bluuebunny/crossref_metadata_2025 huggingface dataset:
Identification of autoantigens and their potential post-translational modification in EGPA and severe eosinophilic asthma
Authors: Esposito Ilaria , Kontra Ioanna , Giacomassi Chiara , Manou-Stathopoulou Sotiria , Brown James , Stratton Richard , Verykokou Galateia , Buccafusca Roberto , Stevens Michael , Nissim Ahuva , Lewis Myles J. , Pfeffer Paul E.
Published: June 2023

Background

The chronic airway inflammation in severe eosinophilic asthma (SEA) suggests potential autoimmune aetiology with unidentified autoantibodies analogous to myeloperoxidase (MPO) in ANCA-positive EGPA (eosinophilic granulomatosis with polyangiitis). Previous research has shown that oxidative post-translational modification (oxPTM) of proteins is an important mechanism by which autoantibody responses may escape immune tolerance. Autoantibodies to oxPTM autoantigens in SEA have not previously been studied.

Methods

Patients with EGPA and SEA were recruited as well as healthy control participants. Autoantigen agnostic approach: Participant serum was incubated with slides of unstimulated and PMA-stimulated neutrophils and eosinophils, and autoantibodies to granulocytes were identified by immunofluorescence with anti-human IgG FITC antibody. Target autoantigen approach: Candidate proteins were identified from previous literature and FANTOM5 gene set analysis for eosinophil expressed proteins. Serum IgG autoantibodies to these proteins, in native and oxPTM form, were detected by indirect ELISA.

Results

Immunofluorescence studies showed that serum from patients with known ANCA stained for IgG against neutrophils as expected. In addition, serum from 9 of 17 tested SEA patients stained for IgG to PMA-stimulated neutrophils undergoing NETosis. Immunofluorescent staining of eosinophil slides was evident with serum from all participants (healthy and with eosinophilic disease) with diffuse cytoplasmic staining except for one SEA individual in whom subtle nuclear staining was evident. FANTOM5 gene set analysis identified TREM1 (triggering receptor expressed on myeloid cells 1) and IL-1 receptor 2 (IL1R2) as eosinophil-specific targets to test for autoantibody responses in addition to MPO, eosinophil peroxidase (EPX), and Collagen-V identified from previous literature. Indirect ELISAs found high concentrations of serum autoantibodies to Collagen-V, MPO, and TREM1 in a higher proportion of SEA patients than healthy controls. High concentrations of serum autoantibodies to EPX were evident in serum from both healthy and SEA participants. The proportion of patients with positive autoantibody ELISAs was not increased when examining oxPTM compared to native proteins.

Discussion

Although none of the target proteins studied showed high sensitivity for SEA, the high proportion of patients positive for at least one serum autoantibody shows the potential of more research on autoantibody serology to improve diagnostic testing for severe asthma.

Clinical trial registration

ClinicalTrials.gov, identifier, NCT04671446.
A synthetic glycodendropeptide induces methylation changes on regulatory T cells linked to tolerant responses in anaphylactic-mice
Authors: Núñez Rafael , Rodríguez María J. , Lebrón-Martín Clara , Martín-Astorga María del Carmen , Ramos-Soriano Javier , Rojo Javier , Torres María J. , Cañas José A. , Mayorga Cristobalina
Published: June 2023

Introduction

Lipid transfer proteins (LTPs) are allergens found in a wide range of plant-foods. Specifically, Pru p 3, the major allergen of peach, is commonly responsible for severe allergic reactions. The need for new alternatives to conventional food allergy treatments, like restrictive diets, suggests allergen immunotherapy as a promising option. It has been demonstrated that sublingual immunotherapy (SLIT) with synthetic glycodendropeptides, such as D1ManPrup3, containing mannose and Pru p 3 peptides induced tolerance in mice and that the persistence of this effect depends on treatment dose (2nM or 5nM). Moreover, it produces changes associated with differential gene expression and methylation profile of dendritic cells, as well as phenotypical changes in regulatory T cells (Treg). However, there are no works addressing the study of epigenetic changes in terms of methylation in the cell subsets that sustain tolerant responses, Treg. Therefore, in this work, DNA methylation changes in splenic-Treg from Pru p 3 anaphylactic mice were evaluated.

Methods

It was performed by whole genome bisulphite sequencing comparing SLIT-D1ManPrup3 treated mice: tolerant (2nM D1ManPrup3), desensitized (5nM D1ManPrup3), and sensitized but not treated (antigen-only), with anaphylactic mice.

Results

Most of the methylation changes were found in the gene promoters from both SLIT-treated groups, desensitized (1,580) and tolerant (1,576), followed by the antigen-only (1,151) group. Although tolerant and desensitized mice showed a similar number of methylation changes, only 445 genes were shared in both. Remarkably, interesting methylation changes were observed on the promoter regions of critical transcription factors for Treg function like Stat4, Stat5a, Stat5b, Foxp3, and Gata3. In fact, Foxp3 was observed exclusively as hypomethylated in tolerant group, whereas Gata3 was only hypomethylated in the desensitized mice.

Discussion

In conclusion, diverse D1ManPrup3 doses induce different responses (tolerance or desensitization) in mice, which are reflected by differential methylation changes in Tregs.
Exploration of the impact of multimode thermal therapy versus radiofrequency ablation on CD8+ T effector cells of liver malignancies based on single cell transcriptomics
Authors: Wang Ying , Wang Guang-Zhi , Chen Chao , Huang Hao-Zhe , Wang Yao-Hui , He Xin-Hong , Xu Lisa X. , Xu Li-Chao , Li Wen-Tao
Published: June 2023

Introduction

Multimode thermal therapy (MTT) is an innovative interventional therapy developed for the treatment of liver malignancies. When compared to the conventional radiofrequency ablation (RFA), MTT typically offers improved prognosis for patients. However, the effect of MTT on the peripheral immune environment and the mechanisms underlying the enhanced prognosis have yet to be explored. The aim of this study was to further investigate the mechanisms responsible for the difference in prognosis between the two therapies.

Methods

In this study, peripheral blood samples were collected from four patients treated with MTT and two patients treated with RFA for liver malignancies at different time points before and after the treatment. Single cell sequencing was performed on the blood samples to compare and analyze the activation pathways of peripheral immune cells following the MTT and RFA treatment.

Results

There was no significant effect of either therapy on the composition of immune cells in peripheral blood. However, the differential gene expression and pathway enrichment analysis demonstrated enhanced activation of T cells in the MTT group compared to the RFA group. In particular, there was a remarkable increase in TNF-α signaling via NF-κB, as well as the expression of IFN-α and IFN-γ in the CD8+ effector T (CD8+ Teff) cells subpopulation, when compared to the RFA group. This may be related to the upregulation of PI3KR1 expression after MTT, which promotes the activation of PI3K-AKT-mTOR pathway.

Conclusion

This study confirmed that MTT could more effectively activate peripheral CD8+ Teff cells in patients compared with RFA and promote the effector function, thus resulting in a better prognosis. These results provide a theoretical basis for the clinical application of MTT therapy.
The roles of XJ13 and XJ44-specific mutations within the Candid #1 GPC in Junin virus attenuation
Authors: Manning John Tyler , Maruyama Junki , Wanninger Timothy , Reyna Rachel A. , Stevenson Heather L. , Peng Bi-Hung , Mantlo Emily K. , Huang Cheng , Paessler Slobodan
Published: June 2023

Junin virus (JUNV) is a member of the Arenaviridae family of viruses and is the pathogen responsible for causing Argentine hemorrhagic fever, a potentially lethal disease endemic to Argentina. A live attenuated vaccine for human use, called Candid#1, is approved only in Argentina. Candid#1 vaccine strain of Junin virus was obtained through serial passage in mouse brain tissues followed by passage in Fetal Rhesus macaque lung fibroblast (FRhL) cells. Previously, the mutations responsible for attenuation of this virus in Guinea pigs were mapped in the gene encoding for glycoprotein precursor (GPC) protein. The resulting Candid#1 glycoprotein complex has been shown to cause endoplasmic reticulum (ER) stress in vitro resulting in the degradation of the GPC. To evaluate the attenuating properties of specific mutations within GPC, we created recombinant viruses expressing GPC mutations specific to key Candid#1 passages and evaluated their pathogenicity in our outbred Hartley guinea pig model of Argentine hemorrhagic fever. Here, we provide evidence that early mutations in GPC obtained through serial passaging attenuate the visceral disease and increase immunogenicity in guinea pigs. Specific mutations acquired prior to the 13th mouse brain passage (XJ13) are responsible for attenuation of the visceral disease while having no impact on the neurovirulence of Junin virus. Additionally, our findings demonstrate that the mutation within an N-linked glycosylation motif, acquired prior to the 44th mouse brain passage (XJ44), is unstable but necessary for complete attenuation and enhanced immunogenicity of Candid#1 vaccine strain. The highly conserved N-linked glycosylation profiles of arenavirus glycoproteins could therefore be viable targets for designing attenuating viruses for vaccine development against other arenavirus-associated illnesses.
The molecular basis of the neutralization breadth of the RBD-specific antibody CoV11
Authors: Tolbert William D. , Chen Yaozong , Sun Lulu , Benlarbi Mehdi , Ding Shilei , Manickam Rohini , Pangaro Emily , Nguyen Dung N. , Gottumukkala Suneetha , Côté Marceline , Gonzalez Frank J. , Finzi Andrés , Tehrani Zahra R. , Sajadi Mohammad M. , Pazgier Marzena
Published: June 2023

SARS-CoV-2, the virus behind the COVID-19 pandemic, has changed over time to the extent that the current virus is substantially different from what originally led to the pandemic in 2019–2020. Viral variants have modified the severity and transmissibility of the disease and continue do so. How much of this change is due to viral fitness versus a response to immune pressure is hard to define. One class of antibodies that continues to afford some level of protection from emerging variants are those that closely overlap the binding site for angiotensin-converting enzyme 2 (ACE2) on the receptor binding domain (RBD). Some members of this class that were identified early in the course of the pandemic arose from the VH 3-53 germline gene (IGHV3-53*01) and had short heavy chain complementarity-determining region 3s (CDR H3s). Here, we describe the molecular basis of the SARS-CoV-2 RBD recognition by the anti-RBD monoclonal antibody CoV11 isolated early in the COVID-19 pandemic and show how its unique mode of binding the RBD determines its neutralization breadth. CoV11 utilizes a heavy chain VH 3-53 and a light chain VK 3-20 germline sequence to bind to the RBD. Two of CoV11’s four heavy chain changes from the VH 3-53 germline sequence, ThrFWR H128 to Ile and SerCDR H131 to Arg, and some unique features in its CDR H3 increase its affinity to the RBD, while the four light chain changes from the VK 3-20 germline sequence sit outside of the RBD binding site. Antibodies of this type can retain significant affinity and neutralization potency against variants of concern (VOCs) that have diverged significantly from original virus lineage such as the prevalent omicron variant. We also discuss the mechanism by which VH 3-53 encoded antibodies recognize spike antigen and show how minimal changes to their sequence, their choice of light chain, and their mode of binding influence their affinity and impact their neutralization breadth.
Mucosal immunization with lipopeptides derived from conserved regions of SARS-CoV-2 antigens induce robust cellular and cross-variant humoral immune responses in mice
Authors: Patel Raj S. , Agrawal Babita
Published: June 2023

Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), the causative agent of COVID-19, has infected >600 million people in the ongoing global pandemic. Several variants of the SARS-CoV-2 have emerged in the last >2 years, challenging the continued efficacy of current COVID vaccines. Therefore, there is a crucial need to investigate a highly cross-protective vaccine effective against variants of SARS-CoV-2. In this study, we examined seven lipopeptides derived from highly conserved, immunodominant epitopes from the S, N, and M proteins of SARS-CoV-2, that are predicted to contain epitopes for clinically protective B cells, helper T cells (TH) and cytotoxic T cells (CTL). Intranasal immunization of mice with most of the lipopeptides led to significantly higher splenocyte proliferation and cytokine production, mucosal and systemic antibody responses, and induction of effector B and T lymphocytes in both lungs and spleen, compared to immunizations with the corresponding peptides without lipid. Immunizations with Spike-derived lipopeptides led to cross-reactive IgG, IgM and IgA responses against Alpha, Beta, Delta, and Omicron Spike proteins as well as neutralizing antibodies. These studies support their potential for development as components of a cross-protective SARS-CoV-2 vaccine.
Liver organoids: a promising three-dimensional model for insights and innovations in tumor progression and precision medicine of liver cancer
Authors: Chen Yukun , Liu Yujun , Chen Shimin , Zhang Long , Rao Jiawei , Lu Xinjun , Ma Yi
Published: June 2023

Primary liver cancer (PLC) is one type of cancer with high incidence rate and high mortality rate in the worldwide. Systemic therapy is the major treatment for PLC, including surgical resection, immunotherapy and targeted therapy. However, mainly due to the heterogeneity of tumors, responses to the above drug therapy differ from person to person, indicating the urgent needs for personalized treatment for PLC. Organoids are 3D models derived from adult liver tissues or pluripotent stem cells. Based on the ability to recapitulate the genetic and functional features of in vivo tissues, organoids have assisted biomedical research to make tremendous progress in understanding disease origin, progression and treatment strategies since their invention and application. In liver cancer research, liver organoids contribute greatly to reflecting the heterogeneity of liver cancer and restoring tumor microenvironment (TME) by co-organizing tumor vasculature and stromal components in vitro. Therefore, they provide a promising platform for further investigation into the biology of liver cancer, drug screening and precision medicine for PLC. In this review, we discuss the recent advances of liver organoids in liver cancer, in terms of generation methods, application in precision medicine and TME modeling.
Dectin-1 signaling coordinates innate and adaptive immunity for potent host defense against viral infection
Authors: Kim Hyeong Won , Ko Mi-Kyeong , Park So Hui , Hwang Seong Yun , Kim Dong Hyeon , Park Sun Young , Ko Young-Joon , Kim Su-Mi , Park Jong-Hyeon , Lee Min Ja
Published: June 2023

Background

Most commercial foot-and-mouth disease (FMD) vaccines have various disadvantages, such as low antibody titers, short-lived effects, compromised host defense, and questionable safety.

Objectives

To address these shortcomings, we present a novel FMD vaccine containing Dectin-1 agonist, β-D-glucan, as an immunomodulatory adjuvant. The proposed vaccine was developed to effectively coordinate innate and adaptive immunity for potent host defense against viral infection.

Methods

We demonstrated β-D-glucan mediated innate and adaptive immune responses in mice and pigs in vitro and in vivo. The expressions of pattern recognition receptors, cytokines, transcription factors, and co-stimulatory molecules were promoted via FMD vaccine containing β-D-glucan.

Results

β-D-glucan elicited a robust cellular immune response and early, mid-, and long-term immunity. Moreover, it exhibited potent host defense by modulating host’s innate and adaptive immunity.

Conclusion

Our study provides a promising approach to overcoming the limitations of conventional FMD vaccines. Based on the proposed vaccine’s safety and efficacy, it represents a breakthrough among next-generation FMD vaccines.
The evaluation of JAK inhibitors on effect and safety in alopecia areata: a systematic review and meta-analysis of 2018 patients
Authors: Mao Mei-qi , Ding Yu-xin , Jing Jing , Tang Zhen-wei , Miao Yu-jie , Yang Xiao-shuang , Chen Yu-hong , Chen Sheng-zhao , Wu Xian-jie , Lu Zhong-fa
Published: June 2023

Background

JAK inhibitors treat various autoimmune diseases, but an updated systematic review in treating alopecia areata is currently lacking.

Objective

Evaluate the specific efficacy and safety of JAK inhibitors in alopecia areata by systematic review and meta-analysis.

Methods

Eligible studies in PubMed, Embase, Web of Science, and Clinical Trials up to May 30, 2022, were searched. We enrolled in randomized controlled trials and observational studies of applying JAK inhibitors in alopecia areata.

Results

6 randomized controlled trials with 1455 patients exhibited SALT50 (odd ratio [OR], 5.08; 95% confidence interval [CI], 3.49-7.38), SALT90 (OR, 7.40; 95% CI, 4.34-12.67) and change in SALT score (weighted mean difference [WSD], 5.55; 95% CI, 2.60-8.50) compared to the placebo. The proportion of 26 observational studies with 563 patients of SALT5 was 0.71(95% CI, 0.65-0.78), SALT50 was 0.54(95% CI 0.46-0.63), SALT90 was 0.33(95% CI, 0.24-0.42), and SALT score (WSD, -2.18; 95% CI, -3.12 to -1.23) compared with baseline. Any adverse effects occurred in 921 of 1508 patients; a total of 30 patients discontinued the trial owing to adverse reactions.

Limitations

Few randomized controlled trials met the inclusion criteria and insufficiency of eligible data.

Conclusion

JAK inhibitors are effective in alopecia areata, although associated with an increased risk.
Dengue virus neutralizing antibody: a review of targets, cross-reactivity, and antibody-dependent enhancement
Authors: Sarker Animesh , Dhama Nidhi , Gupta Rinkoo Devi
Published: June 2023

Dengue is the most common viral infection spread by mosquitoes, prevalent in tropical countries. The acute dengue virus (DENV) infection is a benign and primarily febrile illness. However, secondary infection with alternative serotypes can worsen the condition, leading to severe and potentially fatal dengue. The antibody raised by the vaccine or the primary infections are frequently cross-reactive; however, weakly neutralizing, and during subsequent infection, they may increase the odds of antibody-dependent enhancement (ADE). Despite that, many neutralizing antibodies have been identified against the DENV, which are thought to be useful in reducing dengue severity. Indeed, an antibody must be free from ADE for therapeutic application, as it is pretty common in dengue infection and escalates disease severity. Therefore, this review has described the critical characteristics of DENV and the potential immune targets in general. The primary emphasis is given to the envelope protein of DENV, where potential epitopes targeted for generating serotype-specific and cross-reactive antibodies have critically been described. In addition, a novel class of highly neutralizing antibodies targeted to the quaternary structure, similar to viral particles, has also been described. Lastly, we have discussed different aspects of the pathogenesis and ADE, which would provide significant insights into developing safe and effective antibody therapeutics and equivalent protein subunit vaccines.
Biologic drugs in the treatment of chronic inflammatory pulmonary diseases: recent developments and future perspectives
Authors: Plichta Jacek , Kuna Piotr , Panek Michał
Published: June 2023

Chronic inflammatory diseases of the lung are some of the leading causes of mortality and significant morbidity worldwide. Despite the tremendous burden these conditions put on global healthcare, treatment options for most of these diseases remain scarce. Inhaled corticosteroids and beta-adrenergic agonists, while effective for symptom control and widely available, are linked to severe and progressive side effects, affecting long-term patient compliance. Biologic drugs, in particular peptide inhibitors and monoclonal antibodies show promise as therapeutics for chronic pulmonary diseases. Peptide inhibitor-based treatments have already been proposed for a range of diseases, including infectious disease, cancers and even Alzheimer disease, while monoclonal antibodies have already been implemented as therapeutics for a range of conditions. Several biologic agents are currently being developed for the treatment of asthma, chronic obstructive pulmonary disease, idiopathic pulmonary fibrosis and pulmonary sarcoidosis. This article is a review of the biologics already employed in the treatment of chronic inflammatory pulmonary diseases and recent progress in the development of the most promising of those treatments, with particular focus on randomised clinical trial outcomes.
Recognition and location of marine animal sounds using two-stream ConvNet with attention
Authors: Hu Shaoxiang , Hou Rong , Liao Zhiwu , Chen Peng
Published: June 2023

There are abundant resources and many endangered marine animals in the ocean. Using sound to effectively identify and locate them, and estimate their distribution area, has a very important role in the study of the complex diversity of marine animals (Hanny et al., 2013). We design a Two-Stream ConvNet with Attention (TSCA) model, which is a two-stream model combined with attention, in which one branch processes the temporal signal and the other branch processes the frequency domain signal; It makes good use of the characteristics of high time resolution of time domain signal and high recognition rate of frequency domain signal features of sound, and it realizes rapid localization and recognition of sound of marine species. The basic network architecture of the model is YOLO (You Only Look Once) (Joseph et al., 2016). A new loss function focal loss is constructed to strengthen the impact on the tail class of the sample, overcome the problem of data imbalance and avoid over fitting. At the same time, the attention module is constructed to focus on more detailed sound features, so as to improve the noise resistance of the model and achieve high-precision marine species identification and location. In The Watkins Marine Mammal Sound Database, the recognition rate of the algorithm reached 92.04% and the positioning accuracy reached 78.4%.The experimental results show that the algorithm has good robustness, high recognition accuracy and positioning accuracy.
The involvement of antioxidant, stress, and immune-related genes in the responsive mechanisms of common carp (Cyprinus carpio) to hypersalinity exposure
Authors: Ahmed Hassan , Bakry Karima A. , Abdeen Ahmed , El bahgy Halla E. K. , Abdo Mohamed , Imbrea Florin , Fericean Liana , Elshemy Mona A. , Ibrahim Samah F. , Shukry Mustafa , Baloza Samar H. , Emeish Walaa F. A.
Published: June 2023

Salinity stress is one of the marked influencing factors on the ecophysiology of aquaculture and is considered an important reason for the retreat of the fish industry. The current study is an endeavor to elucidate the molecular mechanisms that underlie the response to salinity stress in common carp. Fish (Average weight 5 ± 2 g) were randomly distributed into two groups; the 1st is a control was exposed to tap water (0.2 ppt salinity) and the 2nd is a treated was exposed to hypersalinity (10 ppt salinity) for five days. Serum biochemical indicators including total protein, albumin, globulins, A/G ratio, blood glucose, cortisone, Na+, K+, and Cl- levels were evaluated. Besides, Tumor necrosis factor-α, interleukin-1β, corticotropin-releasing hormone, and catalase enzyme mRNA expression levels were assessed in lymphoid and immunocompetent organs (liver and spleen) and osmoregulatory organs (kidney and gills) by using Real-time qPCR. Hypersalinity adversely affected the biochemical markers; total protein, albumin, and globulins decreased significantly; however, blood glucose, serum cortisol, and sodium markedly increased in fish exposed to hypersalinity compared with the control. In addition, from the molecular point of view, all the evaluated genes were upregulated at a high expression rate in the liver compared with other studied organs after the salinity challenge. On the contrary, hypersalinity modulated the expression of immune-related genes (Tumor necrosis factor-α and interleukin-1β) in the kidney and spleen and upregulated corticotropin-releasing hormone mRNA in all studied organs except gills. In conclusion, the obtained data clarified the molecular and biochemical mechanisms of salinity stress on the liver, kidney, spleen, and gills. Furthermore, it strongly suggests the implication of neural, endocrine, and immune systems in the responsive mechanisms to the salinity stress in carp.
The effect of size, morphology and surface properties of mesoporous silica nanoparticles on pharmacokinetic aspects and potential toxicity concerns
Authors: Niroumand Uranous , Firouzabadi Negar , Goshtasbi Ghazal , Hassani Bahareh , Ghasemiyeh Parisa , Mohammadi-Samani Soliman
Published: June 2023

Mesoporous silica nanoparticles (MSNs) are considered as suitable delivery vehicles considering their unique characteristics. Various physicochemical characteristics of MSNs govern their pharmacokinetic parameters which affect the disposition of these nanoparticles in the body. Along with the advantages of MSNs, the toxicity of nanoparticles entering the body is a major concern. Various factors such as particle size, surface charge, route of administration, etc., may affect organ toxicity of MSNs. The main target organs involved in the metabolism and elimination of MSNs are the kidney and the liver as well as the hematopoietic system. In this review, we first introduced the physicochemical characteristics of MSNs which affect the pharmacokinetic properties including drug absorption and bio-distribution. Thereafter, we discussed the mechanisms by which organ toxicity may occur. In this regard, the effects of various factors on organ-based MSNs toxicities and molecular mechanisms have been summarized. At last, we emphasized on the role of the physicochemical parameters on organ-based toxicities, and the proposed approaches to prevent or at least diminish MSN-related toxicities are discussed in detail.
Sex distinctive patterns in the association between serum bicarbonate and uric acid levels among healthy adults. Qatar biobank data
Authors: Ibrahim Wisam Nabeel , Shi Zumin , Abdallah Atiyeh M. , Abu-Madi Marawan Abdelhamid
Published: June 2023

Background

Uric acid is the final product of purine metabolism and is a potent plasma antioxidant but with pro-inflammatory effects. At high levels, it may increase the risk of developing multiple chronic diseases, such as gout, atherosclerosis, hypertension, and renal diseases. The aim of this study was to assess the sex-specific association between serum bicarbonate and uric acid levels among healthy adults.

Methodology

This retrospective cross-sectional study included 2,989 healthy Qatari adults (36.4 ± 11.1  years) from the Qatar Biobank database. Serum uric acid and bicarbonate levels were estimated alongside other serological markers. Participants free from chronic diseases were divided into four quartiles based on serum bicarbonate levels. The sex-specific relationship between serum bicarbonate and uric acid levels was assessed through univariate and multivariate analyses.

Results

In men, low serum uric acid levels were significantly associated with higher quartiles of serum bicarbonate levels after adjusting for age. The association remained significant after further adjustment for BMI, smoking, and renal function. The subgroup analysis using the restricted cubic spline method confirmed a significant dose–response association between the variation coefficients of uric acid by serum bicarbonate level in men with adjustments for age, BMI, smoking, and renal function. In women, no significant association was found between quartiles of serum bicarbonate and uric acid levels following the same adjustments. However, using the restricted cubic spline method, a significant bidirectional relation was demonstrated between serum bicarbonate and the variation coefficients of uric acid that were positive for serum bicarbonate levels below 25 mEq/L and negative at higher levels.

Conclusion

Serum bicarbonate levels are linearly associated with reduced serum uric acid levels among healthy adult men, which may be a potential protective factor against hyperuricemia-related complications. Further research is needed to determine the underlying mechanisms.
Effect of regional medical disparities on complications in patients with hypertension: Cox’s proportional hazard models
Authors: Yun Choa , Park Minah , Joo Jae Hong , Kang Soo Hyun , Jeong Sung Hoon , Nam Chung-Mo , Park Eun-Cheol , Jang Sung-In
Published: June 2023

Objective

Complications associated with hypertension can be alleviated by providing necessary medical services. However, there may be disparities in their provision depending on regional differences. Thus, this study aimed to examine the effects of regional healthcare disparities on complications in patients with hypertension in South Korea.

Methods

Data from the National Health Insurance Service National Sample Cohort (2004–2019) were analyzed. The position value for the relative composite index was used to identify medically vulnerable regions. The diagnosis of hypertension within the region was also considered. The risk of complications associated with hypertension included cardiovascular, cerebrovascular, and kidney diseases. Cox proportional hazards models were used for statistical analysis.

Results

A total of 246,490 patients were included in this study. Patients who lived in medically vulnerable regions and were diagnosed outside their residential area had a higher risk of complications than those living in non-vulnerable regions and were diagnosed outside the residential area (hazard ratio: 1.156, 95% confidence interval: 1.119–1.195).

Conclusion

Patients living in medically vulnerable regions who were diagnosed outside their residential areas were more likely to have hypertension complications regardless of the type of complication. Necessary policies should be implemented to reduce regional healthcare disparities.
A functional MMP-9-1562C>T polymorphism, MMP-9 serum levels and nephrolithiasis risk in a southern Chinese population
Authors: Ding Qi , Cao Cheng , Shi Ying , Fan Zhijiang , Li Feng , Tu Wenjian , Jin Xiaohua , Zhu Hailiang , Fan Bo
Published: June 2023

Background

The role of matrix metalloproteinase 9 (MMP-9) in the pathophysiology of chronic kidney disease (CKD), which is associated with a nearly two-fold greater risk for urinary calculi compared to people without CKD, has been demonstrated. The aim of the research is to evaluate the association between MMP-9-1562C>T polymorphism, MMP-9 serum levels and nephrolithiasis risk.

Methods

A hospital-based case-control study involving 302 kidney stone patients and 408 controls without kidney stone from southern China was conducted. Sanger sequencing was used to genotype the MMP-9-1562C>T polymorphism. The serum MMP-9 was measured in 105 kidney stone patients and 77 controls by enzyme-linked immunosorbent assay.

Results

Compared to the control group, the CT genotype was more frequent in nephrolithiasis patients (adjusted OR = 1.60, 95% CI = 1.09–2.37: the risk of developing nephrolithiasis in individuals with CT genotype compared to CC genotype). Moreover, there was also a higher frequency of CT/TT genotypes among patients with nephrolithiasis (adjusted OR = 1.49, 95% CI = 1.02–2.19: the risk of developing nephrolithiasis in individuals with CT/TT genotypes compared to CC genotype). The risk remained for the subgroups of patients aged >53, smokers with pack-years of smoking >20, non-drinkers, non-diabetic patients, patients with hypertension, recurrent episodes and calcium oxalate stones (OR = 2.26, 95% CI = 1.31–3.91; OR = 5.47, 95% CI = 1.10–27.30; OR = 1.76, 95% CI = 1.14–2.72; OR = 1.54, 95% CI = 1.03–2.30; OR = 1.97, 95% CI = 1.01–3.82; OR = 1.67, 95% CI = 1.06–2.62; OR = 1.54, 95% CI = 1.02–2.32, respectively). Biochemical parameters did not differ between genotypes. Compared to controls (18.57 ± 5.80 ng/mL), nephrolithiasis patients had significantly higher serum MMP-9 levels (30.17 ± 6.78 ng/mL, p < 0.001). The serum MMP-9 levels of patients with CT/TT genotypes of MMP-9-1562C>T were significantly higher than those with CC genotype (32.00 ± 6.33 vs. 29.13 ± 6.85 ng/mL, p = 0.037).

Conclusion

The MMP-9-1562C>T polymorphism in association with its soluble protein increased the risk of kidney stone, thus suggesting it could be used as a susceptibility biomarker for nephrolithiasis. Further functional studies and larger studies that include environmental exposure data are needed to confirm the findings.
Annexin-V positive extracellular vesicles level is increased in severe COVID-19 disease
Authors: Jacob Valentine , Lambour Alexis , Swinyard Benjamin , Zerbib Yoann , Diouf Momar , Soudet Simon , Brochot Etienne , Six Isabelle , Maizel Julien , Slama Michel , Guillaume Nicolas
Published: June 2023

Objectives

To evaluate extracellular vesicles levels in a cohort of SARS-CoV-2’s patients hospitalized in an intensive care unit with and without COVID-19 associated thromboembolic events.

Methods

In this study, we aim to assess endothelial and platelet membrane-derived extracellular vesicles levels in a cohort of SARS-CoV-2 patients with and without COVID-19-associated thromboembolic events who were hospitalized in an intensive care unit. Annexin-V positive extracellular vesicles levels were prospectively assessed by flow cytometry in one hundred twenty-three critically ill adults diagnosed with acute respiratory distress syndrome associated with a SARS-CoV-2 infection, ten adults diagnosed for moderate SARS-CoV-2 infection and 25 healthy volunteers.

Results

On our critically ill patients, thirty-four patients (27.6%) had a thromboembolic event, Fifty-three (43%) died. Endothelial and platelet membrane-derived extracellular vesicles were drastically increased in SARS-CoV-2 patients hospitalized in the ICU compared to healthy volunteers. Moreover a slighty higher small/large ratio for platelets membrane-derived extracellular vesicles in patients was linked to thrombo-embolic events.

Conclusion

A comparison between total annexin-V positive extracellular vesicles levels in severe and moderate SARS-CoV-2 infection and healthy controls showed a significant increase in patients with severe infection and their sizes could be considered as biomarkers of SARS-CoV-2 associated thrombo-embolic events.
ME/CFS and Long COVID share similar symptoms and biological abnormalities: road map to the literature
Authors: Komaroff Anthony L. , Lipkin W. Ian
Published: June 2023

Some patients remain unwell for months after “recovering” from acute COVID-19. They develop persistent fatigue, cognitive problems, headaches, disrupted sleep, myalgias and arthralgias, post-exertional malaise, orthostatic intolerance and other symptoms that greatly interfere with their ability to function and that can leave some people housebound and disabled. The illness (Long COVID) is similar to myalgic encephalomyelitis/chronic fatigue syndrome (ME/CFS) as well as to persisting illnesses that can follow a wide variety of other infectious agents and following major traumatic injury. Together, these illnesses are projected to cost the U.S. trillions of dollars. In this review, we first compare the symptoms of ME/CFS and Long COVID, noting the considerable similarities and the few differences. We then compare in extensive detail the underlying pathophysiology of these two conditions, focusing on abnormalities of the central and autonomic nervous system, lungs, heart, vasculature, immune system, gut microbiome, energy metabolism and redox balance. This comparison highlights how strong the evidence is for each abnormality, in each illness, and helps to set priorities for future investigation. The review provides a current road map to the extensive literature on the underlying biology of both illnesses.
The use of a scented face mask in pediatric patients may facilitate mask acceptance before anesthesia induction
Authors: Abukawa Yukako , Takano Koji , Hobo Yuko , Hosaka Erika , Kimura Ayano , Suga Yoshifumi , Katori Nobuyuki , Tsubokawa Tsunehisa
Published: June 2023

Background

Scented face masks are commonly used during the induction phase of anesthesia. The present study investigated whether the use of a scented mask improved mask acceptance before the slow induction of anesthesia in pediatric patients.

Methods

This prospective, randomized controlled trial enrolled patients aged 2–10 years who were scheduled to undergo surgery under general anesthesia. Patients were randomly assigned to either of regular unscented (control group) or scented (experimental group) face masks before anesthesia induction with a parent. The primary outcome was the mask acceptance score, rated on a validated 4-point from 1 point (not afraid; easily accepts the mask) to 4 points (afraid of a mask; crying or struggling). The secondary outcome was heart rate assessed by pulse oximetry in the pediatric ward before transfer to the operating room (OR), at the entrance to the OR, at the patient notification of mask fitting by the anesthesiologist, and after mask fitting.

Results

Seventy-seven patients were accessed for eligibility, with 67 enrolled in the study: 33 in the experimental group and 34 in the control group. Mask acceptance was significantly greater among patients aged 2–3 years in the experimental than in the control group (p < 0.05).

Conclusion

The use of a scented mask can improve mask acceptance before anesthesia induction with a parental presence in pediatric patients aged 2–3 years.

Clinical Trial Registration: https://upload.umin.ac.jp/cgi-open-bin/ctr_e/ctr_view.cgi?recptno=R000040819.
Non-traditional risk factors of progression of chronic kidney disease in adult population: a scoping review
Authors: Cisneros-García Diana Lorena , Sandoval-Pinto Elena , Cremades Rosa , Ramírez-de-Arellano Adrián , García-Gutiérrez Mariana , Martínez-de-Pinillos-Valverde Roberto , Sierra-Díaz Erick
Published: June 2023

Chronic kidney disease (CKD) has become a public health concern over the last several years. Nowadays developed countries spend around 3% of their annual health-care budget on patients with CKD. According to the scientific community the most remarkable risk factors for CKD are diabetes and hypertension. Unknown CKD etiology has been reported as a global phenomenon including uncommon risk factors such as: dehydration, leptospirosis, heat stress, water quality, and others. This study aims to report non-traditional risk factors for ESRD based on a scoping review methodology. The scoping review methodology described by Arksey and O’Malley was used by performing an extensive review of the information. A total of 46 manuscripts were reviewed. The non-traditional ESRD risk factors are depicted based on six categories. Gender and ethnicity have been considered as risk factors for ESRD. Erythematous systemic lupus (ESL) is reported as an important risk factor for ESRD. Pesticide use has been an significant risk factor due to its effects on human and environmental health. Some compounds commonly used in homes against insects and plants are related to ESRD. Congenital and hereditary diseases in the urinary tract have been studied as a cause of ESRD in children and young adults. End-stage renal disease is a major concern for public health on a global level. As it can be seen, non-traditional risk factors are several and have different etiologies. It is necessary to put the issue on the table and add it to the public agenda in order to find multidisciplinary solutions.
Impact of Aerobika® oscillating positive expiratory pressure in improving small airway resistance, lung function, symptoms and exercise capacity in chronic obstructive pulmonary disease
Authors: Sahardin Siti Nurhanis , Jailaini Mas Fazlin Mohamad , Abeed Nik Nuratiqah Nik , Ban Andrea Yu-Lin , Hau Ng Boon , Azmel Azat Azrai , Shah Shamsul Azhar , Hamid Mohamed Faisal Abdul
Published: June 2023

Background

Aerobika® oscillating positive expiratory pressure (OPEP) device promotes airway clearance in many respiratory diseases. However, studies have yet to focus on its effectiveness in improving small airway resistance via impulse oscillometry (IOS) measurement in COPD subjects. We aim to evaluate the improvement of small airway resistance (via IOS), lung function (spirometry), exercise capacity [via 6-min walking test (6MWT)], symptoms [COPD assessment test (CAT)] and severe exacerbation events among COPD subjects using Aerobika® OPEP.

Methods

This was a prospective, single-arm interventional study among COPD subjects with small airway disease. Subjects were instructed to use twice daily Aerobika® OPEP (10 min each session); for 24 weeks; as an additional to standard therapy. IOS, spirometry, 6MWT, CAT score and severe exacerbation events were evaluated at baseline, 12 weeks and 24 weeks.

Results

Fifty-three subjects completed the study. Aerobika® usage showed improvement of IOS parameters; e.g. measurement of airway resistance at 5 Hz (R5), cmH20/L/s, (12-week p = 0.008, 24-week p < 0.001), R5% predicted (12-week p = 0.007, 24-week p < 0.001) and small airway resistance (R5–R20), cmH20/L/s, (12-week p = 0.021, 24-week p < 0.001). There were improvement of lung function; e.g. FEV1, L (12-week p = 0.018, 24-week p = 0.001), FEV1% predicted (12-week p = 0.025, 24-week p = 0.001), FEF25–75, L (12-week p = 0.023, 24-week p = 0.002), and FEF25–75% predicted (12-week p = 0.024, 24-week p < 0.001). CAT score improved at 12 weeks (p < 0.001) and 24 weeks (p < 0.001). Subjects had improved exercise capacity (6MWT, metres) after 24 weeks (p = 0.016). However, there was no significant difference in severe exacerbation events 24 weeks before and after Aerobika® usage.

Conclusion

Aerobika® OPEP demonstrated significant improvement in small airway resistance as early as 12 weeks of usage, with sustained improvement at 24 weeks. Aerobika® OPEP administration had significantly improved lung function, 6MWT, and CAT scores over 24 weeks. There was no difference in severe exacerbation events.
Effects of Septoglomus constrictum and Bacillus cereus on the competitive growth of Ageratina adenophora
Authors: Du Ewei , Chen Yaping , Li Yang , Li Yahong , Sun Zhongxiang , Hao Ruoshi , Gui Furong
Published: June 2023

Beneficial microorganisms play a pivotal role in the invasion process of exotic plants, including arbuscular mycorrhizal fungi (AMF) and Bacillus. However, limited research exists on the synergistic influence of AMF and Bacillus on the competition between both invasive and native plants. In this study, pot cultures of Ageratina adenophora monoculture, Rabdosia amethystoides monoculture, and A. adenophora and R. amethystoides mixture were used to investigate the effects of dominant AMF (Septoglomus constrictum, SC) and Bacillus cereus (BC), and the co-inoculation of BC and SC on the competitive growth of A. adenophora. The results showed that inoculation with BC, SC, and BC + SC significantly increased the biomass of A. adenophora by 14.77, 112.07, and 197.74%, respectively, in the competitive growth between A. adenophora and R. amethystoides. Additionally, inoculation with BC increased the biomass of R. amethystoides by 185.07%, while inoculation with SC or BC + SC decreased R. amethystoides biomass by 37.31 and 59.70% compared to the uninoculated treatment. Inoculation with BC significantly increased the nutrient contents in the rhizosphere soil of both plants and promoted their growth. Inoculation with SC or SC + BC notably increased the nitrogen and phosphorus contents of A. adenophora, therefore enhancing its competitiveness. Compared with single inoculation, dual inoculation with SC and BC increased AMF colonization rate and Bacillus density, indicating that SC and BC can form a synergistic effect to further enhance the growth and competitiveness of A. adenophora. This study reveals the distinct role of S. constrictum and B. cereus during the invasion of A. adenophora, and provide new clues to the underlying mechanisms of interaction between invasive plant, AMF and Bacillus.
Microorganisms in coastal wetland sediments: a review on microbial community structure, functional gene, and environmental potential
Authors: Liang Shen , Li Huai , Wu Haitao , Yan Baixing , Song Aiwen
Published: June 2023

Coastal wetlands (CW) are the junction of the terrestrial and marine ecosystems and have special ecological compositions and functions, which are important for maintaining biogeochemical cycles. Microorganisms inhabiting in sediments play key roles in the material cycle of CW. Due to the variable environment of CW and the fact that most CW are affected by human activities and climate change, CW are severely degraded. In-depth understanding of the community structure, function, and environmental potential of microorganisms in CW sediments is essential for wetland restoration and function enhancement. Therefore, this paper summarizes microbial community structure and its influencing factors, discusses the change patterns of microbial functional genes, reveals the potential environmental functions of microorganisms, and further proposes future prospects about CW studies. These results provide some important references for promoting the application of microorganisms in material cycling and pollution remediation of CW.
Shedding light on the composition of extreme microbial dark matter: alternative approaches for culturing extremophiles
Authors: Schultz Júnia , Modolon Flúvio , Peixoto Raquel Silva , Rosado Alexandre Soares
Published: June 2023

More than 20,000 species of prokaryotes (less than 1% of the estimated number of Earth’s microbial species) have been described thus far. However, the vast majority of microbes that inhabit extreme environments remain uncultured and this group is termed “microbial dark matter.” Little is known regarding the ecological functions and biotechnological potential of these underexplored extremophiles, thus representing a vast untapped and uncharacterized biological resource. Advances in microbial cultivation approaches are key for a detailed and comprehensive characterization of the roles of these microbes in shaping the environment and, ultimately, for their biotechnological exploitation, such as for extremophile-derived bioproducts (extremozymes, secondary metabolites, CRISPR Cas systems, and pigments, among others), astrobiology, and space exploration. Additional efforts to enhance culturable diversity are required due to the challenges imposed by extreme culturing and plating conditions. In this review, we summarize methods and technologies used to recover the microbial diversity of extreme environments, while discussing the advantages and disadvantages associated with each of these approaches. Additionally, this review describes alternative culturing strategies to retrieve novel taxa with their unknown genes, metabolisms, and ecological roles, with the ultimate goal of increasing the yields of more efficient bio-based products. This review thus summarizes the strategies used to unveil the hidden diversity of the microbiome of extreme environments and discusses the directions for future studies of microbial dark matter and its potential applications in biotechnology and astrobiology.