bluuebunny/crossref_metadata_2025 huggingface dataset:
The Effect of Intratumoral Interrelation among FOXP3+ Regulatory T Cells on Treatment Response and Survival in Triple-Negative Breast Cancer
Authors: Goda Noriko , Nakashima Chika , Nagamine Ichiro , Otagaki Sunao
Published: April 2022

Triple-negative breast cancer (TNBC) is characterized by an active immune response. We evaluated intratumoral interrelation between FOXP3+ tumor-infiltrating lymphocytes and other cytokines in TNBC. Network analysis refined cytokines significantly correlate with FOPX3 in TNBC. Information on the treatment response and prognosis of patients, and survival data from the TGCA and METABRIC databases were analyzed according to refined cytokines. Interleukin (IL)-33 was significantly expressed by TNBC cell lines compared to luminal cell lines (log2 fold change: 5.31, p < 0.001) and IL-33 and TGFB2 showed a strong correlation with FOXP3 in the TNBC cell line. Immunohistochemistry demonstrated that the IL-33 high group was a significant predictor of complete response of neoadjuvant chemotherapy (odds ratio (OR) 4.12, p < 0.05) and favorable survival compared to the IL-33 low group (OR 6.48, p < 0.05) in TNBC. Survival data from TGCA and METABRIC revealed that FOXP3 was a significantly favorable marker in the IL-33 high group compared to the low IL-33 low group (hazard ratio (HR) 2.1, p = 0.02), and the IL-33 high/TGFB2 high subgroup showed significant favorable prognosis in the FOXP3 high group compared to the FOPX3 low group in TNBC (HR 3.5, p = 0.01). IL-33 and TGFB2 were key cytokines of intratumoral interrelation among FOXP3 in TNBC.
Resveratrol Contrasts IL-6 Pro-Growth Effects and Promotes Autophagy-Mediated Cancer Cell Dormancy in 3D Ovarian Cancer: Role of miR-1305 and of Its Target ARH-I
Authors: Esposito Andrea , Ferraresi Alessandra , Salwa Amreen , Vidoni Chiara , Dhanasekaran Danny N. , Isidoro Ciro
Published: April 2022

Tumor dormancy is the extended period during which patients are asymptomatic before recurrence, and it represents a difficult phenomenon to target pharmacologically. The relapse of tumors, for instance arising from the interruption of dormant metastases, is frequently observed in ovarian cancer patients and determines poor survival. Inflammatory cytokines present in the tumor microenvironment likely contribute to such events. Cancer cell dormancy and autophagy are interconnected at the molecular level through ARH-I (DIRAS3) and BECLIN-1, two tumor suppressors often dysregulated in ovarian cancers. IL-6 disrupts autophagy in ovarian cancer cells via miRNAs downregulation of ARH-I, an effect contrasted by the nutraceutical protein restriction mimetic resveratrol (RV). By using three ovarian cancer cell lines with different genetic background in 2D and 3D models, the latter mimicking the growth of peritoneal metastases, we show that RV keeps the cancer cells in a dormant-like quiescent state contrasting the IL-6 growth-promoting activity. Mechanistically, this effect is mediated by BECLIN-1-dependent autophagy and relies on the availability of ARH-I. We also show that ARH-I (DIRAS3) is a bona fide target of miR-1305, a novel oncomiRNA upregulated by IL-6 and downregulated by RV. Clinically relevant, bioinformatic analysis of a transcriptomic database showed that the high expression of DIRAS3 and MAP1LC3B mRNAs together with that of CDKN1A, directing a cellular dormant phenotype, predicts better overall survival in ovarian cancer patients, and this correlates with MIR1305 downregulation. The possibility of maintaining a permanent cell dormancy in ovarian cancer by the chronic administration of RV should be considered as a therapeutic option to prevent the “awakening” of cancer cells in response to a permissive microenvironment, thus limiting the risk of tumor relapse and metastasis.
Spatial Characterization of Tumor-Infiltrating Lymphocytes and Breast Cancer Progression
Authors: Fassler Danielle J. , Torre-Healy Luke A. , Gupta Rajarsi , Hamilton Alina M. , Kobayashi Soma , Van Alsten Sarah C. , Zhang Yuwei , Kurc Tahsin , Moffitt Richard A. , Troester Melissa A. , Hoadley Katherine A. , Saltz Joel
Published: April 2022

Tumor-infiltrating lymphocytes (TILs) have been established as a robust prognostic biomarker in breast cancer, with emerging utility in predicting treatment response in the adjuvant and neoadjuvant settings. In this study, the role of TILs in predicting overall survival and progression-free interval was evaluated in two independent cohorts of breast cancer from the Cancer Genome Atlas (TCGA BRCA) and the Carolina Breast Cancer Study (UNC CBCS). We utilized machine learning and computer vision algorithms to characterize TIL infiltrates in digital whole-slide images (WSIs) of breast cancer stained with hematoxylin and eosin (H&E). Multiple parameters were used to characterize the global abundance and spatial features of TIL infiltrates. Univariate and multivariate analyses show that large aggregates of peritumoral and intratumoral TILs (forests) were associated with longer survival, whereas the absence of intratumoral TILs (deserts) is associated with increased risk of recurrence. Patients with two or more high-risk spatial features were associated with significantly shorter progression-free interval (PFI). This study demonstrates the practical utility of Pathomics in evaluating the clinical significance of the abundance and spatial patterns of distribution of TIL infiltrates as important biomarkers in breast cancer.
Divergent Roles of Mitochondria Dynamics in Pancreatic Ductal Adenocarcinoma
Authors: Carmona-Carmona Cristian Andres , Dalla Pozza Elisa , Ambrosini Giulia , Errico Andrea , Dando Ilaria
Published: April 2022

Pancreatic ductal adenocarcinoma (PDAC) is one of the most aggressive tumors; it is often diagnosed at an advanced stage and is hardly treatable. These issues are strictly linked to the absence of early diagnostic markers and the low efficacy of treatment approaches. Recently, the study of the metabolic alterations in cancer cells has opened the way to important findings that can be exploited to generate new potential therapies. Within this scenario, mitochondria represent important organelles within which many essential functions are necessary for cell survival, including some key reactions involved in energy metabolism. These organelles remodel their shape by dividing or fusing themselves in response to cellular needs or stimuli. Interestingly, many authors have shown that mitochondrial dynamic equilibrium is altered in many different tumor types. However, up to now, it is not clear whether PDAC cells preferentially take advantage of fusion or fission processes since some studies reported a wide range of different results. This review described the role of both mitochondria arrangement processes, i.e., fusion and fission events, in PDAC, showing that a preference for mitochondria fragmentation could sustain tumor needs. In addition, we also highlight the importance of considering the metabolic arrangement and mitochondria assessment of cancer stem cells, which represent the most aggressive tumor cell type that has been shown to have distinctive metabolic features to that of differentiated tumor cells.
MiR-150-5p Overexpression in Triple-Negative Breast Cancer Contributes to the In Vitro Aggressiveness of This Breast Cancer Subtype
Authors: Sugita Bruna M. , Rodriguez Yara , Fonseca Aline S. , Nunes Souza Emanuelle , Kallakury Bhaskar , Cavalli Iglenir J. , Ribeiro Enilze M. S. F. , Aneja Ritu , Cavalli Luciane R.
Published: April 2022

MiR-150-5p is frequently deregulated in cancer, with expression and mode of action varying according to the tumor type. Here, we investigated the expression levels and role of miR-150-5p in the aggressive breast cancer subtype triple-negative breast cancer (TNBC). MiR-150-5p expression levels were analyzed in tissue samples from 113 patients with invasive breast cancer (56 TNBC and 57 non-TNBC) and 41 adjacent non-tumor tissues (ANT). Overexpression of miR-150-5p was observed in tumor tissues compared with ANT tissues and in TNBC compared with non-TNBC tissues. MiR-150-5p expression levels were significantly associated with high tumor grades and the Caucasian ethnicity. Interestingly, high miR-150-5p levels were associated with prolonged overall survival. Manipulation of miR-150-5p expression in TNBC cells modulated cell proliferation, clonogenicity, migration, and drug resistance. Manipulation of miR-150-5p expression also resulted in altered expression of its mRNA targets, including epithelial-to-mesenchymal transition markers, MYB, and members of the SRC pathway. These findings suggest that miR-150-5p is overexpressed in TNBC and contributes to the aggressiveness of TNBC cells in vitro.
Unveiling the Role of the Tumor Microenvironment in the Treatment of Follicular Lymphoma
Authors: Blanco Mariola , Collazo-Lorduy Ana , Yanguas-Casás Natalia , Calvo Virginia , Provencio Mariano
Published: April 2022

Follicular lymphomas (FL) are neoplasms that resemble normal germinal center (GC) B-cells. Normal GC and neoplastic follicles contain non-neoplastic cells such as T-cells, follicular dendritic cells, cancer associated fibroblasts, and macrophages, which define the tumor microenvironment (TME), which itself is an essential factor in tumor cell survival. The main characteristics of the TME in FL are an increased number of follicular regulatory T-cells (Treg) and follicular helper T-cells (Tfh), M2-polarization of macrophages, and the development of a nodular network by stromal cells that creates a suitable niche for tumor growth. All of them play important roles in tumor angiogenesis, inhibition of apoptosis, and immune evasion, which are key factors in tumor progression and transformation risk. Based on these findings, novel therapies have been developed to target specific mutations present in the TME cells, restore immune suppression, and modulate TME.
Antitumor Properties of Curcumin in Breast Cancer Based on Preclinical Studies: A Systematic Review
Authors: Barcelos Kênia Alves , Mendonça Carolina Rodrigues , Noll Matias , Botelho Ana Flávia , Francischini Cristiane Raquel Dias , Silva Marco Augusto Machado
Published: April 2022

Breast cancer is one of the most common neoplasms among women. Anticancer strategies using natural formulations and phytotherapies are promising antitumor treatment alternatives. This review assesses the antitumor effects of curcumin on breast cancer reported in preclinical in vitro and in vivo animal models. We used five databases to search for preclinical studies published up to May 2021. The assessments included the effects of curcumin on the proliferation, viability, and apoptosis of breast cancer cell lineages and on tumor volume. In total, 60 articles met the inclusion criteria. Curcumin administered at different concentrations and via different routes of administration inhibited proliferation, decreased viability, and induced apoptosis in human and animal breast cancer cells. Nanoparticle formulations of curcumin administered orally, via implant, and intraperitoneally reduced the tumor volume of human and murine mammary cells in vivo. Moreover, curcumin nanoformulations exert positive effects on tumor growth inhibition in animal models of breast cancer. Further randomized clinical trials are warranted to assess the efficacy and safety of curcumin formulations for clinical use.
RB1-Negative Retinal Organoids Display Proliferation of Cone Photoreceptors and Loss of Retinal Differentiation
Authors: Kanber Deniz , Woestefeld Julia , Döpper Hannah , Bozet Morgane , Brenzel Alexandra , Altmüller Janine , Kilpert Fabian , Lohmann Dietmar , Pommerenke Claudia , Steenpass Laura
Published: April 2022

Retinoblastoma is a tumor of the eye in children under the age of five caused by biallelic inactivation of the RB1 tumor suppressor gene in maturing retinal cells. Cancer models are essential for understanding tumor development and in preclinical research. Because of the complex organization of the human retina, such models were challenging to develop for retinoblastoma. Here, we present an organoid model based on differentiation of human embryonic stem cells into neural retina after inactivation of RB1 by CRISPR/Cas9 mutagenesis. Wildtype and RB1 heterozygous mutant retinal organoids were indistinguishable with respect to morphology, temporal development of retinal cell types and global mRNA expression. However, loss of pRB resulted in spatially disorganized organoids and aberrant differentiation, indicated by disintegration of organoids beyond day 130 of differentiation and depletion of most retinal cell types. Only cone photoreceptors were abundant and continued to proliferate, supporting these as candidate cells-of-origin for retinoblastoma. Transcriptome analysis of RB1 knockout organoids and primary retinoblastoma revealed gain of a retinoblastoma expression signature in the organoids, characterized by upregulation of RBL1 (p107), MDM2, DEK, SYK and HELLS. In addition, genes related to immune response and extracellular matrix were specifically upregulated in RB1-negative organoids. In vitro retinal organoids therefore display some features associated with retinoblastoma and, so far, represent the only valid human cancer model for the development of this disease.
Shifting CCR7 towards Its Monomeric Form Augments CCL19 Binding and Uptake
Authors: Gerken Oliver J. , Artinger Marc , Legler Daniel F.
Published: April 2022

The chemokine receptor CCR7, together with its ligands, is responsible for the migration and positioning of adaptive immune cells, and hence critical for launching adaptive immune responses. CCR7 is also induced on certain cancer cells and contributes to metastasis formation. Thus, CCR7 expression and signalling must be tightly regulated for proper function. CCR7, like many other members of the G-protein coupled receptor superfamily, can form homodimers and oligomers. Notably, danger signals associated with pathogen encounter promote oligomerisation of CCR7 and is considered as one layer of regulating its function. Here, we assessed the dimerisation of human CCR7 and several single point mutations using split-luciferase complementation assays. We demonstrate that dimerisation-defective CCR7 mutants can be transported to the cell surface and elicit normal chemokine-driven G-protein activation. By contrast, we discovered that CCR7 mutants whose expression are shifted towards monomers significantly augment their capacities to bind and internalise fluorescently labelled CCL19. Modeling of the receptor suggests that dimerisation-defective CCR7 mutants render the extracellular loops more flexible and less structured, such that the chemokine recognition site located in the binding pocket might become more accessible to its ligand. Overall, we provide new insights into how the dimerisation state of CCR7 affects CCL19 binding and receptor trafficking.
Recapitulation of Retinal Damage in Zebrafish Larvae Infected with Zika Virus
Authors: Maleski Adolfo Luis Almeida , Rosa Joao Gabriel Santos , Bernardo Jefferson Thiago Gonçalves , Astray Renato Mancini , Walker Cristiani Isabel Banderó , Lopes-Ferreira Monica , Lima Carla
Published: April 2022

Zebrafish are increasingly being utilized as a model to investigate infectious diseases and to advance the understanding of pathogen–host interactions. Here, we take advantage of the zebrafish to recapitulate congenital ZIKV infection and, for the first time, demonstrate that it can be used to model infection and reinfection and monitor anti-viral and inflammatory immune responses, as well as brain growth and eye abnormalities during embryonic development. By injecting a Brazilian strain of ZIKV into the yolk sac of one-cell stage embryos, we confirmed that, after 72 h, ZIKV successfully infected larvae, and the physical condition of the virus-infected hosts included gross morphological changes in surviving embryos (84%), with a reduction in larval head size and retinal damage characterized by increased thickness of the lens and inner nuclear layer. Changes in locomotor activity and the inability to perceive visual stimuli are a result of changes in retinal morphology caused by ZIKV. Furthermore, we demonstrated the ability of ZIKV to replicate in zebrafish larvae and infect new healthy larvae, impairing their visual and neurological functions. These data reinforce the deleterious activity of ZIKV in the brain and visual structures and establish the zebrafish as a model to study the molecular mechanisms involved in the pathology of the virus.
Multiple Phosphorylations of SR Protein SRSF3 and Its Binding to m6A Reader YTHDC1 in Human Cells
Authors: Tatsuno Takanori , Ishigaki Yasuhito
Published: April 2022

N6-methyladenosine (m6A) is a well-known RNA modification and has various functions with its binding proteins. Nuclear m6A reader protein YTHDC1 plays a significant role in RNA metabolism including some non-coding RNA such as LINE or circRNA. It is also known to regulate mRNA splicing through recruiting SRSF3 to the targeted mRNAs, which then mediates export of YTHDC1-bound RNA to the cytoplasm. Additionally, it has been indicated that SRSF3 binding to YHTDC1 may be mediated by its dephosphorylated status. However, their binding mechanism, including the positions of dephosphorylated residues of SRSF3, has not been sufficiently investigated. Thus, we explored the mechanism of interaction between SRSF3 and YTHDC1 in human cells. We used co-immunoprecipitation to examine the binding of YTHDC1/SRSF3 through their N- and C-terminal amino-acid residues. Furthermore, dephosphorylation-mimic serine to alanine mutants of SRSF3 indicated the position of phosphorylated residues. Cumulatively, our results demonstrate that YTHDC1 binding to SRSF3 is regulated by not only hypo-phosphorylated residues of arginine/serine-rich (RS) domain of SRSF3 but also other parts of SRSF3 via YTHDC1 N- or C-terminal residues. Our results contribute to the understanding of the complex mechanism of binding between SR protein SRSF3 and the m6A reader YTHDC1 to regulate the expression of mRNA and non-coding RNAs.
DNA Damage Response Inhibitors in Cholangiocarcinoma: Current Progress and Perspectives
Authors: Gönül Geyik Öykü , Anichini Giulia , Ulukaya Engin , Marra Fabio , Raggi Chiara
Published: April 2022

Cholangiocarcinoma (CCA) is a poorly treatable type of cancer and its incidence is dramatically increasing. The lack of understanding of the biology of this tumor has slowed down the identification of novel targets and the development of effective treatments. Based on next generation sequencing profiling, alterations in DNA damage response (DDR)-related genes are paving the way for DDR-targeting strategies in CCA. Based on the notion of synthetic lethality, several DDR-inhibitors (DDRi) have been developed with the aim of accumulating enough DNA damage to induce cell death in tumor cells. Observing that DDRi alone could be insufficient for clinical use in CCA patients, the combination of DNA-damaging regimens with targeted approaches has started to be considered, as evidenced by many emerging clinical trials. Hence, novel therapeutic strategies combining DDRi with patient-specific targeted drugs could be the next level for treating cholangiocarcinoma.
Phytoliths from Woody Plants: A Review
Authors: An Xiaohong , Xie Binrong
Published: April 2022

Phytoliths are efficient proxies in archaeology, plant taxonomy, palaeoenvironment, and palaeoecology reconstruction, the research of which has been developing rapidly in recent years. Phytolith morphology is the basis of phytolith research. The morphological identification and classification of grass phytoliths are clear and detailed enough for application. However, the morphology of phytoliths from woody plants is ambiguous and unsystematic because of the relatively rare research on modern phytoliths and consequently seldom used in archaeology and palaeoenvironment reconstruction. This paper summarizes and concludes the research of woody phytolith morphology in the past decades. Previous studies show that palms and conifers produce some diagnostic phytoliths for identification and classification. There is progress in micromorphology, morphometry, and taxonomic identification of palms and conifers phytoliths. The phytolith morphology of broad-leaved trees is summarized according to produced parts of phytoliths in plants. The potential of further classification for broad-leaved phytoliths was discussed.
Optimal Population Coding for Dynamic Input by Nonequilibrium Networks
Authors: Chen Kevin S.
Published: April 2022

The efficient coding hypothesis states that neural response should maximize its information about the external input. Theoretical studies focus on optimal response in single neuron and population code in networks with weak pairwise interactions. However, more biological settings with asymmetric connectivity and the encoding for dynamical stimuli have not been well-characterized. Here, we study the collective response in a kinetic Ising model that encodes the dynamic input. We apply gradient-based method and mean-field approximation to reconstruct networks given the neural code that encodes dynamic input patterns. We measure network asymmetry, decoding performance, and entropy production from networks that generate optimal population code. We analyze how stimulus correlation, time scale, and reliability of the network affect optimal encoding networks. Specifically, we find network dynamics altered by statistics of the dynamic input, identify stimulus encoding strategies, and show optimal effective temperature in the asymmetric networks. We further discuss how this approach connects to the Bayesian framework and continuous recurrent neural networks. Together, these results bridge concepts of nonequilibrium physics with the analyses of dynamics and coding in networks.
Biodiesel Is Dead: Long Life to Advanced Biofuels—A Comprehensive Critical Review
Authors: Estevez Rafael , Aguado-Deblas Laura , López-Tenllado Francisco J. , Luna Carlos , Calero Juan , Romero Antonio A. , Bautista Felipa M. , Luna Diego
Published: April 2022

Many countries are immersed in several strategies to reduce the carbon dioxide (CO2) emissions of internal combustion engines. One option is the substitution of these engines by electric and/or hydrogen engines. However, apart from the strategic and logistical difficulties associated with this change, the application of electric or hydrogen engines in heavy transport, e.g., trucks, shipping, and aircrafts, also presents technological difficulties in the short-medium term. In addition, the replacement of the current car fleet will take decades. This is why the use of biofuels is presented as the only viable alternative to diminishing CO2 emissions in the very near future. Nowadays, it is assumed that vegetable oils will be the main raw material for replacing fossil fuels in diesel engines. In this context, it has also been assumed that the reduction in the viscosity of straight vegetable oils (SVO) must be performed through a transesterification reaction with methanol in order to obtain the mixture of fatty acid methyl esters (FAMEs) that constitute biodiesel. Nevertheless, the complexity in the industrial production of this biofuel, mainly due to the costs of eliminating the glycerol produced, has caused a significant delay in the energy transition. For this reason, several advanced biofuels that avoid the glycerol production and exhibit similar properties to fossil diesel have been developed. In this way, “green diesels” have emerged as products of different processes, such as the cracking or pyrolysis of vegetable oil, as well as catalytic (hydro)cracking. In addition, some biodiesel-like biofuels, such as Gliperol (DMC-Biod) or Ecodiesel, as well as straight vegetable oils, in blends with plant-based sources with low viscosity have been described as renewable biofuels capable of performing in combustion ignition engines. After evaluating the research carried out in the last decades, it can be concluded that green diesel and biodiesel-like biofuels could constitute the main alternative to addressing the energy transition, although green diesel will be the principal option in aviation fuel.
Forest Management Practices and Costs for Family Forest Landowners in Georgia, USA
Authors: Godar Chhetri Sagar , Parker Jake , Izlar Robert L. , Li Yanshu
Published: April 2022

Forests owned by individuals and family landowners account for about two-thirds of Georgia’s private forests. This study provides a snapshot of the status and trend of forest management practices of Georgia family forest landowners and the unit costs associated with significant management activities through a survey of the consulting foresters practicing in the state. Family forest landowners increasingly managed pines intensively with various management regimes. Hardwood and mixed forests accounted for more than half of Georgia’s private forests, but they were mainly managed in a custodial manner. Besides receiving revenue from timber sales, many landowners in Georgia received additional income from hunting leases and selling pine straw. The results have important implications for the financial returns of timber investment and the long-term timber supply of the state. It also provides essential information to county assessors for fair and equitable timberland valuation for property tax purposes.
Cultivation Potential and Uses of Paulownia Wood: A Review
Authors: Jakubowski Marcin
Published: April 2022

This review aimed to determine the current state of research on the growth conditions and use pertaining to paulownia wood, mainly in European countries where paulownia has been introduced only relatively recently. Several studies carried out on Paulownia hybrids have shown significant differences in the growth dynamics of individual clones in their response to local environmental and climatic conditions. For example, dry biomass production yields in the second year of cultivation range from 1.5 t ha−1 to as much as 14 t ha−1. This diversity has manifested itself not only in growth characteristics but also in the properties of the wood and the possibilities for its use. Despite having clear similarities to the genus Paulownia, the cultivation of species and hybrids under different conditions has produced varying results. The best growing conditions for this wood (that make economic sense) are in the Middle East and Southern Europe. These regions have accumulated the most experience because of the earlier establishment of the crop. Today, paulownia cultivation is dominated by hybrids with selected traits that are propagated mainly in vitro. The most commonly planted hybrids include the clones in vitro 112, Cotevisa 2 and Shan Tong. The growth results and production capacity in central European countries are lower compared to Southern Europe. Experiments on paulownia cultivation are still relatively young, mainly consisting of replicating the cultivation of hybrids developed in Asia or Southern Europe. However, agronomic procedures are being developed and reactions to local climatic conditions are being studied. It is likely that, in the next few years, the profitability of growing paulownia in these regions will become apparent.
The Effect of Target Log Length on Log Recovery and Harvesting Cost: The Example of Short-Rotation Poplar Plantations
Authors: Spinelli Raffaele , Kováč Barnabáš , Heger Patrik , Heilig Dávid , Heil Bálint , Kovács Gábor , Magagnotti Natascia
Published: April 2022

Log production is the main target of new short-rotation poplar plantations, and their profitability depends on maximizing log yield. The authors set up a controlled experiment to determine the log yield increase obtained by shortening log length specification from 4 to 2 m, and to quantify the additional cost incurred by this change. The experiment indicated that reducing log length specifications allows a significant increase (+40%) in log yield in low-yielding (<25 BDT ha−1) plantations, only. Such increase is matched by a parallel increase in harvesting cost (+33%) that must be balanced against the recovered additional value. Measures are suggested to mitigate the harvesting cost increment, such as: dual log length specifications, modifications of the forwarder load bay and changing from cut-to-length to whole-tree harvesting.
Snake Venom and 3D Microenvironment Cell Culture: From Production to Drug Development
Authors: Kato Ellen Emi , Viala Vincent Louis , Sampaio Sandra Coccuzzo
Published: April 2022

Snake venoms are a natural biological source of bioactive compounds, mainly composed of proteins and peptides with specific pathophysiological functions. The diversity of protein families found in snake venoms is reflected by the range of targets and toxicological effects observed, and consequently, a wide variety of potential pharmacological activities. In this context, in vitro biomimetic models such as spheroid and organoid systems, which are three-dimensional (3D) cell culture models, enable extensive screening and identification of substances with pharmacological potential and the determination of the mechanisms underlying their activities. In this review we summarize the main findings of 3D microenvironment cell culture as a promising model for snake venom research, from producing snake toxins on venom gland organoids to screening pharmacological active compounds on spheroids for drug development.
Effect of Hypoxia on Glucose Transporter 1 and 3 Gene Expression in Placental Mesenchymal Stem Cells Derived from Growth-Restricted Fetuses
Authors: Chang Yao-Lung , Chang Shuenn-Dyh , Chao An-Shine , Sieber Martin , Tsai Chia-Lung , Cheng Po-Jen
Published: April 2022

(1) Background: Glucose is transferred from maternal blood to the fetus by glucose transporters. What is the effect of hypoxia on the gene expression of placenta glucose transporter 1 (GLUT1) and glucose transporter 3 (GLUT3) in growth-restricted fetus is interesting. (2) Methods: The gene expression of GLUT1 and GLUT3 and the protein expression of HIF-1α were evaluated under nonhypoxic conditions and after 4 and 8 h under hypoxic conditions in placental mesenchymal stem cells derived from monochorionic twin pregnancies with selective intrauterine growth restriction. (3) Results: The gene expressions of GLUT1 and GLUT3 under hypoxia conditions were higher in placental mesenchymal stem cells derived from appropriate-for-gestational-age fetuses than in those from selective intrauterine growth-restricted fetuses. However, the protein expression of hypoxia induced factor-1 α (HIF-1α) at hypoxia condition was not lower in placenta mesenchymal stem cells from selective intrauterine growth-restricted fetuses than in placental mesenchymal stem cells from appropriate-for-gestational-age fetuses. (4) Conclusions: Hypoxia-induced upregulation of GLUT1 and GLUT3 expression was decreased in placental mesenchymal stem cells from selective intrauterine growth-restricted fetuses but not due to decreased HIF-1α expression. Selective growth-restricted fetuses have less capacity for hypoxia-induced upregulation of placental glucose transport.
Use of Host Feeding Behavior and Gut Microbiome Data in Estimating Variance Components and Predicting Growth and Body Composition Traits in Swine
Authors: He Yuqing , Tiezzi Francesco , Jiang Jicai , Howard Jeremy T. , Huang Yijian , Gray Kent , Choi Jung-Woo , Maltecca Christian
Published: April 2022

The purpose of this study was to investigate the use of feeding behavior in conjunction with gut microbiome sampled at two growth stages in predicting growth and body composition traits of finishing pigs. Six hundred and fifty-one purebred boars of three breeds: Duroc (DR), Landrace (LR), and Large White (LW), were studied. Feeding activities were recorded individually from 99 to 163 days of age. The 16S rRNA gene sequences were obtained from each pig at 123 ± 4 and 158 ± 4 days of age. When pigs reached market weight, body weight (BW), ultrasound backfat thickness (BF), ultrasound loin depth (LD), and ultrasound intramuscular fat (IMF) content were measured on live animals. Three models including feeding behavior (Model_FB), gut microbiota (Model_M), or both (Model_FB_M) as predictors, were investigated. Prediction accuracies were evaluated through cross-validation across genetic backgrounds using the leave-one-breed-out strategy and across rearing environments using the leave-one-room-out approach. The proportions of phenotypic variance of growth and body composition traits explained by feeding behavior ranged from 0.02 to 0.30, and from 0.20 to 0.52 when using gut microbiota composition. Overall prediction accuracy (averaged over traits and time points) of phenotypes was 0.24 and 0.33 for Model_FB, 0.27 and 0.19 for Model_M, and 0.40 and 0.35 for Model_FB_M for the across-breed and across-room scenarios, respectively. This study shows how feeding behavior and gut microbiota composition provide non-redundant information in predicting growth in swine.
Implementing Early Phase Treatments for COVID-19 in Outpatient Settings: Challenges at a Tertiary Care Center in Italy and Future Outlooks
Authors: Manciulli Tommaso , Lagi Filippo , Barbiero Anna , Fognani Marco , Di Lauria Nicoletta , Malcontenti Costanza , Fiorelli Costanza , Spinicci Michele , Ceccherini Vega , D’Onofrio Paola , Angileri Manuela , Malentacchi Francesca , Cecchi Michele , Rossolini Gian Maria , Tomaiuolo Matteo , Zammarchi Lorenzo , Bartoloni Alessandro
Published: April 2022

We present a brief commentary illustrating the current COVID-19 outpatient treatment options in Italy. We also report our experience setting up a service dedicated to these patients in the wake of the rise in COVID-19 cases observed in January 2022. We also gathered data on the daily costs faced by our outpatient service, based at a tertiary care center located in Florence, Italy. We present them with some considerations on future outlooks on the use of outpatient treatment in COVID-19.
Correlation Analysis between Urban Elements and COVID-19 Transmission Using Social Media Data
Authors: Wang Ru , Liu Lingbo , Wu Hao , Peng Zhenghong
Published: April 2022

The outbreak of the COVID-19 has become a worldwide public health challenge for contemporary cities during the background of globalization and planetary urbanization. However, spatial factors affecting the transmission of the disease in urban spaces remain unclear. Based on geotagged COVID-19 cases from social media data in the early stage of the pandemic, this study explored the correlation between different infectious outcomes of COVID-19 transmission and various factors of the urban environment in the main urban area of Wuhan, utilizing the multiple regression model. The result shows that most spatial factors were strongly correlated to case aggregation areas of COVID-19 in terms of population density, human mobility and environmental quality, which provides urban planners and administrators valuable insights for building healthy and safe cities in an uncertain future.
Sleep Quality among Patients with Type 2 Diabetes: A Cross-Sectional Study in the East Coast Region of Peninsular Malaysia
Authors: Nasir Nor Fareshah Mohd , Draman Nani , Zulkifli Maryam Mohd , Muhamad Rosediani , Draman Samsul
Published: April 2022

Poor sleep is related to type 2 diabetes and adversely influences a person’s quality of life. This study aimed to evaluate sleep quality in patients with type 2 diabetes (T2DM), its associated factors, and its relationship with quality of life. A cross-sectional study was conducted at a primary care clinic in a tertiary hospital on the east coast of Malaysia. This study included 350 participants (175 men and 175 women). Data were collected using the Malay version of the Pittsburgh Sleep Quality Index (PSQI-M) with a cut-off point of >5 as poor sleep, the Malay version of Diabetes Distress Scale (MDDS-17) and the revised Malay version of T2DM-related quality of life (Rv-DQOL). Statistical analysis was conducted using the SPSS software version 26.0. The respondents’ median (interquartile range (IQR)) age was 62.0 (11.0) years, and poor sleep was reported in 32% (95% confidence interval (CI) = 27.1, 36.9) of the participants. Multivariate logistic regression analysis revealed that poor sleep quality was significantly associated with nocturia (odds ratio (OR) = 2.04; 95% CI = 1.24, 3.35), restless legs syndrome (OR = 2.17; 95% CI = 1.32–3.56) and emotional burden (OR = 2.37; 95% CI = 1.41–3.98). However, no statistically significant association was observed between sleep quality and quality of life among our participants.
Physical Activity Trends in Korean Adults from Korea National Health and Nutritional Examination Survey from 2014 to 2019
Authors: Sung Hoyong , Kim Geonhui , Ma Xiaonan , Choe Harim , Han Yunmin , Yoon Jiyeon , Ryu Yeun , Kim Yeon Soo
Published: April 2022

The current study aimed to examine the adherence trend for aerobic and muscle-strengthening physical activity (PA) guidelines among Korean adults using the Korea National Health and Nutritional Examination Survey from 2014 to 2019. Korean adults (N = 2642) were included in the current study to examine the trend of PA adherence from 2014 to 2019. The PA guidelines are: (a) aerobic activity (a minimum of 150 min moderate to vigorous PA weekly) and (b) muscle-strengthening activity (a minimum of two days weekly). Self-report questionnaires in the survey measured both activities. The adherence to PA guidelines by survey year was examined using a multivariable logistic regression analysis adjusted for covariates. There was a significant decreasing trend in which the adherence rate to aerobic PA guidelines changed from 57.0% in 2014 to 45.6% in 2019 (p < 0.001). On the other hand, the trend in adherence rate to muscle-strengthening activity was not significant (p = 0.976). The adherence rate to muscle-strengthening activity guideline was slightly increased but still low from 20.8% to 23.3% during 2014–2019. The aerobic PA guidelines are significantly decreasing, and more than half of the Korean adults in 2019 have not followed the guidelines. In addition, there has been a slight increase in muscle-strengthening activity; however, the adherence rate is meager. Therefore, this study suggests that Korean adults’ aerobic and muscle-strengthening PA participation is necessary for their low adherence rate and decline tendency.
Optimization of Ecological Water Replenishment Scheme Based on the Interval Fuzzy Two-Stage Stochastic Programming Method: Boluo Lake National Nature Reserve, Jilin Province, China
Authors: Yang Hao , He Wei , Li Yu
Published: April 2022

In this paper, a fuzzy mathematical programming method is introduced on the basis of the interval two-stage stochastic programming (ITSP) optimisation model for the wetland ecological water replenishment scheme in Boluo Lake National Nature Reserve. The minimum ecological water supply is taken as the objective function, and the lake bubble water diversion capacity, lake bubble water supply capacity, water diversion sequence, ecological service value, and minimum capacity of the wetland water supply are taken as constraints. The ecological water replenishment schemes of five lakes in the Boluo Lake National Nature Reserve are optimised at the levels of low flow years, normal flow years, and high flow years, and an optimised model for the wetland ecological water replenishment scheme in Boluo Lake National Nature Reserve based on the interval fuzzy two-stage stochastic programming (IFTSP) method is constructed. The model fully considers the waste of water resources and the protection of migratory bird habitat and makes rational allocation of water resources to make full use of flood resources. The IFTSP model proposed herein fully considers the fuzzy and uncertain characteristics of the planning area in the lake bubble area of Boluo Lake National Nature Reserve and improves the decision-making efficiency of decision-makers by providing technical support for smooth implementation of the ecological water replenishment project in nature reserves. The model can also be used as a theoretical guide for ecological recharge projects in other regions of the world.
Effects of Pyrolysis Temperature and Chemical Modification on the Adsorption of Cd and As(V) by Biochar Derived from Pteris vittata
Authors: Sugawara Kazuki , Ichio Kouhei , Ichikawa Yumiko , Ogawa Hitoshi , Suzuki Seiichi
Published: April 2022

Phytoremediation can be applied successfully to solve the serious worldwide issue of arsenic (As) and cadmium (Cd) pollution. However, the treatment of biomass containing toxic elements after remediation is a challenge. In this study, we investigated the effective use of biomass resources by converting the As hyperaccumulator P. vittata into biochar to adsorb toxic elements. Plant biomass containing As was calcined at 600, 800, and 1200 °C, and its surface structure and adsorption performances for As(V) and Cd were evaluated. Pyrolysis at 1200 °C increased the specific surface area of the biochar, but it did not significantly affect its adsorption capacity for toxic elements. The calcined biochar had very high adsorption capacities of 90% and 95% for As(V) and Cd, respectively, adsorbing 6000 mmol/g-biochar for As(V) and 4000 mmol/g-biochar for Cd. The As(V) adsorption rate was improved by FeCl3 treatment. However, the adsorption capacity for Cd was not significantly affected by the NaOH treatment. In conclusion, it was found that after phytoremediation using P. vittata biomass, it can be effectively used as an environmental purification material by conversion to biochar. Furthermore, chemical modification with FeCl3 improves the biochar’s adsorption performance.
The Effects of Workplace Loneliness on the Psychological Detachment and Emotional Exhaustion of Hotel Employees
Authors: Jung Yoon-Sik , Jung Hyo-Sun , Yoon Hye-Hyun
Published: April 2022

This study was aimed at establishing whether loneliness among hotel employees in the workplace affects their psychological and emotional experiences by empirically investigating their perceptions of negative situations. A self-administered questionnaire was distributed to 300 hotel employees, after which confirmatory factor analysis was conducted to reassess the reliability and validity of the measured questionnaire items. A model of workplace loneliness, psychological detachment, and emotional exhaustion was developed and examined through structural equation modeling. The results showed that the hotel employees experienced workplace loneliness and expressed a desire to be psychologically detached from their jobs for recovery. Workplace loneliness also contributed to emotional exhaustion. Theoretical and practical implications, as well as limitations and future research directions, are discussed.
ARMAX Forecast Model for Estimating the Annual radon Activity Concentration in Confined Environment by Short Measurements Performed by Active Detectors
Authors: Pepperosa Andrea , Remetti Romolo , Perondi Francesca
Published: April 2022

This work aims to implement a forecast model that, combined with the use of active instrumentation for a rather limited time, and with the knowledge of a set of data referring to the environmental parameters of the place to be monitored, can estimate the concentration of indoor radon activity for longer time periods. This model has been built through the MATLAB program, exploiting the theories of time series and, in particular, ARMAX models, to reproduce the variation in the concentration of radon activity. The model validation has been carried out by comparing real vs. simulated values. In addition, analytic treatment of input data, such as temperature, pressure, and relative humidity, can reduce the influence of sudden transients allowing for better stability of the model. The final goal is to estimate the annual radon activity concentration on the basis of spot measurements carried out by active instrumentation, such to avoid the need to measure for an entire calendar year by the use of passive detectors. The first experimental results obtained in conjunction with active radon measurement demonstrates the applicability of the method not only for forecasting future average concentrations, but also for optimizing remedial actions.
Effects of a Self-Directed Clinical Practicum on Self-Confidence and Satisfaction with Clinical Practicum among South Korean Nursing Students: A Mixed-Methods Study
Authors: Park Hyangjin , Cho Haeryun
Published: April 2022

In self-directed learning, students take the initiative to identify learning goals, choose learning strategies, and evaluate learning outcomes. This study aimed to explore the effects of a self-directed clinical practicum on nursing students’ self-confidence and satisfaction with the clinical practicum. This mixed-methods study used a non-equivalent control group with a pre- and post-test quasi-experimental design and content analysis. Participants were 111 nursing students (experimental group = 55, control group = 56). Quantitative (self-confidence and satisfaction with the clinical practicum) and qualitative (reflective diaries) data were collected. The experimental group had significantly increased scores for self-confidence and satisfaction with the clinical practicum compared with the control group. Four themes regarding the experience of the self-directed clinical practicum were identified: perceived linking of academic knowledge and practice, perceived development of nursing competency, enjoying the clinical practicum, and establishing nursing identity as a student. The self-directed clinical practicum developed as part of this study was found to be an effective education method for nursing students.
Recreational Nitrous Oxide Use and Associated Factors among Health Profession Students in France
Authors: Inquimbert Camille , Maitre Yoann , Moulis Estelle , Gremillet Vincent , Tramini Paul , Valcarcel Jean , Carayon Delphine
Published: April 2022

The first aim of this study was to investigate the recreational use of nitrous oxide (N2O) among health profession students at Montpellier University (France). The second aim was to identify the factors associated with N2O use. All students in medicine, dentistry, pharmacy and midwifery of the Montpellier University were contacted by email to participate in the survey. The students answered directly online by filling out anonymously a questionnaire including demographic information and questions about N2O, illicit drugs and alcohol use. Ethical approval was granted by the ethics committee of the Montpellier University. The sample comprised 593 students (mean age = 22.3 ± 2.6 yr), with 68.6% of females. Lifetime N2O use was reported by 76.6% and frequent alcohol use by 30.5% of the respondents. The lifetime use of cannabis, ‘poppers’, cocaine, ecstasy and LSD was 26.8%, 54.6%, 9.6%, 10.1% and 2.0% respectively. In multivariate analysis, the substances significantly associated with lifetime N2O were alcohol drinking and ‘poppers’ use. With respect to this self-nominated sample, our results indicate that respondents who were alcohol drinkers, were poppers users, follow longer studies, divert medical products for recreational use or were members of a students’ corporation had higher odds of lifetime N2O use.