bluuebunny/crossref_metadata_2025 huggingface dataset:
The Smart Aging Platform for Assessing Early Phases of Cognitive Impairment in Patients With Neurodegenerative Diseases
Authors: Bottiroli Sara , Bernini Sara , Cavallini Elena , Sinforiani Elena , Zucchella Chiara , Pazzi Stefania , Cristiani Paolo , Vecchi Tomaso , Tost Daniela , Sandrini Giorgio , Tassorelli Cristina
Published: March 2021

Background:Smart Aging is a serious game (SG) platform that generates a 3D virtual reality environment in which users perform a set of screening tasks designed to allow evaluation of global cognition. Each task replicates activities of daily living performed in a familiar environment. The main goal of the present study was to ascertain whether Smart Aging could differentiate between different types and levels of cognitive impairment in patients with neurodegenerative disease.

Methods:Ninety-one subjects (mean age = 70.29 ± 7.70 years)—healthy older adults (HCs,n= 23), patients with single-domain amnesic mild cognitive impairment (aMCI,n= 23), patients with single-domain executive Parkinson's disease MCI (PD-MCI,n= 20), and patients with mild Alzheimer's disease (mild AD,n= 25)—were enrolled in the study. All participants underwent cognitive evaluations performed using both traditional neuropsychological assessment tools, including the Mini-Mental State Examination (MMSE), Montreal Overall Cognitive Assessment (MoCA), and the Smart Aging platform. We analyzed global scores on Smart Aging indices (i.e., accuracy, time, distance) as well as the Smart Aging total score, looking for differences between the four groups.

Results:The findings revealed significant between-group differences in all the Smart Aging indices: accuracy (p< 0.001), time (p< 0.001), distance (p< 0.001), and total Smart Aging score (p< 0.001). The HCs outperformed the mild AD, aMCI, and PD-MCI patients in terms of accuracy, time, distance, and Smart Aging total score. In addition, the mild AD group was outperformed both by the HCs and by the aMCI and PD-MCI patients on accuracy and distance. No significant differences were found between aMCI and PD-MCI patients. Finally, the Smart Aging scores significantly correlated with the results of the neuropsychological assessments used.

Conclusion:These findings, although preliminary due to the small sample size, suggest the validity of Smart Aging as a screening tool for the detection of cognitive impairment in patients with neurodegenerative diseases.
A Mixed Methods Research Study of Parental Perception of Physical Activity and Quality of Life of Children Under Home Lock Down in the COVID-19 Pandemic
Authors: López-Aymes Gabriela , Valadez María de los Dolores , Rodríguez-Naveiras Elena , Castellanos-Simons Doris , Aguirre Triana , Borges África
Published: March 2021

Household confinement due to the rapid spread of the pandemic caused by COVID-19 has brought very significant changes, such as the forced stay-at-home of children due to the closure of schools. This has meant drastic changes in the organization of daily life and restrictions on their activities, including exercise, which could affect the quality of life of the children due to its importance. In order to study the relationship between physical activity and psychological well-being of minors, a study has been carried out with Mixed Methods Research, combining survey methodology with transversal design with qualitative methodology using discourse analysis. A total of 234 parents of minors in Spain and several Spanish-speaking countries in America participated. The instrument was a questionnaire in Google Forms, which included the Kidscreen-27 quality of life scale. The results show significant differences in both the type of physical activity and its frequency due to age, and differences in parents’ perception of whether their children’s physical activity levels were sufficient or not, both on the health, mood and school subscales, and in the categorization of open responses referring to concerns due to the pandemic, analyzed with the ALCESTE technique. The relationship between physical activity of children and adolescents and quality of life is clearly concluded.
Executive Functions in Tobacco Use Disorder: New Challenges and Opportunities
Authors: Martín Ríos Raquel , López-Torrecillas Francisca , Martín Tamayo Ignacio
Published: March 2021

There is increasing evidence that executive functions have significative effects on nicotine abuse. An unresolved challenge for smoking cessation interventions is the detection of factors associated with nicotine use. In order to understand how cognition is affected by nicotine abuse, this study was designed to determine the relationship between years of smoking addiction and several variables of executive functions. The sample was composed of 174 smokers, whose age ranged between 27 and 69 years old (M = 47.44; SD = 8.48). Smokers were assessed at baseline with measures of cognitive inhibition [Go/No Go Task and Five Digit Test (FDT)], updating [Visual Search and Attention Test (VSAT) and Letter-Number Sequencing (WAIS IV)] and shifting [Delay Discounting Task (DDT) and Iowa Gambling Task (IGT)] while the outcome measure was years of smoking. The linear regression and correlation analysis highlighting that the variable which has the strongest association with years of smoking is updating. Multivariate analysis of variance (MANCOVA) followed by Tukey post-hoc tests revealed significant differences such that heavy smoking indicated worse performance than light smoking on updating tasks. These findings report the ability of working memory to predict years of smoking and suggest that cigarette packaging warning may experience a loss of effectiveness in heavy smokers.
Political Trust Influences the Relationship Between Income and Life Satisfaction in Europe: Differential Associations With Trust at National, Community, and Individual Level
Authors: Clench-Aas Jocelyne , Holte Arne
Published: March 2021

Background: A high level of well-being is associated with personal, community and national income, as well as personal, social and political trust. How these measures relate to each other within and between countries and within and across structural levels of society is largely unknown. To study this, we propose a three-layer nested socio-structural model. Each layer (individual, community, country) contains a measure of income, trust and satisfaction.

Method: With this model, we analyzed data from two waves of the European Social Survey (ESS, 2006, 2012) in 19 countries (N = 72,461; weighted N = 73,307) with multilevel techniques. Indicators were personal, community, and national income; personal, social and political trust; and personal life satisfaction, social and political satisfaction.

Results: Personal life satisfaction was associated with all income and trust variables. Greatest effect on personal life satisfaction, came from the national level, including political trust and income. However, 2/3 of the variance in personal life satisfaction came from income, that is personal, community and national. Within each socio-structural level, satisfaction was associated with income, but significantly modified by trust. When income and trust at all three levels were included, there was a significant association of the national layer on the social layer, and of the social layer on the individual layer as to the income–personal life satisfaction relationship. Consistent with the “the buffer hypothesis,” all three forms of trust acted as a buffer against the effect of personal income on life satisfaction. Low-trust countries had strong income–personal life satisfaction associations and the moderating role of trust was also stronger. High- and medium-trust countries had no such associations. Likewise, direct associations between political and personal trust were much stronger in the low-trust countries.

Conclusion: The model presented in this study provides authorities with a framework for policies that will improve the general well-being of their population. Trust and income strongly influence personal life satisfaction. Money is the most important. However, trust forcefully dampens the effect of income. Politicians who want to enhance their population's personal life satisfaction, should raise the levels of trust in their electorate.
Impact of Public Health Education Program on the Novel Coronavirus Outbreak in the United States
Authors: Iboi Enahoro , Richardson Ariana , Ruffin Rachel , Ingram DeAndrea , Clark Jailyn , Hawkins Jala , McKinney Maati , Horne Nianza , Ponder Reyla , Denton Zoe , Agusto Folashade B. , Oduro Bismark , Akinyemi Lanre
Published: March 2021

The coronavirus outbreak in the United States continues to pose a serious threat to human lives. Public health measures to slow down the spread of the virus involve using a face mask, social-distancing, and frequent hand washing. Since the beginning of the pandemic, there has been a global campaign on the use of non-pharmaceutical interventions (NPIs) to curtail the spread of the virus. However, the number of cases, mortality, and hospitalization continue to rise globally, including in the United States. We developed a mathematical model to assess the impact of a public health education program on the coronavirus outbreak in the United States. Our simulation showed the prospect of an effective public health education program in reducing both the cumulative and daily mortality of the novel coronavirus. Finally, our result suggests the need to obey public health measures as loss of willingness would increase the cumulative and daily mortality in the United States.
Evaluation of Lettuce Growth, Yield, and Economic Viability Grown Vertically on Unutilized Building Wall in Dhaka City
Authors: Islam Rinita , Solaiman Abul Hasnat M. , Kabir Md. Humayun , Arefin S. M. Anamul , Azad Md. Obyedul Kalam , Siddiqee Mahbubul H. , Alsanius Beatrix W. , Naznin Most Tahera
Published: March 2021

Production of safe food in the densely populated areas of the developing countries is the most challenging issue due to the speedy urbanization, fragile food transportation facilities, and reduced farmlands. Given this background, a study was conducted to evaluate the agronomic properties and economic viability of lettuce grown vertically in the wall of building in Dhaka city, Bangladesh. Two lettuce cultivars (V1: Green wave and V2: New red fire) and three organic growing media (P1: 40% soil + 40% vermicompost + 20% coir; P2: 50% soil + 50% vermicompost; P3: 20% soil + 40% vermicompost + 40% spent mushroom compost) along with control (P0:100% soil) were used. The results revealed that plant height, leaf area, fresh weight, dry weight, and total yield of leaf lettuce were significantly increased when the green-leafed cultivar (VI) was grown in the P1 compared to all other treatments, but V2 got maximum sensory attribute scores when grown in the P1. Lettuce leaves grown in the formulated growing media (P1, P2, and P3) had higher microbial infestation whereas, a lower content occurred in the P0. The higher economic return was observed in V1P1. These results provided baseline information for further study on urban commercial vertical farming on the building walls. These demonstrate the agronomic and economic potential for vertical farming in densely populated areas but emphasize the need for optimized food safety strategies.
Revealing New Candidate Genes for Teat Number Relevant Traits in Duroc Pigs Using Genome-Wide Association Studies
Authors: Li Yang , Pu Lei , Shi Liangyu , Gao Hongding , Zhang Pengfei , Wang Lixian , Zhao Fuping
Published: March 2021

The number of teats is related to the nursing ability of sows. In the present study, we conducted genome-wide association studies (GWAS) for traits related to teat number in Duroc pig population. Two mixed models, one for counted and another for binary phenotypic traits, were employed to analyze seven traits: the right (RTN), left (LTN), and total (TTN) teat numbers; maximum teat number on a side (MAX); left minus right side teat number (LR); the absolute value of LR (ALR); and the presence of symmetry between left and right teat numbers (SLR). We identified 11, 1, 4, 13, and 9 significant SNPs associated with traits RTN, LTN, MAX, TTN, and SLR, respectively. One significant SNP (MARC0038565) was found to be simultaneous associated with RTN, LTN, MAX and TTN. Two annotated genes (VRTN and SYNDIG1L) were located in genomic region around this SNP. Three significant SNPs were shown to be associated with TTN, RTN and MAX traits. Seven significant SNPs were simultaneously detected in two traits of TTN and RTN. Other two SNPs were only identified in TTN. These 13 SNPs were clustered in the genomic region between 96.10—98.09 Mb on chromosome 7. Moreover, nine significant SNPs were shown to be significantly associated with SLR. In total, four and 22 SNPs surpassed genome-wide significance and suggestive significance levels, respectively. Among candidate genes annotated, eight genes have documented association with the teat number relevant traits. Out of them, DPF3 genes on Sus scrofa chromosome (SSC) 7 and the NRP1 gene on SSC 10 were new candidate genes identified in this study. Our findings demonstrate the genetic mechanism of teat number relevant traits and provide a reference to further improve reproductive performances in practical pig breeding programs.
Immunoregulatory Effects of Porcine Plasma Protein Concentrates on Rat Intestinal Epithelial Cells and Splenocytes
Authors: Hernández-Chirlaque Cristina , Aranda Carlos J. , Ocón Borja , Polo Javier , Martínez-Augustin Olga , Sánchez de Medina Fermín
Published: March 2021

Serum protein concentrates have been shown to exert in vivo anti-inflammatory effects. Specific effects on different cell types and their mechanism of action remain unraveled. We aimed to characterize the immunomodulatory effect of two porcine plasma protein concentrates, spray dried serum (SDS) and an immunoglobulin concentrate (IC), currently used as animal nutritional supplements with established in vivo immunomodulatory properties. Cytokine production by the intestinal epithelial cell line IEC18 and by primary cultures of rat splenocytes was studied. The molecular pathways involved were explored with specific inhibitors and gene knockdown. Our results indicate that both products induced GROα and MCP-1 production in IEC18 cells by a MyD88/NF-κB-dependent mechanism. Inhibition of TNF production was observed in rat primary splenocyte cultures. The immunoglobulin concentrate induced IL-10 expression in primary splenocytes and lymphocytes. The effect on TNF was independent of IL-10 production or the stimulation of NF-kB, MAPKs, AKT, or RAGE. In conclusion, SDS and IC directly regulate intestinal and systemic immune response in murine intestinal epithelial cells and in T lymphocytes and monocytes.
Clinical and Histopathological Features of Renal Maldevelopment in Boxer Dogs: A Retrospective Case Series (1999–2018)
Authors: Cavalera Maria Alfonsa , Gernone Floriana , Uva Annamaria , D’Ippolito Paola , Roura Xavier , Zatelli Andrea
Published: March 2021

Renal maldevelopment (RM) has been proposed to replace the old and sometimes misused term “renal dysplasia” in dogs. Although renal dysplasia has been described in Boxers, hereditary transmission has only been hypothesized. This study reports clinical and renal histological findings in Boxer dogs with RM, proposing a possible mode of inheritance. Medical records of 9 female Boxer dogs, older than 5 months and with a clinical diagnosis of chronic kidney disease prior to one year of age, were retrospectively reviewed. Polyuria and polydipsia (PU/PD), decreased appetite, weight loss, lethargy and weakness were described in all affected dogs. Common laboratory findings were proteinuria, diluted urine, non-regenerative anemia, azotemia, hyperphosphatemia, hypoalbuminemia and hypercholesterolemia. Histopathology of the kidneys revealed the presence of immature glomeruli in all dogs, which is consistent with RM. In 7 related dogs, the pedigree analysis showed that a simple autosomal recessive trait may be a possible mode of inheritance. Renal maldevelopment should be suspected in young Boxer dogs with a history of PU/PD, decreased appetite, weight loss, lethargy, weakness and proteinuria. Due to its possible inheritance, an early diagnosis of RM may allow clinicians to promptly identify other potentially affected dogs among the relatives of the diagnosed case.
Artistic Freedom or Animal Cruelty? Contemporary Visual Art Practice That Involves Live and Deceased Animals
Authors: Coleman Ellie , Scollen Rebecca , Batorowicz Beata , Akenson David
Published: March 2021

This paper examines a selection of 21st-century international examples of exhibited visual artworks involving live or deceased animals. It seeks to reveal the risks and benefits of unique encounters with animals through art and to consider the ethical implications of artwork deploying animals. Australian and international animal protection laws are not explicit when it comes to the sourcing of animals for art nor for the direct inclusion of animals in artworks. This lack leads to a variety of artistic practices, some considered ethical while others are viewed as controversial, bordering on animal cruelty. Artwork selection is determined by a focus on high-profile artists who intentionally use animals in their practice and whose reputation has been fostered by this intention. The study provides insight into how the intentional use of ethically sourced animals within art practice can be a method of addressing hierarchal human–animal imbalances. Further, this study identifies unethical practices that may be best avoided regardless of the pro-animal political statements the artists put forward. Recommendations of how to better determine what is an acceptable use of animals in art with a view to informing legal guidelines and artistic best practice are presented.
The Relation between Hair-Cortisol Concentration and Various Welfare Assessments of Dutch Dairy Farms
Authors: van Eerdenburg Frank J. C. M. , Hof Tessa , Doeve Benthe , Ravesloot Lars , Zeinstra Elly C. , Nordquist Rebecca E. , van der Staay Franz Josef
Published: March 2021

Many protocols have been developed to assess farm animal welfare. However, the validity of these protocols is still subject to debate. The present study aimed to compare nine welfare assessment protocols, namely: (1) Welfare Quality© (WQ), (2) a modified version of Welfare Quality (WQ Mod), which has a better discriminative power, (3) WelzijnsWijzer (Welfare Indicator; WW), (4) a new Welfare Monitor (WM), (5) Continue Welzijns Monitor (Continuous Welfare Monitor; CWM), (6) KoeKompas (Cow Compass; KK), (7) Cow Comfort Scoring System (CCSS), (8) Stall Standing Index (SSI) and (9) a Welfare Index (WI Tuyttens). In addition, a simple welfare estimation by veterinarians (Estimate vets, EV) was added. Rank correlation coefficients were calculated between each of the welfare assessment protocol scores and mean hair cortisol concentrations from 10 cows at 58 dairy farms spread over the Netherlands. Because it has been suggested that the hair cortisol level is related to stress, experienced over a long period of time, we expected a negative correlation between cortisol and the result of the welfare protocol scores. Only the simple welfare estimation by veterinarians (EV) (ρ = −0.28) had a poor, but significant, negative correlation with hair cortisol. This correlations, however, failed to reach significance after correction of p-values for multiple correlations. Most of the results of the different welfare assessment protocols had a poor, fair or strong positive correlation with each other, supporting the notion that they measure something similar. Additional analyses revealed that the modified Welfare Quality protocol parameters housing (ρ = −0.30), the new Welfare Monitor (WM) parameter health (ρ = −0.33), and milk yield (ρ = −0.33) showed negative correlations with cortisol. We conclude that because only five out of all the parameter scores from the welfare assessment protocols showed a negative, albeit weak, correlation with cortisol, hair cortisol levels may not provide a long term indicator for stress in dairy cattle, or alternatively, that the protocols might not yield valid indices for cow welfare.
Emotional States of African Elephants (Loxodonta africana) Kept for Animal–Visitor Interactions, as Perceived by People Differing in Age and Knowledge of the Species
Authors: Pollastri Ilaria , Normando Simona , Contiero Barbara , Vogt Gregory , Gelli Donatella , Sergi Veronica , Stagni Elena , Hensman Sean , Mercugliano Elena , de Mori Barbara
Published: March 2021

This study aimed to investigate how three groups of people of differing ages, and with differing knowledge of the species, perceived the emotional state of African elephants (Loxodonta africana) managed in captive and semi-captive environments. Fifteen video-clips of 18 elephants, observed during three different daily routines (release from and return to the night boma; interactions with visitors), were used for a free choice profiling assessment (FCP) and then analyzed with quantitative methods. A general Procrustes analysis identified two main descriptive dimensions of elephant behavioral expression explaining 27% and 19% of the variability in the children group, 19% and 23.7% in adults, and 21.8% and 17% in the expert group. All the descriptors the observers came up with showed a low level of correlation on the identified dimensions. All three observers’ groups showed a degree of separation between captive and semi-captive management. Spearman analyses showed that stereotypic “trunk swirling” behavior correlated negatively with first dimension (free/friendly versus sad/bored) in the children’s group; second dimension (agitated/confident versus angry/bored) amongst the adults; and first dimension (active/excited versus agitated/bored) amongst the experts. More studies are needed to investigate other potential differences in assessing elephants’ emotional states by visitors of different ages and backgrounds.
Nucleoredoxin Knockdown in SH-SY5Y Cells Promotes Cell Renewal
Authors: Valek Lucie , Tegeder Irmgard
Published: March 2021

Nucleoredoxin (NXN) is a redox regulator of Disheveled and thereby of WNT signaling. Deficiency in mice leads to cranial dysmorphisms and defects of heart, brain, and bone, suggesting defects of cell fate determination. We used shRNA-mediated knockdown of NXN in SH-SY5Y neuroblastoma cells to study its impact on neuronal cells. We expected that shNXN cells would easily succumb to redox stress, but there were no differences in viability on stimulation with hydrogen peroxide. Instead, the proliferation of naïve shNXN cells was increased with a higher rate of mitotic cells in cell cycle analyses. In addition, basal respiratory rates were higher, whereas the relative change in oxygen consumption upon mitochondrial stressors was similar to control cells. shNXN cells had an increased expression of redox-sensitive heat shock proteins, Hsc70/HSPA8 and HSP90, and autophagy markers suggested an increase in autophagosome formation upon stimulation with bafilomycin and higher flux under low dose rapamycin. A high rate of self-renewal, autophagy, and upregulation of redox-sensitive chaperones appears to be an attractive anti-aging combination if it were to occur in neurons in vivo for which SH-SY5Y cells are a model.
Particle Emissions and Disc Temperature Profiles from a Commercial Brake System Tested on a Dynamometer under Real-World Cycles
Authors: Mamakos Athanasios , Kolbeck Katharina , Arndt Michael , Schröder Thomas , Bernhard Matthias
Published: March 2021

The particle emissions from a commercial brake system utilizing copper-free pads have been characterized on a brake dynamometer under two real-world driving cycles. These included a novel cycle developed from analysis of the database of the World Harmonized Test Procedure (WLTP-Brake) and a short version of the Los Angeles City Traffic cycle (3h-LACT) developed in the framework of the European LowBraSys project. Disc temperature measurements using an array of embedded thermocouples revealed a large temporal and spatial non-uniformity with the radial temperature distribution depending also on the test procedure. Averaging over the duration of the cycle, it effectively reduced the influence of thermocouple positioning, allowing for more reliable quantification of the effectiveness of convective cooling. Particulate Matter (PM) emissions were similar for both cycles with PM2.5 averaging at 2.2 (±0.2) mg/km over the WLTP-Brake and 2.2 (±0.2) mg/km over the 3h-LACT, respectively. The corresponding PM10 emissions were 5.6 (±0.2) mg/km and 8.6 (±0.7) mg/km, respectively. The measurements revealed the formation of nanosized particles peaking at 10 nm, which were thermally stable at 350 °C under both cycles. Volatile nanoparticles were observed over the more demanding 3h-LACT cycle, with their emission rates decreasing with increasing the tunnel flow, suggesting nucleation of organic vapors released during braking as a potential formation process.
Balloons and Quadcopters: Intercomparison of Two Low-Cost Wind Profiling Methods
Authors: Varentsov Mikhail , Stepanenko Victor , Repina Irina , Artamonov Arseniy , Bogomolov Vasiliy , Kuksova Natalia , Marchuk Ekaterina , Pashkin Artem , Varentsov Alexander
Published: March 2021

Experimental field campaigns are an essential part of atmospheric research, as well as of university education in the field of atmospheric physics and meteorology. Experimental field observations are needed to improve the understanding of the surface-atmosphere interaction and atmospheric boundary layer (ABL) physics and develop corresponding model parameterizations. Information on the ABL wind profiles is essential for the interpretation of other observations. However, wind profile measurements above the surface layer remain challenging and expensive, especially for the field campaigns performed in remote places and harsh conditions. In this study, we consider the experience of using two low-cost methods for the wind profiling, which may be easily applied in the field studies with modest demands on logistical opportunities, available infrastructure, and budget. The first one is a classical and well-known method of pilot balloon sounding, i.e., when balloon is treated as a Lagrangian particle and tracked by theodolite observations of angular coordinates. Second one is based on a vertical sounding with a popular and relatively cheap mass-market quadcopter DJI Phantom 4 Pro and utilizes its built-in opportunity to restore the wind vector from quadcopter tilt angles. Both methods demonstrated reasonable agreement and applicability even in harsh weather conditions and complex terrain. Advantages and shortcomings of these methods, as well as practical recommendations for their use are discussed. For the drone-based wind estimation, the importance of calibration by comparison to high-quality wind observations is shown.
Nanostructure, Self-Assembly, Mechanical Properties, and Antioxidant Activity of a Lupin-Derived Peptide Hydrogel
Authors: Pugliese Raffaele , Arnoldi Anna , Lammi Carmen
Published: March 2021

Naturally occurring food peptides are frequently used in the life sciences due to their beneficial effects through their impact on specific biochemical pathways. Furthermore, they are often leveraged for applications in areas as diverse as bioengineering, medicine, agriculture, and even fashion. However, progress toward understanding their self-assembling properties as functional materials are often hindered by their long aromatic and charged residue-enriched sequences encrypted in the parent protein sequence. In this study, we elucidate the nanostructure and the hierarchical self-assembly propensity of a lupin-derived peptide which belongs to the α-conglutin (11S globulin, legumin-like protein), with a straightforward N-terminal biotinylated oligoglycine tag-based methodology for controlling the nanostructures, biomechanics, and biological features. Extensive characterization was performed via Circular Dichroism (CD) spectroscopy, Fourier Transform Infrared spectroscopy (FT-IR), rheological measurements, and Atomic Force Microscopy (AFM) analyses. By using the biotin tag, we obtained a thixotropic lupin-derived peptide hydrogel (named BT13) with tunable mechanical properties (from 2 to 11 kPa), without impairing its spontaneous formation of β-sheet secondary structures. Lastly, we demonstrated that this hydrogel has antioxidant activity. Altogether, our findings address multiple challenges associated with the development of naturally occurring food peptide-based hydrogels, offering a new tool to both fine tune the mechanical properties and tailor the antioxidant activities, providing new research directions across food chemistry, biochemistry, and bioengineering.
Mechanistic Insights into Alzheimer’s Disease Unveiled through the Investigation of Disturbances in Central Metabolites and Metabolic Pathways
Authors: González-Domínguez Raúl , González-Domínguez Álvaro , Sayago Ana , González-Sanz Juan Diego , Lechuga-Sancho Alfonso María , Fernández-Recamales Ángeles
Published: March 2021

Hydrophilic metabolites are closely involved in multiple primary metabolic pathways and, consequently, play an essential role in the onset and progression of multifactorial human disorders, such as Alzheimer’s disease. This review article provides a comprehensive revision of the literature published on the use of mass spectrometry-based metabolomics platforms for approaching the central metabolome in Alzheimer’s disease research, including direct mass spectrometry, gas chromatography-mass spectrometry, hydrophilic interaction liquid chromatography-mass spectrometry, and capillary electrophoresis-mass spectrometry. Overall, mounting evidence points to profound disturbances that affect a multitude of central metabolic pathways, such as the energy-related metabolism, the urea cycle, the homeostasis of amino acids, fatty acids and nucleotides, neurotransmission, and others.
Development and Carcinogenesis: Roles of GATA Factors in the Sympathoadrenal and Urogenital Systems
Authors: Moriguchi Takashi
Published: March 2021

The GATA family of transcription factors consists of six proteins (GATA1-6) that control a variety of physiological and pathological processes. In particular, GATA2 and GATA3 are coexpressed in a number of tissues, including in the urogenital and sympathoadrenal systems, in which both factors participate in the developmental process and tissue maintenance. Furthermore, accumulating studies have demonstrated that GATA2 and GATA3 are involved in distinct types of inherited diseases as well as carcinogenesis in diverse tissues. This review summarizes our current knowledge of how GATA2 and GATA3 participate in the transcriptional regulatory circuitry during the development of the sympathoadrenal and urogenital systems, and how their dysregulation results in the carcinogenesis of neuroblastoma, renal urothelial, and gynecologic cancers.
Study of Two Constraints Impacting Measurements of Human Glycemia Using a Microwave Sensor
Authors: Zidane Mohamed Amine , Amar Hichem , Rouane Amar
Published: March 2021

The measurement of glycemia is impacted by several constraints; those constraints have to be identified and quantified when designing an electromagnetic noninvasive sensor. The second phase concerns the level of the influence of these constraints. In this work, we investigated the impact of vein radius located in the forearm on a resonant microwave sensor to measure glycemia. We performed a numerical simulation using COMSOL Multiphysics of a proposed tissue model that was in contact with a microwave resonator. Some other factors affect the measurement, such as temperature, perfusion, sensor positioning and motion, tissue heterogeneity, and other biological activity. The sensor must be robust to the above-mentioned constraints. Because vein size changes from one person to another, the dielectric properties seen by the sensor will be different. This has been demonstrated by the change created in the resonance frequency of the simulated sensor for different vein sizes. The second constraint that was assessed is the dosimetry. The specific absorption rate (SAR) of any electromagnetic device should be evaluated and compared with SAR limits in the safety standards to ensure the safety of the user. Simulation results are in good agreement with SAR limits in the safety standards.
Auditory Beat Stimulation Modulates Memory-Related Single-Neuron Activity in the Human Medial Temporal Lobe
Authors: Derner Marlene , Chaieb Leila , Dehnen Gert , Reber Thomas P. , Borger Valeri , Surges Rainer , Staresina Bernhard P. , Mormann Florian , Fell Juergen
Published: March 2021

Auditory beats are amplitude-modulated signals (monaural beats) or signals that subjectively cause the perception of an amplitude modulation (binaural beats). We investigated the effects of monaural and binaural 5 Hz beat stimulation on neural activity and memory performance in neurosurgical patients performing an associative recognition task. Previously, we had reported that these beat stimulation conditions modulated memory performance in opposite directions. Here, we analyzed data from a patient subgroup, in which microwires were implanted in the amygdala, hippocampus, entorhinal cortex and parahippocampal cortex. We identified neurons responding with firing rate changes to binaural versus monaural 5 Hz beat stimulation. In these neurons, we correlated the differences in firing rates for binaural versus monaural beats to the memory-related differences for remembered versus forgotten items and associations. In the left hemisphere, we detected statistically significant negative correlations between firing rate differences for binaural versus monaural beats and remembered versus forgotten items/associations. Importantly, such negative correlations were also observed between beat stimulation-related firing rate differences in the pre-stimulus window and memory-related firing rate differences in the post-stimulus windows. In line with concepts of homeostatic plasticity, our findings suggest that beat stimulation is linked to memory performance via shifting baseline firing levels.
Spatiotemporal Characteristics of Neural Dynamics in Theta Oscillations Related to the Inhibition of Habitual Behavior
Authors: Kang Jae-Hwan , Kim Junsuk , Cho Yang Seok , Kim Sung-Phil
Published: March 2021

The human brain carries out cognitive control for the inhibition of habitual behaviors by suppressing some familiar but inappropriate behaviors instead of engaging specific goal-directed behavior flexibly in a given situation. To examine the characteristics of neural dynamics related to such inhibition of habitual behaviors, we used a modified rock–paper–scissors (RPS) task that consisted of a basic, a lose-, and a win-conditioned game. Spectral and phase synchrony analyses were conducted to examine the acquired electroencephalogram signals across the entire brain during all RPS tasks. Temporal variations in frontal theta power activities were directly in line with the stream of RPS procedures in accordance with the task conditions. The lose-conditioned RPS task gave rise to increases in the local frontal power and global phase-synchronized pairs of theta oscillations. The activation of the global phase-synchronized network preceded the activation of frontal theta power. These results demonstrate that the frontal regions play a pivotal role in the inhibition of habitual behaviors—stereotyped and ingrained stimulus–response mappings that have been established over time. This study suggests that frontal theta oscillations may be engaged during the cognitive inhibition of habitual behaviors and that these oscillations characterize the degree of cognitive load required to inhibit habitual behaviors.
Menstrual Headache in Women with Chronic Migraine Treated with Erenumab: An Observational Case Series
Authors: Ornello Raffaele , Frattale Ilaria , Caponnetto Valeria , De Matteis Eleonora , Pistoia Francesca , Sacco Simona
Published: March 2021

Background: We aimed to assess the differences between menstrual and non-menstrual headache in women with chronic migraine treated with erenumab. Methods: We included fertile women from a single center. Patients were defined as responders to erenumab if reporting a ≥50% decrease in monthly headache days, as compared to pre-treatment for more than half of the treatment period. Premenstrual days were defined as the two days preceding menstruation, while menstrual days were defined as the first three days of menstruation. Results: We included 18 women (11 erenumab responders and 7 erenumab non-responders) contributing to a total of 103 menstrual cycles and 2926 days. The proportion of headache days was higher in menstrual than in premenstrual and non-menstrual days in erenumab responders (34.4% vs. 14.8% vs. 16.3%, respectively; p < 0.001) and in erenumab non-responders (71.4% vs. 53.6% vs. 48.3%, respectively; p < 0.001). Headache days with ≥2 acute medications were higher in menstrual than in premenstrual or non-menstrual headache days in erenumab non-responders (p = 0.002) but not in erenumab responders (p = 0.620). Conclusions: Our data suggest that migraine is more frequent during than outside menstrual days even in women treated with erenumab.
Corticospinal Tract and Related Grey Matter Morphometric Shape Analysis in ALS Phenotypes: A Fractal Dimension Study
Authors: Rajagopalan Venkateswaran , Pioro Erik P.
Published: March 2021

A pathological hallmark of amyotrophic lateral sclerosis (ALS) is corticospinal tract (CST) degeneration resulting in upper motor neuron (UMN) dysfunction. No quantitative test is available to easily assess UMN pathways. Brain neuroimaging in ALS promises to potentially change this through identifying biomarkers of UMN dysfunction that may accelerate diagnosis and track disease progression. Fractal dimension (FD) has successfully been used to quantify brain grey matter (GM) and white matter (WM) shape complexity in various neurological disorders. Therefore, we investigated CST and whole brain GM and WM morphometric changes using FD analyses in ALS patients with different phenotypes. We hypothesized that FD would detect differences between ALS patients and neurologic controls and even between the ALS subgroups. Neuroimaging was performed in neurologic controls (n = 14), and ALS patients (n = 75). ALS patients were assigned into four groups based on their clinical or radiographic phenotypes. FD values were estimated for brain WM and GM structures. Patients with ALS and frontotemporal dementia (ALS-FTD) showed significantly higher CST FD values and lower primary motor and sensory cortex GM FD values compared to other ALS groups. No other group of ALS patients revealed significant FD value changes when compared to neurologic controls or with other ALS patient groups. These findings support a more severe disease process in ALS-FTD patients compared to other ALS patient groups. FD value measures may be a sensitive index to evaluate GM and WM (including CST) degeneration in ALS patients.
Searching for Flexibility in Corporate Real Estate Portfolio: Six Co-Working Strategies for User Corporations
Authors: Echeverri Natalia , Jylhä Tuuli , Koppels Philip
Published: March 2021

The increasing competitive pressures and dynamic user preferences have resulted in a fast-paced and uncertain business environment. In the face of these circumstances, organizations are looking into alternatives to incorporate flexibility to become more adaptive and responsive to change. In this line, co-working, typically associated with freelancers, entrepreneurs, and startups, has become a particularly interesting alternative in the market that has caught the attention of corporate occupiers. Therefore, the aim of this paper is to identify co-working strategies that can be implemented as part of the corporate real estate portfolio, in alignment with the flexibility demands of the organization. This nascent research topic is studied through 5 qualitative case studies including in-depth, semi-structured interviews with corporate real estate managers and related case documentation. The results evidence the different motivations that the organizations have when incorporating co-working in their property portfolio. As seen across the cases, organizations in different stages of maturity are implementing co-working as the main office location or as a temporary or complementary space solution, through six different strategies: (1) Swing Space, (2) Expansion Space, (3) Core and Flex, (4) Touchdown Space, (5) Testing Market, and (6) Temporary Projects and Staff. This research evidences that each strategy plays a specific role in the corporate real estate portfolio and implies different sources of flexibility that support the physical, functional, and financial flexibility demands of the organization.
Convolutional Neural Network-Based Clinical Predictors of Oral Dysplasia: Class Activation Map Analysis of Deep Learning Results
Authors: Camalan Seda , Mahmood Hanya , Binol Hamidullah , Araújo Anna Luiza Damaceno , Santos-Silva Alan Roger , Vargas Pablo Agustin , Lopes Marcio Ajudarte , Khurram Syed Ali , Gurcan Metin N.
Published: March 2021

Oral cancer/oral squamous cell carcinoma is among the top ten most common cancers globally, with over 500,000 new cases and 350,000 associated deaths every year worldwide. There is a critical need for objective, novel technologies that facilitate early, accurate diagnosis. For this purpose, we have developed a method to classify images as “suspicious” and “normal” by performing transfer learning on Inception-ResNet-V2 and generated automated heat maps to highlight the region of the images most likely to be involved in decision making. We have tested the developed method’s feasibility on two independent datasets of clinical photographic images of 30 and 24 patients from the UK and Brazil, respectively. Both 10-fold cross-validation and leave-one-patient-out validation methods were performed to test the system, achieving accuracies of 73.6% (±19%) and 90.9% (±12%), F1-scores of 97.9% and 87.2%, and precision values of 95.4% and 99.3% at recall values of 100.0% and 81.1% on these two respective cohorts. This study presents several novel findings and approaches, namely the development and validation of our methods on two datasets collected in different countries showing that using patches instead of the whole lesion image leads to better performance and analyzing which regions of the images are predictive of the classes using class activation map analysis.
Surgical Outcome of Trigeminal Schwannomas
Authors: Aftahy Amir Kaywan , Groll Maximilian , Barz Melanie , Wagner Arthur , Lange Nicole , Butenschön Vicki Marie , Delbridge Claire , Bernhardt Denise , Meyer Bernhard , Negwer Chiara , Gempt Jens
Published: March 2021

(1) Background: As resection of trigeminal schwannomas is challenging, due to anatomical involvement of the anterior, middle and posterior fossa, the appropriate approach is important. We report our experience with surgical resection of trigeminal schwannomas by simple and classic skull-base approaches. (2) Methods: We performed a retrospective single-center study including patients who underwent surgery for trigeminal schwannoma tumors between June 2007 and May 2020, concentrating on surgical technique, extent of resection, postoperative outcome and complications. (3) Results: We included 13 patients (median age 57.5 with range of 36-83 years, 53.8% (7/13) female. The most common preoperative clinical presentations were facial pain in six (46.2%), hypoacusis in four (30.8%), trigeminal nerve hypesthesia in 11 (V1 46.2% (6/13), V2 (61.5% (8/13), V3 46.2% (6/13)) and headache in three (23.1%) patients. In three cases, the tumor was resected in a two-stage technique. The intradural subtemporal approach was performed in six cases, the extradural technique in two cases, the retrosigmoid approach in five cases, a Kawase approach in two cases and the transnasal endoscopic approach in one case. The gross total resection rate was 76.9% (10/13) and the median follow-up time 24.0 (0–136) months. Three (23.1%) patients developed postoperative anesthesia in at least one branch of the trigeminal nerve. Trigeminal motor function was preserved in 11 (84.6%) patients. Ten of the 11 patients (76.9%) who reported decreased gustation, cerebellar ataxia, visual impairment, or headache improved postoperatively. Two (15.4%) patients exhibited minimal facial palsy (House and Brackmann II–III), which resolved during the follow-up. The total adverse event rate requiring surgical intervention during follow-up was 7.7%. Surgery-related mortality was 0%. (4) Conclusions: Trigeminal schwannomas are rare benign lesions with intra- and extracranial extension. Considering the low operative morbidity and satisfying functional outcome, gross total resection of trigeminal schwannomas is achievable by classic, but also individually tailored approaches. More invasive or combined techniques were not needed with meticulous surgical planning.
Targeting Chronic Myeloid Leukemia Stem/Progenitor Cells Using Venetoclax-Loaded Immunoliposome
Authors: Houshmand Mohammad , Garello Francesca , Stefania Rachele , Gaidano Valentina , Cignetti Alessandro , Spinelli Michela , Fava Carmen , Nikougoftar Zarif Mahin , Galimberti Sara , Pungolino Ester , Annunziata Mario , Luciano Luigia , Specchia Giorgina , Bocchia Monica , Binotto Gianni , Bonifacio Massimiliano , Martino Bruno , Pregno Patrizia , Stagno Fabio , Iurlo Alessandra , Russo Sabina , Aime Silvio , Circosta Paola , Saglio Giuseppe
Published: March 2021

CML is a hematopoietic stem-cell disorder emanating from breakpoint cluster region/Abelson murine leukemia 1 (BCR/ABL) translocation. Introduction of different TKIs revolutionized treatment outcome in CML patients, but CML LSCs seem insensitive to TKIs and are detectable in newly diagnosed and resistant CML patients and in patients who discontinued therapy. It has been reported that CML LSCs aberrantly express some CD markers such as CD26 that can be used for the diagnosis and for targeting. In this study, we confirmed the presence of CD26+ CML LSCs in newly diagnosed and resistant CML patients. To selectively target CML LSCs/progenitor cells that express CD26 and to spare normal HSCs/progenitor cells, we designed a venetoclax-loaded immunoliposome (IL-VX). Our results showed that by using this system we could selectively target CD26+ cells while sparing CD26− cells. The efficiency of venetoclax in targeting CML LSCs has been reported and our system demonstrated a higher potency in cell death induction in comparison to free venetoclax. Meanwhile, treatment of patient samples with IL-VX significantly reduced CD26+ cells in both stem cells and progenitor cells population. In conclusion, this approach showed that selective elimination of CD26+ CML LSCs/progenitor cells can be obtained in vitro, which might allow in vivo reduction of side effects and attainment of treatment-free, long-lasting remission in CML patients.
Correction: Isao N., et al. Transcatheter Arterial Embolization Treatment for Bleeding Visceral Artery Pseudoaneurysms in Patients with Pancreatitis or Following Pancreatic Surgery. Cancers 2020, 12, 2733
Authors: Numoto Isao , Tsurusaki Masakatsu , Oda Teruyoshi , Yagyu Yukinobu , Ishii Kazunari , Murakami Takamichi
Published: March 2021

The authors are sorry to report that the overall survival reported in their recently published paper was incorrect [...]