bluuebunny/crossref_metadata_2025 huggingface dataset:
Antibiotic Resistance and Virulence Profiles of Gram-Negative Bacteria Isolated from Loggerhead Sea Turtles (Caretta caretta) of the Island of Maio, Cape Verde
Authors: Fernandes Matilde , Grilo Miguel L. , Carneiro Carla , Cunha Eva , Tavares Luís , Patino-Martinez Juan , Oliveira Manuela
Published: June 2021

Previous studies revealed high levels of antimicrobial resistance (AMR) in loggerhead sea turtles (Caretta caretta), describing this species as prime reservoir of antimicrobial-resistant bacteria. This study aimed to characterise, for the first time, the AMR and virulence profiles of Gram-negative bacteria isolated from 33 nesting loggerhead turtles of the island of Maio, Cape Verde. Cloacal, oral, and egg content swab samples (n = 99) were collected and analysed using conventional bacteriological techniques. Shewanella putrefaciens, Morganella morganii, and Vibrio alginolyticus were isolated from the samples under study. The isolates obtained from this loggerhead subpopulation (North-East Atlantic) revealed lower levels of AMR, compared with the results of studies performed in other subpopulations (e.g., Mediterranean). However, the detection of resistance to carbapenems and multiple antimicrobial resistance indices higher than 0.20, raises concern about the potential association of these animals to points of high antimicrobial exposure. Furthermore, virulence phenotypic characterisation revealed that the isolates presented complex virulence profiles, including the ability to produce biofilms. Finally, due to their pathogenic potential, and considering the evidence of illegal consumption of turtle-related products on the island of Maio, the identified bacteria may represent a significant threat to public health.
Correlating Structure and Morphology of Andiroba Leaf (Carapa guianensis Aubl.) by Microscopy and Fractal Theory Analyses
Authors: Matos Robert S. , Ţălu Ştefan , Mota Gunar V. S. , Pinto Erveton P. , Pires Marcelo A. , Abraçado Leida G. , Ferreira Nilson S.
Published: June 2021

The Amazon rainforest is considered a megadiverse biome, where several species of its rich flora are still unknown. The anatomy of their leaves usually identifies species. In this paper, we present a complete characterization of the leaf surface of Amazon Carapa guianensis Aubl. (Andiroba), using microscopy and fractal theory to be considered a possible tool for investigating different leaves spatial patterns, especially in species with similar leaf architecture. The SEM results revealed the cellular structures and other non-cellular structures that make up the leaf architecture, both for the abaxial and adaxial sides. The cells responsible for the plant photosynthesis process were observed in the internal structure of the leaf. The wettability analysis showed that the abaxial side is more hydrophobic, while the adaxial side is more hydrophilic. AFM images exposed the relevant details of the microstructure of the leaf abaxial side, such as stomata, pores, furrows, contour, particles, and rough profiles generated by topographic irregularities. The statistical parameters revealed that the scale size influences the topographic roughness, surface asymmetry, and shape of the height distribution, also observed by advanced parameters obtained according to the standard of the international organization for standardization (ISO). The fractal and advanced fractal parameters confirmed changes in spatial patterns as a function of scale size. The largest area exhibited greater spatial complexity, low dominant spatial frequencies, more excellent surface percolation, intermediate topographic homogeneity, and high uniformity of spatial patterns.
Energy-Efficient Load Balancing Algorithm for Workflow Scheduling in Cloud Data Centers Using Queuing and Thresholds
Authors: Malik Nimra , Sardaraz Muhammad , Tahir Muhammad , Shah Babar , Ali Gohar , Moreira Fernando
Published: June 2021

Cloud computing is a rapidly growing technology that has been implemented in various fields in recent years, such as business, research, industry, and computing. Cloud computing provides different services over the internet, thus eliminating the need for personalized hardware and other resources. Cloud computing environments face some challenges in terms of resource utilization, energy efficiency, heterogeneous resources, etc. Tasks scheduling and virtual machines (VMs) are used as consolidation techniques in order to tackle these issues. Tasks scheduling has been extensively studied in the literature. The problem has been studied with different parameters and objectives. In this article, we address the problem of energy consumption and efficient resource utilization in virtualized cloud data centers. The proposed algorithm is based on task classification and thresholds for efficient scheduling and better resource utilization. In the first phase, workflow tasks are pre-processed to avoid bottlenecks by placing tasks with more dependencies and long execution times in separate queues. In the next step, tasks are classified based on the intensities of the required resources. Finally, Particle Swarm Optimization (PSO) is used to select the best schedules. Experiments were performed to validate the proposed technique. Comparative results obtained on benchmark datasets are presented. The results show the effectiveness of the proposed algorithm over that of the other algorithms to which it was compared in terms of energy consumption, makespan, and load balancing.
A Linkage Representation of the Human Hand Skeletal System Using CT Hand Scan Images
Authors: Cao Ying , Yang Xiaopeng , Lim Zhichan , Jung Hayoung , Park Dougho , You Heecheon
Published: June 2021

The present study proposed a method for establishing a linkage representation of the human hand skeletal system. Hand skeletons of 15 male subjects were reconstructed from computed tomography (CT) scans in 10 different postures selected from a natural hand-closing motion. The wrist joint center was estimated as the intersection of the centerline of the metacarpal of the middle finger and the distal wrist crease. The remaining joint centers were kinematically estimated based on the relative motion between the distal bone segment and the proximal bone segment of a given joint. A hand linkage representation was then formed by connecting the derived joint centers. Regression models for predicting internal hand link lengths using hand length as the independent variable were established. In addition, regression models for predicting the joint center coordinates of the thumb carpometacarpal (CMC) and finger metacarpophalangeal (MCP) joints using hand length or hand breadth were established. Our models showed higher R2 values and lower maximum standard errors than the existing models. The findings of the present study can be applied to hand models for ergonomic design and biomechanical modeling.
Traffic Incident Detection Based on Dynamic Graph Embedding in Vehicular Edge Computing
Authors: Li Gen , Nguyen Tri-Hai , Jung Jason J.
Published: June 2021

With a large of time series dataset from the Internet of Things in Ambient Intelligence-enabled smart environments, many supervised learning-based anomaly detection methods have been investigated but ignored the correlation among the time series. To address this issue, we present a new idea for anomaly detection based on dynamic graph embedding, in which the dynamic graph comprises the multiple time series and their correlation in each time interval. We propose an entropy for measuring a graph’s information injunction with a correlation matrix to define similarity between graphs. A dynamic graph embedding model based on the graph similarity is proposed to cluster the graphs for anomaly detection. We implement the proposed model in vehicular edge computing for traffic incident detection. The experiments are carried out using traffic data produced by the Simulation of Urban Mobility framework. The experimental findings reveal that the proposed method achieves better results than the baselines by 14.5% and 18.1% on average with respect to F1-score and accuracy, respectively.
Optimum Shape Design of Geometrically Nonlinear Submerged Arches Using the Coral Reefs Optimization with Substrate Layers Algorithm
Authors: Pérez-Aracil Jorge , Camacho-Gómez Carlos , Hernández-Díaz Alejandro Mateo , Pereira Emiliano , Salcedo-Sanz Sancho
Published: June 2021

In this paper, a novel procedure for optimal design of geometrically nonlinear submerged arches is proposed. It is based on the Coral Reefs Optimization with Substrate Layers algorithm, a multi-method ensemble evolutionary approach for solving optimization problems. A novel arch shape parameterization is combined with the Coral Reefs Optimization with Substrate Layers algorithm. This new parameterization allows considering geometrical parameters in the design process, in addition to the reduction of the bending moment carried out by the classical design approach. The importance of considering the second-order behaviour of the arch structure is shown by different numerical experiments. Moreover, it is shown that the use of Coral Reefs Optimization with Substrate Layers algorithm leads to nearly-optimal solutions, ensuring the stability of the structure, reducing the maximum absolute bending moment value, and complying with the serviceability structural restrictions.
Gaussian Distribution Model for Detecting Dangerous Operating Conditions in Industrial Fish Farming
Authors: Silva Luís Cicero Bezerra da , Lopes Bruna Daniela Mendes , Blanquet Isidro Manuel , Marques Carlos Alberto Ferreira
Published: June 2021

The development of better monitoring technologies, the early combat of outbreaks, massive mortality, and promoting sustainability are challenges that the aquaculture industry still faces, and the development of solutions for this is an open problem. In this paper, focusing our attention on monitoring technologies as a promising solution to these issues, we report a Gaussian distribution model for detecting dangerous operating conditions in industrial fish farming. This approach allows us to indicate through a 2D image visualization when fish production is under normal, warning, or dangerous operating conditions. Furthermore, our proposed method has promising possibilities for application in the most varied fields of science, given that the mathematical procedure described allows us to discover the fundamental statistical structure of physical, chemical, and biological systems governed by laws of a probabilistic nature.
BioECG: Improving ECG Biometrics with Deep Learning and Enhanced Datasets
Authors: Tirado-Martin Paloma , Sanchez-Reillo Raul
Published: June 2021

Nowadays, Deep Learning tools have been widely applied in biometrics. Electrocardiogram (ECG) biometrics is not the exception. However, the algorithm performances rely heavily on a representative dataset for training. ECGs suffer constant temporal variations, and it is even more relevant to collect databases that can represent these conditions. Nonetheless, the restriction in database publications obstructs further research on this topic. This work was developed with the help of a database that represents potential scenarios in biometric recognition as data was acquired in different days, physical activities and positions. The classification was implemented with a Deep Learning network, BioECG, avoiding complex and time-consuming signal transformations. An exhaustive tuning was completed including variations in enrollment length, improving ECG verification for more complex and realistic biometric conditions. Finally, this work studied one-day and two-days enrollments and their effects. Two-days enrollments resulted in huge general improvements even when verification was accomplished with more unstable signals. EER was improved in 63% when including a change of position, up to almost 99% when visits were in a different day and up to 91% if the user experienced a heartbeat increase after exercise.
Instance-Based Learning Following Physician Reasoning for Assistance during Medical Consultation
Authors: Galnares Matías , Nesmachnow Sergio , Simini Franco
Published: June 2021

This article presents an automatic system for modeling clinical knowledge to follow a physician’s reasoning in medical consultation. Instance-based learning is applied to provide suggestions when recording electronic medical records. The system was validated on a real case study involving advanced medical students. The proposed system is accurate and efficient: 2.5× more efficient than a baseline empirical tool for suggestions and two orders of magnitude faster than a Bayesian learning method, when processing a testbed of 250 clinical case types. The research provides a framework to implement a real-time system to assist physicians during medical consultations.
Black Carbon Emissions from the Siberian Fires 2019: Modelling of the Atmospheric Transport and Possible Impact on the Radiation Balance in the Arctic Region
Authors: Kostrykin Sergey , Revokatova Anastasia , Chernenkov Alexey , Ginzburg Veronika , Polumieva Polina , Zelenova Maria
Published: June 2021

The work is devoted to the study of the climatic effects of black carbon (BC) transferred from forest fires to the Arctic zone. The HYSPLIT (The Hybrid Single-Particle Lagrangian Integrated Trajectory model) trajectory model was used to initially assess the potential for particle transport from fires. The results of the trajectory analysis of the 2019 fires showed that the probability of the transfer of particles to the Arctic ranges from 1% to 10%, and in some cases increases to 20%. Detailed studies of the possible influence of BC ejected as a result of fires became possible by using the climate model of the INMCM5 (Institute of Numerical Mathematics Climate Model). The results of the numerical experiments have shown that the maximum concentration of BC in the Arctic atmosphere is observed in July and August and is associated with emissions from fires. The deposition of BC in the Arctic increases by about 1.5–2 times in the same months, in comparison with simulation without forest fire emissions. This caused an average decrease in solar radiation forcing of 0.3–0.4 Wt/m2 and an increase in atmospheric radiation heating of up to 5–6 Wt/m2. To assess the radiation forcing from BC contaminated snow, we used the dependences of the change in the snow albedo on the snow depth, and the albedo of the underlying surface for a given amount of BC fallen on the snow. These dependences were constructed on the basis of the SNICAR (Snow, Ice, and Aerosol Radiative) model. According to our calculations, the direct radiative forcing from BC in the atmosphere with a clear sky is a maximum of 4–5 W/m2 in July and August.
Skull Vibration-Induced Nystagmus Test in a Human Model of Horizontal Canal Plugging
Authors: Dumas Georges , Fabre Christol , Charpiot Anne , Fath Lea , Chaney-Vuong Hella , Perrin Philippe , Schmerber Sébastien
Published: June 2021

Background/Aim: the aim of this study was to assess the skull vibration-induced nystagmus test (SVINT) results and vestibular residual function after horizontal semicircular canal (HSCC) plugging. Methods: In this retrospective chart review performed in a tertiary referral center, 11 patients who underwent unilateral horizontal semicircular canal plugging (uHSCCP) for disabling Menière’s disease (MD) were included. The skull vibration-induced nystagmus (SVIN) slow-phase velocity (SPV) was compared with the results of the caloric test (CaT), video head impulse test (VHIT), and cervical vestibular-evoked myogenic potentials (cVEMP) performed on the same day. Results: Overall, 10 patients had a strong SVIN beating toward the intact side (Horizontal SVIN-SPV: 8.8°/s ± 5.6°/s), 10 had a significant or severe ipsilateral CaT hypofunction, 10 had an ipsilateral horizontal VHIT gain impairment, and 3 had altered cVEMP on the operated side. Five had sensorineural hearing worsening. SVIN-positive results were correlated with CaT and horizontal VHIT (HVHIT) results (p < 0.05) but not with cVEMP. SVIN-SPV was correlated with CaT hypofunction in % (p < 0.05). Comparison of pre- and postoperative CaT % hypofunction showed a significant worsening (p = 0.028). Conclusion: SVINT results in a human model of horizontal canal plugging are well correlated with vestibular tests exploring horizontal canal function, but not with cVEMP. SVINT always showed a strong lesional nystagmus beating away from the lesion side. SVIN acts as a good marker of HSCC function. This surgical technique showed invasiveness regarding horizontal canal vestibular function.
A Decision Support Model for Measuring Technological Progress and Productivity Growth: The Case of Commercial Banks in Vietnam
Authors: Wang Chia-Nan , Nguyen Ngoc-Ai-Thy , Dang Thanh-Tuan , Trinh Thi-Thuy-Quynh
Published: June 2021

The interactive relationship between the banking system and enterprise makes up the role that affects a national economy. Significantly, the relationship between banking and technology has become tighter over the past few decades. An assessment of bank performance is critical for understanding their position and provides valuable information to practitioners. In this paper, we assess the performance of the top 18 commercial banks in Vietnam during 2015–2019. The assessment utilizes two data envelopment analysis (DEA) models while involving the banks’ performance in six dimensions, including assets, deposits, operating expenses, liabilities as inputs, while treating loans and net income as outputs. Using the Malmquist measurement, the total productivity growth indexes of the banks are obtained, which are decomposed into technical and technological evolutions. Window analysis is used to compute the efficiencies of the banks in every single year in 2015–2019. From the results of Malmquist, most banks are found to decrease their Malmquist productivity indexes from 2015 to 2019, wherein both of their technical and technological indexes declined. Window analysis indicates B6-SHBank, B1-Vietinbank, and B18-PetrolimexGroup as the most efficient banks during 2015–2019, and in the interim, B16-BaoVietBank, B11-NationalCitizen, and B13-VietnamMaritime ranked on the bottom line. The managerial implications of this research help to reflect the comprehensive insights of the top Vietnamese commercial bank performance and offer a strategic guideline for decision-makers toward sustainable development in the banking industry.
Self-Organized Structuring of Recurrent Neuronal Networks for Reliable Information Transmission
Authors: Miner Daniel , Wörgötter Florentin , Tetzlaff Christian , Fauth Michael
Published: June 2021

Our brains process information using a layered hierarchical network architecture, with abundant connections within each layer and sparse long-range connections between layers. As these long-range connections are mostly unchanged after development, each layer has to locally self-organize in response to new inputs to enable information routing between the sparse in- and output connections. Here we demonstrate that this can be achieved by a well-established model of cortical self-organization based on a well-orchestrated interplay between several plasticity processes. After this self-organization, stimuli conveyed by sparse inputs can be rapidly read out from a layer using only very few long-range connections. To achieve this information routing, the neurons that are stimulated form feed-forward projections into the unstimulated parts of the same layer and get more neurons to represent the stimulus. Hereby, the plasticity processes ensure that each neuron only receives projections from and responds to only one stimulus such that the network is partitioned into parts with different preferred stimuli. Along this line, we show that the relation between the network activity and connectivity self-organizes into a biologically plausible regime. Finally, we argue how the emerging connectivity may minimize the metabolic cost for maintaining a network structure that rapidly transmits stimulus information despite sparse input and output connectivity.
Influence of Varying Dietary ω6 to ω3 Fatty Acid Ratios on the Hepatic Transcriptome, and Association with Phenotypic Traits (Growth, Somatic Indices, and Tissue Lipid Composition), in Atlantic Salmon (Salmo salar)
Authors: Katan Tomer , Xue Xi , Caballero-Solares Albert , Taylor Richard G. , Parrish Christopher C. , Rise Matthew L.
Published: June 2021

The importance of dietary omega-6 to omega-3 (ω6:ω3) fatty acid (FA) ratios for human health has been extensively examined. However, its impact on fish physiology, and the underlying molecular mechanisms, are less well understood. This study investigated the influence of plant-based diets (12-week exposure) with varying ω6:ω3 (0.4–2.7) on the hepatic transcriptome of Atlantic salmon. Using 44 K microarray analysis, genes involved in immune and inflammatory response (lect2a, itgb5, helz2a, p43), lipid metabolism (helz2a), cell proliferation (htra1b), control of muscle and neuronal development (mef2d) and translation (eif2a, eif4b1, p43) were identified; these were differentially expressed between the two extreme ω6:ω3 dietary treatments (high ω6 vs. high ω3) at week 12. Eight out of 10 microarray-identified transcripts showed an agreement in the direction of expression fold-change between the microarray and qPCR studies. The PPARα activation-related transcript helz2a was confirmed by qPCR to be down-regulated by high ω6 diet compared with high ω3 diet. The transcript expression of two helz2 paralogues was positively correlated with ω3, and negatively with ω6 FA in both liver and muscle, thus indicating their potential as biomarkers of tissue ω6:ω3 variation. Mef2d expression in liver was suppressed in the high ω6 compared to the balanced diet (ω6:ω3 of 2.7 and 0.9, respectively) fed fish, and showed negative correlations with ω6:ω3 in both tissues. The hepatic expression of two lect2 paralogues was negatively correlated with viscerosomatic index, while htra1b correlated negatively with salmon weight gain and condition factor. Finally, p43 and eif2a were positively correlated with liver Σω3, while these transcripts and eif4b2 showed negative correlations with 18:2ω6 in the liver. This suggested that some aspects of protein synthesis were influenced by dietary ω6:ω3. In summary, this nutrigenomic study identified hepatic transcripts responsive to dietary variation in ω6:ω3, and relationships of transcript expression with tissue (liver, muscle) lipid composition and other phenotypic traits.
Intervention Effect of Non-Invasive Brain Stimulation on Cognitive Functions among People with Traumatic Brain Injury: A Systematic Review and Meta-Analysis
Authors: Ahorsu Daniel Kwasi , Adjaottor Emma Sethina , Lam Bess Yin Hung
Published: June 2021

This systematic review and meta-analysis aggregated and examined the treatment effect of non-invasive brain stimulation (NIBS) (transcranial direct current stimulation and transcranial magnetic stimulation) on cognitive functions in people with traumatic brain injury (TBI). A systematic search was conducted using databases (PubMed, Web of Science, Scopus, PsycINFO, EMBASE) for studies with keywords related to non-randomized and randomized control trials of NIBS among people with TBI. Nine out of 1790 NIBS studies with 197 TBI participants (103 active vs. 94 sham) that met the inclusion and exclusion criteria of the present study were finally selected for meta-analysis using Comprehensive Meta-Analysis software (version 3). Results showed that the overall effect of NIBS on cognition in people with TBI was moderately significant (g = 0.304, 95% CI = 0.055 to 0.553) with very low heterogeneity across studies (I2 = 0.000, Tau = 0.000). Specifically, significant and marginally significant moderate effect sizes were found for cognitive sub-domains including attention, memory, and executive function. The present findings suggest that NIBS is moderately effective in improving cognitive functions among people with TBI. In particular, NIBS may be used as an alternative and/or an adjunct treatment to the traditional approach in rehabilitating cognitive functions in people with TBI.
The Basic Psychological Needs in the Classroom Scale (BPN-CS)
Authors: Conesa Pedro Javier , Duñabeitia Jon Andoni
Published: June 2021

Recent experimental and theoretical studies have shown that the assessment of students’ satisfaction of their basic psychological needs (BPN) can be a powerful resource to identify different areas to improve their well-being, engagement, or learning achievement in school contexts. However, currently, the number of validated tools to assess the satisfaction of the BPN is very low, hindering informed decision-making strategies at the educational level. The aim of this study was to develop and validate the Basic Psychological Needs in the Classroom Scale (BPN-CS) instrument, adapting existing instruments and putting the new tool to the test. The BPN-CS was developed to measure the level of satisfaction of autonomy, competence, relatedness, and novelty in the classroom. We tested the scale on a representative sample of 1344 Spanish elementary school students from 8 to 13 years old. A series of analyses were run in order to test the internal consistency of the main factors as well as to prove the convergent and divergent validity of the instrument. In summary, the BPN-CS is presented as a reliable and valid self-report instrument to measure basic psychological needs in a classroom context with elementary school pupils in the Spanish context.
Mycobiome and Cancer: What Is the Evidence?
Authors: Vallianou Natalia , Kounatidis Dimitris , Christodoulatos Gerasimos Socrates , Panagopoulos Fotis , Karampela Irene , Dalamaga Maria
Published: June 2021

Background: To date, most researchhas focused on the bacterial composition of the human microbiota. In this review, we synopsize recent data on the human mycobiome and cancer, highlighting specific cancer types based on current available evidence, presenting interesting perspectives and limitations of studies and laboratory methodologies. Recent findings: Head and neck cancer carcinoma (HNCC), colorectal carcinoma (CRC) and pancreatic ductal adenocarcinoma (PDA) have been associated with dissimilarities in the composition of mycobiota between cancer cases and non-cancer participants. Overall, fungal dysbiosis with decreased fungal richness and diversity was common in cancer patients; however, a specific mycobiotic signature in HNSCC or CRC has not emerged. Different strains of Candida albicans have been identified among cases with HNCC, whilst Lichtheimia corymbifera, a member of the Mucoraceae family, has been shown to predominate among patients with oral tongue cancer. Virulence factors of Candida spp. include the formation of biofilm and filamentation, and the secretion of toxins and metabolites. CRC patients present a dysregulated ratio of Basidiomycota/Ascomycota. Abundance of Malassezia has been linked to the occurrence and progression of CRC and PDA, particularly in animal models of PDA. Interestingly, Schizophyllum, a component of the oral mycobiome, may exhibit anti-cancer potential. Conclusion: The human mycobiome, per se, along with its interactions with the human bacteriome and the host, may be implicated in the promotion and progression of carcinogenesis. Fungi may be used as diagnostic and prognostic/predictive tools or treatment targets for cancer in the coming years. More large-scale, prospective, multicentric and longitudinal studies with an integrative multi-omics methodology are required to examine the precise contribution of the mycobiome in the etiopathogenesis of cancer, and to delineate whether changes that occur in the mycobiome are causal or consequent of cancer.
A Systems Approach to Brain Tumor Treatment
Authors: Park James H. , de Lomana Adrian Lopez Garcia , Marzese Diego M. , Juarez Tiffany , Feroze Abdullah , Hothi Parvinder , Cobbs Charles , Patel Anoop P. , Kesari Santosh , Huang Sui , Baliga Nitin S.
Published: June 2021

Brain tumors are among the most lethal tumors. Glioblastoma, the most frequent primary brain tumor in adults, has a median survival time of approximately 15 months after diagnosis or a five-year survival rate of 10%; the recurrence rate is nearly 90%. Unfortunately, this prognosis has not improved for several decades. The lack of progress in the treatment of brain tumors has been attributed to their high rate of primary therapy resistance. Challenges such as pronounced inter-patient variability, intratumoral heterogeneity, and drug delivery across the blood–brain barrier hinder progress. A comprehensive, multiscale understanding of the disease, from the molecular to the whole tumor level, is needed to address the intratumor heterogeneity resulting from the coexistence of a diversity of neoplastic and non-neoplastic cell types in the tumor tissue. By contrast, inter-patient variability must be addressed by subtyping brain tumors to stratify patients and identify the best-matched drug(s) and therapies for a particular patient or cohort of patients. Accomplishing these diverse tasks will require a new framework, one involving a systems perspective in assessing the immense complexity of brain tumors. This would in turn entail a shift in how clinical medicine interfaces with the rapidly advancing high-throughput (HTP) technologies that have enabled the omics-scale profiling of molecular features of brain tumors from the single-cell to the tissue level. However, several gaps must be closed before such a framework can fulfill the promise of precision and personalized medicine for brain tumors. Ultimately, the goal is to integrate seamlessly multiscale systems analyses of patient tumors and clinical medicine. Accomplishing this goal would facilitate the rational design of therapeutic strategies matched to the characteristics of patients and their tumors. Here, we discuss some of the technologies, methodologies, and computational tools that will facilitate the realization of this vision to practice.
Interventions to Improve Sexual Health in Women Living with and Surviving Cancer: Review and Recommendations
Authors: Sopfe Jenna , Pettigrew Jessica , Afghahi Anosheh , Appiah Leslie C. , Coons Helen L.
Published: June 2021

Sexual health concerns, both physical and psychological, are common and represent an unmet need among women with and surviving cancer. Sexual challenges and conditions negatively impact body image, satisfaction, relationships, well-being, and quality of life, yet are widely reported to be under-recognized and undertreated. To guide clinical care and future research on sexual function in women with cancer, we performed a scoping review of interventions for sexual health concerns, including sexual function, body image, genitourinary symptoms, and hot flashes. Relevant publications between 2005 and 2020 were identified by searching PubMed with a combination of medical subject headings and keywords. Articles were included if they focused on the aforementioned topics, were primary research publications, and included female cancer survivors. Studies focusing on women receiving hormone therapy for breast cancer were also included. A total of 91 investigations conducted in the US and abroad were reviewed. Most commonly, interventions included a component of psychoeducation, although pharmacologic, exercise, and other approaches have been evaluated. Many studies have focused on survivors of breast or gynecologic cancer, among other sampling and methodological limitations. These limitations underscore the need for more work on this vital survivorship issue. Recommendations for future research in this area are also offered.
New Molecular Mechanisms and Clinical Impact of circRNAs in Human Cancer
Authors: Fontemaggi Giulia , Turco Chiara , Esposito Gabriella , Di Agostino Silvia
Published: June 2021

Next generation RNA sequencing techniques, implemented in the recent years, have allowed us to identify circular RNAs (circRNAs), covalently closed loop structures resulting in RNA molecules that are more stable than linear RNAs. This class of non-coding RNA is emerging to be involved in a variety of cell functions during development, differentiation, and in many diseases, including cancer. Among the described biological activities, circRNAs have been implicated in microRNA (miRNA) sequestration, modulation of protein–protein interactions and regulation of mRNA transcription. In human cancer, circRNAs were implicated in the control of oncogenic activities such as tumor cell proliferation, epithelial-mesenchymal transition, invasion, metastasis and chemoresistance. The most widely described mechanism of action of circRNAs is their ability to act as competing endogenous RNAs (ceRNAs) for miRNAs, lncRNAs and mRNAs, thus impacting along their axis, despite the fact that a variety of additional mechanisms of action are emerging, representing an open and expanding field of study. Furthermore, research is currently focusing on understanding the possible implications of circRNAs in diagnostics, prognosis prediction, effectiveness of therapies and, eventually, therapeutic intervention in human cancer. The purpose of this review is to discuss new knowledge on the mechanisms of circRNA action, beyond ceRNA, their impact on human cancer and to dissect their potential value as biomarkers and therapeutic targets.
Quadruplex Ligands in Cancer Therapy
Authors: Sanchez-Martin Victoria , Soriano Miguel , Garcia-Salcedo Jose Antonio
Published: June 2021

Nucleic acids can adopt alternative secondary conformations including four-stranded structures known as quadruplexes. To date, quadruplexes have been demonstrated to exist both in human chromatin DNA and RNA. In particular, quadruplexes are found in guanine-rich sequences constituting G-quadruplexes, and in cytosine-rich sequences forming i-Motifs as a counterpart. Quadruplexes are associated with key biological processes ranging from transcription and translation of several oncogenes and tumor suppressors to telomeres maintenance and genome instability. In this context, quadruplexes have prompted investigations on their possible role in cancer biology and the evaluation of small-molecule ligands as potential therapeutic agents. This review aims to provide an updated close-up view of the literature on quadruplex ligands in cancer therapy, by grouping together ligands for DNA and RNA G-quadruplexes and DNA i-Motifs.
Docetaxel-Mediated Uptake and Retention of Gold Nanoparticles in Tumor Cells and in Cancer-Associated Fibroblasts
Authors: Alhussan Abdulaziz , Bromma Kyle , Perez Monica Mesa , Beckham Wayne , Alexander Abraham S , Howard Perry L , Chithrani Devika B
Published: June 2021

Due to recent advances in nanotechnology, the application of nanoparticles (NPs) in cancer therapy has become a leading area in cancer research. Despite the importance of cancer-associated fibroblasts (CAFs) in creating an optimal niche for tumor cells to grow extensively, most of the work has been focused on tumor cells. Therefore, to effectively use NPs for therapeutic purposes, it is important to elucidate the extent of NP uptake and retention in tumor cells and CAFs. Three tumor cell lines and three CAF cell lines were studied using gold NPs (GNPs) as a model NP system. We found a seven-fold increase in NP uptake in CAFs compared to tumor cells. The retention percentage of NPs was three-fold higher in tumor cells as compared to CAFs. Furthermore, NP uptake and retention were significantly enhanced using a 50 nM concentration of docetaxel (DTX). NP uptake was improved by a factor of three in tumor cells and a factor of two in CAFs, while the retention of NPs was two-fold higher in tumor cells compared to CAFs, 72 h post-treatment with DTX. However, the quantity of NPs in CAFs was still three-fold higher compared to tumor cells. Our quantitative data were supported by qualitative imaging data. We believe that targeting of NPs in the presence of DTX is a very promising approach to accumulate a higher percentage of NPs and maintain a longer retention in both tumor cells and CAFs for achieving the full therapeutic potential of cancer nanotechnology.
Recent Progress and Challenges in the Diagnosis and Treatment of Gastrointestinal Stromal Tumors
Authors: Nishida Toshirou , Yoshinaga Shigetaka , Takahashi Tsuyoshi , Naito Yoichi
Published: June 2021

Gastrointestinal stromal tumors (GISTs) are the most frequent malignant mesenchymal tumors in the gastrointestinal tract. The clinical incidence of GISTs is estimated 10/million/year; however, the true incidence is complicated by frequent findings of tiny GISTs, of which the natural history is unknown. The initial work-up with endoscopy and endoscopic ultrasonography plays important roles in the differential diagnosis of GISTs. Surgery is the only modality for the permanent cure of localized GISTs. In terms of safety and prognostic outcomes, laparoscopy is similar to laparotomy for GIST treatment, including tumors larger than 5 cm. GIST progression is driven by mutations in KIT or PDGFRA or by other rare gene alterations, all of which are mutually exclusive. Tyrosine kinase inhibitors (TKIs) are the standard therapy for metastatic/recurrent GISTs. Molecular alterations are the most reliable biomarkers for TKIs and for other drugs, such as NTRK inhibitors. The pathological and genetic diagnosis prior to treatment has been challenging; however, a newly developed endoscopic device may be useful for diagnosis. In the era of precision medicine, cancer genome profiling by targeted gene panel analysis may enable potential targeted therapy even for GISTs without KIT or PDGFRA mutations.
Tumor Classification Should Be Based on Biology and Not Consensus: Re-Defining Tumors Based on Biology May Accelerate Progress, An Experience of Gastric Cancer
Authors: Waldum Helge
Published: June 2021

Malignant tumors are a consequence of genetic changes mainly occurring during cell division, sometimes with a congenital component. Therefore, accelerated cell divisions will necessarily predispose individuals, whether due to conditions of chronic cell destruction or hormonal overstimulation. It has been postulated that two genetic hits are necessary for the development of malignancy (Knudson). The correct view is probably that the number of genetic changes needed depends on the role the mutated genes have in proliferation and growth control. Hormones should accordingly be regarded as complete carcinogens. In this review based upon experience of gastric cancer where gastrin is central in the pathogenesis, it is argued that oxyntic atrophy—and not metaplasia as postulated by Correa—is the central precancer change in gastric mucosa. Moreover, the target cell of gastrin, the enterochromaffin-like (ECL) cell, is central in gastric carcinogenesis and most probably the cell of origin of gastric carcinomas of the diffuse type according to Lauren (a classification probable in accordance with biology). The distinction between adenocarcinomas and neuroendocrine carcinomas based upon a certain percentage of cancer cells with neuroendocrine differentiation is questioned. To make progress in the treatment of cancer, a correct classification system and knowledge of the pathogenesis are necessary.
Global Proteomic Profiling of Pediatric AML: A Pilot Study
Authors: Nguyen Nam H. K. , Wu Huiyun , Tan Haiyan , Peng Junmin , Rubnitz Jeffrey E. , Cao Xueyuan , Pounds Stanley , Lamba Jatinder K.
Published: June 2021

Acute Myeloid Leukemia (AML) is a heterogeneous disease with several recurrent cytogenetic abnormalities. Despite genomics and transcriptomics profiling efforts to understand AML’s heterogeneity, studies focused on the proteomic profiles associated with pediatric AML cytogenetic features remain limited. Furthermore, the majority of biological functions within cells are operated by proteins (i.e., enzymes) and most drugs target the proteome rather than the genome or transcriptome, thus, highlighting the significance of studying proteomics. Here, we present our results from a pilot study investigating global proteomic profiles of leukemic cells obtained at diagnosis from 16 pediatric AML patients using a robust TMT-LC/LC-MS/MS platform. The proteome profiles were compared among patients with or without core binding factor (CBF) translocation indicated by a t(8;21) or inv(16) cytogenetic abnormality, minimal residual disease status at the end of the first cycle of chemotherapy (MRD1), and in vitro chemosensitivity of leukemic cells to cytarabine (Ara-C LC50). Our results established proteomic differences between CBF and non-CBF AML subtypes, providing insights to AML subtypes physiology, and identified potential druggable proteome targets such as THY1 (CD90), NEBL, CTSF, COL2A1, CAT, MGLL (MAGL), MACROH2A2, CLIP2 (isoform 1 and 2), ANPEP (CD13), MMP14, and AK5.
Modern Diagnosis of Early Esophageal Cancer: From Blood Biomarkers to Advanced Endoscopy and Artificial Intelligence
Authors: Visaggi Pierfrancesco , Barberio Brigida , Ghisa Matteo , Ribolsi Mentore , Savarino Vincenzo , Fassan Matteo , Valmasoni Michele , Marchi Santino , de Bortoli Nicola , Savarino Edoardo
Published: June 2021

Esophageal cancer (EC) is the seventh most common cancer and the sixth cause of cancer death worldwide. Histologically, esophageal squamous cell carcinoma (ESCC) and esophageal adenocarcinoma (EAC) account for up to 90% and 20% of all ECs, respectively. Clinical symptoms such as dysphagia, odynophagia, and bolus impaction occur late in the natural history of the disease, and the diagnosis is often delayed. The prognosis of ESCC and EAC is poor in advanced stages, being survival rates less than 20% at five years. However, when the diagnosis is achieved early, curative treatment is possible, and survival exceeds 80%. For these reasons, mass screening strategies for EC are highly desirable, and several options are currently under investigation. Blood biomarkers offer an inexpensive, non-invasive screening strategy for cancers, and novel technologies have allowed the identification of candidate markers for EC. The esophagus is easily accessible via endoscopy, and endoscopic imaging represents the gold standard for cancer surveillance. However, lesion recognition during endoscopic procedures is hampered by interobserver variability. To fill this gap, artificial intelligence (AI) has recently been explored and provided encouraging results. In this review, we provide a summary of currently available options to achieve early diagnosis of EC, focusing on blood biomarkers, advanced endoscopy, and AI.
Targeting the Epidermal Growth Factor Receptor in EGFR-Mutated Lung Cancer: Current and Emerging Therapies
Authors: Khaddour Karam , Jonna Sushma , Deneka Alexander , Patel Jyoti D. , Abazeed Mohamed E. , Golemis Erica , Borghaei Hossein , Boumber Yanis
Published: June 2021

Epidermal growth factor receptor-targeting tyrosine kinase inhibitors (EGFR TKIs) are the standard of care for patients with EGFR-mutated metastatic lung cancer. While EGFR TKIs have initially high response rates, inherent and acquired resistance constitute a major challenge to the longitudinal treatment. Ongoing work is aimed at understanding the molecular basis of these resistance mechanisms, with exciting new studies evaluating novel agents and combination therapies to improve control of tumors with all forms of EGFR mutation. In this review, we first provide a discussion of EGFR-mutated lung cancer and the efficacy of available EGFR TKIs in the clinical setting against both common and rare EGFR mutations. Second, we discuss common resistance mechanisms that lead to therapy failure during treatment with EGFR TKIs. Third, we review novel approaches aimed at improving outcomes and overcoming resistance to EGFR TKIs. Finally, we highlight recent breakthroughs in the use of EGFR TKIs in non-metastatic EGFR-mutated lung cancer.
Palladium-Catalyzed Dehydrogenative C-2 Alkenylation of 5-Arylimidazoles and Related Azoles with Styrenes
Authors: Lessi Marco , Nania Attilio , Pittari Melania , Lodone Laura , Cuzzola Angela , Bellina Fabio
Published: June 2021

The construction of carbon–carbon bonds by direct involvement of two unactivated carbon–hydrogen bonds, without any directing group, ensures a high atom economy of the entire process. Here, we describe a simple protocol for the Pd(II)/Cu(II)-promoted intermolecular cross-dehydrogenative coupling (CDC) of 5-arylimidazoles, benzimidazoles, benzoxazole and 4,5-diphenylimidazole at their C-2 position with functionalized styrenes. This specific CDC, known as the Fujiwara–Moritani reaction or oxidative Heck coupling, also allowed the C-4 alkenylation of the imidazole nucleus when both 2 and 5 positions were occupied.
Regulation of the Actin Cytoskeleton via Rho GTPase Signalling in Dictyostelium and Mammalian Cells: A Parallel Slalom
Authors: Filić Vedrana , Mijanović Lucija , Putar Darija , Talajić Antea , Ćetković Helena , Weber Igor
Published: June 2021

Both Dictyostelium amoebae and mammalian cells are endowed with an elaborate actin cytoskeleton that enables them to perform a multitude of tasks essential for survival. Although these organisms diverged more than a billion years ago, their cells share the capability of chemotactic migration, large-scale endocytosis, binary division effected by actomyosin contraction, and various types of adhesions to other cells and to the extracellular environment. The composition and dynamics of the transient actin-based structures that are engaged in these processes are also astonishingly similar in these evolutionary distant organisms. The question arises whether this remarkable resemblance in the cellular motility hardware is accompanied by a similar correspondence in matching software, the signalling networks that govern the assembly of the actin cytoskeleton. Small GTPases from the Rho family play pivotal roles in the control of the actin cytoskeleton dynamics. Indicatively, Dictyostelium matches mammals in the number of these proteins. We give an overview of the Rho signalling pathways that regulate the actin dynamics in Dictyostelium and compare them with similar signalling networks in mammals. We also provide a phylogeny of Rho GTPases in Amoebozoa, which shows a variability of the Rho inventories across different clades found also in Metazoa.
Evaluation of SnS:Cu Thin Film Properties Obtained by USP Technique to Implement It as an Absorbent Layer in Solar Cells Using SCAPS
Authors: Rodríguez-Castro Sergio , Álvarez-Macías Carlos , Rivero Michel , Salgado-Conrado Lizbeth , Loera-Palomo Rodrigo , Reyes-Durán Bernardo , Narro-Ríos Jorge
Published: June 2021

Tin sulfide doped with copper (SnS:Cu) thin films were deposited on glass substrates by the ultrasonic spray pyrolysis (USP) technique at different concentration ratios (y = [Cu]/[Sn] = 0% (undoped), 2%, 5% and 10%). The aim of this work is to analyze the effect of copper on structural, morphological, and optoelectronic properties of SnS:Cu and discuss their possible application as an absorber layer in a solar cell structure proposed which is simulated using SCAPS software. X-ray diffraction (XRD) reveals an orthorhombic structure in the undoped sample and a cubic structure in doped ones. Raman spectroscopy suggests a possible unit cell size change due to the addition of Cu. Scanning electron microscopy (SEM) shows growth in grain density with an increasing y. Image analysis based on second-order features was used to discuss grain distribution. UV-VIS spectroscopy helps to find an increase of bandgap for the doped samples when copper concentration increases, going from 1.82 eV in the doped film y = 2% to 2.2 eV in the 10% doped samples. A value of 3.51 eV was found for the undoped sample y = 0%. A rise in both carrier concentration and mobility but a decrease in resistivity when y is increased was observed through the Hall–Van der Pauw technique. Simulations by SCAPS helped conclude that considering the material thickness, the SnS:Cu compound can be an alternative for implementation in the manufacturing of solar cells as an absorber layer since it is possible to obtain the optoelectronic properties necessary using the UPS economical technique.