bluuebunny/crossref_metadata_2025 huggingface dataset:
Interdecadal Distribution of Persistent Organic Pollutants in Deep-Sea Chemosynthetic Bivalves
Authors: Ikuta Tetsuro , Nakajima Ryota , Tsuchiya Masashi , Chiba Sanae , Fujikura Katsunori
Published: November 2021

Marine ecosystems are continuously subjected to anthropogenic environmental pollution. Understanding the spread of pollution and the potential risks it poses to deep-sea ecosystems is important for developing better conservation measures. Here, we identified non-negligible levels of persistent organic pollutants in deep-sea chemosynthetic bivalves with limited or no filter feeding. The bivalves were collected from two sites: one located near a highly populated region and the other located relatively far from human activity. Analyses of samples collected nearly every decade in a period of 30 years suggested that environmental policy restrictions might be effective in reducing chemical pollution. However, the detection of contamination in deep-sea chemosynthetic animals suggests that the pollution could be spreading globally to chemosynthetic organisms with limited or no feeding. To protect these highly endemic and vulnerable deep-sea chemosynthetic ecosystems, our findings indicate that further research on chemical contamination and its effects on these ecosystems is required.
An Integrated, Probabilistic Modeling Approach to Assess the Evolution of Barrier-Island Systems Over the Twenty-First Century
Authors: Bamunawala Janaka , van der Spek Ad , Dastgheib Ali , Murray A. Brad , Ranasinghe Roshanka
Published: November 2021

Barrier-island systems, spanning ∼7% of the world’s coastlines, are of great importance to society because not only they provide attractive, liveable space for coastal communities but also act as the first line of defense from coastal storms. As many of these unique coastal systems are affected by both oceanic and terrestrial processes, it is necessary to consider the holistic behavior of applicable terrestrial and coastal processes when investigating their evolution under plausible future scenarios for climate change, population growth and human activities. Such holistic assessments, also accounting for uncertainties, can readily be achieved via reduced-complexity modeling techniques, owing to their much faster simulation times compared to sophisticated process-based models. Here, we develop and demonstrate a novel probabilistic modeling framework to obtain stochastic projections of barrier-island evolution over the twenty-first century while accounting for relevant oceanic and terrestrial processes under climate change impacts and anthropogenic activities. The model is here demonstrated at the Chandeleur islands (Louisiana, United States) under the four Intergovernmental Panel on Climate Change (IPCC) greenhouse gas emission scenarios (i.e., Representative Concentration Pathways 2.6, 4.5, 6.0, and 8.5) with results indicating that there are significant uncertainties in projected end-century barrier-island migration distance and available barrier freeboard under the high emission scenario RCP 8.5. The range of uncertainties in these projections underscores the value of stochastic projections in supporting the development of effective adaptation strategies for these fragile coastal systems.
Biological Abundance and Diversity in Organic-Rich Sediments From a Florida Barrier Island Lagoon
Authors: Fuller Kate M. , Fox Austin L. , Jacoby Charles A. , Trefry John H.
Published: November 2021

Organic-rich sediments in estuaries and the coastal ocean are often a product of land clearing, runoff of excess nutrients and other human activities. They can harbor pollutants, oxygen-consuming microbes and toxic hydrogen sulfide (H2S), thereby creating a hostile environment for infauna. In one barrier island lagoon, the Indian River Lagoon (IRL), Florida, layers of organic-rich sediments have increased substantially in thickness and areal extent over the past 60 years. Geochemical properties of these muddy sediments have been described; however, less is known about their habitability. We analyzed infauna and geochemical properties of 102 samples taken during wet and dry seasons at 17 locations spanning 60 km of the lagoon. We quantified infaunal abundance and diversity (Shannon-Wiener, H′) and determined Pearson’s correlation coefficients for effective number of species (ENS = eH′) vs. sediment porosity (ϕ = 0.69–0.95), organic carbon (1–8%), nitrogen (0.1–0.7%), silt + clay (16–99%), porewater H2S (5–3,600 μM), and other environmental variables. Small bivalves accounted for 70% of the organisms collected, followed by gastropods, polychaetes and other biota. The bivalves were predominantly Macoma spp., Mulinia lateralis and Parastarte triquetra with average abundances of 3,896, 2,049, and 926 individuals per m2, respectively. High abundance of some species, such as Macoma, showed that these opportunists had adapted to poor quality sediments. More than two-thirds of the 35 species collected were present at <100 individuals per m2 of sediment. Cluster analysis identified four groups of stations with significantly different geochemical properties. Permutation analyses of variance indicated that the four groups also represented statistically different infaunal communities. Diversity decreased with increasing sediment concentrations of organic carbon, nitrogen and silt + clay; however, community richness at our most prolific station along the perimeter of muddy deposits was ∼7 times lower than found previously in sandy sediments from the IRL. The results identified areas where infaunal communities have experienced the greatest stress due to accumulation of organic-rich sediments. Results from this study help support management plans for remediation of organic-rich mud and improvement of sediment and water quality, especially in areas identified with low ENS.
Cell Therapy: Types, Regulation, and Clinical Benefits
Authors: El-Kadiry Abed El-Hakim , Rafei Moutih , Shammaa Riam
Published: November 2021

Cell therapy practices date back to the 19thcentury and continue to expand on investigational and investment grounds. Cell therapy includes stem cell- and non–stem cell-based, unicellular and multicellular therapies, with different immunophenotypic profiles, isolation techniques, mechanisms of action, and regulatory levels. Following the steps of their predecessor cell therapies that have become established or commercialized, investigational and premarket approval-exempt cell therapies continue to provide patients with promising therapeutic benefits in different disease areas. In this review article, we delineate the vast types of cell therapy, including stem cell-based and non–stem cell-based cell therapies, and create the first-in-literature compilation of the different “multicellular” therapies used in clinical settings. Besides providing the nuts and bolts of FDA policies regulating their use, we discuss the benefits of cell therapies reported in 3 therapeutic areas—regenerative medicine, immune diseases, and cancer. Finally, we contemplate the recent attention shift toward combined therapy approaches, highlighting the factors that render multicellular therapies a more attractive option than their unicellular counterparts.
Effects of Expression of Streptococcus pneumoniae PspC on the Ability of Streptococcus mitis to Evade Complement-Mediated Immunity
Authors: Marshall Helina , José Ricardo J. , Kilian Mogens , Petersen Fernanda C. , Brown Jeremy S.
Published: November 2021

Streptococcus pneumoniae and Streptococcus mitis are genetically closely related and both frequently colonise the naso-oropharynx, yet S. pneumoniae is a common cause of invasive infections whereas S. mitis is only weakly pathogenic. We hypothesise that sensitivity to innate immunity may underlie these differences in virulence phenotype. We compared the sensitivity of S. pneumoniae and S. mitis strains to complement-mediated immunity, demonstrating S. mitis strains were susceptible to complement-mediated opsonophagocytosis. S. pneumoniae resistance to complement is partially dependent on binding of the complement regulator Factor H by the surface protein PspC. However, S. mitis was unable to bind factor H. The S. pneumoniae TIGR4 strain pspC was expressed in the S. mitis SK142 strain to create a S. mitis pspC+ strain. Immunoblots demonstrated the S. mitis pspC+ strain expressed PspC, and flow cytometry confirmed this resulted in Factor H binding to S. mitis, reduced susceptibility to complement and improved survival in whole human blood compared to the wild-type S. mitis strain. However, in mouse models the S. mitis pspC+ strain remained unable to establish persistent infection. Unlike S. pneumoniae strains, culture in serum or blood did not support increased CFU of the S. mitis strains. These results suggest S. mitis is highly sensitive to opsonisation with complement partially due to an inability to bind Factor H, but even when complement sensitivity was reduced by expression of pspC, poor growth in physiological fluid limited the virulence of S. mitis in mice.
Molecular Surveillance of Carbapenem-Resistant Gram-Negative Bacteria in Liver Transplant Candidates
Authors: Schultze Tilman G. , Ferstl Philip G. , Villinger David , Hogardt Michael , Bechstein Wolf O. , Göttig Stephan , Wichelhaus Thomas A. , Zeuzem Stefan , Trebicka Jonel , Waidmann Oliver , Welker Martin-Walter , Kempf Volkhard A. J.
Published: November 2021

Background: Carbapenem-resistant Gram-negative bacteria (CRGN) cause life-threatening infections due to limited antimicrobial treatment options. The occurrence of CRGN is often linked to hospitalization and antimicrobial treatment but remains incompletely understood. CRGN are common in patients with severe illness (e.g., liver transplantation patients). Using whole-genome sequencing (WGS), we aimed to elucidate the evolution of CRGN in this vulnerable cohort and to reconstruct potential transmission routes.

Methods: From 351 patients evaluated for liver transplantation, 18 CRGN isolates (from 17 patients) were analyzed. Using WGS and bioinformatic analysis, genotypes and phylogenetic relationships were explored. Potential epidemiological links were assessed by analysis of patient charts.

Results: Carbapenem-resistant (CR) Klebsiella pneumoniae (n=9) and CR Pseudomonas aeruginosa (n=7) were the predominating pathogens. In silico analysis revealed that 14/18 CRGN did not harbor carbapenemase-coding genes, whereas in 4/18 CRGN, carbapenemases (VIM-1, VIM-2, OXA-232, and OXA-72) were detected. Among all isolates, there was no evidence of plasmid transfer-mediated carbapenem resistance. A close phylogenetic relatedness was found for three K. pneumoniae isolates. Although no epidemiological context was comprehensible for the CRGN isolates, evidence was found that the isolates resulted of a transmission of a carbapenem-susceptible ancestor before individual radiation into CRGN.

Conclusion: The integrative epidemiological study reveals a high diversity of CRGN in liver cirrhosis patients. Mutation of carbapenem-susceptible ancestors appears to be the dominant way of CR acquisition rather than in-hospital transmission of CRGN or carbapenemase-encoding genetic elements. This study underlines the need to avoid transmission of carbapenem-susceptible ancestors in vulnerable patient cohorts.
A Brief, Individualized Exercise Program at Intensities Below the Ventilatory Threshold Exerts Therapeutic Effects for Depression: A Pilot Study
Authors: Sakai Yuri , Chen Chong , Toyomaki Atsuhito , Hashimoto Naoki , Kitagawa Kan , Inoue Takao , Sato Asumi , Makihara Keisuke , Kameyama Rie , Wakatsuki Yumi , Udo Niki , Shirakawa Ryosuke , Yokota Takashi , Nakagawa Shin , Kusumi Ichiro
Published: November 2021

Due to the fact that existing pharmacological treatments for depression are not ideal, effort has been devoted to the development of complementary, alternative therapies such as physical exercise. The antidepressant effect of exercise is well documented. However, current recommendations and prescriptions of exercise may be too demanding for depressed patients, as some complain about the design of exercise programs and depression is associated with reduced motivation and capacity to exercise. Therefore, appropriately designed, patient-friendly exercise programs may prove critical for the long-term maintenance and therapeutic effects of exercise. In this pilot study, we developed an exercise program based on patients’ individual level of ventilatory threshold (VT), a submaximal index of aerobic capacity measured by Cardiopulmonary Exercise Testing (CPX). Compared to traditional measures, CPX provides more trustable indices of aerobic capacity and more homogenous exercise prescriptions. The main episode of the program consisted of 15–25 min of cycling twice a week at an intensity that approached but never went higher than subjects’ VT (considered low to moderate in intensity). We found that in patients diagnosed with major depressive disorder or persistent depressive disorder (n = 8), the program resulted in a significant reduction in depressive symptoms at week 8, which was maintained at week 16. Meanwhile, patients’ social functioning, quality of life, and cognitive functions improved. Although we used a single arm, non-randomized design, our results suggest that even a brief, low to moderate intensity exercise program may exert therapeutic effects for depression and CPX may be a useful tool for exercise prescriptions.
Genetic Pathways and Functional Subnetworks for the Complex Nature of Bipolar Disorder in Genome-Wide Association Study
Authors: Kuo Chan-Yen , Chen Tsu-Yi , Kao Pei-Hsiu , Huang Winifred , Cho Chun-Ruei , Lai Ya-Syuan , Yiang Giou-Teng , Kao Chung-Feng
Published: November 2021

Bipolar disorder is a complex psychiatric trait that is also recognized as a high substantial heritability from a worldwide distribution. The success in identifying susceptibility loci for bipolar disorder (BPD) has been limited due to its complex genetic architecture. Growing evidence from association studies including genome-wide association (GWA) studies points to the need of improved analytic strategies to pinpoint the missing heritability for BPD. More importantly, many studies indicate that BPD has a strong association with dementia. We conducted advanced pathway analytics strategies to investigate synergistic effects of multilocus within biologically functional pathways, and further demonstrated functional effects among proteins in subnetworks to examine mechanisms underlying the complex nature of bipolarity using a GWA dataset for BPD. We allowed bipolar susceptible loci to play a role that takes larger weights in pathway-based analytic approaches. Having significantly informative genes identified from enriched pathways, we further built function-specific subnetworks of protein interactions using MetaCore. The gene-wise scores (i.e., minimum p-value) were corrected for the gene-length, and the results were corrected for multiple tests using Benjamini and Hochberg’s method. We found 87 enriched pathways that are significant for BPD; of which 36 pathways were reported. Most of them are involved with several metabolic processes, neural systems, immune system, molecular transport, cellular communication, and signal transduction. Three significant and function-related subnetworks with multiple hotspots were reported to link with several Gene Ontology processes for BPD. Our comprehensive pathway-network frameworks demonstrated that the use of prior knowledge is promising to facilitate our understanding between complex psychiatric disorders (e.g., BPD) and dementia for the access to the connection and clinical implications, along with the development and progression of dementia.
Serpinc1 Acts as a Tumor Suppressor in Hepatocellular Carcinoma Through Inducing Apoptosis and Blocking Macrophage Polarization in an Ubiquitin-Proteasome Manner
Authors: Xu Dacai , Wu Jiawen , Dong Liang , Luo Wenwen , Li Lanying , Tang Daolin , Liu Jinbao
Published: November 2021

Serpinc1 is a serine protease inhibitor in the coagulation cascade, but its role in tumor biology remains obscure. Here, we report an unexpected role of serpinc1 in suppression of hepatocellular carcinoma (HCC). In HCC patients, the mRNA and protein expression of serpinc1 is upregulated, which is negatively correlated with tumor grade, and has a better prognosis than patients with low serpinc1. In addition, patients with high expression of serpinc1 generally have a better tumor immune microenvironment, accompanied by changes in multiple immune cells and mediators. In particular, tumor-promoting M2 macrophages are negatively correlated with serpinc1 expression and the prognosis of HCC patients. In vitro experiments further show that overexpression of serpinc1 inhibits the growth of HCC cells (HepG2 and SMMC7721) by inducing apoptosis. Accordingly, cell co-culture experiments reveal the direct role of serpinc1-overexpressed HCC cells in inhibiting the formation of M2 macrophages. Subsequent unbiased quantitative proteomic and ubiquitinome analyses identify that multiple poly-ubiquitination of proteins involved in signal pathways (such as autophagy, apoptosis, lactate metabolism, and VEGF signaling) are regulated by serpinc1. Overall, these findings establish a serpinc1-dependent ubiquitin-proteasome system to control apoptosis and antitumor immunity.
SOX9: Advances in Gynecological Malignancies
Authors: Chen Huan , He Yujie , Wen Xiangping , Shao Shihong , Liu Yujie , Wang Jinjin
Published: November 2021

Transcription factors of the SOX family were first discovered in mammals in 1990. The sex-determining region Y box 9 belongs to the SOX transcription factor family. It plays an important role in inducing tissue and cell morphogenesis, survival, and many developmental processes. Furthermore, it has been shown to be an oncogene in many tumors. Gynecological malignancies are tumors that occur in the female reproductive system and seriously threaten the lives of patients. Common gynecological malignancies include ovarian cancer, cervical cancer, and endometrial cancer. So far, the molecular mechanisms related to the incidence and development of gynecological malignancies remain unclear. This makes it particularly important to discover their common causative molecule and thus provide an effective therapeutic target. In recent years, studies have found that multiple mechanisms are involved in regulating the expression of the sex-determining region Y box 9, leading to the occurrence and development of gynecological malignancies. In this review, we discuss the prognostic value of SOX9 expression and the potential of targeting SOX9 for gynecological malignancy treatment. We also discuss progress regarding the role of SOX9 in gynecological malignancy pathogenesis through its mediation of important mechanisms, including tumor initiation and proliferation, apoptosis, migration, invasion, chemoresistance, and stem cell maintenance.
Modulatory Effects of Alpha- and Gamma-Tocopherol on the Mitochondrial Respiratory Capacity and Membrane Potential in an In Vitro Model of Alzheimer’s Disease
Authors: Pahrudin Arrozi Aslina , Wan Ngah Wan Zurinah , Ahmad Damanhuri Hanafi , Makpol Suzana
Published: November 2021

Increased amyloid-beta (Aβ) and amyloid precursor protein (APP) in the brains of Alzheimer’s disease (AD) patients are common pathological hallmarks mediating the disease progression. Growing evidence also suggests that mitochondrial abnormalities are an early feature in the pathogenesis of AD. Intervention with antioxidants has received great interest as a molecular strategy for the manipulation of mitochondrial function. Our previous preliminary study using in vitro cell models expressing different types of APP demonstrated that treatment with alpha-tocopherol (ATF) or gamma-tocopherol (GTF) modulates mitochondrial function by reducing mitochondrial reactive oxygen species (ROS), increasing the production of ATP and preventing apoptosis events, especially in cells expressing the mutant APP form. Thus, we hypothesized that ATF or GTF treatment might also alter mitochondrial metabolic pathways such as oxidative phosphorylation. The present study aimed to investigate the role of ATF and GTF in modulating mitochondrial oxidative metabolism using high-resolution respirometry. Our results showed that both ATF and GTF increased the respiratory capacity and membrane potential in the ROUTINE and OXPHOSCI-LINKED states as well as complex IV enzyme activity in wild-type and mutant APP-overexpressing SH-SY5Y cells. Although preliminary, these findings indicate that ATF and GTF modulate mitochondrial oxidative metabolism in APP-overexpressing cells and, in part, may contribute to the planning of strategies for utilizing vitamin E isomers against mitochondrial-related diseases such as AD.
Tetrandrine Modulates Rheb-mTOR Signaling-Mediated Selective Autophagy and Protects Pulmonary Fibrosis
Authors: Liu Yuanyuan , Zhong Wenshan , Zhang Jinming , Chen Weimou , lu Ye , Qiao Yujie , Zeng Zhaojin , Huang Haohua , Cai Shaoxi , Dong Hangming
Published: November 2021

Idiopathic pulmonary fibrosis is a progressive fatal disease characterized by interstitial remodeling, with high lethality and a lack of effective medical therapies. Tetrandrine has been proposed to present anti-fibrotic effects, but the efficacy and mechanisms have not been systematically evaluated. We sought to study the potential therapeutic effects and mechanisms of tetrandrine against lung fibrosis. The anti-fibrotic effects of tetrandrine were evaluated in bleomycin-induced mouse models and TGF-β1-stimulated murine lung fibroblasts. We performed Chromatin Immunoprecipitation (ChIP), Immunoprecipitation (IP), and mRFP-GFP-MAP1LC3B adenovirus construct to investigate the novel mechanisms of tetrandrine-induced autophagy. Tetrandrine decreased TGF-β1-induced expression of α-smooth muscle actin, fibronectin, vimentin, and type 1 collagen and proliferation in fibroblasts. Tetrandrine restored TGF-β1-induced impaired autophagy flux, accompanied by enhanced interaction of SQSTM1 and MAP1LC3-Ⅱ. ChIP studies revealed that tetrandrine induced autophagy via increasing binding of NRF2 and SQSTM1 promoter. Furthermore, tetrandrine inhibited TGF-β1-induced phosphorylation of mTOR by reducing activation of Rheb. In vivo tetrandrine suppressed the bleomycin-induced expression of fibrotic markers and improved pulmonary function. Our data suggest that protective effect of tetrandrine against lung fibrosis might be through promoting Rheb-mTOR and NRF2-SQSTM1 mediated autophagy. Tetrandrine may thus be potentially employed as a novel therapeutic medicine against IPF.
β-hydroxybutyrate Alleviates Learning and Memory Impairment Through the SIRT1 Pathway in D-Galactose-Injured Mice
Authors: Yang Xiaojing , Wang Ruonan , Zhou Hailun , Wang Li , Wang Rui , Li Haomin , Tan Baodong , Wu Qiong , Xu Xin , Cui Lianxu , Li Zaiyu , Li Hua
Published: November 2021

Learning and memory impairment is a common clinical symptom of aging and nervous system injuries, and seriously affects quality of life. Memory impairment is associated with increased oxidative stress (OS) and inflammatory response. β-hydroxybutyrate (BHBA) is a water-soluble endogenous small-molecule ketone body that easily crosses the blood-brain barrier and has shown neuroprotection activities. In this study, we investigated the effects and mechanisms of BHBA on D-galactose (D-gal)-induced memory impairment in mice by in vitro and in vivo experiments. BHBA was administered intragastrically to D-gal-injured C57BL/6 mice for 42 days. Water maze performance, the morphology of the hippocampus with Nissl staining, the ACh content, OS, and inflammation status were examined. To further investigate the mechanism, hippocampal neuronal cells (HT22) were treated with BHBA with or without the SIRT1 inhibitor or small interfering RNAs against sirt1 (si-SIRT1) before incubation with D-gal. BHBA significantly improved water maze performance; increased the ACh content, SOD activity, and SIRT1 expression; and decreased AChE and LDH activity, ROS, MDA, IL-1β, TNF-α contents, and NLRP3 expression. Further studies with the SIRT inhibitor or siRNAs against sirt1 reversed the above effects of BHBA. Collectively, BHBA inhibited hippocampal OS and the inflammation process to alleviate learning and memory impairment through activating the SIRT1 pathway in D-gal-injured mice, suggesting that BHBA could be a potential option for drug development of learning and memory impairment induced by nervous system injuries.
Physiologically Based Modeling of the Effect of Physiological and Anthropometric Variability on Indocyanine Green Based Liver Function Tests
Authors: Köller Adrian , Grzegorzewski Jan , König Matthias
Published: November 2021

Accurate evaluation of liver function is a central task in hepatology. Dynamic liver function tests (DLFT) based on the time-dependent elimination of a test substance provide an important tool for such a functional assessment. These tests are used in the diagnosis and monitoring of liver disease as well as in the planning of hepatobiliary surgery. A key challenge in the evaluation of liver function with DLFTs is the large inter-individual variability. Indocyanine green (ICG) is a widely applied test compound used for the evaluation of liver function. After an intravenous administration, pharmacokinetic (PK) parameters are calculated from the plasma disappearance curve of ICG which provide an estimate of liver function. The hepatic elimination of ICG is affected by physiological factors such as hepatic blood flow or binding of ICG to plasma proteins, anthropometric factors such as body weight, age, and sex, or the protein amount of the organic anion-transporting polypeptide 1B3 (OATP1B3) mediating the hepatic uptake of ICG. Being able to account for and better understand these various sources of inter-individual variability would allow to improve the power of ICG based DLFTs and move toward an individualized evaluation of liver function. Within this work we systematically analyzed the effect of various factors on ICG elimination by the means of computational modeling. For the analysis, a recently developed and validated physiologically based pharmacokinetics (PBPK) model of ICG distribution and hepatic elimination was utilized. Key results are (i) a systematic analysis of the variability in ICG elimination due to hepatic blood flow, cardiac output, OATP1B3 abundance, liver volume, body weight and plasma bilirubin level; (ii) the evaluation of the inter-individual variability in ICG elimination via a large in silico cohort of n = 100,000 subjects based on the NHANES cohort with special focus on stratification by age, sex, and body weight; (iii) the evaluation of the effect of various degrees of cirrhosis on variability in ICG elimination. The presented results are an important step toward individualizing liver function tests by elucidating the effects of confounding physiological and anthropometric parameters in the evaluation of liver function via ICG.
Adolescents With Cancer Need Trustworthy Information and Prefer to Receive It From a Human Source Rather Than From the Internet: A Qualitative Study
Authors: Schwartz-Attias Irit , Raz Haya , Natanzon-Bracha Tamar , Finkelstein Adi , Kreitler Shulamith
Published: November 2021

Background: In pediatric cancer, the legal obligation to provide information is usually toward the parents who are the authorized signatories of the informed consent form. It is now known that aside from providing information to the parents, it is also very important to provide information to the children and adolescents themselves. The question is how the adolescents relate to this. What information do they already possess and what would they like to know? Would they wish to hear the truth in all situations and at what stage? What are their preferred sources of information?

Method: A qualitative study that included in-depth interviews with 19 adolescents with cancer, aged 8.5–18, who were receiving active treatments and had been diagnosed at least 1 month previously. The interviews were guided by 15 open-ended questions.

Findings: The analysis of the interviews indicated that adolescents know quite a lot about the course of their disease and the information they lack is mainly etiological. The participants reported a lack of knowledge concerning sexuality and a sense of discomfort talking about it, leaving them with open questions. They all claimed that it is important to tell the truth: “Even if the truth is difficult, it is important to tell it.” The participants reported that information can be scary, so it must be structured and adapted to the age and emotional readiness of the individual. Most of the participants prefer not to use the internet as an information resource due to the profusion of stressful and non-adapted information.

Conclusion: Adolescents with cancer need trustworthy information and prefer to receive it from a human source rather than from the internet. Not telling the truth can lead them to feel fear and loneliness. The medical staff must operate in sensitive and creative ways to provide adolescents with access to information on various subjects, including sexuality, which they are ashamed to talk about, leaving them with a sense of shame and a lack of knowledge in this area.
Uncover the Offensive Side of Disparagement Humor: An fMRI Study
Authors: Bartolo Angela , Ballotta Daniela , Nocetti Luca , Baraldi Patrizia , Nichelli Paolo Frigio , Benuzzi Francesca
Published: November 2021

Disparagement humor is a kind of humor that denigrates, belittles an individual or a social group. In the aim to unveil the offensive side of these kinds of jokes, we have run an event-related fMRI study asking 30 healthy volunteers to judge the level of fun of a series of verbal stimuli that ended with a sentence that was socially inappropriate but funny (disparagement joke -DJ), socially inappropriate but not funny (SI) or neutral (N). Behavioral results showed disparagement jokes are perceived as funny and at the same time offensive. However, the level of offense in DJ is lower than that registered in SI stimuli. Functional data showed that DJ activated the insula, the SMA, the precuneus, the ACC, the dorsal striatum (the caudate nucleus), and the thalamus. These activations suggest that in DJ a feeling of mirth (and/or a desire to laugh) derived from the joke (e.g., SMA and precuneus) and the perception of the jokes’ social inappropriateness (e.g., ACC and insula) coexist. Furthermore, DJ and SI share a common network related to mentalizing and to the processing of negative feelings, namely the medial prefrontal cortex, the putamen and the right thalamus.
Preparedness and Readiness Strategies for Addressing the COVID-19 Pandemic in Fragile and Conflict Settings: Experiences of the Gaza Strip
Authors: Abuzerr Samer , Abu-Aita Said , Al-Najjar Ismail , Abuhabib Azzam , Al-Jourany Heba , Zinszer Kate
Published: November 2021

The COVID-19 pandemic is a global public health threat of serious concern, especially in conflict settings that face fragility and lack adequate resources and capacities. Gaza suffers from a blockade imposed by the Israeli occupation, environmental deterioration, confiscation of lands, demolition of houses and hospitals, restrictions on movement, lack of control over natural resources, and financial constraints. Gaza's population is consequently living in a poor humanitarian situation with high unemployment rates, poverty, over-crowdedness, and a weak health system. This makes Gaza incredibly fragile and affects its ability to respond to the COVID-19 pandemic effectively. The pandemic is expected to deepen Gaza's systems' fragility, which is already overstretched beyond their limits. This will hinder its capacity to deal with the pandemic, and other pre-existing pressing humanitarian needs. Therefore, in this review, we comprehensively explored Gaza's policy failures and successes related to the COVID-19 preparedness and response by state and non-state actors and recommend potential solutions and alternatives. We have addressed critical issues including the health system, water, sanitation, hygiene, socio-economic, education, food security, and others. In Gaza, effectiveness in combating the COVID-19 pandemic can only come from committed political will, transparency from all regulators, strategic dialogue, comprehensive planning, and active international support.
1,800 MHz Radiofrequency Electromagnetic Irradiation Impairs Neurite Outgrowth With a Decrease in Rap1-GTP in Primary Mouse Hippocampal Neurons and Neuro2a Cells
Authors: Li Yanqi , Deng Ping , Chen Chunhai , Ma Qinlong , Pi Huifeng , He Mindi , Lu Yonghui , Gao Peng , Zhou Chao , He Zhixin , Zhang Yanwen , Yu Zhengping , Zhang Lei
Published: November 2021

Background: With the global popularity of communication devices such as mobile phones, there are increasing concerns regarding the effect of radiofrequency electromagnetic radiation (RF-EMR) on the brain, one of the most important organs sensitive to RF-EMR exposure at 1,800 MHz. However, the effects of RF-EMR exposure on neuronal cells are unclear. Neurite outgrowth plays a critical role in brain development, therefore, determining the effects of 1,800 MHz RF-EMR exposure on neurite outgrowth is important for exploring its effects on brain development.

Objectives: We aimed to investigate the effects of 1,800 MHz RF-EMR exposure for 48 h on neurite outgrowth in neuronal cells and to explore the associated role of the Rap1 signaling pathway.

Material and Methods: Primary hippocampal neurons from C57BL/6 mice and Neuro2a cells were exposed to 1,800 MHz RF-EMR at a specific absorption rate (SAR) value of 4 W/kg for 48 h. CCK-8 assays were used to determine the cell viability after 24, 48, and 72 h of irradiation. Neurite outgrowth of primary hippocampal neurons (DIV 2) and Neuro2a cells was observed with a 20 × optical microscope and recognized by ImageJ software. Rap1a and Rap1b gene expressions were detected by real-time quantitative PCR. Rap1, Rap1a, Rap1b, Rap1GAP, and p-MEK1/2 protein expressions were detected by western blot. Rap1-GTP expression was detected by immunoprecipitation. The role of Rap1-GTP was assessed by transfecting a constitutively active mutant plasmid (Rap1-Gly_Val-GFP) into Neuro2a cells.

Results: Exposure to 1,800 MHz RF-EMR for 24, 48, and 72 h at 4 W/kg did not influence cell viability. The neurite length, primary and secondary neurite numbers, and branch points of primary mouse hippocampal neurons were significantly impaired by 48-h RF-EMR exposure. The neurite-bearing cell percentage and neurite length of Neuro2a cells were also inhibited by 48-h RF-EMR exposure. Rap1 activity was inhibited by 48-h RF-EMR with no detectable alteration in either gene or protein expression of Rap1. The protein expression of Rap1GAP increased after 48-h RF-EMR exposure, while the expression of p-MEK1/2 protein decreased. Overexpression of constitutively active Rap1 reversed the decrease in Rap1-GTP and the neurite outgrowth impairment in Neuro2a cells induced by 1,800 MHz RF-EMR exposure for 48 h.

Conclusion: Rap1 activity and related signaling pathways are involved in the disturbance of neurite outgrowth induced by 48-h 1,800 MHz RF-EMR exposure. The effects of RF-EMR exposure on neuronal development in infants and children deserve greater focus.
Interference Utilization Precoding in Multi-Cluster IoT Networks
Authors: Wang Yuanchen , Lim Eng Gee , Xue Xiaoping , Zhu Guangyu , Pei Rui , Wei Zhongxiang
Published: November 2021

In Internet-of-Things, downlink multi-device interference has long been considered as a harmful element deteriorating system performance, and thus the principle of the classic interference-mitigation based precoding is to suppress the multi-device interference by exploiting the spatial orthogonality. In recent years, a judicious interference utilization precoding has been developed, which is capable of exploiting multi-device interference as a beneficial element for improving device’s reception performance, thus reducing downlink communication latency. In this review paper, we aim to review the emerging interference utilization precoding techniques. We first briefly introduce the concept of constructive interference, and then we present two generic downlink interference-utilization optimizations, which utilizes the multi-device interference for enhancing system performance. Afterwards, the application of interference utilization precoding is discussed in multi-cluster scenario. Finally, some open challenges and future research topics are envisaged.
Prognostic Enigma of Pancreatic Solid Pseudopapillary Neoplasm: A Single-Center Experience of 63 Patients
Authors: Wang Xinbo , Zhu Daojun , Bao Wei , Li Min , Wang Sizhen , Shen Rongxi
Published: November 2021

Background: Studies investigating prognostic factors of solid pseudopapillary neoplasm (SPN) have been published with conflicting findings.

Methods: Retrospective analysis of 63 consecutive cases of SPN in our institution from January 2010 to December 2019 was carried out. The clinicopathological features, treatment practices along with survival associations were collected and analyzed.

Results: Fifteen patients (23.8%) were male, and 48 (76.2%) were female, with a median age of 34.0 ± 14.5 years. The larger tumor size was correlated with the more mixed components (p = 0.000) and the higher Ki-67 index (p = 0.042). No recurrence was found in the nine patients whose tumors fulfilled the WHO criteria for malignancy due to the presence of at least perineural invasion (6.4%), angiovascular invasion (2.3%), and/or adjacent organ invasion (6.4%). Microscopic infiltrative growth was detected in 9 (14.3%) tumors, which was correlated significantly with the WHO criteria (p = 0.002), capsule invasion (p = 0.005), and pancreatic parenchyma invasion (p = 0.001), but not with disease-free survival (p = 0.13). CD99 was found to be positively expressed in 88.9% (40/45) of tumors and more likely to have depressed Ki-67 index (p = 0.016). After a median follow-up of 58 months, only two patients (3.2%) had a recurrence after their first operation outside of our hospital. No patient died due to tumor progression.

Conclusions: Although survival is favorable with aggressive surgery, it is actually difficult to assess the prognostic factors of resected SPNs. Future investigations into the role of clinicopathological evaluation will unveil the prognostic enigma of pancreatic SPN after resection.
Global Spread and Molecular Characterization of CTX-M-Producing Salmonella Typhimurium Isolates
Authors: Guo Lili , Zhao Yongda
Published: November 2021

This study aimed to determine the global prevalence and molecular characterization of CTX-M-producing Salmonella Typhimurium isolates. A total of 330 (15.2%, 330/21779) blaCTX-M-positive S. Typhimurium were obtained from the public databases in July 2021. Thirteen variants were found in the 330 members of the blaCTX-M group, and blaCTX-M-9 (26.4%, 88/330) was the most prevalent. The majority of blaCTX-M-positive S. Typhimurium were obtained from humans (59.7%, 197/330) and animals (31.5%, 104/330). The number of blaCTX-M-positive S. Typhimurium increased annually (p < 0.0001). These isolates were primarily found from China, the United Kingdom, Australia, the USA, and Germany. In addition, these isolates possessed 14 distinct sequence types (ST), and three predominated: ST34 (42.7%, 141/330), ST19 (37.0%, 122/330), and ST313 (10.3%, 34/330). The majority of ST34 S. Typhimurium isolates were distributed in China and mainly from swine. However, the majority of ST19 were distributed in the United Kingdom and Australia. Analysis of contigs showed that the major type of blaCTX-M-carrying plasmid was identified as IncI plasmid (52.9%, 27/51) and IncHI2 plasmid (17.6%, 9/51) in 51 blaCTX-M-positive S. Typhimurium isolates. In addition, WGS analysis further revealed that blaCTX-M co-existed with nine antibiotic-resistant genes with a detection rate over 50%, conferring resistance to five classes of antimicrobials. The 154 virulence genes were detected among these isolates, of which 107 virulence genes were highly common. This study revealed that China has been severely contaminated by blaCTX-M-positive S. Typhimurium isolates, these isolates possessed numerous ARGs and virulence genes, and highlighted that continued vigilance for blaCTX-M-positive S. Typhimurium in animals and humans is urgently needed.
Dominant Contributions of Secondary Aerosols and Vehicle Emissions to Water-Soluble Inorganic Ions of PM2.5 in an Urban Site in the Metropolitan Hangzhou, China
Authors: Xiong Chun , Yu Shaocai , Chen Xue , Li Zhen , Zhang Yibo , Li Mengying , Liu Weiping , Li Pengfei , Seinfeld John H.
Published: November 2021

Water soluble inorganic ions (WSIIs) are important components in PM2.5 and could strongly affect the acidity and hygroscopicity of PM2.5. In order to achieve the seasonal characteristics and determine the potential sources of WSIIs in PM2.5 in Hangzhou, online systems were used to measure hourly mass concentrations of WSIIs (SO42−, NO3−, NH4+, Cl−, Na+, K+, Ca2+ and Mg2+) as well as PM2.5, NO2 and SO2 at an urban site for one month each season (May, August, October, December) in 2017. Results showed that the hourly mass concentrations of PM2.5 during the whole campaign varied from 1 to 292 μg·m−3 with the mean of 56.03 μg·m−3. The mean mass concentration of WSIIs was 26.49 ± 20.78 μg·m−3, which contributed 48.28% to averaged PM2.5 mass. SNA (SO42−, NO3− and NH4+) were the most abundant ions in PM2.5 and on average, they comprised 41.57% of PM2.5 mass. PM2.5, NO2, SO2 and WSIIs showed higher mass concentrations in December, possibly due to higher energy consumption emissions, unfavorable meteorological factors (e.g., lower wind speed and temperature) and regional transport. Results from PCA models showed that secondary aerosols and vehicle emissions were the dominant sources of WSIIs in the observations. Our findings highlight the importance of stronger controls on precursor (e.g., SO2 and NO2) emissions in Hangzhou, and show that industrial areas should be controlled at local and regional scales in the future.
Storm Naming in the Eastern Mediterranean: Procedures, Events Review and Impact on the Citizens Risk Perception and Readiness
Authors: Kotroni Vassiliki , Lagouvardos Konstantinos , Bezes Antonis , Dafis Stavros , Galanaki Elisavet , Giannaros Christos , Giannaros Theodore , Karagiannidis Athanasios , Koletsis Ioannis , Kopania Theodora , Papagiannaki Katerina , Papavasileiou Georgios , Vafeiadis Vasilis , Vougioulas Eustratios
Published: November 2021

This paper is devoted to the discussion of the practice of storm naming that has been initiated in January 2017 for the first time in the Eastern Mediterranean Region. Namely the METEO Unit at NOA, taking into consideration that storm naming facilitates meteorologists, researchers, authorities, civil protection officers, the media and citizens to communicate the forecasts of high-impact weather events, started storm naming in January 2017 and has named 35 storms up to September 2021. The criteria of storm naming are discussed, and a synopsis of the events is presented. The monthly distribution shows that 57% of the named storms occurred during the winter period, with January being the month with the highest percentage of occurrence of named storms (28%). The impact of storm naming on citizens risk perception and increased awareness has been also assessed through an internet-based questionnaire that was launched on the fourth year of the storm naming practice in Greece. Overall, results indicate a significant impact of storm naming on the readiness of citizens through the activation of perceptual and cognitive mechanisms.
Endogenous Oxytocin Levels in Autism—A Meta-Analysis
Authors: Moerkerke Matthijs , Peeters Mathieu , de Vries Lyssa , Daniels Nicky , Steyaert Jean , Alaerts Kaat , Boets Bart
Published: November 2021

Oxytocin (OT) circuitry plays a major role in the mediation of prosocial behavior. Individuals with autism spectrum disorder (ASD) are characterized by impairments in social interaction and communication and have been suggested to display deficiencies in central OT mechanisms. The current preregistered meta-analysis evaluated potential group differences in endogenous OT levels between individuals with ASD and neurotypical (NT) controls. We included 18 studies comprising a total of 1422 participants. We found that endogenous OT levels are lower in children with ASD as compared to NT controls (n = 1123; g = −0.60; p = 0.006), but this effect seems to disappear in adolescent (n = 152; g = −0.20; p = 0.53) and adult populations (n = 147; g = 0.27; p = 0.45). Secondly, while no significant subgroup differences were found in regard to sex, the group difference in OT levels of individuals with versus without ASD seems to be only present in the studies with male participants (n = 814; g = −0.44; p = 0.08) and not female participants (n = 192; g = 0.11; p = 0.47). More research that employs more homogeneous methods is necessary to investigate potential developmental changes in endogenous OT levels, both in typical and atypical development, and to explore the possible use of OT level measurement as a diagnostic marker of ASD.
Cardiac Relapse of Acute Lymphoblastic Leukemia Following Hematopoietic Stem Cell Transplantation: A Case Report and Review of Literature
Authors: Sheikh Irtiza N. , Ragoonanan Dristhi , Franklin Anna , Srinivasan Chandra , Zhao Bhiong , Petropoulos Demetrios , Mahadeo Kris M. , Tewari Priti , Khazal Sajad J.
Published: November 2021

Isolated extramedullary relapse of acute lymphoblastic leukemia (ALL) occurs in soft tissues and various organs outside the testis and central nervous system. Treatments such as hematopoietic stem cell transplantation and more novel modalities such as immunotherapy have eradicated ALL at extramedullary sites. In some instances, survival times for relapsed ALL at these sites are longer than those for relapsed disease involving only the bone marrow. Isolated relapse of ALL in the myocardium is rare, especially in children, making diagnosis and treatment of it difficult. More recent treatment options such as chimeric antigen receptor T-cell therapy carry a high risk of cytokine release syndrome and associated risk of worsening cardiac function. Herein we present the case of an 11-year-old boy who presented with relapsed symptomatic B-cell ALL in the myocardium following allogeneic hematopoietic stem cell transplantation. This is an unusual presentation of relapsed ALL and this case demonstrates the associated challenges in its diagnosis and treatment. The case report is followed by a literature review of the advances in treatment of pediatric leukemia and their application to extramedullary relapse of this disease in particular.