bluuebunny/crossref_metadata_2025 huggingface dataset:
SLC4A4, FRAS1, and SULT1A1 Genetic Variations Associated With Dabigatran Metabolism in a Healthy Chinese Population
Authors: Xie Qiufen , Li Yuan , Liu Zhiyan , Mu Guangyan , Zhang Hanxu , Zhou Shuang , Wang Zhe , Wang Zining , Jiang Jie , Li Xin , Xiang Qian , Cui Yimin
Published: May 2022

Background: The purpose of this study was to identify genetic variations associated with the metabolism of dabigatran in healthy Chinese subjects, with particular focus given to pharmacokinetics (PK) and pharmacodynamics (PD).

Methods: Healthy Chinese adults aged 18–65 years with unknown genotypes from a bioequivalence trial were included according to the protocol registered at ClinicalTrial.org (NCT03161496). All subjects received a single dose (150 mg) of dabigatran etexilate. PK (main outcomes: area under the concentration-time, AUC0-t, of total and free dabigatran) and PD (main outcomes: anti-FIIa activity, APTT, and PT) parameters were evaluated. Whole-exome sequencing and genome-wide association analyses were performed. Additionally, candidate gene association analyses related to dabigatran were conducted.

Results: A total of 118 healthy Chinese subjects were enrolled in this study. According to the p-value suggestive threshold (1.0 × 10−4), the following three SNPs were found to be associated with the AUC0–t of total dabigatran: SLC4A4 SNP rs138389345 (p = 5.99 × 10−5), FRAS1 SNP rs6835769 (p = 6.88 × 10−5), and SULT1A1 SNP rs9282862 (p = 7.44 × 10−5). Furthermore, these SNPs were also found to have significant influences on the AUC0–t of free dabigatran, maximum plasma concentration, and anti-FIIa activity (p < 0.05). Moreover, we identified 30 new potential SNPs of 13 reported candidate genes (ABCB1, ABCC2, ABCG2, CYP2B6, CYP1A2, CYP2C19, CYP3A5, CES1, SLCO1B1, SLC22A1, UGT1A1, UGT1A9, and UGT2B7) that were associated with drug metabolism.

Conclusion: Genetic variations were indeed found to impact dabigatran metabolism in a population of healthy Chinese subjects. Further research is needed to explore the more detailed functions of these SNPs. Additionally, our results should be verified in studies that use larger sample sizes and investigate other ethnicities.
Genome-Wide Analysis of NBS-LRR Genes From an Early-Diverging Angiosperm Euryale ferox
Authors: Qian Lan-Hua , Wu Jia-Yi , Wang Yue , Zou Xin , Zhou Guang-Can , Sun Xiao-Qin
Published: May 2022

NBS-LRR genes are the largest gene family in plants conferring resistance to pathogens. At present, studies on the evolution of NBS-LRR genes in angiosperms mainly focused on monocots and eudicots, while studies on NBS-LRR genes in the basal angiosperms are limited. Euryale ferox represents an early-diverging angiosperm order, Nymphaeales, and confronts various pathogens during its lifetime, which can cause serious economic losses in terms of yield and quality. In this study, we performed a genome-wide identification and analysis of NBS-LRR genes in E. ferox. All 131 identified NBS-LRR genes could be divided into three subclasses according to different domain combinations, including 18 RNLs, 40 CNLs, and 73 TNLs. The E. ferox NBS-LRR genes are unevenly distributed on 29 chromosomes; 87 genes are clustered at 18 multigene loci, and 44 genes are singletons. Gene duplication analysis revealed that segmental duplications acted as a major mechanism for NBS-LRR gene expansions but not for RNL genes, because 18 RNL genes were scattered over 11 chromosomes without synteny loci, indicating that the expansion of RNL genes could have been caused by ectopic duplications. Ancestral gene reconciliation based on phylogenetic analysis revealed that there were at least 122 ancestral NBS-LRR lineages in the common ancestor of the three Nymphaeaceae species, suggesting that NBS-LRR genes expanded slightly during speciation in E. ferox. Transcriptome analysis showed that the majority of NBS-LRR genes were at a low level of expression without pathogen stimulation. Overall, this study characterized the profile of NBS-LRR genes in E. ferox and should serve as a valuable resource for disease resistance breeding in E. ferox.
A Novel Five-Gene Signature Related to Clinical Outcome and Immune Microenvironment in Breast Cancer
Authors: Yang Yi , Liu Hong-Li , Liu Yi-Jing
Published: May 2022

Breast cancer (BC) is the most frequent cancer in women and the main cause of cancer-related deaths in the globe, according to the World Health Organization. The need for biomarkers that can help predict survival or guide treatment decisions in BC patients is critical in order to provide each patient with an individualized treatment plan due to the wide range of prognoses and therapeutic responses. A reliable prognostic model is essential for determining the best course of treatment for patients. Patients’ clinical and pathological data, as well as their mRNA expression levels at level 3, were gleaned from the TCGA databases. Differentially expressed genes (DEGs) between BC and non-tumor specimens were identified. Tumor immunity analyses have been utilized in order to decipher molecular pathways and their relationship to the immune system. The expressions of KIF4A in BC cells were determined by RT-PCR. To evaluate the involvement of KIF4A in BC cell proliferation, CCK-8 tests were used. In this study, utilizing FC > 4 and p < 0.05, we identified 140 upregulated genes and 513 down-regulated genes. A five-gene signature comprising SFRP1, SAA1, RBP4, KIF4A and COL11A1 was developed for the prediction of overall survivals of BC. Overall survival was distinctly worse for patients in the high-risk group than those in the low-risk group. Cancerous and aggressiveness-related pathways and decreased B cell, T cell CD4+, T cell CD8+, Neutrophil and Myeloid dendritic cells levels were seen in the high-risk group. In addition, we found that KIF4A was highly expressed in BC and its silence resulted in the suppression of the proliferation of BC cells. Taken together, as a possible prognostic factor for BC, the five-gene profile created and verified in this investigation could guide the immunotherapy selection.
Cholinergic Signaling Attenuates Pro-Inflammatory Interleukin-8 Response in Colonic Epithelial Cells
Authors: Müller Isabelle , Kym Urs , Galati Virginie , Tharakan Sasha , Subotic Ulrike , Krebs Thomas , Stathopoulos Eleuthere , Schmittenbecher Peter , Cholewa Dietmar , Romero Philipp , Reingruber Bertram ,   NIGStudy Group, Holland-Cunz Stefan , Keck Simone
Published: May 2022

Infants affected by Hirschsprung disease (HSCR), a neurodevelopmental congenital disorder, lack ganglia of the intrinsic enteric nervous system (aganglionosis) in a variable length of the colon, and are prone to developing severe Hirschsprung-associated enterocolitis (HAEC). HSCR patients typically show abnormal dense innervation of extrinsic cholinergic nerve fibers throughout the aganglionic rectosigmoid. Cholinergic signaling has been reported to reduce inflammatory response. Consequently, a sparse extrinsic cholinergic innervation in the mucosa of the rectosigmoid correlates with increased inflammatory immune cell frequencies and higher incidence of HAEC in HSCR patients. However, whether cholinergic signals influence the pro-inflammatory immune response of intestinal epithelial cells (IEC) is unknown. Here, we analyzed colonic IEC isolated from 43 HSCR patients with either a low or high mucosal cholinergic innervation density (fiber-low versus fiber-high) as well as from control tissue. Compared to fiber-high samples, IEC purified from fiber-low rectosigmoid expressed significantly higher levels of IL-8 but not TNF-α, IL-10, TGF-β1, Muc-2 or tight junction proteins. IEC from fiber-low rectosigmoid showed higher IL-8 protein concentrations in cell lysates as well as prominent IL-8 immunoreactivity compared to IEC from fiber-high tissue. Using the human colonic IEC cell line SW480 we demonstrated that cholinergic signals suppress lipopolysaccharide-induced IL-8 secretion via the alpha 7 nicotinic acetylcholine receptor (a7nAChR). In conclusion, we showed for the first time that the presence of a dense mucosal cholinergic innervation is associated with decreased secretion of IEC-derived pro-inflammatory IL-8 in the rectosigmoid of HSCR patients likely dependent on a7nAChR activation. Owing to the association between IL-8 and enterocolitis-prone, fiber-low HSCR patients, targeted therapies against IL-8 might be a promising immunotherapy candidate for HAEC treatment.
Unlocking the Untapped Potential of Endothelial Kinase and Phosphatase Involvement in Sepsis for Drug Treatment Design
Authors: Luxen Matthijs , van Meurs Matijs , Molema Grietje
Published: May 2022

Sepsis is a devastating clinical condition that can lead to multiple organ failure and death. Despite advancements in our understanding of molecular mechanisms underlying sepsis and sepsis-associated multiple organ failure, no effective therapeutic treatment to directly counteract it has yet been established. The endothelium is considered to play an important role in sepsis. This review highlights a number of signal transduction pathways involved in endothelial inflammatory activation and dysregulated endothelial barrier function in response to sepsis conditions. Within these pathways – NF-κB, Rac1/RhoA GTPases, AP-1, APC/S1P, Angpt/Tie2, and VEGF/VEGFR2 – we focus on the role of kinases and phosphatases as potential druggable targets for therapeutic intervention. Animal studies and clinical trials that have been conducted for this purpose are discussed, highlighting reasons why they might not have resulted in the expected outcomes, and which lessons can be learned from this. Lastly, opportunities and challenges that sepsis and sepsis-associated multiple organ failure research are currently facing are presented, including recommendations on improved experimental design to increase the translational power of preclinical research to the clinic.
Bioaccumulation of Mercury and Other Trace Elements in the Edible Holothurian Holothuria (Halodeima) atra in Relation to Gold Mining Activities in North Sulawesi, Indonesia
Authors: Tamburini Marco , Badocco Denis , Ercadi Riccardo , Turicchia Eva , Zampa Greta , Gasparini Fabio , Ballarin Loriano , Guerra Roberta , Lasut Markus T. , Makapedua Daisy M. , Mamuaja Jane , Pastore Paolo , Ponti Massimo
Published: May 2022

Artisanal and small-scale gold mines (ASGMs) have been accompanied by widespread usage of mercury amalgamation to extract gold from ores, putting Indonesia among the top three global emitters of this pollutant and posing potential risks to the marine ecosystem and human health. Although the use of mercury has been largely eliminated following the signature of the Minamata Convention on Mercury, the practice of mercury amalgamation in ASGM has persisted in several regions, including the North Sulawesi. This study assesses how on the contamination of mercury and other trace elements coming from both industrial mines and ASGMs affects marine sediments and their bioaccumulation in two tissues (body wall and guts) of the edible holothurian Holothuria (Halodeima) atra, by comparing samples collected downstream of four mining areas to four control sites in the North Sulawesi province, Indonesia. In sediments, mean concentrations of arsenic, gold, cobalt, chromium, copper, mercury, nickel, lead, antimony, and zinc were significantly higher at sites receiving mine discharges than at control sites. Downstream to gold mines, compared to control sites, significant higher concentrations of As, Au, Cr, Hg, and Ni in holothurians body walls and of As, Au, Co, Cr, Cu, Hg, Pb, Sb, Sn, and Zn in holothurians guts were found. In general, higher contaminations in sediments and tissues were found at the site near the oldest artisanal mine. Trace element levels in H. atra specimens in North Sulawesi were generally higher than those reported in other regions. In the study area, these holothurians significantly bioaccumulate Hg, As, Zn, Cd, Cu, Sn, and biota-sediment accumulation factors were higher in guts than in body walls. From an environmental and human health perspective, Hg is resulted the most concerning element in surface sediment and H. atra specimens. Based on this evidence, further studies are urgently needed to understand better the effect of mercury and other potentially toxic trace elements in marine ecosystems and food webs in mining areas both in North Sulawesi and in many still poorly investigated southeast Pacific areas.
Dysnatremia in Gastrointestinal Disorders
Authors: Do Catherine , Evans Gretta J. , DeAguero Joshua , Escobar G. Patricia , Lin Henry C. , Wagner Brent
Published: May 2022

The primary solute of the milieu intérieur is sodium and accompanying anions. The solvent is water. The kidneys acutely regulate homeostasis in filtration, secretion, and resorption of electrolytes, non-electrolytes, and minerals while balancing water retention and clearance. The gastrointestinal absorptive and secretory functions enable food digestion and water absorption needed to sustain life. Gastrointestinal perturbations including vomiting and diarrhea can lead to significant volume and electrolyte losses, overwhelming the renal homeostatic compensatory mechanisms. Dysnatremia, potassium and acid-base disturbances can result from gastrointestinal pathophysiologic processes. Understanding the renal and gastrointestinal contributions to homeostatis are important for the clinical evaluation of perturbed volume disturbances.
Prognostic Significance of PD-L1 Expression and Standardized Uptake Values in the Primary Lesions of Stage IV Adenocarcinoma Lung Cancer
Authors: Tien Cong Bui , Cam Phuong Pham , Thai Pham-Van , Thuong Vu-Le , Quang Hung Nguyen , Hang Dong-Thi , Anh Tuan Hoang , Minh Khuy Doan , Tuyen Pham-Van , Minh Duc Nguyen
Published: May 2022

Background

This study evaluated the prognostic ability of 18F-fluorodeoxyglucose (18F-FDG) positron emission tomography (PET)/computed tomography (CT) in patients with stage IV adenocarcinoma lung cancer to detect protein death-ligand 1 (PD-L1) expression levels.

Methods

In total, 86 patients with stage IV adenocarcinoma lung cancer underwent 18F-FDG PET/CT imaging and PD-L1 expression evaluation before treatment from February 2019 to November 2020 at Bach Mai Hospital, Hanoi, Vietnam. The assessed patient characteristics in this study included sex, age, smoking status, epidermal growth factor receptor (EGFR) mutation, PD-L1 expression level, survival status, tumor, node, and metastasis (TNM) stage, and metastasis locations.

Results

The average age was 62.23 ± 9.51 years, and men and women represented 67.4% and 32.6% of the population, respectively. The EGFR mutation rate was 36%. PD-L1 expression was negative (detected in <1% of the tumor) in 40.7% of cases and positive in 59.3% of cases (detected in 1–49% of the tumor in 32.6%; detected in ≥50% of the tumor in 26.7%). The mean maximum standardized uptake value (SUVmax) was 11.09 ± 3.94. SUVmax was significantly higher in PD-L1–positive tumors than in PD-L1–negative tumors (12.24 ± 4.01 and 9.43 ± 3.22, respectively; p = 0.001). Receiver operating characteristic curve analysis revealed an area under the curve of SUVmax was 0.681 (95% confidence interval 0.570–0.793, p = 0.004). Compared with PD-L1–negative cases, SUVmax was significantly different in all PD-L1–positive cases (p = 0.001), weakly PD-L1–positive cases (1–49%, p = 0.005), and strongly PD-L1–positive cases (≥50%, p = 0.003). PD-L1 expression levels were significantly associated with SUVmax (p = 0.001), tumor size (p = 0.022), and EGFR mutation status (p = 0.045).

Conclusions

SUVmax in the primary lesions was able to predict PD-L1 expression and may play a role in predicting PD-L1 immunotherapy efficacy in patients with stage IV lung adenocarcinoma.
A Highly Sensitive and Specific Detection Method for Mycobacterium tuberculosis Fluoroquinolone Resistance Mutations Utilizing the CRISPR-Cas13a System
Authors: Bai Xiaopeng , Gao Panqi , Qian Keli , Yang Jiandong , Deng Haijun , Fu Tiwei , Hu Yuan , Han Miaomiao , Zheng Huizhi , Cao Xiaoxia , Liu Yuliang , Lu Yaoqin , Huang Ailong , Long Quanxin
Published: May 2022

Objectives

CRISPR-Cas13a system-based nucleic acid detection methods are reported to have rapid and sensitive DNA detection. However, the screening strategy for crRNAs that enables CRISPR-Cas13a single-base resolution DNA detection of human pathogens remains unclear.

Methods

A combined rational design and target mutation-anchoring CRISPR RNA (crRNA) screening strategy was proposed.

Results

A set of crRNAs was found to enable the CRISPR-Cas13 system to dramatically distinguish fluroquinolone resistance mutations in clinically isolated Mycobacterium tuberculosis strains from the highly homologous wild type, with a signal ratio ranging from 8.29 to 38.22 in different mutation sites. For the evaluation of clinical performance using genomic DNA from clinically isolated M. tuberculosis, the specificity and sensitivity were 100 and 91.4%, respectively, compared with culture-based phenotypic assays.

Conclusion

These results demonstrated that the CRISPR-Cas13a system has potential for use in single nucleotide polymorphism (SNP) detection after tuning crRNAs. We believe this crRNA screening strategy will be used extensively for early drug resistance monitoring and guidance for clinical treatment.
Genome-Wide Association Mapping of Virulence Genes in Wheat Karnal Bunt Fungus Tilletia indica Using Double Digest Restriction-Site Associated DNA-Genotyping by Sequencing Approach
Authors: Shakouka Mohamad Ayham , Gurjar Malkhan Singh , Aggarwal Rashmi , Saharan Mahender Singh , Gogoi Robin , Bainsla Kumar Naresh , Agarwal Shweta , Kumar Tej Pratap Jitendra , Bayaa Bassam , Khatib Fateh
Published: May 2022

Tilletia indica is a quarantine fungal pathogen that poses a serious biosecurity threat to wheat-exporting countries. Acquiring genetic data for the pathogenicity characters of T. indica is still a challenge for wheat breeders and geneticists. In the current study, double digest restriction-site associated-DNA genotyping by sequencing was carried out for 39 T. indica isolates collected from different locations in India. The generated libraries upon sequencing were with 3,346,759 raw reads on average, and 151 x 2 nucleotides read length. The obtained bases per read ranged from 87 Mb in Ti 25 to 1,708 Mb in Ti 39, with 505 Mb on average per read. Trait association mapping was performed using 41,473 SNPs, infection phenotyping data, population structure, and Kinship matrix, to find single nucleotide polymorphisms (SNPs) linked to virulence genes. Population structure analysis divided the T. indica population in India into three subpopulations with genetic mixing in each subpopulation. However, the division was not in accordance with the degree of virulence. Trait association mapping revealed the presence of 13 SNPs associated with virulence. Using sequences analysis tools, one gene (g4132) near a significant SNP was predicted to be an effector, and its relative expression was assessed and found upregulated upon infection.
Complementary Effects of Virus Population Are Required for Efficient Virus Infection
Authors: Sun Yuechao , Zhang Yu , Zhang Xiaobo
Published: May 2022

It is believed that the virions of a virus infecting a host may share the identical viral genome and characteristics. However, the role of genomic heterogeneity of the virions of a virus in virus infection has not been extensively explored. To address this issue, white spot syndrome virus (WSSV), a DNA virus infecting crustaceans, was characterized in the current study. In WSSV, differences in two nucleotides of the viral genome generated two types of WSSV, forming a virus population that consisted of Type A WSSV (encoding WSSV lncRNA-24) and Type B WSSV (encoding the wsv195 gene) at a ratio of 1:3. The virus populations in all virus-infected cells and tissues of different hosts exhibited a stable 1:3 structure. WSSV lncRNA-24 in Type A WSSV promoted virus infection by binding to shrimp and WSSV miRNAs, while the wsv195 gene in Type B WSSV played an essential role in virus infection. Loss of Type A WSSV or Type B WSSV in the WSSV population led to a 100-fold decrease in viral copy number in shrimp. Simultaneous loss of both types of WSSV prevented virus infection. These results indicated that the virus infection process was completed by two types of WSSV encoding different functional genes, revealing the complementary effects of WSSV population. Therefore, our study highlights the importance of the complementarity of virus population components in virus infection.
Improving the Molecular Diagnosis of Malaria: Droplet Digital PCR-Based Method Using Saliva as a DNA Source
Authors: Costa Gabriel Luíz , Alvarenga Denise Anete Madureira , Aguiar Anna Caroline Campos , Louzada Jaime , Pereira Dhélio Batista , de Oliveira Tatiana Flávia , Fonseca Júnior Antônio Augusto , Carvalho Luzia Helena , Ferreira Alves de Brito Cristiana , Nóbrega de Sousa Taís
Published: May 2022

Malaria is an acute febrile disease caused by a protozoan of the genus Plasmodium. Light microscopy (LM) is the gold standard for the diagnosis of malaria. Despite this method being rapid and inexpensive, it has a low limit of detection, which hampers the identification of low parasitemia infections. By using multicopy targets and highly sensitive molecular techniques, it is possible to change this scenario. In this study, we evaluated the performance of droplet digital PCR (ddPCR) to detect Plasmodium DNA obtained from saliva samples (whole saliva and buccal swab) of 157 individuals exposed to malaria transmission from the Brazilian Amazon region. We used the highly sensitive ddPCR method with non-ribosomal multicopy targets for Plasmodium vivax (Pvr47) and Plasmodium falciparum (Pfr364). There was good concordance between the quantitative real-time PCR (qPCR) results from the saliva and blood, except for mixed-species infections. The sensitivity of qPCR was 93% for blood, 77% for saliva, and 47% for swabs. Parasite DNA was not detected in saliva samples in low-density infections compared with the detection in blood samples. ddPCR showed increased sensitivity for detecting Plasmodium in the blood and swabs (99% in blood, 73% in saliva, and 59% in swabs). Notably, ddPCR detected more mixed infections in the blood (15%), saliva (9%), and swabs (18%) than qPCR. Our data showed that the differences between ddPCR and qPCR were the result of a higher number of P. falciparum infections detected by ddPCR. Overall, there was a moderate correlation between parasite densities estimated by the different methods in the blood. Our findings highlight the possibility of using non-invasive sample collection methods for malaria diagnosis by targeting multicopy sequences combined with highly sensitive molecular methods.
Combinatorial Engineering Enables Photoautotrophic Growth in High Cell Density Phosphite-Buffered Media to Support Engineered Chlamydomonas reinhardtii Bio-Production Concepts
Authors: Abdallah Malak N. , Wellman Gordon B. , Overmans Sebastian , Lauersen Kyle J.
Published: May 2022

Chlamydomonas reinhardtii has emerged as a powerful green cell factory for metabolic engineering of sustainable products created from the photosynthetic lifestyle of this microalga. Advances in nuclear genome modification and transgene expression are allowing robust engineering strategies to be demonstrated in this host. However, commonly used lab strains are not equipped with features to enable their broader implementation in non-sterile conditions and high-cell density concepts. Here, we used combinatorial chloroplast and nuclear genome engineering to augment the metabolism of the C. reinhardtii strain UVM4 with publicly available genetic tools to enable the use of inorganic phosphite and nitrate as sole sources of phosphorous and nitrogen, respectively. We present recipes to create phosphite-buffered media solutions that enable high cell density algal cultivation. We then combined previously reported engineering strategies to produce the heterologous sesquiterpenoid patchoulol to high titers from our engineered green cell factories and show these products are possible to produce in non-sterile conditions. Our work presents a straightforward means to generate C. reinhardtii strains for broader application in bio-processes for the sustainable generation of products from green microalgae.
A Recombinant Porcine Reproductive and Respiratory Syndrome Virus Stably Expressing a Gaussia Luciferase for Antiviral Drug Screening Assay and Luciferase-Based Neutralization Assay
Authors: Li Yanhua , Ren Cicheng , Li Chenxi , Xiao Yihong , Zhou Yanyang
Published: May 2022

The reverse genetics system is a valuable tool in the virological study of RNA viruses. With the availability of reverse genetics, the porcine reproductive and respiratory syndrome virus (PRRSV) has been utilized as a viral vector for the expression of foreign genes of interest. Here, we constructed a full-length cDNA clone of a highly pathogenic PRRSV (HP-PRRSV) TA-12 strain. Using this cDNA clone, we generated a reporter virus expressing a gaussia luciferase (Gluc) via an additional subgenomic RNA between ORF7 and 3′UTR. This reporter virus exhibited similar growth kinetics to the wild-type (WT) virus and remained genetically stable for at least ten passages in MARC-145 cells. In cells infected with this reporter virus, the correlation between the expression levels of Gluc in culture media and the virus titers suggested that Gluc is a good indicator of the reporter virus infection. With this reporter virus, we further established the Gluc readout-based assays for antiviral drug screening and serum neutralizing antibody detection that exhibited comparable performance to the classical assays. Taken together, we established a reverse genetics system of HP-PRRSV and generated a novel reporter virus that could serve as a valuable tool for antiviral drug screening and serum neutralizing antibody detection.
ceRNAshiny: An Interactive R/Shiny App for Identification and Analysis of ceRNA Regulation
Authors: Song Yueqiang , Li Jia , Mao Yiming , Zhang Xi
Published: May 2022

The competing endogenous RNA (ceRNA) network is a newly discovered post-transcriptional regulation that controls both physiological and pathological progresses. Increasing research studies have been pivoted on this theory to explore the function of novel non-coding RNAs, pseudogenes, circular RNAs, and messenger RNAs. Although there are several R packages or computational tools to analyze ceRNA networks, an urgent need for easy-to-use computational tools still remains to identify ceRNA regulation. Besides, the conventional tools were mainly devoted to investigating ceRNAs in malignancies instead of those in neurodegenerative diseases. To fill this gap, we developed ceRNAshiny, an interactive R/Shiny application, which integrates widely used computational methods and databases to provide and visualize the construction and analysis of the ceRNA network, including differential gene analysis and functional annotation. In addition, demo data in ceRNAshiny could provide ceRNA network analyses about neurodegenerative diseases such as Parkinson’s disease. Overall, ceRNAshiny is a user-friendly application that benefits all researchers, especially those who lack an established bioinformatic pipeline and are interested in studying ceRNA networks.
Cost-Effective Transcriptome-Wide Profiling of Circular RNAs by the Improved-tdMDA-NGS Method
Authors: Guria Ashirbad , Sharma Priyanka , Srikakulam Nagesh , Baby Akhil , Natesan Sankar , Pandi Gopal
Published: May 2022

Covalently closed circular RNAs are neoteric to the eukaryotic family of long non-coding RNAs emerging as a result of 5′–3′ backsplicing from exonic, intronic, or intergenic regions spanning the parental gene. Owing to their unique structure and stability, circular RNAs have a multitude of functional properties such as micro-RNA and protein sponges, direct and indirect modulators of gene expression, protein translation, and many unproven activities apart from being potential biomarkers. However, due to their low abundance, most of the global circular RNA identification is carried out by high-throughput NGS-based approaches requiring millions of sequencing reads. This lag in methodological advancements demands for newer, more refined, and efficient identification techniques. Here, we aim to show an improved version of our previously reported template-dependent multiple displacement amplification (tdMDA)-NGS method by superimposing the ribosomal depletion step and use of H minus reverse transcriptase and RNase H. Implication of tdMDA using highly replicative Phi29 DNA polymerase after minimizing the linear and ribosomal RNA content further intensifies its detection limit toward even the abysmally expressing circular RNA at a low NGS depth, thereby decreasing the cost of identifying a single circular RNA. A >11-fold and >6-fold increase in total circular RNA was identified from the improved-tdMDA-NGS method over the traditional method of circRNA sequencing using DCC and CIRI2 pipelines, respectively, from Oryza sativa subsp. Indica. Furthermore, the reliability of the improved-tdMDA-NGS method was also asserted in HeLa cell lines, showing a significant fold difference in comparison with the existing traditional method of circRNA sequencing. Among the identified circular RNAs, a significant percentage from both rice (∼58%) and HeLa cell lines (∼84%) is found to be matched with the previously reported circular RNAs, suggesting that the improved-tdMDA-NGS method can be adapted to detect and characterize the circular RNAs from different biological systems.
Increased Risk for Dementia in Patients With Inflammatory Bowel Disease: A Systematic Review and Meta-Analysis of Population-Based Studies
Authors: Liu Mengsi , Li Dongxiu , Hong Xia , Sun Zhen
Published: May 2022

Background

Mounting evidence suggests that there may be a causal relationship or common pathogenic pathway between inflammatory bowel disease (IBD) and dementia. However, inconsistent results have emerged from epidemiological studies. We therefore conducted this review to clarify the relationship between IBD and dementia.

Methods

We systematically searched PubMed, Web of Science, Embase, and Cochrane library to identify all studies exploring the relationship between IBD and dementia published as of September 2021. Risk estimates were pooled using both fixed and random-effects models.

Results

Six studies involving 2,334,472 subjects were included. Pooled results suggested that the risk of developing dementia significantly increased after IBD diagnosis (HR = 1.27, 95% CI: 1.10–1.47, P = 0.001), which did not vary by age, gender, dementia subtype, or IBD subtype. Whereas, the dementia incidence before IBD diagnosis and the comorbidity rate of dementia in IBD patients were similar to those without IBD (HR = 0.92, 95% CI: 0.68–1.25; 0.82, 95% CI: 0.64–1.06, respectively). However, current evidence was insufficient to establish a causal relationship.

Conclusion

This study shows an unidirectional association between IBD and dementia; patients with IBD have an increased risk of dementia, and it may be beneficial to develop individualized dementia screening strategies for this population. Future research needs to further investigate whether effective therapies of IBD can reduce this risk and pathophysiological mechanisms of the association.
Aerobic Physical Exercise as a Non-medical Intervention for Brain Dysfunction: State of the Art and Beyond
Authors: Jia Yuxiang , Yao Yu , Zhuo Limin , Chen Xingxing , Yan Cuina , Ji Yonghua , Tao Jie , Zhu Yudan
Published: May 2022

Brain disorders, including stroke, Alzheimer's disease, depression, and chronic pain, are difficult to effectively treat. These major brain disorders have high incidence and mortality rates in the general population, and seriously affect not only the patient's quality of life, but also increases the burden of social medical care. Aerobic physical exercise is considered an effective adjuvant therapy for preventing and treating major brain disorders. Although the underlying regulatory mechanisms are still unknown, systemic processes may be involved. Here, this review aimed to reveal that aerobic physical exercise improved depression and several brain functions, including cognitive functions, and provided chronic pain relief. We concluded that aerobic physical exercise helps to maintain the regulatory mechanisms of brain homeostasis through anti-inflammatory mechanisms and enhanced synaptic plasticity and inhibition of hippocampal atrophy and neuronal apoptosis. In addition, we also discussed the cross-system mechanisms of aerobic exercise in regulating imbalances in brain function, such as the “bone-brain axis.” Furthermore, our findings provide a scientific basis for the clinical application of aerobic physical exercise in the fight against brain disorders.
Chronic Cognitive Impairment in AQP4+ NMOSD With Improvement in Cognition on Eculizumab: A Report of Two Cases
Authors: Saab Georges , Munoz David G. , Rotstein Dalia L.
Published: May 2022

Cognitive impairment may be associated with aquaporin-4 antibody positive (AQP4+) NMOSD, particularly where there is prominent cerebral, corpus callosum, or thalamic involvement. It is unclear to what extent this phenomenon may be treatable after months to years. We describe two cases of AQP4+ NMOSD with cognitive impairment persisting over more than 6 months, where cognition improved after eculizumab was initiated. In the first case, a 51-year-old woman presented with a 2-month history of cognitive decline and ataxia, and diffuse involvement of the corpus callosum on MRI. AQP4 antibody testing returned positive. Cognitive impairment persisted on therapy with mycophenolate, then rituximab. She was switched to eculizumab from rituximab 18 months after disease onset because of breakthrough optic neuritis; memory and cognitive function improved on eculizumab. In the second case, a 26-year-old woman initially presented with visual, auditory and tactile hallucinations, and impairment in activities of daily living, and was given a diagnosis of schizophrenia. Nine months later she was hospitalized for increasing confusion. MRI showed leukoencephalopathy and diffuse involvement of the corpus callosum with multiple enhancing callosal lesions. AQP4 antibody testing was positive and CSF testing for other antibodies of autoimmune encephalitis was negative. She had some improvement in cognition with high dose corticosteroids but remained significantly impaired. On follow-up, her repeat MRI showed a small new right inferomedial frontal enhancing lesion although she did not complain of any new cognitive issues, her MOCA score was 21/30, and she was started on eculizumab. Two months after eculizumab initiation she and her family reported cognitive improvement and MOCA score was 25/30. Common features of these two cases included extensive callosal involvement and an element of ongoing gadolinium enhancement on MRI. Our experience suggests the possibility that cognitive impairment may be amenable to immunotherapy in certain cases of NMOSD.
Bifurcated Aneurysm Location Predicts In-Stent Stenosis After Neuroform-EZ Stent-Assisted Coiling for Intracranial Aneurysm
Authors: You Wei , Feng Junqiang , Ge Huijian , Jin Hengwei , Liu Peng , Li Youxiang , Jiang Yuhua , Liu Xinke
Published: May 2022

Background and Purpose

The Neuroform EZ stent system (Boston Scientific Corporation, Fremont, CA, United States) is a fourth-generation intracranial aneurysm stent designed specifically for the cerebrovasculature to support aneurysm treatment. In this study, we analyzed our consecutive series of patients with aneurysm treated with the Neuroform EZ stent, with special attention to the occurrence of in-stent stenosis (ISS).

Methods

A retrospective review of our center's electronic database was conducted to identify all patients with intracranial aneurysms who underwent aneurysm treatment with the Neuroform EZ stent between January 2016 and October 2018. Patients with at least one digital subtraction angiography (DSA) follow-up in our hospital were enrolled in this study. In-stent stenosis (ISS) was graded as mild (<2–5%), moderate (25–50%), or severe (>50%).

Results

The study included 114 patients (78 women, 68.4%; median age 57.2 ± 9 years) with a total of 116 aneurysms. Of the 116 lesions, 20 were identified with ISS (17.2%) at a mean follow-up of 6.9 ± 1.7 months, and ISS was mild in 30% (6/20), moderate in 50% (10/20), and severe in 20% (4/20). No patients were symptomatic or required further intervention. Patients who developed ISS were younger than those without ISS (52.6 ± 7.8 vs. 57.9 ± 9; p = 0.016). The proportion of aneurysms located at the artery bifurcation was significantly higher in patients with stenosis than located at the sidewall artery (37.9 vs. 10.3%; p = 0.002). In the multivariable analysis, the patients' age (OR = 0.94; 95% CI 0.88–0.998; p = 0.02) and bifurcated aneurysm location (OR = 4.59; 95% CI 1.54–13.67; p = 0.006) were independent predictors of ISS.

Conclusions

In this retrospective study, the incidence of ISS after Neuroform EZ stent placement was 17.2%, and all the ISS cases were asymptomatic. Patients with younger age and bifurcated aneurysm location are more likely to develop ISS. Although Neuroform EZ stent is particularly suitable for bifurcated aneurysms, the ISS for this location should be focused upon.
Improving Visualization Methods of Utility-Weighted Disability Outcomes for Stroke Trials
Authors: Tokunboh Ivie , Sung Eleanor Mina , Chatfield Fiona , Gaines Nathan , Nour May , Starkman Sidney , Saver Jeffrey L.
Published: May 2022

Background

The modified Rankin Scale (mRS) is the most common endpoint in acute stroke trials, but its power is limited when analyzed dichotomously and its indication of effect size is challenging to interpret when analyzed ordinally. To address these issues, the utility-weighted-mRS (UW-mRS) has been developed as a patient-centered, linear scale. However, appropriate data visualizations of UW-mRS results are needed, as current stacked bar chart displays do not convey crucial utility-weighting information.

Design/Methods

Two UW-mRS display formats were devised: (1) Utility Staircase charts, and (2) choropleth-stacked-bar-charts (CSBCs). In Utility Staircase displays, mRS segment height reflects the utility value of each mRS level. In CSBCs, mRS segment color intensity reflects the utility of each mRS level. Utility Staircase and CSBC figures were generated for 15 randomized comparisons of acute ischemic/hemorrhagic stroke therapies, including fibrinolysis, endovascular reperfusion, blood pressure moderation, and hemicraniectomy. Display accuracy in showing utility outcomes was assessed with the Tufte-lie-factor and ease-of-use assessed by formal ratings completed by a panel of 4 neurologists and emergency physicians and one nurse-coordinator.

Results

The Utility Staircase and CSBC displays rapidly conveyed patient-centered valuation of trial outcome distributions not available in conventional ordinal stacked bar charts. Tufte-lie-factor (LF) scores indicated “substantial distortion” of utility-valued outcomes for 93% (14/15) of conventional stacked bar charts, vs. “no distortion” for all Utility Staircase and CSBC displays. Clinician ratings on the Figural Display Questionnaire indicated that utility information encoded in row height (Utility Staircase display) was more readily assimilated than that conveyed in segment hue intensity (CSBC), both superior to conventional stacked bar charts.

Conclusions

Utility Staircase displays are an efficient graphical format for conveying utility weighted–modified Rankin Scale primary endpoint results of acute stroke trials, and choropleth-stacked-bar-charts a good alternative. Both are more accurate in depicting quantitative, health-related quality of life results and preferred by clinician users for utility results visualization, compared with conventional stacked bar charts.
Total Dairy Consumption Is Not Associated With Likelihood of a First Clinical Diagnosis of Central Nervous System Demyelination
Authors: Dieu Dao Ying Rachel , Dunlop Eleanor , Daly Alison , Lucas Robyn M. , Probst Yasmine , Black Lucinda J.
Published: May 2022

Background

The evidence associating consumption of dairy products and risk of MS is contradictory and inconclusive.

Objective

To test associations between dairy consumption and the likelihood of a first clinical diagnosis of central nervous system demyelination (FCD), a common precursor to MS.

Methods

We used data from the 2003–2006 Ausimmune Study, a population-based Australian, multicentre, matched case-control study (272 cases, 519 controls). Total dairy consumption (servings/day) was calculated by summing consumption of milk, cheese and yogurt. Covariate-adjusted treatment effects using augmented inverse probability weighting was used to test for associations with FCD. We conducted sensitivity analyses in the subset of participants who had had a classic first demyelinating event (FDE), defined as a single, first episode of symptoms suggestive of CNS demyelination.

Results

There were no statistically significant associations between total dairy consumption (per one serving/day) and FCD (adjusted OR 1.00; 95% CI 0.93, 1.07; p = 0.979). However, yogurt consumption (vs. no yogurt consumption) was associated with an 11% decreased likelihood of FDE (adjusted OR 0.89; 95% CI 0.89, 0.79; p = 0.046).

Conclusion

While total dairy consumption was not associated with FCD in this Australian case-control study, yogurt consumption was associated with reduced likelihood of FDE.
Dietary Klebsormidium sp. Supplementation Improves Growth Performance, Antioxidant and Anti-Inflammatory Status, Metabolism, and Mid-Intestine Morphology of Litopenaeus Vannamei
Authors: Fang HaoHang , Zhuang ZhenXiao , Huang LuoDong , Zhao Wei , Niu Jin
Published: May 2022

Filamentous microalga Klebsormidium sp. has huge potential to become a natural and healthy additive in aquatic feed since it contains various bioactive nutrients, such as linoleic acid (LA), carotenoids, and chlorophylls. Therefore, an eight-week feeding experiment was performed to evaluate the effects of dietary Klebsormidium sp. on the growth performance, antioxidant and anti-inflammatory status, metabolism, and mid-intestine morphology of Litopenaeus vannamei. Two isonitrogenous and isolipid diets supplemented with and without 5% Klebsormidium sp. were prepared. Results showed that L. vannamei fed with Klebsormidium sp. had better growth performance and feed utilization by optimizing mid-intestine morphology and improving the carbohydrate metabolism. In addition, Klebsormidium sp. also enhanced the antioxidant capacity of L. vannamei by downregulating antioxidant parameters (hepatopancreas T-SOD, hepatopancreas GSH-PX, hemolymph T-SOD, hemolymph MDA) and RNA expression levels of antioxidant genes (gsh-px and cat). Furthermore, the supplementations of dietary Klebsormidium sp. significantly improved hepatopancreas health by downregulating RNA expression levels of pro-inflammatory related genes (relish and rho). Therefore, a dose of 5% Klebsormidium sp. is recommended for the daily diet of L. vannamei to improve the growth performance, antioxidant and anti-inflammatory status, metabolism, and mid-intestine morphology of shrimp.
Association of Dietary Protein Intake and Grip Strength Among Adults Aged 19+ Years: NHANES 2011–2014 Analysis
Authors: Pikosky Matthew A. , Cifelli Christopher J. , Agarwal Sanjiv , Fulgoni Victor L.
Published: May 2022

Background

Research on the role of protein in the diet has evolved beyond a focus on quantity to include the impact of its quality and distribution across meal times in an effort to optimize dietary protein recommendations.

Objective

To determine the association of dietary protein amount, type, and intake pattern with grip strength in adults.

Design

Data from the National Health and Nutrition Examination Survey (NHANES) 2011–2014 for adults 19 + years (N = 9,214) were used with exclusions for pregnant and lactating women. Intakes of dietary total protein (TP), animal protein (AP, including dairy), plant protein (PP), and leucine (Leu) were determined using day 1 24 h dietary recall data after adjusting for the complex sample design of NHANES. Regression analyses were used to assess the association of dietary protein and leucine intake quartiles, and whether consuming > 20 g of dietary protein at one or more meals was related to grip strength with adjustment for age, gender, and ethnicity.

Results

Mean intake of TP among adults aged 19 + years was 83.6 ± 0.5 g/day, and 2/3rd of this was from animal sources (including dairy). Grip strength increased (p < 0.05) with increasing quartiles of TP, AP, PP, and leucine among all adults 19 + years (β = 1.340.19, 1.27 ± 0.19, 0.76 ± 0.20, and 1.33 ± 0.23, respectively), 19–50 years (β = 1.14 ± 0.27, 1.06 ± 0.25, 0.77 ± 0.30, and 1.18 ± 0.27, respectively), and 51 + years (β = 0.95 ± 0.26, 1.08 ± 0.27, and 1.05 ± 0.27, respectively, for TP, AP, and Leu); however, the increase was more pronounced for AP than PP. Grip strength also increased (p < 0.05) with increasing the number of meal occasions containing > 20 g of dietary protein (β = 1.50 ± 0.20, 1.41 ± 0.25, and 0.91 ± 0.37 for 19+, 19–50, and 51 + years, respectively), and significant increases were detected for two meals compared to zero meals.

Conclusion

Dietary protein quantity, quality, and distribution should be considered collectively when looking to optimize protein intake to support muscle strength and function.
Effect of Fermentation on the Bioactive Compounds of the Black Soybean and Their Anti-Alzheimer’s Activity
Authors: Shabbir Umair , Tyagi Akanksha , Ham Hun Ju , Elahi Fazle , Oh Deog-Hwan
Published: May 2022

Black soybean is one of the nutritious crops and is being used in traditional medicines in Asian countries. In the present study, we fermented black soybean and screened against in vitro Alzheimer’s disease (AD) biomarkers such as cholinesterase enzymes, inflammatory factors, oxidative stress, and presence of γ-aminobutyric acid (GABA) levels. Firstly, we fermented black soybean with different lactic acid bacteria (LABs) and selected the Pediococcus acidilactici as the best LAB on the basis of GABA levels in the fermentate. We have found that black soybean fermented with P. acidilactici significantly inhibited the inflammatory factors (proteinase, protein denaturation, and lipoxygenase) and cholinesterase enzymes than non-fermented samples. An increase in the antioxidant capacity (FRAP, ABTS, and DPPH), anthocyanins, phenolics, flavonoids, and GABA content was also observed in fermented samples. Moreover, UHPLC-ESI-QTOF-MS/MS technique identified 38 bioactive components, including polyphenols, amino acids, and fatty acids. Among identified components, eight bioactive compounds were quantified, and an increase in the concentration of daidzein, genistein, glycitein, (+)-catechin, quercetin, and gallic acid was observed in fermented samples. However, the concentration of rutin and soyasaponin was higher in raw samples. These results indicated that fermentation of black soybean with P. acidilactici is a promising approach that can be used to develop functional foods to inhibit/prevent AD and other neurodegenerative diseases.
Research Status and Prospect for Vibration, Noise and Temperature Rise-Based Effect of Food Transport Pumps on the Characteristics of Liquid Foods
Authors: Jia XiaoQi , Li Songyu , Li Bo , Zhang Li , Ding Qiangmin , Gao Panlong , Zhu ZuChao
Published: May 2022

In the field of food processing, the processing of liquid foods has always played an important role. Liquid foods have high requirements for the processing environment and equipment. As the core equipment in liquid foods processing, food transport pumps are widely used in liquid foods production, processing and transportation. Most liquid foods are non-Newtonian and vulnerable to vibration, noise, and temperature rise produced by rotary motions of food transport pumps in operation, which can finally affect foods safety. Therefore, this review summarizes the impact of mechanical vibration, noise, and temperature rise on liquid food products, with the aim of ensuring food safety while designing a cleaner, safer and more reliable food transport pumps in the future.