bluuebunny/crossref_metadata_2025 huggingface dataset:
Anticonvulsant Effects of Topiramate and Lacosamide on Pilocarpine-Induced Status Epilepticus in Rats: A Role of Reactive Oxygen Species and Inflammation
Authors: Shishmanova-Doseva Michaela , Peychev Lyudmil , Yoanidu Lyubka , Uzunova Yordanka , Atanasova Milena , Georgieva Katerina , Tchekalarova Jana
Published: February 2021

Background: Status epilepticus (SE) is a neurological disorder characterized by a prolonged epileptic activity followed by subsequent epileptogenic processes. The aim of the present study was to evaluate the early effects of topiramate (TPM) and lacosamide (LCM) treatment on oxidative stress and inflammatory damage in a model of pilocarpine-induced SE. Methods: Male Wistar rats were randomly divided into six groups and the two antiepileptic drugs (AEDs), TPM (40 and 80 mg/kg, i.p.) and LCM (10 and 30 mg/kg, i.p.), were injected three times repeatedly after pilocarpine administration. Rats were sacrificed 24 h post-SE and several parameters of oxidative stress and inflammatory response have been explored in the hippocampus. Results: The two drugs TPM and LCM, in both doses used, succeeded in attenuating the number of motor seizures compared to the SE-veh group 30 min after administration. Pilocarpine-induced SE decreased the superoxide dismutase (SOD) activity and reduced glutathione (GSH) levels while increasing the catalase (CAT) activity, malondialdehyde (MDA), and IL-1β levels compared to the control group. Groups with SE did not affect the TNF-α levels. The treatment with a higher dose of 30 mg/kg LCM restored to control level the SOD activity in the SE group. The two AEDs, in both doses applied, also normalized the CAT activity and MDA levels to control values. In conclusion, we suggest that the antioxidant effect of TPM and LCM might contribute to their anticonvulsant effect against pilocarpine-induced SE, whereas their weak anti-inflammatory effect in the hippocampus is a consequence of reduced SE severity.
Disentangling Ethiopian Honey Bee (Apis mellifera) Populations Based on Standard Morphometric and Genetic Analyses
Authors: Hailu Teweldemedhn Gebretinsae , D'Alvise Paul , Hasselmann Martin
Published: February 2021

The diversity and local differentiation of honey bees are subjects of broad general interest. In particular, the classification of Ethiopian honey bees has been a subject of debate for decades. Here, we conducted an integrated analysis based on classical morphometrics and a putative nuclear marker (denoted r7-frag) for elevational adaptation to classify and characterize these honey bees. Therefore, 660 worker bees were collected out of 66 colonies from highland, midland and lowland agro-ecological zones (AEZs) and were analyzed in reference to populations from neighboring countries. Multivariate morphometric analyses show that our Ethiopian samples are separate from Apis mellifera scutellata, A. m. jemenitica, A. m. litorea and A. m. monticola, but are closely related to A. m. simensis reference. Linear discriminant analysis showed differentiation according to AEZs in the form of highland, midland and lowland ecotypes. Moreover, size was positively correlated with elevation. Similarly, our Ethiopian samples were differentiated from A. m. monticola and A. m. scutellata based on r7-frag. There was a low tendency towards genetic differentiation between the Ethiopian samples, likely impacted by increased gene flow. However, the differentiation slightly increased with increasing elevational differences, demonstrated by the highland bees that showed higher differentiation from the lowland bees (FST = 0.024) compared to the midland bees (FST = 0.015). An allelic length polymorphism was detected (denoted as d) within r7-frag, showing a patterned distribution strongly associated with AEZ (X2 = 11.84, p < 0.01) and found predominantly in highland and midland bees of some pocket areas. In conclusion, the Ethiopian honey bees represented in this study are characterized by high gene flow that suppresses differentiation.
Ultrasound or Sectional Imaging Techniques as Screening Tools for Hepatocellular Carcinoma: Fall Forward or Move Forward?
Authors: Sparchez Zeno , Craciun Rares , Caraiani Cosmin , Horhat Adelina , Nenu Iuliana , Procopet Bogdan , Sparchez Mihaela , Stefanescu Horia , Mocan Tudor
Published: February 2021

Hepatocellular carcinoma (HCC) is probably the epitome of a screening target, with a well-defined high-risk population, accessible screening methods, and multiple curative-intent treatments available for early disease. Per major societies guideline consensus, biannual ultrasound (US) surveillance of the at-risk patients is the current standard of care worldwide. Yet, despite its documented success in the past decades, this standard is far from perfect. While the whole community is working to further tighten the knots, a worrying number of cases still slip through this safety net. Consequently, these patients lose their chance to a curative solution which leads to a high disease burden with disproportionate mortality. While US will probably remain the fundamental staple in the screening strategy, key questions are seeking better answers. How can its caveats be addressed, and the technique be improved? When are further steps needed? How to increase accuracy without giving up on accessibility? This narrative review discusses the place of US surveillance in the bigger HCC picture, trying to navigate through its strengths and limits based on the most recent available evidence.
Different Features of Interleukin-37 and Interleukin-18 as Disease Activity Markers of Adult-Onset Still’s Disease
Authors: Nam Seoung Wan , Kang SuMan , Lee Jun Hyeok , Yoo Dae Hyun
Published: February 2021

The aim of this study was to evaluate the usefulness of serum interleukin (IL)-37 and IL-18 as disease activity markers of adult-onset Still’s disease (AOSD) and to compare their related clinical features. Forty-five patients with a set of high and subsequent low disease activity status of AOSD were enrolled. Modified Pouchot (mPouchot) score and serologic disease activity markers including levels of IL-37 and IL-18 were compared between high and low disease activity status. The relationships between disease activity parameters and differences in levels of cytokines according to each disease manifestation were evaluated in high disease activity status. mPouchot score and all disease activity markers including IL-37 and IL-18 significantly declined after treatment. Though both cytokines positively correlated with mPouchot score, the two did not correlate with each other in high disease activity status. IL-18 positively correlated with ferritin, AST, and LDH while IL-37 correlated better with CRP. The expression level of IL-37 was related to leukocytosis while IL-18 was related to pleuritis, pneumonitis, abnormal LFT, and hyperferritinemia. In addition, patients in the IL-18 dominant group presented with higher LDH levels and required a higher mean corticosteroid dose. In conclusion, IL-37 and IL-18 are disease activity markers reflecting different aspects of AOSD that can complement each other.
Appropriate Number of Treatment Sessions in Virtual Reality-Based Individual Cognitive Behavioral Therapy for Social Anxiety Disorder
Authors: Jeong Hyu Seok , Lee Jee Hyun , Kim Hesun Erin , Kim Jae-Jin
Published: February 2021

Virtual reality (VR) was introduced to maximize the effect of cognitive behavioral therapy (CBT) by efficiently performing exposure therapy. The purpose of this study was to find out whether VR-based individual CBT with relatively few treatment sessions is effective in improving social anxiety disorder (SAD). This therapy was applied to 115 patients with SAD who were retrospectively classified into 43 patients who completed the nine or 10 sessions normally (normal termination group), 52 patients who finished the sessions early (early termination group), and 20 patients who had extended the sessions (session extension group). The Brief Fear of Negative Evaluation Scale (BFNE) scores tended to decrease in all groups as the session progressed, and the slope of decrease was the steepest in the early termination group and the least steep in the session extension group. Severity of social anxiety in the last session and symptom reduction rate showed no significant group difference. Our findings suggest that short-term VR-based individual CBT of nine to 10 sessions may be effective. When the therapeutic effect is insufficient during this period, the additional benefit may be minimal if the session is simply extended. The improvement in the early termination group suggests that even shorter sessions of five or six can also be effective.
Scedosporium spp. from Clinical Setting in Argentina, with the Proposal of the New Pathogenic Species Scedosporium americanum
Authors: Abrantes Ruben A. , Refojo Nicolás , Hevia Alejandra I. , Fernández Julián , Isla Guillermina , Córdoba Susana , Dávalos María F. , Lubovich Silvina , Maldonado Ivana , Davel Graciela O. , Stchigel Alberto M.
Published: February 2021

Species of the genus Scedosporium (family Microascaceae, phylum Ascomycota) are responsible for a wide range of opportunistic human infections, and have a low susceptibility to most antifungal drugs. It is well known that the pattern of Scedosporium species distribution varies according to geographic region. To assess the diversity of Scedosporium species in Argentina involved in human infections, we carried out a retrospective study reviewing 49 strains from clinical samples sent for diagnosis to the National Clinical Mycology Reference Laboratory between 1985 and 2019. Then, a phenotypic characterization, a phylogenetic study and and in vitro susceptibility test to antifungals were carried out. An analysis of combined nucleotide sequences dataset of the internal transcribed spacer of the ribosomal DNA (ITS) and of a fragment of the β-tubulin gene (BT2) demonstrated that 92% of the strains belonged to the species S. boydii, S. apiospermum and S. angustum, all them pertaining to S. apiospermum species complex. However, two strains (4%) were identified as S. aurantiacum, a species never reported in clinical settings in the Americas’. Surprisingly, one of them displayed a polycytella-like conidiogenesis, up to date only reported for S. apiospermum. In addition, the strain DMic 165285 was phylogenetically located far away from the rest of the species, so is proposed as the novel species Scedosporium americanum. On the other hand, from all seven antifungals tested, voriconazole and posaconazole were the most active drugs against Scedosporium spp.
Towards Personalised Contrast Injection: Artificial-Intelligence-Derived Body Composition and Liver Enhancement in Computed Tomography
Authors: de Jong Daan J. , Veldhuis Wouter B. , Wessels Frank J. , de Vos Bob , Moeskops Pim , Kok Madeleine
Published: February 2021

In contrast-enhanced computed tomography, total body weight adapted contrast injection protocols have proven successful in achieving a homogeneous enhancement of vascular structures and liver parenchyma. However, because solid organs have greater perfusion than adipose tissue, the lean body weight (fat-free mass) rather than the total body weight is theorised to cause even more homogeneous enhancement. We included 102 consecutive patients who underwent a multiphase abdominal computed tomography between March 2016 and October 2019. Patients received contrast media (300 mgI/mL) according to bodyweight categories. Using regions of interest, we measured the Hounsfield unit (HU) increase in liver attenuation from unenhanced to contrast-enhanced computed tomography. Furthermore, subjective image quality was graded using a four-point Likert scale. An artificial intelligence algorithm automatically segmented and determined the body compositions and calculated the percentages of lean body weight. The hepatic enhancements were adjusted for iodine dose and iodine dose per total body weight, as well as percentage lean body weight. The associations between enhancement and total body weight, body mass index, and lean body weight were analysed using linear regression. Patients had a median age of 68 years (IQR: 58–74), a total body weight of 81 kg (IQR: 73–90), a body mass index of 26 kg/m2 (SD: ±4.2), and a lean body weight percentage of 50% (IQR: 36–55). Mean liver enhancements in the portal venous phase were 61 ± 12 HU (≤70 kg), 53 ± 10 HU (70–90 kg), and 53 ± 7 HU (≥90 kg). The majority (93%) of scans were rated as good or excellent. Regression analysis showed significant correlations between liver enhancement corrected for injected total iodine and total body weight (r = 0.53; p < 0.001) and between liver enhancement corrected for lean body weight and the percentage of lean body weight (r = 0.73; p < 0.001). Most benefits from personalising iodine injection using %LBW additive to total body weight would be achieved in patients under 90 kg. Liver enhancement is more strongly associated with the percentage of lean body weight than with the total body weight or body mass index. The observed variation in liver enhancement might be reduced by a personalised injection based on the artificial-intelligence-determined percentage of lean body weight.
Reversing Channels and Unsettling Binaries: Rethinking Migration and Agrarian Change under Expanded Border and Immigration Enforcement
Authors: Johnson Richard L.
Published: February 2021

Unauthorized migration under global regimes of border and immigration enforcement has become more risky and costly than ever. Despite the increasing challenges of reaching, remaining in, and remitting from destination countries, scholarship exploring the implications of migration for agricultural and environmental change in migrant-sending regions has largely overlooked the prevalent experiences and consequences of “failed” migration. Drawing from recent fieldwork in Central America with deportees, this paper demonstrates how contemporary migration at times reverses the “channels” of agrarian change in migrant-sending regions: instead of driving remittance inflow and labor loss, migration under contemporary enforcement can result in debt and asset dispossession, increased vulnerability, and heightened labor exploitation. Diverse migration outcomes under expanded enforcement also reveal a need to move beyond the analytical binary that emphasizes differentiations between migrant and non-migrant groups while overlooking the profound socioeconomic unevenness experienced among migrants themselves. With grounding in critical agrarian studies, feminist geographies, and emerging political ecologies of migration, this paper argues that increased attention to the highly dynamic and diverse lived experiences of migration under expanded enforcement stands to enhance our understanding of the multiple ways in which contemporary out-migration shapes livelihoods and landscapes in migrant-sending regions.
Zinc Metalloproteins in Epigenetics and Their Crosstalk
Authors: Yusuf Abdurrahman Pharmacy , Abubakar Murtala Bello , Malami Ibrahim , Ibrahim Kasimu Ghandi , Abubakar Bilyaminu , Bello Muhammad Bashir , Qusty Naeem , Elazab Sara T. , Imam Mustapha Umar , Alexiou Athanasios , Batiha Gaber El-Saber
Published: February 2021

More than half a century ago, zinc was established as an essential micronutrient for normal human physiology. In silico data suggest that about 10% of the human proteome potentially binds zinc. Many proteins with zinc-binding domains (ZBDs) are involved in epigenetic modifications such as DNA methylation and histone modifications, which regulate transcription in physiological and pathological conditions. Zinc metalloproteins in epigenetics are mainly zinc metalloenzymes and zinc finger proteins (ZFPs), which are classified into writers, erasers, readers, editors, and feeders. Altogether, these classes of proteins engage in crosstalk that fundamentally maintains the epigenome’s modus operandi. Changes in the expression or function of these proteins induced by zinc deficiency or loss of function mutations in their ZBDs may lead to aberrant epigenetic reprogramming, which may worsen the risk of non-communicable chronic diseases. This review attempts to address zinc’s role and its proteins in natural epigenetic programming and artificial reprogramming and briefly discusses how the ZBDs in these proteins interact with the chromatin.
In Vitro Evaluation of Desensitizing Agents Containing Bioactive Scaffolds of Nanofibers on Dentin Remineralization
Authors: Bastos-Bitencourt Natália , Velo Marilia , Nascimento Tatiana , Scotti Cassiana , da Fonseca Maria Gardennia , Goulart Luiz , Castellano Lucio , Ishikiriama Sergio , Bombonatti Juliana , Sauro Salvatore
Published: February 2021

This study evaluated the effect of the incorporation of bioactive nanofibers in desensitizing agents on dentin permeability. Sixty disks of dentin were randomly distributed in four groups (n = 15). Distribution was based on the desensitizing agents, fluoride varnish and self-etching adhesive, and the presence of nanofibers: C (self-etching adhesive Clearfil SE Bond), CN (Clearfil SE Bond with 1% nanofiber), D (Duraphat varnish), and DN (Duraphat varnish with 1% nanofiber). Dentin permeability was determined using hydraulic conductivity. For a qualitative analysis, confocal laser microscopy and scanning electron microscopy were performed. The C group showed the lowest hydraulic conductance (Lp%) (89.33), while the DN group showed the highest Lp% (116.06). No statistical significance was observed in the Lp% values in all groups after the treatment and 6% citric acid challenge (p > 0.239). In the images, the CN group presented a higher superficial and intratubular deposition. In addition, this group presented a more homogeneous dentin surface and wide occlusion of dentinal tubules than the other treatments. Despite there being no statistical differences among the treatments employed, the images showed that the CN group presented a higher surface and intratubular deposition compared to the other treatments, even after the acid challenge.
Influence of Old Concrete Age, Interface Roughness and Freeze-Thawing Attack on New-to-Old Concrete Structure
Authors: Fan Jingchong , Wu Lili , Zhang Bo
Published: February 2021

The bonding surface structure generated by the repair of concrete structures has been paid more attention as a weak point. The effects of old concrete age, interface roughness, and freeze-thawing (F-T) attack on adhesive interface are comprehensively investigated. In this study, six kinds of interface roughness and five different old concrete age are designed. The interfacial bonding property is mainly evaluated by splitting tensile strength (fts). Fractal analysis was used to characterize the interface roughness using laser scanning data. In general, the fts increased with the increasing value of interface fractal dimension. The relationship between fts and fractal dimension value was further analyzed, considering the old concrete ages and the F-T cycles. The results show that the effect of roughness on the bonding property of new-to-old concrete is more significant than the age of old concrete, and the influence of the F-T cycles on the bonding surface is mainly reflected in the initial stage of the F-T deterioration process. The relative dynamic elasticity modulus decreased obviously under F-T cycles, especially for the specimens with low interface roughness. In combination with the results of two non-destructive methods (ultrasonic non-destructive test and relative dynamic elastic modulus test), the larger roughness and the smaller age of old concrete can improve the bond performance.
The Rheometric Analysis of the Polymer Modifier’s Properties in the Environment of Hydrated Cement
Authors: Moskalova Khrystyna , Aniskin Aleksej , Kozina Goran , Soldo Božo
Published: February 2021

This paper investigates the effect of polymer modifiers (re-dispersible powder, multifunctional additives, methylhydroxyethylcellulose) on the rheological behavior of emulsions, saturated of calcium hydrosilicates to simulate a hydrating cement structure. The subjects of the study were modified emulsions which had varied concentrations of each additive and they were examined comparatively to a base emulsion. Tests were performed with a CR-rheometer (“Himpribor-1”, Tula, Russia) applying the Searle measuring principle at various shear rates to characterize viscosity properties. The performance of modified mixtures within the operating period was analyzed by using two parameters—effective viscosity (η) and the proportion of structural failure (|m|). The test results showed that the most important factor influencing rheological characteristics is the addition of methylhydroxyethylcellulose additive—the higher additive amount in the emulsion, the higher the viscosity. Furthermore it was noted in the work that adding olefin sulfonate sodium salt causes reduced viscosities as well as lower shear moduli. If ethylhydroxyethylcellulose and ethylene vinyl acetate additives are used in the same mixture together, the rate of structural failure |m| can be relatively similar and low regardless of whether the mixture has large or small viscosity values.
Design of Nonlinear Control of Gas Turbine Engine Based on Constant Eigenvectors
Authors: Valeev Sagit , Kondratyeva Natalya
Published: February 2021

A gas turbine engine represents a complex dynamic control object. Its characteristics change depending on the state of the environment and the regimes of its operation. This paper discusses an algorithmic approach to the design of a nonlinear controller, based on the concept of constant eigenvectors and analytical design of the control system. The proposed design method makes it possible to ensure the stability and the required quality of transient processes at different acceleration modes. In this case, the constancy of the matrix of the canonical basis of the closed-loop control system is assumed, which guarantees stability. The design of a neural network dynamic model of a gas turbine engine based on a neural network approximator with one input and multiple outputs is considered. An example of the design of a nonlinear controller for a gas turbine engine is considered, the neural network model of which is given in the state space. The application of neural network approximation of controller coefficients is presented.
Accommodating Taste and Scale Heterogeneity for Front-Seat Passenger’ Choice of Seat Belt Usage
Authors: Rezapour Mahdi , Ksaibati Khaled
Published: February 2021

There is growing interest in implementation of the mixed model to account for heterogeneity across population observations. However, it has been argued that the assumption of independent and identically distributed (i.i.d) error terms might not be realistic, and for some observations the scale of the error is greater than others. Consequently, that might result in the error terms’ scale to be varied across those observations. As the standard mixed model could not account for the aforementioned attribute of the observations, extended model, allowing for scale heterogeneity, has been proposed to relax the equal error terms across observations. Thus, in this study we extended the mixed model to the model with heterogeneity in scale, or generalized multinomial logit model (GMNL), to see if accounting for the scale heterogeneity, by adding more flexibility to the distribution, would result in an improvement in the model fit. The study used the choice data related to wearing seat belt across front-seat passengers in Wyoming, with all attributes being individual-specific. The results highlighted that although the effect of the scale parameter was significant, the scale effect was trivial, and accounting for the effect at the cost of added parameters would result in a loss of model fit compared with the standard mixed model. Besides considering the standard mixed and the GMNL, the models with correlated random parameters were considered. The results highlighted that despite having significant correlation across the majority of the random parameters, the goodness of fits favors more parsimonious models with no correlation. The results of this study are specific to the dataset used in this study, and due to the possible fact that the heterogeneity in observations related to the front-seat passengers seat belt use might not be extreme, and do not require extra layer to account for the scale heterogeneity, or accounting for the scale heterogeneity at the cost of added parameters might not be required. Extensive discussion has been made in the content of this paper about the model parameters’ estimations and the mathematical formulation of the methods.
On Laplacian Eigenvalues of the Zero-Divisor Graph Associated to the Ring of Integers Modulo n
Authors: Rather Bilal A. , Pirzada Shariefuddin , Naikoo Tariq A. , Shang Yilun
Published: February 2021

Given a commutative ring R with identity 1≠0, let the set Z(R) denote the set of zero-divisors and let Z*(R)=Z(R)∖{0} be the set of non-zero zero-divisors of R. The zero-divisor graph of R, denoted by Γ(R), is a simple graph whose vertex set is Z*(R) and each pair of vertices in Z*(R) are adjacent when their product is 0. In this article, we find the structure and Laplacian spectrum of the zero-divisor graphs Γ(Zn) for n=pN1qN2, where p<q are primes and N1,N2 are positive integers.
Calculated Shoulder to Gauge Ratio of Fatigue Specimens in PWR Environment
Authors: Simonovski Igor , Mclennan Alec , Mottershead Kevin , Gill Peter , Platts Norman , Bruchhausen Matthias , Waters Joshua L. , Vankeerberghen Marc , Moreno Germán Barrera , Gomez Sergio Arrieta , Novotny Radek
Published: February 2021

A ratio of shoulder to gauge displacements (S2G) is calculated for three different fatigue specimens in a pressurized water environment. This ratio needs to be known beforehand to determine the applied shoulder displacements during the experiment that would result in the desired strain amplitude in the gauge section. Significant impact of both the applied constitutive law and specimen geometry on the S2G is observed. The calculation using the fully elastic constitutive law results in the highest S2G values and compares very well with the analytical values. However, this approach disregards the plastic deformation within the specimens that mostly develops in the gauge section. Using the constitutive laws derived from actual fatigue curves captures the material behaviour under cyclic loading better and results in lower S2G values compared to the ones obtained with the fully elastic constitutive law. Calculating S2G values using elastic–plastic constitutive law based on the monotonic uniaxial tensile test should be avoided as they are significantly lower compared to the ones computed with elastic–plastic laws derived from hysteresis loops at half-life.
Evaluation of Harmonic Structure Obtained in Mechanically Milled Powders and Pulse Plasma Sintered Compacts of Austenitic Steel
Authors: Oleszak Dariusz , Sadurska Aleksandra , Cieślak Grzegorz
Published: February 2021

The paper describes an attempt to obtain harmonic structure (HS) in AISI308L steel. Harmonic structure is the term related to the microstructure fabricated by mechanical milling of metallic powders under soft milling conditions, resulting in the formation of plastically deformed, grain-refined shell and unchanged core. This microstructure can be preserved after successful powder compaction. The powders of AISI308L steel were milled under soft condition up to 50 h and then compacted by pulse plasma sintering at 900–1100 °C. For powders and compacts XRD, SEM and hardness measurements were applied as characterization techniques. The milling process resulted in austenite transformation into nanocrystalline ferrite and formation of grain refined outer layer. The applied pulse plasma sintering parameters allowed preservation of this microstructure and manufacturing of compacts with homogeneous distribution of elements, relative density above 95% and hardness in the range 167–185 HV, depending on sintering temperature. Simultaneously, the starting phase composition was restored, i.e., austenite with 12% contribution of ferrite. The crystallite size of austenite was about 20 nm and was significantly smaller then in starting powders.
Task Planner for Robotic Disassembly of Electric Vehicle Battery Pack
Authors: Choux Martin , Marti Bigorra Eduard , Tyapin Ilya
Published: February 2021

The rapidly growing deployment of Electric Vehicles (EV) put strong demands on the development of Lithium-Ion Batteries (LIBs) but also into its dismantling process, a necessary step for circular economy. The aim of this study is therefore to develop an autonomous task planner for the dismantling of EV Lithium-Ion Battery pack to a module level through the design and implementation of a computer vision system. This research contributes to moving closer towards fully automated EV battery robotic dismantling, an inevitable step for a sustainable world transition to an electric economy. For the proposed task planner the main functions consist in identifying LIB components and their locations, in creating a feasible dismantling plan, and lastly in moving the robot to the detected dismantling positions. Results show that the proposed method has measurement errors lower than 5 mm. In addition, the system is able to perform all the steps in the order and with a total average time of 34 s. The computer vision, robotics and battery disassembly have been successfully unified, resulting in a designed and tested task planner well suited for product with large variations and uncertainties.
Targeted Plasma Metabolic Profiles and Risk of Recurrence in Stage II and III Colorectal Cancer Patients: Results from an International Cohort Consortium
Authors: Ose Jennifer , Gigic Biljana , Brezina Stefanie , Lin Tengda , Baierl Andreas , Geijsen Anne J. M. R. , van Roekel Eline , Robinot Nivonirina , Gicquiau Audrey , Achaintre David , Keski-Rahkonen Pekka , van Duijnhoven Fränzel J. B. , Gumpenberger Tanja , Holowatyj Andreana N. , Kok Dieuwertje E. , Koole Annaleen , Schrotz-King Petra , Ulrich Alexis B. , Schneider Martin , Ulvik Arve , Ueland Per-Magne , Weijenberg Matty P. , Habermann Nina , Scalbert Augustin , Gsur Andrea , Ulrich Cornelia M.
Published: February 2021

The identification of patients at high-risk for colorectal cancer (CRC) recurrence remains an unmet clinical need. The aim of this study was to investigate associations of metabolites with risk of recurrence in stage II/III CRC patients. A targeted metabolomics assay (128 metabolites measured) was performed on pre-surgery collected EDTA plasma samples from n = 440 newly diagnosed stage II/III CRC patients. Patients have been recruited from four prospective cohort studies as part of an international consortium: Metabolomic profiles throughout the continuum of CRC (MetaboCCC). Cox proportional hazard models were computed to investigate associations of metabolites with recurrence, adjusted for age, sex, tumor stage, tumor site, body mass index, and cohort; false discovery rate (FDR) was used to account for multiple testing. Sixty-nine patients (15%) had a recurrence after a median follow-up time of 20 months. We identified 13 metabolites that were nominally associated with a reduced risk of recurrence. None of the associations were statistically significant after controlling for multiple testing. Pathway topology analyses did not reveal statistically significant associations between recurrence and alterations in metabolic pathways (e.g., sphingolipid metabolism p = 0.04; pFDR = 1.00). To conclude, we did not observe statistically significant associations between metabolites and CRC recurrence using a well-established metabolomics assay. The observed results require follow-up in larger studies.
Unraveling the Gut Microbiome of the Invasive Small Indian Mongoose (Urva auropunctata) in the Caribbean
Authors: Becker Anne A. M. J. , Hill KC , Butaye Patrick
Published: February 2021

Small Indian mongooses (Urva auropunctata) are among the most pervasive predators to disrupt the native ecology on Caribbean islands and are strongly entrenched in their areas of introduction. Few studies, however, have considered the microbial ecology of such biological invasions. In this study, we investigated the gut microbiota of invasive small Indian mongooses in terms of taxonomic diversity and functional potential. To this end, we collected fecal samples from 60 free-roaming mongooses trapped in different vegetation zones on the island Saint Kitts. The core gut microbiome, assessed by 16S rRNA amplicon gene sequencing on the Ion S5TM XL platform, reflects a carnivore-like signature with a dominant abundance of Firmicutes (54.96%), followed by Proteobacteria (13.98%) and Fusobacteria (12.39%), and a relatively minor contribution of Actinobacteria (10.4%) and Bacteroidetes (6.40%). Mongooses trapped at coastal sites exhibited a higher relative abundance of Fusobacterium spp. whereas those trapped in scrubland areas were enriched in Bacteroidetes, but there was no site-specific difference in predicted metabolic properties. Between males and females, beta-diversity was not significantly different and no sex-specific strategies for energy production were observed. However, the relative abundance of Gammaproteobacteria, and more specifically, Enterobacteriaceae, was significantly higher in males. This first description of the microbial profile of small Indian mongooses provides new insights into their bioecology and can serve as a springboard to further elucidating this invasive predator’s impact throughout the Caribbean.
Pyrazole Scaffold Synthesis, Functionalization, and Applications in Alzheimer’s Disease and Parkinson’s Disease Treatment (2011–2020)
Authors: Li Xuefei , Yu Yanbo , Tu Zhude
Published: February 2021

The remarkable prevalence of pyrazole scaffolds in a versatile array of bioactive molecules ranging from apixaban, an anticoagulant used to treat and prevent blood clots and stroke, to bixafen, a pyrazole-carboxamide fungicide used to control diseases of rapeseed and cereal plants, has encouraged both medicinal and organic chemists to explore new methods in developing pyrazole-containing compounds for different applications. Although numerous synthetic strategies have been developed in the last 10 years, there has not been a comprehensive overview of synthesis and the implication of recent advances for treating neurodegenerative disease. This review first presents the advances in pyrazole scaffold synthesis and their functionalization that have been published during the last decade (2011–2020). We then narrow the focus to the application of these strategies in the development of therapeutics for neurodegenerative diseases, particularly for Alzheimer’s disease (AD) and Parkinson’s disease (PD).
Generative Adversarial Learning of Protein Tertiary Structures
Authors: Rahman Taseef , Du Yuanqi , Zhao Liang , Shehu Amarda
Published: February 2021

Protein molecules are inherently dynamic and modulate their interactions with different molecular partners by accessing different tertiary structures under physiological conditions. Elucidating such structures remains challenging. Current momentum in deep learning and the powerful performance of generative adversarial networks (GANs) in complex domains, such as computer vision, inspires us to investigate GANs on their ability to generate physically-realistic protein tertiary structures. The analysis presented here shows that several GAN models fail to capture complex, distal structural patterns present in protein tertiary structures. The study additionally reveals that mechanisms touted as effective in stabilizing the training of a GAN model are not all effective, and that performance based on loss alone may be orthogonal to performance based on the quality of generated datasets. A novel contribution in this study is the demonstration that Wasserstein GAN strikes a good balance and manages to capture both local and distal patterns, thus presenting a first step towards more powerful deep generative models for exploring a possibly very diverse set of structures supporting diverse activities of a protein molecule in the cell.
1,3-Diketone Calix[4]arene Derivatives—A New Type of Versatile Ligands for Metal Complexes and Nanoparticles
Authors: Podyachev Sergey N. , Zairov Rustem R. , Mustafina Asiya R.
Published: February 2021

The present review is aimed at highlighting outlooks for cyclophanic 1,3-diketones as a new type of versatile ligands and building blocks of the nanomaterial for sensing and bioimaging. Thus, the main synthetic routes for achieving the structural diversity of cyclophanic 1,3-diketones are discussed. The structural diversity is demonstrated by variation of both cyclophanic backbones (calix[4]arene, calix[4]resorcinarene and thiacalix[4]arene) and embedding of different substituents onto lower or upper macrocyclic rims. The structural features of the cyclophanic 1,3-diketones are correlated with their ability to form lanthanide complexes exhibiting both lanthanide-centered luminescence and magnetic relaxivity parameters convenient for contrast effect in magnetic resonance imaging (MRI). The revealed structure–property relationships and the applicability of facile one-pot transformation of the complexes to hydrophilic nanoparticles demonstrates the advantages of 1,3-diketone calix[4]arene ligands and their complexes in developing of nanomaterials for sensing and bioimaging.
Molecular Understanding of Electrochemical–Mechanical Responses in Carbon-Coated Silicon Nanotubes during Lithiation
Authors: Feng Chen , Liu Shiyuan , Li Junjie , Li Maoyuan , Cheng Siyi , Chen Chen , Shi Tielin , Tang Zirong
Published: February 2021

Carbon-coated silicon nanotube (SiNT@CNT) anodes show tremendous potential in high-performance lithium ion batteries (LIBs). Unfortunately, to realize the commercial application, it is still required to further optimize the structural design for better durability and safety. Here, the electrochemical and mechanical evolution in lithiated SiNT@CNT nanohybrids are investigated using large-scale atomistic simulations. More importantly, the lithiation responses of SiNW@CNT nanohybrids are also investigated in the same simulation conditions as references. The simulations quantitatively reveal that the inner hole of the SiNT alleviates the compressive stress concentration between a-LixSi and C phases, resulting in the SiNT@CNT having a higher Li capacity and faster lithiation rate than SiNW@CNT. The contact mode significantly regulates the stress distribution at the inner hole surface, further affecting the morphological evolution and structural stability. The inner hole of bare SiNT shows good structural stability due to no stress concentration, while that of concentric SiNT@CNT undergoes dramatic shrinkage due to compressive stress concentration, and that of eccentric SiNT@CNT is deformed due to the mismatch of stress distribution. These findings not only enrich the atomic understanding of the electrochemical–mechanical coupled mechanism in lithiated SiNT@CNT nanohybrids but also provide feasible solutions to optimize the charging strategy and tune the nanostructure of SiNT-based electrode materials.
Electric Transport in Gold-Covered Sodium–Alginate Free-Standing Foils
Authors: Barone Carlo , Bertoldo Monica , Capelli Raffaella , Dinelli Franco , Maccagnani Piera , Martucciello Nadia , Mauro Costantino , Pagano Sergio
Published: February 2021

The electric transport properties of flexible and transparent conducting bilayers, realized by sputtering ultrathin gold nanometric layers on sodium–alginate free-standing films, were studied. The reported results cover a range of temperatures from 3 to 300 K. In the case of gold layer thicknesses larger than 5 nm, a typical metallic behavior was observed. Conversely, for a gold thickness of 4.5 nm, an unusual resistance temperature dependence was found. The dominant transport mechanism below 70 K was identified as a fluctuation-induced tunneling process. This indicates that the conductive region is not continuous but is formed by gold clusters embedded in the polymeric matrix. Above 70 K, instead, the data can be interpreted using a phenomenological model, which assumes an anomalous expansion of the conductive region upon decreasing the temperature, in the range from 300 to 200 K. The approach herein adopted, complemented with other characterizations, can provide useful information for the development of innovative and green optoelectronics.
Multiple Selection Criteria for Probiotic Strains with High Potential for Obesity Management
Authors: Alard Jeanne , Cudennec Benoit , Boutillier Denise , Peucelle Véronique , Descat Amandine , Decoin Raphaël , Kuylle Sarah , Jablaoui Amin , Rhimi Moez , Wolowczuk Isabelle , Pot Bruno , Tailleux Anne , Maguin Emmanuelle , Holowacz Sophie , Grangette Corinne
Published: February 2021

Since alterations of the gut microbiota have been shown to play a major role in obesity, probiotics have attracted attention. Our aim was to identify probiotic candidates for the management of obesity using a combination of in vitro and in vivo approaches. We evaluated in vitro the ability of 23 strains to limit lipid accumulation in adipocytes and to enhance the secretion of satiety-promoting gut peptide in enteroendocrine cells. Following the in vitro screening, selected strains were further investigated in vivo, single, or as mixtures, using a murine model of diet-induced obesity. Strain Bifidobacterium longum PI10 administrated alone and the mixture of B. animalis subsp. lactis LA804 and Lactobacillus gasseri LA806 limited body weight gain and reduced obesity-associated metabolic dysfunction and inflammation. These protective effects were associated with changes in the hypothalamic gene expression of leptin and leptin receptor as well as with changes in the composition of gut microbiota and the profile of bile acids. This study provides crucial clues to identify new potential probiotics as effective therapeutic approaches in the management of obesity, while also providing some insights into their mechanisms of action.
Association between Sour Taste SNP KCNJ2-rs236514, Diet Quality and Mild Cognitive Impairment in an Elderly Cohort
Authors: Ferraris Celeste , Turner Alexandria , Scarlett Christopher , Veysey Martin , Lucock Mark , Bucher Tamara , Beckett Emma L.
Published: February 2021

Differences in sour-taste thresholds have been identified in cognition-related diseases. Diet is a modulator of cognitive health, and taste perception influences dietary preferences and habits. Heritable genetics and polymorphisms in the KCNJ2 gene involved in the transduction of sour taste have been linked to variations in sour taste and non-gustatory functions. However, relationships between sour taste genetics, mild cognitive impairment, and diet quality are yet to be elucidated. This study investigated the associations between the presence of the KCNJ2-rs236514 variant (A) allele, diet quality indices, and mild cognitive impairment evaluated by the Mini-Mental State Examination (MMSE), in a secondary cross-sectional analysis of data from the Retirement Health & Lifestyle Study. Data from 524 elderly Australians (≥65y) were analyzed, using standard least squares regression and nominal logistic regression modeling, with demographic adjustments applied. Results showed that the presence of the KCNJ2-A allele is associated with increased proportions of participants scoring in the range indicative of mild or more severe cognitive impairment (MMSE score of ≤26) in the total cohort, and males. These associations remained statistically significant after adjusting for age, sex, and diet quality indices. The absence of association between the KCNJ2-A allele and cognitive impairment in women may be related to their higher diet quality scores in all indices. The potential link between sour taste genotype and cognitive impairment scores may be due to both oral and extra-oral functions of sour taste receptors. Further studies are required on the role and relationship of neurotransmitters, sour taste genotypes and sour taste receptors in the brain, and dietary implications, to identify potential risk groups or avenues for therapeutic or prophylactic interventions.
First Detection of the West Nile Virus Koutango Lineage in Sandflies in Niger
Authors: Fall Gamou , Diallo Diawo , Soumaila Hadiza , Ndiaye El Hadji , Lagare Adamou , Sadio Bacary Djilocalisse , Ndione Marie Henriette Dior , Wiley Michael , Dia Moussa , Diop Mamadou , Ba Arame , Sidikou Fati , Ngoy Bienvenu Baruani , Faye Oumar , Testa Jean , Loucoubar Cheikh , Sall Amadou Alpha , Diallo Mawlouth , Faye Ousmane
Published: February 2021

West Nile virus (WNV), belonging to the Flaviviridae family, causes a mosquito-borne disease and shows great genetic diversity, with at least eight different lineages. The Koutango lineage of WNV (WN-KOUTV), mostly associated with ticks and rodents in the wild, is exclusively present in Africa and shows evidence of infection in humans and high virulence in mice. In 2016, in a context of Rift Valley fever (RVF) outbreak in Niger, mosquitoes, biting midges and sandflies were collected for arbovirus isolation using cell culture, immunofluorescence and RT-PCR assays. Whole genome sequencing and in vivo replication studies using mice were later conducted on positive samples. The WN-KOUTV strain was detected in a sandfly pool. The sequence analyses and replication studies confirmed that this strain belonged to the WN-KOUTV lineage and caused 100% mortality of mice. Further studies should be done to assess what genetic traits of WN-KOUTV influence this very high virulence in mice. In addition, given the risk of WN-KOUTV to infect humans, the possibility of multiple vectors as well as birds as reservoirs of WNV, to spread the virus beyond Africa, and the increasing threats of flavivirus infections in the world, it is important to understand the potential of WN-KOUTV to emerge.
Human Papillomavirus and Cellular Pathways: Hits and Targets
Authors: Medda Alessandro , Duca Daria , Chiocca Susanna
Published: February 2021

The Human Papillomavirus (HPV) is the causative agent of different kinds of tumors, including cervical cancers, non-melanoma skin cancers, anogenital cancers, and head and neck cancers. Despite the vaccination campaigns implemented over the last decades, we are far from eradicating HPV-driven malignancies. Moreover, the lack of targeted therapies to tackle HPV-related tumors exacerbates this problem. Biomarkers for early detection of the pathology and more tailored therapeutic approaches are needed, and a complete understanding of HPV-driven tumorigenesis is essential to reach this goal. In this review, we overview the molecular pathways implicated in HPV infection and carcinogenesis, emphasizing the potential targets for new therapeutic strategies as well as new biomarkers.