bluuebunny/crossref_metadata_2025 huggingface dataset:
Intermittent fasting protects against food allergy in a murine model via regulating gut microbiota
Authors: Ma Ru-xue , Hu Jia-qian , Fu Wei , Zhong Jian , Cao Can , Wang Chang-chang , Qi Shi-quan , Zhang Xiao-Lian , Liu Guang-hui , Gao Ya-dong
Published: May 2023

Background

The prevalence of food allergy (FA) is increasing. Decreases in the diversity of gut microbiota may contribute to the pathogenesis of FA by regulating IgE production of B cells. Intermittent fasting (IF) is a popular diet with the potential to regulate glucose metabolism, boosting immune memory and optimizing gut microbiota. The potential effect of long-term IF on the prevention and treatment of FA is still unknown.

Methods

Two IF protocols (16 h fasting/8 h feeding and 24 h fasting/24 h feeding) were conducted on mice for 56 days, while the control mice were free to intake food (free diet group, FrD). To construct the FA model, all mice were sensitized and intragastrical challenged with ovalbumin (OVA) during the second half of IF (day 28 to day 56). Rectal temperature reduction and diarrhea were recorded to evaluate the symptoms of FA. Levels of serum IgE, IgG1, Th1/Th2 cytokines, mRNA expression of spleen T cell related transcriptional factors, and cytokines were examined. H&E, immunofluorescence, and toluidine blue staining were used to assess the structural changes of ileum villi. The composition and abundance of gut microbiota were analyzed by 16srRNA sequencing in cecum feces.

Results

The diarrhea score and rectal temperature reduction were lower in the two fasting groups compared to the FrD groups. Fasting was associated with lower levels of serum OVA-sIgE, OVA-sIgG1, interleukin (IL)-4 and IL-5, and mRNA expression of IL-4, IL-5, and IL-10 in the spleen. While no significant association was observed in interferon (IFN)-γ, tumor necrosis factor (TNF)-α, IL-6, IL-2 levels. Less mast cell infiltration in ileum was observed in the 16h/8h fasting group compared to the FrD group. ZO-1 expression in the ileum of the two fasting groups was higher in IF mice. The 24h/24h fasting reshaped the gut microbiota, with a higher abundance of Alistipes and Rikenellaceae strains compared to the other groups.

Conclusion

In an OVA-induced mice FA model, long-term IF may attenuate FA by reducing Th2 inflammation, maintaining the integrity of the intestinal epithelial barrier, and preventing gut dysbiosis.
Association between inflammatory bowel disease and interleukins, chemokines: a two-sample bidirectional mendelian randomization study
Authors: Fang Guojiu , Kong Fanzhi , Zhang Haiqing , Huang Bin , Zhang Jifa , Zhang Xueli
Published: May 2023

Background

Mendelian randomization (MR) was used to evaluate the bidirectional causal relationship between inflammatory bowel disease (IBD) and interleukins (ILs), chemokines.

Methods

Genetic instruments and summary data of five ILs and six chemokines were obtained from a genome-wide association study database, and instrumental variables related to IBD were obtained from the FinnGen Consortium. Inverse variance weighting (IVW) was used as the main MR analysis method, and several other MR methods including MR-Egger and weighted median were used to confirm the reliability of the results. Sensitivity analyses such as heterogeneity and pleiotropy were also performed.

Results

The IVW method provided evidence to support that genetically predicted IL-16, IL-18, and CXCL10 significantly positively correlated with IBD, while IL-12p70 and CCL23 significantly negatively correlated with IBD. IL-16 and IL-18 had a suggestive association with an increased risk of ulcerative colitis (UC), and CXCL10 had a suggestive association with an increased risk of Crohn’s disease (CD). However, there was no evidence to support that IBD and two main subtypes (UC and CD) are associated with changes in the levels of ILs and chemokines. The results of the sensitivity analyses were robust and no evidence of heterogeneity and horizontal pleiotropy was observed.

Conclusions

The present study showed that some ILs and chemokines affect IBD, but IBD and its main subtypes (UC and CD) have no effect on the level changes of ILs and chemokines.
CD24-Siglec interactions in inflammatory diseases
Authors: Liu Yang , Zheng Pan
Published: May 2023

CD24 is a small glycosylphosphatidylinositol (GPI)-anchored glycoprotein with broad expression in multiple cell types. Due to differential glycosylation, cell surface CD24 have been shown to interact with various receptors to mediate multiple physiological functions. Nearly 15 years ago, CD24 was shown to interact with Siglec G/10 to selectively inhibit inflammatory response to tissue injuries. Subsequent studies demonstrate that sialylated CD24 (SialoCD24) is a major endogenous ligand for CD33-family of Siglecs to protect the host against inflammatory and autoimmune diseases, metabolic disorders and most notably respiratory distress in COVID-19. The discoveries on CD24-Siglec interactions propelled active translational research to treat graft-vs-host diseases, cancer, COVID-19 and metabolic disorders. This mini-review provides a succinct summary on biological significance of CD24-Siglec pathway in regulation of inflammatory diseases with emphasis on clinical translation.
Seroprevalence and durability of antibody responses to AstraZeneca vaccination in Ugandans with prior mild or asymptomatic COVID-19: implications for vaccine policy
Authors: Serwanga Jennifer , Baine Claire , Mugaba Susan , Ankunda Violet , Auma Betty Oliver , Oluka Gerald Kevin , Kato Laban , Kitabye Isaac , Sembera Jackson , Odoch Geoffrey , Ejou Peter , Nalumansi Amina , Gombe Ben , Musenero Monica , Kaleebu Pontiano ,   the COVID-19 Immunoprofiling Team
Published: May 2023

Introduction

The duration and timing of immunity conferred by COVID-19 vaccination in sub-Saharan Africa are crucial for guiding pandemic policy interventions, but systematic data for this region is scarce. This study investigated the antibody response after AstraZeneca vaccination in COVID-19 convalescent Ugandans.

Methods

We recruited 86 participants with a previous rt-PCR-confirmed mild or asymptomatic COVID-19 infection and measured the prevalence and levels of spike-directed IgG, IgM, and IgA antibodies at baseline, 14 and 28 days after the first dose (priming), 14 days after the second dose (boosting), and at six- and nine-months post-priming. We also measured the prevalence and levels of nucleoprotein-directed antibodies to assess breakthrough infections.

Results

Within two weeks of priming, vaccination substantially increased the prevalence and concentrations of spike-directed antibodies (p < 0.0001, Wilcoxon signed rank test), with 97.0% and 66% of vaccinated individuals possessing S-IgG and S-IgA antibodies before administering the booster dose. S-IgM prevalence changed marginally after the initial vaccination and barely after the booster, consistent with an already primed immune system. However, we also observed a rise in nucleoprotein seroprevalence, indicative of breakthroughs six months after the initial vaccination.

Discussion

Our results suggest that vaccination of COVID-19 convalescent individuals with the AstraZeneca vaccine induces a robust and differential spike-directed antibody response. The data highlights the value of vaccination as an effective method for inducing immunity in previously infected individuals and the importance of administering two doses to maintain protective immunity. Monitoring anti-spike IgG and IgA when assessing vaccine-induced antibody responses is suggested for this population; assessing S-IgM will underestimate the response. The AstraZeneca vaccine is a valuable tool in the fight against COVID-19. Further research is needed to determine the durability of vaccine-induced immunity and the potential need for booster doses.
Identification and experimental validation of mitochondria-related genes biomarkers associated with immune infiltration for sepsis
Authors: Shu Qi , She Han , Chen Xi , Zhong Like , Zhu Junfeng , Fang Luo
Published: May 2023

Background

Sepsis remains a complex condition with incomplete understanding of its pathogenesis. Further research is needed to identify prognostic factors, risk stratification tools, and effective diagnostic and therapeutic targets.

Methods

Three GEO datasets (GSE54514, GSE65682, and GSE95233) were used to explore the potential role of mitochondria-related genes (MiRGs) in sepsis. WGCNA and two machine learning algorithms (RF and LASSO) were used to identify the feature of MiRGs. Consensus clustering was subsequently carried out to determine the molecular subtypes for sepsis. CIBERSORT algorithm was conducted to assess the immune cell infiltration of samples. A nomogram was also established to evaluate the diagnostic ability of feature biomarkers via “rms” package.

Results

Three different expressed MiRGs (DE-MiRGs) were identified as sepsis biomarkers. A significant difference in the immune microenvironment landscape was observed between healthy controls and sepsis patients. Among the DE-MiRGs, NDUFB3 was selected to be a potential therapeutic target and its significant elevated expression level was confirmed in sepsis using in vitro experiments and confocal microscopy, indicating its significant contribution to the mitochondrial quality imbalance in the LPS-simulated sepsis model.

Conclusion

By digging the role of these pivotal genes in immune cell infiltration, we gained a better understanding of the molecular immune mechanism in sepsis and identified potential intervention and treatment strategies.
Efficient RNA interference method during caste differentiation with hormone treatment in the termite Reticulitermes speratus (Isoptera: Rhinotermitidae)
Authors: Suzuki Ryutaro , Masuoka Yudai , Suzuki Ryohei H. , Maekawa Kiyoto
Published: May 2023

Unveiling the proximate mechanism of caste differentiation is crucial for understanding insect social evolution, and gene function analysis is an important tool in this endeavor. The RNA interference (RNAi) technique is useful in termites, but its knockdown effects may differ among species. One of the most important model species in the field of termite sociogenomics is Reticulitermes speratus Kolbe (Isoptera: Rhinotermitidae). Presoldier and worker differentiation of this species can be artificially induced by juvenile hormone and 20-hydroxyecdysone application, respectively. However, appropriate RNAi technique of genes expressed during caste differentiation has never been considered. To clarify this issue, first, we injected nine different volumes of nuclease-free water (NFW, 0–404.8 nL) into workers and found that survival and caste differentiation rates were strongly reduced by the application of the top three largest volumes. Second, we injected double-stranded (ds) RNA of ecdysone receptor homolog (RsEcR) (2.0 µg/151.8 nL NFW) into workers with hormone treatments. The expression levels of RsEcR were significantly reduced at 9 days after dsRNA injection. RsEcR RNAi strongly affected both molting events during presoldier and worker differentiation induced by hormone treatments. The present results highlight the need for caution regarding injection volumes for RNAi experiments using hormone treatments. We suggest that the injection of dsRNA solution (2 µg; approximately 100–200 nL) is suitable for RNAi experiments during caste differentiation induced by hormone application in R. speratus.
Quantitative evaluation of sea reclamation activities on tidal creek connectivity
Authors: Man Ying , Zhou Fangwen , Wang Qing , Cui Baoshan
Published: May 2023

Deltas are in a dynamic balance due to the impact of fluvial and coastal flooding, and hydrological connectivity plays an important role. In recent decades, the dynamic equilibrium has been influenced by upstream and local human activities, including sea reclamation activities. However, in most instances, the influence of human activities has not been explicitly distinguished and quantified in detail. In this paper, the influence of sea reclamation activities on hydrological connectivity in the Yellow River Delta was quantified by parameterizing the resistance surfaces (a spatial layer that assigns a value to each landscape feature, indicating the degree to which that variable impedes or promotes movement) that includes sea reclamation activities. By optimizing a functional relationship between landscape features and hydrological connectivity (water flow movement patterns), the values in the resistance surfaces could be assigned. We first calculated hydrological distances among bifurcations from 1985 to 2020 with a 5-year interval representing the hydrological connectivity of each tidal creek. The sea reclamation activities in the YRD were classified into four: reclaimed land, sea enclosure activity, freshwater resource facilities, and engineering in the oil field to create resistance surfaces. We identified that the periods of 1990–1995 and 2000–2005 were under the most severe influence of sea reclamation activities. Sea enclosure activity, freshwater resource facilities, and engineering in oil fields played major roles in composing resistance surfaces. Mariculture (quantified relative resistance value, 1.00), reservoir (0.92), agriculture (0.91), and river (0.97) were the features with the highest resistance values in the initial and mature development stages. The formation of resistance (costs to movement) was due to human activities and natural factors, for example, the evolution of tidal creeks. To develop the resource in tidal flats sustainably, systematic monitoring and sufficient conservation awareness were required. This study contributed to coastal management and planning by providing a quantified assessment of different types of sea reclamation activities.
The applicability of transperceptual and deep learning approaches to the study and mimicry of complex cartilaginous tissues
Authors: Waghorne J. , Howard C. , Hu H. , Pang J. , Peveler W. J. , Harris L. , Barrera O.
Published: May 2023

Introduction: Complex soft tissues, such as knee meniscus, play a crucial role in mobility and joint health but are incredibly difficult to repair and replace when damaged. This difficulty is due to the highly hierarchical and porous nature of the tissues, which, in turn, leads to their unique mechanical properties that provide joint stability, load redistribution, and friction reduction. To design tissue substitutes, the internal architecture of the native tissue needs to be understood and replicated.

Methods: We explore a combined audiovisual approach, a so-called transperceptual approach, to generate artificial architectures mimicking the native architectures. The proposed methodology uses both traditional imagery and sound generated from each image to rapidly compare and contrast the porosity and pore size within the samples. We have trained and tested a generative adversarial network (GAN) on 2D image stacks of a knee meniscus. To understand how the resolution of the set of training images impacts the similarity of the artificial dataset to the original, we have trained the GAN with two datasets. The first consists of 478 pairs of audio and image files for which the images were downsampled to 64 × 64 pixels. The second dataset contains 7,640 pairs of audio and image files for which the full resolution of 256 × 256 pixels is retained, but each image is divided into 16 square sections to maintain the limit of 64 × 64 pixels required by the GAN.

Results: We reconstructed the 2D stacks of artificially generated datasets into 3D objects and ran image analysis algorithms to characterize the architectural parameters statistically (pore size, tortuosity, and pore connectivity). Comparison with the original dataset showed that the artificially generated dataset based on the downsampled images performs best in terms of parameter matching, achieving between 4% and 8% of the mean of grayscale values of the pixels, mean porosity, and pore size of the native dataset.

Discussion: Our audiovisual approach has the potential to be extended to larger datasets to explore how similarities and differences can be audibly recognized across multiple samples.
Uncovering transcriptomic landscape alterations of CAN-2409 in in vitro and in vivo glioma models
Authors: Koch Marilin S. , Zdioruk Mykola , Nowicki Michal O. , Hoetker Michael S. , Herbert Zachary T. , Barone Francesca , Tak Paul P. , Chiocca E. Antonio , Tabatabai Ghazaleh , Lawler Sean E.
Published: May 2023

Rationale

CAN-2409 is a locally delivered oncolytic therapy, which results in vaccination against the injected tumor. CAN-2409 consists of a non-replicating adenovirus armed with the Herpes virus thymidine kinase, which metabolizes ganciclovir into a phosphorylated nucleotide that is incorporated into the tumor cell’s genome, thereby inflicting immunogenic cancer cell death. While CAN-2409’s immunological impact has been well characterized, its effects on the tumor cells transcriptome remains unknown. We compared the transcriptomic landscape after treatment of glioblastoma models with CAN-2409 in vitro and in vivo to assess how the interplay with the tumor microenvironment influences CAN-2409-mediated transcriptome alterations.

Methods

We performed RNA-Seq with CAN-2409 treated patient-derived glioma stem-like cells and tumors of C57/BL6 mice and compared KEGG pathway usage and differential gene expression focusing on immune cell and cytokine profiles. T-cell -killing assays were performed to assess candidate effectors.

Results

PCA analysis showed distinct clustering of control and CAN-2409 samples under both conditions. KEGG pathway analysis revealed significant enrichment for p53 signaling and cell cycle pathway, with similar dynamics for key regulators of both pathways in vitro and in vivo, including MYC, CCNB1, PLK1 and CDC20. Selected alterations (PLK1 and CCNB1) were validated at the protein level. Cytokine expression analysis revealed upregulation of pro-inflammatory IL12a under both conditions; immune cell gene profiling showed reduction of myeloid associated genes. T-cell-killing assays showed increased killing in the presence of IL-12.

Conclusion

CAN-2409 significantly alters the transcriptome both in vitro and in vivo. Comparison of pathway enrichment revealed mutual and differential utilization of pathways under both conditions, suggesting a modulating influence on the cell cycle in tumor cells, and of the tumor microenvironment on the transcriptome in vivo. IL-12 synthesis likely depends on interactions with the tumor microenvironment, and it facilitates CAN-2409 cell killing. This dataset provides potential to understand resistance mechanisms and identify potential biomarkers for future studies.
Plasma virome dynamics in chronic hepatitis B virus infected patients
Authors: Thijssen Marijn , Tacke Frank , Van Espen Lore , Cassiman David , Naser Aldine Mahmoud , Nevens Frederik , Van Ranst Marc , Matthijnssens Jelle , Pourkarim Mahmoud Reza
Published: May 2023

The virome remains an understudied domain of the human microbiome. The role of commensal viruses on the outcome of infections with known pathogens is not well characterized. In this study we aimed to characterize the longitudinal plasma virome dynamics in chronic hepatitis B virus (HBV) infected patients. Eighty-five longitudinal plasma samples were collected from 12 chronic HBV infected individuals that were classified in the four stages of HBV infection. The virome was characterized with an optimized viral extraction protocol and deep-sequenced on a NextSeq 2500 platform. The plasma virome was primarily composed of members of the Anello- Flavi-, and Hepadnaviridae (HBV) families. The virome structure and dynamics did not correlate with the different stages of chronic HBV infection nor with the administration of antiviral therapy. We observed a higher intrapersonal similarity of viral contigs. Genomic analysis of viruses observed in multiple timepoint demonstrated the presence of a dynamic community. This study comprehensively assessed the blood virome structure in chronic HBV infected individuals and provided insights in the longitudinal development of this viral community.
Development of a colloidal gold immunochromatographic strip with enhanced signal for the detection of bovine parvovirus
Authors: Yu Xiaoli , Jiang Yanping , Zhang Songsong , Wang Caihong , Wang Ruichong , Zhang Lanlan , Tao Siming , Cui Wen , Li Jiaxuan , Qiao Xinyuan
Published: May 2023

Bovine parvovirus (BPV) is a pathogen responsible for respiratory and digestive tract symptoms in calves and abortion and stillbirth in pregnant cows. In this study, we developed a colloidal gold immunochromatographic (GICG) strip with an enhanced signal for detecting BPV according to the double-antibody sandwich principle and an enzyme-based signal amplification system to amplify the signal. This system utilizes horseradish peroxidase reacting with a substrate solution containing 3,3′,5,5′-tetramethylbenzidine and dextran sulfate to obtain insoluble blue products on the test and control lines. We optimized different reaction conditions, including the amount of monoclonal antibodies (mAbs), pH of the colloidal gold solution, coating solution, blocking solution, sample pad treatment solution, antibody concentration in the control line, and antibody concentration in the detection line. The sensitivity of the signal-enhanced GICG strip showed that the minimum amount for detecting BPV was 102 TCID50, 10 times higher than that of the traditional GICG strip. The results of the specificity test showed that the signal-enhanced GICG strip had no cross-reactivity with BRV, BVDV, or BRSV. The results of the repeatability test showed that the coefficient of variation between and within batches was less than 5%, showing good repeatability. Moreover, for validation, PCR and the signal-enhanced GICG strip were used to detect 280 clinical bovine fecal samples. The concordance rate compared with PCR was 99.29%. Hence, the developed strip exhibited high sensitivity and specificity for the detection of BPV. Therefore, this strip could be a rapid, convenient, and effective method for the diagnosis of BPV infection in the field.
Herpes simplex virus type I glycoprotein L evades host antiviral innate immunity by abrogating the nuclear translocation of phosphorylated NF-κB sub-unit p65
Authors: Li Zhaolong , Feng Zhihua , Fang Zhou , Chen Jianghua , Chen Wengzhi , Liang Wangwang , Chen Qi
Published: May 2023

Nuclear factor (NF)-κB plays an important role in the innate immune response by inducing antiviral genes’ expression. However, the herpes simplex virus 1 (HSV-1) virus has developed multiple ways to interfere with NF-κB activity to escape the host antiviral response. Here, we found that HSV-1 envelope glycoprotein L(gL) markedly inhibits interferon (IFN) production and its downstream antiviral genes. Our results showed that ectopic expression of gL inhibited IFN-β promoter activation, and decreased IFN-β production, the expression of IFN-stimulated genes (ISGs), and inhibited immunologic stimulant (poly I:C) induced activation of IFN signaling pathway. Depletion of gL by short interfering RNA (siRNA) significantly upregulated IFN-β and ISG production. Further study showed that the N-terminus of the gL bound to the Rel homology domain (RHD) of the p65 and concealed the nuclear localization signal of p65, thereby impeding the translocation of phosphorylated p65 to the nucleus. In summary, our findings indicated that the N-terminal of HSV-1 gL contributes to immune invasion by inhibiting the nuclear translocation of p65.
Immunogenic cell death-led discovery of COVID-19 biomarkers and inflammatory infiltrates
Authors: Zhuo Jianzhen , Wang Ke , Shi Zijun , Yuan Chunlei
Published: May 2023

Immunogenic cell death (ICD) serves a critical role in regulating cell death adequate to activate an adaptive immune response, and it is associated with various inflammation-related diseases. However, the specific role of ICD-related genes in COVID-19 remains unclear. We acquired COVID-19-related information from the GEO database and a total of 14 ICD-related differentially expressed genes (DEGs) were identified. These ICD-related DEGs were closely associated with inflammation and immune activity. Afterward, CASP1, CD4, and EIF2AK3 among the 14 DEGs were selected as feature genes based on LASSO, Random Forest, and SVM-RFE algorithms, which had reliable diagnostic abilities. Moreover, functional enrichment analysis indicated that these feature genes may have a potential role in COVID-19 by being involved in the regulation of immune response and metabolism. Further CIBERSORT analysis demonstrated that the variations in the immune microenvironment of COVID-19 patients may be correlated with CASP1, CD4, and EIF2AK3. Additionally, 33 drugs targeting 3 feature genes had been identified, and the ceRNA network demonstrated a complicated regulative association based on these feature genes. Our work identified that CASP1, CD4, and EIF2AK3 were diagnostic genes of COVID-19 and correlated with immune activity. This study presents a reliable diagnostic signature and offers an overview to investigate the mechanism of COVID-19.
Exploring the therapeutic and anti-tumor properties of morusin: a review of recent advances
Authors: Hafeez Amna , Khan Zeeshan , Armaghan Muhammad , Khan Khushbukhat , Sönmez Gürer Eda , Abdull Razis Ahmad Faizal , Modu Babagana , Almarhoon Zainab M. , Setzer William N. , Sharifi-Rad Javad
Published: May 2023

Morusin is a natural product that has been isolated from the bark of Morus alba, a species of mulberry tree. It belongs to the flavonoid family of chemicals, which is abundantly present in the plant world and is recognized for its wide range of biological activities. Morusin has a number of biological characteristics, including anti-inflammatory, anti-microbial, neuro-protective, and antioxidant capabilities. Morusin has exhibited anti-tumor properties in many different forms of cancer, including breast, prostate, gastric, hepatocarcinoma, glioblastoma, and pancreatic cancer. Potential of morusin as an alternative treatment method for resistant malignancies needs to be explored in animal models in order to move toward clinical trials. In the recent years several novel findings regarding the therapeutic potential of morusin have been made. This aim of this review is to provide an overview of the present understanding of morusin’s beneficial effects on human health as well as provide a comprehensive and up-to-date discussion of morusin’s anti-cancer properties with a special focus on in vitro and in vivo studies. This review will aid future research on the creation of polyphenolic medicines in the prenylflavone family, for the management and treatment of cancers.
Dynamic project planning with digital twin
Authors: Zahno Silvan , Corre Jérôme , Petrovic Darko , Mottiez Gilles , Fracheboud Loïc , Amand Axel , Devènes Steve , Maître Gilbert , Carrino Francesco
Published: May 2023

The digital twin (DT) concept plays a crucial role in Industry 4.0 and the digitalization of manufacturing processes. A DT is a virtual representation of a physical object, system, or process, designed to accurately reflect its real-world counterpart. In manufacturing, existing process data are often incomplete and do not qualify as a DT. However, with the help of specialized communication frameworks and cheaper, easier-to-use sensors, it is possible to integrate the existing manufacturing execution system (MES) and enterprise resource planning (ERP) data with the missing data gathered from the shop floor to create a comprehensive DT. In this paper, we present a digital shop floor decision support system (DSS) for non-linear aluminum manufacturing production. The system is split into five main components: digitization of shop floor orders; merging and sorting of MES, ERP, and shop floor data; custom and genetic optimization algorithms for the aging furnace production step; layout construction mechanism for optimal placement and stacking of orders in the furnace; and a user-friendly graphical user interface (GUI). The system’s performance was evaluated through three tests. The first test measured the efficiency of digitization, the second aimed to quantify time saved in finding packets in the hall, and the last test measured the impact of the optimizer on furnace productivity. The results revealed a 23.5% improvement in furnace capacity, but limitations were identified due to usability and human intervention.
“Huoling Shengji granule” for amyotrophic lateral sclerosis: protocol for a multicenter, randomized, double-blind, riluzole parallel controlled clinical trial
Authors: Liu Xiaolu , Qin Tingting , Li Tao , Shan Lei , Lei Xiang , Xu Xin , Wen Bin , Feng Yi , Yin Ping , Fan Dongsheng
Published: May 2023

Background

There is still a large demand for effective treatments to delay disease deterioration in amyotrophic lateral sclerosis (ALS). Typical symptoms of ALS are considered “flaccidity syndrome” in traditional Chinese medicine (TCM). Huoling Shengji Granule (HLSJ) is a TCM formula used to treat flaccidity syndrome. Results of preclinical tests and a previous clinical study support HLSJ as a novel drug for ALS patients. This trial proposed to examine whether a 48-week course of HLSJ is effective and safe for ALS patients diagnosed with the Chinese medicine syndrome of spleen qi insufficiency and kidney yang deficiency.

Methods and analysis

In this phase II, multicenter, randomized, double-blind, riluzole parallel-controlled, superiority-design study, eligible participants had the equal opportunity to be assigned to receive either HLSJ or riluzole randomly. Eleven specialized ALS centers in Mainland China will recruit 144 patients for this trial. The primary and secondary outcomes included the change in the ALSFRS-R score and the Rasch-Built Overall Amyotrophic Lateral Sclerosis Disability Scale (ROADS) from baseline to Week 48.

Discussion

Here, we endeavored to evaluate TCM for ALS using a standard evidence-based approach for the first time. In addition, the ROADS, a self-report linear-weighted questionnaire, was selected as a secondary outcome measure. We expect to offer a new reference for the outcome evaluation of ALS trials.

Clinical trial registration:http://www.Chictr.org.cn, identifier ChiCTR2100044085.
APOE as potential biomarkers of moyamoya disease
Authors: Wu Haibin , Xu Jiang , Sun Jiarong , Duan Jian , Xiao Jinlin , Ren Quan , Zhou Pengfei , Yan Jian , Li Youping , Xiong Xiaoxing , Zeng Erming
Published: May 2023

Objective

The mechanisms underpinning Moyamoya disease (MMD) remain unclear, and effective biomarkers remain unknown. The purpose of this study was to identify novel serum biomarkers of MMD.

Methods

Serum samples were collected from 23 patients with MMD and 30 healthy controls (HCs). Serum proteins were identified using tandem tandem-mass-tag (TMT) labeling combined with liquid chromatography-tandem mass spectrometry (LC-MS/MS). Differentially expressed proteins (DEPs) in the serum samples were identified using the SwissProt database. The DEPs were assessed using the Kyoto Encyclopedia of Genes and Genomes (KEGG) database, Gene Ontology (GO), and protein-protein interaction (PPI) networks, and hub genes were identified and visualized using Cytoscape software. Microarray datasets GSE157628, GSE189993, and GSE100488 from the Gene Expression Omnibus (GEO) database were collected. Differentially expressed genes (DEGs) and differentially expressed miRNAs (DE-miRNAs) were identified, and miRNA targets of DEGs were predicted using the miRWalk3.0 database. Serum apolipoprotein E (APOE) levels were compared in 33 MMD patients and 28 Moyamoya syndrome (MMS) patients to investigate the potential of APOE to be as an MMD biomarker.

Results

We identified 85 DEPs, of which 34 were up- and 51 down-regulated. Bioinformatics analysis showed that some DEPs were significantly enriched in cholesterol metabolism. A total of 1105 DEGs were identified in the GSE157628 dataset (842 up- and 263 down-regulated), whereas 1290 were identified in the GSE189993 dataset (200 up- and 1,090 down-regulated). The APOE only overlaps with the upregulated gene expression in Proteomic Profiling and in GEO databases. Functional enrichment analysis demonstrated that APOE was associated with cholesterol metabolism. Moreover, 149 miRNAs of APOE were predicted in the miRWalk3.0 database, and hsa-miR-718 was the only DE-miRNA overlap identified in MMD samples. Serum APOE levels were significantly higher in patients with MMD than in those without. The performance of APOE as an individual biomarker to diagnose MMD was remarkable.

Conclusions

We present the first description of the protein profile of patients with MMD. APOE was identified as a potential biomarker for MMD. Cholesterol metabolism was found to potentially be related to MMD, which may provide helpful diagnostic and therapeutic insights for MMD.
Effects of transcutaneous neuromuscular electrical stimulation on post-stroke dysphagia: a systematic review and meta-analysis
Authors: Wang Yuhan , Xu Lu , Wang Linjia , Jiang Minjiao , Zhao Ling
Published: May 2023

Background

Dysphagia is one of the common complications after stroke. It is closely related to lung infection and malnutrition. Neuromuscular electrical stimulation (NMES) is widely used in the treatment of post-stroke dysphagia, but the evidence-based medical evidence of NMES is limited. Therefore, this study aimed to evaluate the clinical efficacy of NMES in patients with post-stroke dysphagia by systematic review and meta-analysis.

Methods

We searched the CNKI, Wanfang, VIP, SinoMed, PubMed, Embase, Cochrane Library, and Web of Science databases for all randomized controlled trials (RCTs) of NMES in the treatment of post-stroke dysphagia from the establishment of the database to 9 June 2022. The risk of bias assessment tool recommended by Cochrane and the GRADE method was used to assess the risk of bias and the quality of evidence. RevMan 5.3 was used for statistical analysis. Sensitivity and subgroup analyses were performed to evaluate the intervention effect more specifically.

Results

A total of 46 RCTs and 3,346 patients with post-stroke dysphagia were included in this study. Our meta-analysis showed that NMES combined with routine swallowing therapy (ST) could effectively improve swallowing function in Penetration-Aspiration Scale (MD = −0.63, 95% CI [−1.15, −0.12], P = 0.01), Functional Oral Intake Scale (MD = 1.32, 95% CI [0.81, 1.83], P < 0.00001), Functional Dysphagia Scale (MD = − 8.81, 95% CI [−16.48, −1.15], P = 0.02), the Standardized Swallowing Assessment (MD = −6.39, 95% CI [−6.56, −6.22], P < 0.00001), the Videofluoroscopic Swallow Study (MD = 1.42, 95% CI [1.28, 1.57], P < 0.00001) and the Water swallow test (MD = −0.78, 95% CI [−0.84, −0.73], P < 0.00001). Furthermore, it could improve the quality of life (MD = 11.90, 95% CI [11.10, 12.70], P < 0.00001), increase the upward movement distance of hyoid bone (MD = 2.84, 95% CI [2.28, 3.40], P < 0.00001) and the forward movement distance of hyoid bone (MD = 4.28, 95% CI [3.93, 4.64], P < 0.00001), reduce the rate of complications (OR = 0.37, 95%CI [0.24, 0.57], P < 0.00001). Subgroup analyses showed that NMES+ST was more effective at 25 Hz, 7 mA or 0–15 mA, and at courses ( ≤ 4 weeks). Moreover, patients with an onset of fewer than 20 days and those older than 60 years appear to have more positive effects after treatment.

Conclusion

NMES combined with ST could effectively increase the forward and upward movement distance of the hyoid bone, improve the quality of life, reduce the rate of complications, and improve the swallowing function of patients with post-stroke dysphagia. However, its safety needs to be further confirmed.

Systematic review registration

https://www.crd.york.ac.uk/PROSPERO, identifier: CRD42022368416.
The effect of the subthreshold oscillation induced by the neurons' resonance upon the electrical stimulation-dependent instability
Authors: Yu Shoujun , Yue Wenji , Guo Tianruo , Liu Yonghong , Zhang Yapeng , Khademi Sara , Zhou Tian , Xu Zhen , Song Bing , Wu Tianzhun , Liu Fenglin , Tai Yanlong , Yu Xuefei , Wang Hao
Published: May 2023

Repetitive electrical nerve stimulation can induce a long-lasting perturbation of the axon's membrane potential, resulting in unstable stimulus-response relationships. Despite being observed in electrophysiology, the precise mechanism underlying electrical stimulation-dependent (ES-dependent) instability is still an open question. This study proposes a model to reveal a facet of this problem: how threshold fluctuation affects electrical nerve stimulations. This study proposes a new method based on a Circuit-Probability theory (C-P theory) to reveal the interlinkages between the subthreshold oscillation induced by neurons' resonance and ES-dependent instability of neural response. Supported by in-vivo studies, this new model predicts several key characteristics of ES-dependent instability and proposes a stimulation method to minimize the instability. This model provides a powerful tool to improve our understanding of the interaction between the external electric field and the complexity of the biophysical characteristics of axons.
Association of predicted fat mass and lean body mass with diabetes: a longitudinal cohort study in an Asian population
Authors: Kuang Maobin , Lu Song , Yang Ruijuan , Chen Huaigang , Zhang Shuhua , Sheng Guotai , Zou Yang
Published: May 2023

Objective

The relationship between body composition fat mass (FM) and lean body mass (LBM) and diabetes risk is currently debated, and the purpose of this study was to examine the association of predicted FM and LBM with diabetes in both sexes.

Methods

The current study was a secondary analysis of data from the NAGALA (NAfld in the Gifu Area, Longitudinal Analysis) cohort study of 15,463 baseline normoglycemic participants. Predicted LBM and FM were calculated for each participant using anthropometric prediction equations developed and validated for different sexes based on the National Health and Nutrition Examination Survey (NHANES) database, and the outcome of interest was diabetes (types not distinguished) onset. Multivariate Cox regression analyses were applied to estimate the hazard ratios (HRs) and 95% confidence intervals (CIs) for the associations of predicted FM and LBM with diabetes risk and further visualized their associations using a restricted cubic spline function.

Results

The incidence density of diabetes was 3.93/1000 person-years over a mean observation period of 6.13 years. In women, predicted LBM and FM were linearly associated with diabetes risk, with each kilogram increase in predicted LBM reducing the diabetes risk by 65% (HR 0.35, 95%CI 0.17, 0.71; P < 0.05), whereas each kilogram increase in predicted FM increased the diabetes risk by 84% (HR 1.84, 95%CI 1.26, 2.69; P < 0.05). In contrast, predicted LBM and FM were non-linearly associated with diabetes risk in men (all P for non-linearity < 0.05), with an L-shaped association between predicted LBM and diabetes risk and a saturation point that minimized the risk of diabetes was 45.4 kg, while predicted FM was associated with diabetes risk in a U-shape pattern and a threshold point with the lowest predicted FM-related diabetes risk was 13.76 kg.

Conclusion

In this Asian population cohort, we found that high LBM and low FM were associated with lower diabetes risk according to anthropometric equations. Based on the results of the non-linear analysis, we believed that it may be appropriate for Asian men to keep their LBM above 45.4 kg and their FM around 13.76 kg.
Fecal metabolomics combined with 16S rRNA gene sequencing to analyze the effect of Jiaotai pill intervention in type 2 diabetes mellitus rats
Authors: Liu Jing , Wang Xu , Li Qiyao , Piao Chengyu , Fan Zuowang , Zhang Yao , Yang Saisai , Wu Xiuhong
Published: May 2023

The occurrence and development of type 2 diabetes mellitus (T2DM) are closely related to gut microbiota. Jiaotai pill (JTP) is used to treat type 2 diabetes mellitus, with definite efficacy in clinical practice. However, it is not clear whether the therapeutic effect is produced by regulating the changes in gut microbiota and its metabolism. In this study, T2DM rat models were established by a high-fat diet and low-dose streptozotocin (STZ). Based on the pharmacodynamic evaluation, the mechanism of JTP in the treatment of type 2 diabetes mellitus was investigated by fecal metabolism and 16S rRNA gene sequencing. The results showed that JTP decreased blood glucose (FBG, HbA1c) and blood lipid (TC, TG, and LDL) levels and alleviated insulin resistance (FINS, IL-10) in T2DM rats. 16S rRNA gene sequencing results revealed that JTP increased microbiota diversity and reversed the disorder of gut microbiota in T2DM rats, and therefore achieved the therapeutic effect in T2DM. JTP regulated 13 differential flora, which were Actinobacteria, Bacteroidetes, Firmicutes, Proteobacteria, Eubacteriaceae, Prevotellaceae, Ruminococcaceae, Clostridium_IV, Clostridium_XlVa, Eubacterium, Fusicatenibacter, Romboutsia, and Roseburia. Metabolomics analysis showed that JTP interfered with 13 biomarkers to play a therapeutic role in type 2 diabetes mellitus. They were L-Valine, Choline, L-Aspartic acid, Serotonin, L-Lysine, L-Histidine, 3-Hydroxybutyric acid, Pyruvic acid, N-Acetylornithine, Arachidonic acid, L-Tryptophan, L-Alanine, and L-Methionine. KEGG metabolic pathway analysis of the above differential metabolites and gut microbiota by using the MetaboAnalyst database and Picrust software. It was found that JTP treated type 2 diabetes mellitus by affecting metabolic pathways such as amino acid metabolism, carbohydrate metabolism, and lipid metabolism. Spearman correlation analysis revealed high correlations for 7 pharmacological indicators, 12 biomarkers, and 11 gut microbiota. In this study, the therapeutic effect and potential mechanism of JTP on type 2 diabetes mellitus were preliminarily demonstrated by gut microbiota and metabolomics, which could provide a theoretical basis for the treatment of T2DM with JTP.
Analysis of predictors of malnutrition in adult hospitalized patients: social determinants and food security
Authors: Ouaijan Krystel , Hwalla Nahla , Kandala Ngianga-Bakwin , Abi Kharma Joelle , Kabengele Mpinga Emmanuel
Published: May 2023

Background

Malnutrition in hospitalized patients is becoming a priority during the patient care process due to its implications for worsening health outcomes. It can be the result of numerous social factors beyond clinical ones. This study aimed to evaluate the link between these various risk factors considered social determinants of health, food security levels, and malnutrition and to identify potential predictors.

Methods

A cross-sectional observational study was conducted on a random sample of adult patients in five different hospitals in Lebanon. Malnutrition was assessed using the Global Leadership Initiative on Malnutrition (GLIM) criteria. Patients were interviewed to collect social and economic characteristics and were categorized into four criteria: (1) area of residence (urbanization level), (2) level of education, (3) employment status, and (4) source of health coverage. The food security level was screened by a validated two-question tool, adapted from the US Department of Agriculture Household Food Security Survey, targeting both quantity and quality.

Results

In a random sample of 343 patients, the prevalence of malnutrition according to the GLIM criteria was 35.6%. Patients with low levels of food security, mainly low quality of food, had higher odds of being malnourished (OR = 2.93). Unemployed or retired patients and those who have only completed only elementary school had higher odds of being diagnosed with malnutrition as compared to those who were employed or had university degrees, respectively (OR = 4.11 and OR = 2.33, respectively). Employment status, education level, and type of health coverage were identified as predictors of malnutrition in the multiple regression model. Household location (urban vs. rural) was not associated with malnutrition.

Conclusion

The social determinants of health identified in our study, mainly the level of education and income level, in addition to food security, were identified as predictors of malnutrition in hospitalized patients. These findings should guide healthcare professionals and national policies to adopt a broader perspective in targeting malnutrition by including social determinants in their nutrition care.
Gene mutation landscape of a rare patient with acute megakaryoblastic leukemia after treatment of intracranial germ cell tumor
Authors: Wang Li-Xin , Liao Wei-Jie , Jiang Yu-Hua , Chen Chao , Lu Wang-Sheng , Yin Feng , Ning Hao-Yong
Published: May 2023

Introduction

It was first reported that germ cell tumor patients suffer from hematologic malignancies 37 years ago. Since then, the number of relevant reports has increased each year, with most cases being mediastinal germ cell tumor. Theories have been proposed to explain this phenomenon, including a shared origin of progenitor cells, the effects of treatment, and independent development. However, up to now, no widely accepted explanation exists. The case with acute megakaryoblastic leukemia and intracranial germ cell tumor has never been reported before and the association is far less known.

Methods

We used whole exome sequencing and gene mutation analysis to study the relationship between intracranial germ cell tumor and acute megakaryoblastic leukemia of our patient.

Results

We report a patient who developed acute megakaryoblastic leukemia after treatment for an intracranial germ cell tumor. Through whole exome sequencing and gene mutation analysis, we identified that both tumors shared the same mutation genes and mutation sites, suggesting they originated from the same progenitor cells and differentiated in the later stage.

Discussion

Our findings provide the first evidence supporting the theory that acute megakaryoblastic leukemia and intracranial germ cell tumor has the same progenitor cells.
Liquid biopsies and minimal residual disease in lymphoid malignancies
Authors: Bou Zerdan Maroun , Kassab Joseph , Saba Ludovic , Haroun Elio , Bou Zerdan Morgan , Allam Sabine , Nasr Lewis , Macaron Walid , Mammadli Mahinbanu , Abou Moussa Sarah , Chaulagain Chakra P.
Published: May 2023

Minimal residual disease (MRD) assessment using peripheral blood instead of bone marrow aspirate/biopsy specimen or the biopsy of the cancerous infiltrated by lymphoid malignancies is an emerging technique with enormous interest of research and technological innovation at the current time. In some lymphoid malignancies (particularly ALL), Studies have shown that MRD monitoring of the peripheral blood may be an adequate alternative to frequent BM aspirations. However, additional studies investigating the biology of liquid biopsies in ALL and its potential as an MRD marker in larger patient cohorts in treatment protocols are warranted. Despite the promising data, there are still limitations in liquid biopsies in lymphoid malignancies, such as standardization of the sample collection and processing, determination of timing and duration for liquid biopsy analysis, and definition of the biological characteristics and specificity of the techniques evaluated such as flow cytometry, molecular techniques, and next generation sequencies. The use of liquid biopsy for detection of minimal residual disease in T-cell lymphoma is still experimental but it has made significant progress in multiple myeloma for example. Recent attempt to use artificial intelligence may help simplify the algorithm for testing and may help avoid inter-observer variation and operator dependency in these highly technically demanding testing process.