considerably. However, we still poorly understand the molecular switch that occurs during the transition from unripe to ripe fruits. The objective of this review was to analyze of the molecular bases of fruit quality in Prunus species through an integrated metabolic, genomic, transcriptomic, and epigenetic approach to better understand the molecular switch involved in the ripening process with important consequences from a breeding point of view.
The Chick Chorioallantoic Membrane Model: A New In Vivo Tool to Evaluate Breast Cancer Stem Cell Activity
Authors: Pinto Marta Teixeira , Ribeiro Ana Sofia , Conde Inês , Carvalho Rita , Paredes Joana
Published: December 2020

The high plasticity of cancer stem-like cells (CSCs) allows them to differentiate and proliferate, specifically when xenotransplanted subcutaneously into immunocompromised mice. CSCs are highly tumorigenic, even when inoculated in small numbers. Thus, in vivo limiting dilution assays (LDA) in mice are the current gold standard method to evaluate CSC enrichment and activity. The chick embryo chorioallantoic membrane (CAM) is a low cost, naturally immune-incompetent and reproducible model widely used to evaluate the spontaneous growth of human tumor cells. Here, we established a CAM-LDA assay able to rapidly reproduce tumor specificities—in particular, the ability of the small population of CSCs to form tumors. We used a panel of organotropic metastatic breast cancer cells, which show an enrichment in a stem cell gene signature, enhanced CD44+/CD24−/low cell surface expression and increased mammosphere-forming efficiency (MFE). The size of CAM-xenografted tumors correlate with the number of inoculated cancer cells, following mice xenograft growth pattern. CAM and mice tumors are histologically comparable, displaying both breast CSC markers CD44 and CD49f. Therefore, we propose a new tool for studying CSC prevalence and function—the chick CAM-LDA—a model with easy handling, accessibility, rapid growth and the absence of ethical and regulatory constraints.
Phenotypic Characterization of Transgenic Mice Expressing Human IGFBP-5
Authors: Nguyen Xinh-Xinh , Sanderson Matthew , Helke Kristi , Feghali-Bostwick Carol
Published: December 2020

Pulmonary fibrosis is one of the important causes of morbidity and mortality in fibroproliferative disorders such as systemic sclerosis (SSc) and idiopathic pulmonary fibrosis (IPF). Insulin-like growth factor binding protein-5 (IGFBP-5) is a conserved member of the IGFBP family of proteins that is overexpressed in SSc and IPF lung tissues. In this study, we investigated the functional role of IGFBP-5 in the development of fibrosis in vivo using a transgenic model. We generated transgenic mice ubiquitously expressing human IGFBP-5 using CRISPR/Cas9 knock-in. Our data show that the heterozygous and homozygous mice are viable and express human IGFBP-5 (hIGFBP-5). Transgenic mice had increased expression of extracellular matrix (ECM) genes, especially Col3a1, Fn, and Lox in lung and skin tissues of mice expressing higher transgene levels. Histologic analysis of the skin tissues showed increased dermal thickness, and the lung histology showed subtle changes in the heterozygous and homozygous mice as compared with the wild-type mice. These changes were more pronounced in animals expressing higher levels of hIGFBP-5. Bleomycin increased ECM gene expression in wild-type mice and accentuated an increase in ECM gene expression in transgenic mice, suggesting that transgene expression exacerbated bleomycin-induced pulmonary fibrosis. Primary lung fibroblasts cultured from lung tissues of homozygous transgenic mice showed significant increases in ECM gene expression and protein levels, further supporting the observation that IGFBP-5 resulted in a fibrotic phenotype in fibroblasts. In summary, transgenic mice expressing human IGFBP-5 could serve as a useful animal model for examining the function of IGFBP-5 in vivo.
Effect of Cultivation Parameters on Fermentation and Hydrogen Production in the Phylum Thermotogae
Authors: Lanzilli Mariamichela , Esercizio Nunzia , Vastano Marco , Xu Zhaohui , Nuzzo Genoveffa , Gallo Carmela , Manzo Emiliano , Fontana Angelo , d’Ippolito Giuliana
Published: December 2020

The phylum Thermotogae is composed of a single class (Thermotogae), 4 orders (Thermotogales, Kosmotogales, Petrotogales, Mesoaciditogales), 5 families (Thermatogaceae, Fervidobacteriaceae, Kosmotogaceae, Petrotogaceae, Mesoaciditogaceae), and 13 genera. They have been isolated from extremely hot environments whose characteristics are reflected in the metabolic and phenotypic properties of the Thermotogae species. The metabolic versatility of Thermotogae members leads to a pool of high value-added products with application potentials in many industry fields. The low risk of contamination associated with their extreme culture conditions has made most species of the phylum attractive candidates in biotechnological processes. Almost all members of the phylum, especially those in the order Thermotogales, can produce bio-hydrogen from a variety of simple and complex sugars with yields close to the theoretical Thauer limit of 4 mol H2/mol consumed glucose. Acetate, lactate, and L-alanine are the major organic end products. Thermotagae fermentation processes are influenced by various factors, such as hydrogen partial pressure, agitation, gas sparging, culture/headspace ratio, inoculum, pH, temperature, nitrogen sources, sulfur sources, inorganic compounds, metal ions, etc. Optimization of these parameters will help to fully unleash the biotechnological potentials of Thermotogae and promote their applications in industry. This article gives an overview of how these operational parameters could impact Thermotogae fermentation in terms of sugar consumption, hydrogen yields, and organic acids production.
Involvement of cAMP-Dependent Protein Kinase in the Nucleus Accumbens in Cocaine Versus Social Interaction Reward
Authors: Amaral Inês M. , Lemos Cristina , Cera Isabella , Dechant Georg , Hofer Alex , El Rawas Rana
Published: December 2020

Evidence suggests that PKA activity in the nucleus accumbens (NAc) plays an essential role in reward-related learning. In this study, we investigated whether PKA is differentially involved in the expression of learning produced by either natural reinforcers or psychostimulants. For that purpose, we inhibited PKA through a bilateral infusion of Rp-cAMPS, a specific PKA inhibitor, directly into the NAc. The effects of PKA inhibition in the NAc on the expression of concurrent conditioned place preference (CPP) for cocaine (drug) and social interaction (natural reward) in rats were evaluated. We found that PKA inhibition increased the expression of cocaine preference. This effect was not due to altered stress levels or decreased social reward. PKA inhibition did not affect the expression of natural reward as intra-NAc Rp-cAMPS infusion did not affect expression of social preference. When rats were trained to express cocaine or social interaction CPP and tested for eventual persisting preference 7 and 14 days after CPP expression, cocaine preference was persistent, but social preference was abolished after the first test. These results suggest that PKA in the NAc is involved in drug reward learning that might lead to addiction and that only drug, but not natural, reward is persistent.
Disruption of 24-Hour Rhythm in Intraocular Pressure Correlates with Retinal Ganglion Cell Loss in Glaucoma
Authors: Neroev Vladimir , Malishevskaya Tatyana , Weinert Dietmar , Astakhov Sergei , Kolomeichuk Sergey , Cornelissen Germaine , Kabitskaya Yana , Boiko Elena , Nemtsova Irina , Gubin Denis
Published: December 2020

Parameters of 24-h rhythm in intraocular pressure (IOP) were assessed in patients with stable or advanced primary open-angle glaucoma (S-POAG/A-POAG) and referenced to the phase of “marker” circadian temperature rhythm of each patient. Body temperature and IOP were measured over a 72-h span in 115 participants (65 S-POAG and 50 A-POAG). Retinal Ganglion Cell (RGC) damage was assessed by high-definition optical coherence tomography. The 24-h IOP rhythm in A-POAG patients peaked during the night, opposite to the daytime phase position in S-POAG patients (p < 0.0001). The 24-h IOP phase correlated with RGC loss (p < 0.0001). The internal phase shift between IOP and body temperature gradually increased with POAG progression (p < 0.001). Angiotensin converting enzyme Alu-repeat deletion/insertion (ACE I/D) emerged as a candidate gene polymorphism, which may play a role in the alteration of the circadian IOP variability in advanced glaucoma. To conclude, a reliable estimation of the 24-h rhythm in IOP requires the degree of RGC damage to be assessed. In advanced POAG, the 24-h phase of IOP tended to occur during the night and correlated with RGC loss, being progressively delayed relative to the phase of temperature.
Multi-Omics Characterization of Inflammatory Bowel Disease-Induced Hyperplasia/Dysplasia in the Rag2−/−/Il10−/− Mouse Model
Authors: Han Qiyuan , Kono Thomas J. Y. , Knutson Charles G. , Parry Nicola M. , Seiler Christopher L. , Fox James G. , Tannenbaum Steven R. , Tretyakova Natalia Y.
Published: December 2020

Epigenetic dysregulation is hypothesized to play a role in the observed association between inflammatory bowel disease (IBD) and colon tumor development. In the present work, DNA methylome, hydroxymethylome, and transcriptome analyses were conducted in proximal colon tissues harvested from the Helicobacter hepaticus (H. hepaticus)-infected murine model of IBD. Reduced representation bisulfite sequencing (RRBS) and oxidative RRBS (oxRRBS) analyses identified 1606 differentially methylated regions (DMR) and 3011 differentially hydroxymethylated regions (DhMR). These DMR/DhMR overlapped with genes that are associated with gastrointestinal disease, inflammatory disease, and cancer. RNA-seq revealed pronounced expression changes of a number of genes associated with inflammation and cancer. Several genes including Duox2, Tgm2, Cdhr5, and Hk2 exhibited changes in both DNA methylation/hydroxymethylation and gene expression levels. Overall, our results suggest that chronic inflammation triggers changes in methylation and hydroxymethylation patterns in the genome, altering the expression of key tumorigenesis genes and potentially contributing to the initiation of colorectal cancer.
Optogenetic Modulation of Neural Progenitor Cells Improves Neuroregenerative Potential
Authors: Giraldo Esther , Palmero-Canton David , Martinez-Rojas Beatriz , Sanchez-Martin Maria del Mar , Moreno-Manzano Victoria
Published: December 2020

Neural progenitor cell (NPC) transplantation possesses enormous potential for the treatment of disorders and injuries of the central nervous system, including the replacement of lost cells or the repair of host neural circuity after spinal cord injury (SCI). Importantly, cell-based therapies in this context still require improvements such as increased cell survival and host circuit integration, and we propose the implementation of optogenetics as a solution. Blue-light stimulation of NPCs engineered to ectopically express the excitatory light-sensitive protein channelrhodopsin-2 (ChR2-NPCs) prompted an influx of cations and a subsequent increase in proliferation and differentiation into oligodendrocytes and neurons and the polarization of astrocytes from a pro-inflammatory phenotype to a pro-regenerative/anti-inflammatory phenotype. Moreover, neurons derived from blue-light-stimulated ChR2-NPCs exhibited both increased branching and axon length and improved axon growth in the presence of axonal inhibitory drugs such as lysophosphatidic acid or chondroitin sulfate proteoglycan. Our results highlight the enormous potential of optogenetically stimulated NPCs as a means to increase neuroregeneration and improve cell therapy outcomes for enhancing better engraftments and cell identity upon transplantation in conditions such as SCI.
Pigment Epithelium-Derived Factor (PEDF) Receptors Are Involved in Survival of Retinal Neurons
Authors: Bürger Susanne , Meng Jie , Zwanzig Annette , Beck Mike , Pankonin Maik , Wiedemann Peter , Eichler Wolfram , Unterlauft Jan Darius
Published: December 2020

The demise of retinal ganglion cells (RGCs) is characteristic of diseases of the retina such as glaucoma and diabetic or ischemic retinopathies. Pigment epithelium-derived factor (PEDF) is a multifunctional secreted protein that mediates neuroprotection and inhibition of angiogenesis in the retina. We have studied expression and regulation of two of several receptors for PEDF, patatin-like phospholipase 2 gene product/PEDF-R and laminin receptor (LR), in serum-starved RGC under normoxia and hypoxia and investigated their involvement in the survival of retinal neuronal cells. We show that PEDF-R and LR are co-expressed in RGC and R28 retinal precursor cells. Expression of both receptors was enhanced in the presence of complex secretions from retinal glial (Müller) cells and upregulated by VEGF and under hypoxic conditions. PEDF-R- and LR-knocked-down cells demonstrated a markedly attenuated expression of anti-apoptotic Bcl-2 family members (Bcl-2, Bcl-xL) and neuroprotective mediators (PEDF, VEGF, BDNF) suggesting that both PEDF-R and LR mediate pro-survival effects of PEDF on RGC. While this study does not provide evidence for a differential survival-promoting influence of either PEDF-R or LR, it nevertheless highlights the importance of both PEDF receptors for the viability of retinal neurons.
The Role of Estrogen Receptors and Their Signaling across Psychiatric Disorders
Authors: Hwang Wu Jeong , Lee Tae Young , Kim Nahrie Suk , Kwon Jun Soo
Published: December 2020

Increasing evidence suggests estrogen and estrogen signaling pathway disturbances across psychiatric disorders. Estrogens are not only crucial in sexual maturation and reproduction but are also highly involved in a wide range of brain functions, such as cognition, memory, neurodevelopment, and neuroplasticity. To add more, the recent findings of its neuroprotective and anti-inflammatory effects have grown interested in investigating its potential therapeutic use to psychiatric disorders. In this review, we analyze the emerging literature on estrogen receptors and psychiatric disorders in cellular, preclinical, and clinical studies. Specifically, we discuss the contribution of estrogen receptor and estrogen signaling to cognition and neuroprotection via mediating multiple neural systems, such as dopaminergic, serotonergic, and glutamatergic systems. Then, we assess their disruptions and their potential implications for pathophysiologies in psychiatric disorders. Further, in this review, current treatment strategies involving estrogen and estrogen signaling are evaluated to suggest a future direction in identifying novel treatment strategies in psychiatric disorders.
Human-Centered AI to Support an Adaptive Management of Human-Machine Transitions with Vehicle Automation
Authors: Bellet Thierry , Banet Aurélie , Petiot Marie , Richard Bertrand , Quick Joshua
Published: December 2020

This article is about the Human-Centered Design (HCD), development and evaluation of an Artificial Intelligence (AI) algorithm aiming to support an adaptive management of Human-Machine Transition (HMT) between car drivers and vehicle automation. The general principle of this algorithm is to monitor (1) the drivers’ behaviors and (2) the situational criticality to manage in real time the Human-Machine Interactions (HMI). This Human-Centered AI (HCAI) approach was designed from real drivers’ needs, difficulties and errors observed at the wheel of an instrumented car. Then, the HCAI algorithm was integrated into demonstrators of Advanced Driving Aid Systems (ADAS) implemented on a driving simulator (dedicated to highway driving or to urban intersection crossing). Finally, user tests were carried out to support their evaluation from the end-users point of view. Thirty participants were invited to practically experience these ADAS supported by the HCAI algorithm. To increase the scope of this evaluation, driving simulator experiments were implemented among three groups of 10 participants, corresponding to three highly contrasted profiles of end-users, having respectively a positive, neutral or reluctant attitude towards vehicle automation. After having introduced the research context and presented the HCAI algorithm designed to contextually manage HMT with vehicle automation, the main results collected among these three profiles of future potential end users are presented. In brief, main findings confirm the efficiency and the effectiveness of the HCAI algorithm, its benefits regarding drivers’ satisfaction, and the high levels of acceptance, perceived utility, usability and attractiveness of this new type of “adaptive vehicle automation”.
Decentralized Actionable Cyber Threat Intelligence for Networks and the Internet of Things
Authors: Mendez Mena Diego , Yang Baijian
Published: December 2020

Security presents itself as one of the biggest threats to the enabling and the deployment of the Internet of Things (IoT). Security challenges are evident in light of recent cybersecurity attacks that targeted major internet service providers and crippled a significant portion of the entire Internet by taking advantage of faulty and ill-protected embedded devices. Many of these devices reside at home networks with user-administrators who are not familiar with network security best practices, making them easy targets for the attackers. Therefore, security solutions are needed to navigate the insecure and untrusted public networks by automating protections through affordable and accessible first-hand network information sharing. This paper proposes and implements a proof of concept (PoC) to secure Internet Service Providers (ISPs), home networks, and home-based IoT devices using blockchain technologies. The results obtained support the idea of a distributed cyber threat intelligence data sharing network capable of protecting various stakeholders.
Evaluating the Effect of Topical Atropine Use for Myopia Control on Intraocular Pressure by Using Machine Learning
Authors: Wu Tzu-En , Chen Hsin-An , Jhou Mao-Jhen , Chen Yen-Ning , Chang Ting-Jen , Lu Chi-Jie
Published: December 2020

Atropine is a common treatment used in children with myopia. However, it probably affects intraocular pressure (IOP) under some conditions. Our research aims to analyze clinical data by using machine learning models to evaluate the effect of 19 important factors on intraocular pressure (IOP) in children with myopia treated with topical atropine. The data is collected on 1545 eyes with spherical equivalent (SE) less than −10.0 diopters (D) treated with atropine for myopia control. Four machine learning models, namely multivariate adaptive regression splines (MARS), classification and regression tree (CART), random forest (RF), and eXtreme gradient boosting (XGBoost), were used. Linear regression (LR) was used for benchmarking. The 10-fold cross-validation method was used to estimate the performance of the five methods. The main outcome measure is that the 19 important factors associated with atropine use that may affect IOP are evaluated using machine learning models. Endpoint IOP at the last visit was set as the target variable. The results show that the top five significant variables, including baseline IOP, recruitment duration, age, total duration and previous cumulative dosage, were identified as most significant for evaluating the effect of atropine use for treating myopia on IOP. We can conclude that the use of machine learning methods to evaluate factors that affect IOP in children with myopia treated with topical atropine is promising. XGBoost is the best predictive model, and baseline IOP is the most accurate predictive factor for endpoint IOP among all machine learning approaches.
Autologous Fat Transplantation for Thumb Carpometacarpal Joint Osteoarthritis (Liparthroplasty): A Case Series with Two Years of Follow-UP
Authors: Froschauer Stefan M. , Holzbauer Matthias , Wenny Raphael , Schmidt Manfred , Huemer Georg M. , Kwasny Oskar , Duscher Dominik
Published: December 2020

Adipose-derived mesenchymal stem cell (ASC) therapy is currently a focus of regenerative medicine. Lipoaspirate is rich in ASCs and is evolving into a promising, less-invasive tool to treat thumb carpometacarpal osteoarthritis as compared with common surgical techniques, for example, trapeziectomy or prosthesis implantation. The present study aimed to examine the effect of 1 mL intraarticular lipoaspirate injection (liparthroplasty) in 31 thumb carpometacarpal osteoarthritis patients (27 woman and four men) with a median age of 58 (interquartile range (IQR) of 10) years and Eaton–Littler Stage 2 or 3. Median pain levels assessed via visual analogue scale significantly decreased from 7 (IQR 2) to 4 (IQR 6) after six months (p < 0.0001) and 2 (IQR 5) after two years (p < 0.0001). Median pre-interventional Disabilities of the Arm, Shoulder and Hand (DASH) scores of 59 (IQR 26) significantly reduced to a value of 40 (IQR 43) after six months (p = 0.004) and to 35 (IQR 34) after two years (p < 0.0001). Subjective grip strength showed no significant improvement. However, the time until recurrence of symptoms was measured and a cumulative remission rate of 58% was detected after two years. Satisfaction rates were 68% after six months and 51% after two years. In conclusion, liparthroplasty represents a promising option to reduce pain and functional impairment and to postpone surgery for a certain period of time.
Clinical Features of Intra-Abdominal Abscess and Intestinal Free-Wall Perforation in Korean Patients with Crohn’s Disease: Results from the CONNECT Study
Authors: Jeong Seok-Hoo , Choi Ja Sung , Kim Jin Woo , Kim Hee Man , Kim Hyun-Soo , Im Jong Pil , Kim Joo Sung , Kim You Sun , Cheon Jae Hee , Kim Won Ho , Ye Byong Duk , Kim Young-Ho , Han Dong Soo
Published: December 2020

Background: In Crohn’s disease (CD), intra-abdominal abscess (IA) and intestinal free-wall perforation (IP) have a common mechanism of transmural inflammation; however, their manifestation is different. Objective: This study aimed to investigate differences in the clinical features between IA and IP in Korean patients with Crohn’s disease. Design: A retrospective cohort study. Setting: Thirty university hospitals and two local hospitals in Korea. Patients: Patients who were diagnosed with CD between July 1982 and December 2008 were enrolled. Main Outcome Measures: Clinical characteristics of IA and IP. Results: Among 1286 patients with CD, 147 (11.4%) had IA and 83 (6.5%) had IP. IA patients were younger than those of IP (24.2 ± 8.6 vs. 30.4 ± 11.1 years, p = 0.001). Location and behavior were significantly different between IA and IP (p = 0.035 and 0.021). In multivariate analyses, perianal fistula was not associated with increased risk of IA and IP, while intestinal stricture was associated with increased risk of IA (OR: 2.72, p < 0.0001) and IP (OR: 2.76, p < 0.0001). In subgroup analyses, 55 (36.5%) IA patients were diagnosed at the diagnosis of CD, and 92 (63.5%) during follow-up of CD, while 47 (56.6%) IP patients were diagnosed at the diagnosis of CD, and 36 (43.3%) during follow-up of CD. Conclusions: There are several differences in the clinical features of IA and IP in Korean patients with CD. The development mechanism is considered as identical, but further investigation should be needed for clinical implication.
Extracellular miRNAs for the Management of Barrett’s Esophagus and Esophageal Adenocarcinoma: A Systematic Review
Authors: Inokuchi Kazumi , Ochiya Takahiro , Matsuzaki Juntaro
Published: December 2020

Esophageal adenocarcinoma (EAC), the major histologic type of esophageal cancer (EC) in Western countries, is a disease with a poor prognosis, primarily due to usual diagnosis at an advanced stage. The prevalence of EAC has increased in recent years, both in Western countries and in Asia. Barrett’s esophagus (BE) is a precursor lesion of EAC. Therefore, early detection and proper management of BE and EAC is important to improve prognosis. Here, we systematically summarize current knowledge about the potential utility of extracellular microRNAs (miRNAs), which are thought to be non-invasive biomarkers for many diseases, for these purposes. A search of the PubMed and Embase databases identified 22 papers about extracellular miRNAs that have potential utility for management of EAC. Among them, 19 were EAC-related and ten were BE-related; some of these dealt with both conditions. The articles included studies reporting diagnosis, prognosis, and treatment responses. Multiple papers report dysregulation of miR-194-5p in BE and miR-21-5p, -25-3p, and -93-5p in EAC. Although it will take time to utilize these miRNAs in clinical practice, they are likely to be useful non-invasive markers in the future.
Comprehensive Perspective for Lung Cancer Characterisation Based on AI Solutions Using CT Images
Authors: Pereira Tania , Freitas Cláudia , Costa José Luis , Morgado Joana , Silva Francisco , Negrão Eduardo , de Lima Beatriz Flor , da Silva Miguel Correia , Madureira António J. , Ramos Isabel , Hespanhol Venceslau , Cunha António , Oliveira Hélder P.
Published: December 2020

Lung cancer is still the leading cause of cancer death in the world. For this reason, novel approaches for early and more accurate diagnosis are needed. Computer-aided decision (CAD) can be an interesting option for a noninvasive tumour characterisation based on thoracic computed tomography (CT) image analysis. Until now, radiomics have been focused on tumour features analysis, and have not considered the information on other lung structures that can have relevant features for tumour genotype classification, especially for epidermal growth factor receptor (EGFR), which is the mutation with the most successful targeted therapies. With this perspective paper, we aim to explore a comprehensive analysis of the need to combine the information from tumours with other lung structures for the next generation of CADs, which could create a high impact on targeted therapies and personalised medicine. The forthcoming artificial intelligence (AI)-based approaches for lung cancer assessment should be able to make a holistic analysis, capturing information from pathological processes involved in cancer development. The powerful and interpretable AI models allow us to identify novel biomarkers of cancer development, contributing to new insights about the pathological processes, and making a more accurate diagnosis to help in the treatment plan selection.
Side Effect/Complication Risk Related to Injection Branch Level of Chemoembolization in Treatment of Metastatic Liver Lesions from Colorectal Cancer
Authors: Szemitko Marcin , Golubinska-Szemitko Elzbieta , Wilk-Milczarek Ewa , Falkowski Aleksander
Published: December 2020

Purpose: Transarterial chemoembolization with drug eluting beads (DEB-TACE) loaded with irinotecan despite having proven efficacy in the treatment of unresectable liver metastases in the course of colorectal cancer (CRC) does not have an established consistent method. In particular, there are discrepancies in the branch level at which microspheres are administered. Lobar embolization supplies microspheres to all vessels supplying a metastatic lesion but exposes the entire liver parenchyma to negative effects from microsphere irinotecan. Superselective chemoembolization compromises healthy liver parenchyma less but may omit small vessels supplying metastatic lesions. Objective: Assessment of the risk of complications and the severity of postembolization syndromes with CRC metastatic liver lesion chemoembolization with irinotecan-loaded microspheres, according to branch level of chemoembolization. Patients and methods: The analysis included 49 patients (27 female/22 male) with liver metastases in the course of CRC, who underwent 192 chemoembolization treatments (mean 3.62 per patient) with microspheres loaded with 100 mg irinotecan. The procedures were performed according to an adopted schema: alternating the right and left lobe of the liver at 3-week intervals. The severity of postembolization syndrome (PES) and the presence of complications were assessed according to the branch level of chemoembolization; microspheres were administered at the branch level of lobar, segmental, or subsegmental arteries. Assessment of adverse events was performed according to the standards of the Cancer Therapy Evaluation Program Common Terminology Criteria for Adverse Events, Version 5.0. Results: The median survival of all patients from the start of chemoembolization was 13 months. With 192 chemoembolization sessions, 14 (7.3%) serious complications were found. The study showed no significant relationship between the branch level of embolizate administration and the presence of complications (p = 0.2307). Postembolization syndrome was diagnosed after 102 chemoembolization treatments, i.e., 53.1% of treatments. A significant correlation was found between the severity of the postembolization syndrome and the branch level of embolization treatment (p = 0.00303). The mean PES severity increased from subsegmental through segmental to lobar administration. Conclusion: Chemoembolization using Irinotecan-loaded microspheres was relatively well tolerated by patients and gave a low risk of significant complications, which did not change with the branch level of microsphere administration. However, an association was found between the branch level of chemoembolization and the severity of postembolization syndrome. Further research is needed to determine the most effective DEB-TACE chemoembolization technique.
The Significance of True Knot of the Umbilical Cord in Long-Term Offspring Neurological Health
Authors: Lichtman Yael , Wainstock Tamar , Walfisch Asnat , Sheiner Eyal
Published: December 2020

We aimed to study both the short- and long-term neurological implications in offspring born with confirmed knotting of the umbilical cord—“true knot of cord”. In this population based cohort study, a comparison of perinatal outcome and long-term neurological hospitalizations was performed on the basis of presence or absence of true knot of cord. A Kaplan–Meier survival curve was constructed to compare the cumulative incidence of neurological hospitalizations between the study groups. Multivariable regression models were used to assess the independent association between true knot of cord, perinatal mortality and long term neurological related hospitalizations, while controlling for potential confounders. The study included 243,639 newborns, of them 1.1% (n = 2606) were diagnosed with true knot of the umbilical cord. Higher rates of intrauterine fetal demise (IUFD) were noted in the exposed group, a finding which remained significant in the multivariable generalized estimation equation, while controlling for confounders. The cumulative incidences of neurological hospitalizations over time were comparable between the groups. The Cox regression confirmed a lack of association between true knot of cord and total long term neurological related hospitalizations. While presence of true knot of the umbilical cord is associated with higher IUFD rates, in our population, however, its presence does not appear to impact the long term neurological health of exposed offspring.
Nano-Structured Polyaniline as a Potential Adsorbent for Methylene Blue Dye Removal from Effluent
Authors: Duhan Monika , Kaur Raminder
Published: December 2020

The textile sector is one of the major culprits of water pollution, and demands immediate attention. The coloured textile effluent, loaded with toxic dyes, when mixed with waterbodies, may harm aquatic life, plants, animals, and humans. Although polyaniline in its different forms was utilised for the adsorption of different dyes, the pure nano-fibrous form of polyaniline, i.e., PANI nanofibers, have reportedly not been used for the removal of dyes from wastewater. The present study aimed to employ nano-structured polyaniline, in the form of polyaniline nanofibers (base; PNB—polyaniline nanofiber base) for the elimination of methylene blue (cationic dye; MB) dye from its solution. The polyaniline nanofiber base (PNB) was synthesised by an interfacial polymerisation technique using ammonium persulphate as the oxidant and toluene as the organic solvent, and was characterised by FTIR, SEM, BET, HRTEM and XRD techniques. The HRTEM and SEM results showed that the average size of the synthesised polyaniline nanofiber base (PNB) was about 60 nm. BET revealed the enhanced surface area of polyaniline nanofiber base (PNB), i.e., 48 m2g−1 in comparison to that of conventionally synthesised polyaniline, which is only 14 m2g−1. The electric conductivity of the polyaniline nanofiber base (PNB) was reportedly lesser (2.3 × 10−2 S/cm) than the salt form of the polyaniline, measured by four probe technique. The batch-wise adsorption of MB was conducted onto the polyaniline nanofiber base (PNB), and the influence of the preliminary dye concentration, duration of contact and polyaniline nanofiber base (PNB) dose, etc., were studied. The equilibrium values of these parameters are reported as 6 mg/L, 60 min and 2 g/L, respectively. The results revealed the 91% sorption of dye onto the polyaniline nanofiber base (PNB). The experimental data were best-fitted to Pseudo-second order (R2 = 0.99) and followed Freundlich isotherm model (R2 = 0.97). On desorption, about 86% of the absorbed dye was recovered and the regenerated adsorbent could be used efficiently for three more cycles.
Coverage Layout Design Rules and Insertion Utilities for CMP-Related Processes
Authors: Shauly Eitan N. , Rosenthal Sagee
Published: December 2020

The continuous scaling needed for higher density and better performance has introduced some new challenges to the planarity processes. This has resulted in new definitions of the layout coverage rules developed by the foundry and provided to the designers. In advanced technologies, the set of rules considers both the global and the local coverage of the front-end-of line (FEOL) dielectric layers, to the back-end-of-line (BEOL) Cu layers and Al layers, to support high-k/Metal Gate process integration. For advance technologies, a new set of rules for dummy feature insertion was developed by the integrated circuit (IC) manufacturers in order to fulfill coverage limits. New models and utilities for fill insertion were developed, taking into consideration the design coverage, thermal effects, sensitive signal line, critical analog and RF devices like inductors, and double patterning requirements, among others. To minimize proximity effects, cell insertion was also introduced. This review is based on published data from leading IC manufacturers with a careful integration of new experimental data accumulated by the authors. We aim to present a typical foundry perspective. The review provides a detailed description of the chemical mechanical polishing (CMP) process and the coverage dependency, followed by a comprehensive description of coverage rules needed for dielectric, poly, and Cu layers used in advanced technologies. Coverage rules verification data are then presented. RF-related aspects of some rules, like the size and the distance of dummy features from inductors, are discussed with additional design-for-manufacturing layout recommendations as developed by the industry.
DEA-Bootstrapping Analysis for Different Models of Spanish Port Governance
Authors: Parra Santiago Jose Ignacio , Camarero Orive Alberto , González Cancelas Nicoletta
Published: December 2020

The Spanish port system is subjected to a Data Envelopment Analysis (DEA)-Bootstrapping analysis of its operational and financial efficiency to be compared to two other scenarios. One of these presents a port cluster based on the grouping of ports because of their proximity, and the second scenario proposes a port cluster based on seafronts. The analysis is made up of a DEA-Bootstrapping of two inputs and two outputs for both the operational and financial efficiency analyses. The results of the DEA-Bootstrapping analysis show a series of results that favour these two scenarios against the present situation, as both the operational and financial efficiency are improved in relation to the current scenario or scenario 0.
A Bluetooth-Based Architecture for Contact Tracing in Healthcare Facilities
Authors: Di Marco Piergiuseppe , Park Pangun , Pratesi Marco , Santucci Fortunato
Published: December 2020

With the latest standard releases, Bluetooth technology is becoming more and more relevant for building and industrial automation. At the same time, Bluetooth is now becoming fundamental for contact tracing applications, to support monitoring and containment of the COVID-19 pandemic. Critical facilities such as nursing homes and hospitals have been severely exposed to the pandemic, but the currently available short-range wireless technology still faces the fundamental limits of proximity accuracy, battery lifetime, and privacy in those complex indoor environments. The aim of this paper is to investigate effective ways of building an architecture with heterogeneous devices to support contact tracing in critical scenarios such as healthcare facilities, while meeting the required level of accuracy and privacy. A framework based on standard Bluetooth mesh networking technology is proposed, and the research challenges are discussed.
A Review of Techniques for Implementing Elliptic Curve Point Multiplication on Hardware
Authors: Verri Lucca Arielle , Mariano Sborz Guilherme , Leithardt Valderi , Beko Marko , Albenes Zeferino Cesar , Parreira Wemerson
Published: December 2020

Cryptography is considered indispensable among security measures applied to data concerning insecure means of transmission. Among various existent algorithms on asymmetric cryptography, we may cite Elliptic Curve Cryptography (ECC), which has been widely used due to its security level and reduced key sizes. When compared to Rivest, Shamir and Adleman (RSA), for example, ECC can maintain security levels with a shorter key. Elliptic Curve Point Multiplication (ECPM) is the main function in ECC, and is the component with the highest hardware cost. Lots of ECPM implementations have been applied on hardware targeting the acceleration of its calculus. This article presents a systematic review of literature on ECPM implementations on both Field-Programmable Gate Array (FPGA) and Application-Specific Integrated Circuit (ASIC). The obtained results show which methods and technologies have been used to implement ECPM on hardware and present some findings of the choices available to the hardware designers.
Social Media Activities and Its Influence on Customer-Brand Relationship: An Empirical Study of Apparel Retailers’ Activity in India
Authors: Sharma Sukanya , Singh Saumya , Kujur Fedric , Das Gairik
Published: December 2020

In this digital era, the internet, and Social Media (SM) has had a radical impact on the shopping behavior of “costumers” The SM provides a platform where “costumers” are exposed to the best product with the best price along with reviews and opinions about the merchandise. So, we can turn our heads and look at a brand in a way as if the brand is speaking to us. This study was an attempt to explore the Social Media Marketing Activities (SMMA) that are being used for the marketing of fashionable products like apparel and to what level the SMMA activities of brands truly strengthen the relationship with customers and motivate purchase intention. Moreover, SMMA has a robust application in developing a marketing strategy for business. It has become a significant tool that collaborates with businesses and people. It is concluded that the “costumer”-brand relationship does have a positive and statistically significant impact on consumers’ purchase intention through SM.
Vulnerability of Subaerial and Submarine Landscapes: The Sand Falls in Cabo San Lucas, Mexico
Authors: Alcérreca-Huerta Juan Carlos , Montiel-Hernández Jorge R. , Callejas-Jiménez Mariana E. , Hernández-Avilés Dulce A. , Anfuso Giorgio , Silva Rodolfo
Published: December 2020

The coastal landscape of the south of the Baja California peninsula provides significant socio-economic benefits based on tourism. An analysis of coastal vulnerability was conducted for Cabo San Lucas, considering wave climate conditions, sediment characterization, beach profiles, and the historical occurrence of coastline changes, hurricanes, and El Niño Southern Oscillation (ENSO) events. The coastal scenery was also classified considering the landscape value of the environment from a touristic point of view, based on human and natural interactions on the landscape. Results show that the vulnerability increases close to the submarine sand falls, near intense urbanization, in resort areas, and at locations with narrow beach and dune widths. The degree of vulnerability along the coast alters abruptly, as urban and recreational sites alternate with natural sites. This coastline has seen exponential development since the 1980s, resulting in highly vulnerable areas with a low, and decreasing, touristic value, as the landscape has been changed into an urban settlement with limited natural attractions. Urban and recreational settlements threaten to cover dunes and reservoirs of natural sediments, increasingly affecting vulnerability in the area as well as the landscape values of many parts of the coast, including the submarine sand falls.
Forest and Landscape Restoration: A Review Emphasizing Principles, Concepts, and Practices
Authors: César Ricardo Gomes , Belei Loren , Badari Carolina Giudice , Viani Ricardo A. G. , Gutierrez Victoria , Chazdon Robin L. , Brancalion Pedro H. S. , Morsello Carla
Published: December 2020

Forest and Landscape Restoration (FLR) is considered worldwide as a powerful approach to recover ecological functionality and to improve human well-being in degraded and deforested landscapes. The literature produced by FLR programs could be a valuable tool to understand how they align with the existing principles of FLR. We conducted a systematic qualitative review to identify the main FLR concepts and definitions adopted in the literature from 1980 to 2017 and the underlying actions commonly suggested to enable FLR implementation. We identified three domains and 12 main associated principles—(i) Project management and governance domain contains five principles: (a) Landscape scale, (b) Prioritization, (c) Legal and normative compliance, (d) Participation, (e) Adaptive management; (ii) Human aspect domain with four principles: (a) Enhance livelihoods, (b) Inclusiveness and equity, (c) Economic diversification, (d) Capacity building; (iii) Ecological Aspects domain with three principles: (a) Biodiversity conservation, (b) Landscape heterogeneity and connectivity, (c) Provision of ecosystem goods and services. Our results showcase variations in FLR principles and how they are linked with practice, especially regarding the lack of social aspects in FLR projects. Finally, we provide a starting point for future tools aiming to improve guidance frameworks for FLR.
“Les copains *dit au revoir”: On Subject–Verb Agreement in L2 French and Cross-Linguistic Influence
Authors: Ågren Malin , Michot Marie-Eve , Granget Cyrille , Gerolimich Sonia , Hadermann Pascale , Stabarin Isabelle
Published: December 2020

This study focuses on the production of subject–verb (SV) agreement in number in L2 French and investigates the role of cross-linguistic influence (CLI) in this particular morphosyntactic domain. CLI is a well-known phenomenon in Second Language Acquisition (SLA) research but it has rarely been investigated systematically in relation to SV agreement in French. The participants of the study are 114 learners with Italian, German, Dutch and Swedish as L1. The source languages are all inflectional languages but they vary in terms of morphological richness in the verb paradigm, ranging from very poor (Swedish) to very rich (Italian). The participants performed an oral narrative task contrasting singular and plural contexts of SV agreement. Results indicate a significant difference between L1 groups in terms of correct SV agreement but they also show that the overall presence of rich verb morphology in the L1 does not, on its own, result in a more correct SV agreement. It is when comparing learners at two different proficiency levels that we observe differences in the rate of L2 development, which may be explained as an effect of CLI. Overall, results indicate a complex interplay of different factors, where the role of CLI must be further investigated in future studies in relation to L2 French.
Haploid Embryogenesis in Isolated Microspore Culture of Carrots (Daucus carota L.)
Authors: Shmykova Natalia , Domblides Elena , Vjurtts Tatiana , Domblides Arthur
Published: December 2020

The process of embryogenesis in isolated microspore culture was studied in eight carrot accessions of different origin. The ½NLN-13 medium supplemented with 0.2 mg/L 2,4D and 0.2mg/L kinetin was used to induce embryogenesis. The temperature treatment was performed at 5–6 °C for three days, followed by cultivation at 25 °C in darkness. As was shown, the first embryogenesis was only observed in microspores at the late vacuolated stage when the nucleus moved from the center to one pole following the long cell axis. Depending on the nucleus position, the microspore can divide into two equal or two different sized cells. Following divisions occurred either in one of these cells or in two. However, microspores that divided into two unequal cells were morphologically different form bi-cellular pollen grain. Embryogenic divisions in bi-cellular pollen grains were not observed. First divisions began by the third day of cultivation, and continued until the globular embryoid stage that was well-seen after the fourth week of cultivation. The already-formed embryoids can develop the secondary embryoids on their surface. Depending on the genotype, up to 1000 secondary embryoids can be produced from one embryoid in the liquid MSm medium supplemented with 0.1 mg/L of kinetin for regeneration. All carrot accessions studied were split into three groups: responsive genotypes, weakly responsive genotypes, and reluctant genotypes. The highest yield was 53 initial embryoids per a 6 cm diameter petri dish. Thus, the Nantskaya 4 cultivar totally produced 256 initial embryoids, out of which 94 developed into green plantlets and 162 into albino plantlets, whereas 97 initial embryoids with 45 albino plantlets formed from them were obtained from Chantenay cultivar.