bluuebunny/crossref_metadata_2025 huggingface dataset:
Encapsulation of Phenolic Compounds from a Grape Cane Pilot-Plant Extract in Hydroxypropyl Beta-Cyclodextrin and Maltodextrin by Spray Drying
Authors: Escobar-Avello Danilo , Avendaño-Godoy Javier , Santos Jorge , Lozano-Castellón Julián , Mardones Claudia , von Baer Dietrich , Luengo Javiana , Lamuela-Raventós Rosa M. , Vallverdú-Queralt Anna , Gómez-Gaete Carolina
Published: July 2021

Grape canes, the main byproducts of the viticulture industry, contain high-value bioactive phenolic compounds, whose application is limited by their instability and poorly solubility in water. Encapsulation in cyclodextrins allows these drawbacks to be overcome. In this work, a grape cane pilot-plant extract (GCPPE) was encapsulated in hydroxypropyl beta-cyclodextrin (HP-β-CD) by a spray-drying technique and the formation of an inclusion complex was confirmed by microscopy and infrared spectroscopy. The phenolic profile of the complex was analyzed by LC-ESI-LTQ-Orbitrap-MS and the encapsulation efficiency of the phenolic compounds was determined. A total of 42 compounds were identified, including stilbenes, flavonoids, and phenolic acids, and a complex of (epi)catechin with β-CD was detected, confirming the interaction between polyphenols and cyclodextrin. The encapsulation efficiency for the total extract was 80.5 ± 1.1%, with restrytisol showing the highest value (97.0 ± 0.6%) and (E)-resveratrol (32.7 ± 2.8%) the lowest value. The antioxidant capacity of the inclusion complex, determined by ORAC-FL, was 5300 ± 472 µmol TE/g DW, which was similar to the value obtained for the unencapsulated extract. This formulation might be used to improve the stability, solubility, and bioavailability of phenolic compounds of the GCPPE for water-soluble food and pharmaceutical applications.
Phenolic Extracts from Extra Virgin Olive Oils Inhibit Dipeptidyl Peptidase IV Activity: In Vitro, Cellular, and In Silico Molecular Modeling Investigations
Authors: Lammi Carmen , Bartolomei Martina , Bollati Carlotta , Cecchi Lorenzo , Bellumori Maria , Sabato Emanuela , Giulio Vistoli , Mulinacci Nadia , Arnoldi Anna
Published: July 2021

Two extra virgin olive oil (EVOO) phenolic extracts (BUO and OMN) modulate DPP-IV activity. The in vitro DPP-IV activity assay was performed at the concentrations of 1, 10, 100, 500, and 1000 μg/mL, showing a dose-dependent inhibition by 6.8 ± 1.9, 17.4 ± 6.1, 37.9 ± 2.4, 57.8 ± 2.9, and 81 ± 1.4% for BUO and by 5.4 ± 1.7, 8.9 ± 0.4, 28.4 ± 7.2, 52 ± 1.3, and 77.5 ± 3.5% for OMN. Moreover, both BUO and OMN reduced the DPP-IV activity expressed by Caco-2 cells by 2.9 ± 0.7, 44.4 ± 0.7, 61.2 ± 1.8, and 85 ± 4.2% and by 3 ± 1.9, 35 ± 9.4, 60 ± 7.2, and 82 ± 2.8%, respectively, at the same doses. The concentration of the most abundant and representative secoiridoids within both extracts was analyzed by nuclear magnetic resonance (1H-NMR). Oleuropein, oleacein, oleocanthal, hydroxytyrosol, and tyrosol, tested alone, reduced the DPP-IV activity, with IC50 of 472.3 ± 21.7, 187 ± 11.4, 354.5 ± 12.7, 741.6 ± 35.7, and 1112 ± 55.6 µM, respectively. Finally, in silico molecular docking simulations permitted the study of the binding mode of these compounds.
A Guidance for Blockchain-Based Digital Transition in Supply Chains
Authors: Della Valle Fabio , Oliver Miquel
Published: July 2021

Blockchains play a crucial role in the digitalization of future supply chains (SCs). In this study, we analyzed the major influences that blockchain-based digital business strategies may play in SC operations. We conducted 18 interviews with international experts from different sectors and analyzed the collected data using the grounded theory approach, identifying four major categories. A set of three matrices is presented to address those elements that may support digital transition procedures in SCs: (1) value of trust and automation, (2) transformative role for operations, and (3) digital business strategy identification. As an additional result, a reference framework was identified for the evaluation and detection of those aspects to be taken into consideration during blockchain adoption in SCs. For use as a guide, this result comprises 22 recommendations and was framed in four progressive steps as follows: (1) identify, (2) assess, (3) design, and (4) assure.
Reliability and Validity of the Ground Reaction Force Asymmetric Index at Seat-Off as a Measure of Lower Limb Functional Muscle Strength: A Preliminary Study
Authors: Kim Ae-Ryoung , Park Dougho , Lee Yang-Soo
Published: July 2021

This study examined the reliability of the newly developed ground reaction force asymmetry index (GRF AI) at seat-off using a low-cost force plate and the validity of this new test by comparing it with other muscle strength-measuring methods and walking speed. This study was a cross-sectional design in general hospital setting. A convenience sample of 47 community-dwelling adults aged ≥40 years was performed. GRF AI is the measurement value obtained by shifting the weight to the right and left while performing sit-to-stand (STS). GRF AI assessed using GRF data at seat-off during an STS test with maximal weight shift to the right and left side and repeated 4 weeks later. Hip and knee extensor strength were measured using hand-held dynamometry; hand grip strength and walking speed were measured using a standardized method. Intrasessional intrarater reliability of the right and left side at Sessions 1 and 2 were high (intraclass correlation coefficients [ICC] = 0.947 and 0.974; 0.931 and 0.970, respectively). In addition, the intersessional intrarater reliability of a single test trial (ICC = 0.911 and 0.930) and the mean of three test trials (ICC = 0.965 and 0.979) was also high. There was a low correlation between right-side GRF AI and right hand grip strength (r = 0.268) and between left-side GRF AI and left hand grip strength (r = 0.316). No significant correlations were found between the GRF AI and other parameters. Although the reliability of the GRF AI was high, the validity was poor. To be clinically useful, this test should be further refined by modifying the test protocol.
Learning Attention-Aware Interactive Features for Fine-Grained Vegetable and Fruit Classification
Authors: Wang Yimin , Xiao Zhifeng , Meng Lingguo
Published: July 2021

Vegetable and fruit recognition can be considered as a fine-grained visual categorization (FGVC) task, which is challenging due to the large intraclass variances and small interclass variances. A mainstream direction to address the challenge is to exploit fine-grained local/global features to enhance the feature extraction and representation in the learning pipeline. However, unlike the human visual system, most of the existing FGVC methods only extract features from individual images during training. In contrast, human beings can learn discriminative features by comparing two different images. Inspired by this intuition, a recent FGVC method, named Attentive Pairwise Interaction Network (API-Net), takes as input an image pair for pairwise feature interaction and demonstrates superior performance in several open FGVC data sets. However, the accuracy of API-Net on VegFru, a domain-specific FGVC data set, is lower than expected, potentially due to the lack of spatialwise attention. Following this direction, we propose an FGVC framework named Attention-aware Interactive Features Network (AIF-Net) that refines the API-Net by integrating an attentive feature extractor into the backbone network. Specifically, we employ a region proposal network (RPN) to generate a collection of informative regions and apply a biattention module to learn global and local attentive feature maps, which are fused and fed into an interactive feature learning subnetwork. The novel neural structure is verified through extensive experiments and shows consistent performance improvement in comparison with the SOTA on the VegFru data set, demonstrating its superiority in fine-grained vegetable and fruit recognition. We also discover that a concatenation fusion operation applied in the feature extractor, along with three top-scoring regions suggested by an RPN, can effectively boost the performance.
English–Welsh Cross-Lingual Embeddings
Authors: Espinosa-Anke Luis , Palmer Geraint , Corcoran Padraig , Filimonov Maxim , Spasić Irena , Knight Dawn
Published: July 2021

Cross-lingual embeddings are vector space representations where word translations tend to be co-located. These representations enable learning transfer across languages, thus bridging the gap between data-rich languages such as English and others. In this paper, we present and evaluate a suite of cross-lingual embeddings for the English–Welsh language pair. To train the bilingual embeddings, a Welsh corpus of approximately 145 M words was combined with an English Wikipedia corpus. We used a bilingual dictionary to frame the problem of learning bilingual mappings as a supervised machine learning task, where a word vector space is first learned independently on a monolingual corpus, after which a linear alignment strategy is applied to map the monolingual embeddings to a common bilingual vector space. Two approaches were used to learn monolingual embeddings, including word2vec and fastText. Three cross-language alignment strategies were explored, including cosine similarity, inverted softmax and cross-domain similarity local scaling (CSLS). We evaluated different combinations of these approaches using two tasks, bilingual dictionary induction, and cross-lingual sentiment analysis. The best results were achieved using monolingual fastText embeddings and the CSLS metric. We also demonstrated that by including a few automatically translated training documents, the performance of a cross-lingual text classifier for Welsh can increase by approximately 20 percent points.
Limbic Encephalitis with HU-Antibodies in T-cell Anaplastic Lymphoma. A Case Report
Authors: Gurrieri Carmela , Visentin Andrea , Bussè Cinzia , Piazza Francesco , Manara Renzo , Trentin Livio , Briani Chiara
Published: July 2021

Limbic encephalitis is a rare paraneoplastic neurological syndrome usually associated with small cell lung cancers, testicular and breast cancers or B-cell lymphomas. We herein report the first patients with paraneoplastic limbic encephalitis associated with HU antibodies and anaplastic T-cell lymphoma.
The Effect of Surgical Mask Use in Anaerobic Running Performance
Authors: Tornero-Aguilera José Francisco , Rubio-Zarapuz Alejandro , Bustamante-Sánchez Alvaro , Clemente-Suárez Vicente Javier
Published: July 2021

COVID-19 restrictions stipulate the mandatory use of surgical masks during outdoor and indoor physical activities. The impact of this on athletic performance and especially on anaerobic physical activities is poorly known. The aim of the present research was to analyze the effect of surgical mask use on the anaerobic running performance of athletes. Modifications in running time, blood lactate, blood glucose, blood oxygen saturation, subjective perceived stress, rating of perceived exertion, and heart rate variability were measured in 50 m and 400 m maximal running tests with and without the use of surgical masks in 72 athletes. The use of a surgical mask increased blood lactate concentration, sympathetic autonomic modulation, perceived exertion, perceived stress, and decreased blood oxygen saturation in 50 and 400 m running tests. Thus, the higher levels of blood lactate and lower blood oxygen saturation require adaptation of the athlete’s rest and recovery periods to the acute workload. The higher level of sympathetic activation makes the acute and chronic control of autonomic modulation essential for an efficient training periodization. Finally, the use of acid buffers such as bicarbonate or sodium citrate would be a recommended ergogenic strategy.
Experiments on Longitudinal and Transverse Bedload Transport in Sine-Generated Meandering Channels
Authors: He Li , Chen Dong , Termini Donatella , Zhang Shiyan , Zhu Zhenhui
Published: July 2021

Bedload grains in consecutive meandering bends either move longitudinally or across the channel centerline. This study traces and quantifies the grains’ movement in two laboratorial sine-generated channels, i.e., one with deflection angle θ0 = 30° and the other 110°. The grains originally paved along the channels are uniform in size with D = 1 mm and are dyed in various colors, according to their initial location. The experiments recorded the changes in the flow patterns, bed deformation, and the gain-loss distribution of the colored grains in the pool-bar complexes. We observed the formation of two types of erosion zones during the process of the bed deformation, i.e., Zone 1 in the foreside of the point bars and Zone 2 near the concave bank downstream of the bend apexes. Most grains eroded from Zone 1 are observed moving longitudinally as opposed to crossing the channel centerline. Contrastingly, the dominant moving direction of the grains eroded from Zone 2 changes from the longitudinal direction to the transversal one as the bed topography evolves. Besides, most building material of the point bars comes from the upstream bends, although low- and highly curved channels behave differently.
Alterations in microRNA Expression during Hematopoietic Stem Cell Mobilization
Authors: Nowicki Mateusz , Szemraj Janusz , Wierzbowska Agnieszka , Pluta Agnieszka , Grzybowska-Izydorczyk Olga , Nowicka Aleksandra , Stelmach Piotr , Czemerska Magdalena , Szmigielska-Kapłon Anna
Published: July 2021

microRNAs play an important role in the regulation of gene expression, cell fate, hematopoiesis, and may influence the efficacy of CD34+ cell mobilization. The present study examines the role of hsa-miR-15a-5p, hsa-miR-16-5p, hsa-miR-34a-5p, hsa-miR-126-3p, hsa-miR-146a-5p, hsa-miR-155-5p, and hsa-miR-223-3p in the course of hematopoietic stem cell mobilization. The numbers of CD34+ cells collected in patients with hematological malignancies (39 multiple myelomas, 11 lymphomas) were determined during mobilization for an autologous hematopoietic stem cell transplantation. The miRNA level was evaluated by RT-PCR. Compared to baseline, a significant decline in hsa-miR-15a-5p, hsa-miR-16-5p, hsa-miR-126-3p, hsa-miR-146a-5p, and hsa-miR-155-5p was observed on the day of the first apheresis (day A). An increase was observed only in the expression of hsa-miR-34a-5p. On day A, a negative correlation was found between hsa-miR-15a-5p and hsa-miR-146a-5p levels and the number of CD34+ cells in peripheral blood. A negative correlation was observed between hsa-miR-146a-5p and the number of collected CD34+ cells after the first apheresis. Good mobilizers, defined according to GITMO criteria, demonstrated a lower hsa-miR-146a-5p level on day A than poor mobilizers. Patients from the hsa-miR-146a-5p “low expressors” collected more CD34+ cells than “high expressors”. Our results suggest that the investigated miRNAs, especially hsa-miR-146a-5p, may influence the efficacy of HSC mobilization.
PI3K as Mediator of Apoptosis and Contractile Dysfunction in TGFβ1-Stimulated Cardiomyocytes
Authors: Brosinsky Paulin , Bornbaum Julia , Warga Björn , Schulz Lisa , Schlüter Klaus-Dieter , Ghigo Alessandra , Hirsch Emilio , Schulz Rainer , Euler Gerhild , Heger Jacqueline
Published: July 2021

Background: TGFβ1 is a growth factor that plays a major role in the remodeling process of the heart by inducing cardiomyocyte dysfunction and apoptosis, as well as fibrosis thereby restricting heart function. TGFβ1 mediates its effect via the TGFβ receptor I (ALK5) and the activation of SMAD transcription factors, but TGFβ1 is also known as activator of phosphoinositide-3-kinase (PI3K) via the non-SMAD signaling pathway. The aim of this study was to investigate whether PI3K is also involved in TGFβ1–induced cardiomyocytes apoptosis and contractile dysfunction. Methods and Results: Incubation of isolated ventricular cardiomyocytes with TGFβ1 resulted in impaired contractile function. Pre-incubation of cells with the PI3K inhibitor Ly294002 or the ALK5 inhibitor SB431542 attenuated the decreased cell shortening in TGFβ1–stimulated cells. Additionally, TGFβ-induced apoptosis was significantly reduced by the PI3K inhibitor Ly294002. Administration of a PI3Kγ-specific inhibitor AS605240 abolished the TGFβ effect on apoptosis and cell shortening. This was also confirmed in cardiomyocytes from PI3Kγ KO mice. Induction of SMAD binding activity and the TGFβ target gene collagen 1 could be blocked by the PI3K inhibitor Ly294002, but not by the specific PI3Kγ inhibitor AS605240. Conclusions: TGFβ1-induced SMAD activation, cardiomyocyte apoptosis, and impaired cell shortening are mediated via both, the ALK5 receptor and PI3K, in adult cardiomyocytes. PI3Kγ specifically contributes to apoptosis induction and impairment of contractile function independent of SMAD signaling.
Unilateral Ureteral Obstruction for 28 Days in Rats Is Not Associated with Changes in Cardiac Function or Alterations in Mitochondrial Function
Authors: Prieto-Carrasco Rodrigo , Silva-Palacios Alejandro , Rojas-Morales Pedro , Aparicio-Trejo Omar Emiliano , Medina-Reyes Estefany Ingrid , Hernández-Cruz Estefani Yaquelin , Sánchez-Garibay Carlos , Salinas-Lara Citlaltepetl , Pavón Natalia , Roldán Francisco Javier , Zazueta Cecilia , Tapia Edilia , Pedraza-Chaverri José
Published: July 2021

Our work evaluated cardiac function and mitochondrial bioenergetics parameters in hearts from male Wistar rats subjected to the UUO model during 28 days of progression. We measured markers of kidney damage and inflammation in plasma and renal fibrosis by histological analysis and Western blot. Cardiac function was evaluated by echocardiography and proteins involved in cardiac damage by Western blot. Oxygen consumption and transmembrane potential were monitored in cardiac mitochondria using high-resolution respirometry. We also determined the activity of ATP synthase and antioxidant enzymes such as glutathione peroxidase, glutathione reductase, and catalase. Our results show that, although renal dysfunction is established in animals subjected to ureteral obstruction, cardiac function is maintained along with mitochondrial function and antioxidant enzymes activity after 28 days of injury evolution. Our results suggest that renocardiac syndrome might develop but belatedly in obstruction-induced renal damage, opening the opportunity for treatment to prevent this condition.
Slithering CSF: Cerebrospinal Fluid Dynamics in the Stationary and Moving Viper Boa, Candoia aspera
Authors: Young Bruce A. , Greer Skye , Cramberg Michael
Published: July 2021

In the viper boa (Candoia aspera), the cerebrospinal fluid (CSF) shows two stable overlapping patterns of pulsations: low-frequency (0.08 Hz) pulses with a mean amplitude of 4.1 mmHg that correspond to the ventilatory cycle, and higher-frequency (0.66 Hz) pulses with a mean amplitude of 1.2 mmHg that correspond to the cardiac cycle. Manual oscillations of anesthetized C. aspera induced propagating sinusoidal body waves. These waves resulted in a different pattern of CSF pulsations with frequencies corresponding to the displacement frequency of the body and with amplitudes greater than those of the cardiac or ventilatory cycles. After recovery from anesthesia, the snakes moved independently using lateral undulation and concertina locomotion. The episodes of lateral undulation produced similar influences on the CSF pressure as were observed during the manual oscillations, though the induced CSF pulsations were of lower amplitude during lateral undulation. No impact on the CSF was found while C. aspera was performing concertina locomotion. The relationship between the propagation of the body and the CSF pulsations suggests that the body movements produce an impulse on the spinal CSF.
Knowledge about Fibromyalgia in Fibromyalgia Patients and Its Relation to HRQoL and Physical Activity
Authors: Mendoza-Muñoz María , Morenas-Martín Jesús , Rodal Miguel , García-Matador Judith , García-Gordillo Miguel Ángel , Calzada-Rodríguez José Ignacio
Published: July 2021

Introduction: Fibromyalgia (FM) affects 2.40% of the Spanish population. The most widespread treatment has been the combination of patient education, pain coping strategies and exercise. With regard to patient education, there are few previous studies on the efficacy of relating FM education in isolation with an improvement in FM, although there are some studies that report that health education programs could modify the perception of quality of life and improve pain. Objectives: the aim was to find out the level of knowledge about FM among patients in Extremadura, to explore the relationship between knowledge of FM and Health-Related Quality of Life (HRQoL) and to analyze the relationship between knowledge of physical activity in FM and the practice of physical activity. Methods: A single-measure cross-sectional study was carried out with 121 women with a mean age of 55.06 (±9.93) years. The following questionnaires were used: Fibromyalgia Knowledge Questionnaire (FKQ); SF12v2 (Short-Form Health Survey); and EURO-QOL-5D-5L (EQ-5D-5L). Results: regarding the level of knowledge of the participants about FM, it was found that 10% had a low knowledge, 49% medium and 41% high. In relation to the associations between the level of knowledge and HRQoL, a weak correlation between EQ-5D-5L and the FKQ in the domain of physical activity (r = 0.243) were found. Conclusions: it can be concluded that the level of knowledge about FM of the patients from Extremadura was medium-high and that there is a direct weak relationship between knowledge about physical activity in FM and HRQoL. However, no association was found between knowledge of physical activity in FM and the practice of physical activity.
Whole-Body Cryotherapy Increases the Activity of Nitric Oxide Synthase in Older Men
Authors: Wiecek Magdalena , Szygula Zbigniew , Gradek Joanna , Kusmierczyk Justyna , Szymura Jadwiga
Published: July 2021

Aging causes oxidative stress, endothelial dysfunction and a reduction in the bioavailability of nitric oxide. The study aim was to determine whether, as a result of repeated whole-body exposure to cryogenic temperature (3 min −130 °C), there is an increase of inducible nitric oxide synthase (iNOS) concentration in senior subjects (59 ± 6 years), and if this effect is stronger in athletes. In 10 long-distance runners (RUN) and 10 untraining (UTR) men, 24 whole-body cryotherapy (WBC) procedures were performed. Prior to WBC, after 12th and 24th treatments and 7 days later, the concentration of iNOS, asymmetric dimethylarginine (ADMA), 3-nitrotyrosine (3-NTR), homocysteine (HCY), C-reactive protein (CRP) and interleukins such as: IL-6, IL-1β, IL-10 were measured. In the RUN and UTR groups, after 24 WBC, iNOS concentration was found to be comparable and significantly higher (F = 5.95, p < 0.01) (large clinical effect size) compared to before 1st WBC and after 12th WBC sessions. There were no changes in the concentration of the remaining markers as a result of WBC (p > 0.05). As a result of applying 24 WBC treatments, using the every-other-day model, iNOS concentration increased in the group of older men, regardless of their physical activity level. Along with this increase, there were no changes in nitro-oxidative stress or inflammation marker levels.
Computational Probing the Methylation Sites Related to EGFR Inhibitor-Responsive Genes
Authors: Yuan Rui , Chen Shilong , Wang Yongcui
Published: July 2021

The emergence of drug resistance is one of the main obstacles to the treatment of lung cancer patients with EGFR inhibitors. Here, to further understand the mechanism of EGFR inhibitors in lung cancer and offer novel therapeutic targets for anti-EGFR-inhibitor resistance via the deep mining of pharmacogenomics data, we associated DNA methylation with drug sensitivities for uncovering the methylation sites related to EGFR inhibitor sensitivity genes. Specifically, we first introduced a grouped regularized regression model (Group Least Absolute Shrinkage and Selection Operator, group lasso) to detect the genes that were closely related to EGFR inhibitor effectiveness. Then, we applied the classical regression model (lasso) to identify the methylation sites associated with the above drug sensitivity genes. The new model was validated on the well-known cancer genomics resource: CTRP. GeneHancer and Encyclopedia of DNA Elements (ENCODE) database searches indicated that the predicted methylation sites related to EGFR inhibitor sensitivity genes were related to regulatory elements. Moreover, the correlation analysis on sensitivity genes and predicted methylation sites suggested that the methylation sites located in the promoter region were more correlated with the expression of EGFR inhibitor sensitivity genes than those located in the enhancer region and the TFBS. Meanwhile, we performed differential expression analysis of genes and predicted methylation sites and found that changes in the methylation level of some sites may affect the expression of the corresponding EGFR inhibitor-responsive genes. Therefore, we supposed that the effectiveness of EGFR inhibitors in lung cancer may be improved by methylation modification in their sensitivity genes.
Enzymatic and Chemical Syntheses of Vacor Analogs of Nicotinamide Riboside, NMN and NAD
Authors: Sverkeli Lars Jansen , Hayat Faisal , Migaud Marie E. , Ziegler Mathias
Published: July 2021

It has recently been demonstrated that the rat poison vacor interferes with mammalian NAD metabolism, because it acts as a nicotinamide analog and is converted by enzymes of the NAD salvage pathway. Thereby, vacor is transformed into the NAD analog vacor adenine dinucleotide (VAD), a molecule that causes cell toxicity. Therefore, vacor may potentially be exploited to kill cancer cells. In this study, we have developed efficient enzymatic and chemical procedures to produce vacor analogs of NAD and nicotinamide riboside (NR). VAD was readily generated by a base-exchange reaction, replacing the nicotinamide moiety of NAD by vacor, catalyzed by Aplysia californica ADP ribosyl cyclase. Additionally, we present the chemical synthesis of the nucleoside version of vacor, vacor riboside (VR). Similar to the physiological NAD precursor, NR, VR was converted to the corresponding mononucleotide (VMN) by nicotinamide riboside kinases (NRKs). This conversion is quantitative and very efficient. Consequently, phosphorylation of VR by NRKs represents a valuable alternative to produce the vacor analog of NMN, compared to its generation from vacor by nicotinamide phosphoribosyltransferase (NamPT).
Leptin-Activity Modulators and Their Potential Pharmaceutical Applications
Authors: Greco Marianna , De Santo Marzia , Comandè Alessandra , Belsito Emilia Lucia , Andò Sebastiano , Liguori Angelo , Leggio Antonella
Published: July 2021

Leptin, a multifunctional hormone primarily, but not exclusively, secreted in adipose tissue, is implicated in a wide range of biological functions that control different processes, such as the regulation of body weight and energy expenditure, reproductive function, immune response, and bone metabolism. In addition, leptin can exert angiogenic and mitogenic actions in peripheral organs. Leptin biological activities are greatly related to its interaction with the leptin receptor. Both leptin excess and leptin deficiency, as well as leptin resistance, are correlated with different human pathologies, such as autoimmune diseases and cancers, making leptin and leptin receptor important drug targets. The development of leptin signaling modulators represents a promising strategy for the treatment of cancers and other leptin-related diseases. In the present manuscript, we provide an update review about leptin-activity modulators, comprising leptin mutants, peptide-based leptin modulators, as well as leptin and leptin receptor specific monoclonal antibodies and nanobodies.
A Proposed Method for Evaluating Drop Jump Performance with One Force Platform
Authors: McMahon John J. , Lake Jason P. , Stratford Callum , Comfort Paul
Published: July 2021

The drop jump (DJ) is commonly utilised to assess athletes. The criterion two force platform (2FP) method of assessing DJ performance involves two adjacent force platforms, one for the box and one for the athlete to rebound from. Most researchers and practitioners only have access to one force platform (1FP) and they rarely account for the often considerable discrepancy between box height and drop height (DH). Therefore, this study aimed to determine the criterion validity of evaluating DJ performance with 1FP. Twenty-six young male sports students performed three DJs, from a 0.30 m and 0.40 m high box, on two adjacent force platforms. The DH, touchdown velocity and several performance variables were calculated using the 2FP and 1FP methods. Ordinary least-products regression identified no fixed or proportional bias between methods for any DJ variable. The mean DH was 10% lower than the 0.30 m box and 14% lower than the 0.40 m high box. This discrepancy highlights the importance of accounting for DH when conducting DJ assessments. In conclusion, the 1FP method of evaluating DJ performance is a valid alternative to the criterion 2FP method and could be embedded into automated force analysis software for researchers and practitioners to utilise.
Environmental Enrichment Rescues Endocannabinoid-Dependent Synaptic Plasticity Lost in Young Adult Male Mice after Ethanol Exposure during Adolescence
Authors: Rico-Barrio Irantzu , Peñasco Sara , Lekunberri Leire , Serrano Maitane , Egaña-Huguet Jon , Mimenza Amaia , Soria-Gomez Edgar , Ramos Almudena , Buceta Ianire , Gerrikagoitia Inmaculada , Mendizabal-Zubiaga Juan , Elezgarai Izaskun , Puente Nagore , Grandes Pedro
Published: July 2021

Binge drinking (BD) is a serious health concern in adolescents as high ethanol (EtOH) consumption can have cognitive sequelae later in life. Remarkably, an enriched environment (EE) in adulthood significantly recovers memory in mice after adolescent BD, and the endocannabinoid, 2-arachydonoyl-glycerol (2-AG), rescues synaptic plasticity and memory impaired in adult rodents upon adolescent EtOH intake. However, the mechanisms by which EE improves memory are unknown. We investigated this in adolescent male C57BL/6J mice exposed to a drinking in the dark (DID) procedure four days per week for a duration of 4 weeks. After DID, the mice were nurtured under an EE for 2 weeks and were subjected to the Barnes Maze Test performed the last 5 days of withdrawal. The EE rescued memory and restored the EtOH-disrupted endocannabinoid (eCB)-dependent excitatory long-term depression at the dentate medial perforant path synapses (MPP-LTD). This recovery was dependent on both the cannabinoid CB1 receptor and group I metabotropic glutamate receptors (mGluRs) and required 2-AG. Also, the EE had a positive effect on mice exposed to water through the transient receptor potential vanilloid 1 (TRPV1) and anandamide (AEA)-dependent MPP long-term potentiation (MPP-LTP). Taken together, EE positively impacts different forms of excitatory synaptic plasticity in water- and EtOH-exposed brains.
Biomimicry-Based Strategies for Urban Heat Island Mitigation: A Numerical Case Study under Tropical Climate
Authors: Araque Kevin , Palacios Paola , Mora Dafni , Chen Austin Miguel
Published: July 2021

In recent years, demographic growth has caused cities to expand their urban areas, increasing the risk of overheating, creating insurmountable microclimatic conditions within the urban area, which is why studies have been carried out on the urban heat island effect (UHI) and its mitigation. Therefore, this research aims to evaluate the cooling potential in the application of strategies based on biomimicry for the microclimate in a historical heritage city of Panama. For this, three case studies (base case, case 1, and case 2) of outdoor thermal comfort were evaluated, in which the Envi-met software was used to emulate and evaluate the thermal performance of these strategies during March (highest temperature month) and October (rainier month). The strategies used were extracted from the contrast of zebra skin, human skin, evaporative cooling, and ant skin. The results showed a reduction of 2.8 °C in the air temperature at 11:00, the radiant temperature decreased by 2.2 °C, and the PET index managed to reduce the thermal comfort indicator among its categories. The importance of thinking based on biomimicry in sustainable strategies is concluded; although significant changes were obtained, high risks of discomfort persist due to the layout and proximity of the building.
Detection of Circulating Tumor Cells and Microbial DNA Fragments in Stage III Colorectal Cancer Patients under Three versus Six Months of Adjuvant Treatment
Authors: Koulouridi Asimina , Messaritakis Ippokratis , Theodorakis Emmanouil , Chondrozoumaki Maria , Sfakianaki Maria , Gouvas Nikolaos , Tsiaoussis John , Mavroudis Dimitrios , Tzardi Maria , Souglakos John
Published: July 2021

Oxaliplatin-fluoropyrimidine combination therapy is the gold standard treatment for patients with stage III colorectal cancer (CRC); however, treatment duration is now under re-evaluation. The aim of the study was the evaluation of the non-inferiority of three over six months treatment with FOLFOX or CAPOX, in stage III CRC patients. Peripheral blood samples from 121 patients were collected, at three time points during treatment and evaluated for circulating tumor cells (CTCs) and microbial DNA detection (16S rRNA, Escherichia coli, Bacteroides fragilis, Candida albicans). Of all patients, 41.3% and 58.7% were treated with FOLFOX and CAPOX, respectively. CTCs were significantly decreased and increased after three and six months of treatment, respectively. CAPOX tends to reduce the CTCs after 3 months, whereas there is a statistically significant increase of CTCs in patients under FOLFOX after 6 months. A significant correlation was demonstrated between microbial DNA detection and both CTCs detection at baseline and CTCs increase between baseline and three months of treatment. To conclude, the current study provides additional evidence of non-inferiority of three over 6 months of treatment, mainly in patients under CAPOX.
A Radiological Scoring System for Differentiation between Enchondroma and Chondrosarcoma
Authors: Miwa Shinji , Yamamoto Norio , Hayashi Katsuhiro , Takeuchi Akihiko , Igarashi Kentaro , Tada Kaoru , Yonezawa Hirotaka , Morinaga Sei , Araki Yoshihiro , Asano Yohei , Saito Shiro , Okuda Miho , Taki Junichi , Ikeda Hiroko , Nojima Takayuki , Tsuchiya Hiroyuki
Published: July 2021

Background: It is challenging to differentiate between enchondromas and atypical cartilaginous tumors (ACTs)/chondrosarcomas. In this study, correlations between radiological findings and final diagnosis were investigated in patients with central cartilaginous tumors. Methods: To evaluate the diagnostic usefulness of radiological findings, correlations between various radiological findings and final diagnoses were investigated in a cohort of 81 patients. Furthermore, a new radiological scoring system was developed by combining radiological findings. Results: Periosteal reaction on X-ray (p = 0.025), endosteal scalloping (p = 0.010) and cortical defect (p = 0.002) on CT, extraskeletal mass (p < 0.001), multilobular lesion (p < 0.001), abnormal signal in adjacent tissue (p = 0.004) on MRI, and increased uptake in bone scan (p = 0.002) and thallium scan (p = 0.027) was significantly correlated with final diagnoses. Based on the correlations between each radiological finding and postoperative histological diagnosis, a radiological scoring system combining these findings was developed. In another cohort of 17 patients, the sensitivity, specificity, and accuracy of the radiological score rates for differentiation between enchondromas and ACTs/chondrosarcomas were 88%, 89%, and 88%, respectively (p = 0.003). Conclusion: Radiological assessment with combined radiological findings is recommended to differentiate between enchondromas and ACT/chondrosarcomas.
Low Levels of Urinary PSA Better Identify Prostate Cancer Patients
Authors: Occhipinti Sergio , Mengozzi Giulio , Oderda Marco , Zitella Andrea , Molinaro Luca , Novelli Francesco , Giovarelli Mirella , Gontero Paolo
Published: July 2021

Serum prostatic specific antigen (PSA) has proven to have limited accuracy in early diagnosis and in making clinical decisions about different therapies for prostate cancer (PCa). This is partially due to the fact that an increase in PSA in the blood is due to the compromised architecture of the prostate, which is only observed in advanced cancer. On the contrary, PSA observed in the urine (uPSA) reflects the quantity produced by the prostate, and therefore can give more information about the presence of disease. We enrolled 574 men scheduled for prostate biopsy at the urology clinic, and levels of uPSA were evaluated. uPSA levels resulted lower among subjects with PCa when compared to patients with negative biopsies. An indirect correlation was observed between uPSA amount and the stage of disease. Loss of expression of PSA appears as a characteristic of prostate cancer development and its evaluation in urine represents an interesting approach for the early detection of the disease and the stratification of patients.
Consistent Major Differences in Sex- and Age-Specific Diagnostic Performance among Nine Faecal Immunochemical Tests Used for Colorectal Cancer Screening
Authors: Gies Anton , Niedermaier Tobias , Alwers Elizabeth , Hielscher Thomas , Weigl Korbinian , Heisser Thomas , Schrotz-King Petra , Hoffmeister Michael , Brenner Hermann
Published: July 2021

Evidence on diagnostic performance of faecal immunochemical tests (FITs) by sex and age is scarce. We aimed to evaluate FIT performance for detection of advanced colorectal neoplasia (AN) by sex and age across nine different FIT brands in a colonoscopy-controlled setting. The faecal samples were obtained from 2042 participants of colonoscopy screening. All eligible cases with AN (n = 216) and 300 randomly selected participants without AN were included. Diagnostic performance for detection of AN was assessed by sex and age (50–64 vs. 65–79 years for each of the nine FITs individually and for all FITs combined. Sensitivity was consistently lower, and specificity was consistently higher for females as compared with males (pooled values at original FIT cutoffs, 25.7% vs. 34.6%, p = 0.12 and 96.2% vs. 90.8%, p < 0.01, respectively). Positive predictive values (PPVs) were similar between both sexes, but negative predictive values (NPVs) were consistently higher for females (pooled values, 91.8% vs. 86.6%, p < 0.01). Sex-specific cutoffs attenuated differences in sensitivities but increased differences in predictive values. According to age, sensitivities and specificities were similar, whereas PPVs were consistently lower and NPVs were consistently higher for the younger participants. A negative FIT is less reliable in ruling out AN among men than among women and among older than among younger participants. Comparisons of measures of diagnostic performance among studies with different sex or age distributions should be interpreted with caution.
HDAC Inhibitors: Dissecting Mechanisms of Action to Counter Tumor Heterogeneity
Authors: Karagiannis Dimitris , Rampias Theodoros
Published: July 2021

Intra-tumoral heterogeneity presents a major obstacle to cancer therapeutics, including conventional chemotherapy, immunotherapy, and targeted therapies. Stochastic events such as mutations, chromosomal aberrations, and epigenetic dysregulation, as well as micro-environmental selection pressures related to nutrient and oxygen availability, immune infiltration, and immunoediting processes can drive immense phenotypic variability in tumor cells. Here, we discuss how histone deacetylase inhibitors, a prominent class of epigenetic drugs, can be leveraged to counter tumor heterogeneity. We examine their effects on cellular processes that contribute to heterogeneity and provide insights on their mechanisms of action that could assist in the development of future therapeutic approaches.
Regulation and Functions of Protumoral Unconventional T Cells in Solid Tumors
Authors: Barsac Emilie , de Amat Herbozo Carolina , Gonzalez Loïc , Baranek Thomas , Mallevaey Thierry , Paget Christophe
Published: July 2021

The vast majority of studies on T cell biology in tumor immunity have focused on peptide-reactive conventional T cells that are restricted to polymorphic major histocompatibility complex molecules. However, emerging evidence indicated that unconventional T cells, including γδ T cells, natural killer T (NKT) cells and mucosal-associated invariant T (MAIT) cells are also involved in tumor immunity. Unconventional T cells span the innate–adaptive continuum and possess the unique ability to rapidly react to nonpeptide antigens via their conserved T cell receptors (TCRs) and/or to activating cytokines to orchestrate many aspects of the immune response. Since unconventional T cell lineages comprise discrete functional subsets, they can mediate both anti- and protumoral activities. Here, we review the current understanding of the functions and regulatory mechanisms of protumoral unconventional T cell subsets in the tumor environment. We also discuss the therapeutic potential of these deleterious subsets in solid cancers and why further feasibility studies are warranted.
Perovskite Zinc Titanate Photocatalysts Synthesized by the Sol–Gel Method and Their Application in the Photocatalytic Degradation of Emerging Contaminants
Authors: Chen Wei-Yu , Wang Ching-Ping , Chen Po-Chou , Lin Kun-Yi Andrew , Ghosh Surajit , Huang Chao-Wei , Nguyen Van-Huy
Published: July 2021

In this study, perovskite ZnTiO3 photocatalysts were fabricated by the sol–gel method. The photocatalytic capability was verified by the degradation of the emerging contaminant, the antibiotic amoxicillin (AMX). For the preparation, the parameters of the calcination temperature and the additional amount of polyvinylpyrrolidone (PVP) and ammonia are discussed, including the calcining temperature (500, 600, 700, 800 °C), the volume of ammonia (750, 1500, 3000 μL), and the weight of PVP (3 g and 5 g). The prepared perovskite ZnTiO3 was characterized by XRD, FESEM, BET, and UV-Vis. It is shown that the perovskite ZnTiO3 photocatalysts are structurally rod-like and ultraviolet light-responsive. Consequently, the synthesis conditions for fabricating the perovskite ZnTiO3 photocatalysts with the highest photocatalytic performance were a calcining temperature of 700 °C, an additional ammonia amount of 1500 μL, and added PVP of 5 g. Moreover, the photocatalytic degradation of perovskite ZnTiO3 photocatalysts on other pollutants, including the antibiotic tetracycline (TC), methyl orange (MO), and methylene blue (MB) dyes, was also examined. This provides the basis for the application of perovskite ZnTiO3 as a photocatalyst to decompose emerging contaminants and organic pollutants in wastewater treatment.
Trafficking to the Cell Surface of Amino Acid Transporter SLC6A14 Upregulated in Cancer Is Controlled by Phosphorylation of SEC24C Protein by AKT Kinase
Authors: Kovalchuk Vasylyna , Nałęcz Katarzyna A.
Published: July 2021

Cancer cells need a constant supply of nutrients. SLC6A14, an amino acid transporter B0,+ (ATB0,+) that is upregulated in many cancers, transports all but acidic amino acids. In its exit from the endoplasmic reticulum (ER), it is recognized by the SEC24C subunit of coatomer II (COPII) for further vesicular trafficking to the plasma membrane. SEC24C has previously been shown to be phosphorylated by protein kinase B/AKT, which is hyper-activated in cancer; therefore, we analyzed the influence of AKT on SLC6A14 trafficking to the cell surface. Studies on overexpressed and endogenous transporters in the breast cancer cell line MCF-7 showed that AKT inhibition with MK-2206 correlated with a transient increase of the transporter in the plasma membrane, not resulting from the inhibition of ER-associated protein degradation. Two-dimensional electrophoresis demonstrated the decreased phosphorylation of SLC6A14 and SEC24C upon AKT inhibition. A proximity ligation assay confirmed this conclusion: AKT inhibition is correlated with decreased SLC6A14 phosphothreonine and SEC24C phosphoserine. Augmented levels of SLC6A14 in plasma membrane led to increased leucine transport. These results show that the inactivation of AKT can rescue amino acid delivery through SLC6A14 trafficking to the cell surface, supporting cancer cell survival. The regulation of the ER export of the amino acid transporter seems to be a novel function of AKT.
Positive Rate of Tests for Group a Streptococcus and Viral Features in Children with Acute Pharyngitis
Authors: Wi Dasom , Choi Soo-Han
Published: July 2021

Group A streptococcus (GAS) is an important cause of acute pharyngitis. We investigated the positive rate of GAS tests and clinical viral features in children with acute pharyngitis. A retrospective review was conducted for patients <15 years old with both rapid antigen detection test (RADT) and throat culture results. Patients were excluded if they were diagnosed with influenza or had received antibiotics within two weeks before these tests. A total of 377 patients were eligible. The median age of patients was 3.5 years, and 45.4% of total patients were <3 years old. Among all patients, 68.7% had at least one viral feature, and 39% had more than two. The overall positiv rate for GAS was 11.4%. The GAS positive rate was significantly lower in patients <3 years old than in older patients (1.8% vs. 19.4%, p < 0.0001). The overall sensitivity and specificity of RADT were 75.0% (95% CI: 57.8–87.9) and 97.9% (95% CI: 95.8–99.2), respectively. The GAS positive rate was not significantly different between patients with and without viral features (12.4% vs. 9.3%, p = 0.4854). In patients aged 3–14 years, the GAS positive rate was not associated with the modified Centor score or the frequency of clinical viral features. Despite a low prevalence of GAS pharyngitis, testing for GAS was frequently performed in children <3 years old in this study. Appropriate use of laboratory testing for GAS pharyngitis and judicious prescription of antibiotics were imperative.
Undara Lava Cave Fauna in Tropical Queensland with an Annotated List of Australian Subterranean Biodiversity Hotspots
Authors: Eberhard Stefan M. , Howarth Francis G.
Published: July 2021

The lava tubes at Undara became internationally recognised in the late 1980s, when 24 species of terrestrial cave-adapted invertebrates (troglobionts) were recorded from Bayliss Cave, making it one of the 20 richest known cave communities in the world at the time. Over the last decades, several of the Undara species have been taxonomically described and a great deal of research has been undertaken in other parts of Australia, which has revealed additional subterranean hotspots. It is therefore timely to update the list of Undara cave fauna, and to evaluate the Undara cave system in relation to other subterranean hotspots in Australia. The updated species list was compiled from the published literature and museum databases. Minimally, 78 species of arthropods have been recorded from 17 lava tube caves in the Undara Basalt. Sixteen species have been taxonomically described; 30 identified to genus and/or morpho-species; and 32 remain unidentified to species or genus level. Thirty troglobionts and one stygobiont species were recorded. Seven caves harboured obligate subterranean species; Bayliss Cave harboured the most obligate subterranean species: 23 troglobionts and one stygobiont. All these caves contained deep zone environments with high humidity, of which three also contained ‘bad air’ (CO2). The unique combination of geomorphic structure and environmental parameters (high humidity) and multiple energy sources (tree roots, bats and guano, organic material wash-in) are the main factors responsible for Bayliss Cave’s extraordinary local richness. Further research is needed to investigate CO2 as a factor influencing troglobiont richness and distribution in ‘bad air’ caves. Undara remains the richest subterranean hotspot in humid tropical Australia; however, significantly richer subterranean assemblages are found in arid and semi-arid calcrete aquifers, karst and iron-ore terrains, mostly in Western Australia.