bluuebunny/crossref_metadata_2025 huggingface dataset:
Association of gestational diabetes mellitus and negative modulation of the specific humoral and cellular immune response against Toxoplasma gondii
Authors: Oliveira-Scussel Ana Carolina de Morais , Ferreira Paula Tatiana Mutão , Resende Renata de Souza , Ratkevicius-Andrade Cristhianne Molinero , Gomes Angelica de Oliveira , Paschoini Marina Carvalho , De Vito Fernanda Bernadelli , Farnesi-de-Assunção Thaís Soares , Silva Marcos Vinícius da , Mineo José Roberto , Rodrigues Denise Bertulucci Rocha , Rodrigues Virmondes
Published: September 2022

In order to evaluate and compare the specific immune response of pregnant women (PW) chronically infected withToxoplasma gondii, with and without gestational diabetes mellitus (GDM), and the humoral response of their respective newborns (NB), the study was carried out on 81 PW (34 GDM and 47 controls) from whose medical records the results of the oral glucose tolerance test (OGTT) were obtained, and blood samples were collected at the third trimester of pregnancy; also, on 45 NBs (20 GDM and 25 controls) from whom umbilical cord blood samples were obtained. Humoral immunity was analyzed by measuring anti-T. gondiitotal IgG, IgG subclasses and IgG avidity. To evaluate cellular immunity, peripheral blood mononuclear cells (PBMC) from 32 PW (16 GDM and 16 controls) were cultured, supernatant cytokines were determined, and flow cytometry was performed to analyze the expression at lymphocytes of surface molecules, cytokines and transcription factors. All PW and NBs were positive for total IgG, and the prevalent subclass was IgG1. There was a negative correlation between the OGTT glycemia of PW and the levels of total IgG, IgG1 and IgG avidity. The IgG avidity of the GDM group was significantly lower than the control group. Patients from the GDM group had a higher number of T lymphocytes expressing markers of cell activation and exhaustion (CD28 and PD-1). In the presence ofT. gondiisoluble antigen (STAg) the amount of CD4+T cells producing IFN-γ, IL-10 and IL-17 was significantly lower in the GDM group, while there was no difference between groups in the number of CD4+CD25HighFOXP3+LAP+ functional Treg cells. Additionally, under STAg stimulus, the secretion of IL-17, IL-4, TNF and IL-2 cytokines at PBMCs culture supernatant was lower in the GDM group. In conclusion, there was a correlation between the increase in blood glucose and the decrease in levels of anti-T. gondiiantibodies, associated with the decreased IgG avidity in patients who develop GDM. Also, the GDM group had decreased immune responses in Th1, Th2 and Th17 profiles, suggesting an association between GDM and the negative modulation of the humoral and cellular immune responses againstT. gondii.
Immunological risk factors for sepsis-associated delirium and mortality in ICU patients
Authors: Lei Wen , Ren Zhiyao , Su Jun , Zheng Xinglong , Gao Lijuan , Xu Yudai , Deng Jieping , Xiao Chanchan , Sheng Shuai , Cheng Yu , Ma Tianshun , Liu Yu , Wang Pengcheng , Luo Oscar Junhong , Chen Guobing , Wang Zhigang
Published: September 2022

Background

A major challenge in intervention of critical patients, especially sepsis-associated delirium (SAD) intervention, is the lack of predictive risk factors. As sepsis and SAD are heavily entangled with inflammatory and immunological processes, to identify the risk factors of SAD and mortality in the intensive care unit (ICU) and determine the underlying molecular mechanisms, the peripheral immune profiles of patients in the ICU were characterized.

Methods

This study contains a cohort of 52 critical patients who were admitted to the ICU of the First Affiliated Hospital of Jinan University. Comorbidity, including sepsis and SAD, of this cohort was diagnosed and recorded. Furthermore, peripheral blood samples were collected on days 1, 3, and 5 of admission for peripheral immune profiling with blood routine examination, flow cytometry, ELISA, RNA-seq, and qPCR.

Results

The patients with SAD had higher mortality during ICU admission and within 28 days of discharge. Compared with survivors, nonsurvivors had higher neutrophilic granulocyte percentage, higher CRP concentration, lower monocyte count, lower monocyte percentage, lower C3 complement level, higher CD14loCD16+ monocytes percentage, and higher levels of IL-6 and TNFα. The CD14hiCD16- monocyte percentage manifested favorable prediction values for the occurrence of SAD. Differentially expressed genes between the nonsurvival and survival groups were mainly associated with immune response and metabolism process. The longitudinal expression pattern of SLC2A1 and STIMATE were different between nonsurvivors and survivors, which were validated by qPCR.

Conclusions

Nonsurvival critical patients have a distinct immune profile when compared with survival patients. CD14hiCD16- monocyte prevalence and expression levels of SLC2A1 and STIMATE may be predictors of SAD and 28-day mortality in ICU patients.
T cell receptor excision circles are potential predictors of survival in adult allogeneic hematopoietic stem cell transplantation recipients with acute myeloid leukemia
Authors: Söderström Anna , Vonlanthen Sofie , Jönsson-Videsäter Kerstin , Mielke Stephan , Lindahl Hannes , Törlén Johan , Uhlin Michael
Published: September 2022

Background

Lymphocyte neogenesis from primary lymphoid organs is essential for a successful reconstitution of immunity after allogeneic hematopoietic stem cell transplantation (HSCT). This single-center retrospective study aimed to evaluate T cell receptor excision circles (TREC) and kappa-deleting recombination excision circles (KREC) as surrogate markers for T and B cell recovery, as predictors for transplantation-related outcomes in adult acute myeloid leukemia (AML) patients.

Methods

Ninety adult patients diagnosed with AML and treated with HSCT between 2010 and 2015 were included in the study. TREC and KREC levels were measured by quantitative PCR at 1, 3, 6, and 12 months after transplantation.

Results

Overall, excision circle levels increased between 3 and 6 months post-HSCT for TREC (p = 0.005) and 1 and 3 months for KREC (p = 0.0007). In a landmark survival analysis at 12 months post-HSCT, TREC levels were associated with superior overall survival (HR: 0.52, 95% CI: 0.34 - 0.81, p = 0.004). The incidence of viral infections within the first 100 days after transplantation was associated with lower TREC levels at 6 months (p = 0.0002). CMV reactivation was likewise associated with lower TREC levels at 6 months (p = 0.02) post-HSCT. KREC levels were not associated with clinical outcomes in statistical analyzes.

Conclusions

Results from the present study indicate that TREC measurement could be considered as part of the post-HSCT monitoring to identify AML patients with inferior survival after transplantation. Further prospective studies are warranted to validate these findings.
Versican enrichment predicts poor prognosis and response to adjuvant therapy and immunotherapy in gastric cancer
Authors: Song Junquan , Wei Rongyuan , Huo Shiying , Liu Chenchen , Liu Xiaowen
Published: September 2022

Background

Increasing evidence has revealed an important role of versican (VCAN) on various aspects of cancer progression. Here, we assessed the impact of VCAN expression on prognosis and the response to adjuvant therapy and immunotherapy in patients with gastric cancer (GC).

Methods

Four independent cohorts containing 1353 patients with GC, were utilized to investigate the effect of VCAN expression on prognosis and response to adjuvant therapy in GC. Two cohorts treated with immune checkpoint blockades were included to assess the predict value of VCAN expression on response to immunotherapy. Moreover, the bulk RNA-seq and single-cell RNA-seq data were analyzed to illustrate the role of VCAN in tumor microenvironment. Clinical outcomes of patient subgroups were compared by Kaplan-Meier curves with the log-rank test.

Result

High VCAN expression was associated with poor prognosis for patients with GC. Compared with patients with high VCAN expression, patients with low VCAN expression benefited more from adjuvant chemotherapy and adjuvant chemoradiotherapy. Moreover, patients with high VCAN expression tended to be resistant to immunotherapy, and VCAN could serve as a promising indicator for predicting the response to immunotherapy. VCANhigh tumors showed a specific microenvironment with more cancer associated fibroblasts infiltration and significant enrichment of stromal relevant signaling pathways.

Conclusion

VCAN could predict the response to adjuvant chemotherapy, adjuvant chemoradiotherapy and immunotherapy in GC, and designing new medicine target to VCAN might be an effective way to improve the efficacy of several treatment options for GC.
Enforcing GLUT3 expression in CD8+ T cells improves fitness and tumor control by promoting glucose uptake and energy storage
Authors: Cribioli Elisabetta , Giordano Attianese Greta Maria Paola , Ginefra Pierpaolo , Signorino-Gelo Amandine , Vuillefroy de Silly Romain , Vannini Nicola , Hess Christoph , Irving Melita , Coukos George
Published: September 2022

Despite the tremendous success of adoptive T-cell therapies (ACT) in fighting certain hematologic malignancies, not all patients respond, a proportion experience relapse, and effective ACT of most solid tumors remains elusive. In order to improve responses to ACT suppressive barriers in the solid tumor microenvironment (TME) including insufficient nutrient availability must be overcome. Here we explored how enforced expression of the high-affinity glucose transporter GLUT3 impacted tumor-directed T cells. Overexpression of GLUT3 in primary murine CD8+ T cells enhanced glucose uptake and increased glycogen and fatty acid storage, and was associated with increased mitochondrial fitness, reduced ROS levels, higher abundance of the anti-apoptotic protein Mcl-1, and better resistance to stress. Importantly, GLUT3-OT1 T cells conferred superior control of B16-OVA melanoma tumors and, in this same model, significantly improved survival. Moreover, a proportion of treated mice were cured and protected from re-challenge, indicative of long-term T cell persistence and memory formation. Enforcing expression of GLUT3 is thus a promising strategy to improve metabolic fitness and sustaining CD8+ T cell effector function in the context of ACT.
Effect of FOXP2 transcription factor on immune infiltration of thyroid cancer and its potential clinical value
Authors: Xu Lianghui , Yang Zheyu , Zhao Qiwu , Feng Haoran , Kuang Jie , Liu Zhuoran , Chen Linxie , Zhan Lin , Yan Jiqi , Cai Wei , Qiu Weihua
Published: September 2022

Background

The clinical outcomes are not always favorable in certain thyroid cancer patients. The effect of Forkhead-box family on immune cells infiltration and tumor microenvironment in thyroid cancer was explored. The role of FOXP2 in tumor invasion and recurrence was investigated consequently.

Methods

TIMER and GEPIA were firstly employed to compare FOXPs expression in normal and cancer tissues from multiple human cancers. The results from database were confirmed by quantitative Real Time-PCR and Western blot in matched thyroid cancer and adjacent normal tissues, in addition to a panel of thyroid cancer cell lines and normal thyroid cell. GEPIA platform was employed to discover the possibility of FOXPs as prognostic indicator. TISIBD and UACLCAN were then employed to estimate the influence of FOXPs on lymph node metastasis and tumor staging. GEPIA analysis was initially employed to analyze correlation of FOXPs and tumor immune infiltrating cells, and TIMER dataset was then included for standardization according to tumor purity.

Result

Different member of FOXPs showed divergence in expression in various cancer tissues. Lower FOXP1, FOXP2 and higher FOXP3, FOXP4 levels could be identified in thyroid cancer tissues when compared with matched normal tissue. There was an inverse correlation between FOXP2, FOXP4 and immune invasion, whereas FOXP1 and FOXP3 were positively correlated. FOXPs showed remarkable correlations with multiply immune cells. More importantly, only FOXP2 showed the significant effect on recurrence and tumor staging.

Conclusion

As immune regulatory factor, the reduction of FOXP2 may affect tumor microenvironments and immune cells infiltration, enhance tumor immune escape, and promote recurrence of thyroid cancer. FOXP2 could be a new potential diagnostic and prognostic marker.
Optic nerve head: A gatekeeper for vitreous infectious insults?
Authors: Lai Wenwen , Huang Jie , Fang Wangyi , Deng Saiyue , Xie Yi , Wang Wei , Qiao Tong , Xu Gezhi , Wang Xiaowei , Ding Fengfei
Published: September 2022

The axons of retinal ganglion cells (RGCs) pass through the optic nerve head (ONH) and form the optic nerve (ON). The ONH serves as an anatomical interface between the vitreous cavity and subarachnoid space. After inducing acute neuroinflammation by intravitreal injection of lipopolysaccharides (LPS), we observed inflammatory activation in the retina, but detect no signs of inflammation in the posterior ON or infiltration of inflammatory cells in the ONH. Therefore, we hypothesized that the ONH functions as a barrier to vitreous inflammation. Using transmission electron microscopy, we identified significant increase in G-ratio in the posterior ON on day 7 post intravitreal injection (PII) of LPS compared with the phosphate buffered saline (PBS) group. Moreover, using confocal imaging of ex vivo tissue extracted from Aldh1L1-eGFP reporter mice, we observed that the ONH astrocytes altered their spatial orientation by elongating their morphology along the axonal axis of RGCs in LPS- versus PBS-treated eyes; this was quantified by the ratio of longitudinal (DL) and transverse (DT) diameter of astrocytes and the proportion of longitudinally locating astrocytes. Supportive evidences were further provided by transmission electron microscopic imaging in rat ONH. We further conducted RNA sequencing of ONH on day 1 PII and found LPS induced clear upregulation of immune and inflammatory pathways. Furthermore, gene set enrichment analysis revealed that astrocyte and microglia contributed prominently to the transcriptomic alterations in ONH. Here, we report that the vitreous infectious insults induce morphological changes of ONH astrocytes and transcriptomic alterations in the ONH. Glial responses in the ONH may defend against vitreous infectious insults and serve as a barrier to inflammation for the central nervous system.
Identification and validation of autophagy-related gene expression for predicting prognosis in patients with idiopathic pulmonary fibrosis
Authors: Huang Guichuan , Xu Xin , Ju Chunrong , Zhong Nanshan , He Jianxing , Tang Xiao Xiao
Published: September 2022

Background

Idiopathic pulmonary fibrosis (IPF) is a chronic, progressive, and fatal fibrotic pulmonary disease with unknow etiology. Owing to lack of reliable prognostic biomarkers and effective treatment measures, patients with IPF usually exhibit poor prognosis. The aim of this study is to establish a risk score prognostic model for predicting the prognosis of patients with IPF based on autophagy-related genes.

Methods

The GSE70866 dataset was obtained from the gene expression omnibus (GEO) database. The autophagy-related genes were collected from the Molecular Signatures Database (MSigDB). Gene enrichment analysis for differentially expressed genes (DEGs) was performed to explore the function of DEGs. Univariate, least absolute shrinkage and selection operator (LASSO), as well as multivariate Cox regression analyses were conducted to identify a multi-gene prognostic model. Receiver operating characteristic (ROC) curve was applied to assess the prediction accuracy of the model. The expression of genes screened from the prognostic model was validated in clinical samples and human lung fibroblasts by qPCR and western blot assays.

Results

Among the 514 autophagy-related genes, a total of 165 genes were identified as DEGs. These DEGs were enriched in autophagy-related processes and pathways. Based on the univariate, LASSO, and multivariate Cox regression analyses, two genes (MET and SH3BP4) were included for establishing the risk score prognostic model. According to the median value of the risk score, patients with IPF were stratified into high-risk and low-risk groups. Patients in high-risk group had shorter overall survival (OS) than low-risk group in both training and test cohorts. Multivariate regression analysis indicated that prognostic model can act as an independent prognostic indicator for IPF. ROC curve analysis confirmed the reliable predictive value of prognostic model. In the validation experiments, upregulated MET expression and downregulated SH3BP4 expression were observed in IPF lung tissues and TGF-β1-activated human lung fibroblasts, which is consistent with results from microarray data analysis.

Conclusion

These findings indicated that the risk score prognostic model based on two autophagy-related genes can effectively predict the prognosis of patients with IPF.
A catalog of the genetic causes of hereditary angioedema in the Canary Islands (Spain)
Authors: Mendoza-Alvarez Alejandro , Tosco-Herrera Eva , Muñoz-Barrera Adrian , Rubio-Rodríguez Luis A. , Alonso-Gonzalez Aitana , Corrales Almudena , Iñigo-Campos Antonio , Almeida-Quintana Lourdes , Martin-Fernandez Elena , Martinez-Beltran Dara , Perez-Rodriguez Eva , Callero Ariel , Garcia-Robaina Jose C. , González-Montelongo Rafaela , Marcelino-Rodriguez Itahisa , Lorenzo-Salazar Jose M. , Flores Carlos
Published: September 2022

Hereditary angioedema (HAE) is a rare disease where known causes involve C1 inhibitor dysfunction or dysregulation of the kinin cascade. The updated HAE management guidelines recommend performing genetic tests to reach a precise diagnosis. Unfortunately, genetic tests are still uncommon in the diagnosis routine. Here, we characterized for the first time the genetic causes of HAE in affected families from the Canary Islands (Spain). Whole-exome sequencing data was obtained from 41 affected patients and unaffected relatives from 29 unrelated families identified in the archipelago. The Hereditary Angioedema Database Annotation (HADA) tool was used for pathogenicity classification and causal variant prioritization among the genes known to cause HAE. Manual reclassification of prioritized variants was used in those families lacking known causal variants. We detected a total of eight different variants causing HAE in this patient series, affecting essentially SERPING1 and F12 genes, one of them being a novel SERPING1 variant (c.686-12A>G) with a predicted splicing effect which was reclassified as likely pathogenic in one family. Altogether, the diagnostic yield by assessing previously reported causal genes and considering variant reclassifications according to the American College of Medical Genetics guidelines reached 66.7% (95% Confidence Interval [CI]: 30.1-91.0) in families with more than one affected member and 10.0% (95% CI: 1.8-33.1) among cases without family information for the disease. Despite the genetic causes of many patients remain to be identified, our results reinforce the need of genetic tests as first-tier diagnostic tool in this disease, as recommended by the international WAO/EAACI guidelines for the management of HAE.
Metaomics unveils the contribution of Alteromonas bacteria to carbon cycling in marine oxygen minimum zones
Authors: Henríquez-Castillo Carlos , Plominsky Alvaro M. , Ramírez-Flandes Salvador , Bertagnolli Anthony D. , Stewart Frank J. , Ulloa Osvaldo
Published: September 2022

Gammaproteobacteria of the genus Alteromonas are prominent members of pelagic marine microbial communities, playing critical roles in the aerobic degradation of particulate organic matter. Comparative genomic studies of these microorganisms have mainly focused on the metabolic and genomic plasticity of strains isolated primarily from oxygenated environments. In this study, we show that Alteromonas significantly contribute to marine microbial communities from suboxic waters ([O2] < 5 uM) in both the free-living (FL) and particle-attached (PA) fractions, but considerably decrease in abundance in the anoxic waters. The highest proportion of Alteromonas transcripts was found within the secondary fluorescence maximum (SFM) of Oxygen Minimum Zones (OMZs). This metatranscriptomic information suggests an in situ coupling of Alteromonas iron (Fe) and carbon metabolisms, and a relevant role of the glyoxylate cycle across the different layers of the OMZs. This study demonstrates that Alteromonas is an abundant and active member of the OMZ microbial communities, with a potentially significant impact on the carbon cycling in these ecosystems. These results provide valuable environmental evidence to support previous culture-based studies assessing the physiology and ecology of these ubiquitous marine heterotrophs under low-oxygen conditions.
A transcriptomics-based meta-analysis identifies a cross-tissue signature for sarcoidosis
Authors: Jiang Yale , Jiang Dingyuan , Costabel Ulrich , Dai Huaping , Wang Chen
Published: September 2022

Sarcoidosis is a granulomatous disease of unknown etiology, immunologically characterized by a Th1 immune response. Transcriptome-wide expression studies in various types of sarcoid tissues contributed to better understanding of disease mechanisms. We performed a systematic database search on Gene Expression Omnibus (GEO) and utilized transcriptomic data from blood and sarcoidosis-affected tissues in a meta-analysis to identify a cross-tissue, cross-platform signature. Datasets were further separated into training and testing sets for development of a diagnostic classifier for sarcoidosis. A total of 690 differentially expressed genes were identified in the analysis among various tissues. 29 of the genes were robustly associated with sarcoidosis in the meta-analysis both in blood and in lung-associated tissues. Top genes included LINC01278 (P = 3.11 × 10–13), GBP5 (P = 5.56 × 10–07), and PSMB9 (P = 1.11 × 10–06). Pathway enrichment analysis revealed activated IFN-γ, IL-1, and IL-18, autophagy, and viral infection response. IL-17 was observed to be enriched in peripheral blood specific signature genes. A 16-gene classifier achieved excellent performance in the independent validation data (AUC 0.711–0.964). This study provides a cross-tissue meta-analysis for expression profiles of sarcoidosis and identifies a diagnostic classifier that potentially can complement more invasive procedures.
The research environment of critical care in three Asian countries: A cross-sectional questionnaire survey
Authors: Kotani Yuki , Na Sungwon , Phua Jason , Shime Nobuaki , Kawasaki Tatsuya , Yasuda Hideto , Jun Jong Hun , Kawaguchi Atsushi
Published: September 2022

Although inadequate research support for intensivists can be one major reason of the poor research productivity, no study has investigated the current research environment in critical care medicine in Asia. The objective of this study was to describe Asian academia in critical care from the research environment perspective. We conducted a cross-sectional questionnaire survey targeting all physician members of the Societies of Intensive/Critical Care Medicine in Japan, South Korea, and Singapore. We collected the characteristics of the participants and their affiliated institutions and the research environment. The outcome was the number of peer-reviewed publications. Multivariable logistic regression analyses examined the association between the outcome and the following five research environmental factors (i.e., country of the respondents, availability of secured time for research activities or research supporting staff for the hospital, practice at a university-affiliated hospital, and years of clinical practice of 10 years or longer). Four hundred ninety responded (overall response rate: 5.6%) to the survey between June 2019 and January 2020. Fifty-five percent worked for a university-affiliated hospital, while 35% worked for a community hospital. Twenty-four percent had secured time for research within their full-time work hours. The multivariable logistic model found that a secured time for the research activities [odds ratio (OR): 2.77; 95% confidence interval (CI), 1.46–5.24], practicing at a university-affiliated hospital (OR: 2.61; 95% CI, 1.19–5.74), having clinical experience of 10 years or longer (OR:11.2; 95%CI, 1.41–88.5), and working in South Korea (OR: 2.18; 95% CI, 1.09–4.34, Reference: Japan) were significantly associated with higher research productivity. Intensivists in the three countries had limited support for their research work. Dedicated time for research was positively associated with the number of research publications.
Clinical characteristics of new-onset acute kidney injury in patients with established acute respiratory distress syndrome: A prospective single-center post hoc observational study
Authors: Cui Xiaoyang , Huang Xu , Yu Xin , Cai Ying , Tian Ye , Zhan Qingyuan
Published: September 2022

Background

We assessed the incidence and clinical characteristics of acute kidney injury (AKI) in acute respiratory distress syndrome (ARDS) patients and its effect on clinical outcomes.

Methods

We conducted a single-center prospective longitudinal study. Patients who met the Berlin definition of ARDS in the medical ICU in China-Japan Friendship Hospital from March 1, 2016, to September 30, 2020, were included. AKI was defined according to the KDIGO clinical practice guidelines. Early and late AKI were defined as AKI occurring within 48 h after ARDS was diagnosed or after 48 h, respectively.

Results

Of the 311 ARDS patients, 161 (51.8%) developed AKI after ICU admission. Independent risk factors for AKI in ARDS patients were age (OR 1.027, 95% CI 1.009–1.045), a history of diabetes mellitus (OR 2.110, 95%CI 1.100–4.046) and chronic kidney disease (CKD) (OR 9.328, 95%CI 2.393–36.363), APACHE II score (OR 1.049, 95%CI 1.008–1.092), average lactate level in the first 3 days (OR 1.965, 95%CI 1.287–3.020) and using ECMO support (OR 2.359, 95%CI 1.154–4.824). Early AKI was found in 91 (56.5%) patients and late AKI was found in 70 (43.5%). Early AKI was related to the patient’s underlying disease and the severity of hospital admission, while late AKI was related to the application of nephrotoxic drugs. The mortality rate of ARDS combined with AKI was 57.1%, which was independently associated with shock (OR 54.943, 95%CI 9.751–309.573).

Conclusion

A significant number of patients with ARDS developed AKI, and the mortality rate for ARDS patients was significantly higher when combined with AKI. Therapeutic drug monitoring should be routinely used to avoid drug toxicity during treatment.
Patients’ knowledge about their involvement in clinical trials. A non-randomized controlled trial
Authors: Juan-Salvadores Pablo , Michel Gómez Marcela Sánchez , Jiménez Díaz Víctor Alfonso , Martínez Reglero Cristina , Iñiguez Romo Andrés
Published: September 2022

Background

Nowadays, good clinical practice should be established in human research. Patient’s rights and autonomy must be respected above the interest of the researcher, making mandatory to raise patient’s awareness on the implications of participating in a clinical study. Contrary to popular belief, this is not always the case. This means that, after signing the informed consent form, some patients have difficulties understanding their responsibilities as participants.

Materials and methods

This study is a prospective, multicenter, non-randomized controlled trial comparative survey conducted on patients enrolled in a clinical trial to evaluate and improve their understanding after an educational intervention was applied to the research staff.

Results

Females were underrepresented in the clinical trials performed in this study, 21.5%. Most of the participants had a low educational level (74.4%). Around 5 and 10% of the research participants were not aware they were part of a clinical study, and more 24% just trusted in the medical decision to be enrolled. After the interventional education, the following items: “given time and resolution of the patient doubts” (p-value = 0.003), “enough written information” (p-value = 0.006), “explanation of the risks of participating in the study,” (p-value = 0.047) and understanding of the information provided to them showed an improvement regarding the study in which they were participating.

Conclusion

The research participants understanding of their involvement in clinical trials is limited. An educational intervention on the research team can improve the process of empowerment and transit of information.
High-throughput nanopore sequencing of Treponema pallidum tandem repeat genes arp and tp0470 reveals clade-specific patterns and recapitulates global whole genome phylogeny
Authors: Lieberman Nicole A. P. , Armstrong Thaddeus D. , Chung Benjamin , Pfalmer Daniel , Hennelly Christopher M. , Haynes Austin , Romeis Emily , Wang Qian-Qiu , Zhang Rui-Li , Kou Cai-Xia , Ciccarese Giulia , Conte Ivano Dal , Cusini Marco , Drago Francesco , Nakayama Shu-ichi , Lee Kenichi , Ohnishi Makoto , Konda Kelika A. , Vargas Silver K. , Eguiluz Maria , Caceres Carlos F. , Klausner Jeffrey D. , Mitja Oriol , Rompalo Anne , Mulcahy Fiona , Hook Edward W. , Hoffman Irving F. , Matoga Mitch M. , Zheng Heping , Yang Bin , Lopez-Medina Eduardo , Ramirez Lady G. , Radolf Justin D. , Hawley Kelly L. , Salazar Juan C. , Lukehart Sheila A. , Seña Arlene C. , Parr Jonathan B. , Giacani Lorenzo , Greninger Alexander L.
Published: September 2022

Sequencing of most Treponema pallidum genomes excludes repeat regions in tp0470 and the tp0433 gene, encoding the acidic repeat protein (arp). As a first step to understanding the evolution and function of these genes and the proteins they encode, we developed a protocol to nanopore sequence tp0470 and arp genes from 212 clinical samples collected from ten countries on six continents. Both tp0470 and arp repeat structures recapitulate the whole genome phylogeny, with subclade-specific patterns emerging. The number of tp0470 repeats is on average appears to be higher in Nichols-like clade strains than in SS14-like clade strains. Consistent with previous studies, we found that 14-repeat arp sequences predominate across both major clades, but the combination and order of repeat type varies among subclades, with many arp sequence variants limited to a single subclade. Although strains that were closely related by whole genome sequencing frequently had the same arp repeat length, this was not always the case. Structural modeling of TP0470 suggested that the eight residue repeats form an extended α-helix, predicted to be periplasmic. Modeling of the ARP revealed a C-terminal sporulation-related repeat (SPOR) domain, predicted to bind denuded peptidoglycan, with repeat regions possibly incorporated into a highly charged β-sheet. Outside of the repeats, all TP0470 and ARP amino acid sequences were identical. Together, our data, along with functional considerations, suggests that both TP0470 and ARP proteins may be involved in T. pallidum cell envelope remodeling and homeostasis, with their highly plastic repeat regions playing as-yet-undetermined roles.
Intramammary infusion of matrine-chitosan hydrogels for treating subclinical bovine mastitis —effects on milk microbiome and metabolites
Authors: Zhang Hua , Wang Ziyue , Yao Hua , Jiang Linshu , Tong Jinjin
Published: September 2022

Background

Bovine metabolism undergoes significant changes during subclinical mastitis, but the relevant molecular mechanisms have not been elucidated. In this study we investigated the changes in milk microbiota and metabolites after intramammary infusion of matrine-chitosan hydrogels (MCHs) in cows with subclinical mastitis.

Methods

Infusions were continued for 7 days, and milk samples were collected on days 1 and 7 for microbiome analysis by 16S rRNA gene sequencing and metabolite profiling by liquid chromatography-mass spectrometry.

Results

MCHs significantly decreased the somatic cell count on day 7 compared to day 1, and the Simpson index indicated that microbial diversity was significantly lower on day 7. The relative abundance of Aerococcus, Corynebacterium_1, Staphylococcus and Firmicutes was significantly decreased on day 7, while Proteobacteria increased. In the milk samples, we identified 74 differentially expressed metabolites. The MCHs infusion group had the most significantly upregulated metabolites including sphingolipids, glycerophospholipids, flavonoids and fatty acyls. The mammary gland metabolic pathways identified after MCHs treatment were consistent with the known antimicrobial and anti-inflammatory properties of matrine that are associated with glycerophospholipid metabolism and the sphingolipid metabolic signaling pathways.

Conclusion

These insights into the immunoregulatory mechanisms and the corresponding biological responses to matrine demonstrate its potential activity in mitigating the harmful effects of bovine mastitis.
OxyR contributes to virulence of Acidovorax citrulli by regulating anti-oxidative stress and expression of flagellin FliC and type IV pili PilA
Authors: Wang Jianan , Liu Jun , Zhao Yuqiang , Sun Minghui , Yu Guixu , Fan Jiaqin , Tian Yanli , Hu Baishi
Published: September 2022

In many bacteria, OxyR acts as a transcriptional regulator that facilitates infection via degrading hydrogen peroxide (H2O2) generated by the host defense response. Previous studies showed that OxyR also plays an important role in regulating biofilm formation, cell motility, pili relate-genes expression, and surface polysaccharide production. However, the role of OxyR has not been determined in Acidovorax citrulli strain xjl12. In the current study, the qRT-PCR and western blot assays revealed that the expression level of oxyR was significantly induced by H2O2. The oxyR deletion mutant of A. citrulli was significantly impaired bacterial tolerance to oxidative stress and reduced catalase (CAT) activity. In addition, oxyR mutant resulted in reduced swimming motility, twitching motility, biofilm formation, virulence, and bacterial growth in planta by significantly affecting flagellin and type IV pili-related gene (fliC and pilA) expression. The qRT-PCR assays and western blot revealed that OxyR positively regulated the expression of fliC and pilA. Furthermore, bacterial one-hybrid assay demonstrated that OxyR directly affected pilA and fliC promoter. Through bacterial two-hybrid assay, it was found that OxyR can directly interact with PilA and FliC. These results suggest that OxyR plays a major role in the regulating of a variety of virulence traits, and provide a foundation for future research on the global effects of OxyR in A. citrulli.
Characteristics of soil microbiota and organic carbon distribution in jackfruit plantation under different fertilization regimes
Authors: Su Lanxi , Bai Tingyu , Wu Gang , Zhao Qingyun , Tan Lehe , Xu Yadong
Published: September 2022

Manure amendment to improve soil organic carbon (SOC) content is an important strategy to sustain ecosystem health and crop production. Here, we utilize an 8-year field experiment to evaluate the impacts of organic and chemical fertilizers on SOC and its labile fractions as well as soil microbial and nematode communities in different soil depths of jackfruit (Artocarpus heterophyllus Lam.). Three treatments were designed in this study, including control with no amendment (CK), organic manure (OM), and chemical fertilizer (CF). Results showed that OM significantly increased the abundance of total nematodes, bacterivores, bacteria, and fungi as well as the value of nematode channel ratio (NCR) and maturity index (MI), but decreased plant-parasites and Shannon diversity (H′). Soil microbial and nematode communities in three soil depths were significantly altered by fertilizer application. Acidobacteria and Chloroflexi dominated the bacterial communities of OM soil, while Nitrospira was more prevalent in CF treatment. Organic manure application stimulated some functional groups of the bacterial community related to the C cycle and saprotroph-symbiotroph fungi, while some groups related to the nitrogen cycle, pathotroph-saprotroph-symbiotroph and pathotroph-saprotroph fungi were predominated in CF treatment. Furthermore, OM enhanced the soil pH, contents of total soil N, P, K, and SOC components, as well as jackfruit yield. Chemical fertilizers significantly affected available N, P, and K contents. The results of network analyses show that more significant co-occurrence relationships between SOC components and nematode feeding groups were found in CK and CF treatments. In contrast, SOC components were more related to microbial communities than to nematode in OM soils. Partial least-squares-path modeling (PLS-PM) revealed that fertilization had significant effects on jackfruit yield, which was composed of positive direct (73.6%) and indirect effects (fertilization → fungal community → yield). It was found that the long-term manure application strategy improves soil quality by increasing SOM, pH, and nutrient contents, and the increased microbivorous nematodes abundance enhanced the grazing pressure on microorganisms and concurrently promoted microbial-derived SOC turnover.
Exploring bacterioplankton communities and their temporal dynamics in the rearing water of a biofloc-based shrimp (Litopenaeus vannamei) aquaculture system
Authors: Kim Su-Kyoung , Song Jaeho , Rajeev Meora , Kim Su Kyoung , Kang Ilnam , Jang In-Kwon , Cho Jang-Cheon
Published: September 2022

Biofloc technology (BFT) has recently gained considerable attention as a sustainable method in shrimp aquaculture. In a successful BFT system, microbial communities are considered a crucial component in their ability to both improve water quality and control microbial pathogens. Yet, bacterioplankton diversity in rearing water and how bacterioplankton community composition changes with shrimp growth are rarely documented. In this study, the Pacific white shrimp,Litopenaeus vannameiwas cultivated in a greenhouse-enclosed BFT system. Rearing water samples were collected on a weekly basis for 5 months (152 days) and water quality variables such as physicochemical parameters and inorganic nutrients were monitored. In parallel, 16S rRNA gene pyrosequencing was employed to investigate the temporal patterns of rearing-water microbiota. The productivity, survival rate, and feed conversion ratio were 3.2–4.4 kg/m3, 74%–89%, and 1.2–1.3, respectively, representing successful super-intensive cultures. The metataxonomic results indicated a highly dynamic bacterioplankton community, with two major shifts over the culture. Members of the phylumPlanctomycetesdominated in rearing water during the early stages, whileActinobacteriadominated during the middle stages, andChloroflexiandTM7dominated during the late stages of culture. The bacterioplankton community fluctuated more in the beginning but stabilized as the culture progressed. Intriguingly, we observed that certain bacterioplankton groups dominated in a culture-stage-specific manner; these groups includeRhodobacteraceae,Flavobacteriaceae,Actinobacteria,andChloroflexi, which either contribute to water quality regulation or possess probiotic potential. Altogether, our results indicate that an operationally successful BFT-based aquaculture system favors the growth and dynamics of specific microbial communities in rearing water. Our study expands the scientific understanding of the practical utilization of microbes in sustainable aquaculture. A thorough understanding of rearing-water microbiota and factors influencing their dynamics will help to establish effective management strategies.
Targeting epigenetic alterations in cancer stem cells
Authors: F. Verona , V. D. Pantina , C. Modica , M. Lo Iacono , C. D’Accardo , G. Porcelli , D. Cricchio , A. Turdo , M. Gaggianesi , S. Di Franco , M. Todaro , V. Veschi , G. Stassi
Published: September 2022

Oncogenes or tumor suppressor genes are rarely mutated in several pediatric tumors and some early stage adult cancers. This suggests that an aberrant epigenetic reprogramming may crucially affect the tumorigenesis of these tumors. Compelling evidence support the hypothesis that cancer stem cells (CSCs), a cell subpopulation within the tumor bulk characterized by self-renewal capacity, metastatic potential and chemo-resistance, may derive from normal stem cells (NSCs) upon an epigenetic deregulation. Thus, a better understanding of the specific epigenetic alterations driving the transformation from NSCs into CSCs may help to identify efficacious treatments to target this aggressive subpopulation. Moreover, deepening the knowledge about these alterations may represent the framework to design novel therapeutic approaches also in the field of regenerative medicine in which bioengineering of NSCs has been evaluated. Here, we provide a broad overview about: 1) the role of aberrant epigenetic modifications contributing to CSC initiation, formation and maintenance, 2) the epigenetic inhibitors in clinical trial able to specifically target the CSC subpopulation, and 3) epigenetic drugs and stem cells used in regenerative medicine for cancer and diseases.
Keeping up with the condensates: The retention, gain, and loss of nuclear membrane-less organelles
Authors: Lacroix Emma , Audas Timothy E.
Published: September 2022

In recent decades, a growing number of biomolecular condensates have been identified in eukaryotic cells. These structures form through phase separation and have been linked to a diverse array of cellular processes. While a checklist of established membrane-bound organelles is present across the eukaryotic domain, less is known about the conservation of membrane-less subcellular structures. Many of these structures can be seen throughout eukaryotes, while others are only thought to be present in metazoans or a limited subset of species. In particular, the nucleus is a hub of biomolecular condensates. Some of these subnuclear domains have been found in a broad range of organisms, which is a characteristic often attributed to essential functionality. However, this does not always appear to be the case. For example, the nucleolus is critical for ribosomal biogenesis and is present throughout the eukaryotic domain, while the Cajal bodies are believed to be similarly conserved, yet these structures are dispensable for organismal survival. Likewise, depletion of the Drosophila melanogaster omega speckles reduces viability, despite the apparent absence of this domain in higher eukaryotes. By reviewing primary research that has analyzed the presence of specific condensates (nucleoli, Cajal bodies, amyloid bodies, nucleolar aggresomes, nuclear speckles, nuclear paraspeckles, nuclear stress bodies, PML bodies, omega speckles, NUN bodies, mei2 dots) in a cross-section of organisms (e.g., human, mouse, D. melanogaster, Caenorhabditis elegans, yeast), we adopt a human-centric view to explore the emergence, retention, and absence of a subset of nuclear biomolecular condensates. This overview is particularly important as numerous biomolecular condensates have been linked to human disease, and their presence in additional species could unlock new and well characterized model systems for health research.
Remote diffusion-weighted imaging lesions and blood pressure variability in primary intracerebral hemorrhage
Authors: Xu Xuhua , Peng Shuangshuang , Zhou Yanli , Li Jiawen , Tong Lusha , Gao Feng
Published: September 2022

Objective

The aim of this study was to examine the association between remote diffusion-weighted imaging lesions (R-DWILs) and blood pressure variability (BPV) in patients with primary intracerebral hemorrhage (ICH).

Methods

We conducted a retrospective review of a consecutive cohort of 375 patients with primary ICH within 24 h onset. R-DWILs were defined as hyperintensity lesions in DWI remote from the hematoma. Blood pressure recordings were extracted up to 24 h post-admission. BPV was measured using SD, coefficient of variation (CV), and successive variation (SV).

Results

Remote DWI lesions were detected in 65 (17.3%) primary ICH patients. In multivariable logistic regression analysis, parameters of BPV were independently associated with R-DWILs, and the results remained consistent after being adjusted with mean SBP. SD, CV, and SV values in the highest quintile, showed 3- to 8-fold increased risk of R-DWILs, compared with the lowest quintile. ΔSBP demonstrated a significant difference in 2 different predictive models. Max SBP only dictated a significant difference in model 1. Mean SBP, admission SBP, and min SBP, failed to present an association with R-DWILs in model 1 or model 2.

Conclusion

Our results provided additional evidence that BPV is associated with the development of R-DWILs in primary ICH.
Characteristics of menstrual disorders and reproductive hormones in women with epilepsy at an Indonesian national referral hospital
Authors: Octaviana Fitri , Sumapraja Kanadi , Wiratman Winnugroho , Indrawati Luh Ari , Budikayanti Astri
Published: September 2022

Objective

Menstrual disorders are more common in women with epilepsy than in those without epilepsy. This study aimed to examine the characteristics of reproductive function in women with epilepsy at an Indonesian national referral hospital.

Methods

A case-control study was conducted from March 2020 to March 2021. Women with and without epilepsy aged ≥18 years were enrolled. All women were premenopausal before epilepsy diagnosis. Data on demographic characteristics, menstrual profiles, epileptic syndrome, seizure type, seizure frequency, etiology, localization, and anticonvulsant medication were collected. Hormone levels (follicle stimulating hormone, luteinizing hormone, prolactin, and estradiol) were measured.

Results

A total of 72 women with and 50 without epilepsy (controls) were included. Dysmenorrhea was more common in women with epilepsy than in those without (59.7 vs. 20%, p < 0.001; odds ratio: 5.931 [95% confidence interval: 2.566–13.709]). Marriage rates were higher in women without epilepsy (82 vs. 45.8%, p < 0.001). No difference was found in hormone levels between the groups. The frequency of seizures was associated with prolactin and estradiol levels (p < 0.001). Polytherapy with clobazam was associated with menstrual cycle regularity. In women with epilepsy with menstrual disorders, valproic acid was associated with higher estradiol levels (p = 0.001) and lamotrigine with lower follicle stimulating hormone levels (p = 0.008).

Significance

Women with epilepsy experienced more dysmenorrhea. A higher frequency of seizures associated with lower prolactin and estradiol levels. Polytherapy with clobazam was associated with irregular menstrual cycles, while valproic acid and lamotrigine was associated with estradiol and follicle stimulating hormone levels.