bluuebunny/crossref_metadata_2025 huggingface dataset:
Reconstitution of human microglia and resident T cells in the brain of humanized DRAGA mice
Authors: Ghosh Roy Sounak , Karim Ahmad F. , Brumeanu Teodor-D. , Casares Sofia A.
Published: June 2024

Humanized mouse models are valuable tools for investigating the human immune system in response to infection and injury. We have previously described the human immune system (HIS)-DRAGA mice (HLA-A2.HLA-DR4.Rag1KO.IL-2RgKO.NOD) generated by infusion of Human Leukocyte Antigen (HLA)-matched, human hematopoietic stem cells from umbilical cord blood. By reconstituting human cells, the HIS-DRAGA mouse model has been utilized as a “surrogate in vivo human model” for infectious diseases such as Human Immunodeficiency Virus (HIV), Influenza, Coronavirus Disease 2019 (COVID-19), scrub typhus, and malaria. This humanized mouse model bypasses ethical concerns about the use of fetal tissues for the humanization of laboratory animals. Here in, we demonstrate the presence of human microglia and T cells in the brain of HIS-DRAGA mice. Microglia are brain-resident macrophages that play pivotal roles against pathogens and cerebral damage, whereas the brain-resident T cells provide surveillance and defense against infections. Our findings suggest that the HIS-DRAGA mouse model offers unique advantages for studying the functions of human microglia and T cells in the brain during infections, degenerative disorders, tumors, and trauma, as well as for testing therapeutics in these pathological conditions.
Effects of vitamin D signaling in cardiovascular disease: centrality of macrophage polarization
Authors: Fliri Anton , Kajiji Shama
Published: June 2024

Among the leading causes of natural death are cardiovascular diseases, cancer, and respiratory diseases. Factors causing illness include genetic predisposition, aging, stress, chronic inflammation, environmental factors, declining autophagy, and endocrine abnormalities including insufficient vitamin D levels. Inconclusive clinical outcomes of vitamin D supplements in cardiovascular diseases demonstrate the need to identify cause-effect relationships without bias. We employed a spectral clustering methodology capable of analyzing large diverse datasets for examining the role of vitamin D's genomic and non-genomic signaling in disease in this study. The results of this investigation showed the following: (1) vitamin D regulates multiple reciprocal feedback loops including p53, macrophage autophagy, nitric oxide, and redox-signaling; (2) these regulatory schemes are involved in over 2,000 diseases. Furthermore, the balance between genomic and non-genomic signaling by vitamin D affects autophagy regulation of macrophage polarization in tissue homeostasis. These findings provide a deeper understanding of how interactions between genomic and non-genomic signaling affect vitamin D pharmacology and offer opportunities for increasing the efficacy of vitamin D-centered treatment of cardiovascular disease and healthy lifespans.
Influencing factors and improvement methods of coronary artery plaque evaluation in CT
Authors: Gao Yaqi , Pan Yao , Jia Chongfu
Published: June 2024

Accurate evaluation of the nature and composition of coronary plaque involves clinical follow-up and prognosis. Coronary CT angiography is the most commonly non-invasive method for plaque evaluation, however, the qualitative and quantitative evaluation of plaque based on CT value is inaccurate, due to the influence of luminal attenuation, tube voltage, parameter setting and the subjectivity.
Plasminogen missense variants and their involvement in cardiovascular and inflammatory disease
Authors: Brito-Robinson Teresa , Ayinuola Yetunde A. , Ploplis Victoria A. , Castellino Francis J.
Published: June 2024

Human plasminogen (PLG), the zymogen of the fibrinolytic protease, plasmin, is a polymorphic protein with two widely distributed codominant alleles, PLG/Asp453 and PLG/Asn453. About 15 other missense or non-synonymous single nucleotide polymorphisms (nsSNPs) of PLG show major, yet different, relative abundances in world populations. Although the existence of these relatively abundant allelic variants is generally acknowledged, they are often overlooked or assumed to be non-pathogenic. In fact, at least half of those major variants are classified as having conflicting pathogenicity, and it is unclear if they contribute to different molecular phenotypes. From those, PLG/K19E and PLG/A601T are examples of two relatively abundant PLG variants that have been associated with PLG deficiencies (PD), but their pathogenic mechanisms are unclear. On the other hand, approximately 50 rare and ultra-rare PLG missense variants have been reported to cause PD as homozygous or compound heterozygous variants, often leading to a debilitating disease known as ligneous conjunctivitis. The true abundance of PD-associated nsSNPs is unknown since they can remain undetected in heterozygous carriers. However, PD variants may also contribute to other diseases. Recently, the ultra-rare autosomal dominant PLG/K311E has been found to be causative of hereditary angioedema (HAE) with normal C1 inhibitor. Two other rare pathogenic PLG missense variants, PLG/R153G and PLG/V709E, appear to affect platelet function and lead to HAE, respectively. Herein, PLG missense variants that are abundant and/or clinically relevant due to association with disease are examined along with their world distribution. Proposed molecular mechanisms are discussed when known or can be reasonably assumed.
Risk factors and prognostic value of endotoxemia in patients with acute myocardial infarction
Authors: Nguyen Maxime , Putot Alain , Masson David , Cottin Yves , Gautier Thomas , Tribouillard Laura , Rérole Anne-Laure , Guinot Pierre-Grégoire , Maza Maud , Pais de Barros Jean-Paul , Deckert Valérie , Farnier Michel , Lagrost Laurent , Zeller Marianne
Published: June 2024

Background

There is increasing evidence regarding the association between endotoxemia and the pathogenesis of atherosclerosis and myocardial infarction (MI). During the acute phase of MI, endotoxemia might increase inflammation and drive adverse cardiovascular (CV) outcomes. We aimed to explore the risk factors and prognostic value of endotoxemia in patients admitted for acute MI.

Methods

Patients admitted to the coronary care unit of Dijon University Hospital for type 1 acute MI between 2013 and 2015 were included. Endotoxemia, assessed by plasma lipopolysaccharide (LPS) concentration, was measured by mass spectrometry. Major adverse CV events were recorded in the year following hospital admission.

Results

Data from 245 consecutive MI patients were analyzed. LPS concentration at admission markedly increased with age and diabetes. High LPS concentration was correlated with metabolic biomarkers (glycemia, triglyceride, and total cholesterol) but not with CV (troponin Ic peak and N-terminal pro-brain natriuretic peptide) or inflammatory biomarkers (C-reactive protein, IL6, IL8, and TNFα). LPS concentration was not associated with in-hospital or 1-year outcomes.

Conclusions

In patients admitted for MI, higher levels of endotoxins were related to pre-existing conditions rather than acute clinical severity. Therefore, endotoxins measured on the day of MI could reflect metabolic chronic endotoxemia rather than MI-related acute gut translocation.
Asking questions that are “close to the bone”: integrating thematic analysis and natural language processing to explore the experiences of people with traumatic brain injuries engaging with patient-reported outcome measures
Authors: Di Basilio Daniela , King Lorraine , Lloyd Sarah , Michael Panayiotis , Shardlow Matthew
Published: June 2024

Introduction

Patient-reported outcomes measures (PROMs) are valuable tools for assessing health-related quality of life and treatment effectiveness in individuals with traumatic brain injuries (TBIs). Understanding the experiences of individuals with TBIs in completing PROMs is crucial for improving their utility and relevance in clinical practice.

Methods

Sixteen semi-structured interviews were conducted with a sample of individuals with TBIs. The interviews were transcribed verbatim and analysed using Thematic Analysis (TA) and Natural Language Processing (NLP) techniques to identify themes and emotional connotations related to the experiences of completing PROMs.

Results

The TA of the data revealed six key themes regarding the experiences of individuals with TBIs in completing PROMs. Participants expressed varying levels of understanding and engagement with PROMs, with factors such as cognitive impairments and communication difficulties influencing their experiences. Additionally, insightful suggestions emerged on the barriers to the completion of PROMs, the factors facilitating it, and the suggestions for improving their contents and delivery methods. The sentiment analyses performed using NLP techniques allowed for the retrieval of the general sentimental and emotional “tones” in the participants’ narratives of their experiences with PROMs, which were mainly characterised by low positive sentiment connotations. Although mostly neutral, participants’ narratives also revealed the presence of emotions such as fear and, to a lesser extent, anger. The combination of a semantic and sentiment analysis of the experiences of people with TBIs rendered valuable information on the views and emotional responses to different aspects of the PROMs.

Discussion

The findings highlighted the complexities involved in administering PROMs to individuals with TBIs and underscored the need for tailored approaches to accommodate their unique challenges. Integrating TA-based and NLP techniques can offer valuable insights into the experiences of individuals with TBIs and enhance the interpretation of qualitative data in this population.
Mouse vascularized adipose spheroids: an organotypic model for thermogenic adipocytes
Authors: Davidsen Laura Ingeborg , Hagberg Carolina E. , Goitea Victor , Lundby Stine Meinild , Larsen Steen , Ebbesen Morten Frendø , Stanic Natasha , Topel Hande , Kornfeld Jan-Wilhelm
Published: June 2024

Adipose tissues, particularly beige and brown adipose tissue, play crucial roles in energy metabolism. Brown adipose tissues’ thermogenic capacity and the appearance of beige cells within white adipose tissue have spurred interest in their metabolic impact and therapeutic potential. Brown and beige fat cells, activated by environmental factors like cold exposure or by pharmacology, share metabolic mechanisms that drive non-shivering thermogenesis. Understanding these two cell types requires advanced, yet broadly applicable in vitro models that reflect the complex microenvironment and vasculature of adipose tissues. Here we present mouse vascularized adipose spheroids of the stromal vascular microenvironment from inguinal white adipose tissue, a tissue with ‘beiging’ capacity in mice and humans. We show that adding a scaffold improves vascular sprouting, enhances spheroid growth, and upregulates adipogenic markers, thus reflecting increased adipocyte maturity. Transcriptional profiling via RNA sequencing revealed distinct metabolic pathways upregulated in our vascularized adipose spheroids, with increased expression of genes involved in glucose metabolism, lipid metabolism, and thermogenesis. Functional assessment demonstrated increased oxygen consumption in vascularized adipose spheroids compared to classical 2D cultures, which was enhanced by β-adrenergic receptor stimulation correlating with elevated β-adrenergic receptor expression. Moreover, stimulation with the naturally occurring adipokine, FGF21, induced Ucp1 mRNA expression in the vascularized adipose spheroids. In conclusion, vascularized inguinal white adipose tissue spheroids provide a physiologically relevant platform to study how the stromal vascular microenvironment shapes adipocyte responses and influence activated thermogenesis in beige adipocytes.
Quantum model prediction for frequency regulation of novel power systems which includes a high proportion of energy storage
Authors: Luo Wenbo , Xu Yufan , Du Wanlin , Wang Shilong , Fan Ziwei
Published: June 2024

As the proportion of renewable energy generation continues to increase, the participation of new energy stations with high-proportion energy storage in power system frequency regulation is of significant importance for stable and secure operation of the new power system. To address this issue, an energy storage control method based on quantum walks and model predictive control (MPC) has been proposed. First, historical frequency deviation signals and energy storage charge–discharge state signals are collected. Simulation data are generated through amplitude encoding and quantum walks, followed by quantum decoding. Subsequently, the decoded data are inputted into the MPC framework for real-time control, with parameters of the predictive model continuously adjusted through a feedback loop. Finally, a novel power system frequency regulation model with high-proportion new energy storage stations is constructed on the MATLAB/Simulink platform. Simulation verification is conducted with the proportional–integral–derivative (PID) and MPC methods as comparative approaches. Simulation results under step disturbances and random disturbances demonstrate that the proposed method exhibits stronger robustness and better control accuracy.
Tuning tRNAs for improved translation
Authors: Weiss Joshua L. , Decker J. C. , Bolano Ariadna , Krahn Natalie
Published: June 2024

Transfer RNAs have been extensively explored as the molecules that translate the genetic code into proteins. At this interface of genetics and biochemistry, tRNAs direct the efficiency of every major step of translation by interacting with a multitude of binding partners. However, due to the variability of tRNA sequences and the abundance of diverse post-transcriptional modifications, a guidebook linking tRNA sequences to specific translational outcomes has yet to be elucidated. Here, we review substantial efforts that have collectively uncovered tRNA engineering principles that can be used as a guide for the tuning of translation fidelity. These principles have allowed for the development of basic research, expansion of the genetic code with non-canonical amino acids, and tRNA therapeutics.
The value of generalized linear mixed models for data analysis in the plant sciences
Authors: Madden Laurence V. , Ojiambo Peter S.
Published: June 2024

Modern data analysis typically involves the fitting of a statistical model to data, which includes estimating the model parameters and their precision (standard errors) and testing hypotheses based on the parameter estimates. Linear mixed models (LMMs) fitted through likelihood methods have been the foundation for data analysis for well over a quarter of a century. These models allow the researcher to simultaneously consider fixed (e.g., treatment) and random (e.g., block and location) effects on the response variables and account for the correlation of observations, when it is assumed that the response variable has a normal distribution. Analysis of variance (ANOVA), which was developed about a century ago, can be considered a special case of the use of an LMM. A wide diversity of experimental and treatment designs, as well as correlations of the response variable, can be handled using these types of models. Many response variables are not normally distributed, of course, such as discrete variables that may or may not be expressed as a percentage (e.g., counts of insects or diseased plants) and continuous variables with asymmetrical distributions (e.g., survival time). As expansions of LMMs, generalized linear mixed models (GLMMs) can be used to analyze the data arising from several non-normal statistical distributions, including the discrete binomial, Poisson, and negative binomial, as well as the continuous gamma and beta. A GLMM allows the data analyst to better match the model to the data rather than to force the data to match a specific model. The increase in computer memory and processing speed, together with the development of user-friendly software and the progress in statistical theory and methodology, has made it practical for non-statisticians to use GLMMs since the late 2000s. The switch from LMMs to GLMMs is deceptive, however, as there are several major issues that must be thought about or judged when using a GLMM, which are mostly resolved for routine analyses with LMMs. These include the consideration of conditional versus marginal distributions and means, overdispersion (for discrete data), the model-fitting method [e.g., maximum likelihood (integral approximation), restricted pseudo-likelihood, and quasi-likelihood], and the choice of link function to relate the mean to the fixed and random effects. The issues are explained conceptually with different model formulations and subsequently with an example involving the percentage of diseased plants in a field study with wheat, as well as with simulated data, starting with a LMM and transitioning to a GLMM. A brief synopsis of the published GLMM-based analyses in the plant agricultural literature is presented to give readers a sense of the range of applications of this approach to data analysis.
Trematode Diplostomum pseudospathaceum inducing differential immune gene expression in sexual and gynogenetic gibel carp (Carassius gibelio): parasites facilitating the coexistence of two reproductive forms of the invasive species
Authors: Fuad Md Mehedi Hasan , Tichopád Tomáš , Ondračková Markéta , Civáňová Křížová Kristína , Seifertová Mária , Voříšková Kristýna , Demko Martin , Vetešník Lukáš , Šimková Andrea
Published: June 2024

Introduction

Parasite-mediated selection is considered one of the potential mechanisms contributing to the coexistence of asexual-sexual complexes. Gibel carp (Carassius gibelio), an invasive fish species in Europe, often forms populations composed of gynogenetic and sexual specimens.

Methods

The experimental infection was induced in gynogenetic and sexual gibel carp using eye-fluke Diplostomum pseudospathaceum (Trematoda), and the transcriptome profile of the spleen as a major immune organ in fish was analyzed to reveal the differentially expressed immunity-associated genes related to D. pseudospathaceum infection differing between gynogenetic and sexual gibel carp.

Results

High parasite infection was found in gynogenetic fish when compared to genetically diverse sexuals. Although metacercariae of D. pseudospathaceum are situated in an immune-privileged organ, our results show that eye trematodes may induce a host immune response. We found differential gene expression induced by eye-fluke infection, with various impacts on gynogenetic and sexual hosts, documenting for the majority of DEGs upregulation in sexuals, and downregulation in asexuals. Differences in gene regulation between gynogenetic and sexual gibel carp were evidenced in many immunity-associated genes. GO analyses revealed the importance of genes assigned to the GO terms: immune function, the Notch signaling pathway, MAP kinase tyrosine/threonine/phosphatase activity, and chemokine receptor activity. KEGG analyses revealed the importance of the genes involved in 12 immunity-associated pathways – specifically, FoxO signaling, adipocytokine signaling, TGF-beta signaling, apoptosis, Notch signaling, C-type lectin receptor signaling, efferocytosis, intestinal immune network for IgA production, insulin signaling, virion - human immunodeficiency virus, Toll-like receptor signaling, and phosphatidylinositol signaling system.

Discussion

Our study indicates the limited potential of asexual fish to cope with higher parasite infection (likely a loss of capacity to induce an effective immune response) and highlights the important role of molecular mechanisms associated with immunity for the coexistence of gynogenetic and sexual gibel carp, potentially contributing to its invasiveness.
Immunoregulatory role of platelet derivatives in the macrophage-mediated immune response
Authors: Anitua Eduardo , Troya María , Alkhraisat Mohammad H.
Published: June 2024

Background

Macrophages are innate immune cells that display remarkable phenotypic heterogeneity and functional plasticity. Due to their involvement in the pathogenesis of several human conditions, macrophages are considered to be an attractive therapeutic target. In line with this, platelet derivatives have been successfully applied in many medical fields and as active participants in innate immunity, cooperation between platelets and macrophages is essential. In this context, the aim of this review is to compile the current evidence regarding the effects of platelet derivatives on the phenotype and functions of macrophages to identify the advantages and shortcomings for feasible future clinical applications.

Methods

A total of 669 articles were identified during the systematic literature search performed in PubMed and Web of Science databases.

Results

A total of 27 articles met the inclusion criteria. Based on published findings, platelet derivatives may play an important role in inducing a dynamic M1/M2 balance and promoting a timely M1-M2 shift. However, the differences in procedures regarding platelet derivatives and macrophages polarization and the occasional lack of information, makes reproducibility and comparison of results extremely challenging. Furthermore, understanding the differences between human macrophages and those derived from animal models, and taking into account the peculiarities of tissue resident macrophages and their ontogeny seem essential for the design of new therapeutic strategies.

Conclusion

Research on the combination of macrophages and platelet derivatives provides relevant information on the function and mechanisms of the immune response.
Paving the way in implementation of SCID newborn screening in developing nations: feasibility study and strategies to move forward in Malaysia
Authors: Kumarasamy Gaayathri , Khairiz Khayrin , Chang Wai Leng , Aye Thin Thin , Ali Adli
Published: June 2024

Early diagnosis and effective management of Primary immunodeficiency diseases (PIDs), particularly severe combined immunodeficiency (SCID), play a crucial role in minimizing associated morbidities and mortality. Newborn screening (NBS) serves as a valuable tool in facilitating these efforts. Timely detection and diagnosis are essential for swiftly implementing isolation measures and ensuring prompt referral for definitive treatment, such as allogeneic hematopoietic stem cell transplantation. The utilization of comprehensive protocols and screening assays, including T cell receptor excision circles (TREC) and kappa-deleting recombination excision circles (KREC), is essential in facilitating early diagnosis of SCID and other PIDs, but their successful application requires clinical expertise and proper implementation strategy. Unfortunately, a notable challenge arises from insufficient funding for the treatment of PIDs. To address these issues, a collaborative approach is imperative, involving advancements in technology, a well-functioning healthcare system, and active engagement from stakeholders. The integration of these elements is essential for overcoming the existing challenges in NBS for PIDs. By fostering synergy between technology providers, healthcare professionals, and governmental stakeholders, we can enhance the efficiency and effectiveness of early diagnosis and intervention, ultimately improving outcomes for individuals with PIDs.
PA-MSHA improves prognosis of patients undergoing radical cystectomy: a retrospective cohort study using inverse probability of treatment weighting
Authors: Zhang Xiaohua , Pei Zixu , Ren Jinglei , Shi Jing , Lu Wenjun , Shui Yuan , Ma Wentao , Zhang Luyang , Ding Hui , Zhang Yunxin , Tian Junqiang , Wang Zhiping
Published: June 2024

Objective

To observe the effect of Pseudomonas aeruginosa mannose-sensitive hemagglutinin (PA-MSHA) on the prognosis and the incidence of lymphatic leakage in patients undergoing radical cystectomy (RC).

Method

A total of 129 patients who underwent RC in Lanzhou University Second Hospital from 2013 to 2022 were enrolled in this study. They were divided into 43 patients treated with PA-MSHA and 86 patients in the control group. Inverse probability of treatment weighting (IPTW) was applied to reduce potential selection bias. Kaplan-Meier method and Cox regression analysis were used to analyze the effect of PA-MSHA on the survival of patients and the incidence of postoperative lymphatic leakage.

Results

The PA-MSHA group exhibited improved overall survival (OS) and cancer-specific survival (CSS) rates compared to the control group. The 3-year and 5-year overall survival (OS) rates for the PA-MSHA group were 69.1% and 53.2%, respectively, compared to 55.6% and 45.3% for the control group (Log-rank=3.218, P=0.072). The 3-year and 5-year cancer-specific survival (CSS) rates for the PA-MSHA group were 73.3% and 56.5%, respectively, compared to 58.0% and 47.3% for the control group (Log-rank=3.218, P=0.072). Additionally, the 3-year and 5-year progression-free survival (PFS) rates for the PA-MSHA group were 74.4% and 56.8%, respectively, compared to 57.1% and 52.2% for the control group (Log-rank=2.016, P=0.156). Multivariate Cox regression analysis indicates that lymph node metastasis and distant metastasis are poor prognostic factors for patients, while the use of PA-MSHA can improve patients’ OS (HR: 0.547, 95%CI: 0.304–0.983, P=0.044), PFS (HR: 0.469, 95%CI: 0.229–0.959, P=0.038) and CSS (HR: 0.484, 95%CI: 0.257–0.908, P=0.024). The same trend was observed in the cohort After IPTW adjustment. Although there was no significant difference in the incidence of postoperative lymphatic leakage [18.6% (8/35) vs. 15.1% (84.9%), P=0.613] and pelvic drainage volume [470 (440) ml vs. 462.5 (430) ml, P=0.814] between PA-MSHA group and control group, PA-MSHA could shorten the median retention time of drainage tube (7.0 d vs 9.0 d) (P=0.021).

Conclusion

PA-MSHA may improve radical cystectomy in patients with OS, PFS, and CSS, shorten the pelvic drainage tube retention time.
Long-term cardiovascular inflammation and fibrosis in a murine model of vasculitis induced by Lactobacillus casei cell wall extract
Authors: Lombardi Pereira Ana Paula , Aubuchon Emily , Moreira Debbie P. , Lane Malcolm , Carvalho Thacyana T. , Mesquita Thassio R. R. , Lee Youngho , Crother Timothy R. , Porritt Rebecca A. , Verri Waldiceu A. , Noval Rivas Magali , Arditi Moshe
Published: June 2024

Background

Kawasaki disease (KD), an acute febrile illness and systemic vasculitis, is the leading cause of acquired heart disease in children in industrialized countries. KD leads to the development of coronary artery aneurysms (CAA) in affected children, which may persist for months and even years after the acute phase of the disease. There is an unmet need to characterize the immune and pathological mechanisms of the long-term complications of KD.

Methods

We examined cardiovascular complications in the Lactobacillus casei cell wall extract (LCWE) mouse model of KD-like vasculitis over 4 months. The long-term immune, pathological, and functional changes occurring in cardiovascular lesions were characterized by histological examination, flow cytometric analysis, immunofluorescent staining of cardiovascular tissues, and transthoracic echocardiogram.

Results

CAA and abdominal aorta dilations were detected up to 16 weeks following LCWE injection and initiation of acute vasculitis. We observed alterations in the composition of circulating immune cell profiles, such as increased monocyte frequencies in the acute phase of the disease and higher counts of neutrophils. We determined a positive correlation between circulating neutrophil and inflammatory monocyte counts and the severity of cardiovascular lesions early after LCWE injection. LCWE-induced KD-like vasculitis was associated with myocarditis and myocardial dysfunction, characterized by diminished ejection fraction and left ventricular remodeling, which worsened over time. We observed extensive fibrosis within the inflamed cardiac tissue early in the disease and myocardial fibrosis in later stages.

Conclusion

Our findings indicate that increased circulating neutrophil counts in the acute phase are a reliable predictor of cardiovascular inflammation severity in LCWE-injected mice. Furthermore, long-term cardiac complications stemming from inflammatory cell infiltrations in the aortic root and coronary arteries, myocardial dysfunction, and myocardial fibrosis persist over long periods and are still detected up to 16 weeks after LCWE injection.
The role of exosomal molecular cargo in exosome biogenesis and disease diagnosis
Authors: Liu Meijin , Wen Zhenzhen , Zhang Tingting , Zhang Linghan , Liu Xiaoyan , Wang Maoyuan
Published: June 2024

Exosomes represent a type of extracellular vesicles derived from the endosomal pathway that transport diverse molecular cargoes such as proteins, lipids, and nucleic acids. These cargoes have emerged as crucial elements impacting disease diagnosis, treatment, and prognosis, and are integral to the process of exosome formation. This review delves into the essential molecular cargoes implicated in the phases of exosome production and release. Emphasis is placed on their significance as cancer biomarkers and potential therapeutic targets, accompanied by an exploration of the obstacles and feasible applications linked to these developments.
FAM20A: a potential diagnostic biomarker for lung squamous cell carcinoma
Authors: Zhang Yalin , Sun Qin , Liang Yangbo , Yang Xian , Wang Hailian , Song Siyuan , Wang Yi , Feng Yong
Published: June 2024

Background

Lung squamous cell carcinoma (LUSC) ranks among the carcinomas with the highest incidence and dismal survival rates, suffering from a lack of effective therapeutic strategies. Consequently, biomarkers facilitating early diagnosis of LUSC could significantly enhance patient survival. This study aims to identify novel biomarkers for LUSC.

Methods

Utilizing the TCGA, GTEx, and CGGA databases, we focused on the gene encoding Family with Sequence Similarity 20, Member A (FAM20A) across various cancers. We then corroborated these bioinformatic predictions with clinical samples. A range of analytical tools, including Kaplan-Meier, MethSurv database, Wilcoxon rank-sum, Kruskal-Wallis tests, Gene Set Enrichment Analysis, and TIMER database, were employed to assess the diagnostic and prognostic value of FAM20A in LUSC. These tools also helped evaluate immune cell infiltration, immune checkpoint genes, DNA repair-related genes, DNA methylation, and tumor-related pathways.

Results

FAM20A expression was found to be significantly reduced in LUSC, correlating with lower survival rates. It exhibited a negative correlation with key proteins in DNA repair signaling pathways, potentially contributing to LUSC’s radiotherapy resistance. Additionally, FAM20A showed a positive correlation with immune checkpoints like CTLA-4, indicating potential heightened sensitivity to immunotherapies targeting these checkpoints.

Conclusion

FAM20A emerges as a promising diagnostic and prognostic biomarker for LUSC, offering potential clinical applications.
Gut microbiome signatures associated with type 2 diabetes in obesity in Mongolia
Authors: Shinoda Akari , Lkhagvajav Tsogtbaatar , Mishima Riko , Therdtatha Phatthanaphong , Jamiyan Dugersuren , Purevdorj Chantsaldulam , Sonomtseren Sainbileg , Chimeddorj Battogtokh , Namdag Bira , Lee Yuan Kun , Demberel Shirchin , Nakayama Jiro
Published: June 2024

Mongolian people possess a unique dietary habit characterized by high consumption of meat and dairy products and fewer vegetables, resulting in the highest obesity rate in East Asia. Although obesity is a known cause of type 2 diabetes (T2D), the T2D rate is moderate in this population; this is known as the “Mongolian paradox.” Since the gut microbiota plays a key role in energy and metabolic homeostasis as an interface between food and body, we investigated gut microbial factors involved in the prevention of the co-occurrence of T2D with obesity in Mongolians. We compared the gut microbiome and metabolome of Mongolian adults with obesity with T2D (DO: n = 31) or without T2D (NDO: n = 35). Dysbiotic signatures were found in the gut microbiome of the DO group; lower levels of Faecalibacterium and Anaerostipes which are known as short-chain fatty acid (SCFA) producers and higher levels of Methanobrevibacter, Desulfovibrio, and Solobacterium which are known to be associated with certain diseases. On the other hand, the NDO group exhibited a higher level of fecal SCFA concentration, particularly acetate. This is consistent with the results of the whole shotgun metagenomic analysis, which revealed a higher relative abundance of SCFA biosynthesis-related genes encoded largely by Anaerostipes hadrus in the NDO group. Multiple logistic regression analysis including host demographic parameters indicated that acetate had the highest negative contribution to the onset of T2D. These findings suggest that SCFAs produced by the gut microbial community participate in preventing the development of T2D in obesity in Mongolians.
Comprehensive in vitro and in vivo evaluation of therapeutic potential of Bacopa-derived asiatic acid against a human oral pathogen Streptococcus mutans
Authors: Jeyasri Rajendran , Muthuramalingam Pandiyan , Priya Arumugam , Alexpandi Rajaiah , Shanmugam N. R. Siva , Nivetha Saminathan , Shin Hyunsuk , Pandian Shunmugiah Karutha , Ravi Arumugam Veera , Ramesh Manikandan
Published: June 2024

Dental caries is a common human oral disease worldwide, caused by an acid-producing bacteria Streptococcus mutans. The use of synthetic drugs and antibiotics to prevent dental caries has been increasing, but this can lead to severe side effects. To solve this issue, developing and developed countries have resorted to herbal medicines as an alternative to synthetic drugs for the treatment and prevention of dental caries. Therefore, there is an urgent need for plant-derived products to treat such diseases. Bacopa monnieri, a well-documented medicinal plant, contains 52 phytocompounds, including the pentacyclic triterpenoid metabolite known as asiatic acid (ASTA). Hence, this study aimed to demonstrate, for the first time, the antibacterial activity of phytocompound ASTA against S. mutans. The findings revealed that ASTA significantly inhibited the growth of S. mutans and the production of virulence factors such as acidurity, acidogenicity, and eDNA synthesis. Molecular docking analysis evaluated the potential activity of ASTA against S. mutans virulence genes, including VicR and GtfC. Furthermore, toxicity assessment of ASTA in human buccal epithelial cells was performed, and no morphological changes were observed. An in vivo analysis using Danio rerio (zebrafish) confirmed that the ASTA treatment significantly increased the survival rates of infected fish by hindering the intestinal colonization of S. mutans. Furthermore, the disease protection potential of ASTA against the pathognomonic symptom of S. mutans infection was proven by the histopathological examination of the gills, gut, and kidney. Overall, these findings suggest that ASTA may be a promising therapeutic and alternative drug for the treatment and prevention of oral infection imposed by S. mutans.
Binding activity and specificity of tail fiber protein 35Q for Salmonella pullorum
Authors: Deng Hewen , Feng Linwan , Shi Kun , Du Rui
Published: June 2024

Salmonella, a prevalent pathogen with significant implications for the poultry industry and food safety, presents a global public health concern. The rise in antibiotic resistance has exacerbated the challenge of prevention. Accurate and sensitive detection methods are essential in combating Salmonella infections. Bacteriophages, viruses capable of targeting and destroying bacteria, leverage their host specificity for accurate microbial detection. Notably, the tail fiber protein of bacteriophages plays a crucial role in recognizing specific hosts, making it a valuable tool for targeted microbial detection. This study focused on the tail fiber protein 35Q of Salmonella pullorum (SP) bacteriophage YSP2, identified through protein sequencing and genome analysis. Bioinformatics analysis revealed similarities between 35Q and other Salmonella bacteriophage tail fiber proteins. The protein was successfully expressed and purified using an Escherichia coli expression system, and its binding activity and specificity were confirmed. ELISA assays and adsorption experiments demonstrated that 35Q interacts with the outer membrane protein (OMP) receptor on bacterial surfaces. This investigation provides valuable insights for targeted Salmonella detection, informs the development of specific therapeutics, and enhances our understanding of the interaction between Salmonella bacteriophages and their hosts.
Chlorhexidine digluconate mouthwash alters the oral microbial composition and affects the prevalence of antimicrobial resistance genes
Authors: Bartsch Sibylle , Kohnert Eva , Kreutz Clemens , Woelber Johan P. , Anderson Annette , Burkhardt Ann-Sophie , Hellwig Elmar , Buchalla Wolfgang , Hiller Karl-Anton , Ratka-Krueger Petra , Cieplik Fabian , Al-Ahmad Ali
Published: June 2024

Introduction

Chlorhexidine (CHX) is a commonly used antiseptic in situations of limited oral hygiene ability such as after periodontal surgery. However, CHX is also considered as a possible factor in the emergence of cross-resistance to antibiotics. The aim of this study was to analyze the changes in the oral microbiota and the prevalence of antimicrobial resistance genes (ARGs) due to CHX treatment.

Materials and methods

We analyzed the oral metagenome of 20 patients who applied a 0.2% CHX mouthwash twice daily for 4 weeks following periodontal surgical procedures. Saliva and supragingival plaque samples were examined before, directly after 4 weeks, and another 4 weeks after discontinuing the CHX treatment.

Results

Alpha-diversity decreased significantly with CHX use. The Bray–Curtis dissimilarity increased in both sample sites and mainly streptococci showed a higher relative abundance after CHX treatment. Although no significant changes of ARGs could be detected, an increase in prevalence was found for genes that encode for tetracycline efflux pumps.

Conclusion

CHX treatment appears to promote a caries-associated bacterial community and the emergence of tetracycline resistance genes. Future research should focus on CHX-related changes in the microbial community and whether the discovered tetracycline resistance genes promote resistance to CHX.
Dickeya fangzhongdai was prevalent and caused taro soft rot when coexisting with the Pectobacterium complex, with a preference for Araceae plants
Authors: Zhang Jingxin , Sun Dayuan , Shen Huifang , Pu Xiaoming , Liu Pingping , Lin Birun , Yang Qiyun
Published: June 2024

Bacterial soft rot caused by coinfection with Dickeya spp. and Pectobacterium spp. in hosts can cause successive changes in fields, and it is difficult to prevent the spread of and control the infection. Pectobacterium spp. are prevalent in the growing areas of tuberous crops, including taro and potato. Recently, Dickeya fangzhongdai has emerged as a virulent pathogen in taro. To determine the prevalence status of the causal agents and evaluate the potential spreading risks of D. fangzhongdai, screening and taxonomic classification were performed on phytopathogenic bacteria collected from different taro-growing areas in Guangdong Province, China, and biological and genomic characteristics were further compared among typical strains from all defined species. The causative agents were verified to be phytobacterial strains of D. fangzhongdai, Pectobacterium aroidearum and Pectobacterium colocasium. P. aroidearum and P. colocasium were found to form a complex preferring Araceae plants and show intensive genomic differentiation, indicating their ancestor had adapted to taro a long time prior. Compared with Pectobacterium spp., D. fangzhongdai was more virulent to taro corms under conditions of exogenous infection and more adaptable at elevated temperatures. D. fangzhongdai strains isolated from taro possessed genomic components of additional T4SSs, which were accompanied by additional copies of the hcp-vgrG genes of the T6SS, and these contributed to the expansion of their genomes. More gene clusters encoding secondary metabolites were found within the D. fangzhongdai strains than within the Pectobacterium complex; interestingly, distinct gene clusters encoding zeamine and arylpolyene were both most similar to those in D. solani that caused potato soft rot. These comparisons provided genomic evidences for that the newly emerging pathogen was potentially equipped to compete with other pathogens. Diagnostic qPCR verified that D. fangzhongdai was prevalent in most of the taro-growing areas and coexisted with the Pectobacterium complex, while the plants enriching D. fangzhongdai were frequently symptomatic at developing corms and adjacent pseudostems and caused severe symptoms. Thus, the emerging need for intensive monitoring on D. fangzhongdai to prevent it from spreading to other taro-growing areas and to other tuberous crops like potato; the adjustment of control strategies based on different pathopoiesis characteristics is recommended.
Machine learning model comparison for freezing of gait prediction in advanced Parkinson’s disease
Authors: Watts Jeremy , Niethammer Martin , Khojandi Anahita , Ramdhani Ritesh
Published: June 2024

Introduction

Freezing of gait (FOG) is a paroxysmal motor phenomenon that increases in prevalence as Parkinson’s disease (PD) progresses. It is associated with a reduced quality of life and an increased risk of falls in this population. Precision-based detection and classification of freezers are critical to developing tailored treatments rooted in kinematic assessments.

Methods

This study analyzed instrumented stand-and-walk (SAW) trials from advanced PD patients with STN-DBS. Each patient performed two SAW trials in their OFF Medication—OFF DBS state. For each trial, gait summary statistics from wearable sensors were analyzed by machine learning classification algorithms. These algorithms include k-nearest neighbors, logistic regression, naïve Bayes, random forest, and support vector machines (SVM). Each of these models were selected for their high interpretability. Each algorithm was tasked with classifying patients whose SAW trials MDS-UPDRS FOG subscore was non-zero as assessed by a trained movement disorder specialist. These algorithms’ performance was evaluated using stratified five-fold cross-validation.

Results

A total of 21 PD subjects were evaluated (average age 64.24 years, 16 males, mean disease duration of 14 years). Fourteen subjects had freezing of gait in the OFF MED/OFF DBS. All machine learning models achieved statistically similar predictive performance (p < 0.05) with high accuracy. Analysis of random forests’ feature estimation revealed the top-ten spatiotemporal predictive features utilized in the model: foot strike angle, coronal range of motion [trunk and lumbar], stride length, gait speed, lateral step variability, and toe-off angle.

Conclusion

These results indicate that machine learning effectively classifies advanced PD patients as freezers or nonfreezers based on SAW trials in their non-medicated/non-stimulated condition. The machine learning models, specifically random forests, not only rely on but utilize salient spatial and temporal gait features for FOG classification.
Depressive symptoms in children and adolescents with epilepsy and primary headache: a cross-sectional observational study
Authors: Pastorino Grazia Maria Giovanna , Olivieri Miriam , Viggiano Andrea , Meccariello Rosaria , Roccella Michele , Parisi Lucia , Cerulli Irelli Emanuele , Di Bonaventura Carlo , Orsini Alessandro , Operto Francesca F.
Published: June 2024

Background

The primary aims of our cross-sectional observational study were: (i) to determine the prevalence of depressive symptoms in children and adolescents with epilepsy compared to controls and (ii) to explore the difference in depressive symptoms in patients with epilepsy only and those with epilepsy and primary headache as a comorbidity. The secondary objective was to explore parental stress levels.

Methods

68 pediatric patients aged 6–18 years (44 with epilepsy only and 24 with epilepsy and headache) and 50 controls were recruited. Depressive profile and parental stress were assessed using Children's Depression Inventory, Second Edition (CDI-2) and Parenting Stress Index-Short Form (PSI-SF).

Results

The group with epilepsy showed significantly high depressive symptoms and parental stress compared to controls. The patients with headache in comorbidity experienced more depressive symptoms than those with epilepsy only.

Conclusion

Depressive symptoms are more prevalent in patients who have comorbid epilepsy and primary headache; therefore, the neurological/psychological mechanisms underlying this condition should be further investigated. The simultaneous presence of epilepsy, headache and depressive symptoms impacts the quality of life of patients and their parents, increasing parental stress and family management.
Effects of buccal acupuncture on postoperative analgesia in elderly patients undergoing laparoscopic radical gastrectomy: a randomized controlled trial
Authors: Zhu Dong-xue , Yang Yan-ling , Yang Lei , Zhao Yuan-yuan , Xie Ya-yun , Wang Wei , Lv Jie , Yu Wan-you
Published: June 2024

Objective

This study aimed to evaluate the efficacy and safety of buccal acupuncture on postoperative analgesia, perioperative stress response and adverse events in elderly patients undergoing laparoscopic radical gastrectomy.

Methods

It was a prospective, outcome assessor-blinded, randomized controlled trial, involving 90 patients aged 65–80 years who were treated with an elective laparoscopic radical gastrectomy. They were randomly assigned to buccal acupuncture group (Group B) and control group (Group C). Buccal acupuncture was applied to patients of Group B before the induction of general anesthesia, while no additional application was given to those in Group C. Patient-controlled intravenous analgesia (PCIA) with sufentanil was postoperatively performed in both groups. Sufentanil consumption and the Visual Analog Scale (VAS) score within 48 h postoperatively were assessed as primary outcomes. Secondary outcomes included peripheral levels of stress markers, intraoperative consumptions of anesthetic drugs and postoperative recovery.

Results

Patients in Group B presented significantly lower VAS scores within 24 h and less consumption of sufentanil within 48 h postoperatively (both p < 0.01). The awaking time, time to extubation and length of stay were significantly shorter in Group B than in Group C (p = 0.005, 0.001 and 0.028, respectively). Compared with Group C, stress response and inflammatory response within 24 h postoperatively were also significantly milder in Group B.

Conclusion

The use of buccal acupuncture before general anesthesia induction favors the postoperative analgesic effect and recovery in elderly patients undergoing laparoscopic radical gastrectomy, the mechanism of which involves relieving postoperative stress response and inflammatory response.

Clinical trial registration

This study was registered in the Chinese Clinical Trial Registry (www.chictr.org.cn) on 15/06/2023 (ChiCTR2300072500).