bluuebunny/crossref_metadata_2025 huggingface dataset:
Clinical and Therapeutic Characteristics of Pituitary TSH-Secreting Adenoma in Adolescent-Onset Patients: Six Case Studies and Literature Review
Authors: Yang Yamei , Liu Jie , Deng Kan , Lu Lin , Zhu Huijuan , Lian Xiaolan , Bao Xinjie , Duan Lian , Yao Yong
Published: December 2021

Background

Thyrotropin-secreting adenoma (TSH-oma) is a very rare kind of functional pituitary adenoma, especially that which occurs in adolescents. However, its potential clinical and therapeutic characteristics are still unknown.

Objectives

The study was aimed to summarize the clinical and therapeutic characteristics of patients with adolescent-onset TSH-oma.

Methods

We retrospectively analyzed six (4.1%) adolescent-onset TSH-oma cases from 148 patients who were diagnosed with TSH-oma at our hospital between January 2012 and October 2020. A literature review was performed on the PubMed online database, and 14 adolescent-onset TSH-oma cases were retrieved. Then, the characteristics of clinical manifestations, treatment outcomes, and follow-ups were analyzed and compared to the adult TSH-oma patients.

Results

Altogether, 20 adolescent-onset cases were included in this study having mean onset age of 13.4 ± 3.3 years. Males were found to be slightly predominant (M: F = 1.5:1) in our study. The median baseline levels of TSH, FT3, and FT4 in adolescent-onset cases were found to be 6.30 [interquartile range (IQR) 9.82] µIU/ml, 9.18 (IQR 11.61) pg/ml, and 3.22 (IQR 1.90) ng/dl, respectively, which were all significantly higher than the adult patients of our hospital. Also, the adolescent-onset cases showed more large tumor ratio (36.8% vs. 9.3%, p = 0.007) compared to the adult patients. Compared to the patients of all ages in the literature, the biochemical remission rate of SSAs (57.1%) and remission rate of TSS (38.9%) were found to be considerably lower in adolescent-onset patients, while the recurrence rate (44.4%) was found to be considerably higher.

Conclusions

Adolescent-onset TSH-oma patients showed higher TSH and thyroid hormone levels, more large tumors, and worse treatment outcomes than adult cases. Hence, early diagnosis, multidisciplinary therapy, and close follow-up should be highlighted to improve the prognosis.
ACCRUE—An Integral Index for Measuring Experimental Relevance in Support of Neutronic Model Validation
Authors: Seo Jeongwon , Abdel-Khalik Hany S. , Epiney Aaron S.
Published: December 2021

A key challenge for the introduction of any design changes, e.g., advanced fuel concepts, first-of-a-kind nuclear reactor designs, etc., is the cost of the associated experiments, which are required by law to validate the use of computer models for the various stages, starting from conceptual design, to deployment, licensing, operation, and safety. To achieve that, a criterion is needed to decide on whether a given experiment, past or planned, is relevant to the application of interest. This allows the analyst to select the best experiments for the given application leading to the highest measures of confidence for the computer model predictions. The state-of-the-art methods rely on the concept of similarity or representativity, which is a linear Gaussian-based inner-product metric measuring the angle—as weighted by a prior model parameters covariance matrix—between two gradients, one representing the application and the other a single validation experiment. This manuscript emphasizes the concept of experimental relevance which extends the basic similarity index to account for the value accrued from past experiments and the associated experimental uncertainties, both currently missing from the extant similarity methods. Accounting for multiple experiments is key to the overall experimental cost reduction by prescreening for redundant information from multiple equally-relevant experiments as measured by the basic similarity index. Accounting for experimental uncertainties is also important as it allows one to select between two different experimental setups, thus providing for a quantitative basis for sensor selection and optimization. The proposed metric is denoted by ACCRUE, short for Accumulative Correlation Coefficient for Relevance of Uncertainties in Experimental validation. Using a number of criticality experiments for highly enriched fast metal systems and low enriched thermal compound systems with accident tolerant fuel concept, the manuscript will compare the performance of the ACCRUE and basic similarity indices for prioritizing the relevance of a group of experiments to the given application.
A Hierarchical Modeling Framework for Cyber-Physical Micro Energy Grid System
Authors: Yang Yi , Lu Guanpeng , Li Zhuangzhuang , Tang Yufeng
Published: December 2021

This paper proposes a hierarchical modeling framework for micro energy grid (MEG) from the perspective of cyber-physical integration, including three layers: object layer, integration layer and decision layer. This modeling framework can fully reveal the interplay of the information flow and energy flow in MEG. The energy hub approach is used to uniformly describe the conversion and distribution of different energy sources in the object layer. The state machine is used to describe the characteristics of energy flow and information flow and their dynamic relationships in the integration layer, where the energy flow describes the dynamic balance of energy between the supply side and demand side and the energy changes of each unit in MEG, and the information flow describes the transferring process of each unit’s operating state and the conditions triggering the state transformation. The optimization objective of the decision layer is established based on the actual requirements with optimal operation. The combination of the three-layer model forms the overall model of the MEG. Finally, a typical MEG system is taken as an example to verify the proposed modeling approach, and the results show that the proposed modeling method effectively improves the observability and optimal operation of the MEG.
Whole-Genome DNA Methylation Dynamics of Sheep Preimplantation Embryo Investigated by Single-Cell DNA Methylome Sequencing
Authors: Zhang Zijing , Xu Jiawei , Lyu Shijie , Xin Xiaoling , Shi Qiaoting , Huang Yongzhen , Yu Xiang , Zhu Xiaoting , Li Zhiming , Wang Xianwei , Lang Limin , Xu Zhaoxue , Wang Eryao
Published: December 2021

The early stages of mammalian embryonic development involve the participation and cooperation of numerous complex processes, including nutritional, genetic, and epigenetic mechanisms. However, in embryos cultured in vitro, a developmental block occurs that affects embryo development and the efficiency of culture. Although the block period is reported to involve the transcriptional repression of maternal genes and transcriptional activation of zygotic genes, how epigenetic factors regulate developmental block is still unclear. In this study, we systematically analyzed whole-genome methylation levels during five stages of sheep oocyte and preimplantation embryo development using single-cell level whole genome bisulphite sequencing (SC-WGBS) technology. Then, we examined several million CpG sites in individual cells at each evaluated developmental stage to identify the methylation changes that take place during the development of sheep preimplantation embryos. Our results showed that two strong waves of methylation changes occurred, namely, demethylation at the 8-cell to 16-cell stage and methylation at the 16-cell to 32-cell stage. Analysis of DNA methylation patterns in different functional regions revealed a stable hypermethylation status in 3′UTRs and gene bodies; however, significant differences were observed in intergenic and promoter regions at different developmental stages. Changes in methylation at different stages of preimplantation embryo development were also compared to investigate the molecular mechanisms involved in sheep embryo development at the methylation level. In conclusion, we report a detailed analysis of the DNA methylation dynamics during the development of sheep preimplantation embryos. Our results provide an explanation for the complex regulatory mechanisms underlying the embryo developmental block based on changes in DNA methylation levels.
Case Report: A Novel Genetic Mutation Causes Idiopathic Infantile Arterial Calcification in Preterm Infants
Authors: Yunfeng Liu , Tongyan Han , Jing Wang , Xiaomei Tong
Published: December 2021

Idiopathic infantile arterial calcification (IIAC), also known as generalized arterial calcification of infancy (GACI), is a heritable ectopic mineralization disorder that results in diffuse arterial calcifications and or stenosis, which are attributed to mutations in the ENPP1 gene. In this case study, we report the development of IIAC in a 2-month-old male preterm infant. The patient presented with severe hypertension and seizures, which revealed diffused calcifications and c.130C > T and c.1112A > T mutations in the ENPP1 gene. With biphosphonate, antihypertensive, and control epilepsy therapy, his blood pressure was maintained at 110–120/50–60 mmHg. Intellectual motor development retardation was anticipated in this patient. To the best of our knowledge, this is the first case in which a novel c.130C > T mutation in the ENPP1 gene has been identified, and the administration of bisphosphonates to patients with IIAC has been assessed.
Comprehensive Analyses of the Expression, Genetic Alteration, Prognosis Significance, and Interaction Networks of m6A Regulators Across Human Cancers
Authors: Shi Xiujuan , Zhang Jieping , Jiang Yuxiong , Zhang Chen , Luo Xiaoli , Wu Jiawen , Li Jue
Published: December 2021

Accumulating lines of evidence indicate that the deregulation of m6A is involved in various cancer types. The m6A RNA methylation is modulated by m6A methyltransferases, demethylases, and reader proteins. Although the aberrant expression of m6A RNA methylation contributes to the development and progression of multiple cancer types, the roles of m6A regulators across numerous types of cancers remain largely unknown. Here, we comprehensively investigated the expression, genetic alteration, and prognosis significance of 20 commonly studied m6A regulators across diverse cancer types using TCGA datasets via bioinformatic analyses. The results revealed that the m6A regulators exhibited widespread dysregulation, genetic alteration, and the modulation of oncogenic pathways across TCGA cancer types. In addition, most of the m6A regulators were closely relevant with significant prognosis in many cancer types. Furthermore, we also constructed the protein–protein interacting network of the 20 m6A regulators, and a more complex interacting regulatory network including m6A regulators and their corresponding interacting factors. Besides, the networks between m6A regulators and their upstream regulators such as miRNAs or transcriptional factors were further constructed in this study. Finally, the possible chemicals targeting each m6A regulator were obtained by bioinformatics analysis and the m6A regulators–potential drugs network was further constructed. Taken together, the comprehensive analyses of m6A regulators might provide novel insights into the m6A regulators’ roles across cancer types and shed light on their potential molecular mechanisms as well as help develop new therapy approaches for cancers.
Polymorphisms Within DNA Double-Strand Breaks Repair-Related Genes Contribute to Structural Chromosome Abnormality in Recurrent Pregnancy Loss
Authors: Cheng Zhenbo , Cheng Dehua , Li Jiancheng , Guo Lihuang , Zhang Wei , Zhang Conghui , Liu Yangxu , Huang Yue , Xu Keqian
Published: December 2021

Background: Structural chromosome abnormality (SCA) is an important cause of human diseases, including recurrent pregnancy loss (RPL). DNA double-strand breaks (DSBs) repair-related genes play critical roles in SCA. The present study aims to investigate the potential contribution of DSBs repair-related gene polymorphisms to SCA.

Methods: Fifty-four affected RPL individuals with SCA, 88 affected RPL individuals without SCA, and 84 controls were analyzed. Targeted whole-exome sequencing (WES) was used for screening single nucleotide polymorphisms in six DSBs repair-related genes (EP300, XRCC6, LIG4, XRCC4, PRKDC, and DCLRE1C), and validation was performed by Sanger sequencing. Finally, we detected the frequency of radiation-induced chromosome translocations in no SCA samples with significant polymorphisms by fluorescence in situ hybridization (FISH).

Results: A total of 35 polymorphisms have been identified and confirmed. Frequencies of EP300 rs20551, XRCC6 rs132788, and LIG4 rs1805388 were significantly different between SCA RPL and no SCA RPL (p = 0.030, 0.031, and 0.040 respectively). Frequencies of those three gene polymorphisms between SCA RPL and controls also were significantly different (p = 0.017, 0.028, and 0.029 respectively). Moreover, the frequency of the G allele at rs20551 locus, the T allele at rs132788 locus and the A allele at rs1805388 locus was significantly higher in SCA RPL than no SCA RPL (OR = 3.227, p = 0.005; OR = 1.978, p = 0.008 and OR = 1.769, p = 0.036 respectively) and controls (OR = 7.130, p = 0.000; OR = 2.157, p = 0.004; OR = 2.397, p = 0.003 respectively). Additionally, the frequency of radiation-induced translocation in no SCA samples with rs20551, rs132788 or rs1805388 was significantly higher compared with the wild type samples (p = 0.015, 0.012, and 0.007 respectively).

Conclusion: Our results suggest that rs20551, rs132788, and rs1805388 might be associated with the risk of SCA. Larger scales of genetic variations studies and functional experiments are necessary to further confirm these findings.
Chloroplast and Nuclear Genetic Diversity Explain the Limited Distribution of Endangered and Endemic Thuja sutchuenensis in China
Authors: Yao Zhi , Wang Xinyu , Wang Kailai , Yu Wenhao , Deng Purong , Dong Jinyi , Li Yonghua , Cui Kaifeng , Liu Yongbo
Published: December 2021

Narrow-ranged species face challenges from natural disasters and human activities, and to address why species distributes only in a limited region is of great significance. Here we investigated the genetic diversity, gene flow, and genetic differentiation in six wild and three cultivated populations of Thuja sutchuenensis, a species that survive only in the Daba mountain chain, using chloroplast simple sequence repeats (cpSSR) and nuclear restriction site-associated DNA sequencing (nRAD-seq). Wild T. sutchuenensis populations were from a common ancestral population at 203 ka, indicating they reached the Daba mountain chain before the start of population contraction at the Last Interglacial (LIG, ∼120–140 ka). T. sutchuenensis populations showed relatively high chloroplast but low nuclear genetic diversity. The genetic differentiation of nRAD-seq in any pairwise comparisons were low, while the cpSSR genetic differentiation values varied with pairwise comparisons of populations. High gene flow and low genetic differentiation resulted in a weak isolation-by-distance effect. The genetic diversity and differentiation of T. sutchuenensis explained its survival in the Daba mountain chain, while its narrow ecological niche from the relatively isolated and unique environment in the “refugia” limited its distribution.
Off-the-Shelf Partial HLA Matching SARS-CoV-2 Antigen Specific T Cell Therapy: A New Possibility for COVID-19 Treatment
Authors: Kim Nayoun , Lee Jong-Min , Oh Eun-Jee , Jekarl Dong Wook , Lee Dong-Gun , Im Keon-Il , Cho Seok-Goo
Published: December 2021

Background

Immunological characteristics of COVID-19 show pathological hyperinflammation associated with lymphopenia and dysfunctional T cell responses. These features provide a rationale for restoring functional T cell immunity in COVID-19 patients by adoptive transfer of SARS-CoV-2 specific T cells.

Methods

To generate SARS-CoV-2 specific T cells, we isolated peripheral blood mononuclear cells from 7 COVID-19 recovered and 13 unexposed donors. Consequently, we stimulated cells with SARS-CoV-2 peptide mixtures covering spike, membrane and nucleocapsid proteins. Then, we culture expanded cells with IL-2 for 21 days. We assessed immunophenotypes, cytokine profiles, antigen specificity of the final cell products.

Results

Our results show that SARS-CoV-2 specific T cells could be expanded in both COVID-19 recovered and unexposed groups. Immunophenotypes were similar in both groups showing CD4+ T cell dominance, but CD8+ and CD3+CD56+ T cells were also present. Antigen specificity was determined by ELISPOT, intracellular cytokine assay, and cytotoxicity assays. One out of 14 individuals who were previously unexposed to SARS-CoV-2 failed to show antigen specificity. Moreover, ex-vivo expanded SARS-CoV-2 specific T cells mainly consisted of central and effector memory subsets with reduced alloreactivity against HLA-unmatched cells suggesting the possibility for the development of third-party partial HLA-matching products.

Discussion

In conclusion, our findings show that SARS-CoV-2 specific T cell can be readily expanded from both COVID-19 and unexposed individuals and can therefore be manufactured as a biopharmaceutical product to treat severe COVID-19 patients.

One Sentence Summary

Ex-vivo expanded SARS-CoV-2 antigen specific T cells developed as third-party partial HLA-matching products may be a promising approach for treating severe COVID-19 patients that do not respond to previous treatment options.
Case Report: In Situ Vaccination by Autologous CD16+ Dendritic Cells and Anti-PD-L 1 Antibody Synergized With Radiotherapy To Boost T Cells-Mediated Antitumor Efficacy In A Psoriatic Patient With Cutaneous Squamous Cell Carcinoma
Authors: Huang Jun-Wei , Kuo Chun-Lin , Wang Li-Tzu , Ma Kevin Sheng-Kai , Huang Wen-Yen , Liu Feng-Cheng , Yang Kuender D. , Yang Bing-Heng
Published: December 2021

The combination of radiotherapy and immunotherapy improves the survival rate of patients with malignancies developed through escape from T-cell-mediated immune surveillance. Immune checkpoint inhibitors, such as anti-programmed cell death protein-ligand 1 (anti-PD-L1) antibody, are used to rescue exhausted T cells. Simultaneously, dendritic cells (DCs) which are antigen-presenting cells that can initiate T-cell activation, are used to induce a tumor-specific immune response. However, the synergistic antitumor efficacy of the aforementioned combinational immunotherapy with intratumoral injection of low-dose DCs has not been reported, and the underlying therapeutic mechanism requires further investigation. Herein, we present the special case of a psoriatic patient with cutaneous squamous cell carcinoma (cSCC) in the right inguinal region, these two diseases characterized by opposing contradiction, further complicating treatments and side-effect management efforts. To treat the intractable SCC without exaggerating psoriasis, we developed the triple-regimen therapy (TRT) with the intratumoral injection of low-dose autologous DCs and anti-PD-L1 combined with radiotherapy. The injected DCs were obtained simply through leukapheresis without prior G-CSF administration for mobilization nor tumor-antigen loading for expansion. The patient received three radiation doses (24, 18, and 18 Gy) combined with three intratumoral injections of anti-PD-L1 antibody (40, 60, and 120 mg) plus autologous DCs (80% of the DC subpopulation being CD16+ myeloid DC with approximate amounts of 7.3 × 104, 2.5 × 106, and 1.7 × 107) within 10 weeks. The efficacy of the TRT was encouraging in shrinking tumor mass with remarkable SUVmax reduction (approximately 42%) on FDG PET-Scan despite relatively low-dose DCs were available. The low-dose intratumoral immunotherapy induced mild cutaneous side effects as expected. The transcriptomes were compared between pre-TRT and post-TRT biopsies to analyze underlying mechanical pathways of the TRT protocol. Over 10 highly significantly enriched T-cell-related pathways (P <0.0001) were identified in post-TRT biopsies. In addition, the activation of both innate and adaptive immunity was significantly enriched in post-TRT peripheral blood samples. We develop the easily accessible TRT which produces both local anti-tumor T-cell responses and systemic antitumor immunity for treating cSCC patients, especially for those with autoimmune disease.
Toward Overcoming Treatment Failure in Rheumatoid Arthritis
Authors: Wang Zhuqian , Huang Jie , Xie Duoli , He Dongyi , Lu Aiping , Liang Chao
Published: December 2021

Rheumatoid arthritis (RA) is an autoimmune disorder characterized by inflammation and bone erosion. The exact mechanism of RA is still unknown, but various immune cytokines, signaling pathways and effector cells are involved. Disease-modifying antirheumatic drugs (DMARDs) are commonly used in RA treatment and classified into different categories. Nevertheless, RA treatment is based on a “trial-and-error” approach, and a substantial proportion of patients show failed therapy for each DMARD. Over the past decades, great efforts have been made to overcome treatment failure, including identification of biomarkers, exploration of the reasons for loss of efficacy, development of sequential or combinational DMARDs strategies and approval of new DMARDs. Here, we summarize these efforts, which would provide valuable insights for accurate RA clinical medication. While gratifying, researchers realize that these efforts are still far from enough to recommend specific DMARDs for individual patients. Precision medicine is an emerging medical model that proposes a highly individualized and tailored approach for disease management. In this review, we also discuss the potential of precision medicine for overcoming RA treatment failure, with the introduction of various cutting-edge technologies and big data.
SARS-CoV-2-Encoded MiRNAs Inhibit Host Type I Interferon Pathway and Mediate Allelic Differential Expression of Susceptible Gene
Authors: Zhu Youwei , Zhang Zhaoyang , Song Jia , Qian Weizhou , Gu Xiangqian , Yang Chaoyong , Shen Nan , Xue Feng , Tang Yuanjia
Published: December 2021

Infection of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), causing the rapid spread of coronavirus disease 2019 (COVID-19), has generated a public health crisis worldwide. The molecular mechanisms of SARS-CoV-2 infection and virus–host interactions are still unclear. In this study, we identified four unique microRNA-like small RNAs encoded by SARS-CoV-2. SCV2-miR-ORF1ab-1-3p and SCV2-miR-ORF1ab-2-5p play an important role in evasion of type I interferon response through targeting several genes in type I interferon signaling pathway. Particularly worth mentioning is that highly expressed SCV2-miR-ORF1ab-2-5p inhibits some key genes in the host innate immune response, such as IRF7, IRF9, STAT2, OAS1, and OAS2. SCV2-miR-ORF1ab-2-5p has also been found to mediate allelic differential expression of COVID-19-susceptible gene OAS1. In conclusion, these results suggest that SARS-CoV-2 uses its miRNAs to evade the type I interferon response and links the functional viral sequence to the susceptible genetic background of the host.
Encephalitic Arboviruses of Africa: Emergence, Clinical Presentation and Neuropathogenesis
Authors: Klein Robyn S.
Published: December 2021

Many mosquito-borne viruses (arboviruses) are endemic in Africa, contributing to systemic and neurological infections in various geographical locations on the continent. While most arboviral infections do not lead to neuroinvasive diseases of the central nervous system, neurologic diseases caused by arboviruses include flaccid paralysis, meningitis, encephalitis, myelitis, encephalomyelitis, neuritis, and post-infectious autoimmune or memory disorders. Here we review endemic members of the Flaviviridae and Togaviridae families that cause neurologic infections, their neuropathogenesis and host neuroimmunological responses in Africa. We also discuss the potential for neuroimmune responses to aide in the development of new diagnostics and therapeutics, and current knowledge gaps to be addressed by arbovirus research.
What Happens to the Immune Microenvironment After PD-1 Inhibitor Therapy?
Authors: Wang Qingyi , Xie Bin , Liu Shuang , Shi Ying , Tao Yongguang , Xiao Desheng , Wang Wenxiang
Published: December 2021

The fruitful results of tumor immunotherapy establish its indispensable status in the regulation of the tumorous immune context. It seems that the treatment of programmed cell death receptor 1 (PD-1) blockade is one of the most promising approaches for cancer control. The significant efficacy of PD-1 inhibitor therapy has been made in several cancer types, such as breast cancer, lung cancer, and multiple myeloma. Even so, the mechanisms of how anti-PD-1 therapy takes effect by impacting the immune microenvironment and how partial patients acquire the resistance to PD-1 blockade have yet to be studied. In this review, we discuss the cross talk between immune cells and how they promote PD-1 blockade efficacy. In addition, we also depict factors that may underlie tumor resistance to PD-1 blockade and feasible solutions in combination with it.
Antimicrobial Activity of Neutrophils Against Mycobacteria
Authors: Parker Heather A. , Forrester Lorna , Kaldor Christopher D. , Dickerhof Nina , Hampton Mark B.
Published: December 2021

The mycobacterium genus contains a broad range of species, including the human pathogensM. tuberculosisandM. leprae. These bacteria are best known for their residence inside host cells. Neutrophils are frequently observed at sites of mycobacterial infection, but their role in clearance is not well understood. In this review, we discuss how neutrophils attempt to control mycobacterial infections, either through the ingestion of bacteria into intracellular phagosomes, or the release of neutrophil extracellular traps (NETs). Despite their powerful antimicrobial activity, including the production of reactive oxidants such as hypochlorous acid, neutrophils appear ineffective in killing pathogenic mycobacteria. We explore mycobacterial resistance mechanisms, and how thwarting neutrophil action exacerbates disease pathology. A better understanding of how mycobacteria protect themselves from neutrophils will aid the development of novel strategies that facilitate bacterial clearance and limit host tissue damage.
Response and Duration of Serum Anti-SARS-CoV-2 Antibodies After Inactivated Vaccination Within 160 Days
Authors: Xu Qiu-Yan , Xue Jian-Hang , Xiao Yao , Jia Zhi-Juan , Wu Meng-Juan , Liu Yan-Yun , Li Wei-Li , Liang Xian-Ming , Yang Tian-Ci
Published: December 2021

Background

A vaccine against coronavirus disease 2019 (COVID-19) with highly effective protection is urgently needed. The anti-severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) antibody response and duration after vaccination are crucial predictive indicators.

Objectives

To evaluate the response and duration for 5 subsets of anti-SARS-CoV-2 antibodies after vaccination and their predictive value for protection.

Methods

We determined the response and duration for 5 subsets of anti-SARS-CoV-2 antibodies (neutralizing antibody, anti-RBD total antibody, anti-Spike IgG, anti-Spike IgM, and anti-Spike IgA) in 61 volunteers within 160 days after the CoronaVac vaccine. A logistic regression model was used to determine the predictors of the persistence of neutralizing antibody persistence.

Results

The seropositivity rates of neutralizing antibody, anti-RBD total antibody, anti-Spike IgG, anti-Spike IgM, and anti-Spike IgA were only 4.92%, 27.87%, 21.31%, 3.28% and 0.00%, respectively, at the end of the first dose (28 days). After the second dose, the seropositivity rates reached peaks of 95.08%, 100.00%, 100.00%, 59.02% and 31.15% in two weeks (42 days). Their decay was obvious and the seropositivity rate remained at 19.67%, 54.10%, 50.82%, 3.28% and 0.00% on day 160, respectively. The level of neutralizing antibody reached a peak of 149.40 (101.00–244.60) IU/mL two weeks after the second dose (42 days) and dropped to 14.23 (7.62–30.73) IU/mL at 160 days, with a half-life of 35.61(95% CI, 32.68 to 39.12) days. Younger participants (≤31 years) had 6.179 times more persistent neutralizing antibodies than older participants (>31 years) (P<0.05). Participants with anti-Spike IgA seropositivity had 4.314 times greater persistence of neutralizing antibodies than participants without anti-Spike IgA seroconversion (P<0.05).

Conclusions

Antibody response for the CoronaVac vaccine was intense and comprehensive with 95.08% neutralizing seropositivity rate, while decay was also obvious after 160 days. Therefore, booster doses should be considered in the vaccine strategies.
Inflammatory Cell Composition and Immune-Related microRNA Signature of Temporal Artery Biopsies From Patients With Giant Cell Arteritis
Authors: Bolha Luka , Hočevar Alojzija , Suljič Alen , Jurčić Vesna
Published: December 2021

Objectives

The aim of this study was to quantitatively assess distinct immune cell subsets comprising inflammatory infiltrate in temporal artery biopsies (TABs) from patients with giant cell arteritis (GCA), and to link the obtained histopathological data with expression profiles of immune-related microRNAs (miRNAs).

Methods

The study included 68 formalin-fixed, paraffin-embedded TABs from treatment-naïve patients, including 30 histologically positive GCA and 16 negative GCA TABs, and 22 control non-GCA TABs. Quantitative assessment of histological parameters was performed using histopathological and immunohistochemical techniques. miRNA expression analysis was performed by quantitative real-time PCR.

Results

Intense transmural mononuclear inflammatory infiltrates in TAB-positive GCA arteries were predominantly composed of CD3+, CD4+ and CD8+ T lymphocytes, and CD68+ macrophages, accompanied by a strong nuclear overexpression of the nuclear factor of activated T cells, cytoplasmic 1 (NFATC) in the lymphocyte infiltrate fraction. Furthermore, TAB-positive GCA arteries were characterized by significant overexpression of nine pro-inflammatory miRNAs (miR-132-3p/-142-3p/-142-5p/-155-5p/-210-3p/-212-3p/-326/-342-5p/-511-5p) and a significant under-expression of six regulatory immune-related miRNAs (miR-30a-5p/-30b-5p/-30c-5p/-30d-5p/-30e-5p/-124-3p), whose expression levels significantly associated with most evaluated histopathological parameters. Notably, we revealed miR-132-3p/-142-3p/-142-5p/-155-5p/-212-3p/-511-5p as major promoters of arterial inflammation and miR-30a-5p/-30c-5p/-30d-5p as putative regulators of NFATC signaling in TAB-positive GCA arteries.

Conclusion

Overall, we demonstrated that an altered arterial tissue-specific pro-inflammatory miRNA signature favors enhanced T cell-driven inflammation and macrophage activity in TAB-positive GCA arteries. Moreover, dysregulation of several immune-related miRNAs seems to contribute crucially to GCA pathogenesis, through impairing their regulatory activity towards T cell-mediated immune responses driven by the calcineurin (CaN)/NFAT signaling pathway, indicating their therapeutic, diagnostic and prognostic potential.
Macrophage Heterogeneity in the Intestinal Cells of Salmon: Hints From Transcriptomic and Imaging Data
Authors: Park Youngjin , Zhang Qirui , Fernandes Jorge M. O. , Wiegertjes Geert F. , Kiron Viswanath
Published: December 2021

The intestine has many types of cells that are present mostly in the epithelium and lamina propria. The importance of the intestinal cells for the mammalian mucosal immune system is well-established. However, there is no in-depth information about many of the intestinal cells in teleosts. In our previous study, we reported that adherent intestinal cells (AIC) predominantly express macrophage-related genes. To gather further evidence that AIC include macrophage-like cells, we compared their phagocytic activity and morphology with those of adherent head kidney cells (AKC), previously characterized as macrophage-like cells. We also compared equally abundant as well as differentially expressed mRNAs and miRNAs between AIC and AKC. AIC had lower phagocytic activity and were larger and more circular than macrophage-like AKC. RNA-Seq data revealed that there were 18309 mRNAs, with 59 miRNAs that were equally abundant between AIC and AKC. Integrative analysis of the mRNA and miRNA transcriptomes revealed macrophage heterogeneity in both AIC and AKC. In addition, analysis of AIC and AKC transcriptomes revealed functional characteristics of mucosal and systemic macrophages. Five pairs with significant negative correlations between miRNA and mRNAs were linked to macrophages and epithelial cells and their interaction could be pointing to macrophage activation and differentiation. The potential macrophage markers suggested in this study should be investigated under different immune conditions to understand the exact macrophage phenotypes.
Global Perspectives on Immunization Against SARS-CoV-2 During Pregnancy and Priorities for Future Research: An International Consensus Paper From the World Association of Infectious Diseases and Immunological Disorders
Authors: Abu-Raya Bahaa , Madhi Shabir A. , Omer Saad B. , Amirthalingam Gayatri , Giles Michelle L. , Flanagan Katie L. , Zimmermann Petra , O’Ryan Miguel , Safadi Marco A. , Papaevangelou Vassiliki , Maertens Kirsten , Wanlapakorn Nasamon , Diaz-Brito Vicens , Tommelein Eline , Esposito Susanna
Published: December 2021

Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection in pregnancy is associated with a higher risk for severe morbidity and mortality when compared with infection in non-pregnant women of childbearing age. An increasing number of countries recommend immunization against SARS-CoV-2 in pregnant women. Recent studies provide preliminary and supportive evidence on safety, immunogenicity and effectiveness of coronavirus disease 2019 (COVID-19) vaccines in pregnant women; however, important knowledge gaps remain which warrant further studies. This collaborative consensus paper provides a review of the current literature on COVID-19 vaccines in pregnant women, identifies knowledge gaps and outlines priorities for future research to optimize protection against SARS-CoV-2 in the pregnant women and their infants.
The Protein Paradox: Elucidating the Complex Nutritional Ecology of the Invasive Berry Pest, Spotted-Wing Drosophila (Diptera: Drosophila suzukii)
Authors: Deans Carrie , Hutchison William D.
Published: December 2021

Spotted-wing drosophila (SWD), Drosophila suzukii, has become one of the most widely studied insect species over the last decade, largely due to its recent invasion and rapid expansion across the Americas and Europe. Unlike other drosophilid species, which colonize rotting fruit, SWD females possess a serrated ovipositor that allows them to lay eggs in intact ripening fruit, causing significant economic problems for fruit/berry producers worldwide. Though an impressive amount of research has been conducted on SWD's ecology and physiology, aspects of their nutritional ecology remain ambiguous. This review synthesizes the research to date to provide a more comprehensive view of SWD's nutritional relationship with its fruit hosts and associated microbes. Overall, data suggest that SWD's ability to utilize novel resources is likely due to changes in their ecological, rather than physiological, niche that are largely mediated by microbial associations. Studies show that SWD's nutrient intake is comparable to other drosophilid species, indicating limited adaptation to feeding on lower-protein resources. Instead, data show that fruit protein content is a reliable predictor of host suitability and that fruit-microbe dynamics have a strong impact on protein availability. In particularly, fruit protein increases after infestation with SWD-associated microbes, suggesting that initially-suboptimal intact fruits can become protein-rich on a timeframe that is relevant for larval nutrition. This body of work suggests that microbial associations between flies and their fruit hosts can compensate for the nutritional differences between intact and rotting fruit, and that these relationships are likely responsible for SWD's expanded nutritional niche.
Large Individual-Level Variability in Diel Activity and Depth Use for the Common Lionfish (Pterois miles)
Authors: Gavriel Tal , Pickholtz Renanel , Belmaker Jonathan
Published: December 2021

The common lionfish, Pterois miles, a notoriously invasive species known for its harmful effect on native fish communities in the Atlantic Ocean, has recently begun spreading across the Mediterranean Sea. The wide niche breadth of the lionfish has been hypothesized to facilitate its invasion success. However, it is unclear to what extent this wide niche-breadth is associated with individual-level variation and repeatable behavior over time. Large individual-level behavioral variations may allow individuals to adapt quickly to local conditions, increasing the species’ chance of invasion success and complicating mitigation efforts. In this study, we used an acoustic telemetry system in P. miles’ native Red Sea environment to explore individual-level variation in depth preference and diel activity. A wide depth range may indicate an ability to tolerate a variety of biotic and abiotic conditions, and variability in diel activity may indicate an ability to exploit multiple diet sources. We found large individual-level variability in P. miles’ activity hours; although all tracked fish were active during both sunrise and sunset, certain individuals had prolonged activity hours to variable extents. Moreover, individuals often change their patterns over time, showing low repeatability. We also found that individuals had different depth preferences and commuted between shallow and deep waters over short periods of time. This study is one of the first to explore diel activity as an individual-level trait in wild fish. The variability found in depth and diel activity is likely one of the reasons P. miles has been so successful in invading the Mediterranean Sea. In addition, this variability may impact mitigation efforts within the Mediterranean Sea as nocturnal individuals from deeper waters might replenish diurnally culled shallow-water populations.
Using Nomograms to Predict the PPCs of Patients With Diffuse Peritonitis Undergoing Emergency Gastrointestinal Surgery
Authors: Xue Qiong , Zhu Yu , Wang Ying , Yang Jian-Jun , Zhou Cheng-Mao
Published: December 2021

Objective: To develop and validate a nomogram model for predicting postoperative pulmonary complications (PPCs) in patients with diffuse peritonitis undergoing emergency gastrointestinal surgery.

Methods: We used the least absolute shrinkage and selection operator (LASSO) regression model to analyze the independent risk factors for PPCs in patients with diffuse peritonitis who underwent emergency gastrointestinal surgery. Using R, we developed and validated a nomogram model for predicting PPCs in patients with diffuse peritonitis undergoing emergency gastrointestinal surgery.

Results: The LASSO regression analysis showed that AGE, American Society of Anesthesiologists physical status classification (ASA), DIAGNOSIS, platelets (on the 3rd day after surgery), cholesterol (on the 3rd day after surgery), ALBUMIN (on the first day after surgery), and preoperative ALBUMIN were independent risk factors for PPCs in patients with diffuse peritonitis undergoing emergency gastrointestinal surgery. The area under the curve (AUC) value of the nomogram model in the training group was 0.8240; its accuracy was 0.7000, and its sensitivity was 0.8658. This demonstrates that the nomogram has a high prediction value. Also in the test group, the AUC value of the model established by the variables AGE, ASA, and platelets (on the 3rd day after surgery), cholesterol (on the 3rd day after surgery), ALBUMIN (on the first day after surgery), and preoperative ALBUMIN was 0.8240; its accuracy was 0.8000; and its specificity was 0.8986. In the validation group, the same results were obtained. The results of the clinical decision curve show that the benefit rate was also high.

Conclusion: Based on the risk factors AGE, ASA, DIAGNOSIS, platelets (on the 3rd day after surgery), cholesterol (on the 3rd day after surgery), ALBUMIN (on the first day after surgery), and preoperative ALBUMIN, the nomogram model established in this study for predicting PPCs in patients with diffuse peritonitis undergoing emergency gastrointestinal surgery has high accuracy and discrimination.
Differences in Baseline Characteristics and Access to Treatment of Newly Diagnosed Patients With IPF in the EMPIRE Countries
Authors: Kolonics-Farkas Abigél Margit , Šterclová Martina , Mogulkoc Nesrin , Lewandowska Katarzyna , Müller Veronika , Hájková Marta , Kramer Mordechai , Jovanovic Dragana , Tekavec-Trkanjec Jasna , Studnicka Michael , Stoeva Natalia , Littnerová Simona , Vašáková Martina
Published: December 2021

Idiopathic pulmonary fibrosis (IPF) is a rare lung disease with poor prognosis. The diagnosis and treatment possibilities are dependent on the health systems of countries. Hence, comparison among countries is difficult due to data heterogeneity. Our aim was to analyse patients with IPF in Central and Eastern Europe using the uniform data from the European Multipartner IPF registry (EMPIRE), which at the time of analysis involved 10 countries. Newly diagnosed IPF patients (N = 2,492, between March 6, 2012 and May 12, 2020) from Czech Republic (N = 971, 39.0%), Turkey (N = 505, 20.3%), Poland (N = 285, 11.4%), Hungary (N = 216, 8.7%), Slovakia (N = 149, 6.0%), Israel (N = 120, 4.8%), Serbia (N = 95, 3.8%), Croatia (N = 87, 3.5%), Austria (N = 55, 2.2%), and Bulgaria (N = 9, 0.4%) were included, and Macedonia, while a member of the registry, was excluded from this analysis due to low number of cases (N = 5) at this timepoint. Baseline characteristics, smoking habit, comorbidities, lung function values, CO diffusion capacity, high-resolution CT (HRCT) pattern, and treatment data were analysed. Patients were significantly older in Austria than in the Czech Republic, Turkey, Hungary, Slovakia, Israel, and Serbia. Ever smokers were most common in Croatia (84.1%) and least frequent in Serbia (39.2%) and Slovakia (42.6%). The baseline forced vital capacity (FVC) was >80% in 44.6% of the patients, between 50 and 80% in 49.3%, and <50% in 6.1%. Most IPF patients with FVC >80% were registered in Poland (63%), while the least in Israel (25%). A typical usual interstitial pneumonia (UIP) pattern was present in 67.6% of all patients, ranging from 43.5% (Austria) to 77.2% (Poland). The majority of patients received antifibrotic therapy (64.5%); 37.4% used pirfenidone (range 7.4–39.8% between countries); and 34.9% nintedanib (range 12.6–56.0% between countries) treatment. In 6.8% of the cases, a therapy switch was initiated between the 2 antifibrotic agents. Significant differences in IPF patient characteristics and access to antifibrotic therapies exist in EMPIRE countries, which needs further investigation and strategies to improve and harmonize patient care and therapy availability in this region.
Recent Developments in Microbe–Plant-Based Bioremediation for Tackling Heavy Metal-Polluted Soils
Authors: Saha Lala , Tiwari Jaya , Bauddh Kuldeep , Ma Ying
Published: December 2021

Soil contamination with heavy metals (HMs) is a serious concern for the developing world due to its non-biodegradability and significant potential to damage the ecosystem and associated services. Rapid industrialization and activities such as mining, manufacturing, and construction are generating a huge quantity of toxic waste which causes environmental hazards. There are various traditional physicochemical techniques such as electro-remediation, immobilization, stabilization, and chemical reduction to clean the contaminants from the soil. However, these methods require high energy, trained manpower, and hazardous chemicals make these techniques costly and non-environment friendly. Bioremediation, which includes microorganism-based, plant-based, microorganism-plant associated, and other innovative methods, is employed to restore the contaminated soils. This review covers some new aspects and dimensions of bioremediation of heavy metal-polluted soils. The bioremediation potential of bacteria and fungi individually and in association with plants has been reviewed and critically examined. It is reported that microbes such as Pseudomonas spp., Bacillus spp., and Aspergillus spp., have high metal tolerance, and bioremediation potential up to 98% both individually and when associated with plants such as Trifolium repens, Helianthus annuus, and Vallisneria denseserrulata. The mechanism of microbe’s detoxification of metals depends upon various aspects which include the internal structure, cell surface properties of microorganisms, and the surrounding environmental conditions have been covered. Further, factors affecting the bioremediation efficiency and their possible solution, along with challenges and future prospects, are also discussed.
Optimized Attenuated Salmonella Typhimurium Suppressed Tumor Growth and Improved Survival in Mice
Authors: Liang Kang , Zhang Rui , Luo Haiyan , Zhang Jinlong , Tian Zhenyuan , Zhang Xiaofen , Zhang Yulin , Ali Md Kaisar , Kong Qingke
Published: December 2021

The gram-negative facultative anaerobic bacteria Salmonella enterica serovar Typhimurium (hereafter S. Typhimurium) has always been considered as one candidate of anti-tumor agents or vectors for delivering drug molecules. In this study, we compared several widely studied S. Typhimurium strains in their anti-tumor properties aiming to screen out the best one for further optimization and use in cancer therapy. In terms of the motility, virulence and anti-tumor efficacy, the three strains 14028, SL1344, and UK-1 were similar and obviously better than LT-2, and UK-1 showed the best phenotypes among them. Therefore, the strain UK-1 (D) was selected for the following studies. Its auxotrophic mutant strain (D1) harboring ∆aroA and ∆purM mutations was further optimized through the modification of lipid A structure, generating a new strain named D2 with stronger immunostimulatory activity. Finally, the ∆asd derivative of D2 was utilized as one live vector to deliver anti-tumor molecules including the angiogenesis inhibitor endostatin and apoptosis inducer TRAIL and the therapeutic and toxic-side effects were evaluated in mouse models of colon carcinoma and melanoma. After intraperitoneal infection, engineered Salmonella bacteria equipped with endostatin and/or TRAIL significantly suppressed the tumor growth and prolonged survival of tumor-bearing mice compared to PBS or bacteria carrying the empty plasmid. Consistently, immunohistochemical studies confirmed the colonization of Salmonella bacteria and the expression of anti-tumor molecules inside tumor tissue, which were accompanied by the increase of cell apoptosis and suppression of tumor angiogenesis. These results demonstrated that the beneficial anti-tumor efficacy of attenuated S. Typhimurium bacteria could be improved through delivery of drug molecules with powerful anti-tumor activities.