bluuebunny/crossref_metadata_2025 huggingface dataset:
Genetic screening for hypertension and COVID-19 reveals functional variation of SPEG potentially associated with severe COVID-19 in women
Authors: Luo Yu-Si , Shen Xiang-Chun , Li Wei , Wu Guo-Feng , Yang Xiao-Meng , Guo Ming-Yang , Chen Fang , Shen Hu-Yan , Zhang Ping-Ping , Gao Han , Nie Ying , Wu Jia-Hong , Mou Rong , Zhang Ke , Cheng Zhong-Shan
Published: January 2023

The coronavirus disease 2019 (COVID-19) pandemic, caused by the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), has led to more than 6.4 million deaths worldwide. The prevalent comorbidity between hypertension and severe COVID-19 suggests common genetic factors may affect the outcome of both diseases. As both hypertension and severe COVID-19 demonstrate sex-biased prevalence, common genetic factors between the two diseases may display sex-biased differential associations. By evaluating COVID-19 association signals of 172-candidate hypertension single nucleotide polymorphisms (SNPs) derived from more than 1 million European individuals in two sex-stratified severe COVID-19 genome-wide association studies from UK BioBank with European ancestry, we revealed one functional cis expression quantitative trait locus of SPEG (rs12474050) showing sex-biased association with severe COVID-19 in women. The risk allele rs12474050*T associates with higher blood pressure. In our study, we found it is significantly correlated with lower SPEG expression in muscle-skeletal but with higher expression in both brain cerebellum and cerebellar hemisphere. Additionally, nominal significances were detected for the association between rs12474050*T and lower SPEG expression in both heart left ventricle and atrial appendage; among these tissues, the SPEG expression is nominally significantly higher in females than in males. Further analysis revealed SPEG is mainly expressed in cardiomyocytes in heart and is upregulated upon SARS-CoV-2 infection, with significantly higher upregulation of SPEG only observed in female but not in male COVID-19 patients compared to both normal female and male individuals, suggesting upregulation of SPEG is a female-specific protective mechanism against COVID-19 induced heart damage. Taken together, our analyses suggest the involvement of SPEG in both hypertension and severe COVID-19 in women, which provides new insights for sex-biased effect of severe COVID-19 in women.
Untargeted metabolomics reveals the effect of rearing systems on bone quality parameters in chickens
Authors: Li Dongfeng , Wu Yongfu , Shi Kai , Shao Minghui , Duan Ying , Yu Minli , Feng Chungang
Published: January 2023

The objective of this study was to investigate the effects of rearing systems on the bone quality parameters in chickens using a metabolomics strategy. A total of 419 male one-day-old chicks were randomly allocated to two groups, a floor rearing group (FRG, n = 173) and a cage rearing group (CRG, n = 246). At 6, 8, 10, and 12 weeks of age, all chickens were radiographed by a digital X-ray machine, and body weight was recorded. At 12 weeks of age, 12 birds were selected from each group to obtain tibia and femur, and bone quality parameters of bone mineral density (BMD), mineral content (BMC), breaking strength (BBS), stiffness, Young’s modulus (YM), ash content, calcium content, and phosphorus content were determined. An untargeted metabolomics assay was performed to identify changes in the serum metabolic profile (n = 8 birds/group). The results showed that cage-reared chickens had wider tibiae and greater body weight compared with floor-reared chickens. There were no significant differences in BMC or BBS between the two groups (p > 0.05), but BMD, ash content, calcium content, and phosphorus content of the tibia and femur of FRG were significantly higher than those of CRG (p < 0.05). Greater stiffness and YM of the femur were also observed in birds raised in the FRG compared with those raised in the CRG (p < 0.05). Taken together, the results suggest that rearing systems affected bone quality parameters. Furthermore, 148 and 149 differential metabolites were identified in positive and negative ion modes by LC-MS/MS analysis, among which 257 metabolites were significantly correlated with 16 bone quality parameters, including leucine, myristoleic acid, glycocholic acid, and N-phenylacetamide. KEGG analysis indicated that 15 metabolic pathways, including six pathways of amino acid metabolism, two pathways of lipid metabolism, and two pathways of carbohydrate metabolism, were responsible for bone quality. Overall, the present study demonstrated the effect of rearing systems on bone quality parameters, and identified several metabolites and metabolic pathways associated with bone quality parameters.
Functional impact of multi-omic interactions in breast cancer subtypes
Authors: Ochoa Soledad , Hernández-Lemus Enrique
Published: January 2023

Multi-omic approaches are expected to deliver a broader molecular view of cancer. However, the promised mechanistic explanations have not quite settled yet. Here, we propose a theoretical and computational analysis framework to semi-automatically produce network models of the regulatory constraints influencing a biological function. This way, we identified functions significantly enriched on the analyzed omics and described associated features, for each of the four breast cancer molecular subtypes. For instance, we identified functions sustaining over-representation of invasion-related processes in the basal subtype and DNA modification processes in the normal tissue. We found limited overlap on the omics-associated functions between subtypes; however, a startling feature intersection within subtype functions also emerged. The examples presented highlight new, potentially regulatory features, with sound biological reasons to expect a connection with the functions. Multi-omic regulatory networks thus constitute reliable models of the way omics are connected, demonstrating a capability for systematic generation of mechanistic hypothesis.
Multi-functional gene ZNF281 identified as a molecular biomarker in soft tissue regeneration and pan-cancer progression
Authors: Hou Xueying , Luan Jie , Fu Su
Published: January 2023

Regeneration and tumorigenesis are indicated as related processes, while regeneration leads to life and the outcome of tumorigenesis is death. Here, we show the upregulation of zfp281 (zinc finger 281) in our adipose de novo regeneration model through RNA-seq analysis. Then, we validated the upregulation of zfp281 in adipose regeneration via immunofluorescence. Following that, we found that ZNF281 (the human homolog of Zfp281) was upregulated in most types of cancer and related to worse prognosis in 10 tumors. We further investigated the role of ZNF281 in cervical squamous cell carcinoma and endocervical adenocarcinoma (CESC), pancreatic adenocarcinoma (PAAD), and stomach adenocarcinoma (STAD) and confirmed the high accuracy in the clinical diagnostic feature. Beyond that, based on these three types of cancers, we analyzed the ZNF281-related tumor immune infiltration and DNA methylation sites and finally built risk prediction models for future disease diagnosis. Taken together, our findings provide new insights into the dual role of ZNF281, and we found that it was a potential biomarker for regeneration and tumor prognosis.
Construction and validation of a novel ferroptosis-related signature for evaluating prognosis and immune microenvironment in ovarian cancer
Authors: Yang Jiani , Wang Chao , Cheng Shanshan , Zhang Yue , Jin Yue , Zhang Nan , Wang Yu
Published: January 2023

Ovarian cancer (OV) is the most lethal form of gynecological malignancy worldwide, with limited therapeutic options and high recurrence rates. However, research focusing on prognostic patterns of ferroptosis-related genes (FRGs) in ovarian cancer is still lacking. From the 6,406 differentially expressed genes (DEGs) between TCGA-OV (n = 376) and GTEx cohort (n = 180), we identified 63 potential ferroptosis-related genes. Through the LASSO-penalized Cox analysis, 3 prognostic genes, SLC7A11, ZFP36, and TTBK2, were finally distinguished. The time-dependent ROC curves and K-M survival analysis performed powerful prognostic ability of the 3-gene signature. Stepwise, we constructed and validated the nomogram based on the 3-gene signature and clinical features, with promising prognostic value in both TCGA (p-value < .0001) and ICGC cohort (p-value = .0064). Gene Set Enrichment Analysis elucidated several potential pathways between the groups stratified by 3-gene signature, while the m6A gene analysis implied higher m6A level in the high-risk group. We applied the CIBERSORT algorithm to distinct tumor immune microenvironment between two groups, with less activated dendritic cells (DCs) and plasma cells, more M0 macrophages infiltration, and higher expression of key immune checkpoint molecules (CD274, CTLA4, HAVCR2, and PDCD1LG2) in the high-risk group. In addition, the low-risk group exhibited more favorable immunotherapy and chemotherapy responses. Collectively, our findings provided new prospects in the role of ferroptosis-related genes, as a promising prediction tool for prognosis and immune responses, in order to assist personalized treatment decision-making among ovarian cancer patients.
Immune-related gene signature to predict TACE refractoriness in patients with hepatocellular carcinoma based on artificial neural network
Authors: Xu Qingyu , Wang Chendong , Yin Guowen
Published: January 2023

Background: Transarterial chemoembolization (TACE) is the standard treatment option for intermediate-stage hepatocellular carcinoma (HCC), while response varies among patients. This study aimed to identify novel immune-related genes (IRGs) and establish a prediction model for TACE refractoriness in HCC patients based on machine learning methods.

Methods: Gene expression data were downloaded from GSE104580 dataset of Gene Expression Omnibus (GEO) database, differential analysis was first performed to screen differentially expressed genes (DEGs). The least absolute shrinkage and selection operator (LASSO) regression analysis was performed to further select significant DEGs. Weighted gene co-expression network analysis (WGCNA) was utilized to build a gene co-expression network and filter the hub genes. Final signature genes were determined by the intersection of LASSO analysis results, WGCNA results and IRGs list. Based on the above results, the artificial neural network (ANN) model was constructed in the training cohort and verified in the validation cohort. Receiver operating characteristics (ROC) analysis was used to assess the prediction accuracy. Correlation of signature genes with tumor microenvironment scores, immune cells and immune checkpoint molecules were further analyzed. The tumor immune dysfunction and exclusion (TIDE) score was used to evaluate the response to immunotherapy.

Results: One hundred and forty-seven samples were included in this study, which was randomly divided into the training cohort (n = 103) and validation cohort (n = 44). In total, 224 genes were identified as DEGs. Further LASSO regression analysis screened out 25 genes from all DEGs. Through the intersection of LASSO results, WGCNA results and IRGs list, S100A9, TREM1, COLEC12, and IFIT1 were integrated to construct the ANN model. The areas under the curves (AUCs) of the model were .887 in training cohort and .765 in validation cohort. The four IRGs also correlated with tumor microenvironment scores, infiltrated immune cells and immune checkpoint genes in various degrees. Patients with TACE-Response, lower expression of COLEC12, S100A9, TREM1 and higher expression of IFIT1 had better response to immunotherapy.

Conclusion: This study constructed and validated an IRG signature to predict the refractoriness to TACE in patients with HCC, which may have the potential to provide insights into the TACE refractoriness in HCC and become the immunotherapeutic targets for HCC patients with TACE refractoriness.
Effect of maternity waiting homes use on maternal and perinatal birth outcomes and its challenges in Amhara region, Northwest Ethiopia
Authors: Molla Muluye , Tesfa Mulugeta , Alle Atsede , Molla Firehiwot , Aschale Abiot , Endalew Bekalu , Gietaneh Wodaje
Published: January 2023

Background

Women's death due to complications of pregnancy and childbirth is still high. Maternity waiting homes are one of the strategies to reduce it. However, there is limited evidence on the effect of using maternity waiting homes on birth outcomes, particularly in this study area. Therefore, this study was aimed to estimate the effect of staying in maternity waiting homes use on maternal and perinatal birth outcomes and its challenges in the Amhara region, Northwest Ethiopia 2018.

Methods

Institutional-based comparative cross-sectional study using both quantitative and qualitative approaches was conducted. Data were collected using structured questionnaire interviews, in-depth interview and chart reviews. Propensity score matching analysis was used to estimate the effect of maternity waiting homes use on birth outcomes. Propensity score matching analysis was used to match potential differences in background characteristics that affect pregnancy outcomes between comparison groups. We used thematic analysis for qualitative data.

Result

A total of 548 pregnant mothers (274 stayed in maternity waiting homes 274 did not stay) took part in this study. The proportion of adverse birth outcomes of mothers who stayed in maternity waiting homes were 15(5.5%) which is lower than those who didn't stay 35 (12.8%). After matching with baseline covariates, mean difference of adverse maternal birth outcomes, the difference between didn't use maternity waiting home and used was 10.4%, at (t = 3.78) at 5% level of significance. Similarly, the mean adverse perinatal birth outcomes difference between mothers who didn't use MWHs and used was 11% (t = 4.33).

Conclusions

Maternity waiting home showed a significant positive effect on birth outcomes. Mothers who stayed in the maternity waiting homes had low adverse maternal and perinatal birth outcomes compared to non-users. Accommodations and quality health care services were the challenges mothers faced during their stay in the maternity waiting homes. Therefore, all concerned bodies should give attention accordingly to maternity waiting home services to reduce adverse birth outcomes through the strengthening of the quality of health care provided.
Immunodominant antibody responses directed to SARS-CoV-2 hotspot mutation sites and risk of immune escape
Authors: Oliveira Jamille Ramos , Ruiz Cesar Manuel Remuzgo , Machado Rafael Rahal Guaragna , Magawa Jhosiene Yukari , Daher Isabela Pazotti , Urbanski Alysson Henrique , Schmitz Gabriela Justamante Händel , Arcuri Helen Andrade , Ferreira Marcelo Alves , Sasahara Greyce Luri , de Medeiros Giuliana Xavier , Júnior Roberto Carlos Vieira Silva , Durigon Edison Luiz , Boscardin Silvia Beatriz , Rosa Daniela Santoro , Schechtman Deborah , Nakaya Helder I. , Cunha-Neto Edecio , Gadermaier Gabriele , Kalil Jorge , Coelho Verônica , Santos Keity Souza
Published: January 2023

Introduction

Considering the likely need for the development of novel effective vaccines adapted to emerging relevant CoV-2 variants, the increasing knowledge of epitope recognition profile among convalescents and afterwards vaccinated with identification of immunodominant regions may provide important information.

Methods

We used an RBD peptide microarray to identify IgG and IgA binding regions in serum of 71 COVID-19 convalescents and 18 vaccinated individuals.

Results

We found a set of immunodominant RBD antibody epitopes, each recognized by more than 30% of the tested cohort, that differ among the two different groups and are within conserved regions among betacoronavirus. Of those, only one peptide, P44 (S415-429), recognized by 68% of convalescents, presented IgG and IgA antibody reactivity that positively correlated with nAb titers, suggesting that this is a relevant RBD region and a potential target of IgG/IgA neutralizing activity.

Discussion

This peptide is localized within the area of contact with ACE-2 and harbors the mutation hotspot site K417 present in gamma (K417T), beta (K417N), and omicron (K417N) variants of concern. The epitope profile of vaccinated individuals differed from convalescents, with a more diverse repertoire of immunodominant peptides, recognized by more than 30% of the cohort. Noteworthy, immunodominant regions of recognition by vaccinated coincide with mutation sites at Omicron BA.1, an important variant emerging after massive vaccination. Together, our data show that immune pressure induced by dominant antibody responses may favor hotspot mutation sites and the selection of variants capable of evading humoral response.
Epigenetic modification-related mechanisms of hepatocellular carcinoma resistance to immune checkpoint inhibition
Authors: Tao Shengwei , Liang Shuhang , Zeng Taofei , Yin Dalong
Published: January 2023

Hepatocellular carcinoma (HCC) constitutes most primary liver cancers and is one of the most lethal and life-threatening malignancies globally. Unfortunately, a substantial proportion of HCC patients are identified at an advanced stage that is unavailable for curative surgery. Thus, palliative therapies represented by multi-tyrosine kinase inhibitors (TKIs) sorafenib remained the front-line treatment over the past decades. Recently, the application of immune checkpoint inhibitors (ICIs), especially targeting the PD-1/PD-L1/CTLA-4 axis, has achieved an inspiring clinical breakthrough for treating unresectable solid tumors. However, many HCC patients with poor responses lead to limited benefits in clinical applications, which has quickly drawn researchers’ attention to the regulatory mechanisms of immune checkpoints in HCC immune evasion. Evasion of immune surveillance by cancer is attributed to intricate reprogramming modulation in the tumor microenvironment. Currently, more and more studies have found that epigenetic modifications, such as chromatin structure remodeling, DNA methylation, histone post-translational modifications, and non-coding RNA levels, may contribute significantly to remodeling the tumor microenvironment to avoid immune clearance, affecting the efficacy of immunotherapy for HCC. This review summarizes the rapidly emerging progress of epigenetic-related changes during HCC resistance to ICIs and discusses the mechanisms of underlying epigenetic therapies available for surmounting immune resistance. Finally, we summarize the clinical advances in combining epigenetic therapies with immunotherapy, aiming to promote the formation of immune combination therapy strategies.
Transcriptome and single-cell analysis reveal the contribution of immunosuppressive microenvironment for promoting glioblastoma progression
Authors: Ni Lulu , Sun Ping , Zhang Sujuan , Qian Bin , Chen Xu , Xiong Mengrui , Li Bing
Published: January 2023

Background and objectives

GBM patients frequently exhibit severe local and systemic immunosuppression, limiting the possible efficacy of immunotherapy strategies. The mechanism through which immunosuppression is established in GBM tumors is the key to successful personalized immunotherapies.

Methods

We divided GBM patients into subtypes according to the expression characteristics of the TME typing-related signature matrix. WGCNA analysis was used to get co-expressed gene modules. The expression activity of hub genes retrieved from co-expressed modules was validated in two single-cell datasets. Then, cell–cell interaction was calculated.

Results

Four subtypes were identified in the TCGA and CGGA RNA-seq datasets simultaneously, one of which was an immunosuppressive subtype rich in immunosuppressive factors with low lymphocyte infiltration and an IDH1 mutation. Three co-expressed gene modules related to the immunosuppressive subtype were identified. These three modules are associated with the inflammatory response, angiogenesis, hypoxia, and carbon metabolism, respectively. The genes of the inflammatory response were mainly related to myeloid cells, especially TAM, angiogenesis was related to blood vessels; hypoxia and glucose metabolism were related to tumors, TAM, and blood vessels. Moreover, there was enhanced interaction between tumor cells and TAM.

Discussion

This research successfully found the immunosuppressive subtype and the major cell types, signal pathways, and molecules involved in the formation of the immunosuppressive subtype and will provide new clues for the improvement of GBM personalized immunotherapy in the future.
Causal association between celiac disease and inflammatory bowel disease: A two-sample bidirectional Mendelian randomization study
Authors: Yuan Shuai , Kim Ji Hun , Xu Pai , Wang Zhao
Published: January 2023

Background

An epidemiological link between celiac disease (CeD) and inflammatory bowel disease (IBD) has been well established recently. In this study, Mendelian randomization (MR) analysis was performed employing pooled data of publicly available genome-wide association studies (GWAS) to determine the causal relationship between CeD and IBD, encompassing ulcerative colitis (UC) and Crohn’s disease (CD).

Methods

Dataset of CeD was acquired from GWAS for 12,041 cases and 12,228 controls. A GWAS of more than 86,000 patients and controls was used to identify genetic variations underlying IBD. MR analyses were performed with an inverse-variance-weighted approach, an MR-Egger regression, a weighted-mode approach, a weighted-median method, and sensitivity analyses of MR pleiotropy residual sum and outlie (MR-PRESSO).

Results

MR demonstrated that genetic predisposition to CeD was linked to a augmented risk of IBD (OR: 1.1408; 95% CI: 1.0614-1.2261; P = 0.0003). In the analysis of the two IBD subtypes, genetic predisposition to CeD was also linked to increased risks of UC (OR: 1.1646; 95% CI: 1.0614-1.2779; P = 0.0012) and CD (OR: 1.1865; 95% CI: 1.0948-1.2859; P = 3.07E-05). Reverse MR analysis results revealed that genetic susceptibility to IBD and CD was correlated with an augmented risk of CeD. However, there was no genetic correlation between UC and CeD. All of the above results were validated with other GWAS databases.

Conclusion

There is a bidirectional causal relationship of CeD with IBD and CD. However, UC only augments the risk of developing CeD.
Recombinant GM-CSF for diseases of GM-CSF insufficiency: Correcting dysfunctional mononuclear phagocyte disorders
Authors: Lazarus Hillard M. , Pitts Katherine , Wang Tisha , Lee Elinor , Buchbinder Elizabeth , Dougan Michael , Armstrong David G. , Paine Robert , Ragsdale Carolyn E. , Boyd Timothy , Rock Edwin P. , Gale Robert Peter
Published: January 2023

Introduction

Endogenous granulocyte-macrophage colony-stimulating factor (GM-CSF), identified by its ability to support differentiation of hematopoietic cells into several types of myeloid cells, is now known to support maturation and maintain the metabolic capacity of mononuclear phagocytes including monocytes, macrophages, and dendritic cells. These cells sense and attack potential pathogens, present antigens to adaptive immune cells, and recruit other immune cells. Recombinant human (rhu) GM-CSF (e.g., sargramostim [glycosylated, yeast-derived rhu GM-CSF]) has immune modulating properties and can restore the normal function of mononuclear phagocytes rendered dysfunctional by deficient or insufficient endogenous GM-CSF.

Methods

We reviewed the emerging biologic and cellular effects of GM-CSF. Experts in clinical disease areas caused by deficient or insufficient endogenous GM-CSF examined the role of GM-CSF in mononuclear phagocyte disorders including autoimmune pulmonary alveolar proteinosis (aPAP), diverse infections (including COVID-19), wound healing, and anti-cancer immune checkpoint inhibitor therapy.

Results

We discuss emerging data for GM-CSF biology including the positive effects on mitochondrial function and cell metabolism, augmentation of phagocytosis and efferocytosis, and immune cell modulation. We further address how giving exogenous rhu GM-CSF may control or treat mononuclear phagocyte dysfunction disorders caused or exacerbated by GM-CSF deficiency or insufficiency. We discuss how rhu GM-CSF may augment the anti-cancer effects of immune checkpoint inhibitor immunotherapy as well as ameliorate immune-related adverse events.

Discussion

We identify research gaps, opportunities, and the concept that rhu GM-CSF, by supporting and restoring the metabolic capacity and function of mononuclear phagocytes, can have significant therapeutic effects. rhu GM-CSF (e.g., sargramostim) might ameliorate multiple diseases of GM-CSF deficiency or insufficiency and address a high unmet medical need.
Remodeling the tumor immune microenvironment with oncolytic viruses expressing miRNAs
Authors: St-Cyr Guillaume , Penarroya Daphné , Daniel Lauren , Giguère Hugo , Alkayyal Almohanad A. , Tai Lee-Hwa
Published: January 2023

MiRNAs (miRNA, miR) play important functions in the tumor microenvironment (TME) by silencing gene expression through RNA interference. They are involved in regulating both tumor progression and tumor suppression. The pathways involved in miRNA processing and the miRNAs themselves are dysregulated in cancer. Consequently, they have become attractive therapeutic targets as underscored by the plethora of miRNA-based therapies currently in pre-clinical and clinical studies. It has been shown that miRNAs can be used to improve oncolytic viruses (OVs) and enable superior viral oncolysis, tumor suppression and immune modulation. In these cases, miRNAs are empirically selected to improve viral oncolysis, which translates into decreased tumor growth in multiple murine models. While this infectious process is critical to OV therapy, optimal immunomodulation is crucial for the establishment of a targeted and durable effect, resulting in cancer eradication. Through numerous mechanisms, OVs elicit a strong antitumor immune response that can also be further improved by miRNAs. They are known to regulate components of the immune TME and promote effector functions, antigen presentation, phenotypical polarization, and varying levels of immunosuppression. Reciprocally, OVs have the power to overcome the limitations encountered in canonical miRNA-based therapies. They deliver therapeutic payloads directly into the TME and facilitate their amplification through selective tumoral tropism and abundant viral replication. This way, off-target effects can be minimized. This review will explore the ways in which miRNAs can synergistically enhance OV immunotherapy to provide the basis for future therapeutics based on this versatile combination platform.
Combination of transcriptional biomarkers and clinical parameters for early prediction of sepsis indued acute respiratory distress syndrome
Authors: Yao Ren-Qi , Shen Zong , Ma Qi-Min , Ling Ping , Wei Chen-Ru , Zheng Li-Yu , Duan Yu , Li Wei , Zhu Feng , Sun Yu , Wu Guo-Sheng
Published: January 2023

Objective

As a common yet intractable complication of severe sepsis, acute respiratory distress syndrome (ARDS) is closely associated with poor clinical outcomes and elevated medical expenses. The aim of the current study is to generate a model combining transcriptional biomarkers and clinical parameters to alarm the development of ARDS in septic patients.

Methods

Gene expression profile (GSE66890) was downloaded from the Gene Expression Omnibus database and clinical data were extracted. Differentially expressed genes (DEGs) from whole blood leukocytes were identified between patients with sepsis alone and septic patients who develop ARDS. ARDS prediction model was constructed using backward stepwise regression and Akaike Information Criterion (AIC). Meanwhile, a nomogram based on this model was established, with subsequent internal validation.

Results

A total of 57 severe septic patients were enrolled in this study, and 28 (49.1%) developed ARDS. Based on the differential expression analysis, six DEGs (BPI, OLFM4, LCN2, CD24, MMP8 and MME) were screened. According to the outcome prediction model, six valuable risk factors (direct lung injury, shock, tumor, BPI, MME and MMP8) were incorporated into a nomogram, which was used to predict the onset of ARDS in septic patients. The calibration curves of the nomogram showed good consistency between the probabilities and observed values. The decision curve analysis also revealed the potential clinical usefulness of the nomogram. The area under the receiver operating characteristic (AUROC) for the prediction of ARDS occurrence in septic patients by the nomogram was 0.86 (95% CI = 0.767-0.952). A sensitivity analysis showed that the AUROC for the prediction of ARDS development in septic patients without direct lung injury was 0.967 (95% CI = 0.896-1.0).

Conclusions

The nomogram based on transcriptional biomarkers and clinical parameters showed a good performance for the prediction of ARDS occurrence in septic patients.
The diagnostic and prognostic value of IgG and IgA anti-citrullinated protein antibodies in patients with early rheumatoid arthritis
Authors: Sieghart Daniela , Konrad Christian , Swiniarski Sascha , Haslacher Helmuth , Aletaha Daniel , Steiner Günter
Published: January 2023

Objectives

Anti-citrullinated peptide antibodies (ACPA) are specific markers for rheumatoid arthritis (RA) and typically measured by assays employing a cyclic citrullinated peptide (CCP) as antigen. This study was aimed at investigating the diagnostic performance of anti-CCP2 and anti-CCP3 IgG and IgA assays in patients with early RA with a particular focus on the potential prognostic value of IgA ACPA.

Methods

The anti-CCP3.1 assay (Inova Diagnostics) measuring IgG and IgA antibodies simultaneously was compared to anti-CCP2 IgG and IgA assays (Thermo Fisher Scientific) employing sera of 184 early RA patients, 360 disease controls and 98 healthy subjects.

Results

Anti-CCP2 IgG and IgA assays showed high specificity versus disease controls (98.9%; 99.4%). Sensitivity was 52.2% (IgG) and 28.8% (IgA), resulting in positive likelihood ratios (LR+) of 47.5 (IgG) and 48.0 (IgA). The anti-CCP3.1 assay proved slightly more sensitive than the anti-CCP2 IgG assay (56%) but specificity was markedly lower (90.8% versus disease controls). However, when using a threefold higher cut-off specificity of the anti-CCP3.1 assay increased (97.5%) while sensitivity (52.7%) became comparable to the anti-CCP2 IgG assay resulting in a LR+ of 21.5. Anti-CCP2 IgA antibodies did not increase the diagnostic sensitivity of ACPA testing, but IgA positive patients showed diminished responses to treatment with anti-TNF biologicals compared to patients who had only IgG antibodies.

Conclusion

Specificity of ACPA assays should be adjusted to reduce the risk of misclassification and a false positive diagnosis. Determination of ACPA IgA might provide important prognostic information concerning therapeutic responses.
Safety and efficacy of plasma exchange treatment in children with AQP4-IgG positive neuromyelitis optica spectrum disorder
Authors: Li Zhichao , Wan Lin , Liu Xinting , Wang Jing , Shi Xiuyu , Zhou Huanfen , Xu Quangang , Wei Shihui , Yang Guang
Published: January 2023

Neuromyelitis optica spectrum disorder (NMOSD), a severe demyelinating disease, is rare among children. Plasma exchange (PE) is widely used as a salvage therapy for severe and corticosteroid-unresponsive patients with NMOSD. Presently, there are limited studies on the safety and efficacy of PE in children with NMOSD. Herein, we report the case of six children with NMOSD who received PE along with the outcomes and adverse events. All six children (female, age at onset 4 years 9 months–13 years 2 months) were AQP4-IgG positive and received standard PE using the COM.TEC Cell Separator. The interval between NMOSD onset and PE was 29 days (range 10–98). Only one patient (P3) who received PE 10 days after acute exacerbations exhibited clinical improvement. Her left visual acuity increased from 0.06 to 0.6 (spectacle-corrected visual acuity was 1.0) and her EDSS score decreased from 4 to 3 points. The other five patients had no clinical improvement and no EDSS scores changes after PE. Adverse events included rashes (P1, P3), acute non-occlusive thrombosis of the internal jugular vein (P1), and thrombocytopenia (P2). In conclusion, the timing of PE initiation as a rescue therapy for severe and corticosteroid-unresponsive pediatric AQP4-IgG positive NMOSD may be crucial to treatment efficacy, and early initiation of PE may be associated with a better outcome. Furthermore, PE has the potential risk for clinically significant adverse effects that should be considered before initiating the therapy and should be weighed against potential benefits.
Diversity of coral-associated pit crabs (Crustacea: Decapoda: Cryptochiridae) from Hong Kong, with description of two new species of Lithoscaptus A. Milne-Edwards, 1862
Authors: Wong Kingsley J. H. , Tsao Yao-Feng , Qiu Jian-Wen , Chan Benny K. K.
Published: January 2023

Highly specialized cryptochirid crabs are obligate symbionts of scleractinian corals in tropical and subtropical seas. General morphologies of cryptochirid crabs remain poorly described due to their small size and difficulties in collection; thus, the current inventory is probably an underestimation. In the present study, we sampled cryptochirid crabs from coral communities in Hong Kong. In the literature, onlyCryptochirus hongkongensis(nowNeotroglocarcinus hongkongensis) with unknown hosts had been recorded in Hong Kong since 1936. In addition to morphological examination, identification in the present study is further supported by sequence divergence of mitochondrial cytochrome c oxidase I (COI) and 16S ribosomal DNA markers. Six operative taxonomic units (OTUs), representing four species and one species complex with two species, were revealed among our material:Cryptochirus coralliodytes,Lithoscaptus paradoxus,Lithoscaptus doughnutsp. nov.,Lithoscaptus scottaesp. nov., andXynomaia shenispecies complex. Morphological description of these species is provided, including description of the two new pseudocryptic species. The hosts of the genusLithoscaptusbelong largely to the Merulinidae, whileL. doughnutsp. nov. inhabits the Plesiastreidae.
Case report: Umbilical vessel aneurysm thrombosis and factor V Leiden mutation leading to fetal demise
Authors: Oualiken Camélia , Martz Olivia , Idrissi Nadia , Harizay Fara Tanjona , Martin Laurent , De Maistre Emmanuel , Ricaud Lou , Tarris Georges
Published: January 2023

Complicated pregnancies are nowadays a major public health concern, with possible lethality or sequelae both for the mother and the fetus. Blood coagulation disorders (including antiphospholipid syndrome, factor V Leiden mutation and antithrombin deficiency) and hypertensive gestational disorders are very well-known contributors of complicated pregnancies with poor fetal outcome, such as intrauterine growth retardation (IUGR) and fetal demise. Less commonly, vascular malformations of the placenta can also potentially lead to serious complications such as IUGR and fetal death. These malformations include hypercoiled umbilical cord, umbilical cord knot, umbilical cord varix, umbilical cord arterial or venous aneurysm, and velamentous insertion of the umbilical cord potentially leading to Benckiser's hemorrhage. Here, we report the case of a 29-year-old Gravida 2 Para 0 mother with previous history of stillbirth and smoking, admitted to the obstetrics department for the absence of fetal movement at 38 weeks of amenorrhea (WA). First-trimester and second-trimester routine ultrasounds were otherwise normal. Ultrasound performed at 38 WA revealed a 83 × 66 × 54 mm cystic heterogenous mass at the umbilical cord insertion. After delivery, fetal and placental pathology as well as maternal blood testing were performed. Fetal pathology was otherwise normal, except for diffuse congestion and meconial overload suggesting acute fetal distress. Fetal karyotype was normal (46 XX). Placental pathology revealed an umbilical artery aneurysm (UAA) at the base of the insertion of the umbilical cord, lined with a CD34+ CD31+ endothelium. After dissection, the aneurysm was filled with hemorrhagic debris, indicating aneurysm thrombosis. Histopathology revealed associated maternal vascular malperfusion (MVM) and increased peri-villous fibrin (IPF). Maternal blood tests revealed heterozygous factor V Leiden mutation, without other associated auto-immune conditions (such as antiphospholipid syndrome). Umbilical artery aneurysms remain extremely rare findings in the placenta, with <20 reported cases. Umbilical artery aneurysms have tendency to be located at the base of the insertion of the placenta, and lead to fetal demise in more than 60% of cases, mainly due to aneurysmal thrombosis, hematoma, possible vascular compression and/or rupture. Umbilical vessel aneurysms can be associated with trisomy 18 or 13. In our case, the association of factor V Leiden mutation, a hypercoagulable state, with UAA could explain massive thrombosis of the aneurysmal lumen and sudden fetal demise. Further consideration of current guidelines for surveillance and management of UAA would allow appropriate planned delivery in maternal care settings.
E, K, B5, B6, and B9 vitamins and their specific immunological effects evaluated by flow cytometry
Authors: Munteanu Camelia , Berindean Ioana , Mihai Mihaela , Pop Bianca , Popa Mihai , Muntean Leon , Petrescu Olivia , Ona Andreea
Published: January 2023

It has been proven that vitamins play an essential role in preventing certain diseases since ancient times. It is thus fruitless to approach the roles of vitamins without making reference to the techniques used in evaluating the effects of these micronutrients. Therefore, the aim of this paper was to summarize the immunological effects of E, K, B5, B6, and B9 vitamins evaluated by flow cytometry. Some of these significant effects were presented and discussed: (a) The role of vitamins E in the prevention and treatment of different types of cancer. (b) The properties of K vitamins in the development and maintenance of pheochromocytoma Cell Line 12 (PC12) cells in Parkinson’s disease; (c) The improvement effect of vitamin B5 on the loss of bone mass in low estrogen conditions; (d) The anticancer role of vitamins B6. (e) The role of Vitamin B9 in the regulation of Treg cells. As such, the flow cytometry technique used to assess these properties is essential to evaluate the immunomodulatory effects of certain vitamins. The technique undergoes constant improvement which makes it possible to determine several parameters with a role in the modulation of the immune function and at the same time increase the accuracy of the methods that highlight them.
Treatment with organic manure inoculated with a biocontrol agent induces soil bacterial communities to inhibit tomato Fusarium wilt disease
Authors: Tang Tongtong , Sun Xing , Liu Qin , Dong Yuanhua , Zha Mingfang
Published: January 2023

Introduction

Organic manure, plant growth-promoting microorganisms, and biocontrol agents are widely used to sustainably control soil-borne diseases. However, how and whether organic manure inoculated with biocontrol agents alters soil microbiota and reduces disease severity is poorly understood.

Methods

Here, we examined changes to the soil microbial community, soil properties, and incidence of Fusarium wilt disease in response to several fertilization regimes. Specifically, we studied the effects of inorganic chemical fertilization (CF), organic manure fertilization (OF), and Erythrobacter sp. YH-07-inoculated organic manure fertilization (BF) on the incidence of Fusarium wilt in tomato across three seasons.

Results

BF-treated soils showed increased microbial abundance, richness, and diversity compared to other treatments, and this trend was stable across seasons. BF-treated soils also exhibited a significantly altered microbial community composition, including increased abundances of Bacillus, Altererythrobacter, Cryptococcus, and Saprospiraceae, and decreased abundances of Chryseolinea and Fusarium. Importantly, BF treatment significantly suppressed the incidence of Fusarium wilt in tomato, likely due to direct suppression by Erythrobacter sp. YH-07 and indirect suppression through changes to the microbial community composition and soil properties.

Discussion

Taken together, these results suggest that Erythrobacter sp. YH-07-inoculated organic manure is a stable and sustainable soil amendment for the suppression of Fusarium wilt diseases.
The moderate substitution of Astragalus sinicus returning for chemical fertilizer improves the N cycle function of key ecological bacterial clusters in soil
Authors: Lv Minghao , Wang Yongdong , Chen Xiaofen , Qin Wenjing , Shi Wencong , Song Weifeng , Chen Jingrui , Xu Changxu
Published: January 2023

Astragalus sinicus (Chinese milk vetch) is a well-established resource of organic fertilizer widely used in paddy soil to partially replace chemical fertilizers. However, the influence of returning A. sinicus to fields on the soil bacterial community remains poorly understood. Here, we used different amounts of A. sinicus partially replacing chemical fertilizers and investigated the changes in soil physicochemical factors and the soil bacterial community structure responses. Returning A. sinicus to the field significantly increased the soil total nitrogen and available phosphorus content (p < 0.05). Weighted gene correlation network analysis (WGCNA) was applied to detect significant associations between the soil microbiome data and physicochemical factors. Two key ecological bacterial clusters (MEturquoise and MEgreen), mainly containing Acidobacteria, Proteobacteria, and Chloroflexi, were significantly correlated with soil nitrogen (N) levels. A. sinicus partially replacing chemical fertilizers reduced the normalized stochasticity ratio (NST) of rare amplicon sequence variants (ASVs), abundant ASVs, MEturquoise, and MEgreen (p < 0.05). Our results further indicated that a moderate amount of A. sinicus returned to the soil effectively mitigated the trend of reduced relative abundance of N fixation function of key ecological clusters caused by chemical fertilizer. However, a large amount of A. sinicus led to a significant increase in relative abundance of denitrification function and a significant decrease in relative abundance of N fixation function of key ecological clusters. This implies that the moderate substitution of A. sinicus returning for chemical fertilizer improves the N cycling function of key ecological bacterial clusters in soil. From the perspective of the bacterial community in paddy soil, this study provides new insight and a reference on how to find a good balance between the amount of A. sinicus returned to the soil and ecological safety.
Development of a colloidal gold immunochromatographic assay strip using monoclonal antibody for rapid detection of porcine deltacoronavirus
Authors: Wang Wei , Fan Baochao , Zhang Xuehan , Guo Rongli , Zhao Yongxiang , Zhou Junming , Zhou Jinzhu , Peng Qi , Zhu Mingjun , Li Jizong , Li Bin
Published: January 2023

Porcine deltacoronavirus (PDCoV) cause diarrhea and dehydration in newborn piglets and has the potential for cross-species transmission. Rapid and early diagnosis is important for preventing and controlling infectious disease. In this study, two monoclonal antibodies (mAbs) were generated, which could specifically recognize recombinant PDCoV nucleocapsid (rPDCoV-N) protein. A colloidal gold immunochromatographic assay (GICA) strip using these mAbs was developed to detect PDCoV antigens within 15 min. Results showed that the detection limit of the GICA strip developed in this study was 103 TCID50/ml for the suspension of virus-infected cell culture and 0.125 μg/ml for rPDCoV-N protein, respectively. Besides, the GICA strip showed high specificity with no cross-reactivity with other porcine pathogenic viruses. Three hundred and twenty-five fecal samples were detected for PDCoV using the GICA strip and reverse transcription-quantitative real-time PCR (RT-qPCR). The coincidence rate of the GICA strip and RT-qPCR was 96.9%. The GICA strip had a diagnostic sensitivity of 88.9% and diagnostic specificity of 98.5%. The specific and efficient detection by the strip provides a convenient, rapid, easy to use and valuable diagnostic tool for PDCoV under laboratory and field conditions.
Effects of constant temperature and daily fluctuating temperature on the transovarial transmission and life cycle of Aedes albopictus infected with Zika virus
Authors: Jian Xian-yi , Jiang Yu-ting , Wang Miao , Jia Nan , Cai Tong , Xing Dan , Li Chun-xiao , Zhao Tong-yan , Guo Xiao-xia , Wu Jia-hong
Published: January 2023

Introduction

Numerous studies on the mosquito life cycle and transmission efficacy were performed under constant temperatures. Mosquito in wild, however, is not exposed to constant temperature but is faced with temperature variation on a daily basis.

Methods

In the present study, the mosquito life cycle and Zika virus transmission efficiency were conducted at daily fluctuating temperatures and constant temperatures. Aedes albopictus was infected with the Zika virus orally. The oviposition and survival of the infected mosquitoes and hatching rate, the growth cycle of larvae at each stage, and the infection rate (IR) of the progeny mosquitoes were performed at two constant temperatures (23°C and 31°C) and a daily temperature range (DTR, 23–31°C).

Results

It showed that the biological parameters of mosquitoes under DTR conditions were significantly different from that under constant temperatures. Mosquitoes in DTR survived longer, laid more eggs (mean number: 36.5 vs. 24.2), and had a higher hatching rate (72.3% vs. 46.5%) but a lower pupation rate (37.9% vs. 81.1%) and emergence rate (72.7% vs. 91.7%) than that in the high-temperature group (constant 31°C). When compared to the low-temperature group (constant 23°C), larvae mosquitoes in DTR developed faster (median days: 9 vs. 23.5) and adult mosquitoes carried higher Zika viral RNA load (median log10 RNA copies/μl: 5.28 vs. 3.86). However, the temperature or temperature pattern has no effect on transovarial transmission.

Discussion

Those results indicated that there are significant differences between mosquito development and reproductive cycles under fluctuating and constant temperature conditions, and fluctuating temperature is more favorable for mosquitos' survival and reproduction. The data would support mapping and predicting the distribution of Aedes mosquitoes in the future and establishing an early warning system for Zika virus epidemics.
Clostridium botulinum type C, D, C/D, and D/C: An update
Authors: Meurens François , Carlin Frédéric , Federighi Michel , Filippitzi Maria-Eleni , Fournier Matthieu , Fravalo Philippe , Ganière Jean-Pierre , Grisot Lionel , Guillier Laurent , Hilaire Didier , Kooh Pauline , Le Bouquin-Leneveu Sophie , Le Maréchal Caroline , Mazuet Christelle , Morvan Hervé , Petit Karine , Vaillancourt Jean-Pierre , Woudstra Cédric
Published: January 2023

Clostridium botulinum is the main causative agent of botulism, a neurological disease encountered in humans as well as animals. Nine types of botulinum neurotoxins (BoNTs) have been described so far. Amongst these “toxinotypes,” the A, the B and E are the most frequently encountered in humans while the C, D, C/D and D/C are mostly affecting domestic and wild birds as well as cattle. In France for instance, many cases and outbreaks are reported in these animal species every year. However, underestimation is very likely at least for avifauna species where the detection of dead animals can be challenging. Knowledge about BoNTs C, D, C/D, and D/C and the diseases they cause in animals and humans is still scarce and unclear. Specifically, the potential role of animal botulism outbreaks in cattle and poultry as a source of human illness needs to be further assessed. In this narrative review, we present the current knowledge about toxinotypes C, D, C/D, and D/C in cattle and poultry with, amongst various other aspects, their epidemiological cycles. We also discuss the zoonotic potential of these toxinotypes and some possible ways of risk mitigation. An adapted and effective management of botulism outbreaks in livestock also requires a better understanding of these less common and known toxinotypes.