bluuebunny/crossref_metadata_2025 huggingface dataset:
Interaction of Neurovascular Signals in the Degraded Condylar Cartilage
Authors: Qin Wenpin , Zhang Zibin , Yan Jianfei , Han Xiaoxiao , Niu Li-Na , Jiao Kai
Published: April 2022

Introduction: Degradation of the condylar cartilage during temporomandibular joint osteoarthritis (TMJ-OA) results in the infiltration of nerves, blood vessels and inflammatory cells from the subchondral bone into the cartilage. The interaction among innervation, angiogenesis and inflammation in the condylar cartilage of TMJ-OA remains largely unknown.

Method: In the present study, microarray-based transcriptome analysis was used to detect, and quantitative real-time polymerase chain reaction was used to validate transcriptome changes in the condylar cartilage from a well-established rat TMJ-OA model. Gene ontology (GO), Kyoto encyclopedia of genes and genomes (KEGG) pathway and protein-protein interaction (PPI) analyses were conducted.

Result: There were 1817 differentially expressed genes (DEGs, fold change ≥2, p < 0.05) between TMJ-OA and control cartilages, with 553 up-regulated and 1,264 down-regulated genes. Among those genes, representative DEGs with known/suspected roles in innervation, angiogenesis and inflammation were further validated by enriched GO terms and KEGG pathways. The DEGs related to innervation were predominately enriched in the GO terms of neurogenesis, generation of neurons, and KEGG pathways of cholinergic synapse and neurotrophin signaling. Genes related to angiogenesis were enriched in GO terms of vasculature and blood vessel development, and KEGG pathways of hypoxia-inducible factor 1 (HIF-1) pathway and calcium signaling pathway. For inflammation, the DEGs were enriched in the GO terms of immune system process and immune response, and KEGG pathways of Toll-like receptor and transforming growth factor β (TGFβ) signaling. Analysis with PPI indicated that the aforementioned DEGs were highly-interacted. Several hub genes such as v-akt murine thymoma viral oncogene homolog 1 (Akt1), glycogen synthase kinase 3β (Gsk3b), fibroblast growth factor 2 (Fgf2) and nerve growth factor receptor (Ngfr) were validated.

Conclusion: The present study demonstrated, for the first time, that intimate interactions exist among innervation, angiogenesis and inflammation in the condylar cartilage of TMJ-OA.
Integrin Crosstalk and Its Effect on the Biological Functions of the Trabecular Meshwork/Schlemm’s Canal
Authors: Faralli Jennifer A. , Filla Mark S. , Peters Donna M.
Published: April 2022

Integrins are a family of heterodimeric receptors composed of an α- and β-subunit that mediate cell-adhesion to a number of extracellular matrix (ECM) proteins in the Trabecular Meshwork/Schlemm’s canal (TM/SC) of the eye. Upon binding an ECM ligand, integrins transmit signals that activate a number of signaling pathways responsible for regulating actin-mediated processes (i.e phagocytosis, cell contractility, and fibronectin fibrillogenesis) that play an important role in regulating intraocular pressure (IOP) and may be involved in glaucoma. An important function of integrin-mediated signaling events is that the activity of one integrin can affect the activity of other integrins in the same cell. This creates a crosstalk that allows TM/SC cells to respond to changes in the ECM presumably induced by the mechanical forces on the TM/SC, aging and disease. In this review, we discuss how integrin crosstalk influences the function of the human TM/SC pathway. In particular, we will discuss how different crosstalk pathways mediated by either the αvβ3 or α4β1 integrins can play opposing roles in the TM when active and therefore act as on/off switches to modulate the cytoskeleton-mediated processes that regulate the outflow of aqueous humor through the TM/SC.
A Multicomponent Polymer-Metal-Enzyme System as Electrochemical Biosensor for H2O2 Detection
Authors: Tong Pengfei , Asif Muhammad , Ajmal Muhammad , Aziz Ayesha , Sun Yimin
Published: April 2022

Herein, an Au nanoparticles-polydopamine-poly acrylic acid-graphene (Au NPs-PDA-PAA-graphene) multicomponent nanohybrid is fabricated by surface functionalization of graphene alongside extensive in-situ growth of Au nanoparticles. The as-obtained nanocomposite possesses good hydrophilicity, excellent biocompatibility and high biomolecules loading capacity, which acts as an ideal platform for enzyme modification. Considering this fact, Horseradish peroxidase is expressively immobilized upon Au NPs-PDA-PAA-graphene surface, in order to lay the foundations of a biosensor that is majorly based on enzymatic activity. The biosensor exhibits higher sensitivity towards the determination of H2O2 with linearity ranging from 0.1 μm upto 20 mm, and the limit of detection going down to 0.02 μm. Encouraged by its acceptable electrocatalytic performance, this multicomponent system can also be easily employed for carrying out the real-time tracking of H2O2 coming out of Macrophage cells. Therefore, this work designs an extraordinarily updated platform for biosensing related applications, and also presents a reliable platform for the direct detection of H2O2in vivo and in vitro, which show great potential in bioelectroanalytical chemistry, cellular biology, and pathophysiology.
Bimetallic Cobalt–Copper Nanoparticle-Decorated Hollow Carbon Nanofibers for Efficient CO2 Electroreduction
Authors: He Congyi , Wang Siyu , Jiang Xingxing , Hu Qi , Yang Hengpan , He Chuanxin
Published: April 2022

Bimetallic materials are one of the most promising catalysts for the electrochemical reduction of CO2, but there are still many challenges to be overcome on the route to industrialization. Herein, a series of carbon nanofiber-supported bimetallic cobalt–copper catalysts (CoxCuy/CFs) are designed and constructed through the electrospinning technique and a subsequent pyrolysis procedure. Small-sized Co–Cu nanoparticles are homogenously distributed on the porous carbon nanofibers, which can significantly improve the utilization rate of metal sites and greatly reduce the loading amount of metals. Moreover, different product distributions and catalytic performance can be obtained in CO2 reduction via adjusting the metal proportion of CoxCuy/CFs. Especially, Co3Cu/CFs can bring forth a 97% total faradaic efficiency (FE) of CO (68%) and HCOOH (29%) at –0.8 VRHE cathode potential in 0.5 M KHCO3 electrolyte. Furthermore, the hierarchical pores can firmly confine the small Co–Cu nanoparticles and keep them from easy agglomeration during electrolysis, eventually leading to 60 h of stability for Co3Cu/CFs in CO2 electroreduction. This study might provide a facile and economic method to fabricate efficient bimetallic catalysts for CO2 electroreduction and other electrocatalysis applications.
Separation of Sulfate Anion From Aqueous Solution Governed by Recognition Chemistry: A Minireview
Authors: Chen Si-Qi , Zhao Wei , Wu Biao
Published: April 2022

The sulfate anion (SO42–) is known as an end metabolite of cysteine and methionine, and its proper concentration is associated with the expression of key functions in the physiological system. Thus, maintaining sulfate concentration at a precise level is of great significance for biology, environments, and industrial productions. Fundamental research for sulfate anion chemistry can help understand sulfate-associated physiological processes and related applications, for example, remediation. In this minireview, we summarized recent research progresses in sulfate recognition and separation using crystallization and liquid–liquid extraction. We focused on the studies wherein molecular recognition is the key element and is considered the driving force for selective sulfate separations from aqueous solution.
The Mediating Effect of Social Anxiety on the Relationship Between Social Media Use and Body Dissatisfaction Among University Students
Authors: Jarrar Yosra , Awobamise Ayodeji O. , Nweke Gabriel E.
Published: April 2022

Body dissatisfaction has become increasingly common among women and young adults and has only become worse in the digital age, where people have increased access to social media and are in constant competition and comparisons with their “friends” on their different social media platforms. While several studies have looked at the relationship between social media and body dissatisfaction, there is an obvious dearth of empirical studies on the mediating role of social anxiety- a gap this study hoped to address. Using a cross-sectional research design, this study examined the mediating role of social anxiety on the relationship between social media usage and body dissatisfaction. The sample consisted of 432 students from Kampala International University and Victoria University in Uganda. The findings show a significant positive relationship between social media usage and body dissatisfaction. The findings prove that heavy users of social media are significantly more likely to suffer from body dissatisfaction. In a similar vein, the findings show that there is a significant positive relationship between social media usage and social anxiety. This suggests that people that frequently make use of social media have a much higher chance of suffering from social anxiety, that is the inability or difficulty to engage in social interactions, than people that rarely or moderately make use of social media. Finally, findings show that social anxiety mediates the relationship between social media usage and body dissatisfaction. It indicates that people with high levels of social anxiety are more likely to suffer from body dissatisfaction as a direct result of heavy social media usage. These findings imply that although heavy users of social media tend to have a more negative perception of their body, if these same users can properly engage in social interactions, then this might mitigate the negative effects of social media usage (in terms of body dissatisfaction).
Adenosine A2a Receptor Regulates Autophagy Flux and Apoptosis to Alleviate Ischemia-Reperfusion Injury via the cAMP/PKA Signaling Pathway
Authors: Xia Yun , He Feng , Moukeila Yacouba Mohamed Bassirou , Zhou Huimin , Li Jingfan , Xiong Ying , Zhang Jingjing , Li Hui , Wang Yanlin , Ke Jianjuan
Published: April 2022

Exploring effective methods to lessen myocardial ischemia-reperfusion injury still has positive significance. The adenosine A2a receptor (A2aR) has played a crucial part in cardiac ischemia-reperfusion injury. Previous studies revealed that the adenosine A2a receptor regulated autophagy, but the specific mechanism in myocardial ischemia-reperfusion injury was still unclear. We established an ischemia-reperfusion model (30 min of ischemia and 2 h of reperfusion) in vivo and a model with oxygen-glucose deprivation for 6 h and reoxygenation for 18 h (OGDR) in vitro. The ischemia-reperfusion injury resulted in prolonged QTc interval, left ventricular systolic dysfunction, and myocardial infarction. In vitro model, we found that the OGDR-induced autophagosomes and apoptosis caused myocardial cell death, as evidenced by a significant increase in the generation of lactate dehydrogenase and creatine kinase-MB. Furthermore, overactivated autophagy with rapamycin showed an anti-apoptotic effect. The interaction between autophagy and apoptosis in myocardial ischemia-reperfusion injury was complex and variable. We discovered that the activation of adenosine A2a receptor could promote the expression of Bcl-2 to inhibit the levels of Beclin-1 and LC3II. The number of autophagosomes exceeded that of autolysosomes under OGDR, but the result reversed after A2aR activation. Activated A2aR with its agonist CGS21680 before reperfusion saved cellular survival through anti-apoptosis and anti-autophagy effect, thus improving ventricular contraction disorders, and visibly reducing myocardial infarction size. The myocardial protection of adenosine A2a receptor after ischemia may involve the cAMP-PKA signaling pathway and the interaction of Bcl-2-Beclin-1.
Evaluation of Stroke Risk in Patients With Atrial Fibrillation Using Morphological and Hemodynamic Characteristics
Authors: Wang Lingfeng , Wang Zidun , Fang Runxin , Li Zhi-Yong
Published: April 2022

Background

It is well known that the thrombus triggering stroke in patients with atrial fibrillation (AF) mainly comes from the left atrial appendage (LAA). This study aims to characterize the morphological and hemodynamic parameters and evaluate their differences between AF patients with and without a stroke history.

Methods

Cardiac CT images were obtained from AF patients with (n = 10) and without a history of stroke (n = 10). 3D models of the left atrium (LA) were reconstructed by processing the CT image, and the LA/LAA morphological parameters were measured. Computational fluid dynamics (CFD) simulations were performed to calculate the hemodynamic parameters in LA. The species-transport model and discrete phase model (DPM) were applied to analyze blood residual ratio and particle residual ratio, two qualitative parameters for thrombus formation and flow-out potential, respectively.

Results

There were significant differences in LAA actual depth (p = 0.002), and direct length (p = 0.049) between the non-stroke and stroke groups. Significant differences were also found in certain hemodynamic parameters. The blood residual ratio in LAA was significantly smaller in the stroke group than in the non-stroke group (p < 0.05). Moreover, the particle residual ratio within LAA was significantly smaller in the stroke groups than in the non-stroke group (p < 0.05).

Conclusion

There are significant differences in both morphological and hemodynamic parameters between AF patients with and without a stroke history. A high blood residual ratio in LAA confirms that thrombus is more likely to form in AF patients. A significantly smaller particle residual ratio in the stroke group may suggest the thrombus formed with LAA is more likely to flow out of LAA, leading to a higher risk of stroke. The proposed morphological and hemodynamic parameters may be additional risk factors that can be used to better risk stratify AF patients.
Association of Sodium-Glucose Cotransporter 2 (SGLT2) Inhibitor Use With Cardiovascular and Renal Outcomes in Type 2 Diabetes Mellitus Patients With Stabilized Acute Myocardial Infarction: A Propensity Score Matching Study
Authors: Chang Ting-Yung , Lu Chi-Ting , Huang Hsin-Lei , Chou Ruey-Hsing , Chang Chun-Chin , Liu Chung-Te , Huang Po-Hsun , Lin Shing-Jong
Published: April 2022

Background

Coronary artery disease (CAD) is one of the leading causes of morbidity and mortality in patients with type 2 diabetes mellitus (T2DM), who are at a greater risk of acute myocardial infarction (AMI) and sudden cardiac death. Sodium-glucose cotransporter 2 (SGLT2) inhibitors have been shown to reduce cardiovascular events and mortality in T2DM patients with a risk of cardiovascular disease. This study aimed to investigate the effect of SGLT2 inhibitor use on the adverse cardiovascular and renal outcomes in T2DM patients with AMI.

Methods

A total of 1,268 patients admitted to the Coronary Care Unit due to AMI were retrospectively screened.Patients taking SGLT2 inhibitors before or during the index AMI hospitalization were assigned as group 1. Patients who never received SGLT2 inhibitors were assigned as group 2. Patients in groups 1 and 2 were matched in a 1:2 ratio, and 198 T2DM patients with stabilized AMI were retrospectively enrolled for the final analysis.

Results

With a mean follow-up period of 23.5 ± 15.7 months, 3 (4.5%) patients in group 1 and 22 (16.7%) patients in group 2 experienced rehospitalization for acute coronary syndrome (ACS), while 1 (1.5%) patient in group 1 and 7 (5.3%) patients in group 2 suffered sudden cardiac death. The Kaplan–Meier curves demonstrated that the patients in group 1 had a lower risk of adverse cardiovascular outcomes. According to the multivariate analysis, the baseline estimated glomerular filtration rate (eGFR) (P = 0.008, 95% CI: 0.944–0.991) and the use of SGLT2 inhibitors (P = 0.039, 95% CI: 0.116–0.947) were both independent predictors of adverse cardiovascular outcomes. On the other hand, the use of SGLT2 inhibitors was not associated with adverse renal outcomes.

Conclusion

In T2DM patients with stabilized AMI, the use of SGLT2 inhibitors was associated with a lower risk of adverse cardiovascular outcomes. In addition, the baseline renal function was also an independent predictor of adverse cardiovascular outcomes.
Teaching History in a Post-pandemic World: The Perceptions of Teachers on Training
Authors: Muñoz Carlos , Torres Bastián , Martínez Rosendo , Carrillo Olga
Published: April 2022

The purposes of the study were (1) to identify the level of knowledge that teachers in training have on globalization and the world health situation in recent years, with the aim of discovering the critical knots that exist; and (2) to understand the perceptions that teachers in training have on the foundations and purposes of history teaching on the current context of globalization and the health situation. The study is part of the project Proyecto FONDECYT Regular No. 1221872 titled El Desarrollo de habilidades de pensamiento histórico para vivir en sociedad. Tensiones, desafíos y propuestas para el sistema escolar chileno (Historical thinking abilities development to live in society. Tensions, challenges, and proposals for the Chilean school system) and part of the project El desarrollo de habilidades, pensamiento histórico de estudiantes de Pedagogía en Historia y Geografía de la Universidad de Concepción: un estudio de caso para la mejora de la formación inicial docente (Skills development, historical thinking of History and Geography teaching students of the Universidad de Concepción: A case study for the improvement of initial teaching training) (UCO-1798). The information was collected through in-depth interviews with 30 teachers in training of both sexes from the last five cohorts. The results show that teachers in training recognize the importance of teaching history in order for people to know their culture and their past, and to commit themselves in the construction of democratic societies. Moreover, and despite the fact that they perceive their university training to be deficient, which is associated with globalization and the pandemic, teachers in training are able to identify elements and characteristics of both phenomena. This enables them to conduct historical analyses that highlight the existence of skills associated with the development of historical thinking.
Low-Temperature Thermal Conductivity of the Two-Phase Superconductor CeRh2As2
Authors: Onishi Seita , Stockert Ulrike , Khim Seunghyun , Banda Jacintha , Brando Manuel , Hassinger Elena
Published: April 2022

CeRh2As2is a rare unconventional superconductor (Tc= 0.26 K) characterized by two adjacent superconducting phases for a magnetic fieldH‖c-axis of the tetragonal crystal structure. Antiferromagnetic order, quadrupole-density-wave order (T0= 0.4 K) and the proximity of this material to a quantum-critical point have also been reported: The coexistence of these phenomena with superconductivity is currently under discussion. Here, we present thermal conductivity and electrical resistivity measurements on a single crystal of CeRh2As2between 60 mK and 200 K and in magnetic fields (H‖c) up to 8 T. Extrapolation of our normal-state data to zero temperature validates the Wiedemann-Franz law within the error bars. TheTdependence of the thermal conductivityκ(T) shows a pronounced drop belowTcwhich is also field dependent and thus interpreted as the signature of superconductivity. However, the large residual resistivity and the lack of sharp anomalies inκ(T) at the expected transition temperatures clearly indicate that samples of much higher purity are required to gain more information about the superconducting gap structure.
Assessing Obesity-Related Adipose Tissue Disease (OrAD) to Improve Precision Medicine for Patients Living With Obesity
Authors: Pincu Yair , Yoel Uri , Haim Yulia , Makarenkov Nataly , Maixner Nitzan , Shaco-Levy Ruthy , Bashan Nava , Dicker Dror , Rudich Assaf
Published: April 2022

Obesity is a heterogenous condition that affects the life and health of patients to different degrees and in different ways. Yet, most approaches to treat obesity are not currently prescribed, at least in a systematic manner, based on individual obesity sub-phenotypes or specifically-predicted health risks. Adipose tissue is one of the most evidently affected tissues in obesity. The degree of adipose tissue changes – “adiposopathy”, or as we propose to relate to herein as Obesity-related Adipose tissue Disease (OrAD), correspond, at least cross-sectionally, to the extent of obesity-related complications inflicted on an individual patient. This potentially provides an opportunity to better personalize anti-obesity management by utilizing the information that can be retrieved by assessing OrAD. This review article will summarize current knowledge on histopathological OrAD features which, beyond cross-sectional analyses, had been shown to predict future obesity-related endpoints and/or the response to specific anti-obesity interventions. In particular, the review explores adipocyte cell size, adipose tissue inflammation, and fibrosis. Rather than highly-specialized methods, we emphasize standard pathology laboratory approaches to assess OrAD, which are readily-available in most clinical settings. We then discuss how OrAD assessment can be streamlined in the obesity/weight-management clinic. We propose that current studies provide sufficient evidence to inspire concerted efforts to better explore the possibility of predicting obesity related clinical endpoints and response to interventions by histological OrAD assessment, in the quest to improve precision medicine in obesity.
Identification and Validation of Autophagy-Related Genes in Diabetic Retinopathy
Authors: Wang Nan , Wei Linfeng , Liu Die , Zhang Quyan , Xia Xiaobo , Ding Lexi , Xiong Siqi
Published: April 2022

Background

Diabetic retinopathy (DR) is one of the most common microvascular complications of diabetes, which is associated with damage of blood-retinal barrier and ischemia of retinal vasculature. It devastates visual acuity due to leakage of retinal vessels and aberrant pathological angiogenesis in diabetic patients. The etiology of DR is complex, accumulated studies have shown that autophagy plays an important role in the pathogenesis of DR, but its specific mechanism needs to be further studied.

Methods

This study chose the online Gene Expression Omnibus (GEO) microarray expression profiling dataset GSE146615 to carry on the research. Autophagy-related genes that were potentially differentially expressed in DR were screened by R software. Then, the differentially expressed autophagy-related genes were analyzed by correlation analysis, tissue-specific gene expression, gene-ontology (GO) enrichment analysis, Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway enrichment analysis and protein-protein interaction (PPI) network analysis. Finally, retinal pigment epithelial cell line (ARPE-19) incubated with high glucose (HG) was used to mimic the DR model, and the mRNA level of key genes was verified by quantitative real-time polymerase chain reaction (qRT-PCR) in vitro.

Results

A total of 23 differentially expressed autophagy-related genes (9 up-regulated genes and 14 down-regulated genes) were identified by differential expression analysis. The analysis of tissue-specific gene expression showed that these differentially expressed autophagy-related genes were enriched in the retina. GO and KEGG enrichment analysis showed that differentially expressed autophagy-related genes were significantly enriched in autophagy-related pathways such as regulation of autophagy and macroautophagy. Then 10 hub genes were identified by PPI network analysis and construction of key modules. Finally, qRT-PCR confirmed that the expression of MAPK3 in the DR model was consistent with the results of bioinformatics analysis of mRNA chip.

Conclusion

Through bioinformatics analysis, we identified 23 potential DR autophagy-related genes, among which the down-regulated expression of MAPK3 may affect the occurrence and development of DR by regulating autophagy. It provides a novel insight into the pathogenesis of DR.
Addressing Consumerism and the Planetary Health Crisis: Behavioral Economics Approach in Public Policy
Authors: Sarkar Atanu
Published: April 2022

A pervasive sense of dissatisfaction is driving an unstoppable longing for materialistic things, resulting in anthropogenic disruptions of the earth’s natural systems. Behavioral economics integrates insights from psychological research into economic science. This policy brief explores how behavioral economics can be a practical approach citizens can use to adopt pro-environmental behavior without significant economic interference. It is worth examining why some people maintain the status quo by not embracing green options despite knowing their positive environmental impacts and even after financial incentives are offered for such options. Human decision anomalies are often driven by simple intuition, with decisions made by mental shortcuts known as heuristics. Nudging people and setting up a choice architecture may be a better way to alter people’s behavior to adopt a pro-environment lifestyle.
Small Run-of-River Dams Affect Taxonomic and Functional β-Diversity, Community Assembly Process of Benthic Diatoms
Authors: Wang Yixia , Wu Naicheng , Tang Tao , Zhou Shuchan , Cai Qinghua
Published: April 2022

Being increasingly constructed worldwide, dams are a main driver of flow regime change and biodiversity decline. Although small run-of-river dams have exceeded the number of large dams, their impacts on taxonomic and functional β-diversity as well as community assembly process of aquatic organisms have been largely neglected. Ninety sites within twenty three small run-of-river dams in the Xiangxi River were selected, and the hydrological and physicochemical variables for each site were measured. We analyzed the traits and β-diversity of benthic diatoms, and explored the key driving mechanism of benthic diatom community assembly. Our results indicated that the construction of small run-of-river dams could affect the β-diversity of benthic diatoms and the mechanism of community assembly. Specifically, we found that small run-of-river dams could change the relative contribution of nestedness components to the trait-based β-diversity of benthic diatoms, but generally the taxonomy-based β-diversity was relatively higher than the trait-based β-diversity. Furthermore, the community assembly process of benthic diatoms was also affected. In areas affected directly by small run-of-river dams, dispersal assembly was the key mechanism for community assembly. Compared to unregulated habitats, the dispersal assembly process between the impacted and the unregulated habitats has been enhanced. We advocate that this study can be expanded to other organisms (such as macroinvertebrates, phytoplankton, fish) in future to fully understand impacts of small run-of-river dams on biodiversity from a multi-trophic level aspect. Based on our results, we suggest that maintaining genetic and ecological connectivity based on an effective impact assessment in dry seasons is a potential solution to mitigate the impacts of such dams, as key to adaptive management and sustainability.
Replicated Spatial Point Pattern Analyses for Ecological Inference: A Tutorial Using the RSPPlme4 Package in R
Authors: Bagchi Robert , LaScaleia Michael C. , Milici Valerie R. , Dalui Dipanjana
Published: April 2022

The analysis of spatial point patterns has greatly advanced our understanding of ecological processes. However, the methods currently available for analyzing replicated spatial point patterns (RSPPs) are rarely used by ecologists. One barrier to the use of RSPP analyses is a lack of software to implement the approaches that have been developed in the statistical literature. Here, we provide a practical guide to RSPP analysis and introduce the RSPPlme4 R package that implements the approaches we discuss. The methods we outline use a linear modeling framework to link variation in the spatial structure of point patterns to discrete and continuous explanatory covariates. We describe methods for linear models and mixed-effects models of RSPPs, including approaches to estimating confidence intervals via semi-parametric bootstrapping. The syntax for model fitting is similar to that used in linear and linear mixed-effects modeling packages in R. The RSPPlme4 package also allows users to easily plot the results of model fits. We hope that this tutorial will make methods for RSPP analysis accessible to a wide range of ecologists and open new avenues for gaining insight into ecological processes from spatial data.
Predictive Ecological Land Classification From Multi-Decadal Satellite Imagery
Authors: Sousa Daniel , Davis Frank W. , Easterday Kelly , Reynolds Mark , Riege Laura , Butterfield H. Scott , Katkowski Moses
Published: April 2022

Ecological land classifications serve diverse purposes including sample stratification, inventory, impact assessment and environmental planning. While popular, data-driven classification approaches can require large training samples, frequently with limited robustness to rapid environmental change. We evaluate the potential to derive useful, durable ecological land classifications from a synthesis of multi-decadal satellite imagery and geospatial environmental data. Using random forests and multivariate regression trees, we analyze 1982–2000 Landsat Thematic Mapper (L45) and 2013–2020 Harmonized Landsat Sentinel (HLS) imagery to develop and then test the predictive skill of an ecological land classification for monitoring Mediterranean-climate oak woodlands at the recently established Jack and Laura Dangermond Preserve (JLDP) near Point Conception, California. Image pixels were processed using spectral and temporal mixture models. Temporal mixture model residual scores were highly correlated with oak canopy cover trends between 2012 and 2020 (r2 = 0.74, p << 0.001). The resulting topoclimatic-edaphic land classification effectively distinguished areas of systematically higher or lower oak dieback during 2012–2020 severe drought, with a fivefold difference in dieback rates between land classes. Our results highlight the largely untapped potential for developing predictive ecological land classifications from multi-decadal satellite imagery to guide scalable, ground-supported monitoring of rapid environmental change.
Case Report: Two Novel L1CAM Mutations in Two Unrelated Chinese Families With X-Linked Hydrocephalus
Authors: Zhou Hang , Yu Qiuxia , Li Yingsi , Fu Fang , Li Ru , Chen Guilan , Wang Dan , Lu Yan , Yang Xin , Li Dongzhi , Liao Can
Published: April 2022

L1 cell adhesion molecule is a type I transmembrane glycoprotein belonging to the immunoglobulin superfamily. Pathogenic mutations of L1CAM can cause L1 syndrome, referred to as a variety of disease spectrums characterized by hydrocephalus. In the present study, we reported two novel variants of L1CAM in two unrelated Chinese families with fetal hydrocephalus history. The woman of family 1, with three consecutive adverse birth histories of male fetuses with hydrocephalus, was identified by an exome sequence with a heterozygous mutation in the L1CAM gene, NM_000425.4: c.1696_1703 + 14del (p. S566Vfs*35), which was predicted to be pathogenic. It is predicted to disrupt RNA splicing and likely leads to an absent or disrupted protein product. In family 2, the mother, previously with once a voluntary termination of pregnancy owning to the fetus with hydrocephalus, was pregnant with a fetus with hydrocephalus in her second pregnancy. After fetal blood sampling, a pathogenic deletion of 1511bp in L1CAM, chromosome X: 153131395-153132905(hg19/GRCh37)/NM_000425.4: c.2043_2432-121del1511 leading to deletion of fibronectin type-III repeats I-II, was identified in the fetus with hydrocephalus inherited from the mother by an exome sequence. On her third pregnancy, a healthy female fetus was born without the L1CAM variant by preimplantation genetic testing for the monogenic disorder. This study emphasizes the importance of ultrasonic manifestation and family history of fetal hydrocephalus for L1CAM diagnosis. Our study expands the genotypes of L1CAM and aids the genetic counseling of fetal hydrocephalus and even preimplantation genetic testing for the monogenic disorder.
Analysis of the lncRNA–miRNA–mRNA Network Reveals a Potential Regulatory Mechanism of EGFR-TKI Resistance in NSCLC
Authors: Ding Dandan , Zhang Jufeng , Luo Zhiming , Wu Huazhen , Lin Zexiao , Liang Weicheng , Xue Xingyang
Published: April 2022

Epidermal growth factor receptor tyrosine kinase inhibitors (EGFR-TKIs) are widely used for patients with EGFR-mutated lung cancer. Despite its initial therapeutic efficacy, most patients eventually develop drug resistance, which leads to a poor prognosis in lung cancer patients. Previous investigations have proved that non-coding RNAs including long non-coding RNAs (lncRNAs), circular RNAs (circRNAs), and microRNAs (miRNAs) contribute to drug resistance by various biological functions, whereas how they regulate EGFR-TKI resistance remains unclear. In this study, we examined gene expression using the microarray technology on gefitinib-resistant NSCLC cells to obtain differentially expressed (DE) lncRNAs and mRNAs. A total of 45 DE-lncRNAs associated with overall survival and 1799 target DE-mRNAs were employed to construct a core lncRNA–miRNA–mRNA network to illustrate underlying molecular mechanisms of how EGFR-TKI resistance occurs in NSCLC. We found that target DE-mRNAs were mainly enriched in pathways involved in EGFR-TKI resistance, especially the target DE-mRNAs regulated by LINC01128 were significantly enriched in the PI3K/Akt signaling pathway, where the synergy of these target DE-mRNAs may play a key role in EGFR-TKI resistance. In addition, downregulated LINC01128, acting as a specific miRNA sponge, decreases PTEN via sponging miR-25-3p. Furthermore, signaling reactions caused by the downregulation of PTEN would activate the PI3K/Akt signaling pathway, which may lead to EGFR-TKI resistance. In addition, a survival analysis indicated the low expression of LINC01128, and PTEN is closely related to poor prognosis in lung adenocarcinoma (LUAD). Therefore, the LINC01128/miR-25-3p/PTEN axis may promote EGFR-TKI resistance via the PI3K/Akt signaling pathway, which provides new insights into the underlying molecular mechanisms of drug resistance to EGFR-TKIs in NSCLC. In addition, our study sheds light on developing novel therapeutic approaches to overcome EGFR-TKI resistance in NSCLC.
Prenatal Exposure to a Climate-Related Disaster Results in Changes of the Placental Transcriptome and Infant Temperament
Authors: Buthmann Jessica , Huang Dennis , Casaccia Patrizia , O’Neill Sarah , Nomura Yoko , Liu Jia
Published: April 2022

Maternal stress during pregnancy exerts long-term effects on the mental well-being of the offspring. However, the long-term effect of prenatal exposure on the offspring’s mental status is only partially understood. The placenta plays a vital role in connecting the maternal side to the fetus, thereby serving as an important interface between maternal exposure and fetal development. Here, we profiled the placental transcriptome of women who were pregnant during a hurricane (Superstorm Sandy), which struck New York City in 2012. The offspring were followed longitudinally and their temperament was assessed during the first 6–12 months of age. The data identified a significant correlation between a Superstorm Sandy stress factor score and infant temperament. Further, analysis of the placental transcriptomes identified an enrichment of functional pathways related to inflammation, extracellular matrix integrity and sensory perception in the specimen from those infants with “Slow-to-Warm-up” temperament during the first year of life. Together, these findings provide initial evidence that maternal exposure to climate-related disasters results in altered placental transcriptome, which may be related to long-term emotional and behavioral consequences in children.
Brain-Specific Increase in Leukotriene Signaling Accompanies Chronic Neuroinflammation and Cognitive Impairment in a Model of Gulf War Illness
Authors: Attaluri Sahithi , Upadhya Raghavendra , Kodali Maheedhar , Madhu Leelavathi N. , Upadhya Dinesh , Shuai Bing , Shetty Ashok K.
Published: April 2022

Persistent cognitive impairment is a primary central nervous system-related symptom in veterans afflicted with chronic Gulf War Illness (GWI). Previous studies in a rat model have revealed that cognitive dysfunction in chronic GWI is associated with neuroinflammation, typified by astrocyte hypertrophy, activated microglia, and enhanced proinflammatory cytokine levels. Studies in a mouse model of GWI have also shown upregulation of several phospholipids that serve as reservoirs of arachidonic acid, a precursor of leukotrienes (LTs). However, it is unknown whether altered LT signaling is a component of chronic neuroinflammatory conditions in GWI. Therefore, this study investigated changes in LT signaling in the brain of rats displaying significant cognitive impairments six months after exposure to GWI-related chemicals and moderate stress. The concentration of cysteinyl LTs (CysLTs), LTB4, and 5-Lipoxygenase (5-LOX), the synthesizing enzyme of LTs, were evaluated. CysLT and LTB4 concentrations were elevated in the hippocampus and the cerebral cortex, along with enhanced 5-LOX expression in neurons and microglia. Such changes were also associated with increased proinflammatory cytokine levels in the hippocampus and the cerebral cortex. Enhanced CysLT and LTB4 levels in the brain could also be gleaned from their concentrations in brain-derived extracellular vesicles in the circulating blood. The circulating blood in GWI rats displayed elevated proinflammatory cytokines with no alterations in CysLT and LTB4 concentrations. The results provide new evidence that a brain-specific increase in LT signaling is another adverse alteration that potentially contributes to the maintenance of chronic neuroinflammation in GWI. Therefore, drugs capable of modulating LT signaling may reduce neuroinflammation and improve cognitive function in GWI. Additional findings demonstrate that altered LT levels in the brain could be tracked efficiently by analyzing brain-derived EVs in the circulating blood.
PreS/2-21-Guided siRNA Nanoparticles Target to Inhibit Hepatitis B Virus Infection and Replication
Authors: Gao Lixia , Yang Jie , Feng Jutao , Liu Ziying , Dong Ying , Luo Jiangyan , Yu Liangzhentian , Wang Jiamei , Fan Hongying , Ma Weifeng , Liu Tiancai
Published: April 2022

A viable therapy is needed to overcome the deadlock of the incurable chronic hepatitis B (CHB). The prolonged existence of covalently closed circular DNA (cccDNA) and integrated HBV DNA in the nucleus of hepatocytes is the root cause of CHB. As a result, it is critical to successfully suppress HBV DNA replication and eliminate cccDNA. RNA interference has been proven in recent research to silence the expression of target genes and thereby decrease HBV replication. However, siRNA is susceptible to be degraded by RNA enzymes in vivo, making it difficult to deliver successfully and lacking of tissue targeting. To exploit the advantages of siRNA technology while also overcoming its limitations, we designed a new strategy and prepared biomimetic nanoparticles that were directed by PreS/2-21 peptides and precisely loaded HBV siRNA. Experiments on these nanoparticles in vitro and in vivo revealed that they are tiny, stable, safe and highly targetable, with high inhibitory effects on HBV DNA, pgRNA, cccDNA, HBeAg and HBsAg. PreS/2-21-directed nanoparticles loaded with HBV gene therapy drugs are expected to be promising for the treatment of CHB.
The Metabolic Basis of ILC Plasticity
Authors: Pelletier Abigaelle , Stockmann Christian
Published: April 2022

Innate Lymphoid Cells (ILCs) are the innate counterpart of adaptive lymphoid T cells. They are key players in the regulation of tissues homeostasis and early inflammatory host responses. ILCs are divided into three groups, and further subdivided into five subsets, that are characterised by distinct transcription factors, surface markers and their cytokine expression profiles. Group 1 ILCs, including natural killer (NK) cells and non-NK cell ILC1s, express T-bet and produce IFN-γ. Group 2 ILCs depend on GATA3 and produce IL-4, IL-5 and IL-13. Group 3 ILCs, composed of ILC3s and Lymphoid Tissue Inducer (LTi) cells, express RORγt and produce IL-17 and IL-22. Even though, the phenotype of each subset is well defined, environmental signals can trigger the interconversion of phenotypes and the plasticity of ILCs, in both mice and humans. Several extrinsic and intrinsic drivers of ILC plasticity have been described. However, the changes in cellular metabolism that underlie ILC plasticity remain largely unexplored. Given that metabolic changes critically affect fate and effector function of several immune cell types, we, here, review recent findings on ILC metabolism and discuss the implications for ILC plasticity.
A Machine Learning Model Based on PET/CT Radiomics and Clinical Characteristics Predicts Tumor Immune Profiles in Non-Small Cell Lung Cancer: A Retrospective Multicohort Study
Authors: Tong Haipeng , Sun Jinju , Fang Jingqin , Zhang Mi , Liu Huan , Xia Renxiang , Zhou Weicheng , Liu Kaijun , Chen Xiao
Published: April 2022

Background

The tumor immune microenvironment (TIME) phenotypes have been reported to mainly impact the efficacy of immunotherapy. Given the increasing use of immunotherapy in cancers, knowing an individual’s TIME phenotypes could be helpful in screening patients who are more likely to respond to immunotherapy. Our study intended to establish, validate, and apply a machine learning model to predict TIME profiles in non-small cell lung cancer (NSCLC) by using 18F-FDG PET/CT radiomics and clinical characteristics.

Methods

The RNA-seq data of 1145 NSCLC patients from The Cancer Genome Atlas (TCGA) cohort were analyzed. Then, 221 NSCLC patients from Daping Hospital (DPH) cohort received18F-FDG PET/CT scans before treatment and CD8 expression of the tumor samples were tested. The Artificial Intelligence Kit software was used to extract radiomic features of PET/CT images and develop a radiomics signature. The models were established by radiomics, clinical features, and radiomics-clinical combination, respectively, the performance of which was calculated by receiver operating curves (ROCs) and compared by DeLong test. Moreover, based on radiomics score (Rad-score) and clinical features, a nomogram was established. Finally, we applied the combined model to evaluate TIME phenotypes of NSCLC patients in The Cancer Imaging Archive (TCIA) cohort (n = 39).

Results

TCGA data showed CD8 expression could represent the TIME profiles in NSCLC. In DPH cohort, PET/CT radiomics model outperformed CT model (AUC: 0.907 vs. 0.861, P = 0.0314) to predict CD8 expression. Further, PET/CT radiomics-clinical combined model (AUC = 0.932) outperformed PET/CT radiomics model (AUC = 0.907, P = 0.0326) or clinical model (AUC = 0.868, P = 0.0036) to predict CD8 expression. In the TCIA cohort, the predicted CD8-high group had significantly higher immune scores and more activated immune pathways than the predicted CD8-low group (P = 0.0421).

Conclusion

Our study indicates that 18F-FDG PET/CT radiomics-clinical combined model could be a clinically practical method to non-invasively detect the tumor immune status in NSCLCs.
pcMSC Modulates Immune Dysregulation in Patients With COVID-19-Induced Refractory Acute Lung Injury
Authors: Chen Mei-Chuan , Lai Kevin Shu-Leung , Chien Ko-Ling , Teng Sing Teck , Lin Yuh-Rong , Chao Wei , Lee Meng-Jung , Wei Po-Li , Huang Yen-Hua , Kuo Han-Pin , Weng Chih-Ming , Chou Chun-Liang
Published: April 2022

Background and Objectives

The novel coronavirus disease 2019 (COVID-19) has been a pandemic health issue in 30 January 2020. The mortality rate is as high as 50% in critically ill patients. Stem cell therapy is effective for those who are refractory to standard treatments. However, the immune responses that underlie stem cell therapy have not been well reported, particularly, in patients associated with moderate to severe acute respiratory distress syndrome (ARDS).

Methods

On Days 0 and 4, an intravenous infusion of 2 × 107 placenta-derived mesenchymal stem cells (pcMSCs) (MatriPlax) were administered to five severe COVID-19 patients refractory to current standard therapies. Peripheral blood inflammatory markers and immune profiles were determined by multi-parameter flow cytometry and studied at Days 0, 4, and 8. Clinical outcomes were also observed.

Results

None of the pc-MSC treated patients experienced 28-day mortality compared with the control group and showed a significant improvement in the PaO2/FiO2 ratio, Murray’s lung injury scores, reduction in serum ferritin, lactate dehydrogenase (LDH), and C-reactive protein (CRP) levels. The cytokine profiles also showed a reduction in IL-1β, IFN-γ, IL-2, and IL-6, and an increase in IL-13 and IL-5 type 2 cytokines within 7 days of therapy. Lymphopenia was also significantly improved after 7 days of treatment. Immune cell profiles showed an increase in the proportions of CD4+ T cells (namely, CD4+ naïve T cells and CD4+ memory T cell subtypes), Treg cells, CD19+ B cells (namely, CD19+ naïve B cells, CD27+ switched B cell subtypes) and dendritic cells, and a significant decrease in the proportion of CD14+ monocytes (namely, CD16- classical and CD16+ non-classical subtypes), and plasma/plasmablast cells. No adverse effects were seen at the serial follow-up visits for 2 months after initial therapy.

Conclusion

pc-MSCs therapy suppressed hyper-inflammatory states of the innate immune response to COVID-19 infection by increasing Treg cells, decreasing monocytes and plasma/plasmablast cells, and promoting CD4+ T cells and CD19+ B cells toward adaptive immune responses in severely critically ill COVID-19 patients with moderate to severe ARDS, especially those who were refractory to current standard care and immunosuppressive therapies.
Evolving Strategies to Eliminate the CD4 T Cells HIV Viral Reservoir via CAR T Cell Immunotherapy
Authors: York Jarrod , Gowrishankar Kavitha , Micklethwaite Kenneth , Palmer Sarah , Cunningham Anthony L. , Nasr Najla
Published: April 2022

Although the advent of ART has significantly reduced the morbidity and mortality associated with HIV infection, the stable pool of HIV in latently infected cells requires lifelong treatment adherence, with the cessation of ART resulting in rapid reactivation of the virus and productive HIV infection. Therefore, these few cells containing replication-competent HIV, known as the latent HIV reservoir, act as the main barrier to immune clearance and HIV cure. While several strategies involving HIV silencing or its reactivation in latently infected cells for elimination by immune responses have been explored, exciting cell based immune therapies involving genetically engineered T cells expressing synthetic chimeric receptors (CAR T cells) are highly appealing and promising. CAR T cells, in contrast to endogenous cytotoxic T cells, can function independently of MHC to target HIV-infected cells, are efficacious and have demonstrated acceptable safety profiles and long-term persistence in peripheral blood. In this review, we present a comprehensive picture of the current efforts to target the HIV latent reservoir, with a focus on CAR T cell therapies. We highlight the current challenges and advances in this field, while discussing the importance of novel CAR designs in the efforts to find a HIV cure.