bluuebunny/crossref_metadata_2025 huggingface dataset:
It’s What and When You Eat: An Overview of Transcriptional and Epigenetic Responses to Dietary Perturbations in Pancreatic Islets
Authors: Brown Matthew R. , Matveyenko Aleksey V.
Published: March 2022

Our ever-changing modern environment is a significant contributor to the increased prevalence of many chronic diseases, and particularly, type 2 diabetes mellitus (T2DM). Although the modern era has ushered in numerous changes to our daily living conditions, changes in “what” and “when” we eat appear to disproportionately fuel the rise of T2DM. The pancreatic islet is a key biological controller of an organism’s glucose homeostasis and thus plays an outsized role to coordinate the response to environmental factors to preserve euglycemia through a delicate balance of endocrine outputs. Both successful and failed adaptation to dynamic environmental stimuli has been postulated to occur due to changes in the transcriptional and epigenetic regulation of pathways associated with islet secretory function and survival. Therefore, in this review we examined and evaluated the current evidence elucidating the key epigenetic mechanisms and transcriptional programs underlying the islet’s coordinated response to the interaction between the timing and the composition of dietary nutrients common to modern lifestyles. With the explosion of next generation sequencing, along with the development of novel informatic and –omic approaches, future work will continue to unravel the environmental-epigenetic relationship in islet biology with the goal of identifying transcriptional and epigenetic targets associated with islet perturbations in T2DM.
The Application Value of the Central Lymph Node Metastasis Risk Assessment Model in Papillary Thyroid Microcarcinoma of Stage cN0: A Study of 828 Patients
Authors: Wang Jinqiu , Sheng Xianneng , Dai Yongping , Zhang Jiabo , Song Lihua , Guo Yu
Published: March 2022

Background

The aim of this study is to build a risk assessment system for central lymph node metastasis (CLNM) in papillary thyroid microcarcinoma (PTMC) of stage cN0 and to explore its application value in clinical practice.

Methods

A total of 500 patients with PTMC who underwent thyroid operation from 2013 to 2015 in Ningbo First Hospital were selected as the model group. Independent risk factors related to CLNM in PTMC were analyzed and determined, and a risk assessment system for CLNM was preliminarily established. Furthermore, the clinicopathological data from 328 PTMC patients with the same conditions as the model group from 2016 to 2017 were further collected as the validation group to verify the diagnostic value of the risk assessment system.

Results

The risk assessment system was based on the score rating (score ≤ 5 was classified as low risk, 6–8 was classified as medium risk, and ≥9 was classified as high-risk). The area under the receiver operating characteristic curve (ROC) was 0.687 (95% CI: 0.635–0.783). According to the risk assessment system, 328 PTMC patients in the validation group were scored. Among the low-risk group, the moderate-risk group, and the high-group, 96.8%, 58.1%, and 43.2% were the CLNM (-) patients, and 3.1%, 41.9%, and 65.8% were CLNM (+) patients, respectively. The area under ROC was 0.837 (95% CI: 0.778–0.869).

Conclusions

The risk assessment system in this study is of diagnostic value and can provide a theoretical foundation for intraoperative decision-making of prophylactic central neck dissection (pCND).
Dynamic Performance Evaluation of Grid-Connected Hybrid Renewable Energy-Based Power Generation for Stability and Power Quality Enhancement in Smart Grid
Authors: Amir Mohammad , Prajapati Anjani Kumar , Refaat Shady S.
Published: March 2022

Today’s stochastic grid system is experiencing huge voltage fluctuations, which is responsible for power quality issues in the smart microgrid network due to its intermittent nature as well as penetration of hybrid renewable resources. Thus, the dynamic performance evaluation and their control are essential to sustaining the stability of the grid network. A d-q controller mechanism is suggested to maintain the balance of the distributed generation network and grid side network. A dynamic control mechanism of voltage source converter (VSC) is presented in the MPPT-based wind power generating station, where an induction generator generates the power by the optimal control of the wind energy-based subsystem. The distributed hybrid generation (solar PV and wind) subsystem’s output terminal is linked to the DC bus bar’s common link via the VSC. A VSI is utilized to convert the desired DC power to alternating current power. To regulate and improve the performance of the proposed hybrid power generating systems (HPGS), a supercapacitor (SC) is used to smooth out the ripple on the distribution side in the power grid. Furthermore, the dynamic stability of grid-connected solar PV and wind power generation systems is investigated. This article also proposed an effective control scheme for the SC in HPGS under the influence of weak grid conditions. This article aimed to validate the efficiency of the VSI topology; a PI controller stability enhancement approach is used in a proposed grid system under various disturbance conditions. Finally, the simulation results and FFT-based power quality response analysis are validated through the effective utilization of an SC.
Comparative Analysis of Codon Bias in the Chloroplast Genomes of Theaceae Species
Authors: Wang Zhanjun , Cai Qianwen , Wang Yue , Li Minhui , Wang Chenchen , Wang Zhaoxia , Jiao Chunyan , Xu Congcong , Wang Hongyan , Zhang Zhaoliang
Published: March 2022

Theaceae species are dicotyledonous angiosperms with extremely high ornamental and economic value. The chloroplast genome is traditionally used to study species evolution, expression of chloroplast genes and chloroplast transformation. Codon usage bias (CUB) analysis is beneficial for investigations of evolutionary relationships and can be used to improve gene expression efficiency in genetic transformation research. However, there are relatively few systematic studies of the CUB in the chloroplast genomes of Theaceae species. In this study, CUB and nucleotide compositions parameters were determined by the scripts written in the Perl language, CodonW 1.4.2, CU.Win2000, RStudio and SPSS 23.0. The chloroplast genome data of 40 Theaceae species were obtained to analyse the codon usage (CU) characteristics of the coding regions and the influence of the source of variation on CUB. To explore the relationship between the CUB and gene expression levels in these 40 Theaceae plastomes, the synonymous codon usage order (SCUO) and measure independent of length and composition (MILC) values were determined. Finally, phylogenetic analysis revealed the genetic evolutionary relationships among these Theaceae species. Our results showed that based on the chloroplast genomes of these 40 Theaceae species, the CUB was for codons containing A/T bases and those that ended with A/T bases. Moreover, there was great commonality in the CUB of the Theaceae species according to comparative analysis of relative synonymous codon usage (RSCU) and relative frequency of synonymous codon (RFSC): these species had 29 identical codons with bias (RSCU > 1), and there were 19 identical high-frequency codons. The CUB of Theaceae species is mainly affected by natural selection. The SCUO value of the 40 Theaceae species was 0.23 or 0.24, and the chloroplast gene expression level was moderate, according to MILC values. Additionally, we observed a positive correlation between the SCUO and MILC values, which indicated that CUB might affect gene expression. Furthermore, the phylogenetic analysis showed that the evolutionary relationships in these 40 Theaceae species were relatively conserved. A systematic study on the CUB and expression of Theaceae species provides further evidence for their evolution and phylogeny.
Adaptation of ACMG-ClinGen Technical Standards for Copy Number Variant Interpretation Concordance
Authors: Zhang Kuo , Lin Guigao , Han Dongsheng , Han Yanxi , Peng Rongxue , Li Jinming
Published: March 2022

This study aimed to evaluate inter-laboratory classification concordance for copy number variants (CNVs) with a semiquantitative point-based scoring metric recommended by the American College of Medical Genetics and Genomics (ACMG) and Clinical Genome Resources (ClinGen). A total of 234 CNVs distributed by the National Center of Clinical Laboratories (NCCLs), and 72 CNVs submitted by different laboratories, were distributed to nine clinical laboratories performing routine clinical CNV testing in China and independently classified across laboratories. The overall inter-laboratory complete classification concordance rate of the 234 distributed CNVs increased from 18% (41/234) to 76% (177/234) using the scoring metric compared to the laboratory's previous method. The overall inter-laboratory complete classification concordance rate of the 72 submitted CNVs was 65% (47/72) using the scoring metrics. The 82 variants that initially did not reach complete concordance classification and 1 additional CNV deletion were reviewed; 34 reached complete agreement, and the overall post-review complete concordance rate was 85% (260/306). Additionally, the overall percentage of classification discordance possibly impacting medical management [i.e., pathogenic (P) or likely pathogenic (LP) vs. variant of uncertain significance (VUS)] was 11% (35/306). The causes of initial and final discordance in the classification were identified. The ACMG-ClinGen framework has promoted consistency in interpreting the clinical significance of CNVs. Continuous training among laboratories, further criteria and additional clarification of the standards, sharing classifications and supporting evidence through public database, and ongoing work for dosage sensitive genes/regions curation will be beneficial for harmonization of CNVs classification.
Cell Differentiation Trajectory in Liver Cirrhosis Predicts Hepatocellular Carcinoma Prognosis and Reveals Potential Biomarkers for Progression of Liver Cirrhosis to Hepatocellular Carcinoma
Authors: He Zhaobin , Peng Cheng , Li Tianen , Li Jie
Published: March 2022

Most hepatocellular carcinoma (HCC) patients occur on a background of liver cirrhosis, the molecular mechanisms of liver cirrhosis and its progression to HCC remain to be fully elucidated. Single cell differentiation trajectory analysis has been used in cell classification and tumor molecular typing, which correlated with disease progression and patient prognosis. Here we use cell differentiation trajectory analysis to investigate the relevance of liver cirrhosis and HCC. Single-cell RNA sequencing (scRNA-seq) data of liver cirrhosis and bulk RNA-seq and clinical data of HCC were downloaded from Gene Expression Omnibus (GEO) and The Cancer Genome Atlas (TCGA) for analysis. HCC samples were divided into three subtypes, based on differentiation-related genes (DRGs) of liver cirrhosis, each with a different expression profile and overall survival (OS). A two- DRGs (CD34 and RAMP3) based prognostic risk scoring (RS) signature was established which could differentiate OS between high-risk and low-risk groups. And expression levels of CD34 and RAMP3 were predominantly high in endothelial cells. By integrating the RS and clinicopathological features, a nomogram was constructed and can accurately predicted the 1-year, 3-years, and 5-years OS. In conclusion, cell differentiation trajectory of liver cirrhosis can predict the prognosis of HCC, and provides new perspectives on the mechanisms of progression of liver cirrhosis to HCC.
Systematic Analysis of Neurotransmitter Receptors in Human Breast Cancer Reveals a Strong Association With Outcome and Uncovers HTR6 as a Survival-Associated Gene Potentially Regulating the Immune Microenvironment
Authors: Zhang Wei , Li Lintai , Li Jianxuan , Yu Haiyan , Zheng Fengping , Yan Bin , Cai Wanxia , Chen Yumei , Yin Lianghong , Tang Donge , Xu Yong , Dai Yong
Published: March 2022

Many epidemiological reports have indicated an increase in the incidence of breast cancer among psychotic patients, suggesting that the targets of antipsychotics, neurotransmitter receptors, may have a role in tumorigenesis. However, the functions of neurotransmitter receptors in cancer are barely known. Here, we analyzed 44 neurotransmitter receptors in breast cancer and revealed that the expression of 34 receptors was positively correlated with relapse-free survival rates (RFS) of patients using the public database (n = 3951). Among all these receptors, we revealed decreased expression of HTR6 in human advanced breast cancer versus tumors in situ using our original data (n = 44). After a pan-cancer analysis including 22 cancers (n = 11262), we disclosed that HTR6 was expressed in 12 tumors and uncovered its influence on survival in seven tumors. Using multi-omics datasets from Linkedomics, we revealed a potential regulatory role of HTR6 in MAPK, JUN, and leukocyte-differentiation pathways through enriching 294 co-expressed phosphorylated proteins of HTR6. Furthermore, we proclaimed a close association of HTR6 expression with the immune microenvironment. Finally, we uncovered two possible reasons for HTR6 down-regulation in breast cancer, including deep deletion in the genome and the up-regulation of FOXA1 in breast cancer, which was a potential negatively regulatory transcription factor of HTR6. Taken together, we revealed a new function of neurotransmitter receptors in breast cancer and identified HTR6 as a survival-related gene potentially regulating the immune microenvironment. The findings in our study would improve our understanding of the pathogenesis of breast cancer and provided a theoretical basis for personalized medication in psychotic patients.
Analysis of Mononuclear Phagocytes Disclosed the Establishment Processes of Two Macrophage Subsets in the Adult Murine Kidney
Authors: Zhu Qian , He Jian , Cao Yangyang , Liu Xiaoli , Nie Wanyun , Han Fei , Shi Peng , Shen Xiao Z.
Published: March 2022

The interstitium of kidney involves a variety of components including resident immune cells, in particular mononuclear phagocytes. However, many proposed markers for distinguishing macrophages or dendritic cells are, in fact, shared by the majority of renal mononuclear phagocytes, which impedes the research of kidney diseases. Here, by employing a flow cytometry strategy and techniques of fate mapping, imaging and lineage depletion, we were able to demarcate renal monocytes, macrophages and dendritic cells and their subsets in mice. In particular, using this strategy, we found that even in steady state, the renal macrophage pool was continuously replenished by bone marrow-derived monocytes in a stepwise process, i.e., from infiltration of classical monocyte, to development of nonclassical monocyte and eventually to differentiation to macrophages. In mechanism, we demonstrated that the ligation of tissue-anchored CX3CL1 and monocytic CX3CR1 was required for promoting monocyte differentiation to macrophages in the kidney, but CX3CL1-CX3CR1 signaling was dispensable in monocyte infiltrating into the kidney. In addition to the bone marrow-derived macrophages, fate mapping in adult mice revealed another population of renal resident macrophages which were embryo-derived and self-maintaining. Thus, the dissecting strategies developed by us would assist in exploration of the biology of renal mononuclear phagocytes.
Single-Cell Multiomics Reveals Clonal T-Cell Expansions and Exhaustion in Blastic Plasmacytoid Dendritic Cell Neoplasm
Authors: DePasquale Erica A. K. , Ssozi Daniel , Ainciburu Marina , Good Jonathan , Noel Jenny , Villanueva Martin A. , Couturier Charles P. , Shalek Alex K. , Aranki Sary F. , Mallidi Hari R. , Griffin Gabriel K. , Lane Andrew A. , van Galen Peter
Published: March 2022

The immune system represents a major barrier to cancer progression, driving the evolution of immunoregulatory interactions between malignant cells and T-cells in the tumor environment. Blastic plasmacytoid dendritic cell neoplasm (BPDCN), a rare acute leukemia with plasmacytoid dendritic cell (pDC) differentiation, provides a unique opportunity to study these interactions. pDCs are key producers of interferon alpha (IFNA) that play an important role in T-cell activation at the interface between the innate and adaptive immune system. To assess how uncontrolled proliferation of malignant BPDCN cells affects the tumor environment, we catalog immune cell heterogeneity in the bone marrow (BM) of five healthy controls and five BPDCN patients by analyzing 52,803 single-cell transcriptomes, including 18,779 T-cells. We test computational techniques for robust cell type classification and find that T-cells in BPDCN patients consistently upregulate interferon alpha (IFNA) response and downregulate tumor necrosis factor alpha (TNFA) pathways. Integrating transcriptional data with T-cell receptor sequencing via shared barcodes reveals significant T-cell exhaustion in BPDCN that is positively correlated with T-cell clonotype expansion. By highlighting new mechanisms of T-cell exhaustion and immune evasion in BPDCN, our results demonstrate the value of single-cell multiomics to understand immune cell interactions in the tumor environment.
Case Report: Lessons Learned From Subsequent Autologous and Allogeneic Hematopoietic Stem Cell Transplantations in a Pediatric Patient With Relapsing Polychondritis
Authors: Veldkamp Saskia R. , Jansen Marc H. A. , Swart Joost F. , Lindemans Caroline A.
Published: March 2022

Background

Autologous hematopoietic stem cell transplantation (autoHSCT) is increasingly being recognized as a treatment option for severe refractory autoimmune diseases (AD). However, efficacy is hampered by high relapse rates. In contrast, allogeneic HSCT (alloHSCT) has high potential to cure AD, but is associated with significant morbidity and mortality, and data in AD are limited. Experience with autoHSCT in relapsing polychondritis, a rare episodic inflammatory disorder characterized by destruction of cartilage, is scarce and alloHSCT has not been described before.

Case Presentation

Here, we present a case of a 9-year-old girl who was diagnosed with relapsing polychondritis, with severe airway involvement requiring a tracheostomy. The disease proved to be steroid-dependent and refractory to a wide array of disease-modifying anti-rheumatic drugs and biologicals. After an autoHSCT procedure, the disease became inactive for a short period of time, until the patient experienced a relapse after 31 days, accompanied by repopulation of effector/memory CD8+ T cells. Because of persistent inflammation and serious steroid toxicity, including severe osteoporosis, growth restriction, and excessive weight gain, the patient was offered an alloHSCT. She experienced transient antibody-mediated immune events post-alloHSCT, which subsided after rituximab. She ultimately developed a balanced immune reconstitution and is currently still in long-term disease remission, 8 years after alloHSCT.

Conclusion

This case adds to the few existing reports on autoHSCT in relapsing polychondritis and gives new insights in its pathogenesis, with a possible role for CD8+ T cells. Moreover, it is the first report of successful alloHSCT as a treatment for children with this severe autoimmune disease.
Molecular Mechanisms Driving IL-10- Producing B Cells Functions: STAT3 and c-MAF as Underestimated Central Key Regulators?
Authors: Michée-Cospolite Magalie , Boudigou Marina , Grasseau Alexis , Simon Quentin , Mignen Olivier , Pers Jacques-Olivier , Cornec Divi , Le Pottier Laëtitia , Hillion Sophie
Published: March 2022

Regulatory B cells (Bregs) have been highlighted in very different pathology settings including autoimmune diseases, allergy, graft rejection, and cancer. Improving tools for the characterization of Bregs has become the main objective especially in humans. Transitional, mature B cells and plasma cells can differentiate into IL-10 producing Bregs in both mice and humans, suggesting that Bregs are not derived from unique precursors but may arise from different competent progenitors at unrestricted development stages. Moreover, in addition to IL-10 production, regulatory B cells used a broad range of suppressing mechanisms to modulate the immune response. Although Bregs have been consistently described in the literature, only a few reports described the molecular aspects that control the acquisition of the regulatory function. In this manuscript, we detailed the latest reports describing the control of IL-10, TGFβ, and GZMB production in different Breg subsets at the molecular level. We focused on the understanding of the role of the transcription factors STAT3 and c-MAF in controlling IL-10 production in murine and human B cells and how these factors may represent an important crossroad of several key drivers of the Breg response. Finally, we provided original data supporting the evidence that MAF is expressed in human IL-10- producing plasmablast and could be inducedin vitrofollowing different stimulation cocktails. At steady state, we reported that MAF is expressed in specific human B-cell tonsillar subsets including the IgD+CD27+unswitched population, germinal center cells and plasmablast.
Tissue-Dependent Adaptations and Functions of Innate Lymphoid Cells
Authors: Murphy Julia M. , Ngai Louis , Mortha Arthur , Crome Sarah Q.
Published: March 2022

Tissue-resident immune cells reside in distinct niches across organs, where they contribute to tissue homeostasis and rapidly respond to perturbations in the local microenvironment. Innate lymphoid cells (ILCs) are a family of innate immune cells that regulate immune and tissue homeostasis. Across anatomical locations throughout the body, ILCs adopt tissue-specific fates, differing from circulating ILC populations. Adaptations of ILCs to microenvironmental changes have been documented in several inflammatory contexts, including obesity, asthma, and inflammatory bowel disease. While our understanding of ILC functions within tissues have predominantly been based on mouse studies, development of advanced single cell platforms to study tissue-resident ILCs in humans and emerging patient-based data is providing new insights into this lymphocyte family. Within this review, we discuss current concepts of ILC fate and function, exploring tissue-specific functions of ILCs and their contribution to health and disease across organ systems.
Application of Regulatory Cell Death in Cancer: Based on Targeted Therapy and Immunotherapy
Authors: Qi Xiaochen , Li Quanlin , Che Xiangyu , Wang Qifei , Wu Guangzhen
Published: March 2022

The development of cancer treatment methods is constantly changing. For common cancers, our treatment methods are still based on conventional treatment methods, such as chemotherapy, radiotherapy, and targeted drug therapy. Nevertheless, the emergence of tumor resistance has a negative impact on treatment. Regulated cell death is a gene-regulated mode of programmed cell death. After receiving specific signal transduction, cells change their physical and chemical properties and the extracellular microenvironment, resulting in structural destruction and decomposition. As research accumulates, we now know that by precisely inducing specific cell death patterns, we can treat cancer with less collateral damage than other treatments. Many newly discovered types of RCD are thought to be useful for cancer treatment. However, some experimental results suggest that some RCDs are not sensitive to cancer cell death, and some may even promote cancer progression. This review summarizes the discovered types of RCDs, reviews their clinical efficacy in cancer treatment, explores their anticancer mechanisms, and discusses the feasibility of some newly discovered RCDs for cancer treatment in combination with the immune and tumor microenvironment.
A Metabolism-Related Gene Landscape Predicts Prostate Cancer Recurrence and Treatment Response
Authors: Zhou Lijie , Fan Ruixin , Luo Yongbo , Zhang Cai , Jia Donghui , Wang Rongli , Zeng Youmiao , Ren Mengda , Du Kaixuan , Pan Wenbang , Yang Jinjian , Tian Fengyan , Gu Chaohui
Published: March 2022

Background

Prostate cancer (PCa) is the most common malignant tumor in men. Although clinical treatments of PCa have made great progress in recent decades, once tolerance to treatments occurs, the disease progresses rapidly after recurrence. PCa exhibits a unique metabolic rewriting that changes from initial neoplasia to advanced neoplasia. However, systematic and comprehensive studies on the relationship of changes in the metabolic landscape of PCa with tumor recurrence and treatment response are lacking. We aimed to construct a metabolism-related gene landscape that predicts PCa recurrence and treatment response.

Methods

In the present study, we used differentially expressed gene analysis, protein–protein interaction (PPI) networks, univariate and multivariate Cox regression, and least absolute shrinkage and selection operator (LASSO) regression to construct and verify a metabolism-related risk model (MRM) to predict the disease-free survival (DFS) and response to treatment for PCa patients.

Results

The MRM predicted patient survival more accurately than the current clinical prognostic indicators. By using two independent PCa datasets (International Cancer Genome Consortium (ICGC) PCa and Taylor) and actual patients to test the model, we also confirmed that the metabolism-related risk score (MRS) was strongly related to PCa progression. Notably, patients in different MRS subgroups had significant differences in metabolic activity, mutant landscape, immune microenvironment, and drug sensitivity. Patients in the high-MRS group were more sensitive to immunotherapy and endocrine therapy, while patients in the low-MRS group were more sensitive to chemotherapy.

Conclusions

We developed an MRM, which might act as a clinical feature to more accurately assess prognosis and guide the selection of appropriate treatment for PCa patients. It is promising for further application in clinical practice.
Effects of Gut Microbiota on Host Adaptive Immunity Under Immune Homeostasis and Tumor Pathology State
Authors: Li Yanan , Ye Zixuan , Zhu Jianguo , Fang Shuguang , Meng Lijuan , Zhou Chen
Published: March 2022

Gut microbiota stimulate and shape the body’s adaptive immune response through bacterial components and its active metabolites, which orchestrates the formation and maintenance of the body’s immune homeostasis. In addition, the imbalances in microbiota-adaptive immunity contribute to the development of tumor and the antitumor efficiency of a series of antitumor therapies at the preclinical and clinical levels. Regardless of significant results, the regulation of gut microbiota on adaptive immunity in immune homeostasis and tumors needs a more thorough understanding. Herein, we highlighted the comprehensive knowledge, status, and limitations in the mechanism of microbiome interaction with adaptive immunity and put forward the prospect of how to translate these insights in inhibiting tumor progression and enhancing the efficacy of antitumor interventions.
Concurrent IgA Nephropathy and Membranous Nephropathy, Is It an Overlap Syndrome?
Authors: He Jia-Wei , Cui Dong-Feng , Zhou Xu-Jie , Chen Pei , Li Yang , Zhang Xue , Wang Yan-Na , Gan Ting , Liu Li-Jun , Shi Su-Fang , Zhu Li , Hou Ping , Lv Ji-Cheng , Zhang Hong
Published: March 2022

IgA nephropathy (IgAN) and membranous nephropathy (MN) are common glomerulonephritis, the presence of which in the same patient– concurrent of IgAN and MN (cIgAN/MN) has been described occasionally. This study aims to show clinical-pathological features of cIgAN/MN and attempts to suggest underlying pathogenesis using disease-specific biomarkers and a genomics approach. This retrospective cohort study described the clinical and pathological data from 137 patients with cIgAN/MN diagnosed in Peking University First Hospital from 2005 to 2019. One hundred primary IgAN and 100 MN cases were randomly selected as disease controls between the same time interval. Moreover, disease-specific biomarkers and polygenic risk score models were conducted to reveal the underlying pathogenesis. The median age of the cIgAN/MN cases was 45-year-old, and 46% were women. Compared to IgAN, patients with cIgAN/MN had a higher level of 24-hour proteinuria excretion but lower microscopic hematuria. They had a lower median level of galactose-deficient IgA1 (Gd-IgA1, 4.00 versus 5.45 μg/ml, P=0.002) as well as the standardized genetic risk scores of developing IgAN (GRSs: 0.05 versus 0.68, P<0.001). Compared to MN, patients with cIgAN/MN had a lower proportion of nephrotic syndrome and a lower level of albumin-to-creatinine ratio. However, the 24-hour proteinuria levels, serum lipid profiles, proportion of hypertension, and pathology classification were similar. Patients with cIgAN/MN had lower levels of plasma autoantibodies against the M-type transmembrane phospholipase A2 receptor (PLA2R) (11.23 versus 36.59 U/ml, P=0.005). Intriguingly, there were no statistical differences in standardized GRSs of developing MN between them (2.77 versus 3.02, P=0.326). Compared to IgAN, cIgAN/MN may lean towards MN more according to clinical-pathological features, disease-specific biomarker levels, and disease-specific genetic risk scores.
Bcl-3: A Double-Edged Sword in Immune Cells and Inflammation
Authors: Liu Hui , Zeng Lin , Yang Yang , Guo Chunlei , Wang Hui
Published: March 2022

The NF-κB transcription factor family controls the transcription of many genes and regulates a number of pivotal biological processes. Its activity is regulated by the IκB family of proteins. Bcl-3 is an atypical member of the IκB protein family that regulates the activity of nuclear factor NF-κB. It can promote or inhibit the expression of NF-κB target genes according to the received cell type and stimulation, impacting various cell functions, such as proliferation and differentiation, induction of apoptosis and immune response. Bcl-3 is also regarded as an environment-dependent cell response regulator that has dual roles in the development of B cells and the differentiation, survival and proliferation of Th cells. Moreover, it also showed a contradictory role in inflammation. At present, in addition to the work aimed at studying the molecular mechanism of Bcl-3, an increasing number of studies have focused on the effects of Bcl-3 on inflammation, immunity and malignant tumors in vivo. In this review, we focus on the latest progress of Bcl-3 in the regulation of the NF-κB pathway and its extensive physiological role in inflammation and immune cells, which may help to provide new ideas and targets for the early diagnosis or targeted treatment of various inflammatory diseases, immunodeficiency diseases and malignant tumors.
The Interplay Between Cervicovaginal Microbial Dysbiosis and Cervicovaginal Immunity
Authors: Wang Ya , Wang Xiaoli , Zhu Meiling , Ge Li , Liu Xiaochen , Su Kaikai , Chen Zhengzheng , Zhao Weidong
Published: March 2022

The cervicovaginal microbiota plays a key role in the health and reproductive outcomes of women. In reality epidemiological studies have demonstrated that there is an association between the structure of cervicovaginal microbiota and reproductive health, although key mechanistic questions regarding these effects remain unanswered and understanding the interplay between the immune system and the structure of the cervicovaginal microbiota. Here, we review existing literature relating to the potential mechanisms underlying the interaction between vaginal microbes and the immune system; we also describe the composition and function of the microbiome and explain the mechanisms underlying the interactions between these microbial communities and various aspects of the immune system. Finally, we also discuss the diseases that are caused by disorders of the reproductive tract and how the immune system is involved. Finally, based on the data presented in this review, the future perspectives in research directions and therapeutic opportunities are explored.
Marine Mammal Interactions With Fisheries: Review of Research and Management Trends Across Commercial and Small-Scale Fisheries
Authors: Jog Ketki , Sutaria Dipani , Diedrich Amy , Grech Alana , Marsh Helene
Published: March 2022

Marine mammal interactions with fisheries, such as bycatch and depredation, are a common occurrence across commercial and small-scale fisheries. We conducted a systematic review to assess the management responses to marine mammal interactions with fisheries. We analyzed literature between 1995 and 2021 to measure research trends in studies on direct and indirect interactions for: (i) high and low to middle-income countries, (ii) fishery operations (commercial and small-scale), and (iii) taxonomic groups. Management responses were categorized using the framework described previously in peer-reviewed studies. Marine mammal bycatch remains a major conservation concern, followed by marine mammal depredation of fishing gear. A high proportion of studies concentrated on commercial fisheries in high-income countries, with an increase in small-scale fisheries in low to middle-income countries between 1999 and 2020. The insufficient understanding of the social dimensions of interactions and the inevitable uncertainties concerning animal and human behaviors are major challenges to effective management. Despite the key role of human behavior and socioeconomics, we found only eight articles that incorporate human dimensions in the management context. Integrating social dimensions of marine mammal interactions with fisheries could help in setting pragmatic conservation priorities based on enhanced understanding of critical knowledge gaps. An area-specific adaptive management framework could be an effective tool in reducing the risk to marine mammals from fisheries by coupling technical solutions with socio-economic and political interventions. We conclude that despite the vast body of literature on this subject, a “silver bullet” management solution to marine mammal interactions with fisheries does not yet exist.
Wind Drifting vs. Pulsating Swimming Jellyfish: Respiratory Metabolism and Composition Differences in Physalis physalis, Velella velella, Aurelia aurita, and Pelagia noctiluca
Authors: Bondyale-Juez Daniel R. , Romero-Kutzner Vanesa , Purcell Jennifer E. , Martínez Ico , Packard Theodore T. , Gómez May
Published: March 2022

Physalia physalis and Velella velella, are among the few marine organisms that harness the wind for their locomotion, whereas other cnidarian jellyfish make use of their pulsating bell-shaped bodies to propel themselves through the seas. We investigate their composition and metabolism compared with two species of pulsating scyphozoan jellyfish, Aurelia aurita and Pelagia noctiluca. Protein (P), lipid (L), carbohydrate (K), and derived energy content (Ec), provided information on the biochemical composition of these species and their relevance as prey. Physiological respiration (R) from oxygen consumption. As well as potential respiration (Φ) from the electron transport system (ETS) activity and the derived respiratory carbon demand (RCD) and heterotrophic energy transformation (HET), allow the comparison of the impact of these two types of propulsion on the metabolism, along with the impact of these organisms as predators. In this study it was found that these hydrozoans depicted a different biochemical composition relative to other gelatinous zooplankton. Lower water content at around 90% was observed, while WM-specific P, L, K, and Ec were higher, showcasing new aspects of these species as prey. The lower R/P in P. physalis and V. velella (1.8 ± 0.7 and 2.9 ± 1.1 μL O2 h–1 mg Prot–1, respectively) and the low R/Φ, around 0.1, indicate lower respiration in wind-driven propulsion compared to pulsation-driven propulsion. Additionally, these results encourage the use and research on enzymatic techniques that are particularly useful for gelatinous research, and the calculation of RCD and HET helps in understanding the physiology and role played by the organisms as predators from carbon and energy perspectives.
Hyperopia-Correcting Phototherapeutic Keratectomy and Its Comparison With Conventional Phototherapeutic Keratectomy
Authors: Hayakawa Hideki , Kamiya Kazutaka , Tsujisawa Tatsuhiko , Takahashi Masahide , Shoji Nobuyuki
Published: March 2022

Purpose

To evaluate hyperopia-correcting phototherapeutic keratectomy (HC-PTK) and to compare the visual and refractive outcomes of HC-PTK and conventional PTK.

Methods

This study comprised a total of 72 eyes of 72 consecutive patients who underwent HC-PTK and conventional PTK for granular corneal dystrophy or band-shaped keratopathy. Preoperatively and 6 months postoperatively, we assessed visual acuity, manifest refraction, and mean keratometry, as well as postoperative corneal higher-order aberrations and adverse events in each PTK group, and compared these metrics between the two groups.

Results

LogMAR BSCVA significantly improved from 0.43 ± 0.47 preoperatively to 0.21 ± 0.38 postoperatively in the HC-PTK group (Wilcoxon signed-rank test, p < 0.001). It was also significantly improved from 0.22 ± 0.21 preoperatively to 0.15 ± 0.12 postoperatively in the conventional PTK group (p = 0.031). Mean refraction significantly changed from 0.27 ± 1.55 diopter (D) preoperatively to 0.50 ± 1.77 D postoperatively, in the HC-PTK group (p = 0.313). By contrast, it was significantly hyperopic from −0.15 ± 2.41 D preoperatively to 1.45 ± 2.46 D postoperatively, in the conventional PTK group (p < 0.001). No significant complications occurred in any case during the follow-up period.

Conclusion

Both HC-PTK and conventional PTK showed a significant improvement of BSCVA and no vision-threatening complications at any time in this series. HC-PTK significantly reduced a hyperopic shift in refraction compared with conventional PTK, suggesting its viability for patients requiring PTK, especially in consideration of preventing this hyperopic issue.
Is It a “Colon Perforation”? A Case Report and Review of the Literature
Authors: Lu Shuangshuang , Yao Xinyu , Shi Jun , Huang Jian , Zhuang Shaohua , Ma Junfang , Liu Yan , Zhang Wei , Yu Lifei , Zhu Ping , Zhu Qiuwei , Shi Ruxia , Zheng Hong , Shao Dong , Pan Yuyan , Bao Shizhen , Qin Li , Huang Lijie , Liu Wenjia , Huang Jin
Published: March 2022

Background

Intrauterine devices (IUDs) are commonly used as a contraceptive method. IUD migration and colon perforation are rare but serious complications occurring sometimes years after insertion.

Case

A 42-year-old woman with complaints of slight abdominal pain underwent a colonoscopy. Colonoscopy showed that a “nail” had penetrated the ascending colon wall and that an arm of the “nail” was embedded in the colon wall. We did not remove the “nail” rashly under colonoscopy. Considering the safety and effectiveness of the patient's operation, we were able to remove the “nail” easily by performing laparoscopic-endoscopic cooperative surgery (LECS) combined with hysteroscopy at the same time.

Conclusion

We report a case of successful removal of a colonic perforation device by colonoscopy, laparoscopy, and hysteroscopy, which is the first method used.
A Systematic Review of Deep Learning Techniques for Tuberculosis Detection From Chest Radiograph
Authors: Oloko-Oba Mustapha , Viriri Serestina
Published: March 2022

The high mortality rate in Tuberculosis (TB) burden regions has increased significantly in the last decades. Despite the possibility of treatment for TB, high burden regions still suffer inadequate screening tools, which result in diagnostic delay and misdiagnosis. These challenges have led to the development of Computer-Aided Diagnostic (CAD) system to detect TB automatically. There are several ways of screening for TB, but Chest X-Ray (CXR) is more prominent and recommended due to its high sensitivity in detecting lung abnormalities. This paper presents the results of a systematic review based on PRISMA procedures that investigate state-of-the-art Deep Learning techniques for screening pulmonary abnormalities related to TB. The systematic review was conducted using an extensive selection of scientific databases as reference sources that grant access to distinctive articles in the field. Four scientific databases were searched to retrieve related articles. Inclusion and exclusion criteria were defined and applied to each article to determine those included in the study. Out of the 489 articles retrieved, 62 were included. Based on the findings in this review, we conclude that CAD systems are promising in tackling the challenges of the TB epidemic and made recommendations for improvement in future studies.
Molecular Epidemiology and Antimicrobial Resistance of Clostridioides difficile in Hospitalized Patients From Mexico
Authors: Aguilar-Zamora Emmanuel , Weimer Bart C. , Torres Roberto C. , Gómez-Delgado Alejandro , Ortiz-Olvera Nayeli , Aparicio-Ozores Gerardo , Barbero-Becerra Varenka J. , Torres Javier , Camorlinga-Ponce Margarita
Published: March 2022

Clostridioides difficile is a global public health problem, which is a primary cause of antibiotic-associated diarrhea in humans. The emergence of hypervirulent and antibiotic-resistant strains is associated with the increased incidence and severity of the disease. There are limited studies on genomic characterization of C. difficile in Latin America. We aimed to learn about the molecular epidemiology and antimicrobial resistance in C. difficile strains from adults and children in hospitals of México. We studied 94 C. difficile isolates from seven hospitals in Mexico City from 2014 to 2018. Whole-genome sequencing (WGS) was used to determine the genotype and examine the toxigenic profiles. Susceptibility to antibiotics was determined by E-test. Multilocus sequence typing (MLST) was used to determine allelic profiles. Results identified 20 different sequence types (ST) in the 94 isolates, mostly clade 2 and clade 1. ST1 was predominant in isolates from adult and children. Toxigenic strains comprised 87.2% of the isolates that were combinations of tcdAB and cdtAB (tcdA+/tcdB+/cdtA+/cdtB+, followed by tcdA+/tcdB+/cdtA−/cdtB−, tcdA−/tcdB+/cdtA−/ cdtB−, and tcdA−/tcdB−/cdtA+/cdtB+). Toxin profiles were more diverse in isolates from children. All 94 isolates were susceptible to metronidazole and vancomycin, whereas a considerable number of isolates were resistant to clindamycin, fluroquinolones, rifampicin, meropenem, and linezolid. Multidrug-resistant isolates (≥3 antibiotics) comprised 65% of the isolates. The correlation between resistant genotypes and phenotypes was evaluated by the kappa test. Mutations in rpoB and rpoC showed moderate concordance with resistance to rifampicin and mutations in fusA substantial concordance with fusidic acid resistance. cfrE, a gene recently described in one Mexican isolate, was present in 65% of strains linezolid resistant, all ST1 organisms. WGS is a powerful tool to genotype and characterize virulence and antibiotic susceptibility patterns.
The Negative Effects of Feces-Associated Microorganisms on the Fitness of the Stored Product Mite Tyrophagus putrescentiae
Authors: Green Stefan J. , Nesvorna Marta , Hubert Jan
Published: March 2022

Feces have been suggested as a major source of microorganisms for recolonization of the gut of stored product mites via coprophagy. The mites can host microorganisms that decrease their fitness, but their transmission is not known. To address the role of fecal microbiota on mite fitness, we performed an experimental study in which the surfaces of mite (Tyrophagus putrescentiae) eggs were sterilized. Mites eggs (15 per experimental box) were then hatched and grown on feedstock with and without feces. These experiments were conducted with four distinct T. putrescentiae populations (5L, 5K, 5N, and 5P), and mite population density after 21 day of cultivation was used to assess mite fitness and the impact of fecal microbiota on fitness. Population density was not affected by the presence of feces in two of the cultures (5L and 5K), while significant effects of feces were observed in the other cultures (5N and 5P). Mite culture microbial communities were analyzed using cultivation-independent next-generation amplicon sequencing of microbial 16S and 18S ribosomal RNA (rRNA) genes in the fitness influenced populations (5N and 5P). Several microbial taxa were associated with fecal treatments and reduced mite fitness, including Staphylococcus and Bartonella-like bacteria, and the fungal genera Yamadazyma, Candida, and Aspergillus. Although coprophagy is the transmission route mites used to obtain beneficial gut bacteria such as Bartonella-like organisms, the results of this study demonstrate that fecal-associated microorganisms can have negative effects on some populations of T. putrescentiae fitness, and this may counteract the positive effects of gut symbiont acquisition.
PaP1, a Broad-Spectrum Lysin-Derived Cationic Peptide to Treat Polymicrobial Skin Infections
Authors: Heselpoth Ryan D. , Euler Chad W. , Fischetti Vincent A.
Published: March 2022

Most skin infections, including those complicating burns, are polymicrobial involving multiple causative bacteria. Add to this the fact that many of these organisms may be antibiotic-resistant, and a simple skin lesion or burn could soon become life-threatening. Membrane-acting cationic peptides from Gram-negative bacteriophage lysins can potentially aid in addressing the urgent need for alternative therapeutics. Such peptides natively constitute an amphipathic region within the structural composition of these lysins and function to permit outer membrane permeabilization in Gram-negative bacteria when added externally. This consequently allows the lysin to access and degrade the peptidoglycan substrate, resulting in rapid hypotonic lysis and bacterial death. When separated from the lysin, some of these cationic peptides kill sensitive bacteria more effectively than the native molecule via both outer and cytoplasmic membrane disruption. In this study, we evaluated the antibacterial properties of a modified cationic peptide from the broad-acting lysin PlyPa01. The peptide, termed PaP1, exhibited potent in vitro bactericidal activity toward numerous high priority Gram-positive and Gram-negative pathogens, including all the antibiotic-resistant ESKAPE pathogens. Both planktonic and biofilm-state bacteria were sensitive to the peptide, and results from time-kill assays revealed PaP1 kills bacteria on contact. The peptide was bactericidal over a wide temperature and pH range and could withstand autoclaving without loss of activity. However, high salt concentrations and complex matrices were found to be largely inhibitory, limiting its use to topical applications. Importantly, unlike other membrane-acting antimicrobials, PaP1 lacked cytotoxicity toward human cells. Results from a murine burn wound infection model using methicillin-resistant Staphylococcus aureus or multidrug-resistant Pseudomonas aeruginosa validated the in vivo antibacterial efficacy of PaP1. In these studies, the peptide enhanced the potency of topical antibiotics used clinically for treating chronic wound infections. Despite the necessity for additional preclinical drug development, the collective data from our study support PaP1 as a potential broad-spectrum monotherapy or adjunctive therapy for the topical treatment of polymicrobial infections and provide a foundation for engineering future lysin-derived peptides with improved antibacterial properties.