bluuebunny/crossref_metadata_2025 huggingface dataset:
Signature of seven cuproptosis-related lncRNAs as a novel biomarker to predict prognosis and therapeutic response in cervical cancer
Authors: Liu Xinyu , Zhou Lei , Gao Minghui , Dong Shuhong , Hu Yanan , Hu Chunjie
Published: September 2022

Background: Given the high incidence and high mortality of cervical cancer (CC) among women in developing countries, identifying reliable biomarkers for the prediction of prognosis and therapeutic response is crucial. We constructed a prognostic signature of cuproptosis-related long non-coding RNAs (lncRNAs) as a reference for individualized clinical treatment.

Methods: A total of seven cuproptosis-related lncRNAs closely related to the prognosis of patients with CC were identified and used to construct a prognostic signature via least absolute shrinkage and selection operator regression analysis in the training set. The predictive performance of the signature was evaluated by Kaplan–Meier (K-M) analysis, receiver operating characteristic (ROC) analysis, and univariate and multivariate Cox analyses. Functional enrichment analysis and single-sample gene set enrichment analysis were conducted to explore the potential mechanisms of the prognostic signature, and a lncRNA–microRNA–mRNA network was created to investigate the underlying regulatory relationships between lncRNAs and cuproptosis in CC. The associations between the prognostic signature and response to immunotherapy and targeted therapy were also assessed. Finally, the prognostic value of the signature was validated using the CC tissues with clinical information in my own center.

Results: A prognostic signature was developed based on seven cuproptosis-related lncRNAs, including five protective factors (AL441992.1, LINC01305, AL354833.2, CNNM3-DT, and SCAT2) and two risk factors (AL354733.3 and AC009902.2). The ROC curves confirmed the superior predictive performance of the signature compared with conventional clinicopathological characteristics in CC. The ion transport-related molecular function and various immune-related biological processes differed significantly between the two risk groups according to functional enrichment analysis. Furthermore, we discovered that individuals in the high-risk group were more likely to respond to immunotherapy and targeted therapies including trametinib and cetuximab than those in the low-risk group. Finally, CC tissues with clinical data from my own center further verify the robustness of the seven-lncRNA risk signature.

Conclusion: We generated a cuproptosis-related lncRNA risk signature that could be used to predict prognosis of CC patients. Moreover, the signature could be used to predict response to immunotherapy and chemotherapy and thus could assist clinicians in making personalized treatment plans for CC patients.
Immediate postpartum anemia and associated factors among women admitted to maternity ward at public hospitals in Harari Regional State, Eastern Ethiopia: A facility-based cross-sectional study
Authors: Abebe Gizaw Taddesse , Kure Mohammed Abdurke , Yadeta Tesfaye Assebe , Roba Kedir Teji , Amante Tariku Dingeta
Published: September 2022

Background

Anemia in the postpartum period remains a considerable public health problem in developing countries, particularly in sub-Saharan Africa. It is the most common indirect cause of maternal morbidity and mortality. It is also a major health problem in women of reproductive age, affecting their quality of life, occupational capacity, lactation, and immunological function. Immediate postpartum anemia has a significant impact on women's quality of life, although its predictors have received little attention in Ethiopia, notably in Harari Regional State. Therefore, this study aimed to determine its magnitude and contributing factors in Eastern Ethiopia.

Methods

A facility-based cross-sectional study was conducted from June 1stto August 30th, 2021, among 484 postpartum women admitted to two public hospitals in Harari Regional State, Eastern Ethiopia. Data were collected using a pre-tested, structured interviewer-administered questionnaire. About 2 mL of blood samples were collected and analyzed using the cell-Dyne 1,800 machine. The collected data were entered into Epi-Data version 4.6 and analyzed using SPSS version 25. A multivariable logistic regression analysis was conducted to estimate the effect of independent variables on immediate postpartum anemia. An adjusted odds ratio (AOR) with a 95% confidence interval (CI) was computed to report the presence of the association. Statistical significance was declared at ap-value of < 0.05.

Results

The overall magnitude of immediate postpartum anemia was 28.1% [95% CI (23.7, 32.1)]. Lack of formal education [AOR: 3.92; 95% CI: (1.85, 8.33)], having antenatal care < 4 visits [AOR: 3.18; 95% CI: (1.53, 6.61)], a history of cesarean delivery [AOR: 3.40; 95% CI: (1.89, 6.10)], a history of maternal blood loss [AOR: 4.78; 95% CI: (2.22, 10.30)], pre-delivery Hgb level < 11 g/dl [AOR:5.46; 95% CI: (3.09,9.67)], and having no iron-folate supplementation [AOR:3.27; 95% CI: (1.31, 8.15)] were factors statistically associated with immediate postpartum anemia.

Conclusions

In this study, nearly one-third of mothers admitted for postpartum care developed anemia within 48 h of giving birth. Women's educational level, frequency of antenatal care, mode of delivery, a history of maternal blood loss, pre-delivery hemoglobin level, and iron-folate supplementation status were identified as immediate postpartum anemia risk factors. Therefore, promoting the benefits of adequate antenatal care and iron-folate supplementation during pregnancy is crucial to avoiding the risks of postpartum anemia.
The NLRP3 inflammasome as a new target in respiratory disorders treatment
Authors: Leszczyńska Katarzyna , Jakubczyk Dominika , Górska Sabina
Published: September 2022

In recent years a continuous increase in new cases of respiratory disorders, such as rhinitis, asthma, and chronic obstructive pulmonary disease (COPD), has been observed. The exact pathomechanism of these diseases is still blurry, resulting in the lack of targeted and effective therapy. The conventional use of treatment strategies, such as antihistamine drugs and/or glucocorticosteroids act mainly symptomatically and have significant side effects. Specific allergen immunotherapy is only useful in the management of specific allergies and selected patients. Therefore, new therapeutic solutions are constantly being sought. The novelty of recent years has been the association between NLRP3 inflammasome activation and the development of airway inflammatory diseases. This seems to be an interesting therapeutic target that may support or even replace traditional therapies in the future. The review presented, discusses the contribution of NLRP3 inflammasome to the development of allergic rhinitis, allergic asthma, and COPD. Moreover, the modulatory properties of probiotics as potential inhibitors of NLRP3 inflammasome are emphasised.
Bifidobacterium breve intervention combined with environmental enrichment alleviates cognitive impairment by regulating the gut microbiota and microbial metabolites in Alzheimer’s disease mice
Authors: Zhu Guangsu , Guo Min , Zhao Jianxin , Zhang Hao , Wang Gang , Chen Wei
Published: September 2022

Alzheimer’s disease (AD) is characterized by behavioral and cognitive impairments and its increasing prevalence imposes a healthcare burden on society. To date, most intervention studies have only focused on a single AD-related factor and have yielded modest cognitive improvements. Here, we show that environmental enrichment (EE) training combined with Bifidobacterium breve CCFM1025 intervention significantly alleviated amyloid-β (Aβ)-induced cognitive impairment and inhibited neuroinflammation in mice. Moreover, we found that EE combined with B. breve CCFM1025 treatment restored AD-associated gut microbiota dysbiosis and reversed microbial metabolites changes. By integrating behavioral and neurological data with metabolomic profiles, we corroborated the microbiota–metabolite–brain interactions, with acetate and tryptophan metabolism as potential drivers. Taken together, our results provide a promising multidomain intervention strategy to prevent cognitive decline and delay the progression of AD through a combination of dietary microbiome-based approaches and lifestyle interventions.
Engineered cord blood megakaryocytes evade killing by allogeneic T-cells for refractory thrombocytopenia
Authors: Kumar Bijender , Afshar-Kharghan Vahid , Mendt Mayela , Sackstein Robert , Tanner Mark R. , Popat Uday , Ramdial Jeremy , Daher May , Jimenez Juan , Basar Rafet , Melo Garcia Luciana , Shanley Mayra , Kaplan Mecit , Wan Xinhai , Nandivada Vandana , Reyes Silva Francia , Woods Vernikka , Gilbert April , Gonzalez-Delgado Ricardo , Acharya Sunil , Lin Paul , Rafei Hind , Banerjee Pinaki Prosad , Shpall Elizabeth J.
Published: September 2022

The current global platelet supply is often insufficient to meet all the transfusion needs of patients, in particular for those with alloimmune thrombocytopenia. To address this issue, we have developed a strategy employing a combination of approaches to achieve more efficient production of functional megakaryocytes (MKs) and platelets collected from cord blood (CB)-derived CD34+ hematopoietic cells. This strategy is based on ex-vivo expansion and differentiation of MKs in the presence of bone marrow niche-mimicking mesenchymal stem cells (MSCs), together with two other key components: (1) To enhance MK polyploidization, we used the potent pharmacological Rho-associated coiled-coil kinase (ROCK) inhibitor, KD045, resulting in liberation of increased numbers of functional platelets both in-vitro and in-vivo; (2) To evade HLA class I T-cell-driven killing of these expanded MKs, we employed CRISPR-Cas9-mediated β-2 microglobulin (β2M) gene knockout (KO). We found that coculturing with MSCs and MK-lineage-specific cytokines significantly increased MK expansion. This was further increased by ROCK inhibition, which induced MK polyploidization and platelet production. Additionally, ex-vivo treatment of MKs with KD045 resulted in significantly higher levels of engraftment and donor chimerism in a mouse model of thrombocytopenia. Finally, β2M KO allowed MKs to evade killing by allogeneic T-cells. Overall, our approaches offer a novel, readily translatable roadmap for producing adult donor-independent platelet products for a variety of clinical indications.
Dynamic changes of cytokine profiles and virological markers during 48 weeks of entecavir treatment for HBeAg-positive chronic hepatitis B
Authors: Li Minghui , Gao Yuanjiao , Yang Liu , Lin Yanjie , Deng Wen , Jiang Tingting , Bi Xiaoyue , Lu Yao , Zhang Lu , Shen Ge , Liu Ruyu , Wu Shuling , Chang Min , Xu Mengjiao , Hu Leiping , Song Rui , Jiang Yuyong , Yi Wei , Xie Yao
Published: September 2022

Objective

The aims of this study were to investigate the kinetic changes of serum, virological, and immunological markers during entecavir (ETV) antiviral therapy and to explore whether these indicators can predict the antiviral efficacy of ETV in hepatitis B e antigen (HBeAg)-positive chronic hepatitis B (CHB) patients.

Methods

HBeAg-positive CHB patients were enrolled and treated with ETV 0.5 mg/day. Clinical biochemical, virological, and serological tests were performed at baseline and every 12 weeks during the 48-week treatment. Plasma levels of cytokines (Flt-3L, IFN-α2, IFN-γ, IL-10, IL-17A, IL-6, TGF-β1, TGF-β2, TGF-β3, and TNF-α) were measured at baseline and at 12 and 24 weeks after treatment. Analysis of the trends of these clinical indicators in ETV antiviral therapy was performed.

Results

A total of 105 HBeAg-positive CHB patients were enrolled, and 100 of them completed 48 weeks of ETV treatment and follow-up. After 48 weeks of treatment, hepatitis B s antigen (HBsAg) decline ≥ 1 log10 was found in seven patients, but no patient achieved HBsAg disappearance. serological HBeAg disappeared in 13 patients, and serological HBeAg transformed in 3 patients. The baseline HBsAg and HBeAg levels, HBV DNA load, IL-10, and TGF-β1 levels in the complete virological response group were lower than those in the incomplete virological response group, while the ALT level in the complete virological response group was higher than that in the incomplete virological response group. Both univariate analysis and multivariate analysis showed that baseline biochemical indexes, virological indexes, and cytokine levels had no correlation with the complete virological response at 48 weeks. In multivariate analysis, low baseline HBV DNA load, and HBeAg and IL-10 levels were significantly associated with ALT normalization after 48 weeks of ETV treatment (HBeAg OR = 1.003, 95% CI 1.001–1.006, p = 0.007; HBV DNA OR = 0.184, 95% CI 0.046–0.739, p = 0.017; IL-10 OR = 0.040, 95% CI 0.972–0.999, p = 0.040).

Conclusion

Cytokine levels changed dynamically during ETV antiviral therapy. Low baseline HBV DNA load, and HBeAg and IL-10 levels were significantly associated with ALT normalization after 48 weeks of ETV treatment.
Research progress of risk factors and early diagnostic biomarkers of gout-induced renal injury
Authors: Wang Sheng , Zhang Liyun , Hao Dongsheng , Wang Lei , Liu Jiaxi , Niu Qing , Mi Liangyu , Peng Xinyue , Gao Jinfang
Published: September 2022

Gout renal injury has an insidious onset, no obvious symptoms, and laboratory abnormalities in the early stages of the disease. The injury is not easily detected, and in many cases, the patients have entered the renal failure stage at the time of diagnosis. Therefore, the detection of gout renal injury–related risk factors and early diagnostic biomarkers of gout renal injury is essential for the prevention and early diagnosis of the disease. This article reviews the research progress in risk factors and early diagnostic biomarkers of gout renal injury.
Increased sIL-2Rα leads to obstruction of IL-2 biological function and Treg cells differentiation in SLE patients via binding to IL-2
Authors: Long Dan , Yu Shujiao , Zhang Lu , Guo Yang , Xu Shumin , Rao Yuting , Huang Zikun , Luo Qing , Li Junming
Published: September 2022

Background

The decrease of IL-2 level is believed to play an important role in the disease occurrence and development of SLE, but the relevant mechanisms have not been fully clarified. Many studies have found that the level of soluble interleukin 2 receptor α (sIL-2Rα) in SLE patients is significantly increased. Considering the fact that sIL-2Rα has the ability to bind IL-2, we want to know whether the increased sIL-2Rα has some impact on the level and function of IL-2 in SLE patients.

Methods

New onset SLE patients, treated SLE patients and healthy volunteers were recruited. The levels of serum IL-2, IL-2 mRNA in CD3+T cells and serum sIL-2Rα were detected and compared in these subjects. Two mixed solid-phase sandwich ELISA system were designed to measure exclusively the heterodimers complex of sIL-2Rα/IL-2. The sera from SLE patients were pretreated with or without immune complex dissociation solution and detected for IL-2 levels. IL-2 standard or serum from HCs were used to co-incubate with recombinant sIL-2Rα or serum samples with high levels of sIL-2Rα and detected for IL-2 levels by ELISA. The inhibitory effect of sIL-2Rα on IL-2 biological activity was investigated by CTLL-2 cell proliferation assay. The frequencies and absolute counts of Treg cells were detected by flow cytometry before and after the addition of recombinant sIL-2Rα.

Results

The levels of serum IL-2 in SLE patients were significantly decreased and negatively correlated with SLEDAI. However, there was no significant difference in IL-2 mRNA levels in CD3+T cells between SLE patients and healthy controls. The levels of serum sIL-2Rα in SLE patients were significantly increased, positively correlated with the SLEDAI and negatively correlated with the levels of serum IL-2. sIL-2Rα was shown to bind to IL-2 to form immune complex, resulting in false reduction in the detection level of serum IL-2 and significant decrease in biological activity of IL-2. The increase of sIL-2Rα was demonstrated to be one of the important mechanisms for the obstruction of Treg cells differentiation in SLE patients.

Conclusion

Increased serum sIL-2Rα can bind to IL-2, leading to obstruction of IL-2 activity and Treg cells differentiation.
IL12 immune therapy clinical trial review: Novel strategies for avoiding CRS-associated cytokines
Authors: Jia Zhiliang , Ragoonanan Dristhi , Mahadeo Kris Michael , Gill Jonathan , Gorlick Richard , Shpal Elizabeth , Li Shulin
Published: September 2022

Interleukin 12 (IL-12) is a naturally occurring cytokine that plays a key role in inducing antitumor immune responses, including induction of antitumor immune memory. Currently, no IL-12-based therapeutic products have been approved for clinical application because of its toxicities. On the basis of this review of clinical trials using primarily wild-type IL-12 and different delivery methods, we conclude that the safe utilization of IL-12 is highly dependent on the tumor-specific localization of IL-12 post administration. In this regard, we have developed a cell membrane-anchored and tumor-targeted IL-12-T (attIL12-T) cell product for avoiding toxicity from both IL-12 and T cells-induced cytokine release syndrome in peripheral tissues. A phase I trial using this product which seeks to avoid systemic toxicity and boost antitumor efficacy is on the horizon. Of note, this product also boosts the impact of CAR-T or TCR-T cell efficacy against solid tumors, providing an alternative approach to utilize CAR-T to overcome tumor resistance.
Comprehensive analysis of m6A/m5C/m1A-related gene expression, immune infiltration, and sensitivity of antineoplastic drugs in glioma
Authors: Zhao Kai , Li Wenhu , Yang Yongtao , Hu Xinyue , Dai Ying , Huang Minhao , Luo Ji , Zhang Kui , Zhao Ninghui
Published: September 2022

This research aims to develop a prognostic glioma marker based on m6A/m5C/m1A genes and investigate the potential role in the tumor immune microenvironment. Data for patients with glioma were downloaded from The Cancer Genome Atlas (TCGA) and Chinese Glioma Genome Atlas (CGGA). The expression of genes related to m6A/m5C/m1A was compared for normal and glioma groups. Gene Ontology and Kyoto Encyclopedia of Genes and Gene enrichment analysis of differentially expressed genes were conducted. Consistent clustering analysis was performed to obtain glioma subtypes and complete the survival analysis and immune analysis. Based on TCGA, Lasso regression analysis was used to obtain a prognostic model, and the CGGA database was used to validate the model. The model-based risk scores and the hub genes with the immune microenvironment, clinical features, and antitumor drug susceptibility were investigated. The clinical glioma tissues were collected to verify the expression of hub genes via immunohistochemistry. Twenty genes were differentially expressed, Consensus cluster analysis identified two molecular clusters. Overall survival was significantly higher in cluster 2 than in cluster 1. Immunological analysis revealed statistically significant differences in 26 immune cells and 17 immune functions between the two clusters. Enrichment analysis detected multiple meaningful pathways. We constructed a prognostic model that consists of WTAP, TRMT6, DNMT1, and DNMT3B. The high-risk and low-risk groups affected the survival prognosis and immune infiltration, which were related to grade, gender, age, and survival status. The prognostic value of the model was validated using another independent cohort CGGA. Clinical correlation and immune analysis revealed that four hub genes were associated with tumor grade, immune cells, and antitumor drug sensitivity, and WTAP was significantly associated with microsatellite instability(MSI). Immunohistochemistry confirmed the high expression of WTAP, DNMT1, and DNMT3B in tumor tissue, but the low expression of TRMT6. This study established a strong prognostic marker based on m6A/m5C/m1A methylation regulators, which can accurately predict the prognosis of patients with gliomas. m6A/m5C/m1A modification mode plays an important role in the tumor microenvironment, can provide valuable information for anti-tumor immunotherapy, and have a profound impact on the clinical characteristics.
From protein-protein interactions to immune modulation: Therapeutic prospects of targeting Neuropilin-1 in high-grade glioma
Authors: Smith Gregory T. , Radin Daniel P. , Tsirka Stella E.
Published: September 2022

In the past several years there has been a marked increase in our understanding of the pathophysiological hallmarks of glioblastoma development and progression, with specific respect to the contribution of the glioma tumor microenvironment to the rapid progression and treatment resistance of high-grade gliomas. Despite these strides, standard of care therapy still only targets rapidly dividing tumor cells in the glioma, and does little to curb the pro-tumorigenic functions of non-cancerous cells entrenched in the glioma microenvironment. This tumor promoting environment as well as the heterogeneity of high-grade gliomas contribute to the poor prognosis of this malignancy. The interaction of non-malignant cells in the microenvironment with the tumor cells accentuate phenotypes such as rapid proliferation or immunosuppression, so therapeutically modulating one target expressed on one cell type may be insufficient to restrain these rapidly developing neoplasias. With this in mind, identifying a target expressed on multiple cell types and understanding how it governs tumor-promoting functions in each cell type may have great utility in better managing this disease. Herein, we review the physiology and pathological effects of Neuropilin-1, a transmembrane co-receptor which mediates signal transduction pathways when associated with multiple other receptors. We discuss its effects on the properties of endothelial cells and on immune cell types within gliomas including glioma-associated macrophages, microglia, cytotoxic T cells and T regulatory cells. We also consider its effects when elaborated on the surface of tumor cells with respect to proliferation, stemness and treatment resistance, and review attempts to target Neuroplin-1 in the clinical setting.
Grouper TRIM23 exerts antiviral activity against iridovirus and nodavirus
Authors: Zhi Linyong , Wang Wenji , Zheng Jiaying , Liu Shanxing , Zhou Sheng , Qin Qiwei , Huang Youhua , Huang Xiaohong
Published: September 2022

TRIM (tripartite motif) proteins have been demonstrated to exert critical roles in host defense against different microbial pathogens. Among them, TRIM23 acts as an important regulatory factor in antiviral immune and inflammatory responses, but the roles of fish TRIM23 against virus infection still remain largely unknown. Here, we investigated the characteristics of TRIM23 homolog from orange spotted grouper (Epinephelus coioides) (EcTRIM23). EcTRIM23 encoded a 580 amino acid peptide, which shared 93.1%, 89.73% and 86.36% identity with golden perch (Perca flavescens), zebrafish (Danio rerio) and human (Homo sapiens), respectively. The transcription levels of EcTRIM23 were significantly up-regulated in response to Singapore grouper iridovirus (SGIV) and red-spotted grouper nervous necrosis virus (RGNNV) infection. EcTRIM23 overexpression in vitro significantly inhibited RGNNV and SGIV replication, evidenced by the delayed cytopathic effect (CPE) progression and the decreased expression of viral core genes. EcTRIM23 significantly increased the expression levels of interferon (IFN) related signaling molecules and pro-inflammatory cytokines, as well as the promoter activities of IFN and NF-κB, suggesting that EcTRIM23 exerted antiviral function by positively regulating host IFN response. Exogenous EcTRIM23 exhibited either diffuse or aggregated localization in grouper cells. After co-transfection, TANK binding kinase 1 (TBK1), TNF receptor associated factor (TRAF) 3 and TRAF4, TRAF5 and TRAF6 were found to interact with EcTRIM23 in grouper cells. Moreover, these proteins could be recruited and co-localized with EcTRIM23 in vitro. Together, our results demonstrated that fish TRIM23 exerted antiviral activity against fish viruses by interacting with multiple host proteins to regulate immune responses.
HUGE pipeline to measure temporal genetic variation in Drosophila suzukii populations for genetic biocontrol applications
Authors: Feltman Nathan R. , Burkness Eric C. , Ebbenga Dominique N. , Hutchison William D. , Smanski Michael J.
Published: September 2022

Understanding the fine-scale genome sequence diversity that exists within natural populations is important for developing models of species migration, temporal stability, and range expansion. For invasive species, agricultural pests, and disease vectors, sequence diversity at specific loci in the genome can impact the efficacy of next-generation genetic biocontrol strategies. Here we describe a pipeline for haplotype-resolution genetic variant discovery and quantification from thousands of Spotted Wing Drosophila (Drosophila suzukii, SWD) isolated at two field sites in the North-Central United States (Minnesota) across two seasons. We observed highly similar single nucleotide polymorphism (SNP) frequencies at each genomic location at each field site and year. This supports the hypotheses that SWD overwinters in Minnesota, is annually populated by the same source populations or a combination of both theories. Also, the stable genetic structure of SWD populations allows for the rational design of genetic biocontrol technologies for population suppression.
Effect of hot etching with HF on the surface topography and bond strength of zirconia
Authors: Liang Zhuoran , Liu Yang , Jiang Yulin , Liu Pan , Zhang Yannan , Meng Fanhao , Liu Min , Cui Zhi , Ma Jinbao , Chen Jianfeng
Published: September 2022

Zirconia has occupied an increasingly important role in oral clinical applications in recent years. However, how to achieve the ideal bonding effect of zirconia is a significant problem that needs to be solved urgently in oral clinics. Hot etching treatment of zirconia is a hot spot of current research, but it is still unclear about the optimal acid solution and the effect of hot etching on the surface topography and bond strength of zirconia. This study evaluated the effect of hot etching with HF and HCl on the surface topography, roughness, crystalline phase, zirconia/resin cement interfacial evaluation and shear bond strength of zirconia. The results showed that the hot etching groups produced completely different topographical changes on the surface of zirconia than the sandblasting group. Obvious interfacial cracks were observed in the sandblasting group. The HF hot etching group achieved the highest roughness values (78.17 ± 4.94 nm) and the highest shear bond strength (25.09 ± 4.09 MPa). Compared with HCl, hot etching with HF could achieve more uniform and dense porous morphology, greater roughness and shear bond strength. Moreover, there were no prominent zirconia/resin cement interfacial cracks and crystal phase transformations on the surface of zirconia.
Hurdles and limitations for design of a radial permeameter conforming to the benchmark requirements
Authors: Sousa Pedro , Lomov Stepan V. , Ivens Jan
Published: September 2022

Experimental permeability measurements saw a considerable increase in accuracy when recommendations and guidelines were imposed upon the realization of two international benchmarks. Such requirements aid the design stage and experimental validation of a permeameter rig however, systematic errors in the measurements still compromise the comparability of measurements obtained by different radial permeameter rigs. Owing to hurdles and limitations in the data acquisition system, validation of the mold cavity and fluid injection system, optical errors in the visual tracking of a flow front, and uncertainties in the measurement of the fluid viscosity, the measurement’s accuracy is yet lower than the required for a standardized process. In this study, the detailed study and calibration of such parameters was able to identify and minimize error sources that would otherwise result in undetected systematic deviations from the expected results. In conclusion, the verification proposed by the radial benchmark does not guarantee the accuracy of the measurement, as the error in the instruments proposed for the verification is comparable to the requirements themselves. This creates a certain uncertainty in the verification that needs to be tackled with more detailed measurement protocols to ensure not only the compliance with the measurement requirements but also to set the limits of the attainable accuracy. The rig was validated by measuring the permeability of the fabric reinforcements used in the radial benchmark exercise. Due to the scattering in the results reported in the benchmark exercise, 13 out of the 19 reported values were excluded to obtain a good estimation of the expected permeability for each volume fraction. Although the rig complied with all recommendations currently in place, the obtained permeability showed a 20% deviation in the K1 direction, while the K2 was within the expected range for the average value. The observed deviation was later found to be caused by an optical distortion, which affected the measurement of the real-world flow front dimensions. A correction for this deviation needs further systematic investigation, also a possible revision of the future standard since a correction for optical distortions is yet not included in the measurement guidelines.
Sickle cell disease chronic joint pain: Clinical assessment based on maladaptive central nervous system plasticity
Authors: Lopes Tiago da Silva , Ballas Samir K. , Santana Jamille Evelyn Rodrigues Souza , de Melo-Carneiro Pedro , Oliveira Lilian Becerra de , Sá Katia Nunes , Lopes Larissa Conceição Dias , Silva Wellington dos Santos , Lucena Rita , Baptista Abrahão Fontes
Published: September 2022

Chronic joint pain (CJP) is among the significant musculoskeletal comorbidities in sickle cell disease (SCD) individuals. However, many healthcare professionals have difficulties in understanding and evaluating it. In addition, most musculoskeletal evaluation procedures do not consider central nervous system (CNS) plasticity associated with CJP, which is frequently maladaptive. This review study highlights the potential mechanisms of CNS maladaptive plasticity related to CJP in SCD and proposes reliable instruments and methods for musculoskeletal assessment adapted to those patients. A review was carried out in the PubMed and SciELO databases, searching for information that could help in the understanding of the mechanisms of CNS maladaptive plasticity related to pain in SCD and that presented assessment instruments/methods that could be used in the clinical setting by healthcare professionals who manage chronic pain in SCD individuals. Some maladaptive CNS plasticity mechanisms seem important in CJP, including the impairment of pain endogenous control systems, central sensitization, motor cortex reorganization, motor control modification, and arthrogenic muscle inhibition. Understanding the link between maladaptive CNS plasticity and CJP mechanisms and its assessment through accurate instruments and methods may help healthcare professionals to increase the quality of treatment offered to SCD patients.
An Updated Review of Recent Advances in Neurosyphilis
Authors: Zhou Jia , Zhang Hanlin , Tang Keyun , Liu Runzhu , Li Jun
Published: September 2022

Neurosyphilis is caused by Treponema pallidum invading the central nervous system, of which the incidence is increasing worldwide. Due to its variable clinical manifestations, diagnosis of neurosyphilis remains challenging, especially the asymptomatic form. This review focuses on recent advances in neurosyphilis, including epidemiology, clinical manifestations, laboratory findings, comorbidities, diagnosis, treatment, prognosis, and basic research. The expansion of men who have sex with men and the infection of human immunodeficiency virus mainly accounted for the increasing incidence of neurosyphilis. The rate of some historically described forms of neurosyphilis in the pre-antibiotic era declined significantly; atypical features are more prevalent. Neurosyphilis, regarded as a great mimicker for neuro-ophthalmic, audio-vestibular, and psychiatric disorders, often presents concomitantly with other diseases, including metabolic disorders. Studies on long non-coding RNAs, miRNAs, chemokines, and metabolites in peripheral blood and cerebrospinal fluid may facilitate exploring the pathogenesis and identifying novel biomarkers of neurosyphilis. The drug resistance of Treponema pallidum to penicillin has not been reported; ceftriaxone was proposed to be more effective than penicillin, whereas few randomized controlled trials supported this view. This study may pave the way for further research, especially the diagnosis and treatment of neurosyphilis.
Portable sauna stimulated-diaphoresis for the treatment of fluid-overload in peritoneal dialysis patients: A pilot study
Authors: Maggiani-Aguilera Pablo , Chávez-Iñiguez Jonathan S. , Navarro-Blackaller Guillermo , Hernández-Morales Karla , Geraldo-Ozuna Ariadna Lizbeth , Alcantar-Villín Luz , Montoya-Montoya Olivia , Luquín-Arellano Víctor Hugo , García-García Guillermo
Published: September 2022

Background

Fluid overload (FO) is a common problem in patients with peritoneal dialysis (PD), it is associated with adverse outcomes and may persist despite adjustements in PD therapy.

Objective

To evaluate the feasibility and safety of stimulated diaphoresis to reduce FO with the use of a portable sauna bath.

Methods

Open-label pilot study in patients on continuous ambulatory peritoneal dialysis (CAPD) and FO. The primary outcome was the treatment-related adverse events; secondary outcomes were changes in over-hydration (OH), body weight and blood pressure, FO symptoms, and sleep quality. Dialysis prescription and daily data were recorded. The intervention period consisted in a 30-min, 45°C sauna bath, daily for 10 days, using a portable sauna bath.

Results

Fifty-one out of 54 total sauna bath sessions were well tolerated. In three (5.5%) sessions adverse effects were reported: transient dizziness in two cases, and a second-degree skin burn in a patient with advanced diabetic neuropathy. OH (6.3 ± 1.2 L vs. 5.5 ± 1.3 L, p = 0.05), body weight (67.7 ± 11.4 vs. 66.8 ± 3.8 kg, p = 0.003), diastolic blood pressure (92 ± 13.5 vs. 83 ± 13.3 mmHg, P = 0.003) and PSQI score (7.3 ± 3.7 vs. 5.1 ± 3.2, p = 0.02) improved significantly between the control and intervention period, respectively.

Conclusions

Stimulated diaphoresis with a portable sauna bath could be a novel, safe, and effective alternative way to reduce FO in CAPD patients. Larger studies are needed to confirm our results.

Clinical trial registration

ClinicalTrials.gov, identifier: NCT03563898.
The association of exercise test variables with long-term mortality in patients with chronic Chagas disease
Authors: Silva Rudson S. , Mendes Fernanda S. N. S. , Fleg Jerome L. , Rodrigues Junior Luiz F. , Vieira Marcelo C. , Xavier Isis G. G. , Costa Henrique S. , Reis Michel S. , Mazzoli-Rocha Flavia , Costa Andrea R. , Holanda Marcelo T. , Veloso Henrique H. , Sperandio da Silva Gilberto M. , Sousa Andréa S. , Saraiva Roberto M. , Hasslocher-Moreno Alejandro Marcel , Mediano Mauro F. F.
Published: September 2022

Background

The identification of variables obtained in the exercise test (ET) associated with increased risk of death is clinically relevant and would provide additional information for the management of Chagas disease (CD). The objective of the present study was to evaluate the association of ET variables with mortality in patients with chronic CD.

Methods

This retrospective longitudinal observational study included 232 patients (median age 46.0 years; 50% women) with CD that were followed at the Evandro Chagas National Institute of Infectious Diseases (Rio de Janeiro, Brazil) and performed an ET between 1989 and 2000. The outcome of interest was all-cause mortality.

Results

There were 103 deaths (44.4%) during a median follow-up of 21.5 years (IQR 25–75% 8.0–27.8), resulting in 24.5 per 1,000 patients/year incidence rate. The ET variables associated with mortality after adjustments for potential confounders were increased maximal (HR 1.02; 95% CI 1.00–1.03 per mmHg) and change (HR 1.03; 95% CI 1.01–1.06 per mmHg) of diastolic blood pressure (DBP) during ET, ventricular tachycardia at rest (HR 3.95; 95% CI 1.14–13.74), during exercise (HR 2.73; 95% CI 1.44–5.20), and recovery (HR 2.60; 95% CI 1.14–5.91), and premature ventricular complexes during recovery (HR 2.06; 1.33–3.21).

Conclusion

Our findings suggest that ET provides important prognostic value for mortality risk assessment in patients with CD, with hemodynamic (increased DBP during exercise) and electrocardiographic (presence of ventricular arrhythmias) variables independently associated with an increased mortality risk in patients with CD. The identification of individuals at higher mortality risk can facilitate the development of intervention strategies (e.g., close follow-up) that may potentially have an impact on the longevity of patients with CD.
Valacyclovir-associated neurotoxicity among patients on hemodialysis and peritoneal dialysis: A nationwide population-based study
Authors: Wang Yi-Chun , Juan Shu-Hui , Li Ching-Hao , Chou Chu-Lin , Chen Li-Ying , Chien Li-Nien , Fang Te-Chao
Published: September 2022

Whether valacyclovir-associated neurotoxicity (VAN) occurs more frequently in patients with end-stage renal disease (ESRD) on dialysis is unknown. This is the first population-based study to examine the risk of VAN associated with ESRD patients on dialysis. Among 2,284,800 patients diagnosed as having herpes zoster from 2002 to 2016, patients with ESRD on dialysis and individuals with normal renal function were enrolled in this study. Following propensity score matching, we compared the risk of altered mental status between valacyclovir users and non-users in the ESRD and normal renal function cohorts over a 30-day follow-up period. In the ESRD cohort, the incidence of altered mental status was 1.68 and 0.52 per 1,000 person-day in valacyclovir users and non-users, respectively, with an adjusted hazard ratio (HR) of 3.22 (95% confidence interval [CI]: 2.04–4.99, P < 0.001). The incidence of altered mental status of valacyclovir users on hemodialysis (HD) and peritoneal dialysis (PD) was higher than that of non-users. The adjusted HR was 3.20 (95% CI: 1.98–5.15, P < 0.001) for those on HD and 3.44 (95% CI: 1.13–10.49, P = 0.030) for those with PD. However, altered mental status was not observed in patients on HD receiving ≤500 mg of valacyclovir three times per week or in those on PD receiving ≤500 mg of valacyclovir per day. The findings demonstrate that adjusting the valacyclovir dosage and monitoring VAN in patients with HD and PD who have herpes zoster is crucial.
Epinephrine extensively changes the biofilm matrix composition in Micrococcus luteus C01 isolated from human skin
Authors: Gannesen Andrei V. , Ziganshin Rustam H. , Zdorovenko Evelina L. , Klimko Alena I. , Ianutsevich Elena A. , Danilova Olga A. , Tereshina Vera M. , Gorbachevskii Maxim V. , Ovcharova Maria A. , Nevolina Ekaterina D. , Martyanov Sergey V. , Shashkov Alexander S. , Dmitrenok Andrey S. , Novikov Andrei A. , Zhurina Marina V. , Botchkova Ekaterina A. , Toukach Philipp V. , Plakunov Vladimir K.
Published: September 2022

The importance of the impact of human hormones on commensal microbiota and microbial biofilms is established in lots of studies. In the present investigation, we continued and extended the research of epinephrine effects on the skin commensal Micrococcus luteus C01 and its biofilms, and also the matrix changes during the biofilm growth. Epinephrine in concentration 4.9 × 10–9 M which is close to normal blood plasma level increased the amount of polysaccharides and extracellular DNA in the matrix, changed extensively its protein, lipid and polysaccharide composition. The Ef-Tu factor was one of the most abundant proteins in the matrix and its amount increased in the presence of the hormone. One of the glucose-mannose polysaccharide was absent in the matrix in presence of epinephrine after 24 h of incubation. The matrix phospholipids were also eradicated by the addition of the hormone. Hence, epinephrine has a great impact on the M. luteus biofilms and their matrix composition, and this fact opens wide perspectives for the future research.
Componential usage patterns in dengue 4 viruses reveal their better evolutionary adaptation to humans
Authors: Li Gun , Shi Liang , Zhang Liang , Xu Bingyi
Published: September 2022

There have been at least four types of dengue outbreaks in the past few years. The evolutionary characteristics of dengue viruses have aroused great concerns. The evolutionary characteristics of dengue 4 viruses are studied in the present study based on their base usage patterns and codon usage patterns. The effective number of codons and relative synonymous codon usage (RSCU) values of four types of dengue viruses were counted or calculated. The Kullback–Leibler (K–L) divergences of relative synonymous codon usage from dengue viruses to humans and the Kullback–Leibler divergences of amino acid usage patterns from dengue viruses to humans were calculated to explore the adaptation levels of dengue viruses. The results suggested that: (1) codon adaptation in dengue 4 viruses occurred through an evolutionary process from 1956 to 2021, (2) overall relative synonymous codon usage values of dengue 4 viruses showed more similarities to humans than those of other subtypes of dengue viruses, and (3) the smaller Kullback–Leibler divergence of amino acid usage and relative synonymous codon usage from dengue viruses to humans indicated that the dengue 4 viruses adapted to human hosts better. All results indicated that both mutation pressure and natural selection pressure contributed to the codon usage pattern of dengue 4 viruses more obvious than to other subtypes of dengue viruses and that the dengue 4 viruses adapted to human hosts better than other types of dengue viruses during their evolutionary process.
Molecular epidemiology and antimicrobial susceptibility of Pseudomonas spp. and Acinetobacter spp. from clinical samples at Jimma medical center, Ethiopia
Authors: Sewunet Tsegaye , Asrat Daniel , Woldeamanuel Yimtubezinash , Aseffa Abraham , Giske Christian G.
Published: September 2022

Introduction

Pseudomonas aeruginosa (P. aeruginosa) and Acinetobacter baumannii (A. baumannii) can cause difficult-to-treat infections. We characterized molecular epidemiology of ceftazidime-resistant P. aeruginosa and carbapenem-resistant A. baumannii at a tertiary hospital in Ethiopia.

Materials and methods

Non-fermenting gram-negative bacilli (n = 80) isolated from admitted patients were subjected for species identification by MALDI-TOF. Pseudomonas species resistant to ceftazidime or meropenem, and Acinetobacter species resistant to meropenem, or imipenem were selected for whole genome sequencing. DNA extracted with EZ1 Advanced XL instrument (Qiagen, Hilden, Germany) was sequenced on Illumina (HiSeq2500) using libraries prepared by NEXTRA-kits (Illumina). Raw reads were assembled using SPAdes 3.13.0, and assembled genomes were used to query databases for resistome profile and sequence types.

Result

Among Pseudomonas species isolated, 31.7% (13/41), and 7.3% (3/41) were non-susceptible to ceftazidime, and meropenem, respectively. Carbapenem-resistance was 56.4% (22/39) among Acinetobacter species. Moreover, 92% (12/13) of Pseudomonas species non-susceptible to ceftazidime and/or meropenem, and 89.4% (17/19) of Acinetobacter species encoded multiple resistance genes for at least three classes of antimicrobials. The prevalent β - lactamase genes were blaOXA–486 (53.8%, 7/13), blaCTX–M–15 (23.0%, 3/13) among Pseudomonas, and blaGES–11 (57.8%, 11/19) among Acinetobacter. The blaOXA–51-like β - lactamase, blaOXA–69 (63.1%, 12/19) was the most prevalent carbapenemase gene among Acinetobacter isolates. Single isolates from both P. aeruginosa, and A. baumannii were detected with the blaNDM–1. Sequence type (ST)1 A. baumannii and ST274 P. aeruginosa were the prevalent sequence types. A cgMLST analysis of the ST1 A. baumannii isolates showed that they were closely related and belonged to the international clonal complex one (ICC1). Similarly, ST274 P. aeruginosa isolates were clonally related.

Conclusion

The prevalence of MDR isolates of Pseudomonas and Acinetobacter spp. was high. A. baumannii isolates were clonally spreading in the admission wards at the hospital. Emergence of blaNDM–1 in the intensive care, and surgical wards of the hospital is a severe threat that requires urgent intervention.
SsUbc2, a determinant of pathogenicity, functions as a key coordinator controlling global transcriptomic reprogramming during mating in sugarcane smut fungus
Authors: Lu Shan , Zhang Haoyang , Guo Feng , Yang Yanfang , Shen Xiaorui , Chen Baoshan
Published: September 2022

The basidiomycete fungus Sporisorium scitamineum is the causative agent of sugarcane smut disease. Mating between two strains of the opposite mating type is essential for filamentous growth and infection in sugarcane plants. However, the mechanisms underlying mating and pathogenicity are still not well understood. In this work we used gene disruption to investigate the role of Ssubc2, the gene encoding a kinase regulator in S. scitamineum. Deletion of Ssubc2 did not alter the haploid cell morphology or growth rate in vitro or tolerance to stress, but mutants with both alleles deleted lost mating ability and infectivity. Deletion of one Ssubc2 allele in a pair with a wild-type strain resulted in impaired mating and reduced virulence. Transcriptome profiling revealed that about a third of genes underwent reprogramming in the wild types during mating. Although gene expression reprogramming occurred in the pairing of Ssubc2-null mutants, their transcriptomic profile differed significantly from that of the wild types, in which 625 genes differed from those present in the wild types that seemed to be among the required genes for a successful mating. These genes include those known to regulate mating and pathogenicity, such as components of the MAPK pathway and hgl1. Additionally, a total of 908 genes were differentially expressed in an out-of-control manner in the mutants. We conclude that SsUbc2 functions as a key factor to coordinate the reprogramming of gene expression at the global level and is essential for the transition from monokaryotic basidial growth to dikaryotic hyphal growth through mating.
Potential of gut-derived short-chain fatty acids to control enteric pathogens
Authors: Zhan Ziyang , Tang Hao , Zhang Ying , Huang Xinxiang , Xu Min
Published: September 2022

Short-chain fatty acids (SCFAs) are a very important group of metabolites located in the gut that play a crucial role in the regulation of gut function and pathogen resistance. Since many enteric pathogens respond differently to various SCFAs, substantial efforts have been made to understand the regulatory effects of SCFA types on enteric pathogens. The application of protein post-translational modifications (PTMs) in bacterial research provides a new perspective for studying the regulation of enteric pathogens by different SCFAs. Existing evidence suggests that the SCFAs acetate, propionate, and butyrate influence bacterial processes by extensively promoting the acylation of key bacterial proteins. SCFAs can also prevent the invasion of pathogenic bacteria by regulating the barrier function and immune status of the host gut. In this review, we describe the mechanisms by which different SCFAs modulate the pathogenicity of enteric pathogens from multiple perspectives. We also explore some recent findings on how enteric pathogens counteract SCFA inhibition. Lastly, we discuss the prospects and limitations of applying SCFAs to control enteric pathogens.