bluuebunny/crossref_metadata_2025 huggingface dataset:
How to Obtain an Orthodontic Virtual Patient through Superimposition of Three-Dimensional Data: A Systematic Review
Authors: Marradi Francesca , Staderini Edoardo , Zimbalatti Maria Antonietta , Rossi Andrea , Grippaudo Cristina , Gallenzi Patrizia
Published: August 2020

Background: This systematic review summarizes the current knowledge on the superimposition of three-dimensional (3D) diagnostic records to realize an orthodontic virtual patient. The aim of this study is to analyze the accuracy of the state-of-the-art digital workflow. Methods: The research was carried out by an electronic and manual query effectuated from ISS (Istituto Superiore di Sanità in Rome) on three different databases (MEDLINE, Cochrane Library and ISI WEB OF SCIENCE) up to 31st January 2020. The search focused on studies that superimposed at least two different 3D records to build up a 3D virtual patient—information about the devices used to acquire 3D data, the software used to match data and the superimposition method applied have been summarized. Results: 1374 titles were retrieved from the electronic search. After title-abstract screening, 65 studies were selected. After full-text analysis, 21 studies were included in the review. Different 3D datasets were used: facial skeleton (FS), extraoral soft tissues (ST) and dentition (DENT). The information provided by the 3D data was superimposed in four different combinations: FS + DENT (13 papers), FS + ST (5 papers), ST + DENT (2 papers) and all the types (FS + ST + DENT) (1 paper). Conclusions: The surface-based method was most frequently used for 3D objects superimposition (11 papers), followed by the point-based method (6 papers), with or without fiducial markers, and the voxel-based method (1 paper). Most of the papers analyzed the accuracy of the superimposition procedure (15 papers), while the remaining were proof-of-principles (10 papers) or compared different methods (3 papers). Further studies should focus on the definition of a gold standard. The patient is going to have a huge advantage from complete digital planning when more information about the spatial relationship of anatomical structures are needed: ectopic, impacted and supernumerary teeth, root resorption and angulations, cleft lip and palate (CL/P), alveolar boundary conditions, periodontally compromised patients, temporary anchorage devices (TADs), maxillary transverse deficiency, airway analyses, obstructive sleep apnea (OSAS), TMJ disorders and orthognathic and cranio-facial surgery.
Reverse Coarsening and the Control of Particle Size Distribution through Surfactant
Authors: Burlakov Victor M. , Goriely Alain
Published: August 2020

The minimization of surface area, as a result of the minimization of (positive) surface energy, is a well-known driving force behind the spontaneous broadening of (nano) particle size distribution. We show that surfactant molecules binding to particle surfaces effectively decrease the surface energy and may change its sign. In this case, contrary to the expected broadening behavior, a minimum of free energy is achieved at the maximum surface area for all particles, i.e., when the particles are identical. Numerical simulations based on the classical Lifshitz–Slyozov–Wagner theory with surfactant-induced surface energy renormalization confirm the collapse of the particle size distribution. As the particle size evolution is much slower than particle nucleation and growth, the manipulation of surface energy with in-situ replacement of surfactant molecules provides a method for controlling particle size distribution with great potential for creating mono-disperse nanoparticles, a key goal of nanotechnology.
Achieving Carbon Neutrality for A Future Large Greenhouse Gas Emitter in Quebec, Canada: A Case Study
Authors: Faubert Patrick , Bouchard Sylvie , Morin Chassé Rémi , Côté Hélène , Dessureault Pierre-Luc , Villeneuve Claude
Published: August 2020

To reach the Paris Agreement targets of holding the global temperature increase below 2 °C above the preindustrial levels, every human activity will need to be carbon neutral by 2050. Feasible means for industries to achieve carbon neutrality must be developed and assessed economically. Herein we present a case study on available solutions to achieve net-zero carbon from the get-go for a planned liquefied natural gas (LNG) plant in Quebec, which would classify as a large Canadian greenhouse gas (GHG) emitter. From a literature review, available options were prioritized with the promoter. Each prioritized potential solution is discussed in light of its feasibility and the associated economic opportunities and challenges. Although net-zero carbon is feasible from the get-go, results show that the promoter should identify opportunities to reduce as much as possible emissions at source, cooperate with other industries for CO2 capture and utilization, replace natural gas from fossil sources by renewable sources and offset the remaining emissions by planting trees and/or buying offsets on the compliance and voluntary markets. As some of these solutions are still to be developed, to ensure timely net-zero pledge for the lifespan of the LNG plant, a portfolio and progressive approach to combine offsets and other options is preferable.
Anthropogenic Photolabile Chlorine in the Cold-Climate City of Montreal
Authors: Hall Ryan , Nepotchatykh Oleg , Nepotchatykh Evguenia , Ariya Parisa A.
Published: August 2020

Chlorine atoms play a key role in the oxidative potential of the atmosphere and biogeochemical cycling of selected elements. This study provides a decadal analysis (2010−2019) of chloride ions in PM2.5 particles in the city of Montreal, where these are most concentrated systematically in the winter (up to 1.6 µg/m3). We also herein present the measurement of photolabile chlorine, which includes chlorine-containing compounds (e.g., Cl2, HOCl, ClNO2, ClNO3, and BrCl) that release chlorine atoms upon interaction with radiation, in urban Montreal, Canada using Cl2-RPGE (Cl2 Reactive Phase Gas Extraction) tubes and quantifying the chlorinated product by GC-MS. Photolabile chlorine in urban Montreal was measured during a discontinuous period primarily in summer 2018 and winter 2019 with a time resolution of 30 min, with concentrations ranging from 3 to 545 ng/m3 expressed as Cl2. The reported values are considered lower limits, as compounds such as HOCl and ClNO2 can only be partially converted in the current setup. The largest peak of gaseous photolabile chlorine occurred in the winter, when significant sources of anthropogenic salt are used in snow removal in the city. This coincides with observed chloride ion measurements in airborne particles, implying that anthropogenic salt addition produces photoactive chlorine. The maximum chlorine signal was consistently obtained during the daytime, which is in accordance with the tropospheric radiation profile. Complementary photochemistry laboratory experiments indicated that upon tropospheric radiation (340 ≤ λ ≤ 400 nm; UVA), an increase (20–100%) was observed, confirming the formation of Cl atoms from photolabile chlorine compounds. Thus, this portable technique is adequate for Cl atoms and photolabile chlorine-containing compounds upon photolysis using UVA lamps. High-resolution S/TEM and energy-dispersive X-ray spectroscopy (EDS) were used to evaluate collected particle morphology and composition. The behavior of complementary pollutants (O3, CO, PM2.5, and NOx) was also briefly discussed. We herein discuss the measurement of photolabile halogens within a northern urban metropolitan environment and the impact of anthropogenic sources on chlorine concentrations.
Statistical Analysis of Microphysical and Dynamical Parameters for Clouds and Precipitation over Nauq Tibetan Plateau in Summertime Using Ka-band Cloud Radar
Authors: Liu Liping , Gao Wenhua
Published: August 2020

A Chinese Ka-band solid-state transmitter cloud radar (CR) was employed to investigate clouds and precipitation over the Tibetan Plateau (TP) in summer 2014. After performing quality control and merging the output from the three work modes of CR, the Doppler spectral density data were analyzed to estimate the vertical air motion (Vair) and particle fall speed (Vfall) in clouds. The reproduced radar reflectivity was employed to retrieve the ice water content (IWC) and ice effective radius (Re). The cloud type classification algorithm was developed to classify cloud conditions into eight different categories. The vertical and daily variations of reflectivity, Vair, Vfall, IWC, and Re were then analyzed, and as a result, four conclusions were formulated. First, the clouds with reflectivity less than −10 dBZ were mainly located above 7 km, and the precipitable particles were formed below this layer (rain echo top) due to the abundant supercooled water therein. Second, the weak updraft in the range of 2–4 km caused the high occurrence of weak clouds during 04:00–12:00 Beijing local time (BT), and the rain echo top did not exceed 7 km due to the existing downdraft in 4–6 km. After 14:00 BT, convective clouds quickly developed, and the averaged updraft, reflectivity, and the echo top notably increased. Third, particular cloud types commonly exhibited weak reflectivity, low IWC, and less vertical variations, while the others more obvious vertical variations with larger IWC and Re. Last, compared with the radar sensitivity and range from radar, Vair biases that were introduced by the Doppler spectra broadening due to turbulence, wind shear, and radar beam width, could be neglected.
Skeletal Muscle Tissue Engineering: Biomaterials-Based Strategies for the Treatment of Volumetric Muscle Loss
Authors: Carnes Meagan E. , Pins George D.
Published: August 2020

Millions of Americans suffer from skeletal muscle injuries annually that can result in volumetric muscle loss (VML), where extensive musculoskeletal damage and tissue loss result in permanent functional deficits. In the case of small-scale injury skeletal muscle is capable of endogenous regeneration through activation of resident satellite cells (SCs). However, this is greatly reduced in VML injuries, which remove native biophysical and biochemical signaling cues and hinder the damaged tissue’s ability to direct regeneration. The current clinical treatment for VML is autologous tissue transfer, but graft failure and scar tissue formation leave patients with limited functional recovery. Tissue engineering of instructive biomaterial scaffolds offers a promising approach for treating VML injuries. Herein, we review the strategic engineering of biophysical and biochemical cues in current scaffold designs that aid in restoring function to these preclinical VML injuries. We also discuss the successes and limitations of the three main biomaterial-based strategies to treat VML injuries: acellular scaffolds, cell-delivery scaffolds, and in vitro tissue engineered constructs. Finally, we examine several innovative approaches to enhancing the design of the next generation of engineered scaffolds to improve the functional regeneration of skeletal muscle following VML injuries.
Physical, Thermal, and Antibacterial Effects of Active Essential Oils with Potential for Biomedical Applications Loaded onto Cellulose Acetate/Polycaprolactone Wet-Spun Microfibers
Authors: Felgueiras Helena P. , Homem Natália C. , Teixeira Marta A. , Ribeiro Ana R. M. , Antunes Joana C. , Amorim Maria Teresa P.
Published: August 2020

New approaches to deal with the growing concern associated with antibiotic-resistant bacteria are emerging daily. Essential oils (EOs) are natural antimicrobial substances with great potential to mitigate this situation. However, their volatile nature, in their liquid-free form, has restricted their generalized application in biomedicine. Here, we propose the use of cellulose acetate (CA)/polycaprolactone (PCL) wet-spun fibers as potential delivery platforms of selected EOs to fight infections caused by Staphylococcus aureus (S. aureus) and Escherichia coli (E. coli). Twenty EOs were selected and screened for their minimal inhibitory concentration (MIC), using the antibiotic ampicillin as positive control. The cinnamon leaf oil (CLO), cajeput oil (CJO), and the clove oil (CO) were the most effective EOs, against the Gram-positive (MIC < 22.38 mg/mL) and the Gram-negative (MIC < 11.19 mg/mL) bacteria. Uniform microfibers were successfully wet-spun from CA/PCL with an averaged diameter of 53.9 ± 4.5 µm, and then modified by immersion with CLO, CJO and CO at 2 × MIC value. EOs incorporation was confirmed by UV-visible spectroscopy, Fourier-transformed infrared spectroscopy, and thermal gravimetric analysis. However, while microfibers contained ampicillin at MIC (control) after the 72 h modification, the CLO, CO and CJO-loaded fibers registered ≈ 14%, 66%, and 76% of their MIC value, respectively. Data showed that even at small amounts the EO-modified microfibers were effective against the tested bacteria, both by killing bacteria more quickly or by disrupting more easily their cytoplasmic membrane than ampicillin. Considering the amount immobilized, CLO-modified fibers were deemed the most effective from the EOs group. These results indicate that CA/PCL microfibers loaded with EOs can be easily produced with increased antibacterial action, envisioning their use as scaffolding materials for the treatment of infections.
Small Molecules in the Venom of the Scorpion Hormurus waigiensis
Authors: Evans Edward R. J. , McIntyre Lachlan , Northfield Tobin D. , Daly Norelle L. , Wilson David T.
Published: August 2020

Despite scorpion stings posing a significant public health issue in particular regions of the world, certain aspects of scorpion venom chemistry remain poorly described. Although there has been extensive research into the identity and activity of scorpion venom peptides, non-peptide small molecules present in the venom have received comparatively little attention. Small molecules can have important functions within venoms; for example, in some spider species the main toxic components of the venom are acylpolyamines. Other molecules can have auxiliary effects that facilitate envenomation, such as purines with hypotensive properties utilised by snakes. In this study, we investigated some non-peptide small molecule constituents of Hormurus waigiensis venom using LC/MS, reversed-phase HPLC, and NMR spectroscopy. We identified adenosine, adenosine monophosphate (AMP), and citric acid within the venom, with low quantities of the amino acids glutamic acid and aspartic acid also being present. Purine nucleosides such as adenosine play important auxiliary functions in snake venoms when injected alongside other venom toxins, and they may have a similar role within H. waigiensis venom. Further research on these and other small molecules in scorpion venoms may elucidate their roles in prey capture and predator defence, and gaining a greater understanding of how scorpion venom components act in combination could allow for the development of improved first aid.
Organoarsenic Compounds with In Vitro Activity against the Malaria Parasite Plasmodium falciparum
Authors: Basova Sofia , Wilke Nathalie , Koch Jan Christoph , Prokop Aram , Berkessel Albrecht , Pradel Gabriele , Ngwa Che Julius
Published: August 2020

The rapid development of parasite drug resistance as well as the lack of medications targeting both the asexual and the sexual blood stages of the malaria parasite necessitate the search for novel antimalarial compounds. Eleven organoarsenic compounds were synthesized and tested for their effect on the asexual blood stages and sexual transmission stages of the malaria parasite Plasmodium falciparum using in vitro assays. The inhibitory potential of the compounds on blood stage viability was tested on the chloroquine (CQ)-sensitive 3D7 and the CQ-resistant Dd2 strain using the Malstat assay. The most effective compounds were subsequently investigated for their effect on impairing gametocyte development and gametogenesis, using the gametocyte-producing NF54 strain in respective cell-based assays. Their potential toxicity was investigated on leukemia cell line Nalm-6 and non-infected erythrocytes. Five out of the 11 compounds showed antiplasmodial activities against 3D7, with half-maximal inhibitory concentration (IC50) values ranging between 1.52 and 8.64 µM. Three of the compounds also acted against Dd2, with the most active compound As-8 exhibiting an IC50 of 0.35 µM. The five compounds also showed significant inhibitory effects on the parasite sexual stages at both IC50 and IC90 concentrations with As-8 displaying the best gametocytocidal activity. No hemolytic and cytotoxic effect was observed for any of the compounds. The organoarsenic compound As-8 may represent a good lead for the design of novel organoarsenic drugs with combined antimalarial and transmission blocking activities.
Phenol-Enriched Virgin Olive Oil Promotes Macrophage-Specific Reverse Cholesterol Transport In Vivo
Authors: Cedó Lídia , Fernández-Castillejo Sara , Rubió Laura , Metso Jari , Santos David , Muñoz-Aguayo Daniel , Rivas-Urbina Andrea , Tondo Mireia , Méndez-Lara Karen Alejandra , Farràs Marta , Jauhiainen Matti , Motilva Maria-José , Fitó Montserrat , Blanco-Vaca Francisco , Solà Rosa , Escolà-Gil Joan Carles
Published: August 2020

The intake of olive oil (OO) enriched with phenolic compounds (PCs) promotes ex vivo HDL-mediated macrophage cholesterol efflux in humans. We aimed to determine the effects of PC-enriched virgin OO on reverse cholesterol transport (RevCT) from macrophages to feces in vivo. Female C57BL/6 mice were given intragastric doses of refined OO (ROO) and a functional unrefined virgin OO enriched with its own PC (FVOO) for 14 days. Our experiments included two independent groups of mice that received intragastric doses of the phenolic extract (PE) used to prepare the FVOO and the vehicle solution (saline), as control, for 14 days. FVOO intake led to a significant increase in serum HDL cholesterol and its ability to induce macrophage cholesterol efflux in vitro when compared with ROO group. This was concomitant with the enhanced macrophage-derived [3H]cholesterol transport to feces in vivo. PE intake per se also increased HDL cholesterol levels and significantly promoted in vivo macrophage-to-feces RevCT rate when compared with saline group. PE upregulated the expression of the main macrophage transporter involved in macrophage cholesterol efflux, the ATP binding cassettea1. Our data provide direct evidence of the crucial role of OO PCs in the induction of macrophage-specific RevCT in vivo.
EDTA Chelation Therapy in the Treatment of Neurodegenerative Diseases: An Update
Authors: Fulgenzi Alessandro , Vietti Daniele , Ferrero Maria Elena
Published: August 2020

We have previously described the role played by toxic-metal burdens in the etiology of neurodegenerative diseases (ND). We herein report an updated evaluation of toxic-metal burdens in human subjects affected or not affected by ND or other chronic diseases. Each subject underwent a chelation test with the chelating agent calcium disodium ethylenediaminetetraacetic acid (CaNA2EDTA or EDTA) to identify the presence of 20 toxic metals in urine samples using inductively coupled plasma mass spectrometry. Our results show the constant presence of toxic metals, such as lead, cadmium, cesium, and aluminum, in all examined subjects but the absence of beryllium and tellurium. Gadolinium was detected in patients undergoing diagnostic magnetic resonance imaging. The presence of toxic metals was always significantly more elevated in ND patients than in healthy controls. Treatment with EDTA chelation therapy removes toxic-metal burdens and improves patient symptoms.
Mitochondrial Metabolism in PDAC: From Better Knowledge to New Targeting Strategies
Authors: Reyes-Castellanos Gabriela , Masoud Rawand , Carrier Alice
Published: August 2020

Cancer cells reprogram their metabolism to meet bioenergetics and biosynthetic demands. The first observation of metabolic reprogramming in cancer cells was made a century ago (“Warburg effect” or aerobic glycolysis), leading to the classical view that cancer metabolism relies on a glycolytic phenotype. There is now accumulating evidence that most cancers also rely on mitochondria to satisfy their metabolic needs. Indeed, the current view of cancer metabolism places mitochondria as key actors in all facets of cancer progression. Importantly, mitochondrial metabolism has become a very promising target in cancer therapy, including for refractory cancers such as Pancreatic Ductal AdenoCarcinoma (PDAC). In particular, mitochondrial oxidative phosphorylation (OXPHOS) is an important target in cancer therapy. Other therapeutic strategies include the targeting of glutamine and fatty acids metabolism, as well as the inhibition of the TriCarboxylic Acid (TCA) cycle intermediates. A better knowledge of how pancreatic cancer cells regulate mitochondrial metabolism will allow the identification of metabolic vulnerabilities and thus novel and more efficient therapeutic options for the benefit of each patient.
Amygdala: Neuroanatomical and Morphophysiological Features in Terms of Neurological and Neurodegenerative Diseases
Authors: Nikolenko Vladimir N. , Oganesyan Marine V. , Rizaeva Negoriya A. , Kudryashova Valentina A. , Nikitina Arina T. , Pavliv Maria P. , Shchedrina Marina A. , Giller Dmitry B. , Bulygin Kirill V. , Sinelnikov Mikhail Y.
Published: August 2020

The amygdala is one of the most discussed structures of the brain. Correlations between its level of activity, size, biochemical organization, and various pathologies are the subject of many studies, and can serve as a marker of existing or future disease. It is hypothesized that the amygdala is not just a structural unit, but includes many other regions in the brain. In this review, we present the updated neuroanatomical and physiological aspects of the amygdala, discussing its involvement in neurodegenerative and neurological diseases. The amygdala plays an important role in the processing of input signals and behavioral synthesis. Lesions in the amygdala have been shown to cause neurological disfunction of ranging severity. Abnormality in the amygdala leads to conditions such as depression, anxiety, autism, and also promotes biochemical and physiological imbalance. The amygdala collects pathological proteins, and this fact can be considered to play a big role in the progression and diagnosis of many degenerative diseases, such as Alzheimer’s disease, chronic traumatic encephalopathy, Lewy body diseases, and hippocampal sclerosis. The amygdala has shown to play a crucial role as a central communication system in the brain, therefore understanding its neuroanatomical and physiological features can open a channel for targeted therapy of neurodegenerative diseases.
The Increased Densities, But Different Distributions, of Both C3 and S100A10 Immunopositive Astrocyte-Like Cells in Alzheimer’s Disease Brains Suggest Possible Roles for Both A1 and A2 Astrocytes in the Disease Pathogenesis
Authors: King Andrew , Szekely Boglarka , Calapkulu Eda , Ali Hanan , Rios Francesca , Jones Shalmai , Troakes Claire
Published: August 2020

There is increasing evidence of astrocyte dysfunction in the pathogenesis of Alzheimer’s disease (AD). Animal studies supported by human post-mortem work have demonstrated two main astrocyte types: the C3 immunopositive neurotoxic A1 astrocytes and the S100A10 immunopositive neuroprotective A2 astrocytes. A1 astrocytes predominate in AD, but the number of cases has been relatively small. We examined post-mortem brains from a larger cohort of AD cases and controls employing C3 and S100 immunohistochemistry to identify the astrocytic subtypes. There were a number of C3 immunopositive astrocyte-like cells (ASLCs) in the control cases, especially in the lower cerebral cortex and white matter. In AD this cell density appeared to be increased in the upper cerebral cortex but was similar to controls in other regions. The S100A10 showed minimal immunopositivity in the control cases in the cortex and white matter, but there was increased ASLC density in upper/lower cortex and white matter in AD compared to controls. In AD and control cases the numbers of C3 immunopositive ASLCs were greater than those for S100A10 ASLCs in all areas studied. It would appear that the relationship between A1 and A2 astrocytes and their possible role in the pathogenesis of AD is complex and requires more research.
End-of-Life in Oncologic Patients’ Dream Content
Authors: Cicolin Alessandro , Boffano Michele , Beccuti Guglielmo , Piana Raimondo , Giordano Alessandra
Published: August 2020

Both non-rapid eye movements and rapid eye movements sleep facilitate the strengthening of newly encoded memory traces, and dream content reflects this process. Numerous studies evaluated the impact of diseases on dream content, with particular reference to cancer, and reported the presence of issues related to death, negative emotions, pain and illness. This study investigates death and illness experiences in 13 consecutive patients with sarcoma compared to paired controls, early after diagnosis, evaluating dream contents, fear of death, mood and anxiety, distress, and severity of disease perception (perceived and communicated). Ten patients and 10 controls completed the study. Dream contents were significantly different between patients and normative data (DreamSat) and patients and controls (higher presence of negative emotions, low familiar settings and characters and no success involving the dreamer). Illness and death were present in 57% of patients’ dreams (0% among controls), but no differences emerged between patients and controls in regard to anxiety and depression, distress and fear of death, even if the severity of illness was correctly perceived. The appearance of emotional elements in dreams and the absence of conscious verbalization of distress and/or depressive or anxious symptoms by patients could be ascribed to the time required for mnestic elaboration (construction/elaboration phase) during sleep.
Advances in the Neurocognition of Music and Language
Authors: Sammler Daniela , Elmer Stefan
Published: August 2020

Neurocomparative music and language research has seen major advances over the past two decades. The goal of this Special Issue “Advances in the Neurocognition of Music and Language” was to showcase the multiple neural analogies between musical and linguistic information processing, their entwined organization in human perception and cognition and to infer the applicability of the combined knowledge in pedagogy and therapy. Here, we summarize the main insights provided by the contributions and integrate them into current frameworks of rhythm processing, neuronal entrainment, predictive coding and cognitive control.
Grammatical Comprehension in Italian Children with Autism Spectrum Disorder
Authors: Barsotti Jessica , Mangani Gloria , Nencioli Roberta , Pfanner Lucia , Tancredi Raffaella , Cosenza Angela , Sesso Gianluca , Narzisi Antonio , Muratori Filippo , Cipriani Paola , Chilosi Anna Maria
Published: August 2020

Language deficits represent one of the most relevant factors that determine the clinical phenotype of children with autism spectrum disorder (ASD). The main aim of the research was to study the grammatical comprehension of children with ASD. A sample of 70 well-diagnosed children (60 boys and 10 girls; aged 4.9–8 years) were prospectively recruited. The results showed that language comprehension is the most impaired language domain in ASD. These findings have important clinical implications, since the persistence of grammatical receptive deficits may have a negative impact on social, adaptive and learning achievements. As for the grammatical profiles, persistent difficulties were found during the school-age years in morphological and syntactic decoding in children with relatively preserved cognitive and expressive language skills. These data and the lack of a statistically significant correlation between the severity of ASD symptoms and language skills are in line with the DSM-5 (Diagnostic and Statistical Manual of Mental Disorders, Fifth Edition) perspective that considers the socio-communication disorder as a nuclear feature of ASD and the language disorder as a specifier of the diagnosis and not as a secondary symptom anymore. The presence of receptive difficulties in school-age ASD children with relatively preserved non-verbal cognitive abilities provides important hints to establish rehabilitative treatments.
Functional Electrical Stimulation Controlled by Motor Imagery Brain-Computer Interface for Rehabilitation
Authors: Choi Inchul , Kwon Gyu Hyun , Lee Sangwon , Nam Chang S.
Published: August 2020

Sensorimotor rhythm (SMR)-based brain–computer interface (BCI) controlled Functional Electrical Stimulation (FES) has gained importance in recent years for the rehabilitation of motor deficits. However, there still remain many research questions to be addressed, such as unstructured Motor Imagery (MI) training procedures; a lack of methods to classify different MI tasks in a single hand, such as grasping and opening; and difficulty in decoding voluntary MI-evoked SMRs compared to FES-driven passive-movement-evoked SMRs. To address these issues, a study that is composed of two phases was conducted to develop and validate an SMR-based BCI-FES system with 2-class MI tasks in a single hand (Phase 1), and investigate the feasibility of the system with stroke and traumatic brain injury (TBI) patients (Phase 2). The results of Phase 1 showed that the accuracy of classifying 2-class MIs (approximately 71.25%) was significantly higher than the true chance level, while that of distinguishing voluntary and passive SMRs was not. In Phase 2, where the patients performed goal-oriented tasks in a semi-asynchronous mode, the effects of the FES existence type and adaptive learning on task performance were evaluated. The results showed that adaptive learning significantly increased the accuracy, and the accuracy after applying adaptive learning under the No-FES condition (61.9%) was significantly higher than the true chance level. The outcomes of the present research would provide insight into SMR-based BCI-controlled FES systems that can connect those with motor disabilities (e.g., stroke and TBI patients) to other people by greatly improving their quality of life. Recommendations for future work with a larger sample size and kinesthetic MI were also presented.
Cerebral Substrates for Controlling Rhythmic Movements
Authors: Konoike Naho , Nakamura Katsuki
Published: August 2020

Our daily lives are filled with rhythmic movements, such as walking, sports, and dancing, but the mechanisms by which the brain controls rhythmic movements are poorly understood. In this review, we examine the literature on neuropsychological studies of patients with focal brain lesions, and functional brain imaging studies primarily using finger-tapping tasks. These studies suggest a close connection between sensory and motor processing of rhythm, with no apparent distinction between the two functions. Thus, we conducted two functional brain imaging studies to survey the rhythm representations relatively independent of sensory and motor functions. First, we determined brain activations related to rhythm processing in a sensory modality-independent manner. Second, we examined body part-independent brain activation related to rhythm reproduction. Based on previous literature, we discuss how brain areas contribute rhythmic motor control. Furthermore, we also discuss the mechanisms by which the brain controls rhythmic movements.
Functional Network Mapping Reveals State-Dependent Response to IGF1 Treatment in Rett Syndrome
Authors: Keogh Conor , Pini Giorgio , Gemo Ilaria , Kaufmann Walter , Tropea Daniela
Published: August 2020

Rett Syndrome (RTT) is a neurodevelopmental disorder associated with mutations in the gene MeCP2, which is involved in the development and function of cortical networks. The clinical presentation of RTT is generally severe and includes developmental regression and marked neurologic impairment. Insulin-Like growth factor 1 (IGF1) ameliorates RTT-relevant phenotypes in animal models and improves some clinical manifestations in early human trials. However, it remains unclear whether IGF1 treatment has an impact on cortical electrophysiology in line with MeCP2’s role in network formation, and whether these electrophysiological changes are related to clinical response. We performed clinical assessments and resting-state electroencephalogram (EEG) recordings in eighteen patients with classic RTT, nine of whom were treated with IGF1. Among the treated patients, we distinguished those who showed improvements after treatment (responders) from those who did not show any changes (nonresponders). Clinical assessments were carried out for all individuals with RTT at baseline and 12 months after treatment. Network measures were derived using statistical modelling techniques based on interelectrode coherence measures. We found significant interaction between treatment groups and timepoints, indicating an effect of IGF1 on network measures. We also found a significant effect of responder status and timepoint, indicating that these changes in network measures are associated with clinical response to treatment. Further, we found baseline variability in network characteristics, and a machine learning model using these measures applied to pretreatment data predicted treatment response with 100% accuracy (100% sensitivity and 100% specificity) in this small patient group. These results highlight the importance of network pathology in RTT, as well as providing preliminary evidence for the potential of network measures as tools for the characterisation of disease subtypes and as biomarkers for clinical trials.
Catalysts for Methane Steam Reforming Reaction: Evaluation of CeO2 Addition to Alumina-Based Washcoat Slurry Formulation
Authors: Palma Vincenzo , Meloni Eugenio , Renda Simona , Martino Marco
Published: August 2020

The effect of the addition of CeO2 to alumina-based washcoat slurry formulation on the methane steam reforming (MSR) reaction was investigated. Five Al2O3-CeO2-based washcoat slurries, differing from each other in the Al2O3/CeO2 ratio (nominal ratio equal to ∞, 0.042, 0.087, 0.250, 0.667) were prepared, dried and calcined; the resulting powders were loaded with nickel as an active metal and the obtained catalysts were tested in MSR reaction. Five cylindrical silicon carbide (SiC) monoliths were washcoated with the prepared slurries and their mechanical resistance was evaluated through the ultrasound adherence test. The activity tests results highlighted the best performance in terms of methane conversion and hydrogen selectivity of the powder catalyst, with the Al2O3/CeO2 percentage nominal ratio equal to 0.042. A structured catalyst was finally prepared by loading a SiC monolith with the most active catalytic formulation and tested in MSR reaction. The performance of the structured catalyst was evaluated in terms of methane conversion and its stability was verified in a time-on-stream test, which allowed for the evaluation of the carbon formation rate; furthermore, its activity was characterized by the estimation of the kinetic parameters. The results highlighted the beneficial effect of ceria addition on the catalytic activity; moreover, compared with data of the literature, the calculated carbon formation rate demonstrated a good resistance of the catalyst to coke formation.
Histone Demethylase KDM5B as a Therapeutic Target for Cancer Therapy
Authors: Jose Anmi , Shenoy Gautham G. , Sunil Rodrigues Gabriel , Kumar Naveena A. N. , Munisamy Murali , Thomas Levin , Kolesar Jill , Rai Ganesha , Rao Praveen P. N. , Rao Mahadev
Published: August 2020

Lysine-specific demethylase 5B (KDM5B/PLU1/JARID1B) is found to be overexpressed in numerous malignancies, including breast, lung, skin, liver, and prostate cancer. Identification of molecules targeting the KDM5B enzyme could be a potential lead in cancer research. Although many KDM5B inhibitors with promising outcomes have been developed so far, its further application in clinical practice is limited due to toxicity and lack of target specificity. Here, we summarize the significance of targeting KDM5B in anticancer therapy and report the molecular docking studies of some known anti-viral agents, decitabine, entecavir, abacavir, penciclovir, and 3-deazaneplanocin A in the catalytic domain JmjC of KDM5B. These studies show the repurposing potential of identified anti-viral agents in cancer therapy.
Effects of Cancer Stem Cells in Triple-Negative Breast Cancer and Brain Metastasis: Challenges and Solutions
Authors: Lee Kha-Liang , Chen Gao , Chen Tai-Yuan , Kuo Yung-Che , Su Yu-Kai
Published: August 2020

A higher propensity of developing brain metastasis exists in triple-negative breast cancer (TNBC). Upon comparing the metastatic patterns of all breast cancer subtypes, patients with TNBC exhibited increased risks of the brain being the initial metastatic site, early brain metastasis development, and shortest brain metastasis-related survival. Notably, the development of brain metastasis differs from that at other sites owing to the brain-unique microvasculature (blood brain barrier (BBB)) and intracerebral microenvironment. Studies of brain metastases from TNBC have revealed the poorest treatment response, mostly because of the relatively backward strategies to target vast disease heterogeneity and poor brain efficacy. Moreover, TNBC is highly associated with the existence of cancer stem cells (CSCs), which contribute to circulating cancer cell survival before BBB extravasation, evasion from immune surveillance, and plasticity in adaptation to the brain-specific microenvironment. We summarized recent literature regarding molecules and pathways and reviewed the effects of CSC biology during the formation of brain metastasis in TNBC. Along with the concept of individualized cancer therapy, certain strategies, namely the patient-derived xenograft model to overcome the lack of treatment-relevant TNBC classification and techniques in BBB disruption to enhance brain efficacy has been proposed in the hope of achieving treatment success.
Relation of Neutrophil Gelatinase-Associated Lipocalin Overexpression to the Resistance to Apoptosis of Tumor B Cells in Chronic Lymphocytic Leukemia
Authors: Bauvois Brigitte , Pramil Elodie , Jondreville Ludovic , Chapiro Elise , Quiney Claire , Maloum Karim , Susin Santos A. , Nguyen-Khac Florence
Published: August 2020

The resistance to apoptosis of chronic lymphocytic leukemia (CLL) cells partly results from the deregulated production of survival signals from leukemic cells. Despite the development of new therapies in CLL, drug resistance and disease relapse still occur. Recently, neutrophil gelatinase-associated lipocalin (NGAL), a secreted glycoprotein, has been suggested to have a critical role in the biology of tumors. Thus, we investigated the relevance of NGAL in CLL pathogenesis, analyzed the expression of its cellular receptor (NGAL-R) on malignant B cells and tested whether CLL cells are resistant to apoptosis through an autocrine process involving NGAL and NGAL-R. We observed that NGAL concentrations were elevated in the serum of CLL patients at diagnosis. After treatment (and regardless of the therapeutic regimen), serum NGAL levels normalized in CLL patients in remission but not in relapsed patients. In parallel, NGAL and NGAL-R were upregulated in leukemic cells from untreated CLL patients when compared to normal peripheral blood mononuclear cells (PBMCs), and returned to basal levels in PBMCs from patients in remission. Cultured CLL cells released endogenous NGAL. Anti-NGAL-R antibodies enhanced NGAL-R+ leukemia cell death. Conversely, recombinant NGAL protected NGAL-R+ CLL cells against apoptosis by activating a STAT3/Mcl-1 signaling pathway. Our results suggest that NGAL and NGAL-R, overexpressed in untreated CLL, participate in the deregulation of the apoptotic machinery in CLL cells, and may be potential therapeutic clues for CLL treatment.
Oncologic Benefit of Adjuvant Chemoradiation after D2 Gastrectomy: A Stepwise Hierarchical Pooled Analysis and Systematic Review
Authors: Rim Chai Hong , Shin In-Soo , Lee Hye Yoon , Yoon Won Sup , Park Sunmin
Published: August 2020

Our study aimed to evaluate the benefits of chemoradiotherapy (CRT) after D2 gastrectomy, as compared to adjuvant chemotherapy, alone. PubMed, MEDLINE, Embase, and the Cochrane Library were systematically searched. We applied stepwise analyses that enabled the evaluation of data from randomized controlled trials (RCTs), balanced studies, and all studies separately and in a hierarchical manner. Thirteen controlled studies, including six RCTs involving 2603 patients, were included. Overall pooled analysis revealed a disease-free survival benefit of CRT (odds ratio (OR): 1.264, p = 0.053), which was more evident in the subgroup analysis of RCTs (OR: 1.440, p = 0.006) and balanced studies (OR: 1.417, p < 0.001). Overall survival was insignificantly different in the overall pooled analysis (OR: 1.124, p = 0.347). However, the difference was marginally significant in the subgroup analysis of balanced studies (OR: 1.279, p = 0.055) and significant in the subgroup analysis of studies involving stage ≥III patients only (OR: 1.663, p = 0.005). Locoregional recurrence (LRR) reduction was noted in the overall pooled analysis (OR: 0.559, p = 0.012; pooled rate: 11.3% vs. 18.1%) and was more robust in the subgroup analyses. Grade ≥3 leukopenia was higher in the CRT arm (OR: 1.387, p = 0.004; pooled rate: 26.4% vs. 15.7%). CRT after D2 gastrectomy should be applied for patients with high risk of LRR (e.g., stage ≥ III), along with efforts to reduce leukopenia.
Molecular Biology of Osteosarcoma
Authors: Czarnecka Anna M. , Synoradzki Kamil , Firlej Wiktoria , Bartnik Ewa , Sobczuk Pawel , Fiedorowicz Michal , Grieb Pawel , Rutkowski Piotr
Published: August 2020

Osteosarcoma (OS) is the most frequent primary bone cancer in children and adolescents and the third most frequent in adults. Many inherited germline mutations are responsible for syndromes that predispose to osteosarcomas including Li Fraumeni syndrome, retinoblastoma syndrome, Werner syndrome, Bloom syndrome or Diamond–Blackfan anemia. TP53 is the most frequently altered gene in osteosarcoma. Among other genes mutated in more than 10% of OS cases, c-Myc plays a role in OS development and promotes cell invasion by activating MEK–ERK pathways. Several genomic studies showed frequent alterations in the RB gene in pediatric OS patients. Osteosarcoma driver mutations have been reported in NOTCH1, FOS, NF2, WIF1, BRCA2, APC, PTCH1 and PRKAR1A genes. Some miRNAs such as miR-21, -34a, -143, -148a, -195a, -199a-3p and -382 regulate the pathogenic activity of MAPK and PI3K/Akt-signaling pathways in osteosarcoma. CD133+ osteosarcoma cells have been shown to exhibit stem-like gene expression and can be tumor-initiating cells and play a role in metastasis and development of drug resistance. Although currently osteosarcoma treatment is based on adriamycin chemoregimens and surgery, there are several potential targeted therapies in development. First of all, activity and safety of cabozantinib in osteosarcoma were studied, as well as sorafenib and pazopanib. Finally, novel bifunctional molecules, of potential imaging and osteosarcoma targeting applications may be used in the future.
Quercetin–Resveratrol Combination for Prostate Cancer Management in TRAMP Mice
Authors: Singh Chandra K. , Chhabra Gagan , Ndiaye Mary A. , Siddiqui Imtiaz A. , Panackal Jennifer E. , Mintie Charlotte A. , Ahmad Nihal
Published: August 2020

Prostate Cancer (PCa) is a leading cause of cancer-related morbidity and mortality in men. Therefore, novel mechanistically-driven approaches are needed for PCa management. Here, we determined the effects of grape antioxidants quercetin and/or resveratrol (60 and 600 mg/kg, respectively, in diet) against PCa in Transgenic Adenocarcinoma of Mouse Prostate (TRAMP)-model in prevention and intervention settings. We found resveratrol alone and in combination significantly inhibited prostate tumorigenesis in prevention setting, while the same was seen only in combination after intervention. The observed effects were associated with marked inhibition in proliferation, oxidative stress, and tumor survival markers, and induced apoptosis markers. Utilizing PCa PCR array analysis with prevention tumor tissues, we identified that quercetin–resveratrol modulates genes involved in promoter methylation, cell cycle, apoptosis, fatty acid metabolism, transcription factors, androgen response, PI3K/AKT and PTEN signaling. Ingenuity Pathway Analysis (IPA) identified IGF1 and BCL2 as central players in two gene networks. Functional annotation predicted increased apoptosis and inhibited cell viability/proliferation, hyperplasia, vasculogenesis, and angiogenesis with dual treatment. Furthermore, IPA predicted upstream inhibition of major PCa signaling VEGF, Ca2+, PI3K, CSF2, PTH). Based on PCR array, we identified decreased levels of EGFR, EGR3, and IL6, and increased levels of IGFBP7 and NKX3.1, overall supporting anti-PCa effects of quercetin–resveratrol.
Metformin and Everolimus: A Promising Combination for Neuroendocrine Tumors Treatment
Authors: Vitali Eleonora , Boemi Ilena , Tarantola Giulia , Piccini Sara , Zerbi Alessandro , Veronesi Giulia , Baldelli Roberto , Mazziotti Gherardo , Smiroldo Valeria , Lavezzi Elisabetta , Spada Anna , Mantovani Giovanna , Lania Andrea G.
Published: August 2020

Introduction: Treatment options for neuroendocrine tumors (NETs) are rarely curative, as NETs frequently show resistance to medical therapy. The use of everolimus, an mTOR inhibitor, is limited by the development of resistance, probably due to the activation of Akt signaling. In this context, the antidiabetic drug metformin is able to inhibit mTOR, providing a rationale for the use of metformin and everolimus in combination. Methods: We investigated the effects of the metformin and everolimus combination on NET cell proliferation, apoptosis, colony formation, cell viability, NET spheroids growth and the involvement of the Akt and mTOR pathways, and also developed everolimus-resistant NET cells to further study this combination. Results: Metformin and everolimus in combination are more effective than monotherapy in inhibiting pancreatic NET (PAN-NET) cell proliferation (−71% ± 13%, p < 0.0001 vs. basal), whereas no additive effects were observed on pulmonary neuroendocrine tumor (PNT) cell proliferation. The combinatorial treatment is more effective than monotherapy in inhibiting colony formation, cell viability, NET spheroids growth rate and mTOR phosphorylation in both NET cell lines. In a PAN-NET cell line, metformin did not affect Akt phosphorylation; conversely, it significantly decreased Akt phosphorylation in a PNT cell line. Using everolimus-resistant NET cells, we confirmed that metformin maintained its effects, acting by two different pathways: Akt-dependent or independent, depending on the cell type, with both leading to mTOR suppression. Conclusions: Considering the promising effects of the everolimus and metformin combination in NET cells, our results provide a rationale for its use in NET patients.