bluuebunny/crossref_metadata_2025 huggingface dataset:
Wearable Biosensors in the Workplace: Perceptions and Perspectives
Authors: Tindale Lauren C. , Chiu Derek , Minielly Nicole , Hrincu Viorica , Talhouk Aline , Illes Judy
Published: July 2022

Objectives

Wearable body and brain sensors are permeating the consumer market and are increasingly being considered for workplace applications with the goal of promoting safety, productivity, health, and wellness. However, the monitoring of physiologic signals in real-time prompts concerns about benefit and risk, ownership of such digital data, data transfer privacy, and the discovery and disclosure of signals of possible health significance. Here we explore the perceptions and perspectives of employers and employees about key ethical considerations regarding the potential use of sensors in the workplace.

Methods

We distributed a survey developed and refined based on key research questions and past literature to a wide range and size of industries in British Columbia, Canada. Both employers (potential Implementers) and employees (potential Users) were invited to participate.

Results

We received 344 survey responses. Most responses were from construction, healthcare, education, government, and utilities sectors. Across genders, industries, and workplace sizes, we found a convergence of opinions on perceived benefit and concern between potential Implementers and potential Users regarding the motivation to use biosensors in the workplace. Potential Implementers and Users also agreed on issues pertaining to safety, privacy, disclosure of findings of possible medical significance, risks, data ownership, data sharing, and transfer of data between workplaces. The greatest variability between potential Users and Implementers pertained to data ownership.

Conclusion

Strong agreement in the perception of biosensor use in the workplace between potential Implementers and Users reflects shared interest, motivation, and responsibility for their use. The use of sensors is rapidly increasing, and transparency about key use factors–both practical and ethical–is essential to maintain the current and desirable level of solidarity.
Assessing Modern Calluna Heathland Fire Temperatures Using Raman Spectroscopy: Implications for Past Regimes and Geothermometry
Authors: Theurer Thomas , Naszarkowski Noemi , Muirhead David K. , Jolley David , Mauquoy Dmitri
Published: July 2022

Charcoal geothermometry continues to offer considerable potential in the study of palaeowildfires over decadal, centennial, millennial, and deep time scales—with substantial implications for the understanding of modern wildfire intensification. Recent developments in the application of Raman spectroscopy to carbonaceous organic material have indicated its capability to potentially reconstruct the palaeocharcoal formation temperature, and equivalent palaeowildfire pyrolysis intensity. Charcoal reflectance geothermometry (which also relies upon microstructural change with thermal maturation) has also been the subject of extensive modern evaluation, with multiple studies highlighting the key influence of energy flux on the resultant charcoal microstructure. The ability to accurately quantify modern wildfire temperatures based upon novel Raman-charcoal analyses has not yet been attempted. Using Raman band width-ratios (i.e., FWHMRa) and accompanying geothermometric trends to natural wildfire charcoals, our results identify differences between microstructurally-derived fire temperatures compared to those recorded during the fire event itself. Subsequent assessments of wildfire energy flux over time indicate no dominant influence for the observed differences, due to the inherent complexity of natural fire systems. Further analysis within this study, regarding the influence of reference pyrolysis methodology on microstructural change, also highlights the difficulty of creating accurate post-fire temperature reconstructions. The application of Raman spectroscopy, however, to the quantification of relative changes in fire temperature continues to prove effective and insightful.
A Systematic Review and Integrated Bioinformatic Analysis of Candidate Genes and Pathways in the Endometrium of Patients With Polycystic Ovary Syndrome During the Implantation Window
Authors: Sutaji Zulazmi , Elias Marjanu Hikmah , Ahmad Mohd Faizal , Karim Abdul Kadir Abdul , Abu Muhammad Azrai
Published: July 2022

Polycystic ovary syndrome (PCOS) is a common disorder with wide-ranging clinical heterogeneity that causes infertility. However, the comprehensive molecular mechanisms of PCOS in causing infertility is remaining unclear. Hence, a comprehensive literature search was conducted using PubMed, Scopus, EBSCOhost, and Science Direct. Medical Subject Heading (MeSH) terms like PCOS, gene expression, implantation window and endometrium were used as the keywords. From 138 studies retrieved, original articles with RNA profiling on human endometrial tissues in PCOS women during the implantation window were included. Study design, sample size, sample type, method, and differentially expressed genes (DEGs) were identified from all publications. The DEGs were analyzed using the software packages DAVID, STRING, and Cytoscape. Three studies that met inclusion criteria were included, and 368 DEGs were identified. Twelve significant clusters from the protein-protein interaction network (PPI) complex were found, and cluster 1 showed very high intermolecular interactions. Five candidate genes (AURKA, CDC25C, KIF23, KIF2C, and NDC80) were identified from the systematic review and integrated bioinformatics analysis. It is concluded that cell cycle is the fundamental biological processes that were dysregulated in the endometrium of PCOS women, affecting decidualization progression in the endometrium during the implantation window.
Investigation of Valence Mixing in Sodium-Ion Battery Cathode Material Prussian White by Mössbauer Spectroscopy
Authors: Ericsson Tore , Häggström Lennart , Ojwang Dickson O. , Brant William R.
Published: July 2022

Prussian white (PW), Na2Fe [Fe(CN)6], is a highly attractive cathode material for sustainable sodium-ion batteries due to its high theoretical capacity of ∼170 mAhg−1 and low-cost synthesis. However, there exists significant variability in the reported electrochemical performance. This variability originates from compositional flexibility possible for all Prussian blue analogs (PBAs) and is exasperated by the difficulty of accurately quantifying the specific composition of PW. This work presents a means of accurately quantifying the vacancy content, valence distribution, and, consequently, the overall composition of PW via Mössbauer spectroscopy. PW cathode material with three different sodium contents was investigated at 295 and 90 K. The observation of only two iron environments for the fully sodiated compound indicated the absence of [Fe(CN)6]4- vacancies. Due to intervalence charge transfer between iron centers at 295 K, accurate determination of valences was not possible. However, by observing the trend of spectral intensities and center shift for the nitrogen-bound and carbon-bound iron, respectively, at 90 K, valence mixing between the iron sites could be quantified. By accounting for valence mixing, the sum of iron valences agreed with the sodium content determined from elemental analysis. Without an agreement between the total valence sum and the determined composition, there exists uncertainty around the accuracy of the elemental analysis and vacancy content determination. Thus, this study offers one more stepping stone toward a more rigorous characterization of composition in PW, which will enable further optimization of properties for battery applications. More broadly, the approach is valuable for characterizing iron-based PBAs in applications where precise composition, valence determination, and control are desired.
Simulation of the Potential Suitable Distribution of the Endangered Cremastra appendiculata in China Under Global Climate Change
Authors: Ouyang Xianheng , Chen Anliang , Brien Strachan Garry , Mao Yangjun , Zuo Luying , Lin Haiping
Published: July 2022

Predicting the spatial distribution of species in relation to suitable areas under global climate change could provide some references for conservation and long-term management strategies for the species. In this study, the MaxEnt was optimized by adjusting the feature combination and regulation magnification parameters with the ENMeval data package. Based on 127 Cremastra appendiculata spatial distribution locations and 14 environmental factors, the potential distribution areas of C. appendiculata under the present and future climate conditions (2050s, 2070s) were simulated, and the dominant environmental factors influencing the spatial distribution of C. appendiculata were analyzed. The feature combination (FC) and the regularization multiplier (RM) were selected as per the Akaike information criterion (AIC). The model showed complexity and degree of over-fitting (delta AICc = 0, omission rate = 0.106, the difference in the curve values between the training and testing areas was 0.021) after establishing the optimal model (FC = LQH and RM = 2.5), and the results indicated that the optimal model performed well in simulating the potential spatial distribution of C. appendiculata (the area under the receiver operating characteristic curve = 0.933). The results showed that the suitable habitat of C. appendiculata currently in China is 187.60 × 104 km2, while the highly suitable habitat is 118.47 × 104 km2, the moderately suitable habitat is 53.25 × 10 4 km2, and the poorly suitable habitat is 15.88 × 104 km2. There is an increasing trend in the suitable habitat of C. appendiculata under six climate scenarios, including SSP1-2.6, SSP2-4.5, and SSP5-8.5 in the 2050s and the 2070s, and that habitat will extend to the northwest as a whole. The highly suitable habitat of C. appendiculata in nature reserves is 0.47 × 104 km2; consequently, there is a large gap in the protection of C. appendiculata. The distribution of C. appendiculata was influenced by the temperature, precipitation, and normalized vegetation index.
Exploring Spatial Distributions and Formation Factors of Brownfields in China: From Macro-Scales
Authors: Zhang Xinjia , Song Yang , Qian Sitong , Wang Shijun , Wu Donghang
Published: July 2022

The spatial distribution pattern of brownfields can help governments at all levels, and investors have more detailed information on land resources, prioritize brownfield redevelopment, and guide urban spatial and strategic planning. Despite increasing global concern, yet knowledge of brownfield distribution patterns at the macro-scale remains limited, especially in China. Derived from the China National Knowledge Infrastructure (CNKI), Web of Science (WOS), and Chinese Industrial Heritage List published between 2001 and 2019, we present the first comprehensive dataset of known brownfield sites and their distributions in China. The results revealed that the dataset contains 816 georeferenced brownfield records from 255 cities. Brownfields were mainly distributed southeast of the “Heihe-Tengchong Line,” with an overall spatial distribution pattern of “East-dense-West-sparse.” In terms of brownfield type, industrial brownfields were the most numerous, followed by mining brownfields. Nearest neighbor indicator analysis suggested that brownfields in China present significant spatial agglomeration characteristics, and that the six types of brownfields manifest different scales of spatial agglomeration. The hot spots were mainly concentrated in the Yangtze River Delta, Beijing–Tianjin–Hebei, and Pearl River Delta urban agglomerations. Factors influencing brownfield formation were related to industrial structure adjustments, resource depletion, accelerated urbanization, and the orientation of national policies, with industrial structure adjustments being the leading cause. Mastering the spatial distribution of brownfields can coordinate land use transformation planning and guide brownfield redevelopment.
Identification and Toxicity Evaluation of Water-Soluble Chemicals Generated by the Photooxidative Degradation of Expanded Polystyrene
Authors: Lee Seulgidaun , Alam Md Badrul , Jung Maeng-Joon , Lee Sangkyu , Liu Kwang-Hyeon , Lee Sang-Han , Kim Sunghwan
Published: July 2022

In this study, expanded polystyrene (EPS) was photodegraded in vitro, and its water-soluble degradation products were extracted using solid-phase extraction. An in vivo test using the MTT assay showed that EPS exhibited increased toxicity upon photodegradation. This clearly demonstrates the necessity of investigating the degradation products at a molecular level, and thus, we conducted analyses using high-resolution mass spectrometry coupled with liquid chromatography. Overall, 68 compounds were detected, of which 13 were identified after comparing the retention times and tandem mass spectra of the extracted compounds with those of standards. The toxicity of the degraded EPS was studied by examination of the detected compounds combined with published reports. In addition, the quantification of the most abundant compounds showed that discarded EPS can generate a significant amount of chemicals by UV degradation. The data in this study show that degraded EPS can pose a significant environmental threat as a source of potentially hazardous chemicals. This study provides a fundamental basis for the evaluation of the fate and toxicity of photodegraded EPS.
Barriers and Facilitators for Population Genetic Screening in Healthy Populations: A Systematic Review
Authors: Shen Emily C. , Srinivasan Swetha , Passero Lauren E. , Allen Caitlin G. , Dixon Madison , Foss Kimberly , Halliburton Brianna , Milko Laura V. , Smit Amelia K. , Carlson Rebecca , Roberts Megan C.
Published: July 2022

Studies suggest that 1–3% of the general population in the United States unknowingly carry a genetic risk factor for a common hereditary disease. Population genetic screening is the process of offering otherwise healthy patients in the general population testing for genomic variants that predispose them to diseases that are clinically actionable, meaning that they can be prevented or mitigated if they are detected early. Population genetic screening may significantly reduce morbidity and mortality from these diseases by informing risk-specific prevention or treatment strategies and facilitating appropriate participation in early detection. To better understand current barriers, facilitators, perceptions, and outcomes related to the implementation of population genetic screening, we conducted a systematic review and searched PubMed, Embase, and Scopus for articles published from date of database inception to May 2020. We included articles that 1) detailed the perspectives of participants in population genetic screening programs and 2) described the barriers, facilitators, perceptions, and outcomes related to population genetic screening programs among patients, healthcare providers, and the public. We excluded articles that 1) focused on direct-to-consumer or risk-based genetic testing and 2) were published before January 2000. Thirty articles met these criteria. Barriers and facilitators to population genetic screening were organized by the Social Ecological Model and further categorized by themes. We found that research in population genetic screening has focused on stakeholder attitudes with all included studies designed to elucidate individuals’ perceptions. Additionally, inadequate knowledge and perceived limited clinical utility presented a barrier for healthcare provider uptake. There were very few studies that conducted long-term follow-up and evaluation of population genetic screening. Our findings suggest that these and other factors, such as prescreen counseling and education, may play a role in the adoption and implementation of population genetic screening. Future studies to investigate macro-level determinants, strategies to increase provider buy-in and knowledge, delivery models for prescreen counseling, and long-term outcomes of population genetic screening are needed for the effective design and implementation of such programs.

Systematic Review Registration: https://www.crd.york.ac.uk/prospero/display_record.php?ID=CRD42020198198
p53: A Regulator of Ferroptosis Induced by Galectin-1 Derived Peptide 3 in MH7A Cells
Authors: Hu Junzheng , Zhang Rui , Chang Qing , Ji Mingliang , Zhang Haixiang , Geng Rui , Li Chao , Wang Zhen
Published: July 2022

Backgrounds: Rheumatoid arthritis synovial fibroblasts (RASFs) are the primary cells responsible for destruction of marginal cartilage in rheumatoid arthritis (RA). G1dP3, a bioactive peptide derived from galectin-1 domain, possesses potent anti-inflammatory and anti-proliferation properties in RASFs. This study aimed to determine the effects of G1dP3 ferroptosis induction in RASFs and to further clarify the possible mechanisms.

Methods: TNF-α was used to establish a RA model in MH7A cells. Cell Counting Kit-8 assays were employed to detect MH7A cell viability with different treatments. The occurrence of ferroptosis was examined by Lipid ROS assay, cellular labile iron pool measurement, reduced glutathione/oxidized glutathione activity, Gpx4 expression and transmission electron microscopy (TEM) morphology observation. Lentiviral-mediated siRNA interference was used to determine the downstream pathway.

Results: G1dP3 markedly suppressed MH7A cell viability induced by TNF-α. G1dP3-treated MH7A cells presented the morphological features of ferroptosis. Moreover, G1dP3 triggered ferroptosis in MH7A cells by promoting the accumulation of lipid peroxides as well as iron deposition. Inhibition of ferroptosis alleviated G1dP3-mediated suppression of MH7A cell viability. Furthermore, G1dP3 increased p53 expression, which in turn transcriptionally suppressed SLC7A11, a key component of system Xc− essential for ferroptosis. Knockdown of p53 abrogated the ferroptotic effects of G1dP3 on MH7A cells.

Conclusion: Our findings reveal that the bioactive peptide G1dP3 promotes RASFs ferroptosis cell death via a p53/SLC7A11 axis-dependent mechanism, suggesting its potential role in the treatment of RA.
Toward a Standard Measure of Abortion Service Quality-A Stakeholder First Approach
Authors: Chakraborty Nirali M. , Pearson Erin , Gerdts Caitlin , Baum Sarah E. , Powell Bill , Montagu Dominic
Published: July 2022

Measurement of the quality of abortion services is essential to service improvement. Currently, its measurement is not standardized, and some of the tools which exist are very long, and may deter use. To address this issue, this study describes a process used to create a new, more concise measure of abortion care quality, which was done with the end users in mind. Using a collaborative approach and engaging numerous stakeholders, we developed an approach to defining and selecting a set of indicators, to be tested against abortion outcomes of interest. Indicators were solicited from 12 abortion service provision entities, cataloged, and grouped within a theoretical framework. A resource group of over 40 participants was engaged through surveys, webinars, and one in-person meeting to provide input in prioritizing the indicators. We began with a list of over 1,000 measures, and engaged stakeholders to reduce the list to 72 indicators for testing. These indicators were supplemented with an additional 39 indicators drawn from qualitative research with clients, in order to ensure the client perspective is well represented. The selected indicators can be applied in pharmacies, facilities, or with hotlines, and for clients of surgical or medical abortion services in all countries. To ensure that the final suggested measures are most impactful for service providers, indicators will be tested against outcomes from 2,000 abortion clients in three countries. Those indicators which are well correlated with outcomes will be prioritized.
The Outcome of Induction Therapy for EBV-Related Hemophagocytic Lymphohistiocytosis: A Model for Risk Stratification
Authors: Cui Tingting , Wang Jingshi , Wang Zhao
Published: July 2022

Background

Epstein–Barr virus (EBV)–related hemophagocytic lymphohistiocytosis (HLH) is an abnormal inflammation caused by EBV infection, which has high mortality during induction therapy.

Objectives

This study is aimed to build a model to predict the risk of death during induction therapy.

Methods

The patients with EBV-HLH admitted from January 2015 to December 2018 were retrospectively reviewed. The primary outcome was death during induction therapy. The interval from receiving therapy to death or the end of induction therapy was the observing time. The patients admitted from January 2015 to December 2017 were assigned to the primary group, and the patients admitted from January to December 2018 were assigned to the validation group.

Results

We included 234 patients with EBV-HLH, of whom 65 (27.4%) died during induction therapy. The middle observing time was 25 days. On the basis of the primary group, the multivariate Cox analysis demonstrated age >18 years, blood urea nitrogen, procalcitonin >2 µg/L, serum CD25, and EBV-DNA in peripheral blood mononuclear cell as the risk factors of death during induction therapy. We developed a nomogram integrating the above factors with high predictive accuracy (c-statistic, 0.86) and stratified all patients into the high-risk and the low-risk groups. On the basis of the validation group, the high-risk patients had a higher risk of death (hazard ratio, 4.93; P = 0.012). In the subgroup analysis based on patients receiving etoposide-based strategy, the mortality in high-risk and low-risk patients was 43.9 and 3.1 per 100 person-weeks, respectively.

Conclusion

We developed a nomogram for risk stratification of patients with EBV-HLH receiving induction therapy.
Pathogenic Mechanism and Multi-omics Analysis of Oral Manifestations in COVID-19
Authors: Hao Ming , Wang Dongxu , Xia Qianyun , Kan Shaoning , Chang Lu , Liu Huimin , Yang Zhijing , Liu Weiwei
Published: July 2022

Coronavirus disease 2019 (COVID-19) is a respiratory infectious disease that seriously threatens human life. The clinical manifestations of severe COVID-19 include acute respiratory distress syndrome and multiple organ failure. Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), the causal agent of COVID-19, spreads through contaminated droplets. SARS-CoV-2 particles have been detected in the saliva of COVID-19 patients, implying that the virus can infect and damage the oral cavity. The oral manifestations of COVID-19 include xerostomia and gustatory dysfunction. Numerous studies showed that the four structural proteins of SARS-CoV-2 are its potential pathogenic factors, especially the S protein, which binds to human ACE2 receptors facilitating the entry of the virus into the host cells. Usually, upon entry into the host cell, a pathogen triggers the host’s immune response. However, a mount of multi-omics and immunological analyses revealed that COVID-19 is caused by immune dysregulation. A decrease in the number and phenotypes of immune cells, IFN-1 production and excessive release of certain cytokines have also been reported. In conclusion, this review summarizes the oral manifestations of COVID-19 and multi-omics analysis of SARS-CoV-2 infection.
In Vitro Exposure of Primary Human T Cells and Monocytes to Polyclonal Stimuli Reveals a Basal Susceptibility to Display an Impaired Cellular Immune Response and Develop Severe COVID-19
Authors: Viurcos-Sanabria Rebeca , Manjarrez-Reyna Aarón N. , Solleiro-Villavicencio Helena , Rizo-Téllez Salma A. , Méndez-García Lucía A. , Viurcos-Sanabria Victoria , González-Sanabria Jacquelina , Arroyo-Valerio América , Carrillo-Ruíz José D. , González-Chávez Antonio , León-Pedroza Jose I. , Flores-Mejía Raúl , Rodríguez-Cortés Octavio , Escobedo Galileo
Published: July 2022

The contribution of the cellular immune response to the severity of coronavirus disease 2019 (COVID-19) is still uncertain because most evidence comes from patients receiving multiple drugs able to change immune function. Herein, we conducted a prospective cohort study and obtained blood samples from 128 unvaccinated healthy volunteers to examine the in vitro response pattern of CD4+ and CD8+ T cells and monocyte subsets to polyclonal stimuli, including anti-CD3, anti-CD28, poly I:C, severe acute respiratory syndrome coronavirus type 2 (SARS-CoV-2) recombinant spike S1 protein, and lipopolysaccharide. Then, we started a six-month follow-up and registered 12 participants who got SARS-CoV-2 infection, from whom we retrospectively analyzed the basal immune response pattern of T cells and monocytes. Of the 12 participants infected, six participants developed mild COVID-19 with self-limiting symptoms such as fever, headache, and anosmia. Conversely, six other participants developed severe COVID-19 with pneumonia, respiratory distress, and hypoxia. Two severe COVID-19 cases required invasive mechanical ventilation. There were no differences between mild and severe cases for demographic, clinical, and biochemical baseline characteristics. In response to polyclonal stimuli, basal production of interleukin-2 (IL-2) and interferon (IFN-) gamma significantly decreased, and the programmed cell death protein 1 (PD-1) increased in CD4+ and CD8+ T cells from participants who posteriorly developed severe COVID-19 compared to mild cases. Likewise, CD14++CD16- classical and CD14+CD16+ non-classical monocytes lost their ability to produce IFN-alpha in response to polyclonal stimuli in participants who developed severe COVID-19 compared to mild cases. Of note, neither the total immunoglobulin G serum titers against the virus nor their neutralizing ability differed between mild and severe cases after a month of clinical recovery. In conclusion, using in vitro polyclonal stimuli, we found a basal immune response pattern associated with a predisposition to developing severe COVID-19, where high PD-1 expression and low IL-2 and IFN-gamma production in CD4+ and CD8+ T cells, and poor IFN-alpha expression in classical and non-classical monocytes are linked to disease worsening. Since antibody titers did not differ between mild and severe cases, these findings suggest cellular immunity may play a more crucial role than humoral immunity in preventing COVID-19 progression.
Clinical Evaluation of Autologous and Allogeneic Stem Cell Therapy for Intrauterine Adhesions: A Systematic Review and Meta-Analysis
Authors: Chen Jia-ming , Huang Qiao-yi , Chen Wei-hong , Lin Shu , Shi Qi-yang
Published: July 2022

Objective

Intrauterine adhesions (IUAs) are a major cause of female infertility. Stem cells can be used to restore endometrial function owing to their regenerative abilities. We compared the safety and efficacy of autologous and allogeneic stem cell treatments in patients with recurrent IUA after conventional therapy based on a systematic review of the related literature.

Methods

The PubMed, Embase, and Cochrane databases were systematically searched. All analysis were performed using Review Manager 5.4. We compared improvements in endometrial thickness, pregnancy rates, menstruation, and side effects after autologous and allogeneic stem cell therapy. The study was registered with PROSPERO, CRD 42022322870.

Results

Our search returned 154 reports, 10 of which met the inclusion criteria, representing 116 patients. Of these, 44 patients in two studies were treated with allogeneic stem cells and 72 patients in eight studies were treated with autologous stem cells. Improvements in endometrial thickness and pregnancy rates after intrauterine device treatment were compared between the autologous and allogeneic stem cell groups. Endometrial thickness increased more after autologous stem cell IUA treatment (mean difference, 1.68; 95% confidence interval [CI]: 1.30–2.07; P < 0.00001), and the pregnancy rate was also improved (relative risk, 1.55; 95% CI: 1.19–2.02, P < 0. 001). No obvious and serious adverse reactions were observed during stem cell therapy in either group.

Conclusions

This meta-analysis and systematic review of the results of randomized trials of autologous and allogeneic stem cell treatments for IUA suggests that autologous stem cells have a better effect in improving the endometrium thickness and pregnancy rate.

Systematic Review Registration

https://www.crd.york.ac.uk/PROSPERO/, identifier CRD42022322870.
Obesity, Inflammation, and Immune System in Osteoarthritis
Authors: Nedunchezhiyan Udhaya , Varughese Ibin , Sun Antonia RuJia , Wu Xiaoxin , Crawford Ross , Prasadam Indira
Published: July 2022

Obesity remains the most important risk factor for the incidence and progression of osteoarthritis (OA). The leading cause of OA was believed to be overloading the joints due to excess weight which in turn leads to the destruction of articular cartilage. However, recent studies have proved otherwise, various other factors like adipose deposition, insulin resistance, and especially the improper coordination of innate and adaptive immune responses may lead to the initiation and progression of obesity-associated OA. It is becoming increasingly evident that multiple inflammatory cells are recruited into the synovial joint that serves an important role in pathological changes in the synovial joint. Polarization of macrophages and macrophage-produced mediators are extensively studied and linked to the inflammatory and destructive responses in the OA synovium and cartilage. However, the role of other major innate immune cells such as neutrophils, eosinophils, and dendritic cells in the pathogenesis of OA has not been fully evaluated. Although cells of the adaptive immune system contribute to the pathogenesis of obesity-induced OA is still under exploration, a quantity of literature indicates OA synovium has an enriched population of T cells and B cells compared with healthy control. The interplay between a variety of immune cells and other cells that reside in the articular joints may constitute a vicious cycle, leading to pathological changes of the articular joint in obese individuals. This review addresses obesity and the role of all the immune cells that are involved in OA and summarised animal studies and human trials and knowledge gaps between the studies have been highlighted. The review also touches base on the interventions currently in clinical trials, different stages of the testing, and their shortcomings are also discussed to understand the future direction which could help in understanding the multifactorial aspects of OA where inflammation has a significant function.
Gut Microflora Modulates Th17/Treg Cell Differentiation in Experimental Autoimmune Prostatitis via the Short-Chain Fatty Acid Propionate
Authors: Du He-Xi , Yue Shao-Yu , Niu Di , Liu Chang , Zhang Li-Gang , Chen Jing , Chen Yang , Guan Yu , Hua Xiao-Liang , Li Chun , Chen Xian-Guo , Zhang Li , Liang Chao-Zhao
Published: July 2022

Chronic prostatitis/chronic pelvic pain syndrome (CP/CPPS) is a very common urological disorder and has been gradually regarded as an immune-mediated disease. Multiple studies have indicated that the gut microflora plays a pivotal part in immune homeostasis and autoimmune disorder development. However, whether the gut microflora affects the CP/CPPS, and the underlying mechanism behind them remain unclear. Here, we built an experimental autoimmune prostatitis (EAP) mouse model by subcutaneous immunity and identified that its Th17/Treg frequency was imbalanced. Using fecal 16s rRNA sequencing and untargeted/targeted metabolomics, we discovered that the diversity and relative abundance of gut microflora and their metabolites were obviously different between the control and the EAP group. Propionic acid, a kind of short-chain fatty acid (SCFA), was decreased in EAP mice compared to that in controls, and supplementation with propionic acid reduced susceptibility to EAP and corrected the imbalance of Th17/Treg cell differentiation in vivo and in vitro. Furthermore, SCFA receptor G-protein-coupled receptor 43 and intracellular histone deacetylase 6 regulated by propionic acid in Th17 and Treg cells were also evaluated. Lastly, we observed that fecal transplantation from EAP mice induced the decrease of Treg cell frequency in recipient mice. Our data showed that gut dysbiosis contributed to a Th17/Treg differentiation imbalance in EAP via the decrease of metabolite propionic acid and provided valuable immunological groundwork for further intervention in immunologic derangement of CP/CPPS by targeting propionic acid.
Cross-Talk of Multiple Types of RNA Modification Regulators Uncovers the Tumor Microenvironment and Immune Infiltrates in Soft Tissue Sarcoma
Authors: Qi Lin , Zhang Wenchao , Ren Xiaolei , Xu Ruiling , Yang Zhimin , Chen Ruiqi , Tu Chao , Li Zhihong
Published: July 2022

Background

Soft-tissue sarcoma (STS) represents a rare and diverse cohort of solid tumors, and encompasses over 100 various histologic and molecular subtypes. In recent years, RNA modifications including m6A, m5C, m1A, and m7G have been demonstrated to regulate immune response and tumorigenesis. Nevertheless, the cross-talk among these RNA modification regulators and related effects upon the tumor microenvironment (TME), immune infiltrates, and immunotherapy in STS remain poorly understood.

Methods

In this study, we comprehensively investigated transcriptional and genetic alterations of 32 RNA modification regulators in STS patients from The Cancer Genome Atlas (TCGA) cohort and validated them in the Gene Expression Omnibus (GEO) cohort. Single-cell transcriptomes were introduced to identify regulators within specific cell types, with own sequencing data and RT-qPCR conducted for biological validation. Distinct regulator clusters and regulator gene subtypes were identified by using unsupervised consensus clustering analysis. We further built the regulator score model based on the prognostic regulator-related differentially expressed genes (DEGs), which could be used to quantitatively assess the risk for individual STS patients. The clinical and biological characteristics of different regulator score groups were further examined.

Results

A total of 455 patients with STS were included in this analysis. The network of 32 RNA modification regulators demonstrated significant correlations within multiple different RNA modification types. Distinct regulator clusters and regulator gene subtypes were characterized by markedly different prognoses and TME landscapes. The low regulator score group in the TCGA-SARC cohort was characterized by poor prognosis. The robustness of the scoring model was further confirmed by the external validation in GSE30929 and GSE17674. The regulator score was negatively correlated with CD4+ T cell, Th2 cell, and Treg cell recruitment and most immunotherapy-predicted pathways, and was also associated with immunotherapy efficacy.

Conclusions

Overall, our study is the first to demonstrate the cross-talk of RNA modification regulators and the potential roles in TME and immune infiltrates in STS. The individualized assessment based on the regulator score model could facilitate and optimize personalized treatment.
Phylogenetic Classification and Functional Review of Autotransporters
Authors: Clarke Kaitlin R. , Hor Lilian , Pilapitiya Akila , Luirink Joen , Paxman Jason J. , Heras Begoña
Published: July 2022

Autotransporters are the core component of a molecular nano-machine that delivers cargo proteins across the outer membrane of Gram-negative bacteria. Part of the type V secretion system, this large family of proteins play a central role in controlling bacterial interactions with their environment by promoting adhesion to surfaces, biofilm formation, host colonization and invasion as well as cytotoxicity and immunomodulation. As such, autotransporters are key facilitators of fitness and pathogenesis and enable co-operation or competition with other bacteria. Recent years have witnessed a dramatic increase in the number of autotransporter sequences reported and a steady rise in functional studies, which further link these proteins to multiple virulence phenotypes. In this review we provide an overview of our current knowledge on classical autotransporter proteins, the archetype of this protein superfamily. We also carry out a phylogenetic analysis of their functional domains and present a new classification system for this exquisitely diverse group of bacterial proteins. The sixteen phylogenetic divisions identified establish sensible relationships between well characterized autotransporters and inform structural and functional predictions of uncharacterized proteins, which may guide future research aimed at addressing multiple unanswered aspects in this group of therapeutically important bacterial factors.
A Novel M6A-Related Genes Signature Can Impact the Immune Status and Predict the Prognosis and Drug Sensitivity of Lung Adenocarcinoma
Authors: Wang Xuewen , Zhao Chengfei , Huang Dandan , Liu Zhoujie , Liu Mengmeng , Lin Fei , Lu Yingyu , Jia Jing , Lin Liqing , Lin Xinhua , Li Huangyuan , Chen Zhiwei
Published: July 2022

Lung adenocarcinoma (LUAD) is a primary cause of cancer-related death around the world and has a poor outcome and high incidence. Treatment options are, however, restricted. One of the most critical factors in cancer and metastasis is the N6-methyladenine (m6A) alteration on RNA. This modification could alter gene expression and even function at numerous levels, such as the stability, translocation and translation of RNA splicing. This study aimed to construct an m6A-related genes signature to accurately predict the prognosis of LUAD patients. From TCGA datasets, the LUAD patient data and m6A-related genes were retrieved. LUAD patients’ mutational features and differentially expressed genes (DEGs) were investigated. An univariate and LASSO model with m6A-related genes were constructed for the prediction of outcomes in LUAD. It was possible to develop a prognostic nomogram that could quantitatively predict LUAD patients’ overall survival chances at 1, 3, and 5 years. Research into biological processes and cell pathways was carried out using GSEA. This study found six m6A-related DEGs in LUAD patients, and three of these DEGs(HNRNPC, IGFBP3 and IGF2BP1) were linked to the clinical outcomes of LUAD patients. We found that the overall survival rate for all LUAD patients with high-risk subgroup was considerably lower. According to ROC curves, the prognostic signature demonstrated a high degree of accuracy in predicting future outcomes. In addition, we created a novel nomogram achieved great accuracy with this one as well. The researchers also found that the novel signature might favorably modulate the immune response, and high-risk scores samples were more susceptible to numerous chemotherapeutic medicines. Overall, we developed a m6A-related gene prognostic signature that effectively predicted outcomes of LUAD patients and gave an immunological perspective for creating customized therapeutics.
Negative Regulation of Zap70 by Lck Forms the Mechanistic Basis of Differential Expression in CD4 and CD8 T Cells
Authors: Damen Hassan , Tebid Christian , Viens Melissa , Roy Denis-Claude , Dave Vibhuti P.
Published: July 2022

Lck and Zap70, two non-receptor tyrosine kinases, play a crucial role in the regulation of membrane proximal TCR signaling critical for thymic selection, CD4/CD8 lineage choice and mature T cell function. Signal initiation upon TCR/CD3 and peptide/MHC interaction induces Lck-mediated phosphorylation of CD3 ITAMs. This is necessary for Zap70 recruitment and its phosphorylation by Lck leading to full Zap70 activation. In its native state Zap70 maintains a closed conformation creating an auto-inhibitory loop, which is relieved by Lck-mediated phosphorylation of Y315/Y319. Zap70 is differentially expressed in thymic subsets and mature T cells with CD8 T cells expressing the highest amount compared to CD4 T cells. However, the mechanistic basis of differential Zap70 expression in thymic subsets and mature T cells is not well understood. Here, we show that Zap70 is degraded relatively faster in DP and mature CD4 T cells compared to CD8 T cells, and inversely correlated with relative level of activated Zap70. Importantly, we found that Zap70 expression is negatively regulated by Lck activity: augmented Lck activity resulting in severe diminution in total Zap70. Moreover, Lck-mediated phosphorylation of Y315/Y319 was essential for Zap70 degradation. Together, these data shed light on the underlying mechanism of Lck-mediated differential modulation of Zap70 expression in thymic subsets and mature T cells.
Comparison of Rapid Cytokine Immunoassays for Functional Immune Phenotyping
Authors: Bonavia Anthony S. , Samuelsen Abigail , Chroneos Zissis C. , Halstead Eric Scott
Published: July 2022

Background

Cell-based functional immune-assays may allow for risk stratification of patients with complex, heterogeneous immune disorders such as sepsis. Given the heterogeneity of patient responses and the uncertain immune pathogenesis of sepsis, these assays must first be defined and calibrated in the healthy population.

Objective

Our objective was to compare the internal consistency and practicality of two immune assays that may provide data on surrogate markers of the innate and adaptive immune response. We hypothesized that a rapid turnaround, microfluidic-based immune assay (ELLA) would be comparable to a dual-color, enzyme-linked immunospot (ELISpot) assay in identifying tumor necrosis factor (TNF) and interferon (IFN)γ production following ex vivo whole blood stimulation.

Design

This was a prospective, observational cohort analysis. Whole blood samples from ten healthy, immune-competent volunteers were stimulated for either 4 hours or 18 hours with lipopolysaccharide, anti-CD3/anti-CD28 antibodies, or phorbol 12-myristate 13-acetate with ionomycin to interrogate innate and adaptive immune responses, respectively.

Measurements and Main Results

ELLA analysis produced more precise measurement of TNF and IFNγ concentrations as compared with ELISpot, as well as a four- to five-log10 dynamic range for TNF and IFNγ concentrations, as compared with a two-log10 dynamic range with ELISpot. Unsupervised clustering accurately predicted the ex vivo immune stimulant used for 90% of samples analyzed via ELLA, as compared with 72% of samples analyzed via ELISpot.

Conclusions

We describe, for the first time, a rapid and precise assay for functional interrogation of the innate and adaptive arms of the immune system in healthy volunteers. The advantages of the ELLA microfluidic platform may represent a step forward in generating a point-of-care test with clinical utility, for identifying deranged immune phenotypes in septic patients.
Interleukin 10 Polymorphisms as Risk Factors for Progression to Chagas Disease Cardiomyopathy: A Case-Control Study and Meta-Analysis
Authors: Grijalva Alicia , Gallo Vaulet Lucia , Agüero Roberto Nicolas , Toledano Analia , Risso Marikena Guadalupe , Quarroz Braghini Juan , Sosa David , Ruybal Paula , Repetto Silvia , Alba Soto Catalina Dirney
Published: July 2022

Background

Chagas disease is a lifelong infection caused by the protozoa Trypanosoma cruzi endemic in Latin-America and emergent worldwide. Decades after primary infection, 20-30% of infected people develop chronic Chagas cardiomyopathy (CCC) while the others remain asymptomatic. CCC pathogenesis is complex but associated with sustained pro-inflammatory response leading to tissue damage. Hence, levels of IL-10 could have a determinant role in CCC etiology. Studies with Latin-American populations have addressed the association of genetic variants of IL-10 and the risk of developing CCC with inconsistent results. We carried out a case control study to explore the association between IL-10-1082G>A (rs18008969), -819C>T (rs1800871), -592A>C (rs1800872) polymorphisms and CCC in a population attending a hospital in Buenos Aires Argentina. Next, a systematic review of the literature and a meta-analysis were conducted combining present and previous studies to further study this association.

Methods

Our case control study included 122 individuals with chronic T. cruzi infection including 64 patients with any degree of CCC and 58 asymptomatic individuals. Genotyping of IL-10 -1082G>A, -819C>T, -592A>C polymorphisms was performed by capillary sequencing of the region spanning the three polymorphic sites and univariate and multivariate statistical analysis was undertaken. Databases in English, Spanish and Portuguese language were searched for papers related to these polymorphisms and Chagas disease up to December 2021. A metanalysis of the selected literature and our study was performed based on the random effect model.

Results

In our cohort, we found a significant association between TT genotype of -819 rs1800871 and AA genotype of -592 rs1800872 with CCC under the codominant (OR=5.00; 95%CI=1.12-23.87 P=0,04) and the recessive models (OR=5.37; 95%CI=1.12-25.68; P=0,03). Of the genotypes conformed by the three polymorphic positions, the homozygous genotype ATA was significantly associated with increased risk of CCC. The results of the meta-analysis of 754 cases and 385 controls showed that the TT genotype of -819C>T was associated with increased CCC risk according to the dominant model (OR=1.13; 95% CI=1.02–1.25; P=0,03).

Conclusion

The genotype TT at -819 rs1800871 contributes to the genetic susceptibility to CCC making this polymorphism a suitable candidate to be included in a panel of predictive biomarkers of disease progression.
Plastic-Associated Microbial Communities in Aquaculture Areas
Authors: Mohsen Mohamed , Lin Chenggang , Hamouda Hamed I. , Al-Zayat Ahmed M. , Yang Hongsheng
Published: July 2022

Microorganisms colonize plastics in the aquatic environment but their composition on plastics used in aquaculture remains poorly studied. Microorganisms play a significant role in aquaculture in terms of water quality and the health of cultivated species. In the current study, we explored the composition of microorganisms on floating plastics and their surrounding water collected from ponds and open aquaculture areas. Using scanning electron microscopy, the diversity of microbial communities, primarily diatoms, and bacteria were identified on the plastic surfaces. Additionally, epifluorescence microscopy revealed that prokaryotes were colonized on all plastic samples from 0.1 to 29.27×103 cells/cm2, with a high abundance found in open aquaculture areas compared to ponds. Bacterial communities were characterized by 16S rRNA sequencing which showed that bacterial communities on plastics were dominated by Proteobacteria, Cyanobacteria, Bacteroidetes, and Actinobacteria. The level of these microbial communities on the plastics differed from those found in the surrounding seawater samples and the abundance of potentially pathogenic bacteria was higher in plastics than in seawater samples. Moreover, hydrocarbon-degrading bacteria were more abundant in the investigated plastic samples than in the water samples. This study contributes to the knowledge regarding the plastisphere community in aquaculture.