bluuebunny/crossref_metadata_2025 huggingface dataset:
PreNNsem: A Heterogeneous Ensemble Learning Framework for Vulnerability Detection in Software
Authors: Wang Lu , Li Xin , Wang Ruiheng , Xin Yang , Gao Mingcheng , Chen Yulin
Published: November 2020

Automated vulnerability detection is one of the critical issues in the realm of software security. Existing solutions to this problem are mostly based on features that are defined by human experts and directly lead to missed potential vulnerability. Deep learning is an effective method for automating the extraction of vulnerability characteristics. Our paper proposes intelligent and automated vulnerability detection while using deep representation learning and heterogeneous ensemble learning. Firstly, we transform sample data from source code by removing segments that are unrelated to the vulnerability in order to reduce code analysis and improve detection efficiency in our experiments. Secondly, we represent the sample data as real vectors by pre-training on the corpus and maintaining its semantic information. Thirdly, the vectors are fed to a deep learning model to obtain the features of vulnerability. Lastly, we train a heterogeneous ensemble classifier. We analyze the effectiveness and resource consumption of different network models, pre-training methods, classifiers, and vulnerabilities separately in order to evaluate the detection method. We also compare our approach with some well-known vulnerability detection commercial tools and academic methods. The experimental results show that our proposed method provides improvements in false positive rate, false negative rate, precision, recall, and F1 score.
Daylighting Performance of Light Shelf Photovoltaics (LSPV) for Office Buildings in Hot Desert-Like Regions
Authors: Mesloub Abdelhakim , Ghosh Aritra
Published: November 2020

Visual comfort and energy consumption for lighting in large office buildings is an area of ongoing research, specifically focusing on the development of a daylight control technique (light shelf) combined with solar energy. This study aims to investigate the optimum performance of light shelf photovoltaics (LSPV) to improve daylight distribution and maximize energy savings for the hot desert-like climate of Saudi Arabia. A radiance simulation analysis was conducted in four phases to evaluate: appropriate height, reflector, internal curved light shelf (LS) angle, and the integrated photovoltaic (PV) with various coverages (25%, 50%, 75%, and entirely external LS). The results revealed that the optimum is achieved at a height of 1.3 m, the addition of a 30 cm reflector on the top of a window with an internal LS curved angle of 10° with 100% coverage (LSPV1, LSPV2). Such an arrangement reduces the energy consumption by more than 85%, eliminates uncomfortable glare, and provides uniform daylight except for during the winter season. Hence, the optimization of the LSPV system is considered to be an effective solution for sustainable buildings.
Block Compressive Sensing Single-View Video Reconstruction Using Joint Decoding Framework for Low Power Real Time Applications
Authors: Ebrahim Mansoor , Adil Syed Hasan , Raza Kamran , Ali Syed Saad Azhar
Published: November 2020

Several real-time visual monitoring applications such as surveillance, mental state monitoring, driver drowsiness and patient care, require equipping high-quality cameras with wireless sensors to form visual sensors and this creates an enormous amount of data that has to be managed and transmitted at the sensor node. Moreover, as the sensor nodes are battery-operated, power utilization is one of the key concerns that must be considered. One solution to this issue is to reduce the amount of data that has to be transmitted using specific compression techniques. The conventional compression standards are based on complex encoders (which require high processing power) and simple decoders and thus are not pertinent for battery-operated applications, i.e., VSN (primitive hardware). In contrast, compressive sensing (CS) a distributive source coding mechanism, has transformed the standard coding mechanism and is based on the idea of a simple encoder (i.e., transmitting fewer data-low processing requirements) and a complex decoder and is considered a better option for VSN applications. In this paper, a CS-based joint decoding (JD) framework using frame prediction (using keyframes) and residual reconstruction for single-view video is proposed. The idea is to exploit the redundancies present in the key and non-key frames to produce side information to refine the non-key frames’ quality. The proposed method consists of two main steps: frame prediction and residual reconstruction. The final reconstruction is performed by adding a residual frame with the predicted frame. The proposed scheme was validated on various arrangements. The association among correlated frames and compression performance is also analyzed. Various arrangements of the frames have been studied to select the one that produces better results. The comprehensive experimental analysis proves that the proposed JD method performs notably better than the independent block compressive sensing scheme at different subrates for various video sequences with low, moderate and high motion contents. Also, the proposed scheme outperforms the conventional CS video reconstruction schemes at lower subrates. Further, the proposed scheme was quantized and compared with conventional video codecs (DISCOVER, H-263, H264) at various bitrates to evaluate its efficiency (rate-distortion, encoding, decoding).
Analysis of Bidirectional ADR-Enabled Class B LoRaWAN Networks in Industrial Scenarios
Authors: Todoli-Ferrandis David , Silvestre-Blanes Javier , Sempere-Payá Víctor , Planes-Martínez Ana
Published: November 2020

Low-power wide-area network (LPWAN) technologies are becoming a widespread solution for wireless deployments in many applications, such as smart cities or Industry 4.0. However, there are still challenges to be addressed, such as energy consumption and robustness. To characterize and optimize these types of networks, the authors have developed an optimized use of the adaptative data rate (ADR) mechanism for uplink, proposed its use also for downlink based on the simulator ns-3, and then defined an industrial scenario to test and validate the proposed solution in terms of packet loss and energy.
Development of an AI Userbot for Engineering Design Education Using an Intent and Flow Combined Framework
Authors: Chien Yu-Hung , Yao Chun-Kai
Published: November 2020

As the inclusion of users in the design process receives greater attention, designers need to not only understand users, but also further cooperate with them. Therefore, engineering design education should also follow this trend, in order to enhance students’ ability to communicate and cooperate with users in the design practice. However, it is difficult to find users on teaching sites to cooperate with students because of time and budgetary constraints. With the development of artificial intelligence (AI) technology in recent years, chatbots may be the solution to finding specific users to participate in teaching. This study used Dialogflow and Google Assistant to build a system architecture, and applied methods of persona and semi-structured interviews to develop AI virtual product users. The system has a compound dialog mode (combining intent- and flow-based dialog modes), with which multiple chatbots can cooperate with students in the form of oral dialog. After four college students interacted with AI userbots, it was proven that this system can effectively participate in student design activities in the early stage of design. In the future, more AI userbots could be developed based on this system, according to different engineering design projects for engineering design teaching.
The Flexor Retinaculum Connects the Surrounding Structures into the Medial Ankle Complex
Authors: Szaro Paweł , Ghali Gataa Khaldun , Polaczek Mateusz , Ciszek Bogdan
Published: November 2020

This study aimed to prove the hypothesis that the medial structures of the ankle are interconnected through the flexor retinaculum’s projections. We conducted a retrospective re-evaluation of 132 MRI examinations of the ankle joint from 57 females and 75 males with an age range of 18–65 and a mean age of 35 years. The correlation between the presence of connections between the flexor retinaculum and the deltoid ligament, the spring ligament, the inferior extensor retinaculum, the paratenon, the fibulotalocalcaneal ligament, the fascia covering the abductor hallucis, and the flexor fibrous sheath were studied. The most common connections of the flexor retinaculum were to the deltoid ligament (97%), the fibulotalocalcaneal ligament (84.1%), and the flexor fibrous sheath (83.3%). Interconnection between the flexor retinaculum and the deltoid ligament correlated with the presence of connections between the flexor retinaculum and the inferior extensor retinaculum, the paratenon, and the spring ligament. Side difference was noticed in connections to the flexor fibrous sheath, the deltoid ligament, the fascia on the abductor hallucis, and the paratenon (p < 0.05). The flexor retinaculum formed a more complex anatomical unit with adjacent structures.
Fabrication and Microelectronic Properties of Hybrid Organic–Inorganic (poly(9,9, dioctylfluorene)/p-Si) Heterojunction for Electronic Applications
Authors: Tahir Muhammad , Ilyas Muhammad , Aziz Fakhra , R. Sarker Mahidur , Zeb Muhammad , Ibrahim Mohd Adib , Mohamed Ramizi
Published: November 2020

We report on the microelectronic characteristics of a novel hybrid heterojunction device based on a solution processable semiconducting polymer poly(9,9-dioctylfluorenyl-2,7-diyl)- co-(N,N0-diphenyl)-N,N′di(p-butyl-oxy-pheyl)-1,4-diamino-benzene) (PFB) and p-type silicon (p-Si). The PFB/p-Si heterojunction is prepared by spin coating 20 mg/mL solution of PFB in chloroform on the precleaned polished surface of p-Si substrate. Thermal evaporation of silver (Ag) electrode on top of PFB completes the fabrication of the Ag (90 nm)/PFB (180 nm)/p-Si heterojunction device. Morphology of PFB thin film is studied by using an atomic force microscope (AFM) and scanning electron microscope (SEM), which reveals grains are randomly distributed with slightly different grain sizes and shapes. It leads the film to form nonuniformity and some roughness in its topography that results in limiting the current (I) flow across the film/interface with p-Si. Ultraviolet (UV–vis) absorption and X-ray diffraction (XRD) spectra are measured for optical bandgap and crystal structure analysis of PFB. The key microelectronic parameters—rectification ratio (RR), ideality factor (n), barrier height (Φb), series resistance (Rs) and reverse saturation current (I0)—of the Ag/PFB/p-Si heterojunction are found from current–voltage (I–V) characteristics at room temperature (300 K) in dark conditions (≈0 lux). The Ag/PFB/p-Si heterojunction device exhibits improved microelectronic parameters when compared to those of earlier reported devices that were prepared in the same configuration. This improvement in the device parameters reveals enhancement in the microelectronic properties across the interface/depletion region of the Ag/PFB/p-Si device, which can be attributed to the remarkable electronic properties of PFB such as its relatively high hole mobility and better charge carriers’ conduction. The charge transport mechanisms through the device is also studied. Having the smaller values of I0 ≈ 7 × 10−10 A and n ≈ 3.23, as well as higher shunt resistance (Rsh) of 32 GΩ for the Ag/PFB/p-Si device suggest its potential for many electronic and optoelectronic applications.
Preclinical, Multi-Aspect Assessment of the Reliability of a Photoplethysmography-Based Telemonitoring System to Track Cardiovascular Status
Authors: Kulin Dániel , Antali Flóra , Kulin Sándor , Wafa Dina , Lucz Konrád István , Veres Dániel Sándor , Miklós Zsuzsanna
Published: November 2020

Telemonitoring systems equipped with photoplethysmography-based contour analysis of the digital arterial volume pulse (DVP) can be optimal tools for remote monitoring of cardiovascular patients; however, the method is known to be sensitive to errors. We aimed to show that DVP analysis is a reliable method to track cardiovascular status. We used our proprietary SCN4ALL telemedicine system and analyzed nine parameters derived from the DVP and its second derivative (SDDVP). First, we assessed the repeatability of system measurements by detecting artificial signals. Then test–retest reliability of human measurements was evaluated in healthy individuals under standardized conditions. The SCN4ALL system analyzed each parameter with high accuracy (coefficients of variation (CVs) < 1%). Test–retest reliability of most parameters (stiffness index, reflection index, left ventricular ejection time index, b/a, heart rate) was satisfactory (CVs < 10%) in healthy individuals. However, aging index and d/a ratio derived from the SDDVP were more variable. Photoplethysmography-based pulse contour analysis is a reliable method to monitor cardiovascular status if measurements are performed with a system of high accuracy. Our results highlighted that SDDVP parameters can be interpreted with limitations due to (patho)physiological variations of the DVP. We recommend the evaluation of these parameters only in measurements where all inflections of SDDVP are detected reliably.
Multi-Objective Electric Vehicles Scheduling Using Elitist Non-Dominated Sorting Genetic Algorithm
Authors: Morais Hugo , Sousa Tiago , Castro Rui , Vale Zita
Published: November 2020

The introduction of electric vehicles (EVs) will have an important impact on global power systems, in particular on distribution networks. Several approaches can be used to schedule the charge and discharge of EVs in coordination with the other distributed energy resources connected on the network operated by the distribution system operator (DSO). The aggregators, as virtual power plants (VPPs), can help the system operator in the management of these distributed resources taking into account the network characteristics. In the present work, an innovative hybrid methodology using deterministic and the elitist nondominated sorting genetic algorithm (NSGA-II) for the EV scheduling problem is proposed. The main goal is to test this method with two conflicting functions (cost and greenhouse gas (GHG) emissions minimization) and performing a comparison with a deterministic approach. The proposed method shows clear advantages in relation to the deterministic method, namely concerning the execution time (takes only 2% of the time) without impacting substantially the obtained results in both objectives (less than 5%).
The Periphery Is Beautiful: The Rise of the Portuguese Contemporary Art Market in the 21st Century
Authors: Duarte Adelaide
Published: November 2020

The aim of this article is to characterise the rise of the Portuguese contemporary art market since the beginning of the 21st century, within the broader context of the global contemporary art market. Against a theoretical backdrop of the globalisation of markets for contemporary art and the concept of the periphery, I will analyse Lisbon’s art scene as a local phenomenon that is looking for an international recognition. In doing so, I am focusing on two working hypotheses. The first relates to the efforts made by the gallery sector to raise the international profile of its artists, giving them sought-after widespread recognition, which encompasses a historical perspective on the situation and a prominent role for the younger generation of gallerists. The second intends to observe the role played by private collectors and their contributions towards boosting the art scene, assembling their contemporary art collections and making them available to the public. I conclude that this has led to an upsurge in the contemporary art market in connection with the growing number of validating structures, museums, and art centres, due mainly to the fact that the shortcomings of the public sector are being made up for by private initiatives.
Alternative Spaces & Artist Agency in the Art Market
Authors: Sooudi Olga Kanzaki
Published: November 2020

This article explores what alternative, or artist-led, spaces are in Mumbai today and their role within the city’s artworld. Drawing on ethnographic fieldwork in two alternative spaces, it argues that these are artist attempts to exercise agency in their work for an uncertain market context. In other words, these spaces are a strategy for artists to exercise control over their work in an uncertain art market, and a means to counterbalance their dependence on galleries in their careers. Furthermore, artists do so through collectivist practices. These spaces, I argue, challenge models of artistic and neoliberal work that privilege autonomy, independence, and isolation, as if artists were self-contained silos of productive creative activity and will. Artists instead, in these spaces, insist on the importance of social bonds and connection as a challenge to the instrumentalization and divisive nature of market-led demands on art practice and the model of the solo genius artist-producer. At the same time, their collective activities are oriented towards supporting artists’ individual future market success, suggesting that artist-led spaces are not separate from the art market, and should be considered within the same analytical frame.
Atmospheric Measurements with Unmanned Aerial Systems (UAS)
Authors: Guzman Marcelo I.
Published: November 2020

This Special Issue provides the first literature collection focused on the development and implementation of unmanned aircraft systems (UAS) and their integration with sensors for atmospheric measurements on Earth [...]
Source Apportionment of Aerosol at a Coastal Site and Relationships with Precipitation Chemistry: A Case Study over the Southeast United States
Authors: Corral Andrea F. , Dadashazar Hossein , Stahl Connor , Edwards Eva-Lou , Zuidema Paquita , Sorooshian Armin
Published: November 2020

This study focuses on the long-term aerosol and precipitation chemistry measurements from colocated monitoring sites in Southern Florida between 2013 and 2018. A positive matrix factorization (PMF) model identified six potential emission sources impacting the study area. The PMF model solution yielded the following source concentration profiles: (i) combustion; (ii) fresh sea salt; (iii) aged sea salt; (iv) secondary sulfate; (v) shipping emissions; and (vi) dust. Based on these results, concentration-weighted trajectory maps were developed to identify sources contributing to the PMF factors. Monthly mean precipitation pH values ranged from 4.98 to 5.58, being positively related to crustal species and negatively related to SO42−. Sea salt dominated wet deposition volume-weighted concentrations year-round without much variability in its mass fraction in contrast to stronger seasonal changes in PM2.5 composition where fresh sea salt was far less influential. The highest mean annual deposition fluxes were attributed to Cl−, NO3−, SO42−, and Na+ between April and October. Nitrate is strongly correlated with dust constituents (unlike sea salt) in precipitation samples, indicative of efficient partitioning to dust. Interrelationships between precipitation chemistry and aerosol species based on long-term surface data provide insight into aerosol–cloud–precipitation interactions.
Overlooked Diversity of Ultramicrobacterial Minorities at the Air-Sea Interface
Authors: Rahlff Janina , Giebel Helge-Ansgar , Stolle Christian , Wurl Oliver , Probst Alexander J. , Herlemann Daniel P. R.
Published: November 2020

Members of the Candidate phylum Patescibacteria, also called Candidate Phyla Radiation (CPR), are described as ultramicrobacteria with limited metabolic capacities. Wide diversity and relative abundances up to 80% in anaerobic habitats, e.g., in groundwater or sediments are characteristic for Candidatus Patescibacteria. However, only few studies exist for marine surface water. Here, we report the presence of 40 patescibacterial candidate clades at air-sea interfaces, including the upper water layer, floating foams and the sea-surface microlayer (SML), a < 1 mm layer at the boundary between ocean and atmosphere. Particle-associated (>3 µm) and free-living (3–0.2 µm) samples were obtained from the Jade Bay, North Sea, and 16S rRNA (gene) amplicons were analyzed. Although the abundance of Cand. Patescibacteria representatives were relatively low (<1.3%), members of Cand. Kaiserbacteria and Cand. Gracilibacteria were found in all samples. This suggests profound aerotolerant capacities of these phylogenetic lineages at the air-sea interface. The presence of ultramicrobacteria in the >3 µm fraction implies adhesion to bigger aggregates, potentially in anoxic niches, and a symbiotic lifestyle. Due to their small sizes, Cand. Patescibacteria likely become aerosolized to the atmosphere and dispersed to land with possible implications for affecting microbial communities and associated processes in these ecosystems.
Heat Generation in NMC622 Coin Cells during Electrochemical Cycling: Separation of Reversible and Irreversible Heat Effects
Authors: Zhao Wenjiao , Rohde Magnus , Mohsin Ijaz Ul , Ziebert Carlos , Seifert Hans J.
Published: November 2020

The thermal behavior of a commercial lithium-ion cell with the cathode material LiNi0.6Mn0.2Co0.2O2 (NMC622) was investigated during the cycling process using a Tian-Calvet calorimeter (C80, SETARAM Instrumentation, France). Various current flows of 42.5, 85, and 170 mA corresponding to charging rates of 0.5, 1, and 2 C, respectively, were applied in the measurements. The corresponding heat flow rates were measured by the C80 calorimeter at 30 °C. The reversible heat effect due to the reversible electrochemical reaction was quantified by the entropy change measurement. The irreversible heat effect due to internal resistances was determined by the electrochemical impedance spectroscopy (EIS) and the galvanostatic intermittent titration technique (GITT). The results were compared with the direct measurement of the heat effect by calorimetry during electrochemical cycling.
The Influence of Bottle Design on Perceived Quality of Beer: A Conjoint Analytic Study
Authors: Gislason Styrmir , Bruhn Simon , Christensen Alexander M. , Christensen Mikkel T. , Hansen Mette G. , Kha Thuy Truc , Giacalone Davide
Published: November 2020

Research on the influence of packaging on consumer perception of beer and other alcoholic beverages suggest an important role in capturing consumers’ attention and generating expectations on perceived product quality, and in particular that color, bottle shape, and label design are key aspects. There is, however, a paucity of research looking at interactions between different aspects of packaging design. This is a topical issue given an increasingly saturated market where especially craft breweries strive for differentiation and brand recognition. Situated within this context, the present research used a conjoint analytic approach to investigate the effect of packaging design on consumer perceived quality and liking for beers. Beer images were designed to systematically vary in four design factors—label color, label shape, label complexity, and bottle shape—and evaluated in an online survey with a representative sample of Danish beer drinkers. Two of the design factors—label color and bottle type—significantly affected consumers’ product evaluations, whereas the other two factors did not. Post-hoc analyses of the main effects indicated that the combination of a “Bomber” bottle shape and a warm color scheme in the label as the optimal combination of design factors to maximize consumer preferences. Preference for the Bomber bottle was linked to a perceived premiumness associated with a preference for curvatures (as opposed to angularity), whereas the preference for warm colors was tentatively explained as due to crossmodal correspondences generating favorable sensory expectations for this color scheme.
Development of Open-Field Behaviour in the Medaka, Oryzias latipes
Authors: Lucon-Xiccato Tyrone , Conti Francesca , Loosli Felix , Foulkes Nicholas S. , Bertolucci Cristiano
Published: November 2020

The use of juvenile and larval fish models has been growing in importance for several fields. Accordingly, the evaluation of behavioural tests that can be applied to larvae and juveniles is becoming increasingly important. We tested medaka at four different ages (1, 10, 30, and 120 dph) in the open field test, one of the most commonly used behavioural assays, to investigate its suitability for larvae and juveniles of this species. We also explored ontogenetic variation in behaviour during this test. On average, adult 120-day-old medaka showed higher locomotor activity in terms of distance moved compared with younger fish. Our analysis suggests that this effect was derived from both quantitative changes in locomotion related to the ontogenetic increase in fish size as well as qualitative changes in two aspects of locomotor behaviour. Specifically, time spent moving was similar between 1- and 10-day-old medaka, but progressively increased with development. In addition, we revealed that adult medaka showed constant levels of activity, whereas younger medaka progressively reduced their activity over the course of the entire experiment. The thigmotaxis behaviour typically used to assess anxiety in the open field test emerged at 120 days post-hatching, even though a difference in the temporal pattern of spatial preference emerged earlier, between 10 and 30 days post-hatching. In conclusion, some measures of the open field test such as total distance moved allow behavioural phenotyping in the medaka of all ages, although with some degree of quantitative and qualitative developmental variation. In contrast, immature medaka appear not to exhibit thigmotactic behaviour.
Lymphotropic Viruses: Chronic Inflammation and Induction of Cancers
Authors: Harhaj Edward W. , Shembade Noula
Published: November 2020

Inflammation induced by transcription factors, including Signal Transducers and Activators of Transcription (STATs) and NF-κB, in response to microbial pathogenic infections and ligand dependent receptors stimulation are critical for controlling infections. However, uncontrolled inflammation induced by these transcription factors could lead to immune dysfunction, persistent infection, inflammatory related diseases and the development of cancers. Although the induction of innate immunity and inflammation in response to viral infection is important to control virus replication, its effects can be modulated by lymphotropic viruses including human T-cell leukemia virus type 1 (HTLV-1), Κaposi’s sarcoma herpesvirus (KSHV), and Epstein Barr virus (EBV) during de novo infection as well as latent infection. These lymphotropic viruses persistently activate JAK-STAT and NF-κB pathways. Long-term STAT and NF-κB activation by these viruses leads to the induction of chronic inflammation, which can support the persistence of these viruses and promote virus-mediated cancers. Here, we review how HTLV-1, KSHV and EBV hijack the function of host cell surface molecules (CSMs), which are involved in the regulation of chronic inflammation, innate and adaptive immune responses, cell death and the restoration of tissue homeostasis. Thus, better understanding of CSMs-mediated chronic activation of STATs and NF-κB pathways in lymphotropic virus-infected cells may pave the way for therapeutic intervention in malignancies caused by lymphotropic viruses.
Natural Products Attenuating Biosynthesis, Processing, and Activity of Ras Oncoproteins: State of the Art and Future Perspectives
Authors: Tisi Renata , Gaponenko Vadim , Vanoni Marco , Sacco Elena
Published: November 2020

RAS genes encode signaling proteins, which, in mammalian cells, act as molecular switches regulating critical cellular processes as proliferation, growth, differentiation, survival, motility, and metabolism in response to specific stimuli. Deregulation of Ras functions has a high impact on human health: gain-of-function point mutations in RAS genes are found in some developmental disorders and thirty percent of all human cancers, including the deadliest. For this reason, the pathogenic Ras variants represent important clinical targets against which to develop novel, effective, and possibly selective pharmacological inhibitors. Natural products represent a virtually unlimited resource of structurally different compounds from which one could draw on for this purpose, given the improvements in isolation and screening of active molecules from complex sources. After a summary of Ras proteins molecular and regulatory features and Ras-dependent pathways relevant for drug development, we point out the most promising inhibitory approaches, the known druggable sites of wild-type and oncogenic Ras mutants, and describe the known natural compounds capable of attenuating Ras signaling. Finally, we highlight critical issues and perspectives for the future selection of potential Ras inhibitors from natural sources.
Exosome-Mediated Differentiation of Mouse Embryonic Fibroblasts and Exocrine Cells into β-Like Cells and the Identification of Key miRNAs for Differentiation
Authors: Mandal Paulami , De Debojyoti , Im Dong Uk , Um Sung Hee , Kim Kyeong Kyu
Published: November 2020

Diabetes is a concerning health malady worldwide. Islet or pancreas transplantation is the only long-term treatment available; however, the scarcity of transplantable tissues hampers this approach. Therefore, new cell sources and differentiation approaches are required. Apart from the genetic- and small molecule-based approaches, exosomes could induce cellular differentiation by means of their cargo, including miRNA. We developed a chemical-based protocol to differentiate mouse embryonic fibroblasts (MEFs) into β-like cells and employed mouse insulinoma (MIN6)-derived exosomes in the presence or absence of specific small molecules to encourage their differentiation into β-like cells. The differentiated β-like cells were functional and expressed pancreatic genes such as Pdx1, Nkx6.1, and insulin 1 and 2. We found that the exosome plus small molecule combination differentiated the MEFs most efficiently. Using miRNA-sequencing, we identified miR-127 and miR-709, and found that individually and in combination, the miRNAs differentiated MEFs into β-like cells similar to the exosome treatment. We also confirmed that exocrine cells can be differentiated into β-like cells by exosomes and the exosome-identified miRNAs. A new differentiation approach based on the use of exosome-identified miRNAs could help people afflicted with diabetes
Gut Microbiota and Colorectal Cancer Development: A Closer Look to the Adenoma-Carcinoma Sequence
Authors: Vacante Marco , Ciuni Roberto , Basile Francesco , Biondi Antonio
Published: November 2020

There is wide evidence that CRC could be prevented by regular physical activity, keeping a healthy body weight, and following a healthy and balanced diet. Many sporadic CRCs develop via the traditional adenoma-carcinoma pathway, starting as premalignant lesions represented by conventional, tubular or tubulovillous adenomas. The gut bacteria play a crucial role in regulating the host metabolism and also contribute to preserve intestinal barrier function and an effective immune response against pathogen colonization. The microbiota composition is different among people, and is conditioned by many environmental factors, such as diet, chemical exposure, and the use of antibiotic or other medication. The gut microbiota could be directly involved in the development of colorectal adenomas and the subsequent progression to CRC. Specific gut bacteria, such as Fusobacterium nucleatum, Escherichia coli, and enterotoxigenic Bacteroides fragilis, could be involved in colorectal carcinogenesis. Potential mechanisms of CRC progression may include DNA damage, promotion of chronic inflammation, and release of bioactive carcinogenic metabolites. The aim of this review was to summarize the current knowledge on the role of the gut microbiota in the development of CRC, and discuss major mechanisms of microbiota-related progression of the adenoma-carcinoma sequence.
Percentiles and Reference Values for Accelerometric Gait Assessment in Women Aged 50–80 Years
Authors: Leirós-Rodríguez Raquel , García-Liñeira Jesús , Soto-Rodríguez Anxela , García-Soidán Jose L.
Published: November 2020

Background: The identification of factors that alter postural stability is fundamental in the design of interventions to maintain independence and mobility. This is especially important for women because of their longer life expectancy and higher incidence of falls than in men. We constructed the percentile box charts and determined the values of reference for the accelerometric assessment of the gait in women. Methods: We used a cross-sectional study with 1096 healthy adult women, who were asked to walk a distance of 20 m three times. Results: In all of the variables, a reduction in the magnitude of accelerations was detected as the age of the group advanced. The box charts show the amplitude of the interquartile ranges, which increases as the age of the participants advances. In addition, the interquartile ranges were greater in the variables that refer to the maximum values of the accelerations. Conclusions: The values obtained can be used to assess changes in gait due to aging, trauma and orthopaedic alterations that may alter postural stability and neurodegenerative processes that increase the risk of falling.
Cannabis: Neuropsychiatry and Its Effects on Brain and Behavior
Authors: Colizzi Marco , Bhattacharyya Sagnik
Published: November 2020

Possibly orally transmitted from before circa 2000 B [...]
New Insights into H2S Adsorption on Graphene and Graphene-Like Structures: A Comparative DFT Study
Authors: Salmankhani Azam , Karami Zohre , Mashhadzadeh Amin Hamed , Ganjali Mohammad Reza , Vatanpour Vahid , Esmaeili Amin , Habibzadeh Sajjad , Saeb Mohammad Reza , Fierro Vanessa , Celzard Alain
Published: November 2020

The efficient removal of pollutants from different environments has been one of the great challenges for scientists in recent years. However, the understanding of the mechanisms underlying this phenomenon is still the subject of passionate debates, mainly due to the lack of experimental tools capable of detecting events at the atomic scale. Herein, a comparative theoretical study was carried out to capture the adsorption of H2S on metal oxide surfaces such as zinc oxide (ZnO) and beryllium oxide (BeO), as well as graphene and Ni-decorated graphene. A simulation based on density-functional theory (DFT) was carried out by adopting General Gradient Approximation (GGA) under the Perdew–Burke–Ernzerhof (PBE) function. The calculations quantified H2S adsorption on the considered metal oxide sheets as well as on the non-decorated graphene having a physical nature. In contrast, H2S adsorbed on Ni-decorated graphene sheet gave an adsorption energy of −1.64 eV due to the interaction of S and Ni atoms through the formation of a covalent bond, proof of chemisorption. It seems that the graphene sheet decorated with Ni atoms is a more suitable adsorbent for H2S molecules than BeO, ZnO, or non-decorated graphene, providing a theoretical basis for future studies.
Novel DNMT3A Germline Variant in a Patient with Multiple Paragangliomas and Papillary Thyroid Carcinoma
Authors: Mellid Sara , Coloma Javier , Calsina Bruna , Monteagudo María , Roldán-Romero Juan M. , Santos María , Leandro-García Luis J. , Lanillos Javier , Martínez-Montes Ángel M. , Rodríguez-Antona Cristina , Montero-Conde Cristina , Martínez-López Joaquín , Ayala Rosa , Matias-Guiu Xavier , Robledo Mercedes , Cascón Alberto
Published: November 2020

Over the past few years, next generation technologies have been applied to unravel the genetics of rare inherited diseases, facilitating the discovery of new susceptibility genes. We recently found germline DNMT3A gain-of-function variants in two patients with head and neck paragangliomas causing a characteristic hypermethylated DNA profile. Here, whole-exome sequencing identifies a novel germline DNMT3A variant (p.Gly332Arg) in a patient with bilateral carotid paragangliomas, papillary thyroid carcinoma and idiopathic intellectual disability. The variant, located in the Pro-Trp-Trp-Pro (PWWP) domain of the protein involved in chromatin targeting, affects a residue mutated in papillary thyroid tumors and located between the two residues found mutated in microcephalic dwarfism patients. Structural modelling of the variant in the DNMT3A PWWP domain predicts that the interaction with H3K36me3 will be altered. An increased methylation of DNMT3A target genes, compatible with a gain-of-function effect of the alteration, was observed in saliva DNA from the proband and in one independent acute myeloid leukemia sample carrying the same p.Gly332Arg variant. Although further studies are needed to support a causal role of DNMT3A variants in paraganglioma, the description of a new DNMT3A alteration in a patient with multiple clinical features suggests a heterogeneous phenotypic spectrum related to DNMT3A germline variants.
Immunophenotypic Landscape and Prognosis of Diffuse Large B-Cell Lymphoma with MYC/BCL2 Double Expression: An Analysis of A Prospectively Immunoprofiled Cohort
Authors: Han Bogyeong , Kim Sehui , Koh Jiwon , Yim Jeemin , Lee Cheol , Heo Dae Seog , Kim Tae Min , Paik Jin Ho , Jeon Yoon Kyung
Published: November 2020

Diffuse large B-cell lymphoma (DLBCL) patients with MYC/BCL2 double expression (DE) show poor prognosis and their clinical outcomes after R-CHOP therapy vary immensely. We investigated the prognostic value of DE in aggressive B-cell lymphoma patients (n = 461), including those with DLBCL (n = 417) and high-grade B-cell lymphoma (HGBL; n = 44), in a prospectively immunoprofiled cohort. DE was observed in 27.8% of DLBCLs and 43.2% of HGBLs (p = 0.058). DE-DLBCL patients were older (p = 0.040) and more frequently exhibited elevated serum LDH levels (p = 0.002), higher international prognostic index (IPI; p = 0.042), non-germinal-center B-cell phenotype (p < 0.001), and poor response to therapy (p = 0.042) compared to non-DE-DLBCL patients. In R-CHOP-treated DLBCL patients, DE status predicted poor PFS and OS independently of IPI (p < 0.001 for both). Additionally, in DE-DLBCL patients, older age (>60 years; p = 0.017), involvement of ≥2 extranodal sites (p = 0.021), bone marrow involvement (p = 0.001), high IPI (p = 0.017), CD10 expression (p = 0.006), poor performance status (p = 0.028), and elevated LDH levels (p < 0.001) were significantly associated with poor OS. Notably, DE-DLBCL patients with normal LDH levels exhibited similar PFS and OS to those of patients with non-DE-DLBCL. Our findings suggest that MYC/BCL2 DE predicts poor prognosis in DLBCL. Risk stratification of DE-DLBCL patients based on LDH levels may guide clinical decision-making for DE-DLBCL patients.
Gap Junctions and Connexins in Cancer Formation, Progression, and Therapy
Authors: Ruch Randall
Published: November 2020

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IDH Signalling Pathway in Cholangiocarcinoma: From Biological Rationale to Therapeutic Targeting
Authors: Salati Massimiliano , Caputo Francesco , Baldessari Cinzia , Galassi Barbara , Grossi Francesco , Dominici Massimo , Ghidini Michele
Published: November 2020

Biliary tract cancers are anatomically distinct and genetically diverse tumors, evenly characterized by poor response to standard treatments and a bleak outlook. The advent of comprehensive genomic profiling using next-generation sequencing has unveiled a plethora of potentially actionable aberrations, changing the view of biliary tract cancers from an “orphan” to a “target-rich” disease. Recently, mutations in isocitrate dehydrogenase genes (IDH1/2) and fusions of the fibroblast growth factor receptor have emerged as the most amenable to molecularly targeted inhibition, with several compounds actively investigated in advanced-phase clinical trials. Specifically, the IDH1 inhibitor ivosidenib has been the first targeted agent to show a survival benefit in a randomized phase III trial of cholangiocarcinoma patients harboring IDH1 mutations. In this review article, we will focus on the IDH1/IDH2 pathway, discussing the preclinical rationale of its targeting as well as the promises and challenges of the clinical development of IDH inhibitors in biliary tract cancers.
Synthetic MIR143-3p Suppresses Cell Growth in Rhabdomyosarcoma Cells by Interrupting RAS Pathways Including PAX3–FOXO1
Authors: Sugito Nobuhiko , Heishima Kazuki , Ito Yuko , Akao Yukihiro
Published: November 2020

Rhabdomyosarcoma (RMS) is a soft tissue sarcoma most frequently found in children. In RMS, there are two major subtypes, embryonal RMS (ERMS) and alveolar RMS (ARMS). ARMS has the worse prognosis of the two owing to the formation of the chimeric PAX3–FOXO1 gene. A novel therapeutic method is required for treating ARMS. In our previous study, we found that the ectopic expression of chemically modified MIR143-3p#12 (CM-MIR143#12), which is RNase-resistant and shows the highest anti-proliferation activity among the synthesized MIR143 derivatives that were tested, induces significant cell growth suppression by targeting KRAS, AKT, and ERK in colorectal cancer cells. The expression of MIR143-3p in RMS was dramatically downregulated compared with that of normal tissue. Ectopic expression of CM-MIR143#12 in RMS cells resulted in a significant growth inhibitory effect through the induction of apoptosis and autophagy. Interestingly, we found that CM-MIR143#12 also silenced the expression of chimeric PAX3–FOXO1 directly and, using siR-KRAS or siR-AKT, that KRAS networks regulated the expression of PAX3–FOXO1 in ARMS cells. In ERMS harboring NRAS mutation, CM-MIR143#12 silenced mutated NRAS. These findings indicate that CM-MIR143#12 efficiently perturbed the RAS signaling pathway, including the ARMS-specific KRAS/PAX3–FOXO1 networks.
Novel FGFR4-Targeting Single-Domain Antibodies for Multiple Targeted Therapies against Rhabdomyosarcoma
Authors: Alijaj Nagjie , Moutel Sandrine , Gouveia Zelia L. , Gray Maxim , Roveri Maurizio , Dzhumashev Dzhangar , Weber Florian , Meier Gianmarco , Luciani Paola , Rössler Jochen K. , Schäfer Beat W. , Perez Franck , Bernasconi Michele
Published: November 2020

The fibroblast growth factor receptor 4 (FGFR4) is overexpressed in rhabdomyosarcoma (RMS) and represents a promising target for treatments based on specific and efficient antibodies. Despite progress, there is an urgent need for targeted treatment options to improve survival rates, and to limit long-term side effects. From phage display libraries we selected FGFR4-specific single-domain antibodies (sdAb) binding to recombinant FGFR4 and validated them by flow cytometry, surface plasmon resonance, and fluorescence microscopy. The specificity of the selected sdAb was verified on FGFR4-wild type and FGFR4-knock out cells. FGFR4-sdAb were used to decorate vincristine-loaded liposomes and to generate chimeric antigen receptor (CAR) T cells. First, incubation of RMS cells with FGFR4-sdAb revealed that FGFR4-sdAb can block FGF19-FGFR4 signaling via the MAPK pathway and could therefore serve as therapeutics for FGFR4-dependent cancers. Second, FGFR4-targeted vincristine-loaded liposomes bound specifically to RMS cells and were internalized by the receptor, demonstrating the potential for active drug delivery to the tumor. Third, FGFR4-CAR T cells, generated with one sdAb candidate, demonstrated strong and specific cytotoxicity against FGFR4 expressing RMS cells. We selected novel FGFR4-sdAb with high specificity and nano- to picomolar affinities for FGFR4 which have the potential to enable multiple FGFR4-targeted cancer therapy approaches.
Therapeutic Strategies for the Management of Hormone Receptor-Positive, Human Epidermal Growth Factor Receptor 2-Positive (HR+/HER2+) Breast Cancer: A Review of the Current Literature
Authors: Thanopoulou Eirini , Khader Leila , Caira Morena , Wardley Andrew , Ettl Johannes , Miglietta Federica , Neven Patrick , Guarneri Valentina
Published: November 2020

Enormous advances have been made in the understanding and treatment of human epidermal growth factor receptor 2-positive breast cancer (HER2+ BC) in the last 30 years that have resulted in survival gains for affected patients. A growing body of evidence suggests that hormone receptor-positive (HR+)/HER2+ BC and HR-negative (HR−)/HER2+ BC are biologically different, with complex molecular bidirectional crosstalk between the estrogen receptor and HER2 pathway potentially affecting sensitivity to both HER2-targeted and endocrine therapy in patients with HR+/HER2+ BC. Subgroup analyses from trials enrolling patients with HER2+ BC and the results of clinical trials specifically designed to evaluate therapy in patients with HR+/HER2+ BC are helping to guide treatment decisions. In this context, encouraging results with strategies aimed at delaying or reversing drug resistance, including extended adjuvant therapy and the addition of drugs targeting alternative pathways, such as cyclin-dependent kinase (CDK) 4 and 6 inhibitors, have recently emerged. We have reached the point where tailoring the treatment according to risk and biology has become the paradigm in early BC. However, further clinical trials are needed that integrate translational research principles and identify and consider specific patient subgroups and biomarkers.
Impact of Coordination Features of Co(II)-Glycine Complex on the Surface Sites of Co/SiO2 for Fischer–Tropsch Synthesis
Authors: Hao Qing-Qing , Hu Min , Xie Zhi-Xia , Ma Xiaoxun , Wang Wei , Ren Hua-Ping
Published: November 2020

To investigate the effect of coordination features of Co(II)-glycine complex on the performance of Co/SiO2 for Fischer–Tropsch (FT) synthesis, Co(II)-glycine complex precursors were prepared by the conventional method, i.e., simply adding glycine to the solution of Co nitrate and novel route, i.e., reaction of glycine with cobalt hydroxide. The SiO2-supported Co catalysts were prepared by using the different Co(II)-glycine complexes. It is found that glycine is an effective chelating agent for improving the dispersion of Co and the mass-specific activity in FT synthesis when the molar ratio of glycine/Co2+ = 3, which is independent to the preparation method in this study. Significantly, the surface Co properties were significantly influenced by the coordination features of the Co2+ and the molar ratio of glycine to Co2+ in the Co(II)-glycine complex. Specifically, the Co(3gly)/SiO2 catalyst prepared by the novel route exhibits smaller and homogenous Co nanoparticles, which result in improved stability compared to Co-3gly/SiO2 prepared by the conventional method. Thus, the newly developed method is more controllable and promising for the synthesis of Co-based catalysts for FT synthesis.
Organocatalyzed Michael Addition to Nitroalkenes via Masked Acetaldehyde
Authors: Giorgianni Giuliana , Nori Valeria , Baschieri Andrea , Palombi Laura , Carlone Armando
Published: November 2020

A novel and safe reaction protocol for the enantioselective enamine-catalysed addition of acetaldehyde to nitroalkenes is presented; this protocol makes use of a safe acetaldehyde precursor to access important intermediates to Active Pharmaceutical Ingredients (APIs), and allows the use of fewer equivalents of acetaldehyde and lower catalyst loadings. The reaction developed proved to be suitable to be performed on gram-scale and to produce key intermediates for the synthesis of pharmacologically active compounds such as pregabalin.