bluuebunny/crossref_metadata_2025 huggingface dataset:
An agent-based model of cardiac allograft vasculopathy: toward a better understanding of chronic rejection dynamics
Authors: Serafini Elisa , Corti Anna , Gallo Diego , Chiastra Claudio , Li Xian C. , Casarin Stefano
Published: September 2023

Cardiac allograft vasculopathy (CAV) is a coronary artery disease affecting 50% of heart transplant (HTx) recipients, and it is the major cause of graft loss. CAV is driven by the interplay of immunological and non-immunological factors, setting off a cascade of events promoting endothelial damage and vascular dysfunction. The etiology and evolution of tissue pathology are largely unknown, making disease management challenging. So far, in vivo models, mostly mouse-based, have been widely used to study CAV, but they are resource-consuming, pose many ethical issues, and allow limited investigation of time points and important biomechanical measurements. Recently, agent-based models (ABMs) proved to be valid computational tools for deciphering mechanobiological mechanisms driving vascular adaptation processes at the cell/tissue level, augmenting cost-effective in vivo lab-based experiments, at the same time guaranteeing richness in observation time points and low consumption of resources. We hypothesize that integrating ABMs with lab-based experiments can aid in vivo research by overcoming those limitations. Accordingly, this work proposes a bidimensional ABM of CAV in a mouse coronary artery cross-section, simulating the arterial wall response to two distinct stimuli: inflammation and hemodynamic disturbances, the latter considered in terms of low wall shear stress (WSS). These stimuli trigger i) inflammatory cell activation and ii) exacerbated vascular cell activities. Moreover, an extensive analysis was performed to investigate the ABM sensitivity to the driving parameters and inputs and gain insights into the ABM working mechanisms. The ABM was able to effectively replicate a 4-week CAV initiation and progression, characterized by lumen area decrease due to progressive intimal thickening in regions exposed to high inflammation and low WSS. Moreover, the parameter and input sensitivity analysis highlighted that the inflammatory-related events rather than the WSS predominantly drive CAV, corroborating the inflammatory nature of the vasculopathy. The proof-of-concept model proposed herein demonstrated its potential in deepening the pathology knowledge and supporting the in vivo analysis of CAV.
Plant and mammalian-derived extracellular vesicles: a new therapeutic approach for the future
Authors: Sall Ibrahima Mamadou , Flaviu Tabaran Alexandru
Published: September 2023

Background: In recent years, extracellular vesicles have been recognized as important mediators of intercellular communication through the transfer of active biomolecules (proteins, lipids, and nucleic acids) across the plant and animal kingdoms and have considerable roles in several physiological and pathological mechanisms, showing great promise as new therapeutic strategies for a variety of pathologies.

Methods: In this study, we carefully reviewed the numerous articles published over the last few decades on the general knowledge of extracellular vesicles, their application in the therapy of various pathologies, and their prospects as an approach for the future.

Results: The recent discovery and characterization of extracellular vesicles (EVs) of diverse origins and biogenesis have altered the current paradigm of intercellular communication, opening up new diagnostic and therapeutic perspectives. Research into these EVs released by plant and mammalian cells has revealed their involvement in a number of physiological and pathological mechanisms, such as embryonic development, immune response, tissue regeneration, and cancer. They are also being studied as potential biomarkers for disease diagnosis and vectors for drug delivery.

Conclusion: Nanovesicles represent powerful tools for intercellular communication and the transfer of bioactive molecules. Their molecular composition and functions can vary according to their origin (plant and mammalian), so their formation, composition, and biological roles open the way to therapeutic applications in a variety of pathologies, which is arousing growing interest in the scientific community.

Clinical Trial Registration:ClinicalTrials.gov identifier: NCT03608631
Current perspectives and trends in nanoparticle drug delivery systems in breast cancer: bibliometric analysis and review
Authors: Sun Sheng , Wang Ye-hui , Gao Xiang , Wang He-yong , Zhang Lu , Wang Na , Li Chun-mei , Xiong Shao-quan
Published: September 2023

The treatment of breast cancer (BC) is a serious challenge due to its heterogeneous nature, multidrug resistance (MDR), and limited therapeutic options. Nanoparticle-based drug delivery systems (NDDSs) represent a promising tool for overcoming toxicity and chemotherapy drug resistance in BC treatment. No bibliometric studies have yet been published on the research landscape of NDDS-based treatment of BC. In this review, we extracted data from 1,752 articles on NDDS-based treatment of BC published between 2012 and 2022 from the Web of Science Core Collection (WOSCC) database. VOSviewer, CiteSpace, and some online platforms were used for bibliometric analysis and visualization. Publication trends were initially observed: in terms of geographical distribution, China and the United States had the most papers on this subject. The highest contributing institution was Sichuan University. In terms of authorship and co-cited authorship, the most prolific author was Yu Zhang. Furthermore, Qiang Zhang and co-workers have made tremendous achievements in the field of NDDS-based BC treatment. The article titled “Nanomedicine in cancer therapy: challenges, opportunities, and clinical applications” had the most citations. The Journal of Controlled Release was one of the most active publishers in the field. “Global cancer statistics 2018: GLOBOCAN estimates of incidence and mortality worldwide for 36 cancers in 185 countries” was the most cited reference. We also analysed “hot” and cutting-edge research for NDDSs in BC treatment. There were nine topic clusters: “tumour microenvironment,” “nanoparticles (drug delivery),” “breast cancer/triple-negative breast cancer,” “combination therapy,” “drug release (pathway),” “multidrug resistance,” “recent advance,” “targeted drug delivery”, and “cancer nanomedicine.” We also reviewed the core themes of research. In summary, this article reviewed the application of NDDSs in the treatment of BC.
VNAR development through antigen immunization of Japanese topeshark (Hemitriakis japanica)
Authors: Takeda Hiroyuki , Ozawa Tatsuhiko , Zenke Hiroki , Ohnuki Yoh , Umeda Yuri , Zhou Wei , Tomoda Honoka , Takechi Akihiko , Narita Kimiyoshi , Shimizu Takaaki , Miyakawa Takuya , Ito Yuji , Sawasaki Tatsuya
Published: September 2023

The VNAR (Variable New Antigen Receptor) is the smallest single-domain antibody derived from the variable domain of IgNAR of cartilaginous fishes. Despite its biomedical and diagnostic potential, research on VNAR has been limited due to the difficulties in obtaining and maintaining immune animals and the lack of research tools. In this study, we investigated the Japanese topeshark as a promising immune animal for the development of VNAR. This shark is an underutilized fishery resource readily available in East Asia coastal waters and can be safely handled without sharp teeth or venomous stingers. The administration of Venus fluorescent protein to Japanese topesharks markedly increased antigen-specific IgM and IgNAR antibodies in the blood. Both the phage-display library and the yeast-display library were constructed using RNA from immunized shark splenocytes. Each library was enriched by biopanning, and multiple antigen-specific VNARs were acquired. The obtained antibodies had affinities of 1 × 10−8 M order and showed high plasticity, retaining their binding activity even after high-temperature or reducing-agent treatment. The dissociation rate of a low-affinity VNAR was significantly improved via dimerization. These results demonstrate the potential utility of the Japanese topeshark for the development of VNAR. Furthermore, we conducted deep sequencing analysis to reveal the quantitative changes in the CDR3-coding sequences, revealing distinct enrichment bias between libraries. VNARs that were primarily enriched in the phage display had CDR3 coding sequences with fewer E. coli rare codons, suggesting translation machinery on the selection and enrichment process during biopanning.
pH stimuli-responsive hydrogels from non-cellulosic biopolymers for drug delivery
Authors: Vegad Udaykumar , Patel Megha , Khunt Dignesh , Zupančič Ožbej , Chauhan Sanjay , Paudel Amrit
Published: September 2023

Over the past several decades, there has been significant growth in the design and development of more efficient and advanced biomaterials based on non-cellulosic biological macromolecules. In this context, hydrogels based on stimuli-responsive non-cellulosic biological macromolecules have garnered significant attention because of their intrinsic physicochemical properties, biological characteristics, and sustainability. Due to their capacity to adapt to physiological pHs with rapid and reversible changes, several researchers have investigated pH-responsive-based non-cellulosic polymers from various materials. pH-responsive hydrogels release therapeutic substances in response to pH changes, providing tailored administration, fewer side effects, and improved treatment efficacy while reducing tissue damage. Because of these qualities, they have been shown to be useful in a wide variety of applications, including the administration of chemotherapeutic drugs, biological material, and natural components. The pH-sensitive biopolymers that are utilized most frequently include chitosan, alginate, hyaluronic acid, guar gum, and dextran. In this review article, the emphasis is placed on pH stimuli-responsive materials that are based on biological macromolecules for the purposes of drug administration.
Rewiring of mitochondrial metabolism in therapy-resistant cancers: permanent and plastic adaptations
Authors: Pendleton Katherine E. , Wang Karen , Echeverria Gloria V.
Published: September 2023

Deregulation of tumor cell metabolism is widely recognized as a “hallmark of cancer.” Many of the selective pressures encountered by tumor cells, such as exposure to anticancer therapies, navigation of the metastatic cascade, and communication with the tumor microenvironment, can elicit further rewiring of tumor cell metabolism. Furthermore, phenotypic plasticity has been recently appreciated as an emerging “hallmark of cancer.” Mitochondria are dynamic organelles and central hubs of metabolism whose roles in cancers have been a major focus of numerous studies. Importantly, therapeutic approaches targeting mitochondria are being developed. Interestingly, both plastic (i.e., reversible) and permanent (i.e., stable) metabolic adaptations have been observed following exposure to anticancer therapeutics. Understanding the plastic or permanent nature of these mechanisms is of crucial importance for devising the initiation, duration, and sequential nature of metabolism-targeting therapies. In this review, we compare permanent and plastic mitochondrial mechanisms driving therapy resistance. We also discuss experimental models of therapy-induced metabolic adaptation, therapeutic implications for targeting permanent and plastic metabolic states, and clinical implications of metabolic adaptations. While the plasticity of metabolic adaptations can make effective therapeutic treatment challenging, understanding the mechanisms behind these plastic phenotypes may lead to promising clinical interventions that will ultimately lead to better overall care for cancer patients.
Role of histone lactylation interference RNA m6A modification and immune microenvironment homeostasis in pulmonary arterial hypertension
Authors: Zhao Shuai-shuai , Liu Jinlong , Wu Qi-cai , Zhou Xue-liang
Published: September 2023

Pulmonary arterial hypertension (PAH) is a severe disease resulting from progressive increases in pulmonary vascular resistance and pulmonary vascular remodeling, ultimately leading to right ventricular failure and even death. Hypoxia, inflammation, immune reactions, and epigenetic modifications all play significant contributory roles in the mechanism of PAH. Increasingly, epigenetic changes and their modifying factors involved in reprogramming through regulation of methylation or the immune microenvironment have been identified. Among them, histone lactylation is a new post-translational modification (PTM), which provides a novel visual angle on the functional mechanism of lactate and provides a promising diagnosis and treatment method for PAH. This review detailed introduces the function of lactate as an important molecule in PAH, and the effects of lactylation on N6-methyladenosine (m6A) and immune cells. It provides a new perspective to further explore the development of lactate regulation of pulmonary hypertension through histone lactylation modification.
Evidence supportive of a bacterial component in the etiology for Alzheimer’s disease and for a temporal-spatial development of a pathogenic microbiome in the brain
Authors: Moné Yves , Earl Joshua P. , Król Jarosław E. , Ahmed Azad , Sen Bhaswati , Ehrlich Garth D. , Lapides Jeffrey R.
Published: September 2023

Background

Over the last few decades, a growing body of evidence has suggested a role for various infectious agents in Alzheimer’s disease (AD) pathogenesis. Despite diverse pathogens (virus, bacteria, fungi) being detected in AD subjects’ brains, research has focused on individual pathogens and only a few studies investigated the hypothesis of a bacterial brain microbiome. We profiled the bacterial communities present in non-demented controls and AD subjects’ brains.

Results

We obtained postmortem samples from the brains of 32 individual subjects, comprising 16 AD and 16 control age-matched subjects with a total of 130 samples from the frontal and temporal lobes and the entorhinal cortex. We used full-length 16S rRNA gene amplification with Pacific Biosciences sequencing technology to identify bacteria. We detected bacteria in the brains of both cohorts with the principal bacteria comprising Cutibacterium acnes (formerly Propionibacterium acnes) and two species each of Acinetobacter and Comamonas genera. We used a hierarchical Bayesian method to detect differences in relative abundance among AD and control groups. Because of large abundance variances, we also employed a new analysis approach based on the Latent Dirichlet Allocation algorithm, used in computational linguistics. This allowed us to identify five sample classes, each revealing a different microbiota. Assuming that samples represented infections that began at different times, we ordered these classes in time, finding that the last class exclusively explained the existence or non-existence of AD.

Conclusions

The AD-related pathogenicity of the brain microbiome seems to be based on a complex polymicrobial dynamic. The time ordering revealed a rise and fall of the abundance of C. acnes with pathogenicity occurring for an off-peak abundance level in association with at least one other bacterium from a set of genera that included Methylobacterium, Bacillus, Caulobacter, Delftia, and Variovorax. C. acnes may also be involved with outcompeting the Comamonas species, which were strongly associated with non-demented brain microbiota, whose early destruction could be the first stage of disease. Our results are also consistent with a leaky blood–brain barrier or lymphatic network that allows bacteria, viruses, fungi, or other pathogens to enter the brain.
The gut microbiota from maintenance hemodialysis patients with sarcopenia influences muscle function in mice
Authors: Tang Jie , Zhang Hailin , Yin Lixia , Zhou Qifan , Zhang Huipin
Published: September 2023

Background

Sarcopenia is a common complication in patients undergoing maintenance hemodialysis (MHD). Growing evidence suggests a close relationship between the gut microbiota and skeletal muscle. However, research on gut microbiota in patients with sarcopenia undergoing MHD (MS) remains scarce. To bridge this knowledge gap, we aimed to evaluate the pathogenic influence of gut microbiota in the skeletal muscle of patients with MS, to clarify the causal association between gut microbiota and skeletal muscle symptoms in patients with MS and identify the potential mechanisms underlying this causal association.

Methods

Fecal samples were collected from 10 patients with MS and 10 patients without MS (MNS). Bacteria were extracted from these samples for transplantation. Mice (n=42) were randomly divided into three groups and, after antibiotic treatment, fecal microbiota transplantation (FMT) was performed once a day for 3 weeks. Skeletal muscle and fecal samples from the mice were collected for 16S rRNA gene sequencing and for histological, real-time PCR, and metabolomic analyses.

Results

Mice colonized with gut microbiota from MS patients exhibited notable decreases in muscle function and muscle mass, compared with FMT from patients with MNS. Moreover, 16S rRNA sequencing revealed that the colonization of MS gut microbiota reduced the abundance of Akkermansia in the mouse intestines. Metabolome analysis revealed that seven metabolic pathways were notably disrupted in mice transplanted with MS microbiota.

Conclusion

This study established a connection between skeletal muscle and the gut microbiota of patients with MS, implying that disruption of the gut microbiota may be a driving factor in the development of skeletal muscle disorders in patients undergoing MHD. This finding lays the foundation for understanding the pathogenesis and potential treatment methods for sarcopenia in patients undergoing MHD.
The incidence of hepatocellular carcinoma and clearance of hepatitis B surface for CHB patients in the indeterminate phase: a systematic review and meta-analysis
Authors: Liu Min , Zhao Taixue , Zhang Yuting , Zhang A-Mei , Geng Jiawei , Xia Xueshan
Published: September 2023

Background

Nearly 30%–40% of patients with chronic hepatitis B do not fall into any of the traditional natural history classification and thus are classified as indeterminate. However, it is unclear whether patients in the indeterminate phase (IP) are at a higher risk for hepatocellular carcinoma (HCC) than those in the defined phases (DP) and would benefit from antiviral therapy. We performed a systematic review and meta-analysis of HCC incidence and HBsAg clearance among patients in the IP versus DP.

Methods

We defined the clinical phases as per the AASLD 2018 hepatitis B guidance. We searched PubMed, Embase, Medline, and Web of Science for relevant studies that reported HCC incidence or HBsAg clearance in IP versus DP patients published between January 2007 and March 2023. Annual HCC incidence and HBsAg clearance rates were pooled using a random/common-effects model.

Results

We analyzed data from 14 studies, comprising 7798 IP patients (222 patients developed HCC and 239 achieved HBsAg clearance) and 10,725 DP patients. The pooled annual HCC incidence was 2.54 cases per 1,000 person-years (95% CI, 1.14–4.39) and HBsAg clearance rate was 12.36 cases per 1,000 person-years (95% CI, 10.70–14.13) for the IP patients. IP patients were associated with significantly higher HCC incidence risk (RR = 1.64, 95% CI, 1.34–2.00) and slightly lower annual HBsAg clearance rate (RR = 0.83, 95% CI, 0.70–0.99) than the DP patients. In addition, HBeAg-negative IP patients (2.31%; 95% CI, 0.87–4.45) showed a significantly higher HCC incidence than those who were HBeAg positive (0.00%; 95% CI, 0.00–0.99) (p< 0.001). The Asia-Pacific region IP patients (4.30%; 95% CI, 2.07–7.27) were also associated with a higher HCC incidence versus Europe (0.05%; 95% CI, 0.00–1.39) (p< 0.001). However, there were no significant differences between different strategies (treated vs. untreated: 2.56%; 95% CI, 1.01–4.63 vs. 1.61%; 95% CI, 0.00–5.81, p = 0.09), and heterogeneity was substantial across the studies (I2 = 89%).

Conclusion

The systematic review and meta-analysis showed a high HCC incidence and low HBsAg clearance among patients in the IP, especially for HBeAg-negative patients and the Asian population. We emphasize that future multicenter prospective cohort studies or randomized trials are needed to verify if expanding antiviral therapy for patients in the IP is associated with reduced HCC risk or good treatment outcomes.
Role of the vaginal microbiome in miscarriage: exploring the relationship
Authors: Saadaoui Marwa , Singh Parul , Ortashi Osman , Al Khodor Souhaila
Published: September 2023

Miscarriage is a devastating pregnancy loss that affects many women worldwide. It is characterized as a spontaneous miscarriage that occurs before 20 weeks of gestation which affects more than 25% of pregnancies. While the causes of miscarriage are complex and multifactorial, recent research has suggested a potential role of the vaginal microbiota. The vaginal microbiome is a dynamic ecosystem of microbes that are essential for preserving vaginal health and avoiding infections. Vaginal dysbiosis has been accompanied with numerous adverse pregnancy complications, such as preterm birth. However, the effect of the vaginal microbiome in miscarriage is not fully understood. This review aims to investigate the link between vaginal microbiota and miscarriage. Also, we investigate the various mechanisms through which the vaginal microbiota may affect miscarriage. Additionally, we examine the implications of these research findings, specifically the possibility of vaginal microbiome screening and targeted interventions to prevent miscarriage.
Diagnostic efficiency of metagenomic next-generation sequencing for suspected infection in allogeneic hematopoietic stem cell transplantation recipients
Authors: Huang Jiayu , Zhao Yeqian , Jiang Chuanhe , Han Dongsheng , Pan Zengkai , Zhang Zilu , Wang Luxiang , Chen Wei , Li Su , Zhao Yanmin , Hu Xiaoxia
Published: September 2023

Introduction

Immunosuppression predisposes allogeneic hematopoietic stem cell transplantation (allo-HSCT) recipients to infection. Prompt and accurate identification of pathogens is crucial to optimize treatment strategies. This multi-center retrospective study aimed to assess the ability of metagenomic next-generation sequencing (mNGS) to detect causative pathogens in febrile allo-HSCT recipients and examined its concordance with conventional microbiological tests (CMT).

Methods

We performed mNGS and CMT on samples obtained from 153 patients with suspected infection during allo-HSCT. Patients were grouped based on their neutropenic status at the time of sampling.

Results

The mNGS test was more sensitive than CMT (81.1% vs. 53.6%, P<0.001) for diagnosing clinically suspected infection, especially in the non-neutropenia cohort. mNGS could detect fungi and viruses better than bacteria, with a higher sensitivity than CMT. Immune events were diagnosed in 57.4% (35/61) of the febrile events with negative mNGS results, and 33.5% (48/143) with negative CMT results (P=0.002). The treatment success rate of the targeted anti-infection strategy was significantly higher when based on mNGS than on empirical antibiotics (85% vs. 56.5%, P=0.004).

Conclusion

The mNGS test is superior to CMT for identifying clinically relevant pathogens, and provides valuable information for anti-infection strategies in allo-HSCT recipients. Additionally, attention should be paid to immune events in patients with negative mNGS results.
Modifying Escherichia coli to mimic Shigella for medical microbiology laboratory teaching: a new strategy to improve biosafety in class
Authors: Zhang Guangyuan , Liu Jia , He Yonglin , Du Yuheng , Xu Lei , Chen Tingting , Guo Yanan , Fu Huichao , Li Anlong , Tian Yunbo , Hu Yan , Yang Chun , Lu Mingqi , Deng Xichuan , Wang Jingsong , Lu Nan
Published: September 2023

Introduction

Laboratory teaching of medical microbiology involves highly pathogenic microorganisms, thus posing potential biosafety risks to the students and the teacher. To address these risks, non/low-pathogenic microorganisms were modified to mimic highly pathogenic ones or highly pathogenic microorganisms were attenuated directly using the CRISPR/Cas9 technology. This study describes the modification of Escherichia coli DH5α to mimic Shigella and its evaluation as a safe alternative for medical laboratory teaching.

Methods

To generate E. coli DH5α△FliC△tnaA2a, the tnaA and FliC genes in E. coli DH5α were knocked out using CRISPR/Cas9 technology; a plasmid bearing the O-antigen determinant of S. flexneri 2a was then constructed and transformed. Acid tolerance assays and guinea pig eye tests were used to assess the viability and pathogenicity, respectively. Questionnaires were used to analyze teaching effectiveness and the opinions of teachers and students.

Results

The survey revealed that most teachers and students were inclined towards real-time laboratory classes than virtual classes or observation of plastic specimens. However, many students did not abide by the safety regulations, and most encountered potential biosafety hazards in the laboratory. E. coli DH5α△FliC△tnaA2a was biochemically and antigenically analogous to S. flexneri 2a and had lower resistance to acid than E. coli. There was no toxicity observed in guinea pigs. Most of teachers and students were unable to distinguish E. coli DH5α△FliC△tnaA2a from pure S. flexneri 2a in class. Students who used E. coli DH5α△FliC△tnaA2a in their practice had similar performance in simulated examinations compared to students who used real S. flexneri 2a, but significantly higher than the virtual experimental group.

Discussion

This approach can be applied to other high-risk pathogenic microorganisms to reduce the potential biosafety risks in medical laboratory-based teaching and provide a new strategy for the development of experimental materials.
Metagenomic characterization of the microbiomes in five different body habitats of otherwise healthy individuals with periodontal disease
Authors: Oh Sujin , Lee Hyo-Jung , Park Kyoung Un
Published: September 2023

Introduction

Recent studies have proposed several plausible mechanisms supporting the association between periodontal disease and systemic disease. However, characterizing the microbial communities in individuals with periodontal disease before onset of other diseases is an important first step in determining how the altered microbial state contributes to disease progression. This study established microbiome profiles for five body habitats of carefully selected, otherwise healthy individuals with periodontal disease.

Methods

Blood, oral (buccal mucosa, dental plaque, and saliva), and stool samples were collected from ten healthy subjects with periodontal disease. Using 16S rRNA metagenomics, the taxonomic and functional compositions of microbiomes were investigated.

Results

The most predominant phylum in blood and stool was Bacillota. Pseudomonadota accounted for the largest proportion of microbes in the buccal mucosa and saliva, whereas Bacteroidota were the most prevalent in dental plaque. Differential abundance analysis revealed that 12 phyla and 139 genera were differentially abundant between body habitats. Comparison of alpha diversity showed that the blood microbiome has the most diverse community close to neither oral nor stool microbiomes. We also predicted the functional configurations of the microbiome in otherwise healthy subjects with periodontal disease. Principal coordinate analysis based on functional abundance revealed distinct clustering of the microbial communities between different body habitats, as also observed for taxonomic abundance. In addition, 13 functional pathways, including lipopolysaccharide biosynthesis, glutathione metabolism, and proteasome, showed differential expression between habitats.

Discussion

Our results offer insight into the effects of the microbiome on systemic health and disease in people with periodontal disease.
Predictors of diastolic deceleration time of coronary flow velocity of infarct related and reference coronary artery assessed by transthoracic Doppler echocardiography in the chronic phase of successfully reperfused anterior myocardial infarction: relation to infarct size
Authors: Giga Vojislav , Tesic Milorad , Beleslin Branko , Boskovic Nikola , Sobic-Saranovic Dragana , Jovanovic Ivana , Nedeljkovic Ivana , Paunovic Ivana , Dedic Srdjan , Djordjevic-Dikic Ana
Published: September 2023

Introduction

High-frequency transthoracic Doppler echocardiography (TDE) enables the assessment of flow velocity and velocity pattern in different coronary arteries, including the assessment of diastolic deceleration time (DDT) of coronary flow velocity. Short DDT of infarct related artery (IRA) (<600 msec) in the acute phase of anterior myocardial infarction (MI) is the predictor of adverse left ventricular (LV) remodeling and prognosis. The significance of DDT of coronary flow velocity assessment in the chronic phase of anterior MI is not well established. Our study aimed to establish the predictors of DDT of the coronary flow velocity of infarct related (left anterior descendent-DDT of LAD) and reference coronary artery, evaluated by TDE, and to assess their relation to infarct size in the chronic phase of successfully reperfused first anterior MI.

Methods

Our study included 40 consecutive patients (34 men, mean age 52 ± 12 years) one month after the first anterior STEMI and single vessel disease successfully treated with primary PCI. All patients underwent SPECT MPI for the assessment of LV volumes, ejection fraction, and percentage of the myocardium with fixed perfusion abnormalities and echocardiographic examination including the evaluation of DDT of IRA and reference coronary artery TDE.

Results

DDT of LAD correlated significantly to the WMSI (r = −0.467, p = 0.002), LV end-systolic volume (r = −0.412, p = 0.008), LV ejection fraction (r = 0.427, p = 0.006), while the strongest correlation was observed between DDT of LAD and the extent of fixed perfusion abnormality (r = −0.627, p < 0.0001), Multivariate analysis revealed percentage of fixed perfusion abnormalities along with DDT of reference coronary artery as the independent predictors of DDT of IRA. DDT of IRA shorter than 886 msec predicts large fixed perfusion abnormalities (>20%) with a sensitivity of 89% and specificity of 62% (AUC 0.842).

Conclusion

DDT of LAD assessed by TDE in the chronic phase of successfully reperfused first anterior MI is a usefull variable for the assessment of microcirculatory function that exclusively reflects the extent of microvascular damage and relates to infarct size.
Associations among risk perception, health efficacy, and health behaviors for cardiovascular disease: an application of risk perception attitude framework
Authors: Guo Zhiting , Chen Yun , Zhang Yuping , Ding Chuanqi , Li Mei , Xu Linyan , Jin Jingfen
Published: September 2023

Background

There is currently a pervasive prevalence of cardiovascular disease (CVD) risk worldwide and an inadequate amount of action is being taken to promote healthy lifestyle habits. The risk perception attitude (RPA) framework, which classifies individuals based on their risk perception and efficacy belief, enables us to predict their preventive behaviors. We applied the RPA framework to analyze CVD prevention behaviors among Chinese adults and extended its application to CVD objective risk.

Methods

A cross-sectional survey was performed in two sites in Zhejiang Province, from March to August 2022, which contained self-reported CVD risk perception, objective CVD risk, efficacy belief, physical activity, healthy diet, and covariates. We used the RPA framework to categorize participants into four groups, then analysis was conducted to estimate inter-group differences in healthy behaviors. We further conducted a hierarchical logistic regression analysis with individuals' health behaviors as the dependent variable, using three blocks of independent variables.

Results

Among 739 participants, healthy physical activity and healthy diet had significant differences among four RPA groups, post hoc tests clarified that the proportion of respondents with healthy PA in the responsive group (61.6%) was significantly higher than that in the other three groups. Risk perception and efficacy belief significantly predicted health behavior against CVD; the relationship between absolute CVD risk and health behavior was moderated by efficacy belief.

Conclusions

Early CVD risk screening is crucial, but tailored support and a proper understanding of personal risk are essential to promote healthy behaviors. Developing communication and behavioral counseling intervention strategies on the basis of the RPA framework has the potential to promote healthy behaviors for CVD prevention.
Case report: Right coronary artery to left ventricular fistula complicated with coronary artery dilation presenting as persistent cardiogenic ischemic chest pain
Authors: Wang Yuehai , Zhang Yuqiang , Wang Fei , Xue Yuzeng
Published: September 2023

We reported a patient with a fistula of the right coronary artery to the left ventricle, accompanied by dilation of the right coronary artery and persistent chest pain. This patient underwent surgical fistula closure surgery, but the fistula recurred. Persistent chest pain reappeared after encountering COVID-19 infection. We analyzed the mechanism of persistent myocardial ischemic chest pain caused by coronary artery fistula in this patient, the impact of surgery on the patient's disease, the possible mechanism of COVID-19 causing persistent ischemic chest pain in this patient, and the possible mechanism of metoprolol in alleviating myocardial ischemic chest pain in this patient.
Assessing network-based earthquake early warning systems in low-seismicity areas
Authors: Ahn Jae-Kwang , Cho Seongheum , Hwang Eui-Hong , Baek Woo-Hyun
Published: September 2023

Earthquake early warning (EEW) technology, designed to alert the public of earthquake risks after initial P-wave detection but before the onset of strong tremors, has developed rapidly. Methodologies from various fields are combined in EEW systems to estimate earthquake locations, magnitudes, and expected intensities based on the initial P-wave data. These systems operate automatically because prompt responses are required. However, as no common evaluation framework for EEW system verification exists, potentially divergent evaluations from reviewers or countries could ensue. Moreover, evaluating EEW systems is more complicated when the target area does not experience frequent earthquakes. We aimed to establish a guidance review process for low-seismicity areas to ensure reliable and stable integrated EEW system operation. We incorporated management aspects through actual system operator surveillance and designed an EEW assessment process based on feedback from our surveys. Using this approach, we created a comprehensive and well-informed evaluation process that considers the diverse perspectives of experts involved in EEWs. Our proposed assessment method allows for a uniform and consistent evaluation process, regardless of changes in the methods or technologies used by EEW systems. The method aims to guide EEW system assessments in low-seismicity areas.
A stratospheric mission – design of a conceptual framework to bring weather balloons and STEM into the classroom
Authors: Connolly Cornelia , Johnson Patrick , Johnson Kevin , Fitzpatrick Mary , O’Keeffe Derek T.
Published: September 2023

Introduction

Integrated STEM education makes learning relevant and applicable, blending the mindset, skillset, and toolset necessary in developing a depth of understanding for science, technology, engineering and mathematics.

Methods

Based on the theoretical framework of Kelley and Knowles the ‘Spaceship Earth’ project was designed to engage primary school children in 4th class (ages 9 and 10 years old) in real-world project-based experiments in the classroom that are used to develop collaborative problem-solving skills and a framework for asking and answering scientific questions. This project involved researchers from two Universities and the Irish National Meteorological Service working collaboratively on a high-altitude balloon mission.

Results

High-altitude balloons have an established track record of safe and effective use in weather forecasting, astronomy, and STEM outreach. During the project lifecycle the children devised experiments that they launched to the stratosphere using the high-altitude balloons. Once the experiments returned to Earth, the children engaged in analysis and discussion about their experiments that extended and deepened their learning.

Discussion

This celestial project framework represents a new dawn of innovation for STEM education and public engagement.
Two-part onboarding for game-based learning environments
Authors: Vidaković Milan , Lara Macarena , Duchi Lorenzo , Whitcomb Alexander , Paas Fred
Published: September 2023

The trend of introducing game-based elements and mechanisms via game-based learning (GBL) and gamification is expanding in higher education, as is research on the elements of gamification design that contribute to their effects on learning. This paper presents a two-part onboarding process as a game-design element, analyzing its underlying mechanisms and potential effects on student learning through theoretical frameworks. First, we introduce a two-part onboarding intervention designed as part of introducing GBL in higher education. The intervention aims to address a challenge students face when taking a GBL module or course: namely, that venturing into a new digital platform often brings with it new and unfamiliar expectations of how students should act and interact in order to effectively engage with the course material as well as with their peers and instructors. Second, we describe two projects through which the intervention evolved to its current form. Third, we analyze and apply two theoretical frameworks—on semiotic domains and cognitive load—to examine the underlying mechanisms by which the intervention may be expected to affect student learning.
Utility of a simplified [18F] sodium fluoride PET imaging method to quantify bone metabolic flux for a wide range of clinical applications
Authors: Puri Tanuj , Frost Michelle L. , Moore Amelia E. B. , Choudhury Ananya , Vinjamuri Sobhan , Mahajan Abhishek , Fynbo Claire , Vrist Marie , Theil Jørn , Kairemo Kalevi , Wong James , Zaidi Habib , Revheim Mona-Elisabeth , Werner Thomas J. , Alavi Abass , Cook Gary J. R. , Blake Glen M.
Published: September 2023

We review the rationale, methodology, and clinical utility of quantitative [18F] sodium fluoride ([18F]NaF) positron emission tomography-computed tomography (PET-CT) imaging to measure bone metabolic flux (Ki, also known as bone plasma clearance), a measurement indicative of the local rate of bone formation at the chosen region of interest. We review the bone remodelling cycle and explain what aspects of bone remodelling are addressed by [18F]NaF PET-CT. We explain how the technique works, what measurements are involved, and what makes [18F]NaF PET-CT a useful tool for the study of bone remodelling. We discuss how these measurements can be simplified without loss of accuracy to make the technique more accessible. Finally, we briefly review some key clinical applications and discuss the potential for future developments. We hope that the simplified method described here will assist in promoting the wider use of the technique.
Hydrochemical evolution and groundwater quality assessment of the Tinejdad-Touroug quaternary aquifer, South-East Morocco
Authors: Ait Said Brahim , Mili El-Mostafa , El Faleh El Mati , Mehdaoui Radouan , Mahboub Abderrahmane , Hamid Fatima Ezzahra , Tlemcani Jihane , El Fakir Rabia
Published: September 2023

The Palm Grove ecosystems situated in the southeastern region of Morocco are highly vulnerable to compromise, encountering significant challenges due to insufficient precipitation and limited availability of groundwater. The objective of this study is to evaluate the groundwater quality of the Tinejdad-Touroug aquifer for domestic and irrigation purposes. Groundwater flows from southwest to northeast mostly in Quaternary conglomerate-lacustrine facies in the Rheris basin. The results show that the domination of the major ions is in the following order: Cl−>HCO3−>SO42−>Na+>Ca2+>Mg2+>NO3−>K+>NO2−>NH4+. Piper diagram showed the predominance of a single mixed chemical facies Cl-SO4-Ca-Mg, as well as the presence of exceptions of some samples that showed other facies variations. The water quality index (WQI) assessments of the campaigns that were examined demonstrate that the recorded percentages of poor quality water ranged from 40% to 90% while the percentages of good quality water varied from 7.7% to 54.5%. The remaining samples reveal different classes with varying percentages. Most of the sites in all campaigns had drinking water parameters that exceeded the values established by the World Health Organization (WHO) and Moroccan standards. Nevertheless, the parameters of Temperature, pH, TH, DO, Ca2+, SO42−, K+, NH4+, and bacteriological parameters were within the required limits. The results of the assessment based on electrical conductivity suggest a significant increase in salinity levels, with an average of 2744.75 µS/cm in 2000, 3248.58 µS/cm in 2007, and 2957.84 µS/cm in 2021. The findings of the study reveal a positive assessment regarding the quality of the water samples examined during the eight sampling campaigns, as indicated by the PI and KR indices. However, additional investigation of the SAR, Na%, and MH indices revealed that three water samples acquired from separate surveys are not appropriate for irrigation purposes, showing that groundwater must be controlled until it can be properly used. The outcomes accentuate the necessity of consistent monitoring and evaluation of water quality parameters to establish the safe and sustainable exploitation of water resources for domestic and agricultural purposes. Elevated salinity levels in Quaternary aquifers resulting from natural mechanisms such as increased rates of evaporation and geological factors may have contributed to the degradation of groundwater quality.
Establishment of a 7-gene expression panel to improve the prognosis classification of gastric cancer patients
Authors: Velásquez Sotomayor Mariana Belén , Campos Segura Anthony Vladimir , Asurza Montalva Ricardo José , Marín-Sánchez Obert , Murillo Carrasco Alexis Germán , Ortiz Rojas César Alexander
Published: September 2023

Gastric cancer (GC) ranks fifth in incidence and fourth in mortality worldwide. The high death rate in patients with GC requires new biomarkers for improving survival estimation. In this study, we performed a transcriptome-based analysis of five publicly available cohorts to identify genes consistently associated with prognosis in GC. Based on the ROC curve, patients were categorized into high and low-expression groups for each gene using the best cutoff point. Genes associated with survival (AUC > 0.5; univariate and multivariate Cox regressions, p < 0.05) were used to model gene expression-based scores by weighted sum using the pooled Cox β regression coefficients. Cox regression (p < 0.05), AUC > 0.5, sensitivity > 0.5, and specificity > 0.5 were considered to identify the best scores. Gene set enrichment analysis (KEGG, REACTOME, and Gene Ontology databases), as well as microenvironment composition and stromal cell signatures prediction (CIBERSORT, EPIC, xCell, MCP-counter, and quanTIseq web tools) were performed. We found 11 genes related to GC survival in the five independent cohorts. Then, we modeled scores by calculating all possible combinations between these genes. Among the 2,047 scores, we identified a panel based on the expression of seven genes. It was named GES7 and is composed of CCDC91, DYNC1I1, FAM83D, LBH, SLITRK5, WTIP, and NAP1L3 genes. GES7 features were validated in two independent external cohorts. Next, GES7 was found to recategorize patients from AJCC TNM stages into a best-fitted prognostic group. The GES7 was associated with activation of the TGF-β pathway and repression of anticancer immune cells. Finally, we compared the GES7 with 30 previous proposed scores, finding that GES7 is one of the most robust scores. As a result, the GES7 is a reliable gene-expression-based signature to improve the prognosis estimation in GC.
Machine learning and bioinformatics analysis to identify autophagy-related biomarkers in peripheral blood for rheumatoid arthritis
Authors: Dong Guoqi , Gao Hui , Chen Yingqi , Yang Huayuan
Published: September 2023

Background: Although rheumatoid arthritis (RA) is a common autoimmune disease, the precise pathogenesis of the disease remains unclear. Recent research has unraveled the role of autophagy in the development of RA. This research aims to explore autophagy-related diagnostic biomarkers in the peripheral blood of RA patients.

Methods: The gene expression profiles of GSE17755 were retrieved from the gene expression ontology (GEO) database. Differentially expressed autophagy-related genes (DE-ARGs) were identified for the subsequent research by inserting autophagy-related genes and differentially expressed genes (DEGs). Three machine learning algorithms, including random forest, support vector machine recursive feature elimination (SVM-RFE), and least absolute shrinkage and selection operator (LASSO), were employed to identify diagnostic biomarkers. A nomogram model was constructed to assess the diagnostic value of the biomarkers. The CIBERSORT algorithm was performed to investigate the correlation of the diagnostic biomarkers with immune cells and immune factors. Finally, the diagnostic efficacy and differential expression trend of diagnostic biomarkers were validated in multiple cohorts containing different tissues and diseases.

Results: In this study, 25 DE-ARGs were identified between RA and healthy individuals. In addition to “macroautophagy” and “autophagy-animal,” DE-ARGs were also associated with several types of programmed cell death and immune-related pathways according to GO and KEGG analysis. Three diagnostic biomarkers, EEF2, HSP90AB1 and TNFSF10, were identified by the random forest, SVM-RFE, and LASSO. The nomogram model demonstrated excellent diagnostic value in GSE17755 (AUC = 0.995, 95% CI: 0.988–0.999). Furthermore, immune infiltration analysis showed a remarkable association between EEF2, HSP90AB1, and TNFSF10 expression with various immune cells and immune factors. The three diagnostic biomarkers also exhibited good diagnostic efficacy and demonstrated the same trend of differential expression in multiple validation cohorts.

Conclusion: This study identified autophagy-related diagnostic biomarkers based on three machine learning algorithms, providing promising targets for the diagnosis and treatment of RA.