bluuebunny/crossref_metadata_2025 huggingface dataset:
Therapeutic Effect of Buyang Huanwu Decoction on the Gut Microbiota and Hippocampal Metabolism in a Rat Model of Cerebral Ischemia
Authors: Tang Rongmei , Yi Jian , Lu Shuangying , Chen Bowei , Liu Baiyan
Published: June 2022

Buyang Huanwu decoction (BHD) is a well-known Chinese herbal prescription. It has been widely used in the clinical treatment of cerebral ischemia (CI) in China. However, the mechanism underlying the treatment of CI with BHD remains to be elucidated. In this study, we combined microbiomic and metabolomic strategies to explore the therapeutic effects of BHD on middle cerebral artery occlusion (MCAO) in rats. Our results showed that BHD could effectively improve neurological severity scores and alleviate neuronal damage in rats with MCAO. BHD could also reduce the level of peripheral proinflammatory cytokines and inhibit neuroinflammation. 16S rRNA sequencing showed that BHD could increase the relative abundances of the genera Lactobacillus, Faecalibacterium, Ruminococcaceae_UCG-002, etc., while decreasing the relative abundances of the genera Escherichia-Shigella, Klebsiella, Streptococcus, Coprococcus_2, Enterococcus, etc. Untargeted metabolomic analysis of hippocampal samples showed that 17 significantly differentially abundant metabolites and 9 enriched metabolic pathways were linked with BHD treatment. We also found that the regulatory effects of BHD on metabolites were correlated with the differentially abundant microbial taxa. The predicted function of the gut microbiota and the metabolic pathway enrichment results showed that purine metabolism, glutamatergic synapses, arginine and proline metabolism, and alanine, aspartic acid and glutamate metabolism were involved in the effects of BHD. These pathways may be related to pathological processes such as excitotoxicity, neuroinflammation, and energy metabolism disorder in CI. In summary, these findings suggest that regulation of hippocampal metabolism and of the composition and function of the gut microbiota may be important mechanisms underlying the effect of BHD in the treatment of CI.
The Role of Egg Yolk in Modulating the Virulence of Salmonella Enterica Serovar Enteritidis
Authors: Xu Yumin , Abdelhamid Ahmed G. , Sabag-Daigle Anice , Sovic Michael G. , Ahmer Brian M.M. , Yousef Ahmed E.
Published: June 2022

Contribution of food vehicles to pathogenicity of disease-causing microorganisms is an important but overlooked research field. The current study was initiated to reveal the relationship between virulence of Salmonella enterica serovar Enteritidis and egg yolk as a hosting medium. Mice were orally challenged with Salmonella Enteritidis cultured in egg yolk or tryptic soy broth (TSB). Additionally, mice were challenged with Salmonella Enteritidis cultured in TSB, followed by administration of sterile egg yolk, to discern the difference between pre-growth of the pathogen and its mere presence in egg yolk during infection. The pathogen’s Lethal dose 50 (LD50) was the lowest when grown in yolk (2.8×102 CFU), compared to 1.1×103 CFU in TSB, and 4.6×103 CFU in TSB followed by administration of sterile yolk. Additionally, mice that orally received Salmonella Enteritidis grown in egg yolk expressed a high death rate. These findings were supported by transcriptional analysis results. Expression of promoters of virulence-related genes (sopB and sseA) in genetically modified Salmonella Enteritidis reporter strains was significantly higher (p < 0.05) when the bacterium was grown in the yolk, compared to that grown in TSB. Sequencing of RNA (RNA-seq) revealed 204 differentially transcribed genes in Salmonella Enteritidis grown in yolk vs. TSB. Yolk-grown Salmonella Enteritidis exhibited upregulated virulence pathways, including type III secretion systems, epithelial cell invasion, and infection processes; these observations were confirmed by RT-qPCR results. The transcriptomic analysis suggested that upregulation of virulence machinery of Salmonella Enteritidis grown in egg yolk was related to increased iron uptake, biotin utilization, flagellar biosynthesis, and export of virulence proteins encoded on Salmonella pathogenicity island 1, 2, 4, and 5. These biological responses may have acted in concert to increase the virulence of Salmonella infection in mice. In conclusion, growth in egg yolk enhanced Salmonella Enteritidis virulence, indicating the significance of this food vehicle to the risk assessment of salmonellosis.
Synergistic Microbicidal Effect of AUR and PEITC Against Staphylococcus aureus Skin Infection
Authors: Chen Haoran , Yang Ning , Yu Liang , Li Jiajia , Zhang Hui , Zheng Yahong , Xu Mengran , Liu Yanyan , Yang Yi , Li Jiabin
Published: June 2022

Given the increasing prevalence ofStaphylococcus aureusantibiotic resistance, there is an urgent need to repurpose approved drugs with known pharmacology and toxicology as an alternative therapeutic strategy. We have reported that the sustained monotherapy of auranofin (AUR) inevitably resulted in reduced susceptibility or even the emergence of resistance to AUR inS. aureus.However, whether drug combination could increase antibacterial activity while preventing AUR resistance is still unknown. Here, we focused on the important role of AUR combined with phenethyl isothiocyanate (PEITC) in skin infection and determined the synergistic antimicrobial effect onS. aureusby using checkerboard assays and time-kill kinetics analysis. This synergistic antimicrobial activity correlated with increased reactive oxygen species (ROS) generation, disruption of bacterial cell structure, and inhibition of biofilm formation. We also showed that AUR synergized with PEITC effectively restored the susceptibility to AURviaregulating thioredoxin reductase (TrxR) and rescued mice from subcutaneous abscesses through eliminatingS. aureuspathogens, including methicillin-resistantS. aureus(MRSA). Collectively, our study indicated that the AUR and PEITC combination had a synergistic antimicrobial impact onS. aureus in vitroandin vivo. These results suggest that AUR and PEITC treatment may be a promising option forS. aureusinfection.
Mechanism of COVID-19 Causing ARDS: Exploring the Possibility of Preventing and Treating SARS-CoV-2
Authors: Zheng Jiajing , Miao Jiameng , Guo Rui , Guo Jinhe , Fan Zheng , Kong Xianbin , Gao Rui , Yang Long
Published: June 2022

Novel coronavirus pneumonia (COVID-19) is spreading worldwide, causing great harm and stress to humans. Since patients with novel coronavirus (SARS-CoV-2) have a high probability of developing acute respiratory distress syndrome (ARDS) in severe cases, the pathways through which SARS-CoV-2 causes lung injury have become a major concern in the scientific field. In this paper, we investigate the relationship between SARS-CoV-2 and lung injury and explore the possible mechanisms of COVID-19 in ARDS from the perspectives of angiotensin-converting enzyme 2 protein, cytokine storm, activation of the immune response, triggering of Fas/FasL signaling pathway to promote apoptosis, JAK/STAT pathway, NF-κB pathway, type I interferon, vitamin D, and explore the possibility of prevention and treatment of COVID-19. To explore the possibility of SARS-CoV-2, and to provide new ideas to stop the development of ARDS in COVID-19 patients.
Prevalence and Predisposing Factors of Non-infectious Cardiac Implantable Electronic Device Lead Masses as Incidental Finding During Transoesophageal Echocardiography: A Retrospective Cohort Study
Authors: Kuecken Tanja , Jasaityte Ruta , Bülow Cara , Gross Jessica , Haase-Fielitz Anja , Neuss Michael , Butter Christian
Published: June 2022

Objectives

In this study, we assessed the prevalence and predisposing factors of non-infectious CIED lead masses as incidental finding during transoesophageal echocardiography (TOE).

Methods

In a retrospective single centre study, we analysed TOE examinations performed for indications other than infectious endocarditis in 141 patients with CIED. Patients with non-suspicious leads and those with incidental non-infectious lead masses were compared with respect to clinical characteristics, anticoagulation, indication for TOE, and CIED lead characteristics. The odds ratios for non-infectious CIED lead masses were calculated.

Results

Non-infectious CIED lead masses were detected in 39 (27.6%) of the 141 patients. They were more often identified on ICD and CRT-D leads compared to pacemaker and CRT-P leads [OR 2.77 (95% CI 1.29–5.95), p = 0.008]. The lifespan of the CIEDs from the first implantation to the index TOE did not differ between both groups. Incidental CIED lead masses were more prevalent in patients who received their device for primary prevention of sudden cardiac death (43.2%) and for resynchronisation (63.6%) but were less prevalent in patients with oral anticoagulation [OR.33 (95% CI.003–1.003), p = 0.048].

Conclusion

Incidental non-infectious CIED lead masses were frequently found in TOE, with highest prevalence in ICD and CRT-D devices implanted for patients with dilated cardiomyopathy. Patients with therapeutic anticoagulation had significantly lower prevalence of CIED lead masses than those without.
Leveraging Mobile-Based Sensors for Clinical Research to Obtain Activity and Health Measures for Disease Monitoring, Prevention, and Treatment
Authors: Dandapani Hari G. , Davoodi Natalie M. , Joerg Lucie C. , Li Melinda M. , Strauss Daniel H. , Fan Kelly , Massachi Talie , Goldberg Elizabeth M.
Published: June 2022

Clinical researchers are using mobile-based sensors to obtain detailed and objective measures of the activity and health of research participants, but many investigators lack expertise in integrating wearables and sensor technologies effectively into their studies. Here, we describe the steps taken to design a study using sensors for disease monitoring in older adults and explore the benefits and drawbacks of our approach. In this study, the Geriatric Acute and Post-acute Fall Prevention Intervention (GAPcare), we created an iOS app to collect data from the Apple Watch's gyroscope, accelerometer, and other sensors; results of cognitive and fitness tests; and participant-entered survey data. We created the study app using ResearchKit, an open-source framework developed by Apple for medical research that includes neuropsychological tests (e.g., of executive function and memory), gait speed, balance, and other health assessments. Data is transmitted via an Application Programming Interface (API) from the app to REDCap for researchers to monitor and analyze in real-time. Employing the lessons learned from GAPcare could help researchers create study-tailored research apps and access timely information about their research participants from wearables and smartphone devices for disease prevention, monitoring, and treatment.
An Integrated Approach in the Assessment of the Vlasina River System Pollution by Toxic Elements
Authors: Sakan Sanja , Mihajlidi-Zelić Aleksandra , Škrivanj Sandra , Frančišković-Bilinski Stanislav , Đorđević Dragana
Published: June 2022

Increasing pollutant levels in surface water are a very important problem in developing countries. In Serbia, the largest rivers are transboundary rivers that cross the border already polluted. Taking this into account, evaluation of the distribution characteristics, ecological risk, and sources of toxic elements in river water and surface sediments in the watercourses of the Vlasina watershed is of great significance for the protection of water resources in Serbia. A total of 17 sediment and 18 water samples were collected and analyzed by Inductively Coupled Plasma—Optical Emission spectrometry (ICP-OES) and Inductively Coupled Plasma—Mass spectrometry (ICP-MS) to determine micro- and macroelements contents. The geo-accumulation index (Igeo) was applied to determine and classify the magnitude of toxic element pollution in this river sediment. The contents of the studied toxic elements were below water and sediment quality guidelines. For studied river water, results of principal component analysis (PCA) indicated the difference in behavior of Cr, Mn, Ni, Cu, and As and V, respectively. Cluster analysis (CA) classified water samples according to As and Cu content. The PCA results revealed that lead in river sediments had different behavior than other elements and can be associated mainly with anthropogenic sources. According to the degree of Igeo, the majority of sediments in the Vlasina region were uncontaminated regarding studied toxic elements. The origin of elements is mostly from natural processes such as soil and rock weathering.
Independent Effects of Species Removal and Asynchrony on Invariability of an Intertidal Rocky Shore Community
Authors: Fica-Rojas Eliseo , Catalán Alexis M. , Broitman Bernardo R. , Pérez-Matus Alejandro , Valdivia Nelson
Published: June 2022

Ecological stability depends on interactions between different levels of biological organization. The insurance effects occur when increasing species diversity leads to more temporally invariable (i.e., more stable) community-level properties, due in part to asynchronous population-level fluctuations. While the study of insurance effects has received considerable attention, the role of dominant species that contribute with particular functional traits across different level of organizations is less understood. Using a field-based manipulative experiment, we investigated how species richness and different types of parameters at the population level, such as the invariability of dominants, population invariability, and population asynchrony, influence the community invariability. The experiment involved the repetitive removal of the canopy forming algaMazzaella laminarioides(hereafter “Mazzaella”) during 32 months in two rocky intertidal sites of northern-central Chile. We predicted that the invariability of dominants enhances community invariability, that the effect of multispecies population-level parameters on community invariability are dependent on species richness, and that subdominant algae are unable to fully compensate the loss of canopies of the dominant species. Biomass of algae and mobile invertebrates was quantified over time. We observed independent effects ofMazzaellaremoval and community-wide asynchrony on community invariability. While canopy removal reduced community invariability, population asynchrony boosted community invariability regardless of the presence of canopies. In addition, filamentous and foliose algae were unable to compensate the loss of biomass triggered by the experimental removal ofMazzaella. Canopy removal led to a severe decrement in the biomass of macrograzers, while, at the same time, increased the biomass of mesograzers. Asynchrony stemmed from compensatory trophic responses of mesograzers to increased abundances of opportunistic algae. Thus, further work on consumer-resource interactions will improve our understanding of the links between population- and community-level aspects of stability.
Secondary DNA Barcodes (CAM, GAPDH, GS, and RpB2) to Characterize Species Complexes and Strengthen the Powdery Mildew Phylogeny
Authors: Bradshaw Michael J. , Guan Guan-Xiu , Nokes Liam , Braun Uwe , Liu Shu-Yan , Pfister Donald H.
Published: June 2022

Powdery mildews are a group of economically and ecologically important plant pathogens. In the past 25 years the use of ribosomal DNA (rDNA) in the powdery mildews has led to major taxonomic revisions. However, the broad scale use of rDNA has also revealed multiple species complexes that cannot be differentiated based on ITS + LSU data alone. Currently, there are only two powdery mildew taxonomic studies that took a multi-locus approach to resolve a species complex. In the present study, we introduce primers to sequence four additional regions (CAM, GAPDH, GS, and RPB2) that have the potential to improve support values in both broad and fine scale phylogenetic analyses. The primers were applied to a broad set of powdery mildew genera in China and the United States, and phylogenetic analyses included some of the common complexes. In taxa with nearly identical ITS sequences the analyses revealed a great amount of diversity. In total 154 non-rDNA sequences from 11 different powdery mildew genera were deposited in NCBI’s GenBank, laying the foundation for secondary barcode databases for powdery mildews. The combined and single loci phylogenetic trees constructed generally followed the previously defined species/genus concepts for the powdery mildews. Future research can use these primers to conduct in depth phylogenetic, and taxonomic studies to elucidate the evolutionary relationships of species and genera within the powdery mildews.
Systematic Construction and Validation of a Novel Macrophage Differentiation–Associated Prognostic Model for Clear Cell Renal Cell Carcinoma
Authors: Liu Chen , Zhang Xuhui , Hu Caoyang , Liang Xuezhi , Cao Xiaoming , Wang Dongwen
Published: June 2022

Background: Clear cell renal cell carcinoma (ccRCC) is a malignant tumor of the human urinary system. Macrophage differentiation is associated with tumorigenesis. Therefore, exploring the prognostic value of macrophage differentiation–associated genes (MDGs) may contribute to better clinical management of ccRCC patients.

Methods: The RNA sequence data of ccRCC were obtained from The Cancer Genome Atlas (TCGA) database. Differentially expressed MDGs were unveiled in ccRCC and normal samples. The prognostic model was established according to the univariate and multivariate Cox regression analyses. By combining clinico-pathological features and prognostic genes, a nomogram was established to predict individual survival probability. The Tumor Immune Estimation Resource (TIMER) database was utilized to analyze the correlation between prognostic genes and immune infiltrating cells. Eventually, the mRNA and protein expression levels of prognostic genes were verified.

Results: A total of 52 differentially expressed prognosis-related MDGs were identified in ccRCC. Afterward, a six-gene prognostic model (ABCG1, KDF1, KITLG, TGFA, HAVCR2, and CD14) was constructed through the Cox analysis. The overall survival in the high-risk group was relatively poor. Moreover, the risk score was identified as an independent prognostic factor. We constructed a prognostic nomogram with a well-fitted calibration curve based on risk score and clinical data. Furthermore, the prognostic genes were significantly related to the level of immune cell infiltration including B cells, CD8+T cells, CD4+T cells, macrophages, neutrophils, and dendritic cells. Finally, the mRNA expression of prognostic genes in clinical ccRCC tissues showed that the ABCG1, HAVCR2, CD14, and TGFA mRNA in tumor samples were increased compared with the adjacent control tissue samples, while KDF1 and KITLG were decreased, which was consistent with the verification results in the GSE53757.

Conclusion: In conclusion, this study identified and validated a macrophage differentiation–associated prognostic model for ccRCC that could be used to predict the outcomes of the ccRCC patients.
Epigenetic and Transcriptomic Regulation Landscape in HPV+ Cancers: Biological and Clinical Implications
Authors: Castro-Oropeza Rosario , Piña-Sánchez Patricia
Published: June 2022

Human Papillomavirus (HPV) is an oncogenic virus that causes the highest number of viral-associated cancer cases and deaths worldwide, with more than 690,000 new cases per year and 342,000 deaths only for cervical cancer (CC). Although the incidence and mortality rates for CC are declining in countries where screening and vaccination programs have been implemented, other types of cancer in which HPV is involved, such as oropharyngeal cancer, are increasing, particularly in men. Mutational and transcriptional profiles of various HPV-associated neoplasms have been described, and accumulated evidence has shown the oncogenic capacity of E6, E7, and E5 genes of high-risk HPV. Interestingly, transcriptomic analysis has revealed that although a vast majority of the human genome is transcribed into RNAs, only 2% of transcripts are translated into proteins. The remaining transcripts lacking protein-coding potential are called non-coding RNAs. In addition to the transfer and ribosomal RNAs, there are regulatory non-coding RNAs classified according to size and structure in long non-coding RNAs (lncRNAs), circular RNAs (circRNAs), and small RNAs; such as microRNAs (miRNAs), piwi-associated RNAs (piRNAs), small nucleolar RNAs (snoRNAs) and endogenous short-interfering RNAs. Recent evidence has shown that lncRNAs, miRNAs, and circRNAs are aberrantly expressed under pathological conditions such as cancer. In addition, those transcripts are dysregulated in HPV-related neoplasms, and their expression correlates with tumor progression, metastasis, poor prognosis, and recurrence. Nuclear lncRNAs are epigenetic regulators involved in controlling gene expression at the transcriptional level through chromatin modification and remodeling. Moreover, disruption of the expression profiles of those lncRNAs affects multiple biological processes such as cell proliferation, apoptosis, and migration. This review highlights the epigenetic alterations induced by HPV, from infection to neoplastic transformation. We condense the epigenetic role of non-coding RNA alterations and their potential as biomarkers in transformation’s early stages and clinical applications. We also summarize the molecular mechanisms of action of nuclear lncRNAs to understand better their role in the epigenetic control of gene expression and how they can drive the malignant phenotype of HPV-related neoplasia. Finally, we review several chemical and epigenetic therapy options to prevent and treat HPV-associated neoplasms.
Integration of Single-Cell Transcriptomics With a High Throughput Functional Screening Assay to Resolve Cell Type, Growth Kinetics, and Stemness Heterogeneity Within the Comma-1D Cell Line
Authors: Dave Arpit , Nekritz Erin , Charytonowicz Daniel , Beaumont Michael , Smith Melissa , Beaumont Kristin , Silva Jose , Sebra Robert
Published: June 2022

Cell lines are one of the most frequently implemented model systems in life sciences research as they provide reproducible high throughput testing. Differentiation of cell cultures varies by line and, in some cases, can result in functional modifications within a population. Although research is increasingly dependent on these in vitro model systems, the heterogeneity within cell lines has not been thoroughly investigated. Here, we have leveraged high throughput single-cell assays to investigate the Comma-1D mouse cell line that is known to differentiate in culture. Using scRNASeq and custom single-cell phenotype assays, we resolve the clonal heterogeneity within the referenced cell line on the genomic and functional level. We performed a cohesive analysis of the transcriptome of 5,195 sequenced cells, of which 85.3% of the total reads successfully mapped to the mm10-3.0.0 reference genome. Across multiple gene expression analysis pipelines, both luminal and myoepithelial lineages were observed. Deep differential gene expression analysis revealed eight subclusters identified as luminal progenitor, luminal differentiated, myoepithelial differentiated, and fibroblast subpopulations—suggesting functional clustering within each lineage. Gene expression of published mammary stem cell (MaSC) markers Epcam, Cd49f, and Sca-1 was detected across the population, with 116 (2.23%) sequenced cells expressing all three markers. To gain insight into functional heterogeneity, cells with patterned MaSC marker expression were isolated and phenotypically investigated through a custom single-cell high throughput assay. The comparison of growth kinetics demonstrates functional heterogeneity within each cell cluster while also illustrating significant limitations in current cell isolation methods. We outlined the upstream use of our novel automated cell identification platform—to be used prior to single-cell culture—for reduced cell stress and improved rare cell identification and capture. Through compounding single-cell pipelines, we better reveal the heterogeneity within Comma-1D to identify subpopulations with specific functional characteristics.
Genome Editing Targets for Improving Nutrient Use Efficiency and Nutrient Stress Adaptation
Authors: Sathee Lekshmy , Jagadhesan B. , Pandesha Pratheek H. , Barman Dipankar , Adavi B Sandeep , Nagar Shivani , Krishna G. K. , Tripathi Shailesh , Jha Shailendra K. , Chinnusamy Viswanathan
Published: June 2022

In recent years, the development of RNA-guided genome editing (CRISPR-Cas9 technology) has revolutionized plant genome editing. Under nutrient deficiency conditions, different transcription factors and regulatory gene networks work together to maintain nutrient homeostasis. Improvement in the use efficiency of nitrogen (N), phosphorus (P) and potassium (K) is essential to ensure sustainable yield with enhanced quality and tolerance to stresses. This review outlines potential targets suitable for genome editing for understanding and improving nutrient use (NtUE) efficiency and nutrient stress tolerance. The different genome editing strategies for employing crucial negative and positive regulators are also described. Negative regulators of nutrient signalling are the potential targets for genome editing, that may improve nutrient uptake and stress signalling under resource-poor conditions. The promoter engineering by CRISPR/dead (d) Cas9 (dCas9) cytosine and adenine base editing and prime editing is a successful strategy to generate precise changes. CRISPR/dCas9 system also offers the added advantage of exploiting transcriptional activators/repressors for overexpression of genes of interest in a targeted manner. CRISPR activation (CRISPRa) and CRISPR interference (CRISPRi) are variants of CRISPR in which a dCas9 dependent transcription activation or interference is achieved. dCas9-SunTag system can be employed to engineer targeted gene activation and DNA methylation in plants. The development of nutrient use efficient plants through CRISPR-Cas technology will enhance the pace of genetic improvement for nutrient stress tolerance of crops and improve the sustainability of agriculture.
Diagnostic, Prognostic, and Immunological Roles of HELLS in Pan-Cancer: A Bioinformatics Analysis
Authors: Liang Xiao , Li Linji , Fan Yuchao
Published: June 2022

Background

Inappropriate repair of DNA damage drives carcinogenesis. Lymphoid-specific helicase (HELLS) is an important component of the chromatin remodeling complex that helps repair DNA through various mechanisms such as DNA methylation, histone posttranslational modification, and nucleosome remodeling. Its role in human cancer initiation and progression has garnered recent attention. Our study aims to provide a more systematic and comprehensive understanding of the role of HELLS in the development and progression of multiple malignancies through analysis of HELLS in cancers.

Methods

We explored the role of HELLS in cancers using The Cancer Genome Atlas (TCGA) and Genotype-Tissue Expression (GTEx) database. Multiple web platforms and software were used for data analysis, including R, Cytoscape, HPA, Archs4, TISIDB, cBioPortal, STRING, GSCALite, and CancerSEA.

Results

High HELLS expression was found in a variety of cancers and differentially expressed across molecular and immune subtypes. HELLS was involved in many cancer pathways. Its expression positively correlated with Th2 and Tcm cells in most cancers. It also correlated with genetic markers of immunomodulators in various cancers.

Conclusions

Our study elucidates the role HELLS plays in promotion, inhibition, and treatment of different cancers. HELLS is a potential cancer diagnostic and prognostic biomarker with immune, targeted, or cytotoxic therapeutic value. This work is a prerequisite to clinical validation and treatment of HELLS in cancers.
Diagnostic Performance of Parasitological, Immunological, Molecular, and Ultrasonographic Tests in Diagnosing Intestinal Schistosomiasis in Fieldworkers From Endemic Municipalities in the Philippines
Authors: Tabios Ian Kim B. , Sato Marcello Otake , Tantengco Ourlad Alzeus G. , Fornillos Raffy Jay C. , Kirinoki Masashi , Sato Megumi , Rojo Raniv D. , Fontanilla Ian Kendrich C. , Chigusa Yuichi , Medina Paul Mark B. , Kikuchi Mihoko , Leonardo Lydia R.
Published: June 2022

Schistosomiasis remains to ha/ve a significant public health impact in the Philippines. The Kato-Katz (K-K) technique is the reference standard and most used technique for definitive diagnosis of intestinal schistosomiasis for control programs in endemic regions. However, this has a very low sensitivity when applied in areas of low endemicity and patients with light infection. Hence, this study determined the diagnostic performance of immunological, molecular, parasitological, and ultrasonographic tests in diagnosing intestinal schistosomiasis in endemic municipalities in the Philippines. We performed a community-based cross-sectional study to determine the positivity of schistosomiasis in Leyte, Philippines. The diagnostic performance of five different detection techniques: (1) three stool K-K with duplicate smears; (2) soluble egg antigen IgG ELISA; (3) urine point-of-care circulating cathodic antigen (POC-CCA) test; (4) detection of Schistosoma japonicum circulating DNA (SjcDNA) in serum and urine samples; (5) focused abdominal ultrasound (US), were also obtained in this study. Multiple stool examinations enhanced the sensitivity of K-K from 26.2% (95% CI [16.4, 38.8]) with single stool to 53.8% (95% CI [41.1, 66.1]) and 69.2% (95% CI [56.4, 80.0]) with two and three stools from consecutive days, respectively. Among the SjcDNA nucleic acid amplification test (NAAT)-based detection assays, loop-mediated isothermal amplification (LAMP) PCR using sera had the highest sensitivity at 92.3% (95% CI [82.2, 97.1]) with LAMP consistently identifying more positive cases in both serum and urine samples. This study showed that single stool K-K, which remains the only diagnostic test available in most endemic areas in the Philippines, had low sensitivity and failed to identify most patients with light infection. SjcDNA detection assay and POC-CCA urine test were more sensitive than stool microscopy in detecting schistosomiasis. On the other hand, US was less sensitive than the widely utilized K-K technique in diagnosing schistosomiasis. This study emphasizes the need to revisit the use of single stool K-K in the surveillance and case detection of schistosomiasis in endemic areas of the Philippines. The availability of advanced and more sensitive diagnostic tests will help better control, prevent, and eliminate schistosomiasis in the country.
microRNA Expression and Its Association With Disability and Brain Atrophy in Multiple Sclerosis Patients Treated With Glatiramer Acetate
Authors: Dominguez-Mozo María I. , Casanova Ignacio , De Torres Laura , Aladro-Benito Yolanda , Perez-Perez Silvia , Garcia-Martínez Angel , Gomez Patricia , Abellan Sara , De Antonio Esther , Lopez-De-Silanes Carlos , Alvarez-Lafuente Roberto
Published: June 2022

Background

MicroRNAs are small non-coding RNA that regulate gene expression at a post-transcriptional level affecting several cellular processes including inflammation, neurodegeneration and remyelination. Different patterns of miRNAs expression have been demonstrated in multiple sclerosis compared to controls, as well as in different courses of the disease. For these reason they have been postulated as promising biomarkers candidates in multiple sclerosis.

Objective

to correlate serum microRNAs profile expression with disability, cognitive functioning and brain volume in patients with remitting-relapsing multiple sclerosis.

Methods

cross-sectional study in relapsing-remitting multiple sclerosis patients treated with glatiramer acetate. Disability was measured with Expanded Disability Status Scale (EDSS) and cognitive function was studied with Symbol Digit Modalities Test (SDMT). Brain volume was analyzed with automatic software NeuroQuant®.

Results

We found an association between miR.146a.5p (rs:0.434, p=0.03) and miR.9.5p (rs:0.516, p=0.028) with EDSS; and miR-146a.5p (rs:-0.476, p=0.016) and miR-126.3p (rs:-0.528, p=0.007) with SDMT. Regarding to the brain volume, miR.9.5p correlated with thalamus (rs:-0.545, p=0.036); miR.200c.3p with pallidum (rs:-0.68, p=0.002) and cerebellum (rs:-0.472, p=0.048); miR-138.5p with amygdala (rs:0.73, p=0.016) and pallidum (rs:0.64, p=0.048); and miR-223.3p with caudate (rs:0.46, p=0.04).

Conclusions

These data support the hypothesis of microRNA as potential biomarkers in this disease. More studies are needed to validate these results and to better understand the role of microRNAs in the pathogenesis, monitoring and therapeutic response of multiple sclerosis.
NETosis in Psoriatic Arthritis: Serum MPO–DNA Complex Level Correlates With Its Disease Activity
Authors: Li Borui , Li Guangtao , Yang Xinlei , Song Zhibo , Wang Yu , Zhang Zhuoli
Published: June 2022

Background

Neutrophil extracellular trap formation (NETosis) has been rarely reported in psoriatic arthritis (PsA). We aimed to explore the involvement of NETosis in the inflammation of PsA.

Methods

Serum myeloperoxidase–DNA (MPO-DNA) complex was detected by a modified enzyme-linked immunosorbent assay and compared among 74 patients with PsA, 58 patients with psoriasis (PsO), and 20 healthy controls. The association of MPO–DNA level with disease activity index at baseline and follow-up was analyzed in patients with PsA. Receiver operating characteristic curve was used to evaluate the predictive value of MPO–DNA for treatment response.

Results

MPO–DNA complex level in serum was significantly increased in patients with PsA/PsO compared to healthy controls (p < 0.001). The level of MPO–DNA was positively associated with DAPSA score and its components (including TJC, SJC, PGA, VAS-pain and CRP, r = 0.25–0.409, all p-values < 0.05). Serum MPO–DNA level was downregualted at 12 weeks after treatment compared to baseline (p = 0.022). The decrease of MPO–DNA level was more dramatic in patients with PsA who achieved both ACR50 and PASI50 response than those achieving neither of them at 12 weeks (p = 0.023). ROC analysis revealed that the serum MPO–DNA level predicted both ACR50 and PASI50 achievement at week 12 (p = 0.04; 95% CIs, 0.56–0.94). Moreover, the baseline MPO–DNA level (p = 0.009; 95% CIs, 0.748–1) and change of MPO–DNA at week 12 from baseline (p = 0.004; 95% CIs, 0.802–1) were associated with the achievement of both ACR70 and PASI75 response at week 24.

Conclusions

NETosis plays an important role in psoriatic diseases. The level of MPO–DNA complex in serum reflects disease activity. Serum MPO–DNA complex may be a useful biomarker to predict the therapeutic response in PsA.
Considerations of CD8+ T Cells for Optimized Vaccine Strategies Against Respiratory Viruses
Authors: Hirai Toshiro , Yoshioka Yasuo
Published: June 2022

The primary goal of vaccines that protect against respiratory viruses appears to be the induction of neutralizing antibodies for a long period. Although this goal need not be changed, recent severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) variants have drawn strong attention to another arm of acquired immunity, CD8+ T cells, which are also called killer T cells. Recent evidence accumulated during the coronavirus disease 2019 (COVID-19) pandemic has revealed that even variants of SARS-CoV-2 that escaped from neutralizing-antibodies that were induced by either infection or vaccination could not escape from CD8+ T cell-mediated immunity. In addition, although traditional vaccine platforms, such as inactivated virus and subunit vaccines, are less efficient in inducing CD8+ T cells, newly introduced platforms for SARS-CoV-2, namely, mRNA and adenoviral vector vaccines, can induce strong CD8+ T cell-mediated immunity in addition to inducing neutralizing antibodies. However, CD8+ T cells function locally and need to be at the site of infection to control it. To fully utilize the protective performance of CD8+ T cells, it would be insufficient to induce only memory cells circulating in blood, using injectable vaccines; mucosal immunization could be required to set up CD8+ T cells for the optimal protection. CD8+ T cells might also contribute to the pathology of the infection, change their function with age and respond differently to booster vaccines in comparison with antibodies. Herein, we overview cutting-edge ideas on CD8+ T cell-mediated immunity that can enable the rational design of vaccines for respiratory viruses.
Different Immunoregulation Roles of Activin A Compared With TGF-β
Authors: Li Fanglin , Long Yiru , Yu Xiaolu , Tong Yongliang , Gong Likun
Published: June 2022

Activin A, a critical member of the transforming growth factor-β (TGF-β) superfamily, is a pluripotent factor involved in allergies, autoimmune diseases, cancers and other diseases with immune disorder. Similar to its family member, TGF-β, activin A also transmits signals through SMAD2/SMAD3, however, they bind to distinct receptors. Recent studies have uncovered that activin A plays a pivotal role in both innate and adaptive immune systems. Here we mainly focus its effects on activation, differentiation, proliferation and function of cells which are indispensable in the immune system and meanwhile make some comparisons with those of TGF-β.
Mechanisms of Direct and Indirect Presentation of Self-Antigens in the Thymus
Authors: Březina Jiří , Vobořil Matouš , Filipp Dominik
Published: June 2022

The inevitability of evolution of the adaptive immune system with its mechanism of randomly rearranging segments of the T cell receptor (TCR) gene is the generation of self-reactive clones. For the sake of prevention of autoimmunity, these clones must be eliminated from the pool of circulating T cells. This process occurs largely in the thymic medulla where the strength of affinity between TCR and self-peptide MHC complexes is the factor determining thymocyte fate. Thus, the display of self-antigens in the thymus by thymic antigen presenting cells, which are comprised of medullary thymic epithelial (mTECs) and dendritic cells (DCs), is fundamental for the establishment of T cell central tolerance. Whereas mTECs produce and present antigens in a direct, self-autonomous manner, thymic DCs can acquire these mTEC-derived antigens by cooperative antigen transfer (CAT), and thus present them indirectly. While the basic characteristics for both direct and indirect presentation of self-antigens are currently known, recent reports that describe the heterogeneity of mTEC and DC subsets, their presentation capacity, and the potentially non-redundant roles in T cell selection processes represents another level of complexity which we are attempting to unravel. In this review, we underscore the seminal studies relevant to these topics with an emphasis on new observations pertinent to the mechanism of CAT and its cellular trajectories underpinning the preferential distribution of thymic epithelial cell-derived self-antigens to specific subsets of DC. Identification of molecular determinants which control CAT would significantly advance our understanding of how the cellularly targeted presentation of thymic self-antigens is functionally coupled to the T cell selection process.
Myxozoan Diversity Infecting Ornamental Fishes Imported to Australia
Authors: Trujillo-González Alejandro , Allas Joshua , Miller Terrence L. , Becker Joy A. , Hutson Kate S.
Published: June 2022

The ornamental fish trade provides a pathway for the global translocation of aquatic parasites. Myxozoa is comprised of highly specialized metazoan parasites of aquatic hosts with a wide host range. Interest in the group has intensified along with the development of aquaculture due to emergent pathogenic myxozoan species in both freshwater and marine environments. However, little is known on myxozoan diversity in the ornamental fish trade. We examined 630 ornamental fish imported from Asia to Australia (representing 24 fish populations, including freshwater and wild caught marine fish species) for myxozoan parasites during 2015. Fish were sampled under Australian quarantine following veterinary certification that they showed no clinical signs of pests and diseases from the exporting country and visual inspection at Australian border control. Myxozoan parasites infected 8 of 12 freshwater populations and 8 of 12 marine fish populations. A total of 12 morphologically distinct Myxobolus spores were detected amongst all goldfish, Carassius auratus populations. Myxidium spores were detected in kissing gourami, Helostoma temminckii, and Ceratomyxa sp. spores were detected in cardinal fishes, Cheilodipterus quinquelineatus, Pterapogon kauderni, and Zoramia leptocantha. Kudoa sp. spores were detected in C. quinquelineatus, Sphaeramia nematoptera and Z. leptocantha. Results of this study show that Australian pre-export health requirements and visual inspections do not reliably detect myxozoan infections. Inspection prior to exportation and at border control should account for the highly cryptic nature of myxozoan parasites and consider alternative detection methods to complement inspections at border control.
Design and Applications of Integrated Transducers in Commercial CMOS Technology
Authors: Rawat Udit , Anderson Jackson D. , Weinstein Dana
Published: June 2022

Monolithic integration of Microelectromechanical Systems (MEMS) directly within CMOS technology offers enhanced functionality for integrated circuits (IC) and the potential improvement of system-level performance for MEMS devices in close proximity to biasing and sense circuits. While the bulk of CMOS-MEMS solutions involve post-processing of CMOS chips to define freely-suspended MEMS structures, there are key applications and conditions under which a solid, unreleased acoustic structure composed of the CMOS stack is preferred. Unreleased CMOS-MEMS devices benefit from lower barrier-to-entry with no post-processing of the CMOS chip, simplified packaging, robustness under acceleration and shock, stress gradient insensitivity, and opportunities for frequency scaling. This paper provides a review of advances in unreleased CMOS-MEMS devices over the past decade, with focus on dispersion engineering of guided waves in CMOS, acoustic confinement, CMOS-MEMS transducers, and large signal modeling. We discuss performance limits with standard capacitive transduction, with emphasis on performance boost with emerging CMOS materials including ferroelectrics under development for memory.
Precision Medicine: An Optimal Approach to Patient Care in Renal Cell Carcinoma
Authors: Sharma Revati , Kannourakis George , Prithviraj Prashanth , Ahmed Nuzhat
Published: June 2022

Renal cell cancer (RCC) is a heterogeneous tumor that shows both intra- and inter-heterogeneity. Heterogeneity is displayed not only in different patients but also among RCC cells in the same tumor, which makes treatment difficult because of varying degrees of responses generated in RCC heterogeneous tumor cells even with targeted treatment. In that context, precision medicine (PM), in terms of individualized treatment catered for a specific patient or groups of patients, can shift the paradigm of treatment in the clinical management of RCC. Recent progress in the biochemical, molecular, and histological characteristics of RCC has thrown light on many deregulated pathways involved in the pathogenesis of RCC. As PM-based therapies are rapidly evolving and few are already in current clinical practice in oncology, one can expect that PM will expand its way toward the robust treatment of patients with RCC. This article provides a comprehensive background on recent strategies and breakthroughs of PM in oncology and provides an overview of the potential applicability of PM in RCC. The article also highlights the drawbacks of PM and provides a holistic approach that goes beyond the involvement of clinicians and encompasses appropriate legislative and administrative care imparted by the healthcare system and insurance providers. It is anticipated that combined efforts from all sectors involved will make PM accessible to RCC and other patients with cancer, making a tremendous positive leap on individualized treatment strategies. This will subsequently enhance the quality of life of patients.
One-Month Outcomes of Intravitreal Anti-VEGF vs. Dexamethasone Implant in the Treatment of Diabetic Macular Edema in Vitrectomized Eyes
Authors: Liang Youling , Yan Bin , Xie Manyun , Meng Zhishang , Ma Jiayue , Ma Bosheng , Luo Jing
Published: June 2022

Objectives

To compare short-term effect of intravitreal ranibizumab with dexamethasone implant for diabetic macular edema (DME) in vitrectomized eyes.

Methods

Single-center, prospective, randomized study of vitrectomized eyes with DME. Study eyes were divided into two groups, receiving ranibizumab (IVV group, n = 35 eyes) or dexamethasone implant (IVD group, n = 35 eyes) respectively. Patients were evaluated at baseline, Week 1 and Month 1. The main outcome measures included best-corrected visual acuity (BCVA), central retinal thickness (CRT) and intraocular pressure (IOP).

Results

BCVA and CRT were similar in the two groups at baseline. At Week 1, the CRT improvement was significant in two groups (P = 0.041 in IVV group, P = 0.030 in IVD group), but at Month 1, only IVD group had significant improvement in CRT (P < 0.001). And BCVA gains were significant at Week 1 (P = 0.029) and Month 1 (P = 0.001) in IVD group, whereas IVV group did not show significant BCVA gains (P = 0.056 at Week1, P = 0.166 at Month 1). The changes of BCVA and CRT were significantly higher in IVD group than IVV group at Month1, but the changes were not significant at Week1.

Conclusions

Comparing to anti-VEGF therapy, DEX implant is more effect in improving BCVA and reducing CRT in vitrectomized eyes at 1 month, which indicated DEX implant is a better strategy.