bluuebunny/crossref_metadata_2025 huggingface dataset:
CXCL2 Impairs Functions of Bone Marrow Mesenchymal Stem Cells and Can Serve as a Serum Marker in High-Fat Diet-Fed Rats
Authors: Bi Jianhai , Li Qiuchen , Yang Zhigang , Cai Lei , Lv Tao , Yang Xun , Yan Li , Liu Xia , Wang Qian , Fu Xin , Xiao Ran
Published: July 2021

In modern society excessive consumption of a high-fat diet (HFD) is a significant risk factor for many diseases such as diabetes, osteoarthritis and certain cancers. Resolving cellular and molecular mechanisms underlying HFD-associated disorders is of great importance to human health. Mesenchymal stem cells (MSCs) are key players in tissue homeostasis and adversely affected by prolonged HFD feeding. Low-grade systemic inflammation induced by HFD is characterized by increased levels of pro-inflammatory cytokines and alters homeostasis in many organs. However, whether, which and how HFD associated inflammatory cytokines impair MSCs remain unclear. Here we demonstrated that HFD induced serum cytokines disturbances, especially a continuous elevation of serum CXCL2 level in rats. Coincidentally, the differentially expressed genes (DEGs) of bone marrow MSCs (BMSCs) which functions were impaired in HFD rats were enriched in cytokine signaling. Further mechanism analysis revealed that CXCL2 treatment in vitro suppresses the adipogenic potential of BMSCs via Rac1 activation, and promoted BMSC migration and senescence by inducing over-production of ELMO1 and reactive oxygen species (ROS) respectively. Moreover, we found that although glycolipid metabolism indicators can be corrected, the CXCL2 elevation and BMSC dysfunctions cannot be fully rescued by diet correction and anti-inflammatory aspirin treatment, indicating the long-lasting deleterious effects of HFD on serum CXCL2 levels and BMSC functions. Altogether, our findings identify CXCL2 as an important regulator in BMSCs functions and may serve as a serum marker to indicate the BMSC dysfunctions induced by HFD. In addition, our findings underscore the intricate link among high-fat intake, chronic inflammation and BMSC dysfunction which may facilitate development of protective strategies for HFD associated diseases.
Review on Recent Progress in Magnetic Nanoparticles: Synthesis, Characterization, and Diverse Applications
Authors: Ali Arbab , Shah Tufail , Ullah Rehmat , Zhou Pingfan , Guo Manlin , Ovais Muhammad , Tan Zhiqiang , Rui YuKui
Published: July 2021

Diverse applications of nanoparticles (NPs) have revolutionized various sectors in society. In the recent decade, particularly magnetic nanoparticles (MNPs) have gained enormous interest owing to their applications in specialized areas such as medicine, cancer theranostics, biosensing, catalysis, agriculture, and the environment. Controlled surface engineering for the design of multi-functional MNPs is vital for achieving desired application. The MNPs have demonstrated great efficacy as thermoelectric materials, imaging agents, drug delivery vehicles, and biosensors. In the present review, first we have briefly discussed main synthetic methods of MNPs, followed by their characterizations and composition. Then we have discussed the potential applications of MNPs in different with representative examples. At the end, we gave an overview on the current challenges and future prospects of MNPs. This comprehensive review not only provides the mechanistic insight into the synthesis, functionalization, and application of MNPs but also outlines the limits and potential prospects.
Lactulose Improves Neurological Outcomes by Repressing Harmful Bacteria and Regulating Inflammatory Reactions in Mice After Stroke
Authors: Yuan Quan , Xin Ling , Han Song , Su Yue , Wu Ruixia , Liu Xiaoxuan , Wuri Jimusi , Li Ran , Yan Tao
Published: July 2021

Background and Objective

Gut microbiota dysbiosis following stroke affects the recovery of neurological function. Administration of prebiotics to counteract post-stroke dysbiosis may be a potential therapeutic strategy to improve neurological function. We aim to observe the effect of lactulose on neurological function outcomes, gut microbiota composition, and plasma metabolites in mice after stroke.

Methods

Male C57BL/6 mice (20–25 g) were randomly divided into three groups: healthy control, photothrombotic stroke + triple-distilled water, and photothrombotic stroke + lactulose. After 14 consecutive days of lactulose administration, feces, plasma, and organs were collected. 16S rDNA sequencing, plasma untargeted metabolomics, qPCR, flow cytometry and Elisa were performed.

Results

Lactulose supplementation significantly improved the functional outcome of stroke, downregulated inflammatory reaction, and increased anti-inflammatory factors in both the brain and gut. In addition, lactulose supplementation repaired intestinal barrier injury, improved gut microbiota dysbiosis, and partially amended metabolic disorder after stroke.

Conclusion

Lactulose promotes functional outcomes after stroke in mice, which may be attributable to repressing harmful bacteria, and metabolic disorder, repairing gut barrier disruption, and reducing inflammatory reactions after stroke.
NS1: A Key Protein in the “Game” Between Influenza A Virus and Host in Innate Immunity
Authors: Ji Zhu-xing , Wang Xiao-quan , Liu Xiu-fan
Published: July 2021

Since the influenza pandemic occurred in 1918, people have recognized the perniciousness of this virus. It can cause mild to severe infections in animals and humans worldwide, with extremely high morbidity and mortality. Since the first day of human discovery of it, the “game” between the influenza virus and the host has never stopped. NS1 protein is the key protein of the influenza virus against host innate immunity. The interaction between viruses and organisms is a complex and dynamic process, in which they restrict each other, but retain their own advantages. In this review, we start by introducing the structure and biological characteristics of NS1, and then investigate the factors that affect pathogenicity of influenza which determined by NS1. In order to uncover the importance of NS1, we analyze the interaction of NS1 protein with interferon system in innate immunity and the molecular mechanism of host antagonism to NS1 protein, highlight the unique biological function of NS1 protein in cell cycle.
Trade-Offs in Phosphorus Acquisition Strategies of Five Common Tree Species in a Tropical Forest of Puerto Rico
Authors: Yaffar Daniela , Defrenne Camille E. , Cabugao Kristine G. , Kivlin Stephanie N. , Childs Joanne , Carvajal Niko , Norby Richard J.
Published: July 2021

Tree species that are successful in tropical lowlands have different acquisition strategies to overcome soil phosphorus (P) limitations. Some of these strategies belowground include adjustments in fine-root traits, such as morphology, architecture, association with arbuscular mycorrhizal fungi, and phosphatase activity. Trade-offs among P-acquisition strategies are expected because of their respective carbon cost. However, empirical evidence remains scarce which hinders our understanding of soil P-acquisition processes in tropical forests. Here, we measured seven fine-root functional traits related to P acquisition of five common tree species in three sites of the Luquillo Experimental Forest in Puerto Rico. We then described species-specific P-acquisition strategies and explored the changes in fine-root trait expression from 6 months before to 6 months after two consecutive hurricanes, Irma and María, passed over the island. We found that variations in root trait expression were driven mainly by the large interspecific differences across the three selected sites. In addition, we revealed a trade-off between highly colonized fine roots with high phosphatase activity and fine roots that have a high degree of branching. Furthermore, the former strategy was adopted by pioneer species (Spathodea campanulata and Cecropia schreberiana), whereas the latter was adopted by non-pioneer species (mostly Dacryodes excelsa and Prestoea montana). Additionally, we found that root trait expression did not change comparing 6 months before and after the hurricanes, with the exception of root phosphatase activity. Altogether, our results suggest a combination of structural and physiological root traits for soil P acquisition in P-poor tropical soils by common tropical tree species, and show stability on most of the root trait expression after hurricane disturbances.
Human Hyaluronidase PH20 Potentiates the Antitumor Activities of Mesothelin-Specific CAR-T Cells Against Gastric Cancer
Authors: Zhao Ruocong , Cui Yuanbin , Zheng Yongfang , Li Shanglin , Lv Jiang , Wu Qiting , Long Youguo , Wang Suna , Yao Yao , Wei Wei , Yang Jie , Wang Bin-Chao , Zhang Zhenfeng , Zeng Hui , Li Yangqiu , Li Peng
Published: July 2021

T cell infiltration into tumors is essential for successful immunotherapy against solid tumors. Herein, we found that the expression of hyaluronic acid synthases (HAS) was negatively correlated with patient survival in multiple types of solid tumors including gastric cancer. HA impeded in vitro anti-tumor activities of anti-mesothelin (MSLN) chimeric antigen receptor T cells (CAR-T cells) against gastric cancer cells by restricting CAR-T cell mobility in vitro. We then constructed a secreted form of the human hyaluronidase PH20 (termed sPH20-IgG2) by replacing the PH20 signal peptide with a tPA signal peptide and attached with IgG2 Fc fragments. We found that overexpression of sPH20-IgG2 promoted CAR-T cell transmigration through an HA-containing matrix but did not affect the cytotoxicity or cytokine secretion of the CAR-T cells. In BGC823 and MKN28 gastric cancer cell xenografts, sPH20-IgG2 promoted anti-mesothelin CAR-T cell infiltration into tumors. Furthermore, mice infused with sPH20-IgG2 overexpressing anti-MSLN CAR-T cells had smaller tumors than mice injected with anti-MSLN CAR-T cells. Thus, we demonstrated that sPH20-IgG2 can enhance the antitumor activity of CAR-T cells against solid tumors by promoting CAR-T cell infiltration.
Transcriptomic Signature Differences Between SARS-CoV-2 and Influenza Virus Infected Patients
Authors: Bibert Stéphanie , Guex Nicolas , Lourenco Joao , Brahier Thomas , Papadimitriou-Olivgeris Matthaios , Damonti Lauro , Manuel Oriol , Liechti Robin , Götz Lou , Tschopp Jonathan , Quinodoz Mathieu , Vollenweider Peter , Pagani Jean-Luc , Oddo Mauro , Hügli Olivier , Lamoth Frédéric , Erard Véronique , Voide Cathy , Delorenzi Mauro , Rufer Nathalie , Candotti Fabio , Rivolta Carlo , Boillat-Blanco Noémie , Bochud Pierre-Yves ,   the RegCOVID Study Group
Published: July 2021

The reason why most individuals with COVID-19 have relatively limited symptoms while other develop respiratory distress with life-threatening complications remains unknown. Increasing evidence suggests that COVID-19 associated adverse outcomes mainly rely on dysregulated immunity. Here, we compared transcriptomic profiles of blood cells from 103 patients with different severity levels of COVID-19 with that of 27 healthy and 22 influenza-infected individuals. Data provided a complete overview of SARS-CoV-2-induced immune signature, including a dramatic defect in IFN responses, a reduction of toxicity-related molecules in NK cells, an increased degranulation of neutrophils, a dysregulation of T cells, a dramatic increase in B cell function and immunoglobulin production, as well as an important over-expression of genes involved in metabolism and cell cycle in patients infected with SARS-CoV-2 compared to those infected with influenza viruses. These features also differed according to COVID-19 severity. Overall and specific gene expression patterns across groups can be visualized on an interactive website (https://bix.unil.ch/covid/). Collectively, these transcriptomic host responses to SARS-CoV-2 infection are discussed in the context of current studies, thereby improving our understanding of COVID-19 pathogenesis and shaping the severity level of COVID-19.
Coordination of the Uptake and Metabolism of Amino Acids in Mycobacterium tuberculosis-Infected Macrophages
Authors: Jiang Qingkui , Shi Lanbo
Published: July 2021

Macrophage polarization to the M1-like phenotype, which is critical for the pro-inflammatory and antimicrobial responses of macrophages against intracellular pathogens, is associated with metabolic reprogramming to the Warburg effect and a high output of NO from increased expression of NOS2. However, there is limited understanding about the uptake and metabolism of other amino acids during M1 polarization. Based on functional analysis of a group of upregulated transporters and enzymes involved in the uptake and/or metabolism of amino acids in Mycobacterium tuberculosis-infected macrophages, plus studies of immune cell activation, we postulate a coherent scheme for amino acid uptake and metabolism during macrophage polarization to the M1-like phenotype. We describe potential mechanisms that the increased arginine metabolism by NOS2 is metabolically coupled with system L transporters LAT1 and LAT2 for the uptake of neutral amino acids, including those that drive mTORC1 signaling toward the M1-like phenotype. We also discuss the underappreciated pleiotropic roles of glutamine metabolism in the metabolic reprogramming of M1-like macrophages. Collectively, our analyses argue that a coordinated amino acid uptake and metabolism constitutes an integral component of the broad metabolic scheme required for macrophage polarization to M1-like phenotype against M. tuberculosis infection. This idea could stimulate future experimental efforts to elucidate the metabolic map of macrophage activation for the development of anti-tuberculosis therapies.
Improvements of Population Fitness and Trophic Status of a Benthic Predatory Fish Following a Trawling Ban
Authors: Tao Lily S. R. , Mak Yanny K. Y. , Ho Valerie C. M. , Sham Ronia C.-t. , Hui Tommy T. Y. , Lau Danny C. P. , Leung Kenneth M. Y.
Published: July 2021

Trawl fisheries have been shown to cause overfishing and destruction of benthic habitats in the seabed. To mitigate these impacts, a trawling ban has been enforced in Hong Kong waters since December 31, 2012 to rehabilitate the ecosystem and enhance fisheries resources. Previous studies demonstrated that reduced trawling activities would increase the heterogeneity of benthic habitats, thereby enhancing species richness and abundance of benthic fauna and providing more prey resources for predatory fishes. This study aimed to test a hypothesis that the population and trophic dynamics of the Bartail flatheadPlatycephalus indicus, a heavily fished benthic predatory fish, at inner and outer Tolo Channel of Hong Kong (i.e., EI and EO) improved with increases in their body size, abundance, biomass, trophic niche, and trophic position after the trawl ban. Samples were collected from trawl surveys before and after the trawl ban to compare the pre-ban and post-ban populations ofP. indicusfrom EI and EO. Body size, abundance, and biomass were assessed in 2004, 2013–2014, and 2015–2016, whereas trophic niche and trophic position were analyzed based on stable isotopes of fish samples collected in dry season of 2012, 2015, and 2018. Following the trawl ban, the abundance and biomass ofP. indicusincreased in EO, with body size increased in EI. Furthermore, as indicated by the results of stable isotope analysis (SIA) on their tissues and prey items, trophic niche, and trophic position ofP. indicusincreased in EI and EO, respectively. Our study demonstrated that the trawl ban had promoted the recovery of a predatory fish population through restoring size structure and trophic dynamics.
The Phage Nucleus and PhuZ Spindle: Defining Features of the Subcellular Organization and Speciation of Nucleus-Forming Jumbo Phages
Authors: Chaikeeratisak Vorrapon , Birkholz Erica A. , Pogliano Joe
Published: July 2021

Bacteriophages and their bacterial hosts are ancient organisms that have been co-evolving for billions of years. Some jumbo phages, those with a genome size larger than 200 kilobases, have recently been discovered to establish complex subcellular organization during replication. Here, we review our current understanding of jumbo phages that form a nucleus-like structure, or “Phage Nucleus,” during replication. The phage nucleus is made of a proteinaceous shell that surrounds replicating phage DNA and imparts a unique subcellular organization that is temporally and spatially controlled within bacterial host cells by a phage-encoded tubulin (PhuZ)-based spindle. This subcellular architecture serves as a replication factory for jumbo Pseudomonas phages and provides a selective advantage when these replicate in some host strains. Throughout the lytic cycle, the phage nucleus compartmentalizes proteins according to function and protects the phage genome from host defense mechanisms. Early during infection, the PhuZ spindle positions the newly formed phage nucleus at midcell and, later in the infection cycle, the spindle rotates the nucleus while delivering capsids and distributing them uniformly on the nuclear surface, where they dock for DNA packaging. During the co-infection of two different nucleus-forming jumbo phages in a bacterial cell, the phage nucleus establishes Subcellular Genetic Isolation that limits the potential for viral genetic exchange by physically separating co-infection genomes, and the PhuZ spindle causes Virogenesis Incompatibility, whereby interacting components from two diverging phages negatively affect phage reproduction. Thus, the phage nucleus and PhuZ spindle are defining cell biological structures that serve roles in both the life cycle of nucleus-forming jumbo phages and phage speciation.
Isolation and Identification of Uranium Tolerant Phosphate-Solubilizing Bacillus spp. and Their Synergistic Strategies to U(VI) Immobilization
Authors: Zhong Juan , Hu Xuewu , Liu Xingyu , Cui Xinglan , Lv Ying , Tang Chuiyun , Zhang Mingjiang , Li Hongxia , Qiu Lang , Sun Weimin
Published: July 2021

The remediation of uranium (U) through phosphate-solubilizing bacteria (PSB) is an emerging technique as well as an interesting phenomenon for transforming mobile U into stable minerals in the environment. While studies are well needed for in-depth understanding of the mechanism of U(VI) immobilization by PSB. In this study, two PSB were isolated from a U-tailing repository site. These bacterial strains (ZJ-1 and ZJ-3) were identified as Bacillus spp. by the sequence analysis of 16S ribosomal RNA (rRNA) genes. Incubation of PSB in liquid medium showed that the isolate ZJ-3 could solubilize more than 230 mg L–1 P from glycerol-3-phosphate and simultaneously removed over 70% of 50 mg L–1 U(VI) within 1 h. During this process, the rapid appearance of yellow precipitates was observed. The microscopic and spectroscopic analysis demonstrated that the precipitates were associated with U-phosphate compound in the form of saleeite-like substances. Besides, scanning electron microscopy coupled with energy-dispersive X-ray (SEM-EDS) and Fourier transform infrared spectroscopy (FTIR) analysis of the precipitates confirmed that the extracellular polymeric substances (EPS) might also play a key role in U sequestration. Furthermore, SEM and FTIR analysis revealed that part of U(VI) was adsorbed on the bacterial surface through cellular phosphate, hydroxy, carboxyl, and amide groups. This study provides new insights into the synergistic strategies enhancing U immobilization rates by Bacillus spp. that uses glycerol-3-phosphate as the phosphorus source, the process of which contributes to harmful pollutant biodegradation.
Effects of Dietary Ferulic Acid on the Intestinal Microbiota and the Associated Changes on the Growth Performance, Serum Cytokine Profile, and Intestinal Morphology in Ducks
Authors: Liu Yang , Lin Qian , Huang Xuan , Jiang Guitao , Li Chuang , Zhang Xu , Liu Shengli , He Lingyun , Liu Yali , Dai Qiuzhong , Huang Xingguo
Published: July 2021

The present study investigated the effects of ferulic acid (FA) on the growth performance, serum cytokine profile, intestinal morphology, and intestinal microbiota in ducks at the growing stage. 300 female Linwu ducks at 28 days of age with similar body weights were randomly divided into five groups. Each group contained six replicates of 10 birds. The dietary treatments were corn-soybean-based diet supplemented with FA at the concentrations of 0 (control), 100, 200, 400, and 800 mg/kg diet. The results demonstrated that dietary FA at the levels of 200, 400, and 800 mg/kg increased the average daily gain (P = 0.01), 400 and 800 mg/kg FA increased the final body weight (P = 0.02), 100, 200, and 800 mg/kg FA increased the serum glutathione (P = 0.01), and 100, 400, and 800 mg/kg FA increased the glutathione peroxidase activities in birds (P < 0.01). Additionally, 200, 400, and 800 mg/kg dietary FA lowered the serum levels of interleukin-2 (P = 0.02) and interleukin-6 (P = 0.04). Moreover, the morphometric study of the intestines indicated that 400 mg/kg FA decreased the crypt depth in jejunum (P = 0.01) and caecum (P = 0.04), and increased the ratio of villus height to crypt depth in jejunum (P = 0.02). Significant linear and/or quadratic relationships were found between FA concentration and the measured parameters. 16S rRNA sequencing revealed that dietary FA increased the populations of genera Faecalibacterium, Paludicola, RF39, and Faecalicoccus in the cecum (P < 0.05), whereas decreased the populations of Anaerofilum and UCG-002 (P < 0.05). The Spearman correlation analysis indicated that phylum Proteobacteria were negatively, but order Oscillospirales, and family Ruminococcaceae were positively related to the parameters of the growth performance. Phylum Bacteroidetes, class Negativicutes and family Rikenellaceae were negatively associated with the parameters of the antioxidative capability. And phylum Cyanobacteria, Elusimicrobia, and Bacteroidetes, class Bacilli, family Rikenellaceae, and genus Prevotella were positively associated with the parameters of the immunological capability. Thus, it was concluded that the supplementations of 400 mg/kg FA in diet was able to improve the growth performance, antioxidative and immunological capabilities, intestinal morphology, and modulated the gut microbial construction of Linwu ducks at the growing stage.
Genomic Diversity of the Ostreid Herpesvirus Type 1 Across Time and Location and Among Host Species
Authors: Morga Benjamin , Jacquot Maude , Pelletier Camille , Chevignon Germain , Dégremont Lionel , Biétry Antoine , Pepin Jean-François , Heurtebise Serge , Escoubas Jean-Michel , Bean Tim P. , Rosani Umberto , Bai Chang-Ming , Renault Tristan , Lamy Jean-Baptiste
Published: July 2021

The mechanisms underlying virus emergence are rarely well understood, making the appearance of outbreaks largely unpredictable. This is particularly true for pathogens with low per-site mutation rates, such as DNA viruses, that do not exhibit a large amount of evolutionary change among genetic sequences sampled at different time points. However, whole-genome sequencing can reveal the accumulation of novel genetic variation between samples, promising to render most, if not all, microbial pathogens measurably evolving and suitable for analytical techniques derived from population genetic theory. Here, we aim to assess the measurability of evolution on epidemiological time scales of the Ostreid herpesvirus 1 (OsHV-1), a double stranded DNA virus of which a new variant, OsHV-1 μVar, emerged in France in 2008, spreading across Europe and causing dramatic economic and ecological damage. We performed phylogenetic analyses of heterochronous (n = 21) OsHV-1 genomes sampled worldwide. Results show sufficient temporal signal in the viral sequences to proceed with phylogenetic molecular clock analyses and they indicate that the genetic diversity seen in these OsHV-1 isolates has arisen within the past three decades. OsHV-1 samples from France and New Zealand did not cluster together suggesting a spatial structuration of the viral populations. The genome-wide study of simple and complex polymorphisms shows that specific genomic regions are deleted in several isolates or accumulate a high number of substitutions. These contrasting and non-random patterns of polymorphism suggest that some genomic regions are affected by strong selective pressures. Interestingly, we also found variant genotypes within all infected individuals. Altogether, these results provide baseline evidence that whole genome sequencing could be used to study population dynamic processes of OsHV-1, and more broadly herpesviruses.
The Impact of Common Epidemiological Factors on Gray and White Matter Volumes in Magnetic Resonance Imaging–Is Prevention of Brain Degeneration Possible?
Authors: Jacków-Nowicka Jagoda , Podgórski Przemysław , Bladowska Joanna , Szcześniak Dorota , Rymaszewska Joanna , Zatońska Katarzyna , Połtyn-Zaradna Katarzyna , Szuba Andrzej , Sa̧siadek Marek , Zimny Anna
Published: July 2021

Introduction: The aim of the study was to evaluate the impact of multiple risk factors (age, diabetes, hypertension, hyperlipidemia, BMI, smoking, alcohol) on the gray and white matter volumes as well as on the burden of white matter hyperintensities (WMH).

Material and Methods: The study group consisted of 554 subjects (age range: 50–69 yrs, F/M: 367/187) recruited from the larger cohort of the Polish fraction of the Prospective Urban Rural Epidemiological (PURE) study. The participants answered questionnaires about their lifestyle, underwent physical and psychological examination (MoCA test), laboratory blood tests followed by brain MRI. Volumetric measurements of the total gray matter (GMvol), total white matter (WMvol) and WHM (WMHvol) normalized to the total intracranial volume were performed using the Computational Anatomy Toolbox 12 (CAT12) and Statistical Parametric Maps 12 (SPM12) based on 3D T1-weighted sequence. The influence of risk factors was assessed using multiple regression analysis before and after correction for multiple comparisons.

Results: Older age was associated with lower GMvol and WMvol, and higher WMHvol (p < 0.001). Smaller GMvol volume was associated with higher WMHvol (p < 0.001). Higher WMHvol was associated with hypertension (p = 0.01) and less significantly with hyperlipidemia (only before correction p = 0.03). Diabetes, abnormal BMI, smoking and alcohol intake did not have any significant impact on GMvol, WMvol or WMHvol (p > 0.05). MoCA score was not influenced by any of the factors.

Conclusions: Gray matter loss is strongly associated with the accumulation of WMH which seems to be potentially preventable by maintaining normal blood pressure and cholesterol levels.
Seizure Diaries and Forecasting With Wearables: Epilepsy Monitoring Outside the Clinic
Authors: Brinkmann Benjamin H. , Karoly Philippa J. , Nurse Ewan S. , Dumanis Sonya B. , Nasseri Mona , Viana Pedro F. , Schulze-Bonhage Andreas , Freestone Dean R. , Worrell Greg , Richardson Mark P. , Cook Mark J.
Published: July 2021

It is a major challenge in clinical epilepsy to diagnose and treat a disease characterized by infrequent seizures based on patient or caregiver reports and limited duration clinical testing. The poor reliability of self-reported seizure diaries for many people with epilepsy is well-established, but these records remain necessary in clinical care and therapeutic studies. A number of wearable devices have emerged, which may be capable of detecting seizures, recording seizure data, and alerting caregivers. Developments in non-invasive wearable sensors to measure accelerometry, photoplethysmography (PPG), electrodermal activity (EDA), electromyography (EMG), and other signals outside of the traditional clinical environment may be able to identify seizure-related changes. Non-invasive scalp electroencephalography (EEG) and minimally invasive subscalp EEG may allow direct measurement of seizure activity. However, significant network and computational infrastructure is needed for continuous, secure transmission of data. The large volume of data acquired by these devices necessitates computer-assisted review and detection to reduce the burden on human reviewers. Furthermore, user acceptability of such devices must be a paramount consideration to ensure adherence with long-term device use. Such devices can identify tonic–clonic seizures, but identification of other seizure semiologies with non-EEG wearables is an ongoing challenge. Identification of electrographic seizures with subscalp EEG systems has recently been demonstrated over long (>6 month) durations, and this shows promise for accurate, objective seizure records. While the ability to detect and forecast seizures from ambulatory intracranial EEG is established, invasive devices may not be acceptable for many individuals with epilepsy. Recent studies show promising results for probabilistic forecasts of seizure risk from long-term wearable devices and electronic diaries of self-reported seizures. There may also be predictive value in individuals' symptoms, mood, and cognitive performance. However, seizure forecasting requires perpetual use of a device for monitoring, increasing the importance of the system's acceptability to users. Furthermore, long-term studies with concurrent EEG confirmation are lacking currently. This review describes the current evidence and challenges in the use of minimally and non-invasive devices for long-term epilepsy monitoring, the essential components in remote monitoring systems, and explores the feasibility to detect and forecast impending seizures via long-term use of these systems.
Peripheral Blood Biomarkers for Early Diagnosis, Severity, and Prognosis of Checkpoint Inhibitor-Related Pneumonitis in Patients With Lung Cancer
Authors: Lin Xinqing , Deng Haiyi , Yang Yilin , Wu Jianhui , Qiu Guihuan , Li Suyang , Xie Xiaohong , Liu Ming , Xie Zhanhong , Qin Yinyin , Song Yong , Zhou Chengzhi
Published: July 2021

Background

Checkpoint inhibitor-related pneumonitis (CIP) is a potentially fatal immune-related adverse event that occurs during treatment with immune checkpoint inhibitors (ICIs). However, the roles played by peripheral blood parameters in CIP development remain unclear. Here, we aimed to identify which blood biomarkers correlated with the development and prognosis of CIP in patients with lung cancer.

Methods

We conducted a retrospective analysis of 87 patients with CIP (CIP group) and 87 patients without CIP (control group). Cytokines, blood routine, lactate dehydrogenase (LDH) and albumin (ALB) were collected at baseline (before ICIs), at onset of pneumonitis (in the CIP group), and before the last dose of ICI (in the control group). We compared the baseline values and changes over time in various blood parameters between the CIP and control groups. The CIP outcomes were collected and compared according to the median values of these parameters.

Results

Squamous carcinoma (odds ratio [OR]: 3.02; p = 0.004) and ICI monotherapy (OR: 6.56; p = 0.004) correlated with a high risk of CIP. In the CIP group, interleukin (IL)-6 and platelet-to-lymphocyte ratio (PLR) at CIP were significantly increased relative to baseline. By contrast, IL-6 and PLR reduced over time in the control group. Significant decrease in absolute lymphocyte count (ALC) and increases in IL-10, neutrophil to lymphocyte ratio (NLR), and LDH levels were observed from baseline to CIP. No significant change in these parameters was observed in the control group relative to baseline. ALB decreased in both groups, but the decrease in the CIP group was greater (9.21% vs. 2.44%; p = 0.020). High IL-6 levels (OR: 5.23, 95% confidence interval [CI]: 1.15–23.86; p = 0.033), and low levels of ALB (OR: 0.16, 95% CI: 0.04–0.64; p = 0.009) measured at the time of CIP symptom onset were associated with severe pneumonitis. Low concentration of IL-6 (hazard ratio [HR]: 0.17, 95% CI: 0.03–0.95; p = 0.044) and high ALB levels (HR: 0.28, 95% CI: 0.08–0.94; p = 0.040) were correlated with favorable overall survival in CIP.

Conclusions

Increase in IL-6, IL-10, NLR, PLR, and LDH levels or reduced ALC and ALB levels were associated with the occurrence of CIP in lung cancer patients. High IL-6 and low ALB levels at onset of CIP were related to severe grade and poor prognosis of CIP.
An Immune-Clinical Prognostic Index (ICPI) for Patients With De Novo Follicular Lymphoma Treated With R-CHOP/CHOP Chemotherapy
Authors: Lu Yaxiao , Yu Jingwei , Gong Wenchen , Su Liping , Sun Xiuhua , Bai Ou , Zhou Hui , Guan Xue , Zhang Tingting , Li Lanfang , Qiu Lihua , Qian Zhengzi , Zhou Shiyong , Meng Bin , Ren Xiubao , Wang Xianhuo , Zhang Huilai
Published: July 2021

Purpose

Although the role of tumor-infiltrating T cells in follicular lymphoma (FL) has been reported previously, the prognostic value of peripheral blood T lymphocyte subsets has not been systematically assessed. Thus, we aim to incorporate T-cell subsets with clinical features to develop a predictive model of clinical outcome.

Methods

We retrospectively screened a total of 1,008 patients, including 252 newly diagnosed de novo FL patients with available peripheral blood T lymphocyte subsets who were randomized to different sets (177 in the training set and 75 in the internal validation set). A nomogram and a novel immune-clinical prognostic index (ICPI) were established according to multivariate Cox regression analysis for progression-free survival (PFS). The concordance index (C-index), Akaike’s information criterion (AIC), and likelihood ratio chi-square were employed to compare the ICPI’s discriminatory capability and homogeneity to that of FLIPI, FLIPI2, and PRIMA-PI. Additional external validation was performed using a dataset (n = 157) from other four centers.

Results

In the training set, multivariate analysis identified five independent prognostic factors (Stage III/IV disease, elevated lactate dehydrogenase (LDH), Hb <120g/L, CD4+ <30.7% and CD8+ >36.6%) for PFS. A novel ICPI was established according to the number of risk factors and stratify patients into 3 risk groups: high, intermediate, and low-risk with 4-5, 2-3, 0-1 risk factors respectively. The hazard ratios for patients in the high and intermediate-risk groups than those in the low-risk were 27.640 and 2.758. The ICPI could stratify patients into different risk groups both in the training set (P < 0.0001), internal validation set (P = 0.0039) and external validation set (P = 0.04). Moreover, in patients treated with RCHOP-like therapy, the ICPI was also predictive (P < 0.0001). In comparison to FLIPI, FLIPI2, and PRIMA-PI (C-index, 0.613-0.647), the ICPI offered adequate discrimination capability with C-index values of 0.679. Additionally, it exhibits good performance based on the lowest AIC and highest likelihood ratio chi-square score.

Conclusions

The ICPI is a novel predictive model with improved prognostic performance for patients with de novo FL treated with R-CHOP/CHOP chemotherapy. It is capable to be used in routine practice and guides individualized precision therapy.
Pyroptosis-Related Gene Signatures Can Robustly Diagnose Skin Cutaneous Melanoma and Predict the Prognosis
Authors: Ju Anji , Tang Jiaze , Chen Shuohua , Fu Yan , Luo Yongzhang
Published: July 2021

Skin cutaneous melanoma (SKCM) is a chronically malignant tumor with a high mortality rate. Pyroptosis, a kind of pro-inflammatory programmed cell death, has been linked to cancer in recent studies. However, the value of pyroptosis in the diagnosis and prognosis of SKCM is not clear. In this study, it was discovered that 20 pyroptosis-related genes (PRGs) differed in expression between SKCM and normal tissues, which were related to diagnosis and prognosis. Firstly, based on these genes, nine machine-learning algorithms were shown to perform well in constructing diagnostic classifiers, including K-Nearest Neighbor (KNN), logistic regression, Support Vector Machine (SVM), Artificial Neural Network (ANN), decision tree, random forest, XGBoost, LightGBM, and CatBoost. Secondly, the least absolute shrinkage and selection operator (LASSO) Cox regression analysis was applied and the prognostic model was constructed based on 9 PRGs. Subgroups in low and high risks determined by the prognostic model were shown to have different survival. Thirdly, functional enrichment analyses were performed by applying the gene set enrichment analysis (GSEA), and results suggested that the risk was related to immune response. In conclusion, the expression signatures of pyroptosis-related genes are effective and robust in the diagnosis and prognosis of SKCM, which is related to immunity.
Compounds Isolated from Wikstroemia taiwanensis Regulate Bone Remodeling by Modulating Osteoblast and Osteoclast Activities
Authors: Imtiyaz Zuha , Lin Yi-Tzu , Liang Fang-Yu , Chiou Wen-Fei , Lee Mei-Hsien
Published: July 2021

Bone remodeling, a dynamic process in which bone formation by osteoblast is preceded by bone resorption by osteoclast, is a vital physiological process for maintaining bone mass and strength, imbalances in which could precipitate osteoporosis. Due to the unilateral mechanism of the existing bone remodeling drugs, identifying compounds that could regulate the balance between osteoclast and osteoblast could improve the treatment of osteoporosis. Here, we show that compounds isolated from Wikstroemia taiwanensis modulate osteoclast and osteoblast activities. Specifically, astragalin (1) and kaempferol 3-O-β-D-apiofuranosyl-(1→6)-β-D-glucopyranoside (2), besides increasing mineral deposition, increased alkaline phosphatase activity (137.2% for 1 and 115.8% for 2) and ESR-α expression (112.8% for 1 and 122.5% for 2) in primary human osteoblasts. In contrast, compounds 1, 2, 3, and 5 inhibited tartrate-resistant acid phosphatase (TRAP) activity in receptor activator of nuclear factor-κB ligand-induced osteoclasts by 40.8, 17.1, 25.9, and 14.5% and also decreased the number of TRAP-positive cells by 51.6, 26.8, 20.5, and 18.6%, respectively. Our findings, therefore, showed that compounds isolated from W. taiwanensis could increase osteoblast activity while simultaneously decreasing osteoclast activity, and hence, warrant further evaluation for development as anti-osteoporosis agents.
Research Progress on Catalpol as Treatment for Atherosclerosis
Authors: He Lei , Zhao Rusheng , Wang Youheng , Liu Huibing , Wang Xuehui
Published: July 2021

Coronary atherosclerotic heart disease, cerebrovascular disease, and peripheral artery disease are common diseases with high morbidity and mortality rates and must be addressed. Their most frequent complications, including myocardial infarction and stroke, are caused by spontaneous thrombotic occlusion and are the most frequent cause of death worldwide. Atherosclerosis (AS) is the most widespread underlying pathological change for the above diseases. Therefore, drugs that interfere with this pathophysiological process must be incorporated in the treatment. Chinese traditional and herbal drugs can effectively treat AS. With the development of traditional Chinese medicine, the active ingredients in common Chinese medicinal materials must be thoroughly purified prior to their application in western medicine. Various proprietary Chinese medicine preparations with remarkable effects have been used in AS treatment. Catalpol, the active component of Rehmannia glutinosa, belongs to iridoid terpene and has anti-inflammatory, antioxidant, insulin resistance improvement, and other related effects. Several reviews have been conducted on this compound and its actions against osteoporosis, neurodegenerative diseases, Alzheimer's disease (AD), Parkinson's disease (PD) and diabetes and its complications. The current review focused on catalpol’s effect on atherosclerotic plaque formation in different animal models. The potential mechanisms of catalpol to ameliorate AS were also summarized in terms of oxidative stress, inflammation, cell aging, apoptosis, and activation of the silent information regulator factor 2-related enzyme 1 (SIRT1) pathway.
Progress in the Application of Drugs for the Treatment of Multiple Sclerosis
Authors: Wei Weipeng , Ma Denglei , Li Lin , Zhang Lan
Published: July 2021

Multiple sclerosis (MS) is an autoimmune and chronic inflammatory demyelinating disease of the central nervous system (CNS), which gives rise to focal lesion in CNS and cause physical disorders. Although environmental factors and susceptibility genes are reported to play a role in the pathogenesis of MS, its etiology still remains unclear. At present, there is no complete cure, but there are drugs that decelerate the progression of MS. Traditional therapies are disease-modifying drugs that control disease severity. MS drugs that are currently marketed mainly aim at the immune system; however, increasing attention is being paid to the development of new treatment strategies targeting the CNS. Further, the number of neuroprotective drugs is presently undergoing clinical trials and may prove useful for the improvement of neuronal function and survival. In this review, we have summarized the recent application of drugs used in MS treatment, mainly introducing new drugs with immunomodulatory, neuroprotective, or regenerative properties and their possible treatment strategies for MS. Additionally, we have presented Food and Drug Administration-approved MS treatment drugs and their administration methods, mechanisms of action, safety, and effectiveness, thereby evaluating their treatment efficacy.
Relatedness Need Satisfaction and the Dark Triad: The Role of Depression and Prevention Focus
Authors: Xiao Mengqi , Wang Zhuofan , Kong Xiaoshan , Ao Xiya , Song Jia , Zhang Peng
Published: July 2021

Dark triad traits are often associated with maladaptive social and interpersonal interactions, such as dishonesty and self-centeredness; thus, it is important to explore predictors of the dark triad in order to better facilitate the reduction of such behaviors. The present study adopted a self-report approach with a total of 5,207 Chinese undergraduate students participated in the study. We found that relatedness need dissatisfaction significantly predicted the presence of dark personalities, which was mediated by prevention focus. Conditional process model analysis found that this mediating effect was stronger when depression levels were lower. Final study results contributed to further understanding predictors of the dark triad. Study limitations and future research directions were also examined.
Predicting One’s Turn With Both Body and Mind: Anticipatory Speech Postures During Dyadic Conversation
Authors: Krause Peter A. , Kawamoto Alan H.
Published: July 2021

In natural conversation, turns are handed off quickly, with the mean downtime commonly ranging from 7 to 423 ms. To achieve this, speakers plan their upcoming speech as their partner’s turn unfolds, holding the audible utterance in abeyance until socially appropriate. The role played by prediction is debated, with some researchers claiming that speakers predict upcoming speech opportunities, and others claiming that speakers wait for detection of turn-final cues. The dynamics of articulatory triggering may speak to this debate. It is often assumed that the prepared utterance is held in a response buffer and then initiated all at once. This assumption is consistent with standard phonetic models in which articulatory actions must follow tightly prescribed patterns of coordination. This assumption has recently been challenged by single-word production experiments in which participants partly positioned their articulators to anticipate upcoming utterances, long before starting the acoustic response. The present study considered whether similar anticipatory postures arise when speakers in conversation await their next opportunity to speak. We analyzed a pre-existing audiovisual database of dyads engaging in unstructured conversation. Video motion tracking was used to determine speakers’ lip areas over time. When utterance-initial syllables began with labial consonants or included rounded vowels, speakers produced distinctly smaller lip areas (compared to other utterances), prior to audible speech. This effect was moderated by the number of words in the upcoming utterance; postures arose up to 3,000 ms before acoustic onset for short utterances of 1–3 words. We discuss the implications for models of conversation and phonetic control.
A Cluster Randomized Trial of Promoting Alternative Thinking Strategies (PATHS®) With Swedish Preschool Children
Authors: Eninger Lilianne , Ferrer-Wreder Laura , Eichas Kyle , Olsson Tina M. , Hau Hanna Ginner , Allodi Mara Westling , Smedler Ann-Charlotte , Sedem Mina , Gull Ingela Clausén , Herkner Birgitta
Published: July 2021

The preschool edition of Promoting Alternative THinking Strategies (PATHS®) is a school-based, teacher implemented universal intervention developed in the United States designed to promote social emotional competence (SEC) in children as a foundation for improved mental health. PATHS is delivered as a curriculum and it is based on theories and research regarding SEC, brain development, and optimal school environments. A majority of children in Sweden attend preschool, which is government-subsidized and follows a national curriculum focusing on both academic and social emotional learning. However, there is not so much focus on formal instruction nor manual-based lessons. The purpose of this study was to assess the short-term (pre- to post-test) effects of PATHS in the Swedish preschool setting. Using a two-wave cluster randomized trial with multi-method and informant assessment (N = 285 4 and 5-year-old Swedish children; n = 145 wait-list control; n = 140 intervention; K = 26 preschools; k = 13 intervention; k = 13 control) we assessed changes in child emotional knowledge, emotional awareness, social problem solving, prosocial play, inhibitory control, and working memory using structural equation modeling (SEM). We included schools with at least one classroom of 4–5-year-old children from three municipalities. We excluded open preschools, parent cooperative preschools, and family day homes. After random assignment, schools were informed of condition assignment. Research team members were not blind to assignment. We hypothesized that relative to children in control schools, children in intervention schools would evidence improvements in social emotional competence as well as other outcomes. Children in PATHS, relative to children in the control, evidenced improvements in working memory and prosocial play, but also showed an increase in hyperactive behaviors. Girls in PATHS, relative to girls in the control, showed improvement in emotional knowledge and reduced anxiety. These results are considered in light of efforts to promote positive development and mental health. The trial registration number at ClinicalTrials.gov is NCT04512157. Main funding was from Swedish Council for Working Life and Social Research, the Swedish Research Council, Formas, and VINNOVA (dnr: 259-2012-71).