bluuebunny/crossref_metadata_2025 huggingface dataset:
The Mechanism Switching the Osteoclast From Short to Long Duration Bone Resorption
Authors: Delaisse Jean-Marie , Søe Kent , Andersen Thomas Levin , Rojek Aleksandra Maria , Marcussen Niels
Published: March 2021

The current models of osteoclastic bone resorption focus on immobile osteoclasts sitting on the bone surface and drilling a pit into the bone matrix. It recently appeared that many osteoclasts also enlarge their pit by moving across the bone surface while resorbing. Drilling a pit thus represents only the start of a resorption event of much larger amplitude. This prolonged resorption activity significantly contributes to pathological bone destruction, but the mechanism whereby the osteoclast engages in this process does not have an answer within the standard bone resorption models. Herein, we review observations that lead to envision how prolonged resorption is possible through simultaneous resorption and migration. According to the standard pit model, the “sealing zone” which surrounds the ruffled border (i.e., the actual resorption apparatus), “anchors” the ruffled border against the bone surface to be resorbed. Herein, we highlight that continuation of resorption demands that the sealing zone “glides” inside the cavity. Thereby, the sealing zone emerges as the structure responsible for orienting and displacing the ruffled border, e.g., directing resorption against the cavity wall. Importantly, sealing zone displacement stringently requires thorough collagen removal from the cavity wall - which renders strong cathepsin K collagenolysis indispensable for engagement of osteoclasts in cavity-enlargement. Furthermore, the sealing zone is associated with generation of new ruffled border at the leading edge, thereby allowing the ruffled border to move ahead. The sealing zone and ruffled border displacements are coordinated with the migration of the cell body, shown to be under control of lamellipodia at the leading edge and of the release of resorption products at the rear. We propose that bone resorption demands more attention to osteoclastic models integrating resorption and migration activities into just one cell phenotype.
Carbon Nanomaterials With Hollow Structures: A Mini-Review
Authors: Liu Fan , Cheng Yu , Tan Junchao , Li Jiantong , Cheng Haoyan , Hu Hao , Du Chunya , Zhao Shuang , Yan Yan , Liu Mingkai
Published: March 2021

Carbon nanomaterials with high electrical conductivity, good chemical, and mechanical stability have attracted increasing attentions and shown wide applications in recent years. In particularly, hollow carbon nanomaterials, which possess ultrahigh specific surface area, large surface-to-volume ratios, and controllable pore size distribution, will benefit to provide abundant active sites, and mass loading vacancy, accelerate electron/ion transfer as well as contribute to the specific density of energy storage systems. In this mini-review, we summarize the recent progresses of hollow carbon nanomaterials by focusing on the synthesis approaches and corresponding nanostructures, including template-free and hard-template carbon hollow structures, metal organic framework-based hollow carbon structures, bowl-like and cage-like structures, as well as hollow fibers. The design and synthesis strategies of these hollow carbon nanomaterials have been systematically discussed. Finally, the emerging challenges and future prospective for developing advanced hollow carbon structures were outlined.
Localized and Systemic Immune Response in Human Reproductive Tract
Authors: Gudisa Rajendra , Goyal Kapil , Gupta Parakriti , Singh Mini P.
Published: March 2021

Sexually transmitted infections (STIs) are one of the significant causes of morbidity and mortality among adolescents and adults across the globe and encompass all the infections transmitted via person-to-person sexual contact. In spite of the widespread approach being used, STIs remain under-reported and many infections have taken an epidemic turn. The biggest roadblock in this is the unraveled basis of immunopathology of these infections, hindering the discovery of potential targets for immunization. Thereby, it is of utmost significance to decipher the hidden basis of these STIs to control the increasing epidemic of less commonly studied STIs. A complex interplay between innate immune defenses, with resident microbiota and mucosal immune response serves as the basis of therapeutic approaches, by targeting the vital steps of this dynamic interaction. The characterization of pathogen-specific antibodies to significant immunogenic molecules may divulge the conceivable protective effects.
Intermuscular Fat Content in Young Chinese Men With Newly Diagnosed Type 2 Diabetes: Based on MR mDIXON-Quant Quantitative Technique
Authors: Yu Fuyao , He Bing , Chen Li , Wang Fengzhe , Zhu Haidong , Dong Yanbin , Pan Shinong
Published: March 2021

Objective

Skeletal muscle fat content is one of the important contributors to insulin resistance (IR), but its diagnostic value remains unknown, especially in the Chinese population. Therefore, we aimed to analyze differences in skeletal muscle fat content and various functional MRI parameters between diabetic patients and control subjects to evaluate the early indicators of diabetes. In addition, we aimed to investigate the associations among skeletal muscle fat content, magnetic resonance parameters of skeletal muscle function and IR in type 2 diabetic patients and control subjects.

Methods

We enrolled 12 patients (age:29-38 years, BMI: 25-28 kg/m2) who were newly diagnosed with type 2 diabetes (intravenous plasma glucose concentration≥11.1mmol/l or fasting blood glucose concentration≥7.0mmol/l) together with 12 control subjects as the control group (age: 26-33 years, BMI: 21-28 kg/m2). Fasting blood samples were collected for the measurement of glucose, insulin, 2-hour postprandial blood glucose (PBG2h), and glycated hemoglobin (HbAlc). The magnetic resonance scan of the lower extremity and abdomen was performed, which can evaluate visceral fat content as well as skeletal muscle metabolism and function through transverse relaxation times (T2), fraction anisotropy (FA) and apparent diffusion coefficient (ADC) values.

Results

We found a significant difference in intermuscular fat (IMAT) between the diabetes group and the control group (p<0.05), the ratio of IMAT in thigh muscles of diabetes group was higher than that of control group. In the entire cohort, IMAT was positively correlated with HOMA-IR, HbAlc, T2, and FA, and the T2 value was correlated with HOMA-IR, PBG2h and HbAlc (p<0.05). There were also significant differences in T2 and FA values between the diabetes group and the control group (p<0.05). According to the ROC, assuming 8.85% of IMAT as the cutoff value, the sensitivity and specificity of IMAT were 100% and 83.3%, respectively. Assuming 39.25ms as the cutoff value, the sensitivity and specificity of T2 value were 66.7% and 91.7%, respectively. All the statistical analyses were adjusted for age, BMI and visceral fat content.

Conclusion

Deposition of IMAT in skeletal muscles seems to be an important determinant for IR in type 2 diabetes. The skeletal muscle IMAT value greater than 8.85% and the T2 value greater than 39.25ms are suggestive of IR.
Association of Complement-Related Proteins in Subjects With and Without Second Trimester Gestational Diabetes
Authors: Ramanjaneya Manjunath , Butler Alexandra E. , Alkasem Meis , Bashir Mohammed , Jerobin Jayakumar , Godwin Angela , Moin Abu Saleh Md , Ahmed Lina , Elrayess Mohamed A. , Hunt Steven C. , Atkin Stephen L. , Abou-Samra Abdul-Badi
Published: March 2021

Introduction

Gestational Diabetes Mellitus (GDM) development is related to underlying metabolic syndrome that is associated with elevated complement C3 and C4. Elevated C3 levels have been associated with preeclampsia and the development of macrosomia.

Methods

This case-control study included 34 pregnant women with GDM and 16 non-diabetic (ND) women in their second trimester. Complement-related proteins were measured and correlated with demographic, biochemical, and pregnancy outcome data.

Results

GDM women were older with a higher BMI (p<0.001); complement C3, C4 and Factor-H were significantly elevated (p=0.001, p=0.05, p=0.01, respectively). When adjusted for age and BMI, Complement C3 (p=0.04) and Factor-H (p=0.04) remained significant. Partial correlation showed significant correlation between C4 with serum alanine aminotransferase (ALT) (p<0.05) and 2nd term diastolic blood pressure (p<0.05); Factor-H and C-reactive protein (CRP; p<0.05). Pearson bivariate analysis revealed significant correlations between C3, C4, and Factor-H and CRP; p<0.05; C3 and gestational age at delivery (GA; p<0.05); C4 and ALT and second-trimester systolic blood pressure (STBP) (p=0.008 and p<0.05, respectively); Factor-H and glycated hemoglobin (HbA1c) (p<0.05). Regression analysis showed that the elevation of C3 could be accounted for by age, BMI, GA and CRP, with CRP being the most important predictor (p=0.02). C4 elevation could be accounted for by ALT, CRP and STBP. CRP predicted Factor-H elevation.

Conclusion

The increased C3, C4 and Factor-H during the second trimester of pregnancy in GDM are not independently associated with GDM; inflammation and high BMI may be responsible for their elevation. The elevation of second trimester C3 in GDM is associated with earlier delivery and further work is needed to determine if this is predictive.
Complex RNA Secondary Structures Mediate Mutually Exclusive Splicing of Coleoptera Dscam1
Authors: Dong Haiyang , Li Lei , Zhu Xiaohua , Shi Jilong , Fu Ying , Zhang Shixin , Shi Yang , Xu Bingbing , Zhang Jian , Shi Feng , Jin Yongfeng
Published: March 2021

Mutually exclusive splicing is an important mechanism for expanding protein diversity. An extreme example is the Down syndrome cell adhesion molecular (Dscam1) gene of insects, containing four clusters of variable exons (exons 4, 6, 9, and 17), which potentially generates tens of thousands of protein isoforms through mutually exclusive splicing, of which regulatory mechanisms are still elusive. Here, we systematically analyzed the variable exon 4, 6, and 9 clusters of Dscam1 in Coleoptera species. Through comparative genomics and RNA secondary structure prediction, we found apparent evidence that the evolutionarily conserved RNA base pairing mediates mutually exclusive splicing in the Dscam1 exon 4 cluster. In contrast to the fly exon 6, most exon 6 selector sequences in Coleoptera species are partially located in the variable exon region. Besides, bidirectional RNA–RNA interactions are predicted to regulate the mutually exclusive splicing of variable exon 9 of Dscam1. Although the docking sites in exon 4 and 9 clusters are clade specific, the docking sites-selector base pairing is conserved in secondary structure level. In short, our result provided a mechanistic framework for the application of long-range RNA base pairings in regulating the mutually exclusive splicing of Coleoptera Dscam1.
The Role of Satellite DNAs in Genome Architecture and Sex Chromosome Evolution in Crambidae Moths
Authors: Cabral-de-Mello Diogo C. , Zrzavá Magda , Kubíčková Svatava , Rendón Pedro , Marec František
Published: March 2021

Tandem repeats are important parts of eukaryotic genomes being crucial e.g., for centromere and telomere function and chromatin modulation. In Lepidoptera, knowledge of tandem repeats is very limited despite the growing number of sequenced genomes. Here we introduce seven new satellite DNAs (satDNAs), which more than doubles the number of currently known lepidopteran satDNAs. The satDNAs were identified in genomes of three species of Crambidae moths, namely Ostrinia nubilalis, Cydalima perspectalis, and Diatraea postlineella, using graph-based computational pipeline RepeatExplorer. These repeats varied in their abundance and showed high variability within and between species, although some degree of conservation was noted. The satDNAs showed a scattered distribution, often on both autosomes and sex chromosomes, with the exception of both satellites in D. postlineella, in which the satDNAs were located at a single autosomal locus. Three satDNAs were abundant on the W chromosomes of O. nubilalis and C. perspectalis, thus contributing to their differentiation from the Z chromosomes. To provide background for the in situ localization of the satDNAs, we performed a detailed cytogenetic analysis of the karyotypes of all three species. This comparative analysis revealed differences in chromosome number, number and location of rDNA clusters, and molecular differentiation of sex chromosomes.
Cyclophilins A, B, and C Role in Human T Lymphocytes Upon Inflammatory Conditions
Authors: Gegunde Sandra , Alfonso Amparo , Alvariño Rebeca , Alonso Eva , Botana Luis M.
Published: March 2021

Cyclophilins (Cyps) are a group of peptidyl-prolyl cis/trans isomerases that play crucial roles in regulatory mechanisms of cellular physiology and pathology in several inflammatory conditions. Their receptor, CD147, also participates in the development and progression of the inflammatory response. Nevertheless, the main function of Cyps and their receptor are yet to be deciphered. The release of CypA and the expression of the CD147 receptor in activated T lymphocytes were already described, however, no data are available about other Cyps in these cells. Therefore, in the present work intra and extracellular CypA, B and C levels were measured followed by induced inflammatory conditions. After activation of T lymphocytes by incubation with concanavalin A, both intra and extracellular Cyps levels and the CD147 membrane receptor expression were increased leading to cell migration towards circulating CypA and CypB as chemoattractants. When CypA was modulated by natural and synthetic compounds, the inflammatory cascade was avoided including T cell migration. Our results strengthen the relationship between CypA, B, and C, their receptor, and the inflammatory process in human T lymphocytes, associating CypC with these cells for the first time.
Toxicity Profile of Combining PD-1/PD-L1 Inhibitors and Thoracic Radiotherapy in Non-Small Cell Lung Cancer: A Systematic Review
Authors: Li Butuo , Jiang Chao , Pang Linlin , Zou Bing , Ding Mingjun , Sun Xindong , Yu Jinming , Wang Linlin
Published: March 2021

Background

The combination of immune checkpoint inhibitors (ICIs) and thoracic radiotherapy (TRT) has shown significant clinical activity in patients with non-small cell lung cancer (NSCLC). However, the currently available data on adverse events (AEs) were derived from a small subset of patients included in prospective clinical trials or retrospective studies. Thus, we conducted this systematic review to determine the AEs associated with this combination treatment.

Methods

An electronic literature search was performed in databases and conference proceedings of prospective clinical trials assessing the combination of ICIs and TRT for patients with NSCLC. The systematic analysis was conducted to determine the profile and incidence of AEs of combination treatment. We further performed the comparison of AEs between programmed cell death 1 (PD-1) and programmed cell death ligand 1 (PD-L1) inhibitors, and sequential and concurrent administration of ICIs and TRT to help identify high risk patients. The systematic analyses were conducted with the Review Manager (version 5.3; The Cochrane Collaboration, Oxford, United Kingdom) and Stata version 12.0 (StataCorp, College Station, TX, USA) software.

Results

Eleven clinical trials involving 1,113 patients with NSCLC were eligible for analysis. The incidence of all-grade AEs was 95.5%; that of high-grade AEs (grade ≥3) was 30.2%. The most frequent all-grade AE was fatigue (49.7%), while pneumonitis was the most common high-grade AE (3.8%) and grade 5 AE (0.6%). Notably, the toxicity profiles of PD-1 and PD-L1 inhibitors were similar. Concurrent treatment was associated with a higher incidence of higher-grade AEs (41.6% vs 24.8%, P=0.17) and pneumonitis (7.1% vs 3.9%, P=0.14) compared to sequential treatment, but no significant difference was observed.

Conclusion

Most AEs of this combination treatment are tolerable; as the most common high-grade AE, pneumonitis deserves the utmost attention of physicians. The toxicity profiles of patients receiving PD-1 or PD-L1 were similar, and no significant difference was observed between concurrent and sequential treatment.
Ganglioside GD3 May Suppress the Functional Activities of Benign Skin T Cells in Cutaneous T-Cell Lymphoma
Authors: Kume Miki , Kiyohara Eiji , Matsumura Yutaka , Koguchi-Yoshioka Hanako , Tanemura Atsushi , Hanaoka Yuma , Taminato Mifue , Tashima Hiroki , Tomita Koichi , Kubo Tateki , Watanabe Rei , Fujimoto Manabu
Published: March 2021

In cutaneous T-cell lymphoma (CTCL), which arises from skin-tropic memory T cells, malignant T cells and benign T cells are confined in the same skin lesions. It is thus difficult to evaluate the phenotypic characteristics and functional activities of benign T cells in CTCL. Disialoganglioside with three glycosyl groups (GD3) is increasingly expressed on the surface of solid malignant tumor cells and takes part in tumor progression and suppression of tumor immunity. However, the role of GD3 in CTCL is not well-understood. In this study, the malignant and benign T cells in CTCL skin lesions were distinguished by flow cytometry and their phenotypic characteristics were compared with those of T cells from control skin specimens. In CTCL skin lesions, the benign T cells included limited resident memory T cells (TRM), which are sessile in skin and known to exert strong antitumor function. The benign T cells showed diminished Th17 property, and the expression of GD3 was high in the malignant T cells. The expression of GD3 in the malignant T cells inversely correlated with IL-17A production from the benign CD4 T cells. GD3 from the malignant T cells was implied to be involved in suppressing the Th17 activity of the benign T cells independent of the regulation of TRM differentiation in CTCL. Revealing the role of GD3 in inhibiting the production of IL-17A in CTCL would aid the understanding of the suppressive mechanism of the antitumor activity by malignant tumor cells.
Lessons From Immune Checkpoint Inhibitor Trials in Hepatocellular Carcinoma
Authors: Mohr Raphael , Jost-Brinkmann Fabian , Özdirik Burcin , Lambrecht Joeri , Hammerich Linda , Loosen Sven H. , Luedde Tom , Demir Münevver , Tacke Frank , Roderburg Christoph
Published: March 2021

The implementation of immune checkpoint inhibitors (ICI) into the clinical management of different malignancies has largely changed our understanding of cancer treatment. After having proven efficacy in different tumor entities such as malignant melanoma and lung cancer, ICI were intensively tested in the setting of hepatocellular carcinoma (HCC). Here they could achieve higher and more durable response rates compared to tyrosine-kinase inhibitors (TKI), that were sole standard of care for the last decade. Most recently, ICI treatment was approved in a first line setting of HCC, for cases not suitable for curative strategies. However, only a subset of patients benefits from ICI therapy, while others experience rapid tumor progression, worsening of liver function and poor prognosis. Efforts are being made to find immune characteristics that predict tumor responsiveness to ICI, but no reliable biomarker could be identified so far. Nevertheless, data convincingly demonstrate that combination therapies (such as dual inhibition of PD-L1 and VEGF) are more effective than the application of single agents. In this review, we will briefly recapitulate the current algorithms for systemic treatment, discuss available results from checkpoint inhibitor trials and give an outlook on future directions of immunotherapy in HCC.
Study of Microwave-Assisted MoS2 and Graphene Composite Counter Electrode for Dye-Sensitized Solar Cells
Authors: Yi Ling , Sun Hengchao , Yang Wen , Chen Weina , Luo Jian , Wang Jinyan , Kang Xing , Luo Detian , Ma Bing , Wang Yanjun , Su Songyong , Wang Zheng
Published: March 2021

Graphene-MoS2 composites were synthesized via one-step microwave-assisted chemical bath deposition and used as counter electrodes for dye-sensitized solar cells, instead of traditional Pt film which has high cost and poor stability. The effects of graphene additive amount on the performance of cells were studied. The results reveal that sheet porous structure graphene and MoS2 particles has been incorporated tightly, which is the benefit of electrical conductivity and catalysis ability. A maximum efficiency of 6.3% has been achieved under 100 mW cm−2 illumination when the Mo:C is 1:1.
Novel Microbial Groups Drive Productivity in an Archean Iron Formation
Authors: Sheik Cody S. , Badalamenti Jonathan P. , Telling Jon , Hsu David , Alexander Scott C. , Bond Daniel R. , Gralnick Jeffrey A. , Lollar Barbara Sherwood , Toner Brandy M.
Published: March 2021

Deep subsurface environments are decoupled from Earth’s surface processes yet diverse, active, and abundant microbial communities thrive in these isolated environments. Microbes inhabiting the deep biosphere face unique challenges such as electron donor/acceptor limitations, pore space/fracture network limitations, and isolation from other microbes within the formation. Of the few systems that have been characterized, it is apparent that nutrient limitations likely facilitate diverse microbe-microbe interactions (i.e., syntrophic, symbiotic, or parasitic) and that these interactions drive biogeochemical cycling of major elements. Here we describe microbial communities living in low temperature, chemically reduced brines at the Soudan Underground Mine State Park, United States. The Soudan Iron mine intersects a massive hematite formation at the southern extent of the Canadian Shield. Fractured rock aquifer brines continuously flow from exploratory boreholes drilled circa 1960 and are enriched in deuterium compared to the global meteoric values, indicating brines have had little contact with surface derived waters, and continually degas low molecular weight hydrocarbons C1-C4. Microbial enrichments suggest that once brines exit the boreholes, oxidation of the hydrocarbons occur. Amplicon sequencing show these borehole communities are low in diversity and dominated by Firmicute and Proteobacteria phyla. From the metagenome assemblies, we recovered approximately thirty genomes with estimated completion over 50%. Analysis of genome taxonomy generally followed the amplicon data, and highlights that several of the genomes represent novel families and genera. Metabolic reconstruction shows two carbon-fixation pathways were dominant, the Wood-Ljungdahl (acetogenesis) and Calvin-Benson-Bassham (via RuBisCo), indicating that inorganic carbon likely enters into the microbial foodweb with differing carbon fractionation potentials. Interestingly, methanogenesis is likely driven by Methanolobus and suggests cycling of methylated compounds and not H2/CO2 or acetate. Furthermore, the abundance of sulfate in brines suggests cryptic sulfur cycling may occur, as we detect possible sulfate reducing and thiosulfate oxidizing microorganisms. Finally, a majority of the microorganisms identified contain genes that would allow them to participate in several element cycles, highlighting that in these deep isolated systems metabolic flexibility may be an important life history trait.
Learned Overweight Internal Model Can Be Activated to Maintain Equilibrium When Tactile Cues Are Uncertain: Evidence From Cortical and Behavioral Approaches
Authors: Lhomond Olivia , Juan Benjamin , Fornerone Theo , Cossin Marion , Paleressompoulle Dany , Prince François , Mouchnino Laurence
Published: March 2021

Human adaptive behavior in sensorimotor control is aimed to increase the confidence in feedforward mechanisms when sensory afferents are uncertain. It is thought that these feedforward mechanisms rely on predictions from internal models. We investigate whether the brain uses an internal model of physical laws (gravitational and inertial forces) to help estimate body equilibrium when tactile inputs from the foot sole are depressed by carrying extra weight. As direct experimental evidence for such a model is limited, we used Judoka athletes thought to have built up internal models of external loads (i.e., opponent weight management) as compared with Non-Athlete participants and Dancers (highly skilled in balance control). Using electroencephalography, we first (experiment 1) tested the hypothesis that the influence of tactile inputs was amplified by descending cortical efferent signals. We compared the amplitude of P1N1 somatosensory cortical potential evoked by electrical stimulation of the foot sole in participants standing still with their eyes closed. We showed smaller P1N1 amplitudes in the Load compared to No Load conditions in both Non-Athletes and Dancers. This decrease neural response to tactile stimulation was associated with greater postural oscillations. By contrast in the Judoka’s group, the neural early response to tactile stimulation was unregulated in the Load condition. This suggests that the brain can selectively increase the functional gain of sensory inputs, during challenging equilibrium tasks when tactile inputs were mechanically depressed by wearing a weighted vest. In Judokas, the activation of regions such as the right posterior inferior parietal cortex (PPC) as early as the P1N1 is likely the source of the neural responses being maintained similar in both Load and No Load conditions. An overweight internal model stored in the right PPC known to be involved in maintaining a coherent representation of one’s body in space can optimize predictive mechanisms in situations with high balance constraints (Experiment 2). This hypothesis has been confirmed by showing that postural reaction evoked by a translation of the support surface on which participants were standing wearing extra-weight was improved in Judokas.
Optimizing the Treatment Schedule of Radiotherapy Combined With Anti-PD-1/PD-L1 Immunotherapy in Metastatic Cancers
Authors: Kong Yuehong , Ma Yifu , Zhao Xiangrong , Pan Jie , Xu Zhi , Zhang Liyuan
Published: March 2021

Immune checkpoint inhibitors (ICIs) targeting programmed cell death protein-1 (PD-1), and programmed cell death ligand-1 (PD-L1) have been approved for a variety of malignant tumors and are widely used to treat patients with metastatic disease. However, the efficacy of PD-1 inhibitors is limited due to tumor heterogeneity, high tumor burden, and “cold” tumor microenvironment. Radiotherapy can improve the anti-tumor effects of PD-1/PD-L1 inhibitors in various ways. As a new radiotherapy method, stereotactic body radiotherapy (SBRT) or hypofractionated radiotherapy (HFRT) provides higher doses per fraction to the target lesions, thus achieving immune activation effects and overcoming tumor resistance to anti-PD-1/PD-L1 treatment, which significantly improves the local and distant control of tumors. However, for different metastatic situations, radiotherapy plays different roles in the combination therapy. In oligometastatic status, radiotherapy can be used as a local radical treatment aiming to eliminate cancers in cooperation with systemic PD-1 inhibitors. In other circumstances, like bulky metastasis or multiple metastatic tumors, radiotherapy can be used as adjuvant to systemic immunotherapy. This review focuses on the underlying mechanisms and optimization strategies for the combination of radiotherapy and anti-PD-1/PD-L1 therapy in metastatic disease.
Lipid Transport and Metabolism at the Blood-Brain Interface: Implications in Health and Disease
Authors: Pifferi Fabien , Laurent Benoit , Plourde Mélanie
Published: March 2021

Many prospective studies have shown that a diet enriched in omega-3 polyunsaturated fatty acids (n-3 PUFAs) can improve cognitive function during normal aging and prevent the development of neurocognitive diseases. However, researchers have not elucidated how n-3 PUFAs are transferred from the blood to the brain or how they relate to cognitive scores. Transport into and out of the central nervous system depends on two main sets of barriers: the blood-brain barrier (BBB) between peripheral blood and brain tissue and the blood-cerebrospinal fluid (CSF) barrier (BCSFB) between the blood and the CSF. In this review, the current knowledge of how lipids cross these barriers to reach the CNS is presented and discussed. Implications of these processes in health and disease, particularly during aging and neurodegenerative diseases, are also addressed. An assessment provided here is that the current knowledge of how lipids cross these barriers in humans is limited, which hence potentially restrains our capacity to intervene in and prevent neurodegenerative diseases.
Attention-Based Deep Entropy Active Learning Using Lexical Algorithm for Mental Health Treatment
Authors: Ahmed Usman , Mukhiya Suresh Kumar , Srivastava Gautam , Lamo Yngve , Lin Jerry Chun-Wei
Published: March 2021

With the increasing prevalence of Internet usage, Internet-Delivered Psychological Treatment (IDPT) has become a valuable tool to develop improved treatments of mental disorders. IDPT becomes complicated and labor intensive because of overlapping emotion in mental health. To create a usable learning application for IDPT requires diverse labeled datasets containing an adequate set of linguistic properties to extract word representations and segmentations of emotions. In medical applications, it is challenging to successfully refine such datasets since emotion-aware labeling is time consuming. Other known issues include vocabulary sizes per class, data source, method of creation, and baseline for the human performance level. This paper focuses on the application of personalized mental health interventions using Natural Language Processing (NLP) and attention-based in-depth entropy active learning. The objective of this research is to increase the trainable instances using a semantic clustering mechanism. For this purpose, we propose a method based on synonym expansion by semantic vectors. Semantic vectors based on semantic information derived from the context in which it appears are clustered. The resulting similarity metrics help to select the subset of unlabeled text by using semantic information. The proposed method separates unlabeled text and includes it in the next active learning mechanism cycle. Our method updates model training by using the new training points. The cycle continues until it reaches an optimal solution, and it converts all the unlabeled text into the training set. Our in-depth experimental results show that the synonym expansion semantic vectors help enhance training accuracy while not harming the results. The bidirectional Long Short-Term Memory (LSTM) architecture with an attention mechanism achieved 0.85 Receiver Operating Characteristic (ROC curve) on the blind test set. The learned embedding is then used to visualize the activated word's contribution to each symptom and find the psychiatrist's qualitative agreement. Our method improves the detection rate of depression symptoms from online forum text using the unlabeled forum texts.
Effect of Street Performance (Busking) on the Environmental Perception of Public Space
Authors: Ho Robbie , Au Wing Tung
Published: March 2021

This is the first experimental study testing the effect of street performance (aka busking) on the subjective environmental perception of public space. It is generally believed that street performance can enhance people’s experience of public space, but studies advocating such a view have not used a control group to explicitly verify the effect of street performance. In response to this methodological limitation, we conducted two studies using experimental design. Study 1 (N = 748) was an online computer-based study where research participants evaluated the extent to which the presence vs. absence of street performance could change their perception of public space. Study 2 (N = 162) was a between-group quasi-experiment in an actual public space where people physically present in the space evaluated the perception of the space with vs. without street performance. Overall, we found converging results that street performance could make public space more visitable, more restorative, and more preferable. The current findings not only fill in a gap in the literature on street performance, but they also inform the policy making and regulations of street performance.
COVID-19-Related Stressors and Chinese Adolescents' Adjustment: The Moderating Role of Coping and Online Learning Satisfaction
Authors: Li Xiaoshan , Tang Xiujuan , Wu Hou , Sun Pengyong , Wang Min , Li Li
Published: March 2021

The present study aims to examine the main and interactive relations of COVID-19-related stressors, coping, and online learning satisfaction with Chinese adolescents' adjustment during the COVID-19 pandemic. A total of 850 adolescents from three Chinese secondary schools participated in the survey during the pandemic outbreak, and the data were analyzed by hierarchical linear regression. The results show that COVID-19-related stressors were a vulnerability factor in predicting adjustment. Adolescents' adjustment could be attributed to both individual-level (e.g., coping) and class-level (e.g., a class-level indicator of coping) characteristics. Specifically, problem-based coping and online learning satisfaction can promote adolescents' adjustment directly or serve as a buffer against the negative impact of stressors on adjustment, while emotion-based coping is a vulnerability factor in predicting adjustment directly or as a risk factor in strengthening the relation between stressors and adjustment. Compared with male adolescents and adolescents with high socio-economic status, female and impoverished adolescents reported poorer adjustment during the COVID-19 pandemic. These findings enrich our understanding of the impact of the COVID-19 pandemic on adolescents' adjustment and are helpful in improving adolescents' adjustment during the pandemic.
Effect of Coronavirus Disease 2019 on the Psychology and Behavior of Patients on Methadone Maintenance Treatment in Wuhan, China: A Clinical Observational Study
Authors: Liu Xuebing , Jin Xiaohan , Zhang Yingying , Zhang Lin , Li Yi , Ma Jun
Published: March 2021

Methadone maintenance treatment (MMT) is a national strategy adopted for the treatment of heroin dependency in China. The sudden outbreak of coronavirus disease 2019 (COVID-19) and the resultant social isolation in Wuhan have also had a significant negative impact on local patients undertaking MMT. In this study, 76 patients on MMT from the Wuhan First Health Clinic were selected as the research objects to investigate the effect of COVID-19 on the levels of stress, anxiety, and depression, as well as the withdrawal symptoms and craving and substance use. Our results revealed that, during the outbreak, the Perceived Stress Scale (PSS) score, HAMA score, HAMD score, and craving in the included patients was significantly higher than that at the baseline and post-epidemic (p < 0.01, p < 0.01, p < 0.01, p < 0.01, respectively); the positive rate of morphine and methamphetamine urine test was significantly lower than that the post-epidemic (p = 0.01, p < 0.01, respectively); the amount of tobacco used during the outbreak and the post-epidemic period was significantly higher than that at the baseline (p < 0.01, p < 0.01, respectively), while the amount of alcohol consumed at the outbreak was significantly higher than at the baseline and the post-epidemic (p < 0.01, p < 0.01, respectively). The negative emotions aroused by the COVID-19 outbreak and the accompanying social isolation to patients on MMT are an important factor of negative reinforcement that adversely affected the patients' craving for drugs and the consumption of legal substances. This finding suggests the need to strengthen the psychological counseling for patients on MMT during severe epidemic, actively alleviating the negative emotions, reducing the risk of substance abuse, and strengthening drug management after the epidemic to prevent the rise of substance (legal or illegal) abuse.
Retrievals of Aerosol Optical Depth and Spectral Absorption From DSCOVR EPIC
Authors: Lyapustin Alexei , Go Sujung , Korkin Sergey , Wang Yujie , Torres Omar , Jethva Hiren , Marshak Alexander
Published: March 2021

A new algorithm is described for joint retrievals of the aerosol optical depth and spectral absorption from EPIC observations in the UV—Vis spectral range. The retrievals are illustrated on examples of the wildfire smoke events over North America, and dust storms over greater Sahara region in 2018. An initial evaluation of single scattering albedo (SSA) at 443 nm over these regions shows a good agreement with AERONET data, generally within the uncertainty of AERONET SSA of ± 0.03. A particularly good agreement is achieved for dust with R~0.62, rmse~0.02, negligible bias, and 85% points within the expected error. This new capability is part of version 2 MAIAC EPIC algorithm. The v2 algorithm has recently completed reprocessing of the EPIC record covering the period of 2015–2020.
New Social Horizons: Anxiety, Isolation, and Animal Crossing During the COVID-19 Pandemic
Authors: Lewis Joanna E. , Trojovsky Mia , Jameson Molly M.
Published: March 2021

Increased participation in activities has been associated with improved positive mental health outcomes. However, there is much debate regarding the net effects of video games on individuals. Typified as a socially isolating activity, many games inherently contain socialization within the environment with game-generated characters or other players. Coinciding with the time of the initial pandemic/quarantine period was the release of a popular socializing and life simulation game, Animal Crossing: New Horizons. We investigated whether participation in this game was related to emotional outcomes associated with pandemics (e.g., loneliness and anxiety). The relationship between deleterious mental health and social gaming, amid a time of enforced reduction in socializing, would allow us to isolate the impact of the introduction of a social video game on improving the quality of life for players of this game. Participants (n = 1053) were asked about their time spent playing video games via an online survey, their socialization in game play, loneliness, and anxiety. We predicted that participants with higher levels of social interaction within the game would report less loneliness and anxiety. Utilizing multiple linear regression analyses, the research found that increased gaming and related activities were predictive of higher anxiety and somewhat related to increased loneliness. However, increased visits to another island were associated with lower levels of loneliness. As such, players may be utilizing gaming as a coping mechanism for anxiety. This research may inform generalized research regarding the influence that social games may have on feelings of loneliness and anxiety.
Upregulation of Fatty Acid Transporters is Associated With Tumor Progression in Non-Muscle-Invasive Bladder Cancer
Authors: Jeong Hoiseon , Oh Hwa Eun , Kim Hyesun , Lee Ju-Han , Lee Eung Seok , Kim Young-Sik , Choi Jung-Woo
Published: March 2021

As patients with non-muscle-invasive bladder cancer (NMIBC) show a high degree of heterogeneity in tumor recurrence or progression, many clinicians demand a detailed risk stratification. Although modified fatty acid metabolism in cancer cells is reported to reflect malignant phenotypes such as metastasis, the impact of fatty acid transporters on NMIBC has never been investigated. This study examined the clinicopathologic implications of fatty acid transporters such as fatty acid transport protein 4 (FATP4), cluster of differentiation 36/fatty acid translocase (CD36/FAT), and long chain acyl CoA synthetase 1 (ACSL1) in 286 NMIBC cases. This study revealed that FATP4, CD36, and ACSL1 were overexpressed in 123 (43.0%), 43 (15.0%), and 35 (12.2%) NMIBC cases, respectively. High FATP4 in tumor cells was associated with high grade (p = 0.004) and high stage (p = 0.039). High CD36 was related to high grade (p < 0.001), high stage (p = 0.002), and non-papillary growth type (p = 0.004). High ACSL1 showed an association with high grade (p < 0.001), high stage (p = 0.01), non-papillary growth type (p = 0.002), and metastasis (p = 0.033). High FATP4 was an independent factor predicting short overall survival (OS) (hazard ratio = 3.32; 95% confidence interval, 1.07–10.31; p = 0.038). In conclusion, upregulation of FATP4, CD36, and ACSL1 might promote the NMIBC progression and could be exploited in clinical risk stratification and targeted therapy.
Rac3 Expression and its Clinicopathological Significance in Patients With Bladder Cancer
Authors: Chen Mei , Nie Zhenyu , Cao Hui , Gao Yuanhui , Wen Xiaohong , Zhang Chong , Zhang Shufang
Published: March 2021

Background: Ras-related C3 botulinum toxin substrate 3 (Rac3) is overexpressed in malignancies and promotes tumor progression. However, the correlations between Rac3 expression and the clinicopathological characteristics and prognoses of patients with bladder cancer (BC) remain unclear.

Methods: Data from The Cancer Genome Atlas (TCGA) were used to analyze Rac3 expression in BC and normal bladder tissues and validated using the Oncomine database, quantitative real-time PCR (qRT-PCR) and western blot. The Kaplan-Meier method was used to analyze the relationship between Rac3 expression and the prognosis of patients with BC. Cox univariate and multivariate analyses of BC patients overall survival (OS) were performed. Signaling pathways that potentially mediate Rac3 activity in BC were then analyzed by gene set enrichment analysis (GSEA).

Results: The Rac3 expression in BC tissues was significantly higher than that in normal bladder tissues. Rac3 expression was significantly correlated with grade and stage. Overexpression of Rac3 was associated with a poor prognosis. GSEA showed that the cell cycle, DNA replication, p53 signaling pathway and mismatch repair were differentially enriched in the high Rac3 expression phenotype. The qRT-PCR and western blot results confirmed that the Rac3 expression in BC tissues was higher than that in normal bladder tissues.

Conclusion: Rac3 is highly expressed in BC, which is related to the advanced clinicopathological variables and adverse prognosis of patients with BC. These results provide a new therapeutic target for BC.
High GP73 Expression Correlates with Poor Response to Neoadjuvant Chemotherapy and Survival in Gastric Cancer: A Tissue Microarray Study
Authors: Shen Jian Guo , Shen Jun , Teng Rong Yue , Wang Lin Bo , Zhao Wen He , Wang Qin Chuan
Published: March 2021

Golgi protein 73 (GP73) is a type II Golgi transmembrane protein which is overexpressed in several cancers, however, its role in gastric cancer is still unclear. The aim of this study is to investigate if high GP73 expression is associated with pathological tumor response to neoadjuvant chemotherapy and prognosis for patients with gastric cancer. A total of 348 patients with gastric cancer, who had undergone surgery between 1999 and 2011 were retrospectively reviewed, GP73 expression was examined in tumor tissues using tissue microarray and the correlations between its expression and pathological response to neoadjuvant chemotherapy as well as patients prognosis were analyzed. We found that GP73 expression was not associated with clinicopathologic features including tumor size, differentiation and TNM stage. High expression of GP73 was associated with less pathological tumor response to neoadjuvant chemotherapy and poor survival in gastric cancer, multivariate analysis showed GP73 expression was an independent predictive factor for pathological response to neoadjuvant chemotherapy and for prognosis in patients with gastric cancer. Our results suggest that GP73 expression correlates with the effect of neoadjuvant chemotherapy and is a promising biomarker to identify patients with poor prognosis.
Factors Associated with Survival From Xp11.2 Translocation Renal Cell Carcinoma Diagnosis—A Systematic Review and Pooled Analysis
Authors: Wu Yuqing , Chen Saisai , Zhang Minhao , Liu Kuangzheng , Jing Jibo , Pan Kehao , Zhang Lihua , Xu Bin , Lu Xiaoming , Chen Ming
Published: March 2021

Purpose: Xp11.2 translocation renal cell carcinoma (Xp11.2 tRCC) is a rare subtype of renal cell carcinoma (RCC), characterized by translocations of Xp11.2 breakpoints, involving of the transcription factor three gene (TFE3). The aim of our study was to comprehensively characterize the clinical characteristics and outcomes, and to identify risk factors associated with OS and PFS in Xp11.2 tRCC patients.

Methods: Literature search on Xp11.2 tRCC was performed using databases such as pubmed EMBASE and Web of Science. Studies were eligible if outcomes data (OS and/or PFS) were reported for patients with a histopathologically confirmed Xp11.2 tRCC. PFS and OS were evaluated using the univariable and multivariable Cox regression model.

Results: There were 80 eligible publications, contributing 415 patients. In multivariable analyses, the T stage at presentation was significantly associated with PFS (HR: 3.87; 95% CI: 1.70 to 8.84; p = 0.001). The median time of PFS was 72 months. In the multivariable analyses, age at diagnosis (HR: 2.16; 95% CI: 1.03 to 4.50; p = 0.041), T stage at presentation (HR: 4.44; 95% CI: 2.16 to 9.09; p < 0.001) and metastasis status at presentation (HR: 2.67; 95% CI: 1.12 to 6.41; p = 0.027) were all associated with OS, with a median follow-up time of 198 months.

Conclusion: T stage at presentation is the only factor that is associated with both PFS and OS in patients with Xp11.2 tRCC. Also, patients over 45 or with metastases are more likely to have poorer OS.
Case Report: Incidentally Discovered a Rare Cystic Lesion of Liver: Multicystic Biliary Hamartoma
Authors: Mu Wentao , Su Peng , Ning Shanglei
Published: March 2021

Multicystic biliary hamartoma (MCBH) is an extremely rare cystic lesion of the liver. A 37-year old male patient was admitted to our hospital for incidentally discovered hepatic cystic lesions on abdominal ultrasonography. Abdominal contrast-enhanced computed tomography (CT) showed a multilocular cystic lesion in the segment VI, with mild enhancement in the septae and peripheral wall within the lesion. Only alanine transaminase (ALT) and carbohydrate antigen 19–9 (CA19–9) increased slightly above normal value. Preoperative tests suggested possibility of a benign mucinous cystic neoplasm (MCN) or intraductal papillary neoplasm of the bile duct (IPNB). Laparoscopic complete resection of the lesion was performed. Histopathological examination showed numerous variably sized ductal structures surrounded by periductal glands and fibrous connective tissues containing small blood vessels and smooth muscle bundles. Immunohistochemical staining (IHC) revealed that dilated ducts were positive for cytokeratin CK19, characteristic for biliary tract. Histopathological findings confirmed diagnosis of multicystic biliary hamartoma (MCBH). No recurrence occurred during 6 months follow-up. In conclusion, MCBH should be differentiating from hepatic cystic lesion and could be resected laparoscopically safely.