bluuebunny/crossref_metadata_2025 huggingface dataset:
Identification of Crucial Gene Modules Related to the Efficiency of Anti-PD-1/PD-L1 Therapy and Comprehensive Analyses of a Novel Signature Based on These Modules
Authors: Wang Wei , Dong Dong , Chen Liang , Wang Heng , Bi Bo , Liu Tianyi
Published: July 2022

Biomarker development for clinical checkpoint inhibition is still in its early stages. It is critical to determine the cause of the lack of a long-term response in patients after immune checkpoint blockade (ICB) treatment and to develop composite biomarkers or signatures to improve personalized approaches. Three modules that were significantly correlated with the immunotherapeutic response were identified. Stimulatory pathways of cellular immunity, extracellular matrix formation-related pathways, and ATP metabolism-related pathways were enriched. Two distinct transcriptional subtypes were determined. Tumor microenvironment (TME) characteristics were highly correlated with “hot” and “cold” tumors. The ICB score was significantly correlated with clinical characteristics including age, Breslow depth, Clerk level, AJCC stage, and T stage. Meanwhile, a low ICB score is characterized by increased activation of immunity, a higher level of immune infiltration, and immune molecule expression. The ICB score showed a robust ability to predict melanoma prognosis in the discovery, internal validation, and external validation cohorts. In addition, a low ICB score was linked to a higher CR/PR rate in the immunotherapeutic cohort. The ICB score could reflect the pre-existing immune features and the expression pattern of “Cold” versus “Hot” tumors in melanoma patients. Thus, it has the potential to serve as a reliable predictor of melanoma prognosis and response to ICB therapy.
Matching Biomedical Ontologies via a Hybrid Graph Attention Network
Authors: Wang Peng , Hu Yunyan
Published: July 2022

Biomedical ontologies have been used extensively to formally define and organize biomedical terminologies, and these ontologies are typically manually created by biomedical experts. With more biomedical ontologies being built independently, matching them to address the problem of heterogeneity and interoperability has become a critical challenge in many biomedical applications. Existing matching methods have mostly focused on capturing features of terminological, structural, and contextual semantics in ontologies. However, these feature engineering-based techniques are not only labor-intensive but also ignore the hidden semantic relations in ontologies. In this study, we propose an alternative biomedical ontology-matching framework BioHAN via a hybrid graph attention network, and that consists of three techniques. First, we propose an effective ontology-enriching method that refines and enriches the ontologies through axioms and external resources. Subsequently, we use hyperbolic graph attention layers to encode hierarchical concepts in a unified hyperbolic space. Finally, we aggregate the features of both the direct and distant neighbors with a graph attention network. Experimental results on real-world biomedical ontologies demonstrate that BioHAN is competitive with the state-of-the-art ontology matching methods.
Identification and Characterization of DNA Demethylase Genes and Their Association With Thermal Stress in Wheat (Triticum aestivum L.)
Authors: Gahlaut Vijay , Samtani Harsha , Gautam Tinku , Khurana Paramjit
Published: July 2022

DNA demethylases (dMTases) are essential proteins in plants that regulate DNA methylation levels. The dMTase genes have been explored in a number of plant species, however, members of this family have not been reported in wheat. We identified 12 wheat dMTase genes divided into two subfamilies: repressor of silencing 1 (ROS1) and DEMETER-Like (DML). The TadMTases in the same subfamily or clade in the phylogenetic tree have similar gene structures, protein motifs, and domains. The promoter sequence contains multiple cis-regulatory elements (CREs) that respond to abiotic stress, hormones, and light, suggesting that the majority of TadMTase genes play a role in wheat growth, development, and stress response. The nuclear localization signals (NLSs), subcellular localization, and SRR motifs were also analyzed. The expression profile analyses revealed that TadMTase genes showed differential gene expression patterns in distinct developmental stages and tissues as well as under heat stress (HS). Furthermore, the qRT-PCR analysis revealed that TadMTase gene expression differed amongst wheat cultivars with varying degrees of HS tolerance. Overall, this work contributes to the understanding of the biological function of wheat dMTases and lays the foundation for future investigations.
Sex chromosome aneuploidies give rise to changes in the circular RNA profile: A circular transcriptome-wide study of Turner and Klinefelter syndrome across different tissues
Authors: Johannsen Emma B. , Just Jesper , Viuff Mette H. , Okholm Trine Line Hauge , Pedersen Steen B. , Meyer Lauritsen Katrine , Trolle Christian , Pedersen Mette Glavind Bülow , Chang Simon , Fedder Jens , Skakkebæk Anne , Gravholt Claus H.
Published: July 2022

Purpose: The landscape of circular RNAs (circRNAs), an important class of non-coding RNAs that regulate gene expression, has never been described in human disorders of sex chromosome aneuploidies. We profiled circRNAs in Turner syndrome females (45,X; TS) and Klinefelter syndrome males (47,XXY; KS) to investigate how circRNAs respond to a missing or an extra X chromosome.

Methods: Samples of blood, muscle and fat were collected from individuals with TS (n = 33) and KS (n = 22) and from male (n = 16) and female (n = 44) controls. CircRNAs were identified using a combination of circRNA identification pipelines (CIRI2, CIRCexplorer2 and circRNA_finder).

Results: Differential expression of circRNAs was observed throughout the genome in TS and KS, in all tissues. The host-genes from which several of these circRNAs were derived, were associated with known phenotypic traits. Furthermore, several differentially expressed circRNAs had the potential to capture micro RNAs that targeted protein-coding genes with altered expression in TS and KS.

Conclusion: Sex chromosome aneuploidies introduce changes in the circRNA transcriptome, demonstrating that the genomic changes in these syndromes are more complex than hitherto thought. CircRNAs may help explain some of the genomic and phenotypic traits observed in these syndromes.
Copy Number Variation of Circulating Tumor DNA (ctDNA) Detected Using NIPT in Neoadjuvant Chemotherapy-Treated Ovarian Cancer Patients
Authors: Sharbatoghli Mina , Fattahi Fahimeh , Aboulkheyr Es Hamidreza , Akbari Arvand , Akhavan Setareh , Ebrahimi Marzieh , Asadi-Lari Mohsen , Totonchi Mehdi , Madjd Zahra
Published: July 2022

Analysis of circulating tumor DNA (ctDNA) can be used to characterize and monitor cancers. Recently, non-invasive prenatal testing (NIPT) as a new next-generation sequencing (NGS)-based approach has been applied for detecting ctDNA. This study aimed to investigate the copy number variations (CNVs) utilizing the non-invasive prenatal testing in plasma ctDNA from ovarian cancer (OC) patients who were treated with neoadjuvant chemotherapy (NAC). The plasma samples of six patients, including stages II–IV, were collected during the pre- and post-NAC treatment that were divided into NAC-sensitive and NAC-resistant groups during the follow-up time. CNV analysis was performed using the NIPT via two methods “an open-source algorithm WISECONDORX and NextGENe software.” Results of these methods were compared in pre- and post-NAC of OC patients. Finally, bioinformatics tools were used for data mining from The Cancer Genome Atlas (TCGA) to investigate CNVs in OC patients. WISECONDORX analysis indicated fewer CNV changes on chromosomes before treatment in the NAC-sensitive rather than NAC-resistant patients. NextGENe data indicated that CNVs are not only observed in the coding genes but also in non-coding genes. CNVs in six genes were identified, including HSF1, TMEM249, MROH1, GSTT2B, ABR, and NOMO2, only in NAC-resistant patients. The comparison of these six genes in NAC-resistant patients with The Cancer Genome Atlas data illustrated that the total alteration frequency is amplification, and the highest incidence of the CNVs (≥35% based on TCGA data) is found in MROH1, TMEM249, and HSF1 genes on the chromosome (Chr) 8. Based on TCGA data, survival analysis showed a significant reduction in the overall survival among chemotherapy-resistant patients as well as a high expression level of these three genes compared to that of sensitive samples (all, p < 0.0001). The continued Chr8 study using WISECONDORX revealed CNV modifications in NAC-resistant patients prior to NAC therapy, but no CNV changes were observed in NAC-sensitive individuals. Our findings showed that low coverage whole-genome sequencing analysis used for NIPT could identify CNVs in ctDNA of OC patients before and after chemotherapy. These CNVs are different in NAC-sensitive and -resistant patients highlighting the potential application of this approach in cancer patient management.
The prognostic value and immune landscape of a cuproptosis-related lncRNA signature in head and neck squamous cell carcinoma
Authors: Li Yao jun , Li Hai yan , Zhang Quan , Wei Sheng li
Published: July 2022

Background: Cuproptosis has been recognized as a novel regulatory cell death, which has been confirmed to promote the occurrence and development of tumors. However, whether cuproptosis-related lncRNA has an impact on the prognosis of squamous cell carcinoma of the head and neck (HNSCC) is still unclear.

Methods: In total, 501 HNSCC tumor samples and 44 normal were downloaded from the TCGA database. Cuproptosis-related lncRNAs were obtained by co-expressed analysis. We got prognostic lncRNA that was associated with cuproptosis by using univariate Cox regression analysis and LASSO Cox regression. Then we constructed and validated the prognostic signature of HNSCC and analyzed the immune landscape of the signature.

Results: The Prognostic Signature is based on 10 cuproptosis-related lncRNAs including AC090587.1, AC004943.2, TTN-AS1, AL162458.1, AC106820.5, AC012313.5, AL132800.1, WDFY3-AS2, CDKN2A-DT, and AL136419.3. The results of overall survival, risk score distribution, and survival status in the low-risk group were better than those in the high-risk group. In addition, all immune checkpoint genes involved were significantly different between the two risk groups (p < 0.05). The risk score was positively correlated with Eosinophils. M0 and M2 phenotype macrophages, mast cells activated, NK cells activated, and negatively related with B cells naive, mast cells resting, plasma cells, CD8T cells, T cells follicular helper, T cells regulatory (Tregs). Consensus clustering was identified in molecular subtypes of HNSC. More high-risk samples concentrated in Cluster1, which had a higher Tumor Immune Dysfunction and Exclusion (TIDE) score and Single Nucleotide Polymorphisms (SNP) alternation than Cluster2.

Conclusion: Our study elucidated the correlation between cuproptosis-related lncRNA with prognosis and immune landscape of HNSCC, which may provide references for further research on the exploration of the mechanism and functions of the prognosis for HNSCC.
A novel risk model based on cuproptosis-related lncRNAs predicted prognosis and indicated immune microenvironment landscape of patients with cutaneous melanoma
Authors: Zhou Yi , Shu Qi , Fu Zailin , Wang Chen , Gu Jianrong , Li Jianbo , Chen Yifang , Xie Minghua
Published: July 2022

Cutaneous melanoma (CM) is an aggressive form of malignancy with poor prognostic value. Cuproptosis is a novel type of cell death regulatory mechanism in tumors. However, the role of cuproptosis-related long noncoding RNAs (lncRNAs) in CM remains elusive. The cuproptosis-related lncRNAs were identified using the Pearson correlation algorithm. Through the univariate and multivariate Cox regression analysis, the prognosis of seven lncRNAs associated with cuproptosis was established and a new risk model was constructed. ESTIMATE, CIBERSORT, and single sample gene set enrichment analyses (ssGSEA) were applied to evaluate the immune microenvironment landscape. The Kaplan–Meier survival analysis revealed that the overall survival (OS) of CM patients in the high-risk group was remarkably lower than that of the low-risk group. The result of the validated cohort and the training cohort indicated that the risk model could produce an accurate prediction of the prognosis of CM. The nomogram result demonstrated that the risk score based on the seven prognostic cuproptosis-related lncRNAs was an independent prognostic indicator feature that distinguished it from other clinical features. The result of the immune microenvironment landscape indicated that the low-risk group showed better immunity than high-risk group. The immunophenoscore (IPS) and immune checkpoints results conveyed a better benefit potential for immunotherapy clinical application in the low-risk groups. The enrichment analysis and the gene set variation analysis (GSVA) were adopted to reveal the role of cuproptosis-related lncRNAs mediated by the immune-related signaling pathways in the development of CM. Altogether, the construction of the risk model based on cuproptosis-related lncRNAs can accurately predict the prognosis of CM and indicate the immune microenvironment of CM, providing a new perspective for the future clinical treatment of CM.
Prognostic Value and Immune Landscapes of m5C-Related lncRNAs in Lung Squamous Cell Carcinoma
Authors: Xu Ruoxin , Zhang Wenxiong
Published: July 2022

5-methylcytosine (m5C) modification is involved in tumor progression. However, the lncRNAs associated with m5C in lung squamous cell carcinoma (LUSC) have not been elucidated. The Cancer Genome Atlas database was used to get the open-accessed transcriptional profiling and clinical information of LUSC patients. All the statistical analyses were performed based on R software v 4.0.0 and SPSS13.0. First, there were 614 m5C-related lncRNAs identified under the criterion of |R|>0.4 and p < 0.001 with m5C genes. Next, a prognosis model based on ERICD, AL021068.1, LINC01341, AC254562.3, and AP002360.1 was established, which showed good prediction efficiency in both the training and validation cohorts. Next, a nomogram plot was established by combining the risk score and clinical features for a better application in clinical settings. Pathway enrichment analysis showed that the pathways of angiogenesis, TGF-β signaling, IL6-JAK-STAT3 signaling, protein secretion, androgen response, interferon-α response, and unfolded protein response were significantly enriched in the high-risk patients. Immune infiltration analysis showed that the risk score was positively correlated with neutrophils, resting CD4+ memory T cells, and M2 macrophages, yet negatively correlated with follicular helper T cells, CD8+ T cells, and activated NK cells. Moreover, we found that high-risk patients might be more sensitive to immunotherapy, imatinib, yet resistant to erlotinib, gefitinib, and vinorelbine. In summary, our prognosis model is an effective tool that could robustly predict LUSC patient prognosis, which had the potential for clinical guidance.
Obstetric risk in pregnancy interacts with hair cortisone levels to reduce gestational length
Authors: Musana Joseph , Cohen Craig R. , Kuppermann Miriam , Gerona Roy , Wanyoro Anthony , Aguilar David , Santos Nicole , Temmerman Marleen , Weiss Sandra J.
Published: July 2022

Background

Maternal psychological stress has been linked to preterm birth. However, the differential contribution of psychological stress versus stress hormones is not clear. Studies focus primarily on perceived stress and cortisol, with few assessing its inter-convertible hormone cortisone. Furthermore, little is known about the potential moderating roles of obstetric risk and fetal sex in the relationship between maternal stress and gestational length. This gap in knowledge is particularly evident for rural women who typically experience chronic multiple stressors during pregnancy. We explored the relationship of hormonal and psychological stress to gestational length and the effects of obstetric risks and fetal sex on this relationship among Kenyan pregnant women.

Methods

The sample included 130 women recruited between 22 to 28 weeks gestation. They completed a clinical and sociodemographic questionnaire together with the Perceived Stress Scale and provided a hair sample for cortisol and cortisone assay. Women underwent an ultrasound to assess weeks of gestation. At delivery, their pregnancy-related health problems were identified using information extracted from medical records to compile each woman's number of pregnancy risks on the Obstetric Medical Risk Index (OMRI).

Results

Perceived stress and hair cortisol were not significant predictors of gestational length. However, a greater number of obstetric risks on the OMRI was associated with shorter gestational length. This effect was further explained by the interaction between obstetric risk and hair cortisone (B = 0.709, p = 0.02). Hair cortisone levels of mothers who had a shorter gestation were significantly higher in mothers with 2 or more risks on the OMRI but not among mothers with only one or no risks (t = 2.39, p = 0.02). Fetal sex had no relationship to gestational length and also had no moderating effect on the relationship between any stress-related metric and gestational length.

Conclusion

Cortisone levels may increase in anticipation of shorter gestation as a compensatory response to increased obstetric risk. Elevated cortisone may be a more sensitive marker of risk for early delivery than cortisol or psychological stress, with salience for both the male and female fetus.
Sildenafil, a Type-5 Phosphodiesterase Inhibitor, Fails to Reverse Myeloid-Derived Suppressor Cell-Mediated T Cell Suppression in Cells Isolated From Tuberculosis Patients
Authors: Leukes Vinzeigh N. , Malherbe Stephanus T. , Hiemstra Andriette , Kotze Leigh A. , Roos Kelly , Keyser Alana , De Swardt Dalene , Gutschmidt Andrea , Walzl Gerhard , du Plessis Nelita
Published: July 2022

Successful TB treatment is hampered by increasing resistance to the two most effective first-line anti-TB drugs, namely isoniazid and rifampicin, thus innovative therapies focused on host processes, termed host-directed therapies (HDTs), are promising novel approaches for increasing treatment efficacy without inducing drug resistance. We assessed the ability of Sildenafil, a type-5 phosphodiesterase inhibitor, as a repurposed compound, to serve as HDT target, by counteracting the suppressive effects of myeloid-derived suppressor cells (MDSC) obtained from active TB cases on T-cell responsiveness. We confirm that MDSC suppress non-specific T-cell activation. We also show that Sildenafil treatment fails to reverse the MDSC-mediated suppression of T-cell functions measured here, namely activation and proliferation. The impact of Sildenafil treatment on improved immunity, using the concentration tested here, is likely to be minimal, but further identification and development of MDSC-targeting TB host-directed therapies are warranted.
V2 hotspot optimized MVA vaccine expressing stabilized HIV-1 Clade C envelope Gp140 delays acquisition of heterologous Clade C Tier 2 challenges in Mamu-A*01 negative Rhesus Macaques
Authors: Styles Tiffany M. , Gangadhara Sailaja , Reddy Pradeep B. J. , Sahoo Anusmita , Shiferaw Ayalensh , Welbourn Sarah , Kozlowski Pamela A. , Derdeyn Cynthia A. , Velu Vijayakumar , Amara Rama Rao
Published: July 2022

Stabilized HIV envelope (Env) trimeric protein immunogens have been shown to induce strong autologous neutralizing antibody response. However, there is limited data on the immunogenicity and efficacy of stabilized Env expressed by a viral vector-based immunogen. Here, we compared the immunogenicity and efficacy of two modified vaccinia Ankara (MVA) vaccines based on variable loop 2 hotspot (V2 HS) optimized C.1086 envelope (Env) sequences, one expressing the membrane anchored gp150 (MVA-150) and the other expressing soluble uncleaved pre-fusion optimized (UFO) gp140 trimer (MVA-UFO) in a DNA prime/MVA boost approach against heterologous tier 2 SHIV1157ipd3N4 intrarectal challenges in rhesus macaques (RMs). Both MVA vaccines also expressed SIVmac239 Gag and form virus-like particles. The DNA vaccine expressed SIVmac239 Gag, C.1086 gp160 Env and rhesus CD40L as a built-in adjuvant. Additionally, all immunizations were administered intradermally (ID) to reduce induction of vaccine-specific IFNγ+ CD4 T cell responses. Our results showed that both MVA-150 and MVA-UFO vaccines induce comparable Env specific IgG responses in serum and rectal secretions. The vaccine-induced serum antibody showed ADCC and ADCVI activities against the challenge virus. Comparison with a previous study that used similar immunogens via intramuscular route (IM) showed that ID immunizations induced markedly lower SHIV specific CD4 and CD8 T cell responses compared to IM immunizations. Following challenge, MVA-UFO vaccinated animals showed a significant delay in acquisition of SHIV1157ipd3N4 infection but only in Mamu-A*01 negative macaques with an estimated vaccine efficacy of 64% per exposure. The MVA-150 group also showed a trend (p=0.1) for delay in acquisition of SHIV infection with an estimated vaccine efficacy of 57%. The vaccine-induced IFNγ secreting CD8 T cell responses showed a direct association and CD4 T cells showed an inverse association with delay in acquisition of SHIV infection. These results demonstrated that both MVA-150 and MVA-UFO immunogens induce comparable humoral and cellular immunity and the latter provides marginally better protection against heterologous tier 2 SHIV infection. They also demonstrate that DNA/MVA vaccinations delivered by ID route induce better antibody and lower CD4 and CD8 T cell responses compared to IM.
The long and winding road: From mouse linkage studies to a novel human therapeutic pathway in type 1 diabetes
Authors: Rojas Manuel , Heuer Luke S. , Zhang Weici , Chen Yi-Guang , Ridgway William M.
Published: July 2022

Autoimmunity involves a loss of immune tolerance to self-proteins due to a combination of genetic susceptibility and environmental provocation, which generates autoreactive T and B cells. Genetic susceptibility affects lymphocyte autoreactivity at the level of central tolerance (e.g., defective, or incomplete MHC-mediated negative selection of self-reactive T cells) and peripheral tolerance (e.g., failure of mechanisms to control circulating self-reactive T cells). T regulatory cell (Treg) mediated suppression is essential for controlling peripheral autoreactive T cells. Understanding the genetic control of Treg development and function and Treg interaction with T effector and other immune cells is thus a key goal of autoimmunity research. Herein, we will review immunogenetic control of tolerance in one of the classic models of autoimmunity, the non-obese diabetic (NOD) mouse model of autoimmune Type 1 diabetes (T1D). We review the long (and still evolving) elucidation of how one susceptibility gene,Cd137, (identified originallyvialinkage studies) affects both the immune response and its regulation in a highly complex fashion. The CD137 (present in both membrane and soluble forms) and the CD137 ligand (CD137L) both signal into a variety of immune cells (bi-directional signaling). The overall outcome of these multitudinous effects (either tolerance or autoimmunity) depends upon the balance between the regulatory signals (predominantly mediated by soluble CD137viathe CD137L pathway) and the effector signals (mediated by both membrane-bound CD137 and CD137L). This immune balance/homeostasis can be decisively affected by genetic (susceptibility vs. resistant alleles) and environmental factors (stimulation of soluble CD137 production). The discovery of the homeostatic immune effect of soluble CD137 on the CD137-CD137L system makes it a promising candidate for immunotherapy to restore tolerance in autoimmune diseases.
Single-Cell RNA-Sequencing Atlas Reveals the Tumor Microenvironment of Metastatic High-Grade Serous Ovarian Carcinoma
Authors: Deng Yingqing , Tan Yuan , Zhou Dongmei , Bai Youhuang , Cao Ting , Zhong Caizhou , Huang Weilai , Ou Yuhua , Guo Linlang , Liu Qianqian , Yin Deling , Chen Lipai , Luo Xiping , Sun Deqiang , Sheng Xiujie
Published: July 2022

Ovarian cancer is the most common and lethal gynecological tumor in women worldwide. High-grade serous ovarian carcinoma (HGSOC) is one of the histological subtypes of epithelial ovarian cancer, accounting for 70%. It often occurs at later stages associated with a more fatal prognosis than endometrioid carcinomas (EC), another subtype of epithelial ovarian cancer. However, the molecular mechanism and biology underlying the metastatic HGSOC (HG_M) immunophenotype remain poorly elusive. Here, we performed single-cell RNA sequencing analyses of primary HGSOC (HG_P) samples, metastatic HGSOC (HG_M) samples, and endometrioid carcinomas (EC) samples. We found that ERBB2 and HOXB-AS3 genes were more amplified in metastasis tumors than in primary tumors. Notably, high-grade serous ovarian cancer metastases are accompanied by dysregulation of multiple pathways. Malignant cells with features of epithelial-mesenchymal transition (EMT) affiliated with poor overall survival were identified. In addition, cancer-associated fibroblasts with EMT-program were enriched in HG_M, participating in angiogenesis and immune regulation, such as IL6/STAT3 pathway activity. Compared with ECs, HGSOCs exhibited higher T cell infiltration. PRDM1 regulators may be involved in T cell exhaustion in ovarian cancer. The CX3CR1_macro subpopulation may play a role in promoting tumor progression in ovarian cancer with high expression of BAG3, IL1B, and VEGFA. The new targets we discovered in this study will be useful in the future, providing guidance on the treatment of ovarian cancer.
CAR T-Cell-Based gene therapy for cancers: new perspectives, challenges, and clinical developments
Authors: Jogalekar Manasi P. , Rajendran Ramya Lakshmi , Khan Fatima , Dmello Crismita , Gangadaran Prakash , Ahn Byeong-Cheol
Published: July 2022

Chimeric antigen receptor (CAR)-T cell therapy is a progressive new pillar in immune cell therapy for cancer. It has yielded remarkable clinical responses in patients with B-cell leukemia or lymphoma. Unfortunately, many challenges remain to be addressed to overcome its ineffectiveness in the treatment of other hematological and solidtumor malignancies. The major hurdles of CAR T-cell therapy are the associated severe life-threatening toxicities such as cytokine release syndrome and limited anti-tumor efficacy. In this review, we briefly discuss cancer immunotherapy and the genetic engineering of T cells and, In detail, the current innovations in CAR T-cell strategies to improve efficacy in treating solid tumors and hematologic malignancies. Furthermore, we also discuss the current challenges in CAR T-cell therapy and new CAR T-cell-derived nanovesicle therapy. Finally, strategies to overcome the current clinical challenges associated with CAR T-cell therapy are included as well.
Incidence and prevalence of tuberculosis in systemic lupus erythematosus patients: A systematic review and meta-analysis
Authors: Wu Qian , Liu Yang , Wang Wei , Zhang Yu , Liu Kui , Chen Song-Hua , Chen Bin
Published: July 2022

Background

Systemic lupus erythematosus (SLE) patients are particularly susceptible to infections, such as pulmonary tuberculosis (PTB) and extrapulmonary tuberculosis (EPTB). This meta-analysis aimed to determine the incidence and prevalence of tuberculosis (TB) in SLE patients.

Methods

The Web of Science, PubMed, Cochrane Library, and Chinese National Knowledge Infrastructure databases were searched for articles of relevant studies published from the dates the databases were established until April 30, 2022. The I2 statistic and Q test were used to evaluate heterogeneity among the analysed studies. Random-effects models were utilised and subgroup analyses were conducted for analysis of the study data.

Results

A total of 35 studies with 46,327 SLE patients were eligible for analysis. The incidence and prevalence of TB among the SLE patients were 1.16 per 100 person-years (95% confidence interval (CI): 0.69-1.93) and 3.59% (95% CI: 2.57%-5.02%), respectively. The pooled prevalence of SLE-PTB and SLE-EPTB was 2.46% (95% CI: 1.73%-3.51%) and 1.42% (95% CI: 0.98%-2.06%), respectively. Subgroup analyses showed that the incidence of SLE-TB was higher in Africa and in countries with a high TB burden than in countries with a low TB burden. The prevalence of SLE-TB was elevated in Asia, in patients taking a mean daily dose of glucocorticoids ≥20 mg, in studies with small sample sizes (n <1000) and ended before 2001.

Conclusions

The available evidence suggests that both the incidence and prevalence of TB in SLE patients are high. This study provides a more specific understanding of SLE-TB, which can help health policymakers in the development of preventive strategies for reducing the SLE-TB burden.
Knowledge Mapping of Exosomes in Autoimmune Diseases: A Bibliometric Analysis (2002–2021)
Authors: Wu Fengping , Gao Jinfang , Kang Jie , Wang Xuexue , Niu Qing , Liu Jiaxi , Zhang Liyun
Published: July 2022

Background

Autoimmune diseases (AIDs) are a class of chronic disabling diseases characterized by inflammation and damage to muscles, joints, bones, and internal organs. Recent studies have shown that much progress has been made in the research of exosomes in AIDs. However, there is no bibliometric analysis in this research field. This study aims to provide a comprehensive overview of the knowledge structure and research hotspots of exosomes in AIDs through bibliometrics.

Method

Publications related to exosomes in AIDs from 2002 to 2021 were searched on the web of science core collection (WoSCC) database. VOSviewers, CiteSpace and R package “bibliometrix” were used to conduct this bibliometric analysis.

Results

312 articles from 48 countries led by China and the United States were included. The number of publications related to exosomes in AIDs is increasing year by year. Central South University, Sun Yat Sen University, Tianjin Medical University and University of Pennsylvania are the main research institutions. Frontiers in immunology is the most popular journal in this field, and Journal of Immunology is the most co-cited journal. These publications come from 473 authors among which Ilias Alevizos, Qianjin Lu, Wei Wei, Jim Xiang and Ming Zhao had published the most papers and Clotilde Théry was co-cited most often. Studying the mechanism of endogenous exosomes in the occurrence and development of AIDs and the therapeutic strategy of exogenous exosomes in AIDs are the main topics in this research field. “Mesenchymal stem cells”, “microRNA”, “biomarkers”, “immunomodulation”, and “therapy” are the primary keywords of emerging research hotspots.

Conclusion

This is the first bibliometric study that comprehensively summarizes the research trends and developments of exosomes in AIDs. This information identifies recent research frontiers and hot directions, which will provide a reference for scholars studying exosomes.
Immunotherapy for EGFR-mutant advanced non-small-cell lung cancer: Current status, possible mechanisms and application prospects
Authors: Shi Chunyan , Wang Yan , Xue Jianxin , Zhou Xiaojuan
Published: July 2022

Immune checkpoint inhibitors (ICIs) are effective against advanced and even perioperative non-small-cell lung cancer (NSCLC) and result in durable clinical benefit, regardless of programmed death ligand-1 (PD-L1) expression status in cancer. Existing clinical evidence shows that the effect of immunotherapy in patients with EGFR-mutant NSCLC after the development of tyrosine kinase inhibitor (TKI) resistance is not satisfactory. However, compared with monotherapy, ICIs combined with chemotherapy can improve the efficacy. Encouragingly, compared with that of patients with sensitive mutations, the progression-free survival of patients with rare mutations who were treated with ICIs was increased. Adequately maximizing the efficacy of ICIs in EGFR-mutant NSCLC patients is worth exploring. In this review, we described preclinical and clinical studies of ICIs or combined therapy for EGFR-mutant NSCLC. We further focused on EGFR mutations and the cancer immune response, with particular attention given to the role of EGFR activation in the cancer-immunity cycle. The mechanisms for the natural resistance to ICIs were explored to identify corresponding countermeasures that made more EGFR-mutant NSCLC patients benefit from ICIs.
IL-10 Overexpression After BCG Vaccination Does Not Impair Control of Mycobacterium tuberculosis Infection
Authors: Ferreira Catarina M. , Micheli Consuelo , Barreira-Silva Palmira , Barbosa Ana Margarida , Resende Mariana , Vilanova Manuel , Silvestre Ricardo , Cunha Cristina , Carvalho Agostinho , Rodrigues Fernando , Correia-Neves Margarida , Castro António Gil , Torrado Egídio
Published: July 2022

Control of tuberculosis depends on the rapid expression of protective CD4+ T-cell responses in the Mycobacterium tuberculosis (Mtb)-infected lungs. We have recently shown that the immunomodulatory cytokine IL-10 acts intrinsically in CD4+ T cells and impairs their parenchymal migratory capacity, thereby preventing control of Mtb infection. Herein, we show that IL-10 overexpression does not impact the protection conferred by the established memory CD4+ T-cell response, as BCG-vaccinated mice overexpressing IL-10 only during Mtb infection display an accelerated, BCG-induced, Ag85b-specific CD4+ T-cell response and control Mtb infection. However, IL-10 inhibits the migration of recently activated ESAT-6-specific CD4+ T cells into the lung parenchyma and impairs the development of ectopic lymphoid structures associated with reduced expression of the chemokine receptors CXCR5 and CCR7. Together, our data support a role for BCG vaccination in preventing the immunosuppressive effects of IL-10 in the fast progression of Mtb infection and may provide valuable insights on the mechanisms contributing to the variable efficacy of BCG vaccination.
A Proposed Scheme of Fishing Quota Allocation to Ensure the Sustainable Development of China’s Marine Capture Fisheries
Authors: Liu Honghong , Peng Daomin , Yang Hyun-Joo , Mu Yongtong , Zhu Yugui
Published: July 2022

The sustainable development of marine capture fisheries (MCFs) plays a significant role in food security, economic development, and employment stability. The lack of information on the sustainability of MCFs, along with the inadequate management of fisheries output controls, has weakened China’s efforts towards a national catch limit target of no more than 10 million tons from capture fisheries until 2020. Furthermore, overfishing and fishery conflicts still exist. In order to try and resolve the above problems and achieve the sustainable use of fishery resources, an evaluation of the development status of these fisheries based on the coupling coordination model has been undertaken. The results show that the social, economic, and biological systems of MCFs in coastal areas of China interact with each other while their development is not coordinated, and regional differences exist. This study integrates the socioeconomic indicators using the catch-share program as a breakthrough methodology to resolve inconsistencies. The results under different allocation schemes suggest that the multifactor scheme is more equitable than the single-factor scheme, which enhances the fairness of the initial distribution.
A Decade of Time Series Sampling Reveals Thermal Variation and Shifts in Pseudo-nitzschia Species Composition That Contribute to Harmful Algal Blooms in an Eastern US Estuary
Authors: Roche Katherine M. , Sterling Alexa R. , Rynearson Tatiana A. , Bertin Matthew J. , Jenkins Bethany D.
Published: July 2022

In 2016-17, shellfish harvesting closed for the first time in Narragansett Bay, Rhode Island, USA, from domoic acid (DA), a neurotoxin produced by diatoms of the Pseudo-nitzschia genus. Pseudo-nitzschia have occurred frequently for over 60 years in Narragansett Bay’s Long-Term Plankton Time Series (NBPTS), therefore it is surprising that the first closure only recently occurred. Pseudo-nitzschia species are known to vary in their toxin production, thus species identification is critical for understanding the underlying ecological causes of these harmful algal blooms (HABs). DNA in plankton biomass can be preserved for many years, so molecular barcoding of archived samples is useful for delineation of taxa over time. This study used amplification of the Pseudo-nitzschia-specific 18S-5.8S rDNA internal transcribed spacer region 1 (ITS1) in plankton samples and high throughput sequencing to characterize Pseudo-nitzschia species composition over a decade in Narragansett Bay, including eight years before the 2016-17 closures and two years following. This metabarcoding method can discriminate nearly all known Pseudo-nitzschia species. Several species recur as year-round residents in Narragansett Bay (P. pungens var. pungens, P. americana, P. multiseries, and P. calliantha). Various other species increased in frequency after 2015, and some appeared for the first time during the closure period. Notably, P. australis, a species prevalent in US West Coast HABs and known for high DA production, was not observed in Narragansett Bay until the 2017 closure but has been present in several years after the closures. Annual differences in Pseudo-nitzschia composition were correlated with physical and chemical conditions, predominantly water temperature. The long-term composition trends of Pseudo-nitzschia in Narragansett Bay serve as a baseline for identifying the introduction of new species, understanding shifting assemblages that contributed to the 2016-17 closures, and monitoring species that may be cause for future concern.
Spatiotemporal Overlap of Baleen Whales and Krill Fisheries in the Western Antarctic Peninsula Region
Authors: Reisinger Ryan R. , Trathan Philip N. , Johnson Christopher M. , Joyce Trevor W. , Durban John W. , Pitman Robert L. , Friedlaender Ari S.
Published: July 2022

In Antarctica, abundant consumers rely on Antarctic krill for food, but krill are also the subject of a commercial fishery. The fishery overlaps in time and space with the foraging areas of these consumers, thus potential competition between krill fisheries and krill consumers is a major management concern. The fishery is managed by the Commission for the Conservation of Antarctic Marine Living Resources with an ecosystem approach, according to which fishing should not interfere with either the population growth of krill, or krill-dependent consumers. Krill catches have become increasingly spatially concentrated in a small number of hotspots, raising concerns about how local depletion of krill impacts consumers. Such concentrated fishing demonstrates that there is a mismatch between the spatial and temporal scale at which krill fisheries are currently managed, and that at which fisheries operate and consumers forage. Information on the seasonal dynamics of predator abundance and their foraging behaviour is fundamental to future precautionary management of the krill fishery. We analysed the spatiotemporal distribution of two major krill consumers – humpback and minke whales – and that of krill fishing, off the Western Antarctic Peninsula. We used whale tracking data (58 humpback whale tracks and 19 minke whale tracks) to develop spatial random forest models predicting the monthly distribution of whale foraging areas from January-July. Using these predictions, we calculated spatiotemporally-explicit geographic overlap between whales and fisheries, the latter represented by krill fishing effort and catch data. Over the krill fishing season, fishing effort and catch hotspots shifted to the southwest, into the Bransfield Strait where effort and catch was highest. Predicted humpback whale foraging areas increased in the Bransfield Strait over the same period, while predicted minke whale foraging areas showed an opposite trend. For both we predicted a whale-fishing interaction hotspot in the Bransfield Strait, strongest in April and May. Our results illustrate the fine spatial scale of likely interactions between baleen whales and the krill fishery, and their concentration over the season, underlining the need for fishery management more closely aligned to the spatiotemporal scale of likely predator-fishery interactions.
Reproductive Cycle and Periodicity of In Situ and Aquarium Female Sand Tiger Sharks Carcharias taurus from the Western North Atlantic
Authors: Wyffels Jennifer T. , George Robert , Christiansen Emily F. , Clauss Tonya M. , Newton Alisa L. , Hyatt Michael W. , Buckner Chris , LePage Véronique , Latson F. Ed , Penfold Linda M.
Published: July 2022

Fundamental characteristics of the reproductive biology of female sand tiger sharks Carcharias taurus are needed to understand the periodicity, seasonality and environmental factors essential for reproduction in this iconic species. Animals in managed care, such as aquariums, provide the unique opportunity for longitudinal study in contrast to in situ sharks that are examined opportunistically, and at a single point in time. Additionally, comparison of reproductive observations from successfully reproducing in situ sharks and aquarium sharks may help elucidate reasons for lack of reproduction among aquarium sharks and aid the development of assisted reproductive techniques for managed populations. Reproductive status of in situ and aquarium female sharks was assessed using ultrasonography and plasma hormone (17β-estradiol, testosterone, and progesterone) monitoring. The reproductive cycle was divided into eight stages based on ovarian activity and uterine contents. In situ sharks were sampled from Delaware Bay (n = 29), North Carolina (n = 39) and South Carolina (n = 11) during April-November from 2015–2020. Nineteen aquarium females from five aquaria were examined longitudinally for two or more consecutive years. Reproductive regionalization was observed among in situ females with the majority (83%) of North Carolina females in an active state of reproduction and all Delaware females in a resting reproductive state. All aquarium females had a pattern of reproductive cycling that was consistent with alternating years of activity and rest with confirmed biennial (n = 7) or triennial (n = 3) reproductive cycles with spring seasonality. In contrast to in situ females, aquarium females often retained uterine eggs for 9-20 months after ovulation in the absence of a developing embryo(s). Pre-ovulatory aquarium females had significantly higher concentrations of 17β-estradiol, testosterone and progesterone than other reproductive stages. For females in the ovulatory stage, in situ females had higher testosterone than aquarium females. Endocrine differences between successfully reproducing in situ females and aquarium females likely contribute to the limited reproductive success observed for this species in managed care and may be a reflection of diminished seasonal cues and environmental differences.
Managed Nitrogen Load Decrease Reduces Chlorophyll and Hypoxia in Warming Temperate Urban Estuary
Authors: Codiga Daniel L. , Stoffel Heather E. , Oviatt Candace A. , Schmidt Courtney E.
Published: July 2022

Many urban estuaries worldwide suffer from excess phytoplankton and hypoxia (low oxygen) due to high nutrient loads. A common water quality management strategy is to require wastewater treatment facility upgrades. This case study examines Narragansett Bay, a warming temperate mid-latitude urban estuary with seasonal periodic hypoxia, during June through September from 2005 to 2019. Within this period, numerous facilities were upgraded to nitrogen removal over several years. The response of the bay is more consistent with “textbook” expectations for reduced chlorophyll and hypoxia than what was seen in many other systems—despite its complex coastline geometry, numerous river inputs, and widely-distributed treatment facilities. River flow drives inter-annual variability with increased load, density stratification, chlorophyll, and hypoxia in wet years. Mean 2013-2019 bay-wide total nitrogen load was 34% less than the 2005-2012 mean, a reduction of about 106 kg yr-1, comparable to the range of flow-driven inter-annual variations. Chlorophyll Index and Hypoxia Index event-based metrics applied to high-frequency time series observations at eight sites quantify exceedances of severe and moderate thresholds. Relatively steady 33% and 16% Chlorophyll Index declines, for severe and moderate thresholds, occurred from about 2007 to 2019. The Hypoxia Index declined markedly by 2009 and 2014 for severe and moderate thresholds, respectively, and remained at or near zero from 2014 to 2019. The load reduction explains chlorophyll and hypoxia declines better than physical processes including river flow, stratification, tidal variations, winds, sea level differences, and temperatures. River flow about 55% higher than the 2005-2019 mean would increase non-treatment facility loads by an amount comparable to the managed load decrease, so future wet summers could partially reverse the improvements. Long-term trends include warming of about 0.5°C decade-1, which reduces oxygen saturation by 0.1 mg l-1 decade-1. This rate is likely a lower bound for temperature-driven oxygen decreases, because warming can also accelerate phytoplankton growth and bacterial consumption. Without warming, the managed load decrease would have curtailed hypoxia more effectively. Climate trends should be at least as important to future eutrophication as the managed load decline because, in addition to warming influences, long-term increases in river flow would increase load and stratification.
Consumer Demand for Environmental, Social, and Ethical Information in Fishery and Aquaculture Product Labels
Authors: Peiró-Signes Angel , Miret-Pastor Lluís , Galati Antonino , Segarra-Oña Marival
Published: July 2022

Customers’ attention to sustainability labels in fishery and aquaculture products (FAPs) has been increasing in the last decades, and the industry has adapted to this growing interest by adopting fish ecolabels. However, there is a growing interest to widen the sustainability concept to include the social and ethical information of the fishery and aquaculture industry and to go further from the voluntary approach on the labeling of these aspects in FAPs. For this reason, using data from 2021 Eurobarometer and using machine learning techniques, we disentangle the characteristics of the FAP buyers that consider the importance of environmental impact, ethical, and social information appearing on FAP labeling. The results confirmed that most of the consumers who consider environmental, social, and ethical aspects when buying FAPs also think that this information should be labeled. In line with other works, young, educated, and environmentally aware consumers in high-income countries are more likely to request this information in the FAP label. One interesting finding of the study relates with the asymmetric impact of the variables and the important group of respondents who do not consider these aspects but also advocate to include them in the FAP label. The study outcomes can be beneficial for policymakers to design future public policies regarding FAP labeling, as well as to be taken into consideration in the marketing policies of fishery and aquaculture producers and retailers.