bluuebunny/crossref_metadata_2025 huggingface dataset:
Chromatin Separation Regulators Predict the Prognosis and Immune Microenvironment Estimation in Lung Adenocarcinoma
Authors: Li Zhaoshui , Ma Zaiqi , Xue Hong , Shen Ruxin , Qin Kun , Zhang Yu , Zheng Xin , Zhang Guodong
Published: July 2022

Background: Abnormal chromosome segregation is identified to be a common hallmark of cancer. However, the specific predictive value of it in lung adenocarcinoma (LUAD) is unclear.

Method: The RNA sequencing and the clinical data of LUAD were acquired from The Cancer Genome Atlas (TACG) database, and the prognosis-related genes were identified. The Kyoto Encyclopedia of Genes and Genomes (KEGG) and Gene Ontology (GO) were carried out for functional enrichment analysis of the prognosis genes. The independent prognosis signature was determined to construct the nomogram Cox model. Unsupervised clustering analysis was performed to identify the distinguishing clusters in LUAD-samples based on the expression of chromosome segregation regulators (CSRs). The differentially expressed genes (DEGs) and the enriched biological processes and pathways between different clusters were identified. The immune environment estimation, including immune cell infiltration, HLA family genes, immune checkpoint genes, and tumor immune dysfunction and exclusion (TIDE), was assessed between the clusters. The potential small-molecular chemotherapeutics for the individual treatments were predicted via the connectivity map (CMap) database.

Results: A total of 2,416 genes were determined as the prognosis-related genes in LUAD. Chromosome segregation is found to be the main bioprocess enriched by the prognostic genes. A total of 48 CSRs were found to be differentially expressed in LUAD samples and were correlated with the poor outcome in LUAD. Nine CSRs were identified as the independent prognostic signatures to construct the nomogram Cox model. The LUAD-samples were divided into two distinct clusters according to the expression of the 48 CSRs. Cell cycle and chromosome segregation regulated genes were enriched in cluster 1, while metabolism regulated genes were enriched in cluster 2. Patients in cluster 2 had a higher score of immune, stroma, and HLA family components, while those in cluster 1 had higher scores of TIDES and immune checkpoint genes. According to the hub genes highly expressed in cluster 1, 74 small-molecular chemotherapeutics were predicted to be effective for the patients at high risk.

Conclusion: Our results indicate that the CSRs were correlated with the poor prognosis and the possible immunotherapy resistance in LUAD.
Identification of a Five-mRNA Signature as a Novel Potential Prognostic Biomarker for Glioblastoma by Integrative Analysis
Authors: Xu Huifang , Zhang Linfang , Xia Xiujuan , Shao Wei
Published: July 2022

Despite the availability of advanced multimodal therapy, the prognosis of patients suffering from glioblastoma (GBM) remains poor. We conducted a genome-wide integrative analysis of mRNA expression profiles in 302 GBM tissues and 209 normal brain tissues from the Gene Expression Omnibus (GEO), The Cancer Genome Atlas (TCGA), and the Genotype-Tissue Expression (GTEx) project to examine the prognostic and predictive value of specific mRNAs in GBM. A total of 26 mRNAs were identified to be closely related to GBM patients’ OS (p < 0.05). Utilizing survival analysis and the Cox regression model, we discovered a set of five mRNAs (PTPRN, ABCC3, MDK, NMB, and RALYL) from these 26 mRNAs that displayed the capacity to stratify patients into high- and low-risk groups with statistically different overall survival in the training set. The model of the five-mRNA biomarker signature was successfully verified on a testing set and independent sets. Moreover, multivariate Cox regression analysis revealed that the five-mRNA biomarker signature was a prognostic factor for the survival of patients with GBM independent of clinical characteristics and molecular features (p < 0.05). Gene set enrichment analysis indicated that the five-mRNA biomarker signature might be implicated in the incidence and development of GBM through its roles in known cancer-related pathways, signaling molecules, and the immune system. Moreover, consistent with the bioinformatics analysis, NMB, ABCC3, and MDK mRNA expression was considerably higher in four human GBM cells, and the expression of PTPRN and RALYL was decreased in GBM cells (p < 0.05). Our study developed a novel candidate model that provides new prospective prognostic biomarkers for GBM.
Generalized Anxiety Disorder and Its Associated Factors Among Pregnant Women During COVID-19 at Public Health Facilities of East Gojjam Zone, 2020: A Multi-Center Cross-Sectional Study
Authors: Bishaw Keralem Anteneh , Andalem Addisu , Amha Haile , wondie Tirusew
Published: July 2022

Introduction

Pregnant women suffer from varying levels of generalized anxiety disorder that result in poor obstetrical outcomes. Therefore, this study aimed to assess the prevalence and factors associated with generalized anxiety disorder among pregnant women attending antenatal care during COVID-19 at the public health facilities in the east Gojjam zone.

Methods

A health facility-based cross-sectional study was conducted, from 1–30 December 2020. A total of 847 pregnant women were included in the study using a systematic random sampling technique. We used an interviewer-administered questionnaire to collect the data. Bivariate and multivariable logistic regression was used to identify factors associated with the outcome variable. Statistical significance was determined using a p-value < 0.05 and a 95% confidence level.

Results

The prevalence of generalized anxiety disorder was 43.7%, with a 95% CI (40.28–47.12). Having <3 the number of children (AOR: 1.53; 95% CI: 1.11–2.13, having a negative attitude about COVID (AOR: 1.47; 95% CI: 1.07–2.02 and having a high-risk perception about COVID (AOR: 1.86; 95% CI: 1.34–2.57 were factors significantly associated with generalized anxiety disorder.

Conclusions

The study found that the prevalence of generalized anxiety disorder was high. Having less than three children, having a negative attitude, and having a high-risk perception of COVID were independent risk factors of generalized anxiety disorder. Appropriate interventions should be considered to address generalized anxiety disorder during the pandemic.
An OGT-STAT5 Axis in Regulatory T Cells Controls Energy and Iron Metabolism
Authors: Zhang Zengdi , Salgado Oscar C. , Liu Bing , Moazzami Zahra , Hogquist Kristin A. , Farrar Michael A. , Ruan Hai-Bin
Published: July 2022

The immunosuppressive regulatory T (Treg) cells exert emerging effects on adipose tissue homeostasis and systemic metabolism. However, the metabolic regulation and effector mechanisms of Treg cells in coping with obesogenic insults are not fully understood. We have previously established an indispensable role of the O-linked N-Acetylglucosamine (O-GlcNAc) signaling in maintaining Treg cell identity and promoting Treg suppressor function, via STAT5 O-GlcNAcylation and activation. Here, we investigate the O-GlcNAc transferase (OGT)-STAT5 axis in driving the immunomodulatory function of Treg cells for metabolic homeostasis. Treg cell-specific OGT deficiency renders mice more vulnerable to high-fat diet (HFD)-induced adiposity and insulin resistance. Conversely, constitutive STAT5 activation in Treg cells confers protection against adipose tissue expansion and impaired glucose and insulin metabolism upon HFD feeding, in part by suppressing adipose lipid uptake and redistributing systemic iron storage. Treg cell function can be augmented by targeting the OGT-STAT5 axis to combat obesity and related metabolic disorders.
Mast Cell Repopulating Ability Is Lost During the Transition From Pre-HSC to FL HSC
Authors: Yoshimoto Momoko , Kosters Astrid , Cornelius Samuel , Valiente Noemi , Cheng Haizi , Latorre Augusto , Nishida Chika , Ghosn Eliver E. B. , Kobayashi Michihiro
Published: July 2022

Recent advances in developmental immunology have revealed a hematopoietic stem cell (HSC)-independent origin for various innate immune lineages, including mast cells (MCs). It is now established that adult bone marrow (BM) long-term HSCs do not regenerate MCs but, instead, the physiological production of MCs starts before the emergence of HSCs in the aorta-gonad-mesonephros (AGM) region and is mostly completed before birth. However, while the AGM region represents a major site of MC generation during ontogeny, whether the first emerging HSCs in the AGM or fetal liver (FL) possess the potential to regenerate MCs is unknown. Here, we combined three fate-mapping mouse models with detailed HSC transplantation assays to determine the potential of AGM and FL HSCs to produce MCs. We show that HSCs from E11.5 AGM and E12.5 FL efficiently repopulated MCs in recipients. In stark contrast, HSCs from ≥E14.5 FL failed to reconstitute MCs. An Endothelial (EC) fate-mapping study confirmed the EC origin of the majority of MCs. Additionally, our HSC-labeling showed that HSCs do not produce MCs in a physiological setting. Hence, although most MCs are generated and maintained via an HSC-independent pathway, the earliest HSCs to emerge in the AGM and seed the early FL can produce MCs, but only during a minimal time window. Our results challenge the stem cell theory in hematology and EC-derived mast cells may contribute to the pathogenesis of postnatal mast cell disorders.
Trained Immunity and HIV Infection
Authors: Sviridov Dmitri , Miller Yury I. , Bukrinsky Michael I.
Published: July 2022

Findings that certain infections induce immunity not only against the causing agent, but also against an unrelated pathogen have intrigued investigators for many years. Recently, underlying mechanisms of this phenomenon have started to come to light. It was found that the key cells responsible for heterologous protection are innate immune cells such as natural killer cells (NKs), dendritic cells, and monocytes/macrophages. These cells are ‘primed’ by initial infection, allowing them to provide enhanced response to subsequent infection by the same or unrelated agent. This phenomenon of innate immune memory was termed ‘trained immunity’. The proposed mechanism for trained immunity involves activation by the first stimulus of metabolic pathways that lead to epigenetic changes, which maintain the cell in a “trained” state, allowing enhanced responses to a subsequent stimulus. Innate immune memory can lead either to enhanced responses or to suppression of subsequent responses (‘tolerance’), depending on the strength and length of the initial stimulation of the immune cells. In the context of HIV infection, innate memory induced by infection is not well understood. In this Hypothesis and Theory article, we discuss evidence for HIV-induced trained immunity in human monocytes, its possible mechanisms, and implications for HIV-associated co-morbidities.
Cardiovascular Toxicity With PD-1/PD-L1 Inhibitors in Cancer Patients: A Systematic Review and Meta-Analysis
Authors: Liu Surui , Gao Wei , Ning Yan , Zou Xiaomeng , Zhang Weike , Zeng Liangjie , Liu Jie
Published: July 2022

Background

PD-1/PD-L1 inhibitors have significantly improved the outcomes of those patients with various malignancies. However, the incidence of adverse events also increased. This meta-analysis aims to systematically evaluate the risk of cardiovascular toxicity in patients treated with PD-1/PD-L1 inhibitors.

Materials and methods

We searched PubMed, Embase, the Cochrane Library databases for all randomized controlled trials (RCTs) comparing all-grade and grade 3-5 cardiovascular toxicity of single-agent PD-1/PD-L1 inhibitors to placebo/chemotherapy, PD-1/PD-L1 inhibitors combined with chemotherapy to chemotherapy, or PD-1/PD-L1 inhibitors combined with CTLA-4 inhibitors to single-agent immune checkpoint inhibitors (ICIs) and pooled our data in a meta-analysis stratified by tumor types and PD-1 or PD-L1 inhibitors. The Mantel-Haenszel method calculated the odds ratio (OR) and its corresponding 95% confidence intervals (CIs).

Results

A total of 50 trials were included in the analysis. Single-agent PD-1/PD-L1 inhibitors increased the risk of all-grade cardiotoxicity compared with placebo (OR=2.11, 95%CI 1.02-4.36, P=0.04). Compared with chemotherapy, patients receiving PD-1/PD-L1 inhibitors combined with chemotherapy had a significant higher risk of all-grade (OR=1.53, 95%CI 1.18-1.99, P=0.001) and grade 3-5 cardiotoxicity (OR=1.63, 95%CI 1.11-2.39, P=0.01) cardiotoxicity, especially patients with non-small cell lung cancer (NSCLC) [all-grade cardiotoxicity (OR=1.97, 95%CI 1.14-3.41, P=0.02) and grade 3-5 cardiotoxicity (OR=2.15, 95%CI 1.08-4.27, P=0.03)]. Subgroup analysis showed that PD-1 inhibitors combined with chemotherapy were associated with a higher risk of grade 3-5 cardiotoxicity (OR=2.08, 95%CI 1.18-3.66, P=0.01). Compared with placebo or chemotherapy, single-agent PD-1/PD-L1 inhibitors did not increase the risk of all-grade of myocarditis, arrhythmia and hypertension. However, PD-1/PD-L1 inhibitors combined with chemotherapy increased the risk of all-grade arrhythmia (OR=1.63, 95%CI 1.07-2.46, P=0.02) [PD-L1 inhibitor-containing treatment (OR=1.75, 95%CI 1.09-2.80, P=0.02)], and the risk of all-grade hypertension (OR=1.34, 95%CI 1.02-1.77, P=0.04) and grade 3-5 hypertension (OR=1.54, 95%CI 1.10-2.15, P=0.01).

Conclusions

Our results suggest that single-agent PD-1/PD-L1 inhibitors increase the risk of all-grade cardiotoxicity, PD-1/PD-L1 inhibitors combined with chemotherapy increase the risk of all-grade and grade 3-5 cardiotoxicity, especially in those patients treated with PD-1 inhibitor-containing treatment and those with NSCLC. In addition, PD-1/PD-L1 inhibitors combined with chemotherapy increase the risk of arrhythmia and hypertension. Therefore, this evidence should be considered when assessing the benefits and risks of PD-1/PD-L1 inhibitors in treating malignancies.

Systematic Review Registration

https://www.crd.york.ac.uk/prospero/, identifier CRD42022303115.
SerpinB3 as a Pro-Inflammatory Mediator in the Progression of Experimental Non-Alcoholic Fatty Liver Disease
Authors: Novo Erica , Cappon Andrea , Villano Gianmarco , Quarta Santina , Cannito Stefania , Bocca Claudia , Turato Cristian , Guido Maria , Maggiora Marina , Protopapa Francesca , Sutti Salvatore , Provera Alessia , Ruvoletto Mariagrazia , Biasiolo Alessandra , Foglia Beatrice , Albano Emanuele , Pontisso Patrizia , Parola Maurizio
Published: July 2022

Non-alcoholic fatty liver disease (NAFLD) is becoming the most common chronic liver disease worldwide. In 20-30% of patients, NAFLD can progress into non-alcoholic steatohepatitis (NASH), eventually leading to fibrosis, cirrhosis and hepatocellular carcinoma development. SerpinB3 (SB3), a hypoxia-inducible factor-2α dependent cysteine protease inhibitor, is up-regulated in hepatocytes during progressive NAFLD and proposed to contribute to disease progression. In this study we investigated the pro-inflammatory role of SB3 by employing phorbol-myristate acetate-differentiated human THP-1 macrophages exposed in vitro to human recombinant SB3 (hrSB3) along with mice overexpressing SB3 in hepatocytes (TG/SB3) or knockout for SB3 (KO/SB3) in which NASH was induced by feeding methionine/choline deficient (MCD) or a choline-deficient, L-amino acid defined (CDAA) diets. In vivo experiments showed that the induction of NASH in TG/SB3 mice was characterized by an impressive increase of liver infiltrating macrophages that formed crown-like aggregates and by an up-regulation of hepatic transcript levels of pro-inflammatory cytokines. All these parameters and the extent of liver damage were significantly blunted in KO/SB3 mice. In vitro experiments confirmed that hrSB3 stimulated macrophage production of M1-cytokines such as TNFα and IL-1β and reactive oxygen species along with that of TGFβ and VEGF through the activation of the NF-kB transcription factor. The opposite changes in liver macrophage activation observed in TG/SB3 or KO/SB3 mice with NASH were associated with a parallel modulation in the expression of triggering receptor expressed on myeloid cells-2 (TREM2), CD9 and galectin-3 markers, recently detected in NASH-associated macrophages. From these results we propose that SB3, produced by activated/injured hepatocytes, may operate as a pro-inflammatory mediator in NASH contributing to the disease progression.
A Novel Artificial Neural Network Prognostic Model Based on a Cancer-Associated Fibroblast Activation Score System in Hepatocellular Carcinoma
Authors: Luo Yiqiao , Tan Huaicheng , Yu Ting , Tian Jiangfang , Shi Huashan
Published: July 2022

Introduction

Hepatocellular carcinoma (HCC) ranks fourth as the most common cause of cancer-related death. It is vital to identify the mechanism of progression and predict the prognosis for patients with HCC. Previous studies have found that cancer-associated fibroblasts (CAFs) promote tumor proliferation and immune exclusion. However, the information about CAF-related genes is still elusive.

Methods

The data were obtained from The Cancer Genome Atlas, International Cancer Genome Consortium, and Gene Expression Omnibus databases. On the basis of single-cell transcriptome and ligand–receptor interaction analysis, CAF-related genes were selected. By performing Cox regression and random forest, we filtered 12 CAF-related prognostic genes for the construction of the ANN model based on the CAF activation score (CAS). Then, functional, immune, mutational, and clinical analyses were performed.

Results

We constructed a novel ANN prognostic model based on 12 CAF-related prognostic genes. Cancer-related pathways were enriched, and higher activated cell crosstalk was identified in high-CAS samples. High immune activity was observed in high-CAS samples. We detected three differentially mutated genes (NBEA, RYR2, and FRAS1) between high- and low-CAS samples. In clinical analyses, we constructed a nomogram to predict the prognosis of patients with HCC. 5-Fluorouracil had higher sensitivity in high-CAS samples than in low-CAS samples. Moreover, some small-molecule drugs and the immune response were predicted.

Conclusion

We constructed a novel ANN model based on CAF-related genes. We revealed information about the ANN model through functional, mutational, immune, and clinical analyses.
Characterization of Immune-Related Molecular Subtypes and a Prognostic Signature Correlating With the Response to Immunotherapy in Patients With Gastric Cancer
Authors: Wang Gaoming , Yang Ludi , Wang Yongkun , Hu Renhao , Zhang Kehui , Guo Taohua , Chen Bo , Jiang Xiaohua , Cui Ran
Published: July 2022

Gastric cancer (GC) is a disease characterized by high molecular and phenotypic heterogeneity and represents a leading cause of cancer-related death worldwide. The tumor immune microenvironment (TIME) affects the response to immunotherapy and the prognosis of patients with GC. Explorations of the TIME in GC and characterization of molecular subtypes might enhance personalized treatment and facilitate clinical decision-making. In this study, two molecular subtypes were defined through unsupervised consensus clustering based on immune-related dysregulated genes. Then, patients with different molecular subtypes of GC were shown to have distinct differences in sensitivity to immune checkpoint blockers (ICBs). The immune-related prognostic signature was established utilizing least absolute shrinkage and selection operator (LASSO)-Cox regression analysis. Three independent external cohorts and the IMvigor210 cohort were introduced to validate the robustness of IPRS. scRNA-seq data of GC samples were used to decipher the underlying mechanisms of how IPRS contributes to the TIME. GC biospecimens were collected for RT-qPCR to further validate our findings. In summary, we characterized the abnormal TIME of GC and constructed a reliable immune-related prognostic signature correlating with the response to immunotherapy. This study may provide new strategies for developing individualized treatments for patients with GC.
A New Crustin Gene Homolog SpCrus8 Identified in Scylla paramamosain Exerting In Vivo Protection Through Opsonization and Immunomodulation
Authors: Jiang Manyu , Chen Roushi , Chen Fangyi , Zhu Xuewu , Wang Ke-Jian
Published: July 2022

Crustins are the most abundant class of antimicrobial peptides in crustaceans and are essential for protecting animals from infection. Among them, type II crustins usually exhibit potent antimicrobial activity. Interestingly, in this study, a newly identified type II crustin gene homolog (named SpCrus8) from mud crab Scylla paramamosain, the recombinant proteins of which (rSpCrus8 and rTrx-SpCrus8) showed no obvious antibacterial effects, but could significantly reduce the bacterial load in crab hemolymph and improve the survival rate of crabs infected with Vibrio alginolyticus. The immune-related function of SpCrus8 and the underlying mechanism deserve further investigation. It was found that the SpCrus8 gene was widely distributed in various tissues of adult crabs. In the hepatopancreas of crabs infected with V. alginolyticus or Staphylococcus aureus, transcripts of the SpCrus8 gene were remarkably induced, indicating that the SpCrus8 gene was involved in the immune response to bacterial infection in vivo. In addition, rSpCrus8 and rTrx-SpCrus8 had strong binding activity not only to microbial surface components (lipopolysaccharide, lipoteichoic acid, peptidoglycan, and glucan), but also to the tested bacteria (S. aureus, Pseudomonas aeruginosa and V. alginolyticus). Notably, rSpCrus8 and rTrx-SpCrus8 could significantly promote hemocyte phagocytosis. After rSpCrus8 and rTrx-SpCrus8 treatment, a large number of fluorescent microspheres were observed to aggregate into clusters and be phagocytosed by multiple hemocytes, while hemocytes in the control group phagocytosed only individual microspheres, indicating that SpCrus8 played an important role in opsonization. When the SpCrus8 gene was knocked down, the expression levels of the key phagocytosis-related genes SpRab5 and SpRab7 were significantly downregulated, as well as the IMD signaling pathway genes SpIKKβ and SpRelish, and another crustin gene SpCrus5. Correspondingly, all the SpIKKβ, SpRelish and SpCrus5 genes were significantly upregulated after rSpCrus8 treatment, suggesting that SpCrus8 might be involved in the immunomodulation of S. paramamosain. Taken together, this study revealed the immune-related functions of the SpCrus8 gene in opsonization and regulation, which will help us further understand the role of the crustin gene family in the immune system of mud crabs and provide new insights into the function of type II crutins.
Preemptive Living-Related Kidney Transplantation Is a Cost-Saving Strategy Compared With Post-dialysis Kidney Transplantation in Thailand
Authors: Phongphithakchai Atthaphong , Phisalprapa Pochamana , Kositamongkol Chayanis , Premasathian Nalinee , Larpparisuth Nuttasith , Skulratanasak Peenida , Vongwiwatana Attapong
Published: July 2022

Background

Compared with other kidney replacement therapies, preemptive kidney transplantation (KT) provides better clinical outcomes, reduces mortality, and improves the quality of life of patients with end-stage kidney disease (ESKD). However, evidence related to the cost-effectiveness of preemptive living-related KT (LRKT) is limited, especially in low- and middle-income countries, such as Thailand. This study compared the cost-effectiveness of LRKT with those of non-preemptive KT strategies.

Methods

Cost and clinical data were obtained from adult patients who underwent KT at Siriraj Hospital, Mahidol University, Thailand. A decision tree and Markov model were used to evaluate and compare the lifetime costs and health-related outcomes of LRKT with those of 2 KT strategies: non-preemptive LRKT and non-preemptive deceased donor KT (DDKT). The model’s input parameters were sourced from the hospital’s database and a systematic review. The primary outcome was incremental cost-effectiveness ratios (ICERs). Costs are reported in 2020 United States dollars (USD). One-way and probabilistic sensitivity analyses were performed.

Results

Of 140 enrolled KT patients, 40 were preemptive LRKT recipients, 50 were non-preemptive LRKT recipients, and the rest were DDKT recipients. There were no significant differences in the baseline demographic data, complications, or rejection rates of the three groups of patients. The average costs per life year gained were $10,647 (preemptive LRKT), $11,708 (non-preemptive LRKT), and $11,486 (DDKT). The QALY gained of the preemptive option was 0.47 compared with the non-preemptive strategies. Preemptive LRKT was the best-buy strategy. The sensitivity analyses indicated that the model was robust. Within all varied ranges of parameters, preemptive LRKT remained cost-saving. The probability of preemptive LRKT being cost-saving was 79.4%. Compared with non-preemptive DDKT, non-preemptive LRKT was not cost-effective at the current Thai willingness-to-pay threshold of $5113/QALY gained.

Conclusions

Preemptive LRKT is a cost-saving strategy compared with non-preemptive KT strategies. Our findings should be considered during evidence-based policy development to promote preemptive LRKT among adults with ESKD in Thailand.
Relation Between Dietary Carotenoid Intake, Serum Concentration, and Mortality Risk of CKD Patients Among US Adults: National Health and Nutrition Examination Survey 2001–2014
Authors: Hu Yuncan , Cai Xiaoyu , Zhang Nanhui , Li Yu , Mao Ya , Ge Shuwang , Yao Ying , Gao Hui
Published: July 2022

Background

Current evidence on the relationship between carotenoids and chronic kidney disease (CKD) patients are limited and controversial.

Methods

Data were obtained from the Nutrition and Health Examination Survey (NHANES) database and the NHANES Linked Mortality File, both from a nationally representative sample. Dietary intake was assessed through 24-h dietary recall, and information was available both on dietary and serum α-carotene, β-carotene, β-cryptoxanthin, lycopene, and lutein/zeaxanthin (combined) through the NHANES cycles used. We used multivariable Cox proportional hazards regression models to estimate the risk for all-cause mortality associated with carotene intakes and serum levels, adjusting for potential confounding factors.

Results

Of the 6,095 CKD participants, 1,924 subjects died (mean follow-up time, 8.1 years). After eliminating all the confounding factors, we found that high levels of total carotene (HR = 0.85, 95% CI, 0.75-0.97, P = 0.011) intakes at baseline were significantly associated with a lower risk of death. And the serum concentrations of carotenoid were also showing that a-carotene (HR = 0.77, 95%CI, 0.65–0.92, P = 0.002), beta-cryptoxanthin (HR = 0.83, 95%CI, 0.70–0.98, P = 0.019), lycopene (HR = 0.77, 95% CI, 0.65–0.91, P = 0.002), and lutein + zeaxanthin (HR = 0.82, 95% CI, 0.70–0.96, P = 0.002) was significantly associated with decreased all-cause mortality of CKD patients. The associations remained similar in the sensitivity analyses.

Conclusion

Findings suggest that high-level carotene dietary intake and the serum concentration were associated with a lower risk of mortality in the CKD population.
Endothelial Glycocalyx Degradation in Critical Illness and Injury
Authors: Patterson Eric K. , Cepinskas Gediminas , Fraser Douglas D.
Published: July 2022

The endothelial glycocalyx is a gel-like layer on the luminal side of blood vessels that is composed of glycosaminoglycans and the proteins that tether them to the plasma membrane. Interest in its properties and function has grown, particularly in the last decade, as its importance to endothelial barrier function has come to light. Endothelial glycocalyx studies have revealed that many critical illnesses result in its degradation or removal, contributing to endothelial dysfunction and barrier break-down. Loss of the endothelial glycocalyx facilitates the direct access of immune cells and deleterious agents (e.g., proteases and reactive oxygen species) to the endothelium, that can then further endothelial cell injury and dysfunction leading to complications such as edema, and thrombosis. Here, we briefly describe the endothelial glycocalyx and the primary components thought to be directly responsible for its degradation. We review recent literature relevant to glycocalyx damage in several critical illnesses (sepsis, COVID-19, trauma and diabetes) that share inflammation as a common denominator with actions by several common agents (hyaluronidases, proteases, reactive oxygen species, etc.). Finally, we briefly cover strategies and therapies that show promise in protecting or helping to rebuild the endothelial glycocalyx such as steroids, protease inhibitors, anticoagulants and resuscitation strategies.
Presumed Protective Role for Anti-Hepatitis B Virus Antibodies Against COVID-19 Severe Cases: A Clinical Study Confirming in silico Hypothesis
Authors: Gdoura Mariem , Touati Raoua , Kalthoum Sana , Ben Slama Rania , Fatnassi Nouel , Mrad Mehdi , Ammari Lamia , Brahmi Nozha , Ben Jazia Amira , Hogga Nahed , Triki Henda , Haddad-Boubaker Sondes
Published: July 2022

Background

Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) is responsible for COVID-19 disease which is known to have a broad clinical spectrum, from asymptomatic to critical presentation leading to death. Many researchers have investigated the factors impacting the course of the disease. Our previous in silico study suggested a possible protective effect of Hepatitis B, Tetanus and Measles vaccines against COVID-19. In continuity, we conducted a cross-sectional clinical study in order to confirm our in silico assumptions regarding the HBs-Ag antibodies.

Methods

A representative sex- and age-matched sample of patients with confirmed COVID-19 was selected (n = 340). All clinical presentations were equally represented. Using an ELISA test, each patient benefited of a serology for the detection and measurement of the anti-HBs specific IgG antibodies. The obtained results allowed determining the different correlations between these antibody titers and the disease severity. The R® software and the MedCalc® software served to calculate the Spearman's coefficient of rank correlation (rho) for the obtained titers per severity group as well as the different other calculations and figure representations.

Results

A significant positive correlation was found with the anti-HBs titers (rho = 0.107; p = 0.04). High anti-HBs titers were significantly associated with the mild presentation of COVID-19. A significant difference was found between the obtained titers per severity class (chi-2 test, p = 0.03).

Discussion/Conclusion

Our findings demonstrated that anti-HBs titers were significantly higher for patients having mild COVID-19 presentations. We presume that being immunized against the HB may play a protective role in the course of the disease. Our study provided more key elements in understanding the disparity of the clinical spectrum among regions.
Serum Calprotectin Level Is Independently Associated With Carotid Plaque Presence in Patients With Psoriatic Arthritis
Authors: Cheng Isaac T. , Meng Huan , Li Martin , Li Edmund K. , Wong Priscilla C. , Lee Jack , Yan Bryan P. , Lee Alex P. W. , So Ho , Tam Lai-Shan
Published: July 2022

Background

Whether calprotectin could play a role in augmenting cardiovascular (CV) risk in patients with psoriatic arthritis (PsA) remains uncertain. The aim of this study is to elucidate the association between serum calprotectin level and subclinical atherosclerosis in patient with PsA.

Method

Seventy-eight PsA patients (age: 52 ± 10 years, 41 [52.6%] male) without CV disease were recruited into this cross-sectional study. Carotid intima-media thickness (cIMT) and the presence of plaque were determined by high-resolution ultrasound. Calprotectin levels in serum were quantified by enzyme-linked immunosorbent assay. The variables associated with the presence of carotid plaque (CP) were selected from the least absolute shrinkage and selection operator (LASSO) regression analysis.

Results

29/78 (37.2%) of patient had carotid plaque (CP+ group). Serum calprotectin level was significantly higher in the CP+ group (CP− group: 564.6 [329.3–910.5] ng/ml; CP+ group: 721.3 [329.3–910.5] ng/ml, P = 0.005). Serum calprotectin level correlated with PsA disease duration (rho = 0.280, P = 0.013) and mean cIMT (rho = 0.249, P = 0.038). Using LASSO regression analysis, the levels of Ln-calprotectin (OR: 3.38, 95% CI [1.37, 9.47]; P = 0.026) and PsA disease duration (OR: 1.09, 95% CI [1.01, 1.18]; P = 0.013) were screened out from a total of 19 variables. The model in predicting the presence of CP was constructed by Ln-calprotectin and PsA disease duration with an area under the receiver-operating characteristic (ROC) curve of 0.744, (95 CI% [0.59, 0.80], P = 0.037).

Conclusion

Serum calprotectin level is associated with the presence of CP in PsA. Further studies are required to confirm whether this pathway is associated with CV events in PsA.
A Review of the Prevention of Mother-to-Child Transmission of Human T-Cell Lymphotrophic Virus Type 1 (HTLV-1) With a Proposed Management Algorithm
Authors: Barr Rachael S. , Drysdale Simon B. , Boullier Mary , Lyall Hermione , Cook Lucy , Collins Graham P. , Kelly Dominic F. , Phelan Lorna , Taylor Graham P.
Published: July 2022

Human T cell lymphotropic virus type 1 (HTLV-1) is a human retrovirus that is endemic in a number of regions across the world. There are an estimated 5–10 million people infected worldwide. Japan is currently the only country with a national antenatal screening programme in place. HTLV-1 is primarily transmitted sexually in adulthood, however it can be transmitted from mother-to-child perinatally. This can occur transplacentally, during the birth process or via breastmilk. If HTLV-1 is transmitted perinatally then the lifetime risk of adult T cell leukemia/lymphoma rises from 5 to 20%, therefore prevention of mother-to-child transmission of HTLV-1 is a public health priority. There are reliable immunological and molecular tests available for HTLV-1 diagnosis during pregnancy and screening should be considered on a country by country basis. Further research on best management is needed particularly for pregnancies in women with high HTLV-1 viral load. A first step would be to establish an international registry of cases and to monitor outcomes for neonates and mothers. We have summarized key risk factors for mother-to-child transmission of HTLV-1 and subsequently propose a pragmatic guideline for management of mothers and infants in pregnancy and the perinatal period to reduce the risk of transmission. This is clinically relevant in order to reduce mother-to-child transmission of HTLV-1 and it's complications.
A Review on Biomarkers for the Evaluation of Autoimmune Cholestatic Liver Diseases and Their Overlap Syndromes
Authors: Nguyen Henry H. , Fritzler Marvin J. , Swain Mark G.
Published: July 2022

Autoimmune cholestatic liver disease includes both Primary Biliary Cholangitis (PBC) and Primary Sclerosing Cholangitis (PSC). Both conditions result in impairment of hepatic bile flow ultimately leading to chronic liver injury, liver fibrosis and eventually end stage cirrhosis. Early and accurate diagnosis are important for the risk stratification, follow up and management of these patients. The underlying pathogenesis of these conditions have not been completely resolved and poses a barrier for the development of new diagnostic and prognostics tools. Current research work suggests that the pathogenesis of autoimmune cholestatic liver disease results from environmental, genetic, and a large component of underlying immune dysfunction. While the current available serum biomarkers and imaging modalities showcases progression in precision medicine for the management of autoimmune cholestatic liver disease, development of new biomarkers are still an area of need in this field. In this review, we will discuss the current and emerging biomarkers in patients with PBC, PSC, and a special population that exhibit overlap syndrome with autoimmune hepatitis (AIH). The use of these biomarkers for diagnosis and prognosis of these patients will be reviewed through the lens of the current understanding of the complex immune pathophysiology of these conditions.
Association of Cerebral Small Vessel Disease With Gait and Balance Disorders
Authors: Su Chen , Yang Xiaoyu , Wei Shuqi , Zhao Renliang
Published: July 2022

Cerebral small vessel disease (CSVD) is a common cerebrovascular disease and an important cause of gait and balance disorders. Gait and balance disorders can further lead to an increased risk of falls and a decreased quality of life. CSVD can damage gait and balance function by affecting cognitive function or directly disrupting motor pathways, and different CSVD imaging features have different characteristics of gait and balance impairment. In this article, the correlation between different imaging features of sporadic CSVD and gait and balance disorders has been reviewed as follows, which can provide beneficial help for standardized management of CSVD.
Machine Learning Techniques for the Diagnosis of Schizophrenia Based on Event-Related Potentials
Authors: Santos Febles Elsa , Ontivero Ortega Marlis , Valdés Sosa Michell , Sahli Hichem
Published: July 2022

Antecedent

The event-related potential (ERP) components P300 and mismatch negativity (MMN) have been linked to cognitive deficits in patients with schizophrenia. The diagnosis of schizophrenia could be improved by applying machine learning procedures to these objective neurophysiological biomarkers. Several studies have attempted to achieve this goal, but no study has examined Multiple Kernel Learning (MKL) classifiers. This algorithm finds optimally a combination of kernel functions, integrating them in a meaningful manner, and thus could improve diagnosis.

Objective

This study aimed to examine the efficacy of the MKL classifier and the Boruta feature selection method for schizophrenia patients (SZ) and healthy controls (HC) single-subject classification.

Methods

A cohort of 54 SZ and 54 HC participants were studied. Three sets of features related to ERP signals were calculated as follows: peak related features, peak to peak related features, and signal related features. The Boruta algorithm was used to evaluate the impact of feature selection on classification performance. An MKL algorithm was applied to address schizophrenia detection.

Results

A classification accuracy of 83% using the whole dataset, and 86% after applying Boruta feature selection was obtained. The variables that contributed most to the classification were mainly related to the latency and amplitude of the auditory P300 paradigm.

Conclusion

This study showed that MKL can be useful in distinguishing between schizophrenic patients and controls when using ERP measures. Moreover, the use of the Boruta algorithm provides an improvement in classification accuracy and computational cost.
Dietary Behavior and Compliance to Bulgarian National Nutrition Guidelines in Patients With Type 1 Diabetes With Longstanding Disease
Authors: Pancheva Rouzha , Dimitrov Lyubomir , Gillon-Keren Michal , Tsochev Kaloyan , Chalakova Tatyana , Usheva Natalya , Nikolova Silviya , Yotov Yoto , Iotova Violeta
Published: July 2022

Introduction

Nutrition education attempts to maintain and enhance good eating habits to achieve optimal metabolic control in people with type 1 diabetes (T1D). Recommendations for patients with T1D are comparable to those of the general population.

This Study Aimed

To investigate dietary habits and adherence to nutritional recommendations of patients with T1D as compared with age, gender, and BMI matched people in Bulgaria.

Methods

A case-control study included 124 patients with T1D with long disease duration (mean duration 25.3 ± 8.2 years) followed up at a diabetes clinic in Varna, Bulgaria for 2 years (2017–2019) and 59 controls matched for gender, age and BMI. A 24-h dietary recall method was used to assess the nutrition of both groups. A standardized questionnaire was applied to assess the frequency of food consumption (Feel4Diabtes). Height and weight were standardly measured, and BMI was calculated. Findings were compared with Bulgarian recommendations and reference values for energy and nutrient intake for healthy adults. The data were analyzed with the statistical package SPSSv21.0 and Jamovi v.22.5.

Results

The nutritional characteristics of T1D men and women differ. Men with T1D had a higher intake of total carbohydrates (CHO) (p = 0.009), a lower intake of total fats (p = 0.007), and monounsaturated fatty acids (p = 0.029) as a percentage of total daily energy compared with the controls. Women with T1D had a different distribution of energy intake per meal compared to controls: they consumed more energy (p = 0.001) and a corresponding share of CHO for lunch, less for dinner (p = 0.015) and had a higher overall healthy diet score when compared to controls (p = 0.02). Adherence to dietary recommendations (e.g., CHO, total fats, saturated fat, fibers) was low in both genders, but lower in the general population compared to people with T1D.

Conclusion

Our data demonstrate that people with T1D consume a healthier diet than the general population, which could be attributed to healthier diet awareness, still far from the recommendations. Introduction of annual consultations with a dietitian may improve long-term outcomes.
Assessment of the Volatile Profiles and Identification of Differentiating Aromas of Wild Undervalued Plants
Authors: Fukalova Fukalova Tamara , Moreno-Peris Estela , García-Martínez María Dolores , Raigón Jiménez María Dolores
Published: July 2022

Wild edible plants have played an important role in traditional diets, including the Mediterranean diet. Many of these plants have acquired an undervalued status, since they are under-appreciated in terms of their nutritional, organoleptic qualities, or their seasonality. However, some of these species are still used in local gastronomy for their aromatic and taste characteristics. This study has investigated the quantitative and qualitative aromatic characteristics of seven undervalued wild plants that determine their organoleptic characteristics. Volatiles of the fresh leaves of each species have been determined by head-space solid-phase microextraction, a sensitive and solvent-free technique, coupled with gas chromatography and mass spectrometry. A total of 37 compounds with remarkable quantitative and qualitative differences were identified. In general, benzenoids and monoterpenoids were the most abundant groups, while branched unsaturated hydrocarbons, fatty alcohols, and sesquiterpenoids were the minor groups. Benzyl nitrile, benzyl isothiocyanate, p-cymene, and 2-hexenal were the main individual volatiles, while benzyl alcohol, eugenol, and α-copaene were the differentiating aromas. The results display that the undervalued species studied could be a suitable choice to include as new environmentally friendly crops, providing a double benefit to producers, because they are a possible way to achieve sustainable production systems, and they are an alternative for consumers, because these plants provide flavors that have high organoleptic qualities.
Dietary Patterns in Association With Hypertension: A Community-Based Study in Eastern China
Authors: Wang Cuicui , Zheng Yanmin , Zhang Ya , Liu Dong , Guo Li , Wang Bo , Zuo Hui
Published: July 2022

Objective

This study aimed to explore the association between dietary patterns and hypertension based on a community–based survey in Suzhou, Eastern China.

Methods

This cross–sectional analysis was undertaken from the subset of the Suzhou Food Consumption and Health State Survey in 2018–2019. Adults aged ≥ 18 years were invited to participate in this survey. Dietary intake was collected by a 24–h dietary recall and a weighing method over three consecutive days (including two weekdays and one weekend day). Dietary patterns were defined using factor analysis. Association between the dietary patterns and hypertension was examined by multivariable logistic regression models with adjustment for covariates. Moreover, sensitivity analysis was used to reinforce our findings.

Results

A total of 2,718 participants were included in the final analysis. Rice-vegetable pattern, fast food pattern, fruit-dairy pattern, and wheat-meat pattern were identified. We observed that the fruit-dairy pattern was inversely associated with hypertension after adjustment for all the covariates (OR = 0.55; 95% CI: 0.40, 0.75; P = 0.002). The association between the wheat-meat pattern and hypertension was attenuated and became statistically nonsignificant in sensitivity analyses. The other two patterns were not significantly associated with hypertension (P > 0.05).

Conclusion

The fruit-dairy pattern was inversely associated with the risk of hypertension among Chinese adults. Our findings further emphasize the important role of optimal diet combination in the prevention of hypertension.
Effects of Variability in Glycemic Indices on Longevity in Chinese Centenarians
Authors: Ji Sheng-han , Dong Chen , Chen Rou , Shen Chen-chen , Xiao Jing , Gu Yun-juan , Gao Jian-lin
Published: July 2022

Background

Large fluctuations in blood glucose levels greatly impact the health and life span of elderly individuals. This study describes the characteristics of variability in glycemic indices in centenarians with the aim of emphasizing the importance of glycemic variability in elderly people.

Methods

We recruited individuals from Rugao City, Jiangsu Province, China from April 2020 to May 2021. The study cohort included 60 centenarians and 60 first-generation offspring, as well as 20 randomly selected non-cohabitant control individuals aged 60–80 years. A FreeStyle Libre H (hospital version) continuous glucose monitoring (CGM) device (Abbott Ireland UK) was used to measure glycemic variability. The indices measured included the time in target glucose range (TIR), time below target glucose range (TBR), time above target glucose range (TAR), mean amplitude of glycemic excursions (MAGE), mean of daily differences (MODD), coefficient of variation (CV), standard deviation of blood glucose (SDBG), continuous overlapping net glycemic action (CONGA), glucose management indicator (GMI) and estimated glycated hemoglobin (eHbA1c). Logistic regression was used to analyze the association between glycemic variability and longevity.

Results

Mean blood glucose (MBG), eHbA1c, GMI, mean fasting plasma glucose (M-FPG) and CONGA were lower in the centenarian group (p all < 0.05). PPGE-2 was higher in the control group than that measured in the centenarian and first-generation offspring groups (p < 0.05). There were no differences between the groups in MAGE, MODD, MAG, or TIR (p > 0.05). The risk of not achieving longevity increased with each one unit increase in MBG by 126% [2.26 (1.05–4.91)], eHbA1c by 67% [1.67 (1.03–2.72)], GMI by 568% [6.68 (1.11–40.30)], M-FPG by 365% [4.65 (1.57–13.75)], M-PPG1h by 98% [1.98 (1.18–3.31)], CONGA1 by 102% [2.02 (1.01–4.06)], Li by 200% [3.00 (1.04–8.61)], and PPGE-2 by 150% [2.50 (1.39–4.50)]. However, the risk of achieving longevity decreased with each unit increase of LBGI by 53% [0.47 (0.28–0.80)], ADRR by 60% [0.40 (0.18–0.86)], and TBR by 11% [0.89 (0.80–0.98)].

Conclusion

Fluctuation in blood glucose levels in centenarians is relatively small. Maintaining an average blood glucose level and keeping blood glucose fluctuations in the normal range is conducive to longevity.