bluuebunny/crossref_metadata_2025 huggingface dataset:
Nutritional Composition, Bioactive Compounds and Functional Evaluation of Various Parts of Cajanus cajan (L.) Millsp
Authors: Yang Shu-Er , Vo Thuy-Lan Thi , Chen Chien-Lin , Yang Nae-Cherng , Chen Chen-I , Song Tuzz-Ying
Published: November 2020

The pigeon pea (Cajanus cajan (L.) Millsp.) is one of the major grain legume crops of the tropical world and recent evidence indicates that it possesses various health benefits. However, to the best of our knowledge, no comparison has been made on the nutritional composition and biological functions of its leaves, seeds, and roots. Therefore, the present study investigates which part of the C. cajan (L.) Millsp plant has the highest potential for development as a health food product. Results show that C. cajan (L.) Millsp roots (CCR) have a higher total polyphenol content (TPC) and total flavonoids flavonoid (TFC) contents than leaves and seeds. The antioxidant, anti-hyperglycemic, and anti-bacterial activities of CCR extracted with hot water (HWCR), 50% ethanol (EECR50), and 95% ethanol (EECR95) were determined. We found that EECR95 had the strongest antioxidant activity, as evaluated by 1,1-Diphenyl-2-picrylhydrazyl radical (DPPH) and 2,2′-azino-bis (3-ethylbenzothiazoline-6-sulfonic acid) (ABTS+) scavenging, and reducing power. EECR95 exhibited higher anti-hyperglycemic ability (inhibition of α-glucosidase and α-amylase activities) and anti-glycation effects (IC50 = 39, 120 and 229 μg/mL, respectively) than HWCR and EECR50. EECR95 also exhibited potent anti-bacterial activities on E. coli, Staphylococcus aureus, Porphyromonas gingivalis, and Streptococcus mutans, with minimum inhibitory concentrations of 113, 180, 16, and 100 μg/mL, respectively. Based on above results, we conclude that CCR has considerable potential for health food development and further studies of CCR in animals to confirm these biological effects and safety issues are warranted.
Water-Soluble Carbohydrate Recovery in Pastures of Perennial Ryegrass (Lolium perenne L.) and Pasture Brome (Bromus valdivianus Phil.) Under Two Defoliation Frequencies Determined by Thermal Time
Authors: Calvache Iván , Balocchi Oscar , Alonso Máximo , Keim Juan Pablo , López Ignacio
Published: November 2020

The objectives of the experiment were to (i) examine the dynamics of WSC use and the recovery of leaf sheaths and blades of Bromus valdivianus Phil. and Lolium perenne L. subjected to two defoliation frequencies (DFs) determined by thermal time (TT); (ii) evaluate how DF influenced regrowth and accumulated herbage mass (AHM) during fall. Defoliation was carried out at frequencies of 135 and 270 accumulated growing degree days (AGDDs) for both species. Twelve plots were arranged in a three-block design. All plots had a conditioning period to establish the assigned DF prior to sampling. From the start of the experiment, “cores” were collected from each plot every three days until the DF was reached. Every core was separated into leaf and sheath material before measuring the WSC concentration. Lolium perenne had concentrated more WSCs than B. valdivianus. Both species adapted their WSC recovery according to the DF. The recovery of WSC was faster under a DF of 135 AGDDs than that of 270 AGDDs. Leaf sheaths contained more WSCs than leaf blades and were identified as WSC storage organs. This period can be used as the optimal defoliation interval in B. valdivianus and L. perenne grazing systems.
Identification of Pomegranate as a New Host of Passiflora Edulis Symptomless Virus (PeSV) and Analysis of PeSV Diversity
Authors: Caglayan Kadriye , Gazel Mona , Roumi Vahid , Kocabag Hamide Deniz , Tunç Bahar , Reynard Jean Sebastien , Ruiz-García Ana Belén , Olmos Antonio , Candresse Thierry
Published: November 2020

Pomegranate is an important crop in the Mediterranean Basin that can be affected by a range of pathogens. With the aim to better understand the impact of viral diseases on pomegranate, two leaf samples from Turkey showing virus-like symptoms such as chlorotic spots and oak-leaf patterns were subjected to high throughput sequencing (HTS). Data analysis indicated the presence of passiflora edulis symptomless virus (PeSV: genus Roymovirus, Potyviridae family) in these two pomegranate samples, consistent with the observation by electron microscopy of flexuous filamentous viral particles 760 to 780 nm long. Further analysis of HTS reads revealed the presence of five PeSV variants in one of the samples and another single variant in the other. PeSV occurrence was also identified from publicly available SRA pomegranate RNA-Seq transcriptomic data from India and China. The genome of these PeSV-pomegranate variants share 78.0–86.8% nucleotide identity with that of the reference isolate from passionfruit (MH379332). The presence of PeSV in pomegranate was confirmed by specific RT-PCR assays targeting either the coat protein (CP) or Nla-Pro genes in 37 cultivated and one ornamental pomegranate out of 133 samples collected from the Eastern Mediterranean region of Turkey. To our knowledge, this is the first application of HTS to assess virus occurrence in pomegranate and the first recognition of pomegranate as a new host for PeSV.
Effect of Saline Conditions on Chemical Profile and the Bioactive Properties of Three Red-Colored Basil Cultivars
Authors: Cruz Luís R. O. , Polyzos Nikolaos , Fernandes Ângela , Petropoulos Spyridon A. , Gioia Francesco Di , Dias Maria Inês , Pinela José , Kostić Marina , Soković Marina , Ferreira Isabel C. F. R. , Barros Lillian
Published: November 2020

The present study investigated the effect of salinity (Control: 1.8 dS/m, S1: 3.0 dS/m and S2: 4.5 dS/m) on the chemical composition and bioactive properties of three basil cultivars (Red Basil, Dark Opal Red and Basilico Rosso). Crop performance was not affected by increasing salinity in DoR and BaR. Fat, ash and carbohydrates content increased by salinity in DoR, whereas energetic value was negatively affected. Free sugars (total and individual compounds) increased under saline conditions (S2) in BaR, whereas reducing trends were observed for the main organic acids and tocopherols in all the cultivars. The major fatty acids were α-linolenic, linoleic and palmitic acids with no consistent salinity effects, while the richest polyphenols were sagerinic acid and eriodictyol-O-malonylhexoside. Finally, basil extracts showed moderate antioxidant and strong antifungal activity. In conclusion, salinity showed a genotype dependent effect on the chemical profile and bioactivities of the tested cultivars.
Environmental Factors and Genetic Parameters of Beef Traits in Fleckvieh Cattle Using Field and Station Testing
Authors: Filipčík Radek , Falta Daniel , Kopec Tomáš , Chládek Gustav , Večeřa Milan , Rečková Zuzana
Published: November 2020

The goal of this study was to analyze the genetic and environmental factors of selected meat yield indicators in Fleckvieh cattle in the Czech Republic, through the application of station (S) and field (F) testing methods. Data collected from fattened bulls were analyzed for F (n = 9378) and for S (n = 6346). In the F method and the S method, the values of the main meat yield indicators were as follows: carcass weight 402.91 kg (F), 339.37 kg (S); carcass daily gain 626.05 g/day (F), 609.74 g/day (S); SEUROP carcass classification 2.73 (F), 2.19 (S). Environmental factors were found to have a significant impact on the selected meat yield indicators; their heritability ranged from 0.14 (SEUROP classification) to 0.33 (dressing percentage). The genetic trend was significantly positive only in relation to those meat yield traits, which had a positive link to the size or weight of the animal. The genetic correlation between observations obtained in the S and F methods of testing was very high in relation to the carcass daily gain (0.8351) and carcass weight (0.8244), while slightly lower correlations were calculated for the SEUROP classification. A genetic evaluation of the degree of fatness is not routinely performed in Fleckvieh populations, and the newly established heritability for this trait ranges between 0.17–0.20. The genetic correlation between beef yield indicators and the exterior trait of muscularity was also established, and shows a strong link to the net daily gain, the SEUROP classification and body weight (0.79–0.97). The aim of the study was to evaluate the genetic and environmental effects on meat yield and also estimate genetic parameters for new traits. We can also state, based on the results, that a strong positive genetic trend is confirmed, especially in traits related to the size or weight of animals. This result can be used in breeding programs of dual-purpose cattle, where we can genetically improve the meat and milk yield through the body size.
Exploring the Diversity of Active Ureolytic Bacteria in the Rumen by Comparison of cDNA and gDNA
Authors: Liu Sijia , Zheng Nan , Zhao Shengguo , Wang Jiaqi
Published: November 2020

In this study we revealed the diversity of active ureolytic bacteria in the rumen by compared ureC amplicons between gDNA and cDNA. Rumen fluid was collected from four Holstein dairy cows with rumen fistulas at 0, 2, and 6 h after morning feeding. Total microbial gDNA and RNA were isolated, and the RNA was reverse-transcribed into cDNA. The ureC gene amplicons of gDNA and cDNA were produced and sequenced by MiSeq. These results revealed that the sampling time had no significant difference on the alphssa and beta diversity indices of the ureolytic bacteria. The Shannon diversity of the ureC gene for cDNA was greater than that for gDNA (p < 0.05). There were significant difference in the beta diversity of ureolytic bacteria between gDNA and cDNA (p < 0.01), which indicates a shift in the community of active ureolytic bacteria. Approximately 67% of ureC sequences from cDNA could not be confidently classified at the genus level. The active ureolytic bacteria were mainly from Helicobacter, Herbaspirillum, Clostridium, Paenibacillus, Synechococcus, and Sphingobacterium sp. Changes in the operational taxonomic units revealed that the top abundant ureC genes were mostly consistent between gDNA and cDNA, and most differences occurred in the ureC genes with lower abundances. These results revealed distinct ureolytic bacteria community profiles based on gDNA and cDNA. The dominant ureolytic bacteria had high transcriptional activity, and the differential were mainly distributed in the genus of low abundance.
Meningitis Caused by Streptococcus agalactiae in Nile Tilapia (Oreochromis niloticus): Infection and Inflammatory Response
Authors: Eto Silas Fernandes , Fernandes Dayanne Carla , Moraes Alessandra Cristina de , Alecrim João Victor da Costa , Souza Pedro Galdino de , Carvalho Fabíola Christian Almeida de , Charlie-Silva Ives , Belo Marco Antonio de Andrade , Pizauro João Martins
Published: November 2020

Streptococcus agalactiae (Sta) of Lancefield group B is the primary etiological agent of bacterial meningitis in Nile tilapia and newborn humans. Thus, the study of this disease is of fundamental importance for aquaculture and human medicine. Additionally, elucidation of the mechanisms involved in the host–pathogenic response is important for the success of new therapies. In the present study, we elucidated important aspects of the innate immune response in the brain tissue of Nile tilapia (Oreochromis niloticus) infected by Sta. The neuroinflammatory process in the meninges started with the migration of MHC class II and CD68 + cells, production of TNF-alpha, and the effective immune response to Sta was mediated by the increased iNOs+. In conclusion, the present study brings a partial understanding of the pathophysiological and neuroinflammatory mechanisms in meningitis in Sta infected tilapia, enabling important advances in the therapy of this disease as well as the possibility of using this biological model to understand human meningitis.
Antioxidant and Anti-Inflammatory Activities of Cytocompatible Salvia officinalis Extracts: A Comparison between Traditional and Soxhlet Extraction
Authors: Vieira Sara F. , Ferreira Helena , Neves Nuno M.
Published: November 2020

Chronic inflammation is characterized by an overproduction of several inflammatory mediators (e.g., reactive species and interleukins -IL) that play a central role in numerous diseases. The available therapies are often associated with serious side effects and, consequently, the need for safer drugs is of utmost importance. A plant traditionally used in the treatment of inflammatory conditions is Salvia officinalis. Therefore, conventional maceration and infusion of its leaves were performed to obtain hydroethanolic (HE-T) and aqueous extracts (AE-T), respectively. Their efficacy was compared to soxhlet extracts, namely aqueous (AE-S), hydroethanolic (HE-S), and ethanolic extracts (EE-S). Thin-layer chromatography demonstrated the presence of rosmarinic acid, carnosol, and/or carnosic acid in the different extracts. Generally, soxhlet provided extracts with higher antioxidant activities than traditional extraction. Moreover, under an inflammatory scenario, EE-S were the most effective, followed by HE-S, HE-T, AE-T, and AE-S, in the reduction of IL-6 and TNF-α production. Interestingly, the extracts presented higher or similar anti-inflammatory activity than diclofenac, salicylic acid, and celecoxib. In conclusion, the extraction method and the solvents of extraction influenced the antioxidant activity, but mainly the anti-inflammatory activity of the extracts. Therefore, this natural resource can enable the development of effective treatments for oxidative stress and inflammatory diseases.
The Applicability of Total Color Difference ΔE for Determining the Blooming Time in Longissimus Lumborum and Semimembranosus Muscles from Holstein-Friesian Bulls at Different Ageing Times
Authors: Tkacz Katarzyna , Modzelewska-Kapituła Monika , Więk Adam , Nogalski Zenon
Published: November 2020

This study was conducted to determine the optimal blooming time in beef muscles based on ΔE, and to analyze the effects of muscle type and ageing time on beef color and blooming. Beef color was determined on freshly cut longissimus lumborum (LL, n = 8) and semimembranosus (SM, n = 8) muscles on days 1, 9, and 14 of ageing during 60 min blooming at 5 min intervals. It was found that ΔE0, representing the difference in color between freshly cut muscles and subsequently analyzed samples, supported the determination of the optimal blooming time, which varied across ageing times (15, 20, 25 min for the LL muscle, and 10, 15, 20 min for the SM muscle on days 1, 9, and 14 of ageing, respectively). Beef color was affected by both muscle type and ageing. The values of color parameters increased between days 1 and 9 of ageing. The results may have practical applications because beef should be presented to consumers and restaurant owners approximately 25 min after cutting, when its color has fully developed.
Determining Risk Factors for the Development of Temporomandibular Disorders during Orthodontic Treatment
Authors: Ugolini Alessandro , Garbarino Federico , Di Vece Luca , Silvestrini-Biavati Francesca , Lanteri Valentina
Published: November 2020

Temporomandibular disorders (TMD) represent a complex disease with a multifactorial etiology. Despite several studies on the subject, a causal relationship between orthodontic treatment and different forms of TMD has not been established. The aim of this study was to analyze the effect of orthodontic treatment on two aspects of TMD: myofascial pain and disc displacement. This retrospective cohort study followed 224 orthodontic adult patients at three points in time: before treatment (T0), immediately after treatment (T1), and one year after treatment (T2). Disc displacement and myofascial pain were evaluated through a clinical assessment and with a semi-structured interview, along with headache, neck, and shoulder pain parameters and behavioral and somatic accompanying symptoms. Multivariate logistic regression was used to identify risk factors that could influence the development of TMD in these patients. There was a non-significant increase in disc displacement during orthodontic treatment, which mostly resolved after completion of treatment. Myofascial pain scores worsened during treatment, but improved when compared with the baseline once treatment was complete (T0 = 51.3%, T1 = 64.6%, T2 = 44.9%). Female gender (aOR = 1.9, CI 95%, 1.23–2.36), the presence of somatic symptoms (aOR = 3.6, CI 95%, 2.01–5.84), and symptoms of anxiety or depression (aOR = 2.2, CI 95%, 1.14–4.51) were significant risk factors associated with the development of TMD. There is a low and not significant risk of TMD development during orthodontic treatment. When TMD occurred, they resolved within 1 year of the end of treatment.
Biorefinery: The Production of Isobutanol from Biomass Feedstocks
Authors: Su Yide , Zhang Weiwei , Zhang Aili , Shao Wenju
Published: November 2020

Environmental issues have prompted the vigorous development of biorefineries that use agricultural waste and other biomass feedstock as raw materials. However, most current biorefinery products are cellulosic ethanol. There is an urgent need for biorefineries to expand into new bioproducts. Isobutanol is an important bulk chemical with properties that are close to gasoline, making it a very promising biofuel. The use of microorganisms to produce isobutanol has been extensively studied, but there is still a considerable gap to achieving the industrial production of isobutanol from biomass. This review summarizes current metabolic engineering strategies that have been applied to biomass isobutanol production and recent advances in the production of isobutanol from different biomass feedstocks.
Wind Reversal in Bubbly Natural Convection
Authors: Oresta Paolo , Fabbiano Laura , Vacca Gaetano
Published: November 2020

The multi-phase Rayleigh–Bènard convection has been weakly investigated, even though it plays a leading role in the theoretical and applied physics of the heat transfer enhancement. For the case of moderate turbulent convection, a rather unexpected result is an unusual kind of wind reversal, in the sense that the fluid is found to be strongly influenced by the bubbles, whereas the bubbles themselves appear to be little affected by the fluid, despite the relative smallness of the Stokes numbers. The wind reversal induced by the bubbles dispersed in the fluid is a new and remarkable phenomenon in multi-phase flows that provides further perspectives in understanding the complex physics leading the enhancement of thermal convection. For this reason, the fundamental research proposed in this paper aimed to identify a space of control parameters and the physical mechanisms responsible for the wind reversal induced by dispersed bubbles in a confined convective flow. The strength of the following description lies in an innovative numerical approach, based on the multi-scale physics induced by the coupling of the local thermal and mechanical mechanisms arising between each bubble and the surrounding fluid. The continuous phase has been solved numerically using the direct numerical simulation (DNS) technique and each bubble has been tracked by means of a particle Lagrangian model.
New Record of Dust Input and Provenance During Glacial Periods in Western Australia Shelf (IODP Expedition 356, Site U1461) from the Middle to Late Pleistocene
Authors: Courtillat Margot , Hallenberger Maximilian , Bassetti Maria-Angela , Aubert Dominique , Jeandel Catherine , Reuning Lars , Korpanty Chelsea , Moissette Pierre , Mounic Stéphanie , Saavedra-Pellitero Mariem
Published: November 2020

International Ocean Discovery Program (IODP) Expedition 356 Site U1461 represents one of the few records from the North West Australian shelf that provides information about aridity fluctuations in Australia during the Quaternary. A combination of chronostratigraphic indicators revealed the (partial) preservation of two major glaciations (Marine Isotope Stage (MIS) 2 and MIS 12) in the sedimentary record. The faunal content (mainly benthic foraminifera, corals and bryozoans) was analyzed to estimate paleo-environments and paleo-depths in order to determine if these sediments have been remobilized by reworking processes. Despite the occurrence of a depositional hiatus (including MIS 5d to MIS 9-time interval), the excellent preservation of faunal content suggests that the preserved sediment is in situ. The geochemical composition of the sediments (Nd and major elements) indicates that during MIS 12 riverine input was likely reduced because of enhanced aridity, and the sediment provenance (mainly atmospheric dust) is likely in the central (Lake Eyre) or eastern (Murray Darling Basin) parts of the Australian continent. MIS 2 is confirmed to be one of the driest periods recorded in Australia but with mixed dust sources from the eastern and western parts of the continent. More humid conditions followed the glacial maximum, which might correspond to the peak of the Indian-Australian Summer Monsoon.
Oscillation of Emden–Fowler-Type Neutral Delay Differential Equations
Authors: Santra Shyam Sundar , Nofal Taher A. , Alotaibi Hammad , Bazighifan Omar
Published: November 2020

In this work, we consider a type of second-order functional differential equations and establish qualitative properties of their solutions. These new results complement and improve a number of results reported in the literature. Finally, we provide an example that illustrates our results.
Investigating How the Disclosure of Production Methods Influences Consumers’ Sensory Perceptions of Sparkling Wines
Authors: Hayward Lydia , Barton Alanah , McSweeney Matthew B.
Published: November 2020

The primary objective was to identify how the disclosure of production methods, including sustainable practices, would impact consumers’ sensory perceptions. The secondary objective was to identify the attributes consumers use to describe Nova Scotia (NS) sparkling wines. The first trial used projective mapping (PM) and ultra-flash profiling (UFP) to describe eight sparkling wines (n = 77). In the second trial, a check-all-that-apply (CATA) questionnaire and 9-point hedonic scales were used (n = 101). Three sparkling wines, from the previous trial, were evaluated blinded and with a production claim. The first trial found that consumers separated the wines based on their fruit- or earth-like attributes. In the CATA trial, desirable attributes, such as sweet and smooth, were used more frequently to describe the wines with sustainable production methods. No significant differences were found in the overall liking scores after the disclosure of the production methods (α = 0.05). These findings indicate that disclosure of production methods did not impact participants’ sensory perceptions of sparkling wine. In addition, an evaluation among different generations should be considered, as millennials have been found to hold sustainable practices to greater value.
Cannabidiol: A Potential New Alternative for the Treatment of Anxiety, Depression, and Psychotic Disorders
Authors: García-Gutiérrez María S. , Navarrete Francisco , Gasparyan Ani , Austrich-Olivares Amaya , Sala Francisco , Manzanares Jorge
Published: November 2020

The potential therapeutic use of some Cannabis sativa plant compounds has been attracting great interest, especially for managing neuropsychiatric disorders due to the relative lack of efficacy of the current treatments. Numerous studies have been carried out using the main phytocannabinoids, tetrahydrocannabinol (THC) and cannabidiol (CBD). CBD displays an interesting pharmacological profile without the potential for becoming a drug of abuse, unlike THC. In this review, we focused on the anxiolytic, antidepressant, and antipsychotic effects of CBD found in animal and human studies. In rodents, results suggest that the effects of CBD depend on the dose, the strain, the administration time course (acute vs. chronic), and the route of administration. In addition, certain key targets have been related with these CBD pharmacological actions, including cannabinoid receptors (CB1r and CB2r), 5-HT1A receptor and neurogenesis factors. Preliminary clinical trials also support the efficacy of CBD as an anxiolytic, antipsychotic, and antidepressant, and more importantly, a positive risk-benefit profile. These promising results support the development of large-scale studies to further evaluate CBD as a potential new drug for the treatment of these psychiatric disorders.
Astrocytic Connexin43 Channels as Candidate Targets in Epilepsy Treatment
Authors: Walrave Laura , Vinken Mathieu , Leybaert Luc , Smolders Ilse
Published: November 2020

In epilepsy research, emphasis is put on exploring non-neuronal targets such as astrocytic proteins, since many patients remain pharmacoresistant to current treatments, which almost all target neuronal mechanisms. This paper reviews available data on astrocytic connexin43 (Cx43) signaling in seizures and epilepsy. Cx43 is a widely expressed transmembrane protein and the constituent of gap junctions (GJs) and hemichannels (HCs), allowing intercellular and extracellular communication, respectively. A plethora of research papers show altered Cx43 mRNA levels, protein expression, phosphorylation state, distribution and/or functional coupling in human epileptic tissue and experimental models. Human Cx43 mutations are linked to seizures as well, as 30% of patients with oculodentodigital dysplasia (ODDD), a rare genetic condition caused by mutations in the GJA1 gene coding for Cx43 protein, exhibit neurological symptoms including seizures. Cx30/Cx43 double knock-out mice show increased susceptibility to evoked epileptiform events in brain slices due to impaired GJ-mediated redistribution of K+ and glutamate and display a higher frequency of spontaneous generalized chronic seizures in an epilepsy model. Contradictory, Cx30/Cx43 GJs can traffic nutrients to high-energy demanding neurons and initiate astrocytic Ca2+ waves and hyper synchronization, thereby supporting proconvulsant effects. The general connexin channel blocker carbenoxolone and blockers from the fenamate family diminish epileptiform activity in vitro and improve seizure outcome in vivo. In addition, interventions with more selective peptide inhibitors of HCs display anticonvulsant actions. To conclude, further studies aiming to disentangle distinct roles of HCs and GJs are necessary and tools specifically targeting Cx43 HCs may facilitate the search for novel epilepsy treatments.
The Proteasome Activators Blm10/PA200 Enhance the Proteasomal Degradation of N-Terminal Huntingtin
Authors: Aladdin Azzam , Yao Yanhua , Yang Ciyu , Kahlert Günther , Ghani Marvi , Király Nikolett , Boratkó Anita , Uray Karen , Dittmar Gunnar , Tar Krisztina
Published: November 2020

The Blm10/PA200 family of proteasome activators modulates the peptidase activity of the core particle (20S CP). They participate in opening the 20S CP gate, thus facilitating the degradation of unstructured proteins such as tau and Dnm1 in a ubiquitin- and ATP-independent manner. Furthermore, PA200 also participates in the degradation of acetylated histones. In our study, we use a combination of yeast and human cell systems to investigate the role of Blm10/PA200 in the degradation of N-terminal Huntingtin fragments (N-Htt). We demonstrate that the human PA200 binds to N-Htt. The loss of Blm10 in yeast or PA200 in human cells results in increased mutant N-Htt aggregate formation and elevated cellular toxicity. Furthermore, Blm10 in vitro accelerates the proteasomal degradation of soluble N-Htt. Collectively, our data suggest N-Htt as a new substrate for Blm10/PA200-proteasomes and point to new approaches in Huntington’s disease (HD) research.
The Raven’s Coloured Progressive Matrices in Healthy Children: A Qualitative Approach
Authors: Smirni Daniela
Published: November 2020

Studies on the structure of intelligence refer to two main theoretical models: the first one considers intelligence as a unitary construct, the second one assumes the involvement of a plurality of factors. Studies using Raven’s Coloured Progressive Matrices (RCPM) tasks have often highlighted the involvement of different cognitive abilities and brain structures, but in the clinical setting, RCPM measurement continues to be used as a single score. The current study aimed to analyse the RCPM performance following qualitative clustering, in order to provide an interpretation of the intelligence assessment through a factorial criterion. The RCPM have been administered to a large group of typically developing children between 6 and 11 years of age. The sample was divided into twelve age groups, and the performance of each age group was shown. Three qualitative item clusters were identified through a factorial criterion. Data showed that performance on RCPM may arise from different cognitive abilities, starting from basic attentional skills up to the more complex ones that require perceptual or analogical reasoning. The qualitative parameters could provide more effective diagnostic and treatment suggestions than a single total score in the clinical setting, and may be crucial for focusing on strength and weakness in the intellectual functionality evaluation of children.
Association between Structural Connectivity and Generalized Cognitive Spectrum in Alzheimer’s Disease
Authors: Lombardi Angela , Amoroso Nicola , Diacono Domenico , Monaco Alfonso , Logroscino Giancarlo , De Blasi Roberto , Bellotti Roberto , Tangaro Sabina
Published: November 2020

Modeling disease progression through the cognitive scores has become an attractive challenge in the field of computational neuroscience due to its importance for early diagnosis of Alzheimer’s disease (AD). Several scores such as Alzheimer’s Disease Assessment Scale cognitive total score, Mini Mental State Exam score and Rey Auditory Verbal Learning Test provide a quantitative assessment of the cognitive conditions of the patients and are commonly used as objective criteria for clinical diagnosis of dementia and mild cognitive impairment (MCI). On the other hand, connectivity patterns extracted from diffusion tensor imaging (DTI) have been successfully used to classify AD and MCI subjects with machine learning algorithms proving their potential application in the clinical setting. In this work, we carried out a pilot study to investigate the strength of association between DTI structural connectivity of a mixed ADNI cohort and cognitive spectrum in AD. We developed a machine learning framework to find a generalized cognitive score that summarizes the different functional domains reflected by each cognitive clinical index and to identify the connectivity biomarkers more significantly associated with the score. The results indicate that the efficiency and the centrality of some regions can effectively track cognitive impairment in AD showing a significant correlation with the generalized cognitive score (R = 0.7).
Does the Occurrence of Particular Symptoms and Outcomes of Arterial Ischemic Stroke Depend on Sex in Pediatric Patients?—A Pilot Study
Authors: Kopyta Ilona , Dobrucka-Głowacka Anna , Cebula Agnieszka , Sarecka-Hujar Beata
Published: November 2020

Arterial ischemic stroke (AIS) in childhood is reported to occur more frequently in boys, which may lead to the assumption that the prevalence of post-stroke deficits is sex related. The present study aimed to evaluate sex-related differences in functional outcomes (hemiparesis, seizures, aphasia, and motor disturbances other than hemiparesis) in pediatric patients with AIS. A total of 89 children (52 boys and 37 girls; mean age at stroke onset: 8.4 ± 5.6 years) were evaluated retrospectively based on data from medical records. The patients were divided into subgroups according to age (i.e., infants and toddlers, children, and adolescents), stroke subtype (i.e., lacunar anterior circulation infarct (LACI), total anterior circulation infarct (TACI), partial anterior circulation infarct (PACI), posterior circulation infarct (POCI)) and stroke location (i.e., anterior stroke, posterior stroke). Significant differences in the prevalence of stroke subtypes between girls and boys were observed (p = 0.034). POCI stroke were found to be more frequent in boys than in girls (OR = 8.57 95%CI 1.05–70.23, p = 0.023). Males predominated in the total group and in all analyzed age subgroups. The proportions of boys within the subgroups according to stroke subtype were extremely high for the POCI and TACI stroke subgroups. On the other hand, girls predominated in the LACI stroke subgroup. Frequency of central type facial nerve palsy and other symptoms of AIS were found to significantly differ between male subgroups according to stroke subtype (p = 0.050 and p < 0.001, respectively), as well as between children with anterior stroke and those with posterior stroke (p = 0.059 and p < 0.001, respectively). Post-stroke seizures appeared significantly more commonly in girls with TACI and POCI stroke than in girls with LACI and PACI stroke (p = 0.022). In turn, the prevalence of post-stroke hemiparesis differed between stroke subtypes in boys (p = 0.026). In conclusion, sex may have an impact in predisposing to a certain type of AIS in the patient. Post-stroke seizure may be related to stroke subtype in girls and hemiparesis in boys. However, further studies are needed to confirm the results.
Childhood ADHD and Early-Onset Bipolar Disorder Comorbidity: A Case Report
Authors: Tatsiopoulou Paraskevi , Porfyri Georgia-Nektaria , Bonti Eleni , Diakogiannis Ioannis
Published: November 2020

Introduction: Recent research has highlighted an increased rate of co-morbidity between the neurodevelopmental-behavioral disorder of attention deficit hyperactivity disorder (ADHD) and a variety of psychiatric disorders, such as mood disorders or bipolar disorder (BD). The etiology and clinical course of BD are considered to be determined by both genetic and environmental factors, either aggravating or improving. Aim: This follow-up study of an adolescent aimed to clarify the co-morbidity between ADHD and BD. We also discuss the controversies surrounding the two diagnoses in younger populations and describe several aspects of concern regarding diagnosis, differential diagnosis, therapeutic planning/intervention, and prognosis. Methods: Reporting of a two-year follow-up study of a bipolar 15-year-old female patient with a previous diagnosis of ADHD during childhood. Results: Despite the occurrence of major risk factors, such as early onset and positive family history, the patient’s condition rapidly remitted with medication, without relapse and/or rehospitalization during the following two years, due to the stability of her cooperation, and support of a stable and caring familial environment. Early diagnosis of BD and differential diagnoses of ADHD are considered crucial protective factors leading to an appropriate planning of treatment. In addition, parental involvement and empathic attitude towards the patient supported the latter to cooperate and comply with the treatment, enhancing positive outcomes and stability. Conclusions: Research is required into the reliability and validity of diagnostic protocols and criteria for BD in children and adolescents, and also into the development of individualized therapeutic planning.
Is the Proteome of Bronchoalveolar Lavage Extracellular Vesicles a Marker of Advanced Lung Cancer?
Authors: Carvalho Ana Sofia , Moraes Maria Carolina Strano , Hyun Na Chan , Fierro-Monti Ivo , Henriques Andreia , Zahedi Sara , Bodo Cristian , Tranfield Erin M , Sousa Ana Laura , Farinho Ana , Rodrigues Luís Vaz , Pinto Paula , Bárbara Cristina , Mota Leonor , Abreu Tiago Tavares de , Semedo Júlio , Seixas Susana , Kumar Prashant , Costa-Silva Bruno , Pandey Akhilesh , Matthiesen Rune
Published: November 2020

Acellular bronchoalveolar lavage (BAL) proteomics can partially separate lung cancer from non-lung cancer patients based on principal component analysis and multivariate analysis. Furthermore, the variance in the proteomics data sets is correlated mainly with lung cancer status and, to a lesser extent, smoking status and gender. Despite these advances BAL small and large extracellular vehicles (EVs) proteomes reveal aberrant protein expression in paracrine signaling mechanisms in cancer initiation and progression. We consequently present a case-control study of 24 bronchoalveolar lavage extracellular vesicle samples which were analyzed by state-of-the-art liquid chromatography-mass spectrometry (LC-MS). We obtained evidence that BAL EVs proteome complexity correlated with lung cancer stage 4 and mortality within two years´ follow-up (p value = 0.006). The potential therapeutic target DNMT3B complex is significantly up-regulated in tumor tissue and BAL EVs. The computational analysis of the immune and fibroblast cell markers in EVs suggests that patients who deceased within the follow-up period display higher marker expression indicative of innate immune and fibroblast cells (four out of five cases). This study provides insights into the proteome content of BAL EVs and their correlation to clinical outcomes.
Molecular and Immune Biomarkers for Cutaneous Melanoma: Current Status and Future Prospects
Authors: Pilla Lorenzo , Alberti Andrea , Di Mauro Pierluigi , Gemelli Maria , Cogliati Viola , Cazzaniga Marina Elena , Bidoli Paolo , Maccalli Cristina
Published: November 2020

Advances in the genomic, molecular and immunological make-up of melanoma allowed the development of novel targeted therapy and of immunotherapy, leading to changes in the paradigm of therapeutic interventions and improvement of patients’ overall survival. Nevertheless, the mechanisms regulating either the responsiveness or the resistance of melanoma patients to therapies are still mostly unknown. The development of either the combinations or of the sequential treatment of different agents has been investigated but without a strongly molecularly motivated rationale. The need for robust biomarkers to predict patients’ responsiveness to defined therapies and for their stratification is still unmet. Progress in immunological assays and genomic techniques as long as improvement in designing and performing studies monitoring the expression of these markers along with the evolution of the disease allowed to identify candidate biomarkers. However, none of them achieved a definitive role in predicting patients’ clinical outcomes. Along this line, the cross-talk of melanoma cells with tumor microenvironment plays an important role in the evolution of the disease and needs to be considered in light of the role of predictive biomarkers. The overview of the relationship between the molecular basis of melanoma and targeted therapies is provided in this review, highlighting the benefit for clinical responses and the limitations. Moreover, the role of different candidate biomarkers is described together with the technical approaches for their identification. The provided evidence shows that progress has been achieved in understanding the molecular basis of melanoma and in designing advanced therapeutic strategies. Nevertheless, the molecular determinants of melanoma and their role as biomarkers predicting patients’ responsiveness to therapies warrant further investigation with the vision of developing more effective precision medicine.
Exploring the Role of Osteosarcoma-Derived Extracellular Vesicles in Pre-Metastatic Niche Formation and Metastasis in the 143-B Xenograft Mouse Osteosarcoma Model
Authors: Mazumdar Alekhya , Urdinez Joaquin , Boro Aleksandar , Arlt Matthias J. E. , Egli Fabian E. , Niederöst Barbara , Jaeger Patrick K. , Moschini Greta , Muff Roman , Fuchs Bruno , Snedeker Jess G. , Gvozdenovic Ana
Published: November 2020

The pre-metastatic niche (PMN) is a tumor-driven microenvironment in distant organs that can foster and support the survival and growth of disseminated tumor cells. This facilitates the establishment of secondary lesions that eventually form overt metastasis, the main cause of cancer-related death. In recent years, tumor-derived extracellular-vesicles (EVs) have emerged as potentially key drivers of the PMN. The role of the PMN in osteosarcoma metastasis is poorly understood and the potential contribution of osteosarcoma cell-derived EVs to PMN formation has not been investigated so far. Here, we characterize pulmonary PMN development using the spontaneously metastasizing 143-B xenograft osteosarcoma mouse model. We demonstrate the accumulation of CD11b+ myeloid cells in the pre-metastatic lungs of tumor-bearing mice. We also establish that highly metastatic 143-B and poorly metastatic SAOS-2 osteosarcoma cell-derived EV education in naïve mice can recapitulate the recruitment of myeloid cells to the lungs. Surprisingly, despite EV-induced myeloid cell infiltration in the pre-metastatic lungs, 143-B and SAOS-2 EVs do not contribute towards the 143-B metastatic burden in the context of both spontaneous as well as experimental metastasis in severe-combined immunodeficient (SCID) mice. Taken together, OS-derived EVs alone may not be able to form a functional PMN, and may perhaps require a combination of tumor-secreted factors along with EVs to do so. Additionally, our study gives a valuable insight into the PMN complexity by providing the transcriptomic signature of the premetastatic lungs in an osteosarcoma xenograft model for the first time. In conclusion, identification of regulators of cellular and molecular changes in the pre-metastatic lungs might lead to the development of a combination therapies in the future that interrupt PMN formation and combat osteosarcoma metastasis.
Challenges and Therapeutic Opportunities of Autophagy in Cancer Therapy
Authors: Silva Valdenizia R. , Neves Sara P. , Santos Luciano de S. , Dias Rosane B. , Bezerra Daniel P.
Published: November 2020

Autophagy is a physiological cellular process that is crucial for development and can occurs in response to nutrient deprivation or metabolic disorders. Interestingly, autophagy plays a dual role in cancer cells—while in some situations, it has a cytoprotective effect that causes chemotherapy resistance, in others, it has a cytotoxic effect in which some compounds induce autophagy-mediated cell death. In this review, we summarize strategies aimed at autophagy for the treatment of cancer, including studies of drugs that can modulate autophagy-mediated resistance, and/or drugs that cause autophagy-mediated cancer cell death. In addition, the role of autophagy in the biology of cancer stem cells has also been discussed.
DNAJA3/Tid1 Is Required for Mitochondrial DNA Maintenance and Regulates Migration and Invasion of Human Gastric Cancer Cells
Authors: Wang Sheng-Fan , Huang Kuo-Hung , Tseng Wei-Chuan , Lo Jeng-Fan , Li Anna Fen-Yau , Fang Wen-Liang , Chen Chian-Feng , Yeh Tien-Shun , Chang Yuh-Lih , Chou Yueh-Ching , Hung Hung-Hsu , Lee Hsin-Chen
Published: November 2020

Background: Gastric cancer is a common health issue. Deregulated cellular energetics is regarded as a cancer hallmark and mitochondrial dysfunction might contribute to cancer progression. Tid1, a mitochondrial co-chaperone, may play a role as a tumor suppressor in various cancers, but the role of Tid1 in gastric cancers remains under investigated. Methods: The clinical TCGA online database and immunohistochemical staining for Tid1 expression in tumor samples of gastric cancer patients were analyzed. Tid1 knockdown by siRNA was applied to investigate the role of Tid1 in gastric cancer cells. Results: Low Tid1 protein-expressing gastric cancer patients had a poorer prognosis and higher lymph node invasion than high Tid1-expressing patients. Knockdown of Tid1 did not increase cell proliferation, colony/tumor sphere formation, or chemotherapy resistance in gastric cancer cells. However, Tid1 knockdown increased cell migration and invasion. Moreover, Tid1 knockdown reduced the mtDNA copy number of gastric cancer cells. In addition, the Tid1-galectin-7-MMP-9 axis might be associated with Tid1 knockdown–induced cell migration and invasion of gastric cancer cells. Conclusions: Tid1 is required for mtDNA maintenance and regulates migration and invasion of gastric cancer cells. Tid1 deletion may be a poor prognostic factor in gastric cancers and could be further investigated for development of gastric cancer treatments.
IL3RA-Targeting Antibody–Drug Conjugate BAY-943 with a Kinesin Spindle Protein Inhibitor Payload Shows Efficacy in Preclinical Models of Hematologic Malignancies
Authors: Kirchhoff Dennis , Stelte-Ludwig Beatrix , Lerchen Hans-Georg , Wengner Antje Margret , Ahsen Oliver von , Buchmann Pascale , Märsch Stephan , Mahlert Christoph , Greven Simone , Dietz Lisa , Erkelenz Michael , Zierz Ruprecht , Johanssen Sandra , Mumberg Dominik , Sommer Anette
Published: November 2020

IL3RA (CD123) is the alpha subunit of the interleukin 3 (IL-3) receptor, which regulates the proliferation, survival, and differentiation of hematopoietic cells. IL3RA is frequently expressed in acute myeloid leukemia (AML) and classical Hodgkin lymphoma (HL), presenting an opportunity to treat AML and HL with an IL3RA-directed antibody–drug conjugate (ADC). Here, we describe BAY-943 (IL3RA-ADC), a novel IL3RA-targeting ADC consisting of a humanized anti-IL3RA antibody conjugated to a potent proprietary kinesin spindle protein inhibitor (KSPi). In vitro, IL3RA-ADC showed potent and selective antiproliferative efficacy in a panel of IL3RA-expressing AML and HL cell lines. In vivo, IL3RA-ADC improved survival and reduced tumor burden in IL3RA-positive human AML cell line-derived (MOLM-13 and MV-4-11) as well as in patient-derived xenograft (PDX) models (AM7577 and AML11655) in mice. Furthermore, IL3RA-ADC induced complete tumor remission in 12 out of 13 mice in an IL3RA-positive HL cell line-derived xenograft model (HDLM-2). IL3RA-ADC was well-tolerated and showed no signs of thrombocytopenia, neutropenia, or liver toxicity in rats, or in cynomolgus monkeys when dosed up to 20 mg/kg. Overall, the preclinical results support the further development of BAY-943 as an innovative approach for the treatment of IL3RA-positive hematologic malignancies.
The Genomics of Myelodysplastic Syndromes: Origins of Disease Evolution, Biological Pathways, and Prognostic Implications
Authors: Awada Hassan , Thapa Bicky , Visconte Valeria
Published: November 2020

The molecular pathogenesis of myelodysplastic syndrome (MDS) is complex due to the high rate of genomic heterogeneity. Significant advances have been made in the last decade which elucidated the landscape of molecular alterations (cytogenetic abnormalities, gene mutations) in MDS. Seminal experimental studies have clarified the role of diverse gene mutations in the context of disease phenotypes, but the lack of faithful murine models and/or cell lines spontaneously carrying certain gene mutations have hampered the knowledge on how and why specific pathways are associated with MDS pathogenesis. Here, we summarize the genomics of MDS and provide an overview on the deregulation of pathways and the latest molecular targeted therapeutics.
Hot Topics in Safety for Pediatric Anesthesia
Authors: Lorinc Amanda , Walters Camila , Lovejoy Hannah , Crockett Christy , Reddy Srijaya
Published: November 2020

Anesthesiology is one of the leading medical specialties in patient safety. Pediatric anesthesiology is inherently higher risk than adult anesthesia due to differences in the physiology in children. In this review, we aimed to describe the highest yield safety topics for pediatric anesthesia and efforts to ameliorate risk. Conclusions: Pediatric anesthesiology has made great strides in patient perioperative safety with initiatives including the creation of a specialty society, quality and safety committees, large multi-institutional research efforts, and quality improvement initiatives. Common pediatric peri-operative events are now monitored with multi-institution and organization collaborative efforts, such as Wake Up Safe.