bluuebunny/crossref_metadata_2025 huggingface dataset:
Living in Temporary Ponds Loading Giant Genomes: The Neotropical Annual Killifish Genus Austrolebias as New Outstanding Evolutionary Model
Authors: García Graciela , Gutiérrez Verónica , Ríos Néstor
Published: June 2022

The term Annual killifish describes a short-lived and amazing group of vertebrates inhabiting temporary ponds exposed to an extremely variable environment during its short lifespan in South America and Africa, leading to the death of the entire adult population during the dry season. Austrolebias is a specious genus of the family Rivulidae, with ∼58 currently recognized species, extensively distributed in the temperate Neotropical region. Herein, we reviewed different aspects of the evolutionary biology with emphasis on the genome dynamic linked to the burst speciation process in this genus. Austrolebias constitutes an excellent model to study the genomic evolutionary processes underlying speciation events, since all the species of this genus analyzed so far share an unusually large genome size, with an average DNA content of 5.95 ± 0.45 picograms per diploid cell (mean C-value of about 2.98 pg). The drastic nuclear DNA–increasing would be associated with a considerable proportion of transposable elements (TEs) found in the Austrolebias genomes. The genomic proportion of the moderately repetitive DNA in the A. charrua genome represents approximately twice (45%) the amount of the repetitive components of the highly related sympatric and syntopic rivulinae taxon Cynopoecilus melanotaenia (25%), as well as from other rivulids and actinopterygian fish. These events could explain the great genome instability, the high genetic diversity, chromosome variability, as well as the morphological diversity in species of Austrolebias. Thus, species of this genus represent new model systems linking different evolutionary processes: drastic genome increase, massive TEs genomic representation, high chromosome instability, occurrence of natural hybridization between sister species, and burst speciation events.
Autoimmune Cytopenias in Common Variable Immunodeficiency Are a Diagnostic and Therapeutic Conundrum: An Update
Authors: Chawla Sanchi , Barman Prabal , Tyagi Rahul , Jindal Ankur Kumar , Sharma Saniya , Rawat Amit , Singh Surjit
Published: June 2022

Common variable immunodeficiency (CVID) is the most common symptomatic primary immunodeficiency (PID). CVID is a heterogenous condition and clinical manifestations may vary from increased susceptibility to infections to autoimmune manifestations, granulomatous disease, polyclonal lymphoproliferation, and increased risk of malignancy. Autoimmune manifestations may, at times, be the first and only clinical presentation of CVID, resulting in diagnostic dilemma for the treating physician.

Autoimmune cytopenias (autoimmune haemolytic anaemia and/or thrombocytopenia) are the most common autoimmune complications seen in patients with CVID. Laboratory investigations such as antinuclear antibodies, direct Coomb’s test and anti-platelet antibodies may not be useful in patients with CVID because of lack of specific antibody response. Moreover, presence of autoimmune cytopenias may pose a significant therapeutic challenge as use of immunosuppressive agents can be contentious in these circumstances. It has been suggested that serum immunoglobulins must be checked in all patients presenting with autoimmune cytopenia such as immune thrombocytopenia or autoimmune haemolytic anaemia.

It has been observed that patients with CVID and autoimmune cytopenias have a different clinical and immunological profile as compared to patients with CVID who do not have an autoimmune footprint. Monogenic defects have been identified in 10-50% of all patients with CVID depending upon the population studied. Monogenic defects are more likely to be identified in patients with CVID with autoimmune complications. Common genetic defects that may lead to CVID with an autoimmune phenotype include nuclear factor kappa B subunit 1 (NF-kB1), Lipopolysaccharide (LPS)-responsive beige-like anchor protein (LRBA), cytotoxic T lymphocyte antigen 4 (CTLA4), Phosphoinositide 3-kinase (PI3K), inducible T-cell costimulatory (ICOS), IKAROS and interferon regulatory factor-2 binding protein 2 (IRF2BP2).

In this review, we update on recent advances in pathophysiology and management of CVID with autoimmune cytopenias.
Identification of Key Genes as Early Warning Signals of Acute Myocardial Infarction Based on Weighted Gene Correlation Network Analysis and Dynamic Network Biomarker Algorithm
Authors: Song Chenxi , Qiao Zheng , Chen Luonan , Ge Jing , Zhang Rui , Yuan Sheng , Bian Xiaohui , Wang Chunyue , Liu Qianqian , Jia Lei , Fu Rui , Dou Kefei
Published: June 2022

Purpose

The specific mechanisms and biomarkersunderlying the progression of stable coronary artery disease (CAD) to acute myocardial infarction (AMI) remain unclear. The current study aims to explore novel gene biomarkers associated with CAD progression by analyzing the transcriptomic sequencing data of peripheral blood monocytes in different stages of CAD.

Material and Methods

A total of 24 age- and sex- matched patients at different CAD stages who received coronary angiography were enrolled, which included 8 patients with normal coronary angiography, 8 patients with angiographic intermediate lesion, and 8 patients with AMI. The RNA from peripheral blood monocytes was extracted and transcriptome sequenced to analyze the gene expression and the differentially expressed genes (DEG). A Gene Oncology (GO) enrichment analysis was performed to analyze the biological function of genes. Weighted gene correlation network analysis (WGCNA) was performed to classify genes into several gene modules with similar expression profiles, and correlation analysis was carried out to explore the association of each gene module with a clinical trait. The dynamic network biomarker (DNB) algorithm was used to calculate the key genes that promote disease progression. Finally, the overlapping genes between different analytic methods were explored.

Results

WGCNA analysis identified a total of nine gene modules, of which two modules have the highest positive association with CAD stages. GO enrichment analysis indicated that the biological function of genes in these two gene modules was closely related to inflammatory response, which included T-cell activation, cell response to inflammatory stimuli, lymphocyte activation, cytokine production, and the apoptotic signaling pathway. DNB analysis identified a total of 103 genes that may play key roles in the progression of atherosclerosis plaque. The overlapping genes between DEG/WGCAN and DNB analysis identified the following 13 genes that may play key roles in the progression of atherosclerosis disease: SGPP2, DAZAP2, INSIG1, CD82, OLR1, ARL6IP1, LIMS1, CCL5, CDK7, HBP1, PLAU, SELENOS, and DNAJB6.

Conclusions

The current study identified a total of 13 genes that may play key roles in the progression of atherosclerotic plaque and provides new insights for early warning biomarkers and underlying mechanisms underlying the progression of CAD.
The Promise of Targeting Hypoxia to Improve Cancer Immunotherapy: Mirage or Reality?
Authors: Janji Bassam , Chouaib Salem
Published: June 2022

Almost all solid tumors display hypoxic areas in the tumor microenvironment associated with therapeutic failure. It is now well established that the abnormal growth of malignant solid tumors exacerbates their susceptibility to hypoxia. Therefore, targeting hypoxia remains an attractive strategy to sensitize tumors to various therapies. Tumor cell adaptions to hypoxia are primarily mediated by hypoxia-inducible factor-1 alpha (HIF-1α). Sensing hypoxia by HIF-1α impairs the apoptotic potential of tumor cells, thus increasing their proliferative capacity and contributing to the development of a chaotic vasculature in the tumor microenvironment. Therefore, in addition to the negative impact of hypoxia on tumor response to chemo- and radio-therapies, hypoxia has also been described as a major hijacker of the tumor response by impairing the tumor cell susceptibility to immune cell killing. This review is not intended to provide a comprehensive overview of the work published by several groups on the multiple mechanisms by which hypoxia impairs the anti-tumor immunity and establishes the immunosuppressive tumor microenvironment. There are several excellent reviews highlighting the value of targeting hypoxia to improve the benefit of immunotherapy. Here, we first provide a brief overview of the mechanisms involved in the establishment of hypoxic stress in the tumor microenvironment. We then discuss our recently published data on how targeting hypoxia, by deleting a critical domain in HIF-1α, contributes to the improvement of the anti-tumor immune response. Our aim is to support the current dogma about the relevance of targeting hypoxia in cancer immunotherapy.
Differential Engraftment of Parental A20 PD-L1 WT and PD-L1 KO Leukemia Cells in Semiallogeneic Recipients in the Context of PD-L1/PD-1 Interaction and NK Cell-Mediated Hybrid Resistance
Authors: del Rio Maria-Luisa , Perez-Simon Jose-Antonio , Rodriguez-Barbosa Jose-Ignacio
Published: June 2022

The contribution of natural killer (NK) cells to tumor rejection in the context of programmed death-ligand 1/programmed death 1 (PD-L1/PD-1) blockade is a matter of intense debate. To elucidate the role of PD-L1 expression on tumor cells and the functional consequences of engaging PD-1 receptor on cytotoxic cells, PD-L1 expression was genetically inactivated and WT or PD-L1-deficient parental tumor cells were adoptively transferred intravenously into F1 recipients. The engraftment of PD-L1-deficient A20 tumor cells in the spleen and liver of F1 recipients was impaired compared with A20 PD-L1 WT tumor counterparts. To elucidate the mechanism responsible for this differential tumor engraftment and determine the relevance of the role of the PD-L1/PD-1 pathway in the interplay of tumor cells/NK cells, a short-term competitive tumor implantation assay in the peritoneal cavity of semiallogeneic F1 recipients was designed. The results presented herein showed that NK cells killed target tumor cells with similar efficiency regardless of PD-L1 expression, whereas PD-L1 expression on A20 tumor cells conferred significant tumor protection against rejection by CD8 T cells confirming the role of the co-inhibitory receptor PD-1 in the modulation of their cytotoxic activity. In summary, PD-L1 expression on A20 leukemia tumor cells modulates CD8 T-cell-mediated responses to tumor-specific antigens but does not contribute to inhibit NK cell-mediated hybrid resistance, which correlates with the inability to detect PD-1 expression on NK cells neither under steady-state conditions nor under inflammatory conditions.
Naive T Cells in Graft Versus Host Disease and Graft Versus Leukemia: Innocent or Guilty?
Authors: Dekker Linde , Sanders Evy , Lindemans Caroline A. , de Koning Coco , Nierkens Stefan
Published: June 2022

The outcome of allogeneic hematopoietic cell transplantation (allo-HCT) largely depends on the development and management of graft-versus-host disease (GvHD), infections, and the occurrence of relapse of malignancies. Recent studies showed a lower incidence of chronic GvHD and severe acute GvHD in patients receiving naive T cell depleted grafts compared to patients receiving complete T cell depleted grafts. On the other hand, the incidence of acute GvHD in patients receiving cord blood grafts containing only naive T cells is rather low, while potent graft-versus-leukemia (GvL) responses have been observed. These data suggest the significance of naive T cells as both drivers and regulators of allogeneic reactions. The naive T cell pool was previously thought to be a quiescent, homogenous pool of antigen-inexperienced cells. However, recent studies showed important differences in phenotype, differentiation status, location, and function within the naive T cell population. Therefore, the adequate recovery of these seemingly innocent T cells might be relevant in the imminent allogeneic reactions after allo-HCT. Here, an extensive review on naive T cells and their contribution to the development of GvHD and GvL responses after allo-HCT is provided. In addition, strategies specifically directed to stimulate adequate reconstitution of naive T cells while reducing the risk of GvHD are discussed. A better understanding of the relation between naive T cells and alloreactivity after allo-HCT could provide opportunities to improve GvHD prevention, while maintaining GvL effects to lower relapse risk.
Neutrophil Infiltration Characterized by Upregulation of S100A8, S100A9, S100A12 and CXCR2 Is Associated With the Co-Occurrence of Crohn’s Disease and Peripheral Artery Disease
Authors: Yao Ziping , Zhang Bihui , Niu Guochen , Yan Ziguang , Tong Xiaoqiang , Zou Yinghua , Li Yuan , Yang Min
Published: June 2022

Background

Crohn’s disease (CD) and peripheral arterial disease (PAD) are closely related. The pathophysiological mechanisms underlying the coexistence of CD and PAD are unknown. The aim of this study was to investigate the key molecules and pathways mediating the co-occurrence of CD and PAD through quantitative bioinformatic analysis of a public RNA sequencing database.

Methods

Datasets of CD (GSE111889) and PAD (GSE120642) were downloaded from the Gene Expression Omnibus (GEO) database. Differentially expressed genes (DEGs) were analyzed using the ‘edgeR’ and ‘limma’ packages of R. Gene Ontology and Kyoto Encyclopedia analyses of common DEGs were performed to explore the functions of DEGs. Protein–protein interaction (PPI) networks were established by the Search Tool for the Retrieval of Interacting Genes (STRING) database and visualized by Cytoscape. Hub genes were selected using the plugin cytoHubba. Hub gene validation was performed in GSE95095 for CD and GSE134431 for PAD. Receiver operating characteristic curves were used to evaluate the predictive values of the hub genes. Gene set enrichment analysis and immune infiltration of the hub genes were performed.

Results

A total of 54 common DEGs (2 downregulated and 52 upregulated) were identified. Pathways of neutrophil chemotaxis, neutrophil migration and cytokine and cytokine receptors were enriched in CD and PAD. S100A8, S100A9, S100A12 and CXCR2 were identified as hub genes after validation, with all area under the curve > 0.7 for both CD and PAD. Neutrophil infiltration was associated with upregulation of the hub genes. Pathways of immune processes, including neutrophil activation, neutrophil chemotaxis, neutrophil migration were significantly correlated with high expression of S100A8, S100A9, S100A12 and CXCR2 in both CD and PAD.

Conclusions

This bioinformatic study elucidates S100A8, S100A9, S100A12 and CXCR2 as hub genes for the co-occurrence of Crohn’s disease and peripheral artery disease. Inflammation and immune regulation modulated by neutrophil infiltration play a central role in the development of CD and PAD and may be potential targets for diagnosis and treatment.
Gestational Diabetes Mellitus Changes Human Colostrum Immune Composition
Authors: Avellar Ana Carolina de Sena , Oliveira Mariana Naves , Caixeta Felipe , Souza Rafaela Cristina Vieira e , Teixeira Andréa , Faria Ana Maria Caetano , Silveira-Nunes Gabriela , Faria Elaine Spezialli , Maioli Tatiani Uceli
Published: June 2022

Breast milk is considered a complete food for babies. Up to 7 days postpartum, it is known as colostrum, rich in immunological compounds, responsible for providing nutrition and ensuring immune protection. However, some maternal factors, such as gestational diabetes mellitus (GDM), can change the concentration of bioactive compounds present in the colostrum and may affect the development of the newborn’s immune system. The effect of GDM on colostrum cytokine, chemokine, and growth factors is not well described. Thus, the present study evaluated whether the occurrence of GDM changes the concentration of biomarkers in the colostrum. A cross-sectional study was carried out on postpartum women who had healthy pregnancies and women who had been diagnosed with GDM. A sample of colostrum was collected for Luminex analysis. Our results showed that GDM mothers had higher secretion of cytokines and chemokines in the colostrum, with a higher concentration of IFN-g, IL-6, and IL-15, and a lower concentration of IL-1ra. Among growth factors, we identified a decreased concentration of GM-CSF in the colostrum of GDM mothers. Thus, the data obtained support the idea that the disease leads to immune alterations in the colostrum.
Role of CNSs Conserved Distal Cis-Regulatory Elements in CD4 + T Cell Development and Differentiation
Authors: Long Xunyi , Luo Chen , Zhu Zhengming
Published: June 2022

Naïve CD4+ T cells differentiate into diverse subsets of effector cells and perform various homeostatic and immune functions. The differentiation and maintenance of these different subsets are controlled through the upregulation and silencing of master genes. Mechanistic studies of the regulation of these master genes identified conserved and distal intronic regulatory elements, which are accessible subsets of conserved non-coding sequences (CNSs), acting as cis-regulatory elements in a lineage-specific manner that controls the function of CD4+ T cells. Abnormal CNS activity is associated with incorrect expression of master genes and development of autoimmune diseases or immune suppression. Here, we describe the function of several conserved, distal cis-regulatory elements at the Foxp3, Rorc, Il-4, Il-10 and Il-17 gene locus were shown to play important roles in CD4+ T cells differentiation. Together, this review briefly outlines currently known CNSs, with a focus on their regulations and functions in complexes modulating the differentiation and maintenance of various CD4+ T cells subsets, in health and disease contexts, as well as during the conversion of T regulatory cells to T helper 17 cells. This article will provide a comprehensive view of CNSs conserved distal cis-regulatory elements at a few loci that control aspects of CD4+ T cells function.
Using Oyster Shells for Customized 3-D Structures for Monitoring Ecosystem Shifts on Ascidians Diversity
Authors: Marques Luisa , Teixeira Guilherme , Calado Ricardo , Lillebø Ana Isabel
Published: June 2022

Biofouling communities are broadly distributed and there is a growing need to understand, monitor, and prevent their dispersal and colonization. Ascidians are a major group of fouling organisms but have remained poorly studied in this context. Furthermore, the search for improved sustainable practices regarding shipping networks, biofouling management, treatments, and monitorization has made headway rapidly. The present study surveyed and established a baseline for the ascidian biofouling community in a coastal lagoon, by operationalizing the concept of artificial substrate units (ASU) through a customized 3-D unit with the shape of a triangular-based pyramid, a nature-based structure that simulates natural habitats, made with oyster shells sourced from local aquaculture farms. The ASU were grouped into a five-replicate star-shaped, to be collected at each sampling moment. Throughout the 295 days (from May to December of 2020) of the present study covering five different locations of Ria de Aveiro (Portugal) coastal lagoon, a total of 12 species of ascidians were collected. While Ascidiella aspersa, Microcosmus sp., and Molgula sp. 1 were registered in all the locations surveyed, the remaining nine ascidian species were dominant only in specific locations of the coastal lagoon. Values of total abundance presented an overall increasing trend in all locations surveyed, with maximum values corresponding to summer periods. Two locations (Oyster Farm and Integrated Multi-Trophic Aquaculture Farm) recorded the highest abundance values. The present findings demonstrated that the ASU employed using oyster shells, a widely available co-product of oyster farming, can be considered an efficient support structure for short- or long-term monitoring of the ascidian community, as well as fouling communities in general. Hydrodynamics, seasonality, and nutrient-enriched waters were the main contributors to the establishment of ascidians. For the first time, Clavelina lepadiformis and A. aspersa were collected and reported in coastal waters of mainland Portugal. While preventing the settlement of fouling communities can be extremely difficult, an improved understanding of existing communities of these organisms can undoubtedly contribute to the development of improved management practices to control them. An updated list of all ascidian species recorded to date from coastal waters of mainland Portugal is also presented.
Characteristics and Prognosis of Antibody Non-responders With Coronavirus Disease 2019
Authors: Ding Junyu , Liu Changxin , Wang Zhao , Guo Hua , Zhang Kan , Ma Lin , Wang Bo , Zhao Huijun , Song Manya , Guan Xizhou
Published: June 2022

Background

Coronavirus disease 2019 (COVID-19), caused by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), has been spreading globally. Information regarding the characteristics and prognosis of antibody non-responders to COVID-19 is limited.

Methods

In this retrospective, single-center study, we included all patients with confirmed COVID-19 using real-time reverse transcriptase-polymerase chain reaction (RT-PCR) admitted to the Fire God Mountain hospital from February 3, 2020, to April 14, 2020. A total of 1,921 patients were divided into the antibody-negative (n = 94) and antibody-positive (n = 1,827) groups, and 1:1 propensity score matching was used to match the two groups.

Results

In the antibody-negative group, 40 patients (42.6%) were men, and 49 (52.1%) were older than 65 years. Cough was the most common symptom in the antibody negative group. White blood cell counts, neutrophils, C-reactive protein, procalcitonin, interleukin-6, lactate dehydrogenase, creatine kinase, creatine kinase isoenzyme, urea nitrogen, and creatinine were significantly higher in the antibody-negative patients than in the antibody-positive group (P < 0.005). The number of days of nucleic acid-negative conversion in the antibody-negative group was shorter than that in the antibody-positive group (P < 0.001). The hospitalization time of the antibody-negative patients was shorter than that of the antibody-positive patients (P < 0.001).

Conclusion

Some COVID-19 patients without specific antibodies had mild symptoms; however, the inflammatory reaction caused by innate clinical immunity was more intense than those associated with antibodies. Non-specific immune responses played an essential role in virus clearance. There was no direct correlation between excessive inflammatory response and adverse outcomes in patients. The risk of reinfection and vaccination strategies for antibody-negative patients need to be further explored.
SARS-CoV-2 in Kidney Transplant Patients: A Real-Life Experience
Authors: Pinchera Biagio , Spirito Lorenzo , Ferreri Lucia , Rocca Roberto La , Celentano Giuseppe , Buonomo Antonio Riccardo , Foggia Maria , Scotto Riccardo , Federico Stefano , Gentile Ivan , Carrano Rosa ,   “Federico II” COVID-19 Team
Published: June 2022

Background

The COVID-19 pandemic has significantly impacted the management of solid organ transplant recipients and on clinical evolution in post-transplantation. Little is known on the impact of SARS-CoV-2 infection in these patients. The severity and lethality of this disease in solid organ transplant patients are higher thanin the general population. This study aims to describe clinical characteristics of SARS-CoV-2 infection in solid organ transplant recipients followed in our center.

Methods

In this observational study, we enrolled all kidney transplant recipientsattending the A.O.U. Federico II of Naples from March 2020 to January 2021. For each patient we evaluated the epidemiological and clinical characteristics as well as outcome.

Results

We enrolled 369 kidney transplant patients (229, male, 62%). Of these, 51 (13.8%) acquired SARS-CoV-2 infection and 29 showed symptomatic disease. Of the 51 patients with the infection, 48 (94.11%) had at least one comorbidity and such comorbidities did not constitute a risk factor for a more severe disease. Hospitalization was necessary for 7 (13.7%) patients. Of these, 2 required low-flow oxygen supplementation, 3 non-invasive/high flow ventilation and 2 invasive ventilation. Finally, 2 patients died.

Conclusions

Our study shows a lower mortality and hospitalization rate compared to figures available in the literature (4% vs. 13–30% and 14% vs. 32–100%, respectively). Furthermore, the comorbidities examined (hypertension, dyslipidemia, and diabetes) did not constitute a risk factor for a more severe disease condition in this patient category. Further studies with larger sample size are necessary to confirm these data.
Risk Factors for the Onset of Frozen Shoulder in Middle-Aged and Elderly Subjects Within 1 Year of Discharge From a Hospitalization That Involved Intravenous Infusion: A Prospective Cohort Study
Authors: Cao Wenping , Chen Jiangnan , Pu Jianfeng , Fan Yunwu , Cao Ye
Published: June 2022

Aim

To investigate the incidence of frozen shoulder and risk factors for the onset of frozen shoulder in middle-aged and elderly subjects within 1 year of discharge from a hospitalization that involved intravenous infusion in Zhangjiagang Second People's Hospital.

Methods

A total of 1,900 subjects who were discharged from a hospitalization that involved intravenous infusion in the hospital between May 2020 and September 2020 met the inclusion criteria for this study: 950 subjects had a mean daily duration of intravenous infusion ≤ 2 h (low exposure) and 950 subjects had a mean daily duration of intravenous infusion ≥3 h (high exposure). Subjects were followed up by telephone at 6 months ± 1 week and 12 months ± 1 week after discharge the incidence of frozen shoulder.

Results

The cumulative incidence rate of frozen shoulder within 1 year of discharge was 5.2%. Multivariate logistic regression analysis revealed the risk of frozen shoulder was higher in subjects with a mean daily duration of intravenous infusion ≥3 h compared to ≤ 2 h (OR = 3.082, 95% CI 1.919–4.949, P < 0.001); subjects hospitalized for 11–30 days had a higher risk of frozen shoulder compared to those hospitalized for 10 days or less (OR = 6.836, 95%CI 4.363–10.709, P < 0.001); subjects who were overweight/ obese (BMI ≥ 25 kg/m2) had a higher risk of frozen shoulder compared to those of normal weight (BMI 18.5–24.9 kg/m2) (OR = 2.166, 95%CI 1.376–3.410, P = 0.001); subjects in the 56–70-year-old age group had a higher risk of developing frozen shoulder compared to those in the 40–55-year-old age group (OR = 1.977, 95%CI 1.154–3.387, P = 0.013); diabetes increased the risk of frozen shoulder (OR = 3.009, 95%CI 1.826–4.959, P < 0.001). The 71–85 years old age group and hypertension were statistically significant in univariate analysis but not in multivariate analysis (P > 0.05).

Conclusion

Compared with middle-aged and elderly in the general population, middle-aged and elderly subjects who received intravenous infusion during a hospitalization had a higher cumulative incidence rate of frozen shoulder within 1 year after discharge. Independent risk factors for the onset of frozen shoulder included mean daily duration of intravenous infusion ≥3 h, length of hospital stay 11–30 days, BMI ≥ 25 kg/m2, age 56–70 years, and diabetes.
The Role of Ultrasound in Temporomandibular Joint Disorders: An Update and Future Perspectives
Authors: Maranini Beatrice , Ciancio Giovanni , Mandrioli Stefano , Galiè Manlio , Govoni Marcello
Published: June 2022

Temporomandibular joint (TMJ) disorder is the second most common chronic pain condition affecting the general population after back pain. It encompasses a complex set of conditions, manifesting with jaw pain and limitation in mouth opening, influencing chewing, eating, speaking, and facial expression. TMJ dysfunction could be related to mechanical abnormalities or underlying inflammatory arthropathies, such as rheumatoid arthritis (RA) or juvenile idiopathic arthritis (JIA). TMJ exhibits a complex anatomy, and thus a thorough investigation is required to detect the TMJ abnormalities. Importantly, TMJ involvement can be completely asymptomatic during the early stages of the disease, showing no clinically detectable signs, exposing patients to delayed diagnosis, and progressive irreversible condylar damage. For the prevention of JIA complications, early diagnosis is therefore essential. Currently, magnetic resonance imaging (MRI) is described in the literature as the gold standard method to evaluate TMJ. However, it is a high-cost procedure, not available in all centers, and requires a long time for image acquisition, which could represent a problem notably in the pediatric population. It also suffers restricted usage in patients with claustrophobia. Ultrasonography (US) has emerged in recent years as an alternative diagnostic method, as it is less expensive, not invasive, and does not demand special facilities. In this narrative review, we will investigate the power of US in TMJ disorders based on the most relevant literature data, from an early screening of TMJ changes to differential diagnosis and monitoring. We then propose a potential algorithm to optimize the management of TMJ pathology, questioning what would be the role of ultrasonographic study.
Identifying Distinct Risk Thresholds of Glycated Hemoglobin and Systolic Blood Pressure for Rapid Albuminuria Progression in Type 2 Diabetes From NHANES (1999–2018)
Authors: Xu Jiahui , Xue Yan , Chen Qingguang , Han Xu , Cai Mengjie , Tian Jing , Jin Shenyi , Lu Hao
Published: June 2022

Background

It is widely recognized that glycated hemoglobin (HbA1c) and systolic blood pressure (SBP) are two key risk factors for albuminuria and renal function impairment in patients with type 2 diabetes mellitus (T2DM). Our study aimed to identify the specific numerical relationship of albumin/creatinine ratio (ACR) with HbA1c and SBP among a large population of adults with T2DM.

Method

A total of 8,626 patients with T2DM were included in the data analysis from the National Health and Nutrition Examination Surveys (NHANES) (1999-2018). The multiple linear regressions were used to examine the associations of ACR with HbA1c and SBP. Generalized additive models with smooth functions were performed to identify the non-linear relations between variables and interactions were also tested.

Results

Significantly threshold effects were observed between ACR and HbA1c or SBP after multivariable adjustment, with the risk threshold values HbA1c = 6.4% and SBP = 127 mmHg, respectively. Once above thresholds were exceeded, the lnACR increased dramatically with higher levels of HbA1c (β = 0.23, 95 CI%:0.14, 0.32, P < 0.001) and SBP (β = 0.03, 95 CI%:0.03, 0.04, P < 0.001). Subgroup analysis showed high protein diet was related to higher ACR. In addition, a higher risk of ACR progression was observed in central obesity participants with HbA1C ≥ 6.4% or hyperuricemia participants with SBP ≥ 127 mmHg among patients withT2DM.

Conclusion

We identified thresholds of HbA1c and SBP to stratify patients with T2DM through rapid albuminuria progression. These might provide a clinical reference value for preventing and controlling diabetes kidney disease.
Gut Microbiome Differences in Rescued Common Kestrels (Falco tinnunculus) Before and After Captivity
Authors: Zhang Kangqing , Wang Xinxiang , Gong Xiang , Sui Jinling
Published: June 2022

Gut microbes significantly impact animal health, yet research on the gut microbiota of most birds, especially raptors, is lacking. This study investigated the effects of dietary and environmental changes on the composition and abundance of gut microbiota in 17 rescued common kestrels (Falco tinnunculus) through 16S rRNA gene high-throughput sequencing of microorganisms in the feces of the birds. Firmicutes (relative abundance, 43.63%), Proteobacteria (37.26%), Actinobacteria (7.31%), and Bacteroidetes (5.48%) were the dominant phyla in the gut microbiota of the common kestrels. A comparison of the gut microbiota before and after captivity revealed that community composition and abundance of the common kestrel gut microbiota differed among different living conditions including diet and environment. At the phylum level, the abundance of Firmicutes was higher (P < 0.05), and that of Proteobacteria was lower (P < 0.05), after captivity (54.62 and 27.16%, respectively) compared with before captivity (33.67 and 46.41%, respectively), but no significant differences were found among other phyla. At the genus level, the abundance of Lactobacillus was higher (P < 0.05) after captivity (15.77%) compared with the abundance before captivity (5.02%). Hierarchical clustering and principal component analyses showed that common kestrels in different living conditions exhibited differences (P < 0.05) in gut microbiota at phylum and genus levels. Functional prediction of gene sequences using PICRUSt2 further revealed that pathways related to glucose metabolism and amino acid metabolism were enhanced (P < 0.05) after captivity. Collectively, the findings from this study demonstrated that the relative abundance of specific microbes in the gut of the rescued common kestrels either increased or decreased, and that dietary and environment changes might be the predominant factors affecting the gut microbiota of these birds during rescue or captivity.
Arginine Catabolism and Polyamine Biosynthesis Pathway Disparities Within Francisella tularensis Subpopulations
Authors: Yue Yinshi , Puniya Bhanwar Lal , Helikar Tomáš , Girardo Benjamin , Hinrichs Steven H. , Larson Marilynn A.
Published: June 2022

Francisella tularensis is a highly infectious zoonotic pathogen with as few as 10 organisms causing tularemia, a disease that is fatal if untreated. Although F. tularensis subspecies tularensis (type A) and subspecies holarctica (type B) share over 99.5% average nucleotide identity, notable differences exist in genomic organization and pathogenicity. The type A clade has been further divided into subtypes A.I and A.II, with A.I strains being recognized as some of the most virulent bacterial pathogens known. In this study, we report on major disparities that exist between the F. tularensis subpopulations in arginine catabolism and subsequent polyamine biosynthesis. The genes involved in these pathways include the speHEA and aguAB operons, along with metK. In the hypervirulent F. tularensis A.I clade, such as the A.I prototype strain SCHU S4, these genes were found to be intact and highly transcribed. In contrast, both subtype A.II and type B strains have a truncated speA gene, while the type B clade also has a disrupted aguA and truncated aguB. Ablation of the chromosomal speE gene that encodes a spermidine synthase reduced subtype A.I SCHU S4 growth rate, whereas the growth rate of type B LVS was enhanced. These results demonstrate that spermine synthase SpeE promotes faster replication in the F. tularensis A.I clade, whereas type B strains do not rely on this enzyme for in vitro fitness. Our ongoing studies on amino acid and polyamine flux within hypervirulent A.I strains should provide a better understanding of the factors that contribute to F. tularensis pathogenicity.
Mini Review: Risk Assessment, Clinical Manifestation, Prediction, and Prognosis of Mucormycosis: Implications for Pathogen- and Human-Derived Biomarkers
Authors: Acosta-España Jaime David , Voigt Kerstin
Published: June 2022

Mucormycosis is a fungal disease caused by members of the fungal order Mucorales, which are abundantly found in terrestrial environments. The fungi propagate clonally via mitospores, which are transmitted to humans through the air and cause superficial or invasive infections. The disease has emerged in recent years and coincides generally with immunosuppression on the patient side. Mucormycosis is still rarely recognized in the clinical because of its unspecific symptoms which often triggers misdiagnosis with bacterial or viral infections leading to prolonged therapeutic cycles and loss of valuable time to manage mucormycosis properly. Infected patients develop various clinical forms, most notably ranging from rhinocerebral via pulmonary to gastrointestinal forms. Traditional diagnosis is based on culture and histopathologic examinations of the affected tissue. But, the achievement of a precise result is time-consuming, labor-intensive, requires mycological expertise and the finding appears often too late. A rapid and precise diagnosis is mandatory because symptoms are non-specific and the disease is rapidly progressing with often fatal outcome. Mucormycosis was increasingly associated with other infections and underlying conditions and risk factors causing comorbidities, which are difficult to successfully manage. This mini-review summarizes the current knowledge on the epidemiology and causative agents of mucormycosis, transmission, risk factors, clinical presentation, diagnosis, and highlights the lack of appropriate biomarkers on the pathogen and the host sides for rapid pathogen and host susceptibility detection, respectively. Fungal antigens and single nucleotide polymorphisms (SNPs) in human host genes are useful for the assessment of susceptibility. This mini-review addresses possibilities for early prediction of susceptibility to mucormycosis based on forecasting of the risk of infection with fungal pathogens other than Mucorales. The topic of early prediction and diagnosis of mucormycosis represents a current research gap and highlights the importance of potential future developments in the area of risk assessment, susceptibility prognosis in conjunction with early diagnosis to reduce mortality in patients suffering from mucormycosis.
Perspectives on Converting Keratin-Containing Wastes Into Biofertilizers for Sustainable Agriculture
Authors: Li Qingxin
Published: June 2022

Keratin-containing wastes become pollution to the environment if they are not treated properly. On the other hand, these wastes can be converted into value-added products applicable to many fields. Organic fertilizers and biofertilizers are important for sustainable agriculture by providing nutrients to enhance the growth speed of the plant and production. Keratin-containing wastes, therefore, will be an important resource to produce organic fertilizers. Many microorganisms exhibit capabilities to degrade keratins making them attractive to convert keratin-containing wastes into valuable products. In this review, the progress in microbial degradation of keratins is summarized. In addition, perspectives in converting keratin into bio- and organic fertilizers for agriculture are described. With proper treatment, feather wastes which are rich in keratin can be converted into high-value fertilizers to serve as nutrients for plants, reduce environmental pressure and improve the quality of the soil for sustainable agriculture.
The Molecular Mechanism of Yellow Mushroom (Floccularia luteovirens) Response to Strong Ultraviolet Radiation on the Qinghai-Tibet Plateau
Authors: Guo Jing , Xie Zhanling , Jiang Hongchen , Xu Hongyan , Liu Baolong , Meng Qing , Peng Qingqing , Tang Yongpeng , Duan Yingzhu
Published: June 2022

The Qinghai-Tibet Plateau (QTP) is the highest plateau in the world, and its ultraviolet (UV) radiation is much greater than that of other regions in the world. Yellow mushroom (Floccularia luteovirens) is a unique and widely distributed edible fungus on the QTP. However, the molecular mechanism of F. luteovirens’s response to strong UV radiation remains unclear. Herein, we reported the 205 environmental adaptation and information processing genes from genome of F. luteovirens. In addition, we assembled the RNA sequence of UV-affected F. luteovirens at different growth stages. The results showed that in response to strong UV radiation, a total of 11,871 significantly different genes were identified, of which 4,444 genes in the vegetative mycelium (VM) stage were significantly different from the young fruiting bodies (YFB) stage, and only 2,431 genes in the YFB stage were significantly different from fruiting bodies (FB) stage. A total of 225 differentially expressed genes (DEGs) were found to be involved in environmental signal transduction, biochemical reaction preparation and stress response pathway, pigment metabolism pathway, and growth cycle regulation, so as to sense UV radiation, promote repair damage, regulate intracellular homeostasis, and reduce oxidative damage of UV radiation. On the basis of these results, a molecular regulation model was proposed for the response of F. luteovirens to strong UV radiation. These results revealed the molecular mechanism of adaptation of F. luteovirens adapting to strong UV radiation, and provided novel insights into mechanisms of fungi adapting to extreme environmental conditions on the QTP; the production the riboflavin pigment of the endemic fungi (Yellow mushroom) in the QTP was one of the response to extreme environment of the strong UV radiation.
Mitochondrial Dysfunction in Parkinson’s Disease: From Mechanistic Insights to Therapy
Authors: Gao Xiao-Yan , Yang Tuo , Gu Ying , Sun Xiao-Hong
Published: June 2022

Parkinson’s disease (PD) is one of the most common neurodegenerative movement disorders worldwide. There are currently no cures or preventative treatments for PD. Emerging evidence indicates that mitochondrial dysfunction is closely associated with pathogenesis of sporadic and familial PD. Because dopaminergic neurons have high energy demand, cells affected by PD exhibit mitochondrial dysfunction that promotes the disease-defining the loss of dopaminergic neurons in the substantia nigra pars compacta (SNpc). The mitochondrion has a particularly important role as the cellular “powerhouse” of dopaminergic neurons. Therefore, mitochondria have become a promising therapeutic target for PD treatments. This review aims to describe mitochondrial dysfunction in the pathology of PD, outline the genes associated with familial PD and the factors related to sporadic PD, summarize current knowledge on mitochondrial quality control in PD, and give an overview of therapeutic strategies for targeting mitochondria in neuroprotective interventions in PD.
Age Effects on Old/New Recognition Memory Involving Abstract Figures and Non-words
Authors: Toth Monika , Sambeth Anke , Blokland Arjan
Published: June 2022

Age-related memory problems posit a growing concern in our society. This study investigated the impact of age and memory strength on recognition memory of pre-experimentally unfamiliar abstract figures and non-words. We applied a three-phase old/new recognition memory paradigm and manipulated memory strength as a function of the Levels of Processing (deep vs. shallow) and repetition. Older adults relative to the young showed impairment in the correct identification of new items. As indicated by the lower discriminability indexes, the older adults also had difficulties discriminating the strongly (drawn/semantically processed) and the weakly (studied) embedded abstract figures but not the non-words. Age-related differences in reaction times were only evident with the abstract figures. Finally, our results revealed that the recognition performance was equally affected by memory strength in both age groups. The current findings agree with previous research on age-related impairment in new item recognition, which can be attributed to misrecollection and decreased sensitivity to novelty in the older adults than the young. The detected age effects on the discriminability of the drawn and studied abstract figures agree with the age-related impairment in the perceptual encoding hypothesis and support the notion related to the need for environmental support to reduce age effects. The lack of age effects with the non-words indicates that age effects on discriminability are stimulus-dependent. The current results support the notion that recognition memory in aging is only impaired under certain conditions and depends on the stimuli used.
General and Specific Aversive Modulation of Active Avoidance Require Central Amygdala
Authors: Kim Ian T. , Farb Claudia , Hou Mian , Prasad Sunanda , Talley Elyse , Cook Savannah , Campese Vincent D.
Published: June 2022

Three studies provide evidence that the central nucleus of the amygdala, a structure with a well-established role in conditioned freezing, is also required for conditioned facilitation of instrumental avoidance in rats. First, the immediate early gene c-Fos was measured following the presentation of a previously shock-paired tone in subjects trained either on an unsignaled avoidance task or not (in addition to tone only presentations in naïve controls). Significantly elevated expression of c-Fos was found in both the avoidance trained and Pavlovian trained conditions relative to naïve controls (but with no difference between the two trained conditions). In a subsequent study, intracranial infusions of muscimol into the central amygdala significantly attenuated the facilitation of shock-avoidance by a shock-paired Pavlovian cue relative to pre-operative responding. The final study used a virogenetic approach to inhibit the central amygdala prior to testing. This treatment eliminated the transfer of motivational control over shock-avoidance by both a shock-paired Pavlovian stimulus, as well as a cue paired with a perceptually distinct aversive event (i.e., klaxon). These findings provide compelling support for a role of central amygdala in producing aversive Pavlovian-instrumental transfer.
Presenting Patterns of Genetically Determined Developmental Encephalopathies With Epilepsy and Movement Disorders: A Single Tertiary Center Retrospective Cohort Study
Authors: Mastrangelo Mario , Galosi Serena , Cesario Serena , Renzi Alessia , Campea Lucilla , Leuzzi Vincenzo
Published: June 2022

Background

This paper aimed to evaluate the frequency of observation of genetically determined developmental encephalopathies with epilepsy and movement disorders in a specialistic center, the distribution of etiologies and presenting clinical hallmarks, and the mean times for the achievement of molecular genetic diagnosis.

Patients and Methods

Retrospective data about clinical phenotypes, etiology, and diagnostic pathways were collected in all the genetically confirmed patients with developmental encephalopathies with epilepsy and movement disorders referred to our institution between 2010 and 2020. The cohort was divided into two groups according to the predominant movement disorder type: 1) Group A: patients with hyperkinetic movement disorders; 2) Group B: patients with hypokinetic movement disorders. Both groups were analyzed in terms of developmental, epileptic, and movement disorder phenotypes.

Results

The cohort included 69 patients (Group A = 53; Group B = 16). The etiological spectrum was heterogeneous with a predominance of Rett and Angelman syndrome in Group A and neurodegenerative disorders in Group B. A moderate/severe intellectual disability was assessed in 58/69 patients (mean age at the first signs of developmental impairment = 1,87 ± 1,72 years). Group A included patients with an earlier onset of epileptic seizures (2,63 ± 3,15 vs. 4,45 ± 5,55 years of group B) and a predominant generalized motor semiology of seizures at the onset. Focal seizures were the main initial epileptic manifestations in Group B. Seizures were noticed earlier than movement disorders in Group A while the opposite occurred in Group B. A higher increase in molecular genetic diagnosis was obtained in the last five years. Mean diagnostic delay was longer in Group B than in Group A (12,26 ± 13,32 vs. 5.66 ± 6.41 years). Chorea as an initial movement disorder was associated with a significantly longer diagnostic delay and a higher age at etiological diagnosis.

Conclusions

This study suggested: (a) a higher frequency of genetic defects involving neurotransmission, neuronal excitability, or neural development in patients with hyperkinetic movement disorders; (b) a higher frequency of neurodegenerative courses and a longer diagnostic delay in patients with hypokinetic movement disorders.