bluuebunny/crossref_metadata_2025 huggingface dataset:
“It’s something that I do every day.” Exploring interdisciplinarity and stakeholder engagement in tsunami science
Authors: Rödder Simone , Schaumann Felix
Published: September 2022

Tsunamis are natural hazards that can have devastating societal impacts. While tsunamis cannot be prevented, their risk to coastal communities can be mitigated through targeted measures such as early warning, evacuation training or tsunami-aware spatial planning. The particularities of tsunamis–being rare events with high impact and a short yet operable time span for warning–structure the associated research approaches and sociotechnical innovations. In this paper, we explore interdisciplinary knowledge integration and stakeholder engagement in tsunami science based on interviews with researchers from various tsunami-related fields. We find that the interviewees’ academic identities are typically grounded in a disciplinary core, out of which they subsequently cross boundaries. For all respondents, however, it is a matter of course that becoming and being a member of the tsunami community includes the need to communicate across boundaries. Our results show that the idea of early warning unites the tsunami field. Notably, however, it is not the material technology but the political goal of effective early warning that holds an integrative function across disciplines. Furthermore, we find modelling to be seen as the “backbone of everything” tsunami-related, which in combination with visualisation techniques such as a global map of tsunami risks also serves to integrate stakeholders beyond the tsunami research community. Interviewees mention the interaction between scientists and engineers as the exemplary interdisciplinary collaboration in tsunami science. There were fewer examples of collaborations with social scientists, rendering this a demand rather than a lived reality in current tsunami science. Despite the widely shared view that stakeholder engagement is an important element of tsunami science, respondents emphasise the associated challenges and indicate that this practice is not yet sufficiently institutionalised.
Wake-up time and academic performance of university students in Indonesia: A cross-sectional study
Authors: Sofyana Meida , Wibowo Rakhmat Ari , Agustiningsih Denny
Published: September 2022

Several studies have highlighted the link between sleep, learning, and memory. Strong evidence shows that sleep deprivation can affect a student’s ability to learn and academic performance. While delayed sleep-wake phase disorder was prevalent among young adults, available evidence showed an inconclusive association between sleep times and academic performance in university students. Therefore, we conducted a cross-sectional study among university students in Indonesia to collect their sleep duration, bedtime, wake-up time, and academic performance. An analysis of 588 university students in Indonesia found that only 38.6% of students sufficiently slept, and their median bedtime and wake-up time was 11:30 pm and 5:30 am, respectively. Gender and wake-up time accounted for a 5.8% variation in academic performance (adjusted R2 = 4.5%) after controlling for sleep duration, bedtime, body mass index, the field of study, batch year, and physical activity. Male had 0.116 [95% Confidence Interval (CI) −0.167 to −0.064] lower grade point average (p < 0.001) than female and students who wake up later had 0.077 (95% Confidence Interval 0.025 to 0.129) greater grade point average (p = 0.004) than students who wake-up earlier. The prevalence of sleep deprivation related to the delayed sleep-wake phase among university students in Indonesia was high. Since wake-up time was related to the increased grade point average, the university should consider developing sleep-friendly policies and interventions to improve their academic performance.
Placental pathologic lesions associated with stroke in term neonates
Authors: Leon Rachel L. , Kalvacherla Vinay , Andrews Michelle Machie , Thomas Jennifer M. , Mir Imran N. , Chalak Lina F.
Published: September 2022

Objective

To determine the birth prevalence of perinatal stroke in term born infants at our high-volume delivery center and assess the frequency of both gross and histologic placental pathologies associated with perinatal stroke using the Amsterdam Placental Workshop Group Consensus Statement guidelines and definitions.

Study Design

A single-center retrospective cohort study spanning 2010-2020.

Results

There were 129,759 live births at Parkland Hospital during the study period and a total of 18 term born infants leading to a birth prevalence of 1 in 6,829 infants. Perinatal risk factors were found in all but one patient, and 74% presented with seizures. Pathologic placental examination was available in 56% of the cohort and only one patient had normal placental examination. Acute histologic chorioamnionitis was described in five placentas (50%) and an additional two had isolated umbilical and/or chorionic plate vasculitis with or without funisitis compared to a rate of 28% with acute inflammation in a Control group. Chronic inflammation in the form of villitis of unknown etiology was described in three of the acutely inflamed placentas and was high-grade in each of those while none of the placentas from our Control group showed evidence of any chronic lesion.

Conclusion

Both acute and chronic placental inflammation are common in perinatal stroke; placental examination should be considered an essential component to the diagnostic workup.
Network Pharmacology and Bioinformatics Analysis Identifies Potential Therapeutic Targets of Paxlovid Against LUAD/COVID-19
Authors: Zhang Wentao , Yang Zhe , Zhou Fengge , Wei Yanjun , Ma Xiaoqing
Published: September 2022

Background

Coronavirus disease 2019 (COVID-19), caused by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), has caused a pandemic in many countries around the world. The virus is highly contagious and has a high fatality rate. Lung adenocarcinoma (LUAD) patients may have higher susceptibility and mortality to COVID-19. While Paxlovid is the first oral drug approved by the U.S. Food and Drug Administration (FDA) for COVID-19, its specific drug mechanism for lung cancer patients infected with COVID-19 remains to be further studied.

Methods

COVID-19 related genes were obtained from NCBI, GeneCards, and KEGG, and then the transcriptome data for LUAD was downloaded from TCGA. The drug targets of Paxlovid were revealed through BATMAN-TCM, DrugBank, SwissTargetPrediction, and TargetNet. The genes related to susceptibility to COVID-19 in LUAD patients were obtained through differential analysis. The interaction of LUAD/COVID-19 related genes was evaluated and displayed by STRING, and a COX risk regression model was established to screen and evaluate the correlation between genes and clinical characteristics. The Venn diagram was drawn to select the candidate targets of Paxlovid against LUAD/COVID-19, and the functional analysis of the target genes was performed using KEGG and GO enrichment analysis. Finally, Cytoscape was used to screen and visualize the Hub Gene, and Autodock was used for molecular docking between the drug and the target.

Result

Bioinformatics analysis was performed by combining COVID-19-related genes with the gene expression and clinical data of LUAD, including analysis of prognosis-related genes, survival rate, and hub genes screened out by the prognosis model. The key targets of Paxlovid against LUAD/COVID-19 were obtained through network pharmacology, the most important targets include IL6, IL12B, LBP. Furthermore, pathway analysis showed that Paxlovid modulates the IL-17 signaling pathway, the cytokine-cytokine receptor interaction, during LUAD/COVID-19 treatment.

Conclusions

Based on bioinformatics and network pharmacology, the prognostic signature of LUAD/COVID-19 patients was screened. And identified the potential therapeutic targets and molecular pathways of Paxlovid Paxlovid in the treatment of LUAD/COVID. As promising features, prognostic signatures and therapeutic targets shed light on improving the personalized management of patients with LUAD.
Lipocalin-2 is associated with FGF23 in WNT1 and PLS3 osteoporosis
Authors: Loid Petra , Hauta-alus Helena , Mäkitie Outi , Magnusson Per , Mäkitie Riikka E.
Published: September 2022

Background

The pathogenic mechanisms of early-onset osteoporosis caused by WNT1 and PLS3 mutations are incompletely understood and diagnostic biomarkers of these disorders are limited. Recently, lipocalin-2 has been recognized as an osteokine involved in bone development and homeostasis. However, the role of lipocalin-2 in WNT1 and PLS3 osteoporosis is unknown.

Objective

We aimed to investigate if plasma lipocalin-2 could be utilized as a biomarker for WNT1 and PLS3 osteoporosis and to evaluate the association between lipocalin-2 and other parameters of bone metabolism.

Methods

We measured plasma lipocalin-2 in 17 WNT1 and 14 PLS3 mutation-positive patients and compared them to those of 34 mutation-negative (MN) healthy subjects. We investigated possible associations between lipocalin-2 and several bone biomarkers including collagen type I cross-linked C-telopeptide (CTX), alkaline phosphatase (ALP), type I procollagen intact N-terminal propeptide (PINP), intact and C-terminal fibroblast growth factor 23 (FGF23), dickkopf-1 (DKK1) and sclerostin as well as parameters of iron metabolism (iron, transferrin, transferrin saturation, soluble transferrin receptor and ferritin).

Results

We found no differences in plasma lipocalin-2 levels in WNT1 or PLS3 patients compared with MN subjects. However, lipocalin-2 was associated with C-terminal FGF23 in WNT1 patients (r=0.62; p=0.008) and PLS3 patients (r=0.63, p=0.017), and with intact FGF23 in PLS3 patients (r=0.80; p<0.001). In addition, lipocalin-2 correlated with serum transferrin in WNT1 patients (r=0.72; p=0.001).

Conclusion

We conclude that plasma lipocalin-2 is not altered in WNT1 or PLS3 mutation-positive subjects but is associated with FGF23 in abnormal WNT1 or PLS3 signaling and with iron status in abnormal WNT1 signaling.
Association of amino acids related to urea cycle with risk of diabetic nephropathy in two independent cross-sectional studies of Chinese adults
Authors: Cao Penglong , Huang Bing , Hong Mo , Jiang Yuxin , Cao Ran , Chi Chen , Cao Yunfeng , Li Shijun
Published: September 2022

Objective

To investigate the association between amino acids related to the urea cycle and diabetic nephropathy (DN) in two independent cross-sectional studies.

Methods

We obtained the medical records of 145 individuals with DN and 596 individuals without DN who attended an annual health examination at Liaoning Medical University First Affiliated Hospital (LMUFAH), China, from May 2015 to August 2016. From April 2018 to April 2019, we collected medical records of another 741 individuals: 338 individuals with DN and 403 individuals without DN from the Second Affiliated Hospital of Dalian Medical University (DALIAN), China. Binary logistic regression was used to obtain the odds ratio (OR) and 95% confidence interval (CI).

Results

In two independent cross-sectional studies, we observed that citrulline was consistently associated with DN risk [OR (95% CI) of per standard deviation (SD) increase for citrulline in the LMUFAH population: 1.200 (1.006, 1.432); OR (95% CI) of per SD increase for citrulline in the DALIAN population: 1.189 (1.012, 1.396); pooled effect size for citrulline: 1.194 (1.060, 1.345)]. However, ornithine, arginine, and the ratio of arginine to ornithine were consistently unrelated to DN risk, and the ratios of other amino acids in the urea cycle were inconsistently associated with DN risk.

Conclusions

Citrulline was consistently associated with DN risk in two independent cross-sectional studies in Chinese adults.
A higher TyG index is related with a higher prevalence of erectile dysfunction in males between the ages 20-70 in the United States, according to a cross-sectional research
Authors: Li Lin , Yao Hui , Dai Wei , Chen Yan , Liu Heqian , Ding Wei , Liu Yingqing , Tao Lingsong , Wang Jiawei , Chen Mingwei
Published: September 2022

Objective

This study aims to investigate the relationship between triglyceride glucose index (TyG) and erectile dysfunction (ED) among United States (US) adult males.

Methods

A logistic regression analysis, subgroup analysis, and the computation of the dose-response curve were used to investigate the relationship between TyG index and ED prevalence among participants from the 2001-2004 National Health and Nutrition Examination Survey (NHANES) database.

Results

After adjusting for all confounders, each unit increase in TyR index was associated with a 25 percent increase in ED prevalence (OR=1.25, 95%CI:1.03, 1.52), and stratified analysis showed that elevated TyG index was associated with increased ED prevalence in the 50-year old group (OR=1.35, 95% CI:1.05, 1.74), the Mexican-American group (OR=1.50, 95% CI:1.00, 2.23) and BMI 25-29.9 kg/m2 (OR=1.48, 95% CI:1.08, 2.01). The dose-response curve demonstrated a positive linear connection between the TyG index and the risk of ED.

Conclusion

It has been shown that a higher TyG index is associated with a higher prevalence of erectile dysfunction. Although the causal relationship is not clear, it still deserves clinical attention
A bibliometric analysis of RNA methylation in diabetes mellitus and its complications from 2002 to 2022
Authors: Zhang Wenhua , Zhang Shuwen , Dong Chenlu , Guo Shuaijie , Jia Weiyu , Jiang Yijia , Wang Churan , Zhou Mingxue , Gong Yanbing
Published: September 2022

Background

RNA methylation has emerged as an active research field in diabetes mellitus (DM) and its complications, while few bibliometric analyses have been performed. We aimed to visualize the hotspots and trends using bibliometric analysis to provide a comprehensive and objective overview of the current search state in this field.

Methods

The articles and reviews regarding RNA methylation in DM and its complications were from the Web of Science Core Collection. A retrospective bibliometric analysis and science mapping was performed using the CiteSpace software to plot the knowledge maps and predict the hotspots and trends.

Results

Three hundred seventy-five qualified records were retrieved. The annual publications gradually increased over the past 20 years. These publications mainly came from 66 countries led by Canada and 423 institutions. Leiter and Sievenpiper were the most productive authors, and Jenkins ranked first in the cited authors. Diabetes Care was the most co-cited journal. The most common keywords were “Type 2 diabetes”, “cardiovascular disease”, “diabetes mellitus”, and “n 6 methyladenosine”. The extracted keywords mainly clustered in “beta-cell function”, “type 2 diabetes”, “diabetic nephropathy”, “aging”, and “n6-methyladenosine”. N6-methyladenosine (m6A) in DM and its complications were the developing areas of study.

Conclusion

Studies on RNA methylation, especially m6A modification, are the current hotspots and the future trends in type 2 diabetes (T2D) and diabetic nephropathy (DN), as well as a frontier field for other complications of DM. Strengthening future cooperation and exchange between countries and institutions is strongly advisable to promote research developments in this field.
Rodent faunas, their paleogeographic pattern, and responses to climate changes from the early Eocene to the early Oligocene in Asia
Authors: Li Qian , Li Qi , Xu Rancheng , Wang Yuanqing
Published: September 2022

Rodents are an important component in Paleogene terrestrial ecosystems. Their evolution and faunal turnover have likely been influenced and triggered by global climate change. Here, we compiled rodent faunas from the early Eocene to the early Oligocene in Asia to discuss rodent faunal turnover and its correlation with paleogeographic and paleoclimate changes. Successive rodent faunas from the early Eocene to the early Oligocene are recorded in East Asia, and rodent faunal turnover is obviously affected by paleoclimatic changes. During the Ulangochuian (after the middle Eocene climatic optimum), when temperatures declined slowly, the East Asian rodent fauna showed a clear decline in generic diversity and a transformation from ctenodactyloid-dominant to cricetid–dipodid-dominant faunas. During the Eocene–Oligocene transition (EOT) and global cooling, the East Asian rodent fauna exhibited a considerably high generic diversity of cricetids, dipodids, and ctenodactylids. The low temperatures during the Ulangochuian and Ergilian in East Asia served as a habituation ground for the cricetids and dipodids, which became preadapted for the EOT, successfully helping rodents become dominant faunas after EOT. The rodent faunas in South Asia formed a relatively unique group in much of the Eocene and early Oligocene; sometimes, they were closer to European or African than to Asian rodents. The greatly different paleoenvironment probably caused striking differences between the rodent faunas in South Asia and East Asia.
Incorporation of Soil-Derived Covariates in Progeny Testing and Line Selection to Enhance Genomic Prediction Accuracy in Soybean Breeding
Authors: Canella Vieira Caio , Persa Reyna , Chen Pengyin , Jarquin Diego
Published: September 2022

The availability of high-dimensional molecular markers has allowed plant breeding programs to maximize their efficiency through the genomic prediction of a phenotype of interest. Yield is a complex quantitative trait whose expression is sensitive to environmental stimuli. In this research, we investigated the potential of incorporating soil texture information and its interaction with molecular markers via covariance structures for enhancing predictive ability across breeding scenarios. A total of 797 soybean lines derived from 367 unique bi-parental populations were genotyped using the Illumina BARCSoySNP6K and tested for yield during 5 years in Tiptonville silt loam, Sharkey clay, and Malden fine sand environments. Four statistical models were considered, including the GBLUP model (M1), the reaction norm model (M2) including the interaction between molecular markers and the environment (G×E), an extended version of M2 that also includes soil type (S), and the interaction between soil type and molecular markers (G×S) (M3), and a parsimonious version of M3 which discards the G×E term (M4). Four cross-validation scenarios simulating progeny testing and line selection of tested–untested genotypes (TG, UG) in observed–unobserved environments [OE, UE] were implemented (CV2 [TG, OE], CV1 [UG, OE], CV0 [TG, UE], and CV00 [UG, UE]). Across environments, the addition of G×S interaction in M3 decreased the amount of variability captured by the environment (−30.4%) and residual (−39.2%) terms as compared to M1. Within environments, the G×S term in M3 reduced the variability captured by the residual term by 60 and 30% when compared to M1 and M2, respectively. M3 outperformed all the other models in CV2 (0.577), CV1 (0.480), and CV0 (0.488). In addition to the Pearson correlation, other measures were considered to assess predictive ability and these showed that the addition of soil texture seems to structure/dissect the environmental term revealing its components that could enhance or hinder the predictability of a model, especially in the most complex prediction scenario (CV00). Hence, the availability of soil texture information before the growing season could be used to optimize the efficiency of a breeding program by allowing the reconsideration of field experimental design, allocation of resources, reduction of preliminary trials, and shortening of the breeding cycle.
Pan-cancer analysis of prognostic and immunological role of DTYMK in human tumors
Authors: Zhao Huihui , Xie Rongrong , Zhang Chenxi , Lu Guojun , Kong Hui
Published: September 2022

Background: Deoxythymidylate kinase (DTYMK) has been reported to correlate with the progression of hepatocellular carcinoma. However, the role of DTYMK in human cancers is not studied. In this study, we studied the prognostic value, functional states, and correlations with immune infiltration of DTYMK in human cancers.

Methods: The Cancer Genome Atlas (TCGA), Genotype-Tissue Expression (GTEx), UALCAN, Clinical Proteomic Tumor Analysis Consortium (CPTAC), the search tool for the retrieval of interacting genes (STRING), GeneMANIA, cBioPortal, Cancer Single-cell State Atlas (CancerSEA), and Tumor IMmune Estimation Resource (TIMER) databases were utilized to analyze DTYMK in cancers.

Results: In general, DTYMK is abnormally expressed between most human cancer and normal tissues from a pan-cancer perspective. DTYMK can be used as a diagnostic biomarker to differentiate tumor tissues from normal tissues in most tumors. Upregulation of DTYMK predicted poor survival status in most cancer types in TCGA. Moreover, DTYMK expression was correlated with the T stage in ACC, BRCA, KIRC, LIHC, and LUAD, with the N stage in BLCA, HNSC, KICH, KIRC, LUAD, LUSC, and THCA, with the M stage in ACC, KIRC, KIRP, and LUAD, with TNM stage in ACC, KIRC, LIHC, LUAD, and LUSC. In addition, based on single-cell sequencing data, we concluded that the expression of DTYMK was correlated with the functional status of the cell cycle, DNA damage, DNA repair, invasion, EMT, and proliferation. Finally, DTYMK expression was correlated with six infiltrating immune cells, including B cells, CD4+ T cells, CD8+ T cells, neutrophils, macrophages, and dendritic cells by investigating TIMER.

Conclusion: Our findings suggested that abnormally expressed DTYMK was correlated with poor survival, malignant functional status, and immune infiltrates. DTYMK might be served as a potential biomarker for diagnosis and poor prognosis in various cancer types. DTYMK might act as a potential target for immune therapy.
Pretreatment with IPA ameliorates colitis in mice: Colon transcriptome and fecal 16S amplicon profiling
Authors: Fu Yawei , Gao Hu , Hou Xiaohong , Chen Yue , Xu Kang
Published: September 2022

3-Indolepropionic acid (IPA) is a tryptophan metabolite that has anti-inflammatory properties. The present study try to investigate the phylactic effects of IPA on dextran sodium sulfate (DSS)-induced colitis mice. The results showed that IPA pretreatment ameliorated the DSS-induced decrease in growth performance, and intestinal damage and enhanced immunity in mice. RNA-seq analysis of mouse colon samples revealed that the differentially expressed genes (DEGs) were mainly enriched in immune-related pathways. 16S rRNA sequencing showed that IPA pretreatment ameliorated DSS-induced colonic microbiota dysbiosis. Moreover, the expression levels of gut immune genes were positively correlated with the relative abundance of several probiotics, such as Alloprevotella and Catenibacterium. In conclusion, IPA alleviates DSS-induced acute colitis in mice by regulating inflammatory cytokines, balancing the colonic microbiota and modulating the expression of genes related to inflammation, which would also provide a theoretical basis for IPA as a strategy to improve intestinal health.
Evaluation and comparison of adaptive immunity through analyzing the diversities and clonalities of T-cell receptor repertoires in the peripheral blood
Authors: Zhuo Yue , Yang Xin , Shuai Ping , Yang Liangliang , Wen Xueping , Zhong Xuemei , Yang Shihan , Xu Shaoxian , Liu Yuping , Zhang Zhixin
Published: September 2022

The adaptive immune system plays an important role in defending against different kinds of diseases, including infection and cancer. There has been a longtime need for a simple method to quantitatively evaluate the potency of adaptive immunity in our bodies. The tremendously diversified T-cell receptor (TCR) repertoires are the foundation of the adaptive immune system. In this study, we analyzed the expressed TCRβ repertoires in the peripheral blood of 582 healthy donors and 60 cancer patients. The TCR repertoire in each individual is different, with different usages of TCR Vβ and Jβ genes. Importantly, the TCR diversity and clonality change along with age and disease situation. Most elder individuals and cancer patients have elevated numbers of large TCRβ clones and reduced numbers of shared common clones, and thus, they have very low TCR diversity index (D50) values. These results reveal the alteration of the expressed TCRβ repertoire with aging and oncogenesis, and thus, we hypothesize that the TCR diversity and clonality in the peripheral blood might be used to evaluate and compare the adaptive immunities among different individuals in clinical practice.
Cooperative action of SP-A and its trimeric recombinant fragment with polymyxins against Gram-negative respiratory bacteria
Authors: Coya Juan Manuel , Fraile-Ágreda Víctor , de Tapia Lidia , García-Fojeda Belén , Sáenz Alejandra , Bengoechea José A. , Kronqvist Nina , Johansson Jan , Casals Cristina
Published: September 2022

The exploration of therapies combining antimicrobial lung proteins and conventional antibiotics is important due to the growing problem of multidrug-resistant bacteria. The aim of this study was to investigate whether human SP-A and a recombinant trimeric fragment (rfhSP-A) have cooperative antimicrobial activity with antibiotics against pathogenic Gram-negative bacteria. We found that SP-A bound the cationic peptide polymyxin B (PMB) with an apparent dissociation constant (KD) of 0.32 ± 0.04 µM. SP-A showed synergistic microbicidal activity with polymyxin B and E, but not with other antibiotics, against three SP-A-resistant pathogenic bacteria:Klebsiella pneumoniae, non-typableHaemophilus influenzae(NTHi), andPseudomonas aeruginosa. SP-A was not able to bind toK. pneumoniae, NTHi, or to mutant strains thereof expressing long-chain lipopolysaccharides (or lipooligosaccharides) and/or polysaccharide capsules. In the presence of PMB, SP-A induced the formation of SP-A/PMB aggregates that enhance PMB-induced bacterial membrane permeabilization. Furthermore, SP-A bound to a molecular derivative of PMB lacking the acyl chain (PMBN) with aKDof 0.26 ± 0.02 μM, forming SP-A/PMBN aggregates. PMBN has no bactericidal activity but can bind to the outer membrane of Gram-negative bacteria. Surprisingly, SP-A and PMBN showed synergistic bactericidal activity against Gram-negative bacteria. Unlike native supratrimeric SP-A, the trimeric rfhSP-A fragment had small but significant direct bactericidal activity againstK. pneumoniae, NTHi, andP. aeruginosa. rfhSP-A did not bind to PMB under physiological conditions but acted additively with PMB and other antibiotics against these pathogenic bacteria. In summary, our results significantly improve our understanding of the antimicrobial actions of SP-A and its synergistic action with PMB. A peptide based on SP-A may aid the therapeutic use of PMB, a relatively cytotoxic antibiotic that is currently being reintroduced into clinics due to the global problem of antibiotic resistance.
Identification of clinical prognostic features of esophageal cancer based on m6A regulators
Authors: Wang Huimei , Zhang Yiping , Chen Lin , Liu Yufeng , Xu Chen , Jiang Dongxian , Song Qi , Wang Haixing , Wang Liyan , Lin Yu , Chen Yuanmei , Chen Junqiang , Xu Yuanji , Hou Yingyong
Published: September 2022

Background

Esophageal cancer (ESCA) is a common malignancy with high morbidity and mortality. n6-methyladenosine (m6A) regulators have been widely recognized as one of the major causes of cancer development and progression. However, for ESCA, the role of regulators is unclear. The aim of this study was to investigate the role of m6A RNA methylation regulators in the immune regulation and prognosis of ESCA.

Methods

RNA-seq data were downloaded using the Cancer Genome Atlas (TCGA) database, and the expression differences of m6A RNA methylation regulators in ESCA were analyzed. Further m6A methylation regulator markers were constructed, and prognostic and predictive values were assessed using survival analysis and nomograms. Patients were divided into low-risk and high-risk groups. The signature was evaluated in terms of survival, single nucleotide polymorphism (SNP), copy number variation (CNV), tumor mutation burden (TMB), and functional enrichment analysis (TMB). The m6A expression of key genes in clinical specimens was validated using quantitative reverse transcription polymerase chain reaction (qRT-PCR).

Results

In ESCA tissues, most of the 23 regulators were significantly differentially expressed. LASSO regression analysis included 7 m6A-related factors (FMR1, RBMX, IGFBP1, IGFBP2, ALKBH5, RBM15B, METTL14). In addition, this study also identified that the risk model is associated with biological functions, including base metabolism, DNA repair, and mismatch repair. In this study, a nomogram was created to predict the prognosis of ESCA patients. Bioinformatics analysis of human ESCA and normal tissues was performed using qRT-PCR. Finally. Seven genetic features were found to be associated with m6A in ESCA patients. The results of this study suggest that three different clusters of m6A modifications are involved in the immune microenvironment of ESCA, providing important clues for clinical diagnosis and treatment.
Integrated genomic, transcriptomic and metabolomic analysis reveals MDH2 mutation-induced metabolic disorder in recurrent focal segmental glomerulosclerosis
Authors: Shen Qixia , Teng Lisha , Wang Yucheng , Guo Luying , Xu Feng , Huang Hongfeng , Xie Wenqing , Zhou Qin , Chen Ying , Wang Junwen , Mao Youying , Chen Jianghua , Jiang Hong
Published: September 2022

Focal segmental glomerulosclerosis (FSGS) has an over 30% risk of recurrence after kidney transplantation (Ktx) and is associated with an extremely high risk of graft loss. However, mechanisms remain largely unclear. Thus, this study identifies novel genes related to the recurrence of FSGS (rFSGS). Whole genome-wide sequencing and next-generation RNA sequencing were used to identify the candidate mutant genes associated with rFSGS in peripheral blood mononuclear cells (PBMCs) from patients with biopsy-confirmed rFSGS after KTx. To confirm the functional role of the identified gene with the MDH2 c.26C >T mutation, a homozygous MDH2 c.26C >T mutation in HMy2.CIR cell line was induced by CRISPR/Cas9 and co-cultured with podocytes, mesangial cells, or HK2 cells, respectively, to detect the potential pathogenicity of the c.26C >T variant in MDH2. A total of 32 nonsynonymous single nucleotide polymorphisms (SNPs) and 610 differentially expressed genes (DEGs) related to rFSGS were identified. DEGs are mainly enriched in the immune and metabolomic-related pathways. A variant in MDH2, c.26C >T, was found in all patients with rFSGS, which was also accompanied by lower levels of mRNA expression in PBMCs from relapsed patients compared with patients with remission after KTx. Functionally, co-cultures of HMy2.CIR cells overexpressing the mutant MDH2 significantly inhibited the expression of synaptopodin, podocin, and F-actin by podocytes compared with those co-cultured with WT HMy2.CIR cells or podocytes alone. We identified that MDH2 is a novel rFSGS susceptibility gene in patients with recurrence of FSGS after KTx. Mutation of the MDH2 c.26C >T variant may contribute to progressive podocyte injury in rFSGS patients.
Grass carp SERPINA1 inhibits GCRV infection through degrading CF2
Authors: Li Yangyang , Chen Liangming , Huang Rong , Li Yangyu , Yang Cheng , Gui Bin , Li Yongming , Liao Lanjie , Zhu Zuoyan , Wang Yaping
Published: September 2022

SERPINA1, a member of the serine protease inhibitor family, plays a role in viral infection and inflammation by regulating the activities of serine and cysteine proteases. To date, there have been no reports on the immune function of SERPINA1 in fishes. In this study, we first cloned the serpina1 gene of grass carp (Ctenopharyngodon idellus) and found that it could respond rapidly to the infection of Grass carp reovirus (GCRV), and overexpression of serpina1 could enhance the antiviral response of CIK cells. A polyclonal antibody of SERPINA1 was prepared, and the protein interacting with SERPINA1 was screened by CoIP/MS in grass carp hepatopancreas tissue. It was found that SERPINA1 interacted with coagulation factor 2 (CF2) and could degrade it in a dose-dependent manner. In addition, overexpression of cf2 contributed to the infection of GCRV in CIK cells, whereas co-expression of serpina1 and cf2 in grass carp reduced the copy number of GCRV in cells. The results showed that grass carp SERPINA1 could inhibit GCRV infection by degrading CF2. This study proposes that SERPINA1 can inhibit viral infection through interaction with the coagulation factor, providing new insights into the molecular mechanism of SERPINA1’s antiviral function.
Systemic immune-inflammation index and bone mineral density in postmenopausal women: A cross-sectional study of the national health and nutrition examination survey (NHANES) 2007-2018
Authors: Tang Yuchen , Peng Bo , Liu Jinmin , Liu Zhongcheng , Xia Yayi , Geng Bin
Published: September 2022

Background

This study aimed to investigate the association between the systemic immune-inflammation index (SII) and bone mineral density (BMD) and to determine the association between the SII and the risk of osteopenia/osteoporosis among postmenopausal women aged ≥50 years.

Methods

Postmenopausal women aged ≥50 years from the National Health and Nutrition Examination Survey were included. BMD testing was performed using dual-energy X-ray absorptiometry. The SII was calculated based on lymphocyte (LC), neutrophil (NC), and platelet (PC) counts. Moreover, the associations of BMD with SII and other inflammatory markers, including platelet-to-lymphocyte ratio (PLR), neutrophil-to-lymphocyte ratio (NLR), the product of platelet count and neutrophil count (PPN), PC, NC, and LC, were assessed using a multivariable weighted linear regression model. Additionally, the associations of low BMD/osteoporosis with SII and other inflammatory markers were assessed using multivariable weighted logistic regression.

Results

Finally, a total of 893 postmenopausal women with a weighted mean age of 60.90 ± 0.26 years were included finally. This study found that SII was negatively associated with total femur BMD and femoral neck BMD, and postmenopausal women in a higher SII quarter group showed low lumbar spine BMD than the lowest SII quarter group when SII was converted from a continuous variable to a categorical variable. Moreover, increased SII was associated with an increased risk of low BMD and osteoporosis. In addition, this study observed that other inflammatory markers, especially NLR and PPN, were negatively associated with BMD and positively associated with the risk of osteoporosis. Finally, the subgroup analysis showed that the associations between BMD and inflammatory markers were pronounced in postmenopausal women aged ≥65 years or those with normal BMI (<25 kg/m2).

Conclusion

SII may be a valuable and convenient inflammatory marker that could be applied to predict the risk of low BMD or osteoporosis among postmenopausal women aged ≥50. Moreover, postmenopausal women with a high level of SII or other inflammatory markers, such as NLR and PPN, should be aware of the potential risk of osteoporosis. However, given the inherent limitations of the present study, additional large-scale studies are required to investigate the role of SII in osteoporosis further.
Jmjd3/IRF4 axis aggravates myeloid fibroblast activation and m2 macrophage to myofibroblast transition in renal fibrosis
Authors: Liang Hua , Liu Benquan , Gao Ying , Nie Jiayi , Feng Shuyun , Yu Wenqiang , Wen Shihong , Su Xi
Published: September 2022

Renal fibrosis commonly occurs in the process of chronic kidney diseases. Here, we explored the role of Jumonji domain containing 3 (Jmjd3)/interferon regulatory factor 4 (IRF4) axis in activation of myeloid fibroblasts and transition of M2 macrophages into myofibroblasts transition (M2MMT) in kidney fibrosis. In mice, Jmjd3 and IRF4 were highly induced in interstitial cells of kidneys with folic acid or obstructive injury. Jmjd3 deletion in myeloid cells or Jmjd3 inhibitor reduced the levels of IRF4 in injured kidneys. Myeloid Jmjd3 depletion impaired bone marrow-derived fibroblasts activation and M2MMT in folic acid or obstructive nephropathy, resulting in reduction of extracellular matrix (ECM) proteins expression, myofibroblasts formation and renal fibrosis progression. Pharmacological inhibition of Jmjd3 also prevented myeloid fibroblasts activation, M2MMT, and kidney fibrosis development in folic acid nephropathy. Furthermore, IRF4 disruption inhibited myeloid myofibroblasts accumulation, M2MMT, ECM proteins accumulation, and showed milder fibrotic response in obstructed kidneys. Bone marrow transplantation experiment showed that wild-type mice received IRF4-/- bone marrow cells presented less myeloid fibroblasts activation in injured kidneys and exhibited much less kidney fibrosis after unilateral ureteral obstruction. Myeloid Jmjd3 deletion or Jmjd3 inhibitor attenuated expressions of IRF4, α-smooth muscle actin and fibronectin and impeded M2MMT in cultured monocytes exposed to IL-4. Conversely, overexpression IRF4 abrogated the effect of myeloid Jmjd3 deletion on M2MMT. Thus, Jmjd3/IRF4 signaling has a crucial role in myeloid fibroblasts activation, M2 macrophages to myofibroblasts transition, extracellular matrix protein deposition, and kidney fibrosis progression.
Tryptophan metabolism: Mechanism-oriented therapy for neurological and psychiatric disorders
Authors: Li Dan , Yu Shuang , Long Yu , Shi Ai , Deng Jie , Ma Yin , Wen Jing , Li Xiaoqiu , Liu Songyu , Zhang Yulu , Wan Jinyan , Li Nan , Ao Rui
Published: September 2022

Neurological and psychiatric disorders are a category of chronic diseases that are widespread and pose serious mental and physical health problems for patients. The substrates, products, and enzymes of Tryptophan metabolism all contribute to the development of neurological and psychiatric disorders. This paper deals with three metabolic pathways of tryptophan that produce a series of metabolites called tryptophan Catabolics (TRYCATs). These metabolites are involved in pathological processes such as excitotoxicity, neuroinflammation, oxidative stress, and mitochondrial damage and are closely associated with neurological and psychiatric disorders such as Alzheimer’s disease and depression. Here, we review the elements that affect how tryptophan metabolism is regulated, including inflammation and stress, exercise, vitamins, minerals, diet and gut microbes, glucocorticoids, and aging, as well as the downstream regulatory effects of tryptophan metabolism, including the regulation of glutamate (Glu), immunity, G-protein coupled receptor 35 (Gpr35), nicotinic acetylcholine receptor (nAChR), aryl hydrocarbon receptor (AhR), and dopamine (DA). In order to advance the general understanding of tryptophan metabolism in neurological and psychiatric disorders, this paper also summarizes the current situation and effective drugs of tryptophan metabolism in the treatment of neurological and psychiatric disorders and considers its future research prospects.
External validation of the Survival After ROSC in Cardiac Arrest (SARICA) score for predicting survival after return of spontaneous circulation using multinational pan-asian cohorts
Authors: Rajendram Maehanyi Frances , Zarisfi Faraz , Xie Feng , Shahidah Nur , Pek Pin Pin , Yeo Jun Wei , Tan Benjamin Yong-Qiang , Ma Matthew , Do Shin Sang , Tanaka Hideharu , Ong Marcus Eng Hock , Liu Nan , Ho Andrew Fu Wah
Published: September 2022

Aim

Accurate and timely prognostication of patients with out-of-hospital cardiac arrest (OHCA) who attain return of spontaneous circulation (ROSC) is crucial in clinical decision-making, resource allocation, and communication with family. A clinical decision tool, Survival After ROSC in Cardiac Arrest (SARICA), was recently developed, showing excellent performance on internal validation. We aimed to externally validate SARICA in multinational cohorts within the Pan-Asian Resuscitation Outcomes Study.

Materials and methods

This was an international, retrospective cohort study of patients who attained ROSC after OHCA in the Asia Pacific between January 2009 and August 2018. Pediatric (age <18 years) and traumatic arrests were excluded. The SARICA score was calculated for each patient. The primary outcome was survival. We used receiver operating characteristics (ROC) analysis to calculate the model performance of the SARICA score in predicting survival. A calibration belt plot was used to assess calibration.

Results

Out of 207,450 cases of OHCA, 24,897 cases from Taiwan, Japan and South Korea were eligible for inclusion. Of this validation cohort, 30.4% survived. The median SARICA score was 4. Area under the ROC curve (AUC) was 0.759 (95% confidence interval, CI 0.753–0.766) for the total population. A higher AUC was observed in subgroups that received bystander CPR (AUC 0.791, 95% CI 0.782–0.801) and of presumed cardiac etiology (AUC 0.790, 95% CI 0.782–0.797). The model was well-calibrated.

Conclusion

This external validation study of SARICA demonstrated high model performance in a multinational Pan-Asian cohort. Further modification and validation in other populations can be performed to assess its readiness for clinical translation.
Prevalence of cryptococcal meningitis among people living with human immuno-deficiency virus and predictors of mortality in adults on induction therapy in Africa: A systematic review and meta-analysis
Authors: Muzazu Seke G. Y. , Assefa Dawit Getachew , Phiri Christabel , Getinet Tewodros , Solomon Samrawit , Yismaw Gizachew , Manyazewal Tsegahun
Published: September 2022

Background

Cryptococcal meningitis (CM) is a leading cause of adult meningitis in countries with a high burden of HIV. It has remained a significant cause of morbidity and mortality in Africa despite the extensive rollout of HIV antiretroviral therapy (ART). This study aimed to systematically synthesize the evidence on the prevalence of CM among people living with HIV (PLWH) and its predictors of mortality among adults who are on induction antifungal therapy in Africa.

Methods

PubMed/MEDLINE, Embase, and Google Scholar were searched for randomized clinical trials or observational studies published in Africa from 1995 to April 2021. Pooled prevalence of CM among PLWH was calculated using R-studio Version 1.4.1717 software and the data extracted from eligible studies were pooled as percentage with a 95% confidence interval (CI). Predictors of mortality among adults on induction antifungal therapy were synthesized narratively.

Results

Out of 364 studies identified, 17 eligible articles were included in the analysis. The prevalence of CM among PLWH in Africa was 5.11% (95% CI 2.71–9.43%; participants = 10,813; studies = 9; I2 = 97%). In the subgroup analysis, the prevalence was 12.9% (95% CI 4.883–30.0; participants = 533; studies = 3; I2 = 63%) in the years 1995–2010 and 3.18% (95% CI 1.54–6.45; participants = 10,280; studies = 6; I2 = 98%) in the years 2011–2021, with the prevalence significantly decreased by 51% (p = 0.02). Predictors of mortality were fluconazole monotherapy, focal neurological signs, low Glasgow coma scale, and delayed diagnosis of CM at varied timepoint.

Conclusion

Prevalence of CM has significantly decreased from 1996–2010 to 2011–2021 among PLWH on induction therapy in Africa. Fluconazole monotherapy, focal neurological symptoms, diastolic blood pressure < 60 mmHg, and concurrent tuberculosis coinfection were significant predictors of mortality at 2- and 10-weeks timepoints. CM remains a major concern among PLWH despite increases in ART coverage. Improved access to effective antifungal therapies is needed in Africa for timely initiation of combination induction therapy and better treatment outcomes of PLWH.

Systematic review registration

[https://www.crd.york.ac.uk/prospero/display_record.php?RecordID=254113], identifier [CRD42021254113].
Randomized double-blind clinical study in patients with COVID-19 to evaluate the safety and efficacy of a phytomedicine (P2Et)
Authors: Urueña Claudia , Ballesteros-Ramírez Ricardo , Gomez-Cadena Alejandra , Barreto Alfonso , Prieto Karol , Quijano Sandra , Aschner Pablo , Martínez Carlos , Zapata-Cardona Maria I. , El-Ahanidi Hajar , Jandus Camilla , Florez-Alvarez Lizdany , Rugeles Maria Teresa , Zapata-Builes Wildeman , Garcia Angel Alberto , Fiorentino Susana
Published: September 2022

Background

It has been proposed that polyphenols can be used in the development of new therapies against COVID-19, given their ability to interfere with the adsorption and entrance processes of the virus, thus disrupting viral replication. Seeds from Caesalpinia spinosa, have been traditionally used for the treatment of inflammatory pathologies and respiratory diseases. Our team has obtained an extract called P2Et, rich in polyphenols derived from gallic acid with significant antioxidant activity, and the ability to induce complete autophagy in tumor cells and reduce the systemic inflammatory response in animal models.

Methods

In this work, a phase II multicenter randomized double-blind clinical trial on COVID-19 patients was designed to evaluate the impact of the P2Et treatment on the clinical outcome and the immunological parameters related to the evolution of the disease. The Trial was registered with the number No. NCT04410510*. A complementary study in an animal model of lung fibrosis was carried out to evaluate in situ lung changes after P2Et in vivo administration. The ability of P2Et to inhibit the viral load of murine and human coronaviruses in cellular models was also evaluated.

Results

Patients treated with P2Et were discharged on average after 7.4 days of admission vs. 9.6 days in the placebo group. Although a decrease in proinflammatory cytokines such as G-CSF, IL-15, IL-12, IL-6, IP10, MCP-1, MCP-2 and IL-18 was observed in both groups, P2Et decreased to a greater extent G-CSF, IL-6 and IL-18 among others, which are related to lower recovery of patients in the long term. The frequency of T lymphocytes (LT) CD3+, LT double negative (CD3+CD4-CD8-), NK cells increased in the P2Et group where the population of eosinophils was also significantly reduced. In the murine bleomycin model, P2Et also reduced lung inflammation and fibrosis. P2Et was able to reduce the viral replication of murine and human coronaviruses in vitro, showing its dual antiviral and anti-inflammatory role, key in disease control.

Conclusions

Taken together these results suggest that P2Et could be consider as a good co-adjuvant in the treatment of COVID-19.

Clinical trail registration

https://clinicaltrials.gov/ct2/show/NCT04410510, identifier: NCT04410510.