bluuebunny/crossref_metadata_2025 huggingface dataset:
Learned Experience and Resource Dilution: Conceptualizing Sibling Influences on Parents’ Feeding Practices
Authors: Ruggiero Cara F. , McHale Susan M. , Paul Ian M. , Savage Jennifer S.
Published: May 2021

Studies from diverse cultures report mixed results in the relationship between birth order and risk for obesity. Explanations may thus lie in the postnatal period when growth is shaped by the family environment, including parental feeding practices, which may be affected by siblings. Consistent with a family systems perspective, we describe two processes that may explain birth order effects on parental feeding practices and child outcomes: learned experience and resource dilution. Parents learn from experience when earlier-born children influence their parents’ knowledge, expectations, and behavior toward later-born siblings through their behaviors and characteristics—which can have both positive and negative implications. Resource dilution is a process whereby the birth of each child limits the time, attention and other resources parents have to devote to any one of their children. The goal of this review is to provide a theoretical basis for examining potential sibling influences on parental responsive feeding toward developing recommendations for future research and practice aimed at preventing obesity throughout family systems.
Interactions among Reward Sensitivity and Fast-Food Access on Healthy Eating Index Scores in Adolescents: A Cross-Sectional Study
Authors: Wang Shirlene D. , Nicolo Michele , Yi Li , Dunton Genevieve F. , Mason Tyler B.
Published: May 2021

Food cues in the environment may contribute to obesity as the consumption of unhealthy foods may reinforce reward pathways in the brain. To understand how person-level differences in reward sensitivity may be associated with diet quality, this study aimed to examine the moderating role of the availability of fast food in the environment on the relationship between reward sensitivity and diet quality in adolescents. Participants (n = 152; 55% female; Mage: 12.5 ± 0.93 y) completed the drive and reward subscales of the Behavioral Inhibition System (BIS)/Behavioral Activation System (BAS) Scale to assess reward sensitivity and completed two 24 h dietary recalls from which Healthy Eating Index (HEI) scores (total score and subscales of adequacy and moderation) were calculated. Fast-food environment (FFE) was operationalized as the total number of fast-food outlets within 1 km around participants’ home address. Linear regressions were used to examine the main effects and interactions between reward sensitivity and FFE in relation to HEI score. Interactions were found between FFE and BAS drive (p = 0.02) and BAS reward (p < 0.01) on HEI adequacy. There were no interaction effects on HEI moderation or HEI total scores. For individuals who had lower access exposure to fast-food outlets (−1 SD), there was a stronger positive association between higher BAS drive (t = 2.85, p = 0.01, 95% CI (0.35, 1.94)) and HEI adequacy scores and between higher BAS reward (t = 3.27, p > 0.01, 95% CI (0.72, 2.93)) and HEI adequacy scores. By examining reward sensitivity to potential food cues in residential neighborhood food environments, it is possible to understand which adolescents are more sensitive to environmental food cues and implement interventions to buffer these influences.
MAROCOVID: Snapshot Monitoring of Knowledge and Perceptions of Safety Behaviors during the COVID-19 Outbreak in Morocco
Authors: Berni Imane , Menouni Aziza , Zegzouti Younes Filali , Kestemont Marie-Paule , Godderis Lode , El Jaafari Samir
Published: May 2021

To assess whether knowledge, attitude, and perceptions of the COVID-19 pandemic predicted changes in behaviors among the general Moroccan population, a cross-sectional online survey was conducted between 30 March and 20 April involving a total of 14,157 participants. The statistical analysis of the data included univariate and multivariate logistic regression analysis. Our results suggest that less than ten days after the Moroccan government announced “Health state of Emergency” response to the COVID-19 outbreak, public knowledge, attitude and responses to the pandemic were relatively high. More than half the respondents (63.2%) reported that they complied with more than five of nine recommended safety measures, including avoiding going out (93.2%), and frequent handwashing with soap and water (78.2%). Factors associated with an increased likelihood to adopt safety measures included perceptions that COVID-19 was a human health risk, the pandemic will continue for a long time, availability of clear information, and a lack of medicine. The largest predictor of safety behavior change was age; participants older than 55 were more likely to adopt recommended safety behaviors. Although knowledge and perception among the general public was reasonable, more encouragement from government via health education programs is needed to maintain appropriate behaviors.
Environmental Efficiency Assessment of Heavy Pollution Industry by Data Envelopment Analysis and Malmquist Index Analysis: Empirical Evidence from China
Authors: Xu Jun , Jiang Yuchen , Guo Xin , Jiang Li
Published: May 2021

Industrial waste discharged by heavy pollution industry is one of the main causes of global environmental degradation. Research on the environmental efficiency of high-polluting industry is necessary to tackle the problem of global environmental pollution. Using panel data of 19 sub-industries in China’s heavy pollution industry from 2001 to 2015, this article employs Data Envelopment Analysis (DEA) and Malmquist index (MI) to measure the environmental efficiency of heavy pollution industry from both the dynamic and static perspectives. The results show that the environmental efficiency of China’s heavy pollution industry maintains an upward trend but did not reach the optimal level. The general trend shows a phased trend of increasing first and then decreasing. Besides, there are inter-industry differences in the environmental efficiency across the examined sub-industries. Based on the research findings, this article proposes a set of corresponding countermeasures to solve the global pollution problem, such as reducing energy inputs and minimizing the volumes of the main categories of emissions in high-polluting industry, as well as improving the production management in the group of high environmental efficiency and strengthening technical capabilities in the group of low environmental efficiency.
Perspectives on Complexity, Chaos and Thermodynamics in Environmental Pathology
Authors: Manera Maurizio
Published: May 2021

Though complexity science and chaos theory have become a common scientific divulgation theme, medical disciplines, and pathology in particular, still rely on a deterministic, reductionistic approach and still hesitate to fully appreciate the intrinsic complexity of living beings. Herein, complexity, chaos and thermodynamics are introduced with specific regard to biomedical sciences, then their interconnections and implications in environmental pathology are discussed, with particular regard to a morphopathological, image analysis-based approach to biological interfaces. Biomedical disciplines traditionally approach living organisms by dissecting them ideally down to the molecular level in order to gain information about possible molecule to molecule interactions, to derive their macroscopic behaviour. Given the complex and chaotic behaviour of living systems, this approach is extremely limited in terms of obtainable information and may lead to misinterpretation. Environmental pathology, as a multidisciplinary discipline, should grant privilege to an integrated, possibly systemic approach, prone to manage the complex and chaotic aspects characterizing living organisms. Ultimately, environmental pathology should be interested in improving the well-being of individuals and the population, and ideally the health of the entire ecosystem/biosphere and should not focus merely on single diseases, diseased organs/tissues, cells and/or molecules.
Diet and Economic Modelling to Improve the Quality and Affordability of the Australian Diet for Low and Medium Socioeconomic Households
Authors: Blumfield Michelle , Starck Carlene , Keighley Tim , Petocz Peter , Roesler Anna , Abbott Kylie , Cassettari Tim , Marshall Skye , Fayet-Moore Flavia
Published: May 2021

Food costs are a barrier to healthier diet selections, particularly for low socioeconomic households who regularly choose processed foods containing refined grains, added sugars, and added fats. In this study, the objectives were to: (i) identify the nutrient density-to-cost ratio of Australian foods; (ii) model the impact of substituting foods with lower nutrient density-to-cost ratio with those with the highest nutrient density-to-cost ratio for diet quality and affordability in low and medium socioeconomic households; and (iii) evaluate food processing levels. Foods were categorized, coded for processing level, analysed for nutrient density and cost, and ranked by nutrient density-to-cost ratio. The top quartile of nutrient dense, low-cost foods included 54% unprocessed (vegetables and reduced fat dairy), 33% ultra-processed (fortified wholegrain bread and breakfast cereals <20 g sugars/100 g), and 13% processed (fruit juice and canned legumes). Using substitution modelling, diet quality improved by 52% for adults and 71% for children across all households, while diet affordability improved by 25% and 27% for low and medium socioeconomic households, respectively. The results indicate that the quality and affordability of the Australian diet can be improved when nutritious, low-cost foods are selected. Processing levels in the healthier modelled diets suggest that some ultra-processed foods may provide a beneficial source of nutrition when consumed within national food group recommendations.
Accounting Comparability and Cash Holdings in Vietnam
Authors: Nguyen Liem Thanh , Nguyen Khuong Vinh
Published: May 2021

The management of cash requires careful considerations to allow firms to benefit from proper resource allocations while mitigating agency issues. Accounting comparability can play an important role in tackling information asymmetry and agency cost, thus enabling managers to hoard more cash. This research aims to investigate the link between accounting comparability and cash holdings in an emerging market. Using a sample of listed firms in Vietnam from 2010 to 2019 and System Generalized Method of Moments, the study finds that comparability is positively associated with corporate cash holdings, confirming the value of the former as an effective governance mechanism. Additionally, we find a non-linear impact of comparability on cash holdings; in other words, comparability specifically enhances cash holdings for firms with high levels of comparability. We further document that cash holdings improve firm performance only for firms with high levels of comparability. Such evidence implies that only firms with high levels of financial statement comparability show commitment to tackle agency cost and information asymmetry.
A Common Approach to Geo-Referencing Building Models in Industry Foundation Classes for BIM/GIS Integration
Authors: Zhu Junxiang , Wu Peng
Published: May 2021

Previous geo-referencing approaches for building information modeling (BIM) models can be problematic due to: (a) the different interpretations of the term ‘geo-referencing’, (b) the insufficient consideration of the placement hierarchy of the industry foundation classes (IFCs), and (c) the misunderstanding that a common way to embed spatial reference information for IFC is absent. Therefore, the objective of this study is to (1) clarify the meaning of geo-referencing in the context of BIM/GIS data integration, and (2) develop a common geo-referencing approach for IFC. To achieve the goal, a systematic and thorough investigation into the IFC standard was conducted to assess the geo-referencing capability of IFC. Based on the investigation, a geo-referencing approach was established using IFC entities that are common in different IFC versions, which makes the proposed approach common to IFC. Such a geo-referencing approach supports automatic geo-referencing that would facilitate the use of BIM models in GIS, e.g., for the construction of digital twins.
Nicotinamide N-Methyltransferase in Acquisition of Stem Cell Properties and Therapy Resistance in Cancer
Authors: Novak Kujundžić Renata , Prpić Marin , Đaković Nikola , Dabelić Nina , Tomljanović Marko , Mojzeš Anamarija , Fröbe Ana , Trošelj Koraljka Gall
Published: May 2021

The activity of nicotinamide N-methyltransferase (NNMT) is tightly linked to the maintenance of the nicotinamide adenine dinucleotide (NAD+) level. This enzyme catalyzes methylation of nicotinamide (NAM) into methyl nicotinamide (MNAM), which is either excreted or further metabolized to N1-methyl-2-pyridone-5-carboxamide (2-PY) and H2O2. Enzymatic activity of NNMT is important for the prevention of NAM-mediated inhibition of NAD+-consuming enzymes poly–adenosine -diphosphate (ADP), ribose polymerases (PARPs), and sirtuins (SIRTs). Inappropriately high expression and activity of NNMT, commonly present in various types of cancer, has the potential to disrupt NAD+ homeostasis and cellular methylation potential. Largely overlooked, in the context of cancer, is the inhibitory effect of 2-PY on PARP-1 activity, which abrogates NNMT’s positive effect on cellular NAD+ flux by stalling liberation of NAM and reducing NAD+ synthesis in the salvage pathway. This review describes, and discusses, the mechanisms by which NNMT promotes NAD+ depletion and epigenetic reprogramming, leading to the development of metabolic plasticity, evasion of a major tumor suppressive process of cellular senescence, and acquisition of stem cell properties. All these phenomena are related to therapy resistance and worse clinical outcomes.
S1P Lyase Regulates Intestinal Stem Cell Quiescence via Ki-67 and FOXO3
Authors: Schwiebs Anja , Faqar-Uz-Zaman Farha , Herrero San Juan Martina , Radeke Heinfried H.
Published: May 2021

Background: Reduction of the Sphingosine-1-phosphate (S1P) degrading enzyme S1P lyase 1 (SGPL1) initiates colorectal cancer progression with parallel loss of colon function in mice. We aimed to investigate the effect of SGPL1 knockout on the stem cell niche in these mice. Methods: We performed immunohistochemical and multi-fluorescence imaging on tissue sections of wildtype and SGPL1 knockout colons under disease conditions. Furthermore, we generated SGPL1 knockout DLD-1 cells (SGPL1−/−M.Ex1) using CRISPR/Cas9 and characterized cell cycle and AKT signaling pathway via Western blot, immunofluorescence, and FACS analysis. Results: SGPL1 knockout mice were absent of anti-Ki-67 staining in the stem cell niche under disease conditions. This was accompanied by an increase of the negative cell cycle regulator FOXO3 and attenuation of CDK2 activity. SGPL1−/−M.Ex1 cells show a similar FOXO3 increase but no arrest of proliferation, although we found a suppression of the PDK1/AKT signaling pathway, a prolonged G1-phase, and reduced stem cell markers. Conclusions: While already established colon cancer cells find escape mechanisms from cell cycle arrest, in vivo SGPL1 knockout in the colon stem cell niche during progression of colorectal cancer can contribute to cell cycle quiescence. Thus, we propose a new function of the S1P lyase 1 in stemness.
Infection-Associated Mechanisms of Neuro-Inflammation and Neuro-Immune Crosstalk in Chronic Respiratory Diseases
Authors: Camp Belinda , Stegemann-Koniszewski Sabine , Schreiber Jens
Published: May 2021

Chronic obstructive airway diseases are characterized by airflow obstruction and airflow limitation as well as chronic airway inflammation. Especially bronchial asthma and chronic obstructive pulmonary disease (COPD) cause considerable morbidity and mortality worldwide, can be difficult to treat, and ultimately lack cures. While there are substantial knowledge gaps with respect to disease pathophysiology, our awareness of the role of neurological and neuro-immunological processes in the development of symptoms, the progression, and the outcome of these chronic obstructive respiratory diseases, is growing. Likewise, the role of pathogenic and colonizing microorganisms of the respiratory tract in the development and manifestation of asthma and COPD is increasingly appreciated. However, their role remains poorly understood with respect to the underlying mechanisms. Common bacteria and viruses causing respiratory infections and exacerbations of chronic obstructive respiratory diseases have also been implicated to affect the local neuro-immune crosstalk. In this review, we provide an overview of previously described neuro-immune interactions in asthma, COPD, and respiratory infections that support the hypothesis of a neuro-immunological component in the interplay between chronic obstructive respiratory diseases, respiratory infections, and respiratory microbial colonization.
Cancer Cell Metabolism in Hypoxia: Role of HIF-1 as Key Regulator and Therapeutic Target
Authors: Infantino Vittoria , Santarsiero Anna , Convertini Paolo , Todisco Simona , Iacobazzi Vito
Published: May 2021

In order to meet the high energy demand, a metabolic reprogramming occurs in cancer cells. Its role is crucial in promoting tumor survival. Among the substrates in demand, oxygen is fundamental for bioenergetics. Nevertheless, tumor microenvironment is frequently characterized by low-oxygen conditions. Hypoxia-inducible factor 1 (HIF-1) is a pivotal modulator of the metabolic reprogramming which takes place in hypoxic cancer cells. In the hub of cellular bioenergetics, mitochondria are key players in regulating cellular energy. Therefore, a close crosstalk between mitochondria and HIF-1 underlies the metabolic and functional changes of cancer cells. Noteworthy, HIF-1 represents a promising target for novel cancer therapeutics. In this review, we summarize the molecular mechanisms underlying the interplay between HIF-1 and energetic metabolism, with a focus on mitochondria, of hypoxic cancer cells.
Protein Sumoylation Is Crucial for Phagocytosis in Entamoeba histolytica Trophozoites
Authors: Díaz-Hernández Mitzi , Javier-Reyna Rosario , Sotto-Ortega Izaid , García-Rivera Guillermina , Montaño Sarita , Betanzos Abigail , Zanatta Dxinegueela , Orozco Esther
Published: May 2021

Posttranslational modifications provide Entamoeba histolytica proteins the timing and signaling to intervene during different processes, such as phagocytosis. However, SUMOylation has not been studied in E. histolytica yet. Here, we characterized the E. histolytica SUMO gene, its product (EhSUMO), and the relevance of SUMOylation in phagocytosis. Our results indicated that EhSUMO has an extended N-terminus that differentiates SUMO from ubiquitin. It also presents the GG residues at the C-terminus and the ΨKXE/D binding motif, both involved in target protein contact. Additionally, the E. histolytica genome possesses the enzymes belonging to the SUMOylation-deSUMOylation machinery. Confocal microscopy assays disclosed a remarkable EhSUMO membrane activity with convoluted and changing structures in trophozoites during erythrophagocytosis. SUMOylated proteins appeared in pseudopodia, phagocytic channels, and around the adhered and ingested erythrocytes. Docking analysis predicted interaction of EhSUMO with EhADH (an ALIX family protein), and immunoprecipitation and immunofluorescence assays revealed that the association increased during phagocytosis; whereas the EhVps32 (a protein of the ESCRT-III complex)-EhSUMO interaction appeared stronger since basal conditions. In EhSUMO knocked-down trophozoites, the bizarre membranous structures disappeared, and EhSUMO interaction with EhADH and EhVps32 diminished. Our results evidenced the presence of a SUMO gene in E. histolytica and the SUMOylation relevance during phagocytosis. This is supported by bioinformatics screening of many other proteins of E. histolytica involved in phagocytosis, which present putative SUMOylation sites and the ΨKXE/D binding motif.
Biochemistry of Terpenes and Recent Advances in Plant Protection
Authors: Ninkuu Vincent , Zhang Lin , Yan Jianpei , Fu Zhenchao , Yang Tengfeng , Zeng Hongmei
Published: May 2021

Biodiversity is adversely affected by the growing levels of synthetic chemicals released into the environment due to agricultural activities. This has been the driving force for embracing sustainable agriculture. Plant secondary metabolites offer promising alternatives for protecting plants against microbes, feeding herbivores, and weeds. Terpenes are the largest among PSMs and have been extensively studied for their potential as antimicrobial, insecticidal, and weed control agents. They also attract natural enemies of pests and beneficial insects, such as pollinators and dispersers. However, most of these research findings are shelved and fail to pass beyond the laboratory and greenhouse stages. This review provides an overview of terpenes, types, biosynthesis, and their roles in protecting plants against microbial pathogens, insect pests, and weeds to rekindle the debate on using terpenes for the development of environmentally friendly biopesticides and herbicides.
Clinical Significance of Tumor Infiltrating Lymphocytes in Association with Hormone Receptor Expression Patterns in Epithelial Ovarian Cancer
Authors: Han Gwan Hee , Hwang Ilseon , Cho Hanbyoul , Ylaya Kris , Choi Jung-A , Kwon Hyunja , Chung Joon-Yong , Hewitt Stephen M. , Kim Jae-Hoon
Published: May 2021

Hormone receptor expression patterns often correlate with infiltration of specific lymphocytes in tumors. Specifically, the presence of specific tumor-infiltrating lymphocytes (TILs) with particular hormone receptor expression is reportedly associated with breast cancer, however, this has not been revealed in epithelial ovarian cancer (EOC). Therefore, we investigated the association between hormone receptor expression and TILs in EOC. Here we found that ERα, AR, and GR expression increased in EOC, while PR was significantly reduced and ERβ expression showed a reduced trend compared to normal epithelium. Cluster analysis indicated poor disease-free survival (DFS) in AR+/GR+/PR+ subgroup (triple dominant group); while the Cox proportional-hazards model highlighted the triple dominant group as an independent prognostic factor for DFS. In addition, significant upregulation of FoxP3+ TILs, PD-1, and PD-L1 was observed in the triple dominant group compared to other groups. NanoString analyses further suggested that tumor necrosis factor (TNF) and/or NF-κB signaling pathways were activated with significant upregulation of RELA, MAP3K5, TNFAIP3, BCL2L1, RIPK1, TRAF2, PARP1, and AKT1 in the triple dominant EOC group. The triple dominant subgroup correlates with poor prognosis in EOC. Moreover, the TNF and/or NF-κB signaling pathways may be responsible for hormone-mediated inhibition of the immune microenvironment.
O-GlcNAcylation Affects the Pathway Choice of DNA Double-Strand Break Repair
Authors: Averbek Sera , Jakob Burkhard , Durante Marco , Averbeck Nicole B.
Published: May 2021

Exposing cells to DNA damaging agents, such as ionizing radiation (IR) or cytotoxic chemicals, can cause DNA double-strand breaks (DSBs), which are crucial to repair to maintain genetic integrity. O-linked β-N-acetylglucosaminylation (O-GlcNAcylation) is a post-translational modification (PTM), which has been reported to be involved in the DNA damage response (DDR) and chromatin remodeling. Here, we investigated the impact of O-GlcNAcylation on the DDR, DSB repair and chromatin status in more detail. We also applied charged particle irradiation to analyze differences of O-GlcNAcylation and its impact on DSB repair in respect of spatial dose deposition and radiation quality. Various techniques were used, such as the γH2AX foci assay, live cell microscopy and Fluorescence Lifetime Microscopy (FLIM) to detect DSB rejoining, protein accumulation and chromatin states after treating the cells with O-GlcNAc transferase (OGT) or O-GlcNAcase (OGA) inhibitors. We confirmed that O-GlcNAcylation of MDC1 is increased upon irradiation and identified additional repair factors related to Homologous Recombination (HR), CtIP and BRCA1, which were increasingly O-GlcNAcyated upon irradiation. This is consistent with our findings that the function of HR is affected by OGT inhibition. Besides, we found that OGT and OGA activity modulate chromatin compaction states, providing a potential additional level of DNA-repair regulation.
Diabetes Affects the Pituitary Adenylate Cyclase-Activating Polypeptide (PACAP)-Like Immunoreactive Enteric Neurons in the Porcine Digestive Tract
Authors: Palus Katarzyna , Bulc Michał , Całka Jarosław , Zielonka Łukasz , Nowicki Marcin
Published: May 2021

Diabetic gastroenteropathy is a common complication, which develops in patients with long-term diabetes. The pituitary adenylate cyclase-activating polypeptide (PACAP) is a neuropeptide known for its cytoprotective properties and plays an important role in neuronal development, neuromodulation and neuroprotection. The present study was designed to elucidate, for the first time, the impact of prolonged hyperglycaemia conditions on a population of PACAP-like immunoreactive neurons in selected parts of the porcine gastrointestinal tract. The experiment was conducted on 10 juvenile female pigs assigned to two experimental groups: The DM group (pigs with streptozocin-induced diabetes) and the C group (control pigs). Diabetes conditions were induced by a single intravenous injection of streptozocin. Six weeks after the induction of diabetes, all animals were euthanised and further collected, and fixed fragments of the stomach, duodenum, jejunum, ileum and descending colon were processed using the routine double-labelling immunofluorescence technique. Streptozotocin-induced hyperglycaemia caused a significant increase in the population of PACAP-containing enteric neurons in the porcine stomach, small intestines and descending colon. The recorded changes may result from the direct toxic effect of hyperglycaemia on the ENS neurons, oxidative stress or inflammatory conditions accompanying hyperglycaemia and suggest that PACAP is involved in regulatory processes of the GIT function in the course of diabetes.
Immunological Aspects of Skin Aging in Atopic Dermatitis
Authors: Bocheva Georgeta St. , Slominski Radomir M. , Slominski Andrzej T.
Published: May 2021

The cutaneous immune response is important for the regulation of skin aging well as for the development of immune-mediated skin diseases. Aging of the human skin undergoes immunosenescence with immunological alterations and can be affected by environmental stressors and internal factors, thus leading to various epidermal barrier abnormalities. The dysfunctional epidermal barrier, immune dysregulation, and skin dysbiosis in the advanced age, together with the genetic factors, facilitate the late onset of atopic dermatitis (AD) in the elderly, whose cases have recently been on the rise. Controversial to the healthy aged skin, where overproduction of many cytokines is found, the levels of Th2/Th22 related cytokines inversely correlated with age in the skin of older AD patients. As opposed to an endogenously aged skin, the expression of the terminal differentiation markers significantly increases with age in AD. Despite the atenuated barrier disturbances in older AD patients, the aged skin carries an impairment associated with the aging process, which reflects the persistence of AD. The chronicity of AD in older patients might not directly affect skin aging but does not allow spontaneous remission. Thus, adult- and elderly subtypes of AD are considered as a lifelong disease.
Pigmentation Levels Affect Melanoma Responses to Coriolus versicolor Extract and Play a Crucial Role in Melanoma-Mononuclear Cell Crosstalk
Authors: Pawlikowska Małgorzata , Jędrzejewski Tomasz , Slominski Andrzej T. , Brożyna Anna A. , Wrotek Sylwia
Published: May 2021

Melanoma, the malignancy originating from pigment-producing melanocytes, is the most aggressive form of skin cancer and has a poor prognosis once the disease starts to metastasize. The process of melanin synthesis generates an immunosuppressive and mutagenic environment, and can increase melanoma cell resistance to different treatment modalities, including chemo-, radio- or photodynamic therapy. Recently, we have shown that the presence of melanin pigment inhibits the melanoma cell response to bioactive components of Coriolus versicolor (CV) Chinese fungus. Herein, using the same human melanoma cell line in which the level of pigmentation can be controlled by the L-tyrosine concentration in culture medium, we tested the effect of suppression of melanogenesis on the melanoma cell response to CV extract and investigated the cell death pathway induced by fungus extract in sensitized melanoma cells. Our data showed that susceptibility to CV-induced melanoma cell death is significantly increased after cell depigmentation. To the best of our knowledge, we are the first to demonstrate that CV extract can induce RIPK1/RIPK3/MLKL-mediated necroptosis in depigmented melanoma cells. Moreover, using the co-culture system, we showed that inhibition of the tyrosinase activity in melanoma cells modulates cytokine expression in co-cultured mononuclear cells, indicating that depigmentation of melanoma cells may activate immune cells and thereby influence a host anticancer response.
Characterization of the GHB Withdrawal Syndrome
Authors: Wolf Casper J. H. , Beurmanjer Harmen , Dijkstra Boukje A. G. , Geerlings Alexander C. , Spoelder Marcia , Homberg Judith R. , Schellekens Arnt F. A.
Published: May 2021

The gamma-hydroxybutyric acid (GHB) withdrawal syndrome can have a fulminant course, complicated by severe complications such as delirium or seizures. Detoxification by tapering with pharmaceutical GHB is a safe way to manage GHB withdrawal. However, a detailed description of the course of the GHB withdrawal syndrome is currently lacking. This study aimed to (1) describe the course of GHB withdrawal symptoms over time, (2) assess the association between vital signs and withdrawal symptoms, and (3) explore sex differences in GHB withdrawal. In this observational multicenter study, patients with GHB use disorder (n = 285) were tapered off with pharmaceutical GHB. The most reported subjective withdrawal symptoms (SWS) were related to cravings, fatigue, insomnia, sweating and feeling gloomy. The most prevalent objective withdrawal symptoms (OWS) were related to cravings, fatigue, tremors, sweating, and sudden cold/warm feelings. No association between vital signs and SWS/OWS was found. Sex differences were observed in the severity and prevalence of specific withdrawal symptoms. Our results suggest that the GHB withdrawal syndrome under pharmaceutical GHB tapering does not strongly differ from withdrawal syndromes of other sedative drugs. The lack of association between vital signs and other withdrawal symptoms, and the relative stability of vitals over time suggest that vitals are not suitable for withdrawal monitoring. The reported sex differences highlight the importance of a personalized approach in GHB detoxification.
Breast Cancer Cell Re-Dissemination from Lung Metastases—A Mechanism for Enhancing Metastatic Burden
Authors: Borriello Lucia , Condeelis John , Entenberg David , Oktay Maja H.
Published: May 2021

Although metastatic disease is the primary cause of mortality in cancer patients, the mechanisms leading to overwhelming metastatic burden are still incompletely understood. Metastases are the endpoint of a series of multi-step events involving cancer cell intravasation, dissemination to distant organs, and outgrowth to metastatic colonies. Here we show, for the first-time, that breast cancer cells do not solely disseminate to distant organs from primary tumors and metastatic nodules in the lymph nodes, but also do so from lung metastases. Thus, our findings indicate that metastatic dissemination could continue even after the removal of the primary tumor. Provided that the re-disseminated cancer cells initiate growth upon arrival to distant sites, cancer cell re-dissemination from metastatic foci could be one of the crucial mechanisms leading to overt metastases and patient demise. Therefore, the development of new therapeutic strategies to block cancer cell re-dissemination would be crucial to improving survival of patients with metastatic disease.
Pressure Algometry Evaluation of Two Occlusal Splint Designs in Bruxism Management-Randomized, Controlled Clinical Trial
Authors: Dalewski Bartosz , Kamińska Agata , Kiczmer Paweł , Węgrzyn Krzysztof , Pałka Łukasz , Janda Katarzyna , Sobolewska Ewa
Published: May 2021

The aim of this pilot study was to evaluate the short-term effectiveness of two different occlusal devices and their impact on the pressure pain threshold (PPT) values among patients who reported to the Dental Prosthetics Outpatient Clinic of Pomeranian Medical University (Szczecin, Poland) and who were diagnosed with probable bruxism. Two groups were formed (A and B) to which patients were assigned randomly. Each group used a different occlusal splint for bruxism management. The occlusal appliance by Okeson, or the bimaxillary splint, was used overnight by each patient for 30 days of the study. The PPT was measured twice, at the first visit and after 30 days of using each occlusal device, with Wagner Paintest FPX 25 algometer. Bruxism was diagnosed based on data from the patient’s medical history and from the physical examination. Nocturnal Bruxism Criteria according to the International Classification of Sleep Disorders (Third Edition) was used for the patient’s evaluation. Results: similar pain factor (PF) reduction was observed in both the examined groups, regardless of the device used; canine guidance and no guidance were similarly effective in terms of increasing pain resilience.
Endoscopic Vacuum Therapy in Patients with Transmural Defects of the Upper Gastrointestinal Tract: A Systematic Review with Meta-Analysis
Authors: Jung Da Hyun , Yun Hae-Ryong , Lee Se Joon , Kim Na Won , Huh Cheal Wung
Published: May 2021

A transmural defect of the upper gastrointestinal (UGI) tract is a life-threatening condition associated with high morbidity and mortality. Recently, endoscopic vacuum therapy (EVT) was used for managing UGI defects and showed promising results. We conducted a systematic review and meta-analysis to synthesize evidence on the efficacy of EVT in patients with transmural defects of the UGI tract. We searched the PubMed, Cochrane Library, and Embase databases for publications on the effect of EVT on successful closure, mortality, complications, and post-EVT strictures. Methodological quality was assessed using the Newcastle–Ottawa quality assessment scale. This meta-analysis included 29 studies involving 498 participants. The pooled estimate rate of successful closure with EVT was 0.85 (95% confidence interval [CI]: 0.81–0.88). The pooled estimate rates for mortality, complications, and post-EVT strictures were 0.11, 0.10, and 0.14, respectively. According to the etiology of the transmural defect (perforation vs. leak and fistula), no significant difference was observed in successful closure (odds ratio [OR]: 1.45, 95% CI: 0.45–4.67, p = 0.53), mortality (OR: 0.77, 95% CI: 0.24–2.46, p = 0.66), complications (OR: 0.94, 95% CI: 0.17–5.15, p = 0.94), or post-EVT stricture rates (OR: 0.70, 95% CI: 0.12–4.24, p = 0.70). The successful closure rate was significantly higher with EVT than with self-expanding metal stent (SEMS) placement (OR: 3.14, 95% CI: 1.23–7.98, p = 0.02). EVT is an effective and safe treatment for leaks and fistulae, as well as for perforations in the UGI. Moreover, EVT seems to be a better treatment option than SEMS placement for UGI defects.
Outcomes Related to Percutaneous Nephrostomies (PCN) in Malignancy-Associated Ureteric Obstruction: A Systematic Review of the Literature
Authors: New Francesca J. , Deverill Sally J. , Somani Bhaskar K.
Published: May 2021

Background: Malignant ureteric obstruction occurs in a variety of cancers and has been typically associated with a poor prognosis. Percutaneous nephrostomy (PCN) can potentially help increase patient longevity by establishing urinary drainage and treating renal failure. Our aim was to look at the outcomes of PCN in patients with advanced cancer and the impact on the patients’ lifespan and quality of life. Materials and Methods: A literature review was carried out for articles from 2000 to 2020 on PCN in patients with advanced malignancies, using MEDLINE, EMBASE, Scopus, CINAHL, Cochrane Library, clinicaltrials.gov, and Google Scholar. All English-language articles reporting on a minimum of 20 patients who underwent PCN for malignancy-associated ureteric obstruction were included. Results: A total of 21 articles (1674 patients) met the inclusion criteria with a mean of 60.2 years (range: 21–102 years). PCN was performed for ureteric obstruction secondary to urological malignancies (n = −633, 37.8%), gynaecological malignancies (n = 437, 26.1%), colorectal and GI malignancies (n = 216, 12.9%), and other specified malignancies (n = 205, 12.2%). The reported mean survival times varied from 2 to 8.5 months post PCN insertion, with an average survival time of 5.6 months, which depended on the cancer type, stage, and previous treatment. Conclusions: Patients with advanced malignancies who need PCN tend to have a survival rate under 12 months and spend a large proportion of this time in the hospital. Although the advent of newer chemotherapy and immunotherapy options has changed the landscape of managing advanced cancer, decisions on nephrostomy must be balanced with their survival and quality of life, which must be discussed with the patient.
The Vacuolar Morphogenesis Protein Vam6-Like Protein Vlp1 Is Required for Pathogenicity of Cryptococcus neoformans
Authors: Fan Cheng-Li , Liu Tong-Bao
Published: May 2021

Cryptococcus neoformans is an encapsulated yeast pathogen that infects immunocompromised patients to cause fungal meningitis, resulting in hundreds of thousands of deaths each year. F-box protein Fbp1, the key component of the E3 ubiquitin ligase, plays a critical role in fungal development and virulence in fungal pathogens. In this study, we identified a potential substrate of Fbp1, the vacuolar morphogenesis protein Vam6-like protein Vlp1, and evaluated its role in virulence in C. neoformans. Deletion or overexpression of the VLP1 gene results in abnormal capsule formation and melanin production of C. neoformans. Stress tolerance assay showed that the vlp1Δ mutant was sensitive to SDS and NaCl but not to CFW or Congo red, indicating that Vlp1 might regulate the cell membrane integrity in C. neoformans. Fungal virulence assay showed that Vlp1 was essential for the pathogenicity of C. neoformans, as vlp1Δ mutants are avirulent in the mouse systematic infection model of cryptococcosis. The progression of fungal infection revealed that the vlp1Δ mutants were gradually eliminated from the lungs of the mice after infection. Moreover, the vlp1Δ mutants showed a proliferation defect inside macrophages and a viability defect in the host complement system, which likely contributes to the virulence attenuation of the vlp1Δ mutants. In summary, our results revealed that the vacuolar morphogenesis protein Vam6-like protein Vlp1 is essential for the pathogenicity of C. neoformans.
Molecular Epidemiology and Antifungal Susceptibility of Trichophyton Isolates in Greece: Emergence of Terbinafine-Resistant Trichophytonmentagrophytes Type VIII Locally and Globally
Authors: Siopi Maria , Efstathiou Ioanna , Theodoropoulos Konstantinos , Pournaras Spyros , Meletiadis Joseph
Published: May 2021

Trichophyton isolates with reduced susceptibility to antifungals are now increasingly reported worldwide. We therefore studied the molecular epidemiology and the in vitro antifungal susceptibility patterns of Greek Trichophyton isolates over the last 10 years with the newly released EUCAST reference method for dermatophytes. Literature was reviewed to assess the global burden of antifungal resistance in Trichophyton spp. The in vitro susceptibility of 112 Trichophyton spp. molecularly identified clinical isolates (70 T. rubrum, 24 T. mentagrophytes, 12 T. interdigitale and 6 T. tonsurans) was tested against terbinafine, itraconazole, voriconazole and amorolfine (EUCAST E.DEF 11.0). Isolates were genotyped based on the internal transcribed spacer (ITS) sequences and the target gene squalene epoxidase (SQLE) was sequenced for isolates with reduced susceptibility to terbinafine. All T. rubrum, T. interdigitale and T. tonsurans isolates were classified as wild-type (WT) to all antifungals, whereas 9/24 (37.5%) T. mentagrophytes strains displayed elevated terbinafine MICs (0.25–8 mg/L) but not to azoles and amorolfine. All T. interdigitale isolates belonged to ITS Type II, while T. mentagrophytes isolates belonged to ITS Type III* (n = 11), VIII (n = 9) and VII (n = 4). All non-WT T. mentagrophytes isolates belonged to Indian Genotype VIII and harbored Leu393Ser (n = 5) and Phe397Leu (n = 4) SQLE mutations. Terbinafine resistance rates ranged globally from 0–44% for T. rubrum and 0–76% for T. interdigitale/T. mentagrophytes with strong endemicity. High incidence (37.5%) of terbinafine non-WT T. mentagrophytes isolates (all belonging to ITS Type VIII) without cross-resistance to other antifungals was found for the first time in Greece. This finding must alarm for susceptibility testing of dermatophytes at a local scale particularly in non-responding dermatophytoses.
How to Improve the Management of Acute Ischemic Stroke by Modern Technologies, Artificial Intelligence, and New Treatment Methods
Authors: Zeleňák Kamil , Krajina Antonín , Meyer Lukas , Fiehler Jens ,   ESMINT Artificial Intelligence and Robotics Ad hoc Committee, Behme Daniel , Bulja Deniz , Caroff Jildaz , Chotai Amar Ajay , Da Ros Valerio , Gentric Jean-Christophe , Hofmeister Jeremy , Kass-Hout Omar , Kocatürk Özcan , Lynch Jeremy , Pearson Ernesto , Vukasinovic Ivan
Published: May 2021

Stroke remains one of the leading causes of death and disability in Europe. The European Stroke Action Plan (ESAP) defines four main targets for the years 2018 to 2030. The COVID-19 pandemic forced the use of innovative technologies and created pressure to improve internet networks. Moreover, 5G internet network will be helpful for the transfer and collecting of extremely big databases. Nowadays, the speed of internet connection is a limiting factor for robotic systems, which can be controlled and commanded potentially from various places in the world. Innovative technologies can be implemented for acute stroke patient management soon. Artificial intelligence (AI) and robotics are used increasingly often without the exception of medicine. Their implementation can be achieved in every level of stroke care. In this article, all steps of stroke health care processes are discussed in terms of how to improve them (including prehospital diagnosis, consultation, transfer of the patient, diagnosis, techniques of the treatment as well as rehabilitation and usage of AI). New ethical problems have also been discovered. Everything must be aligned to the concept of “time is brain”.
Graphene Infused Ecological Polymer Composites for Electromagnetic Interference Shielding and Heat Management Applications
Authors: Zeranska-Chudek Klaudia , Wróblewska Anna , Kowalczyk Sebastian , Plichta Andrzej , Zdrojek Mariusz
Published: May 2021

In the age of mobile electronics and increased aerospace interest, multifunctional materials such as the polymer composites reported here are interesting alternatives to conventional materials, offering reduced cost and size of an electrical device packaging. We report a detailed study of an ecological and dual-functional polymer composite for electromagnetic interference (EMI) shielding and heat management applications. We studied a series of polylactic acid/graphene nanoplatelet composites with six graphene nanoplatelet loadings, up to 15 wt%, and three different flake lateral sizes (0.2, 5 and 25 μm). The multifunctionality of the composites is realized via high EMI shielding efficiency exceeding 40 dB per 1 mm thick sample and thermal conductivity of 1.72 W/mK at 15 wt% nanofiller loading. The EMI shielding efficiency measurements were conducted in the microwave range between 0.2 to 12 GHz, consisting of the highly relevant X-band (8–12 GHz). Additionally, we investigate the influence of the nanofiller lateral size on the studied physical properties to optimize the studied functionalities per given nanofiller loading.
Experimental Study on the Behaviour of Seismic Actions on a Flexible Glass-Reinforced Plastic Structure Used in Water Transport Pipes
Authors: Ancaș Ana Diana , Așchilean Ioan , Profire Mihai , Țurcanu Florin Emilian , Felseghi Raluca-Andreea
Published: May 2021

This article presents the experimental results obtained by the testing an experimental model of water distribution which is flexible and above-head mounted on a seismic platform, and their validation in a theoretical manner, but also by the Finite Element Method, using the ANSYS simulation program. This type of system shown by the experimental model is desired to be used in practice not only in seismic areas, but also in the areas of heavy road transport, landslides, etc. thorugh the use thereof in the most stressed points of the network (hearth entry/exit, before/after an elbow, etc.) but also on long routes, at optimal distances. The results achieved are related to glass- reinforced plastic (GRP) pipes with a nominal diameter DN = 250 mm, but conclusions may be drawn starting from these to help future research where the mass of the earth is desired to be taken into account. The present results are comprehensive for buried pipes operated dynamically or seismically at low-medium intensity, as this type of earthquake occurs more and more often in Europe. The experimental tests in this article do not have the characteristics necessary for a high intensity seismic action (above 5° Richter).
Nonequilibrium Dynamics of a Magnetic Nanocapsule in a Nematic Liquid Crystal
Authors: Armendáriz José , Híjar Humberto
Published: May 2021

Colloidal particles in nematic liquid crystals show a beautiful variety of complex phenomena with promising applications. Their dynamical behaviour is determined by topology and interactions with the liquid crystal and external fields. Here, a nematic magnetic nanocapsule reoriented periodically by time-varying magnetic fields is studied using numerical simulations. The approach combines Molecular Dynamics to resolve solute–solvent interactions and Nematic Multiparticle Collision Dynamics to incorporate nematohydrodynamic fields and fluctuations. A Saturn ring defect resulting from homeotropic anchoring conditions surrounds the capsule and rotates together with it. Magnetically induced rotations of the capsule can produce transformations of this topological defect, which changes from a disclination curve to a defect structure extending over the surface of the capsule. Transformations occur for large magnetic fields. At moderate fields, elastic torques prevent changes of the topological defect by tilting the capsule out from the rotation plane of the magnetic field.
Fully Symmetric Relativistic Quantum Mechanics and Its Physical Implications
Authors: Tran Bao D. , Musielak Zdzislaw E.
Published: May 2021

A new formulation of relativistic quantum mechanics is presented and applied to a free, massive, and spin-zero elementary particle in the Minkowski spacetime. The reformulation requires that time and space, as well as the timelike and spacelike intervals, are treated equally, which makes the new theory fully symmetric and consistent with the special theory of relativity. The theory correctly reproduces the classical action of a relativistic particle in the path integral formalism, and allows for the introduction of a new quantity called vector-mass, whose physical implications for nonlocality, the uncertainty principle, and quantum vacuum are described and discussed.