bluuebunny/crossref_metadata_2025 huggingface dataset:
CD146 Promotes EMT-Mediated Migration and Invasion of NSCLC via PI3K/Akt Signaling Pathway
Authors: Wei Nan , Wu Xuan , Yu Yi , Zhou Huanhuan , Cui Kai , Zhao Xingru , Zhang Xiaoju
Published: April 2024

Background: Recurrence and metastasis are the main causes of non-small cell lung cancer (NSCLC)-related death. CD146 has been identified as a potential risk factor for poor prognosis, closely related to the distant metastasis and drug resistance in various cancers. However, the clinical significance of CD146 in NSCLC requires further investigation. Materials and Methods: This study explored the correlation between CD146 expression and clinical variables using tumor tissue samples collected from our hospital. CD146 expression levels in NSCLC cell lines and tissues were assessed and compared using immunohistochemistry, real-time polymerase chain reaction (RT-qPCR), flow cytometry, and western blot analysis. The invasion and migration capabilities of tumor cells were determined using transwell and wound healing assays. The levels of proteins related to epithelial-mesenchymal transition (EMT) as well as the underlying PI3K/Akt signaling pathway was measured by western blotting. Results: We discovered that CD146 expression is significantly associated with the EMT signaling pathway. High CD146 expression predicted lymph node metastasis, metastasis to distant organs, advanced Tumor, Node, Metastasis (TNM) staging, and poor survival in NSCLC patients. Wound healing and transwell assays showed that knocking down CD146 significantly suppressed cell migration along with cell invasion in NSCLC, whereas overexpressing CD146 notably enhanced these processes. Western blot analysis revealed significantly reduced levels of N-cadherin, vimentin, snail, twist, PI3K, and AKT phosphorylation in shCD146 H460 cells compared to vector control cells. Treatment with PI3K inhibitor PI3K-IN-1 increased E-cadherin expression levels but reduced N-cadherin, Twist, Vimentin, PI3K, and AKT phosphorylation levels in pcDNA3.1-CD146 A549 cells compared with the vector control cells. Conclusions: CD146 expression acts as a prognostic risk factor for adverse outcomes in NSCLC, promoting invasion and metastasis by activating the EMT through the PI3K/Akt signaling pathway. These findings underscore the potential therapeutic strategies targeting CD146, offering new treatment options for NSCLC patients, especially those at risk of metastasis.
The Metabolism of Coenzyme A and Its Derivatives Plays a Crucial Role in Diseases
Authors: Xie Jumin , Chen Xingyuan , Zheng Mei , Zhu Jingzhe , Mao Hui
Published: April 2024

Coenzyme A (CoA) functions as a crucial carrier of acyl groups within cells, playing a fundamental role in regulating acyl transfer reactions and participating in cellular metabolic processes. As the principal substrate and cofactor engaged in diverse metabolic reactions, CoA and its derivatives exert central influence over various physiological processes, primarily modulating lipid and ketone metabolism, as well as protein modification. This paper presents a comprehensive review of the molecular mechanisms by which CoA influences the onset and progression of cancer, cardiovascular disease (CVD), neurodegenerative disorders, and other illnesses. The main focal points include the following. (1) In cancer, enzymes such as acetyl-CoA synthetase 2, ATP citrate lyase, and acetyl-CoA carboxylase regulate lipid synthesis and energy metabolism by modulating acetyl-CoA levels. (2) In CVD, the effects of enzymes such as stearoyl-CoA desaturase-1, 3-hydroxy-3-methylglutaryl-CoA (HMGC) synthase 2, and HMGC reductase on the formation and advancement of these diseases are elucidated by their regulation of CoA metabolism across multiple organs. (3) In neurodegenerative disorders, the significance of CoA in maintaining cholesterol homeostasis in the brain and its implications on the development of such disorders are thoroughly discussed. The metabolic processes involving CoA and its derivatives span all physiological aspects within cells, playing a critical role in the onset and progression of various diseases. Elucidating the role of CoA in these conditions yields important insights that can serve as valuable references and guidance for disease diagnosis, treatment, and drug development.
UBA2 as a Prognostic Biomarker and Potential Therapeutic Target in Glioma
Authors: Ou Yuhong , Luo Hongtao , Zhang Qiuning , Du Tianqi , Liu Ruifeng , Wang Dandan , Chen Junru , Dong Meng , Wang Yuhang , Yang Zhen , Wang Xiaohu
Published: April 2024

Background: Gliomas are characterized by aggressive behavior, leading to severe disability and high mortality. Ubiquitin-like modifier activating enzyme 2 (UBA2) is a subunit of the E1-activating enzyme involved in the SUMOylation (SUMO, small ubiquitin-related modifier) of numerous proteins. Although the abnormality of UBA2 is linked to the progression of various tumor types, the role of UBA2 in glioma is still unknown. Methods: A bioinformatic analysis using several public databases was conducted to examine the expression level, clinicopathological correlations, and prognostic significance of UBA2 in glioma. The correlation between UBA2 expression and drug sensitivity in cancers was also explored. Multiple cellular experiments were conducted to validate the role of UBA2 in glioma. Results: Analysis of multiple databases and cellular experiments revealed that UBA2 was overexpressed in glioma tissues and cell lines, respectively. UBA2 expression in gliomas correlated with World Health Organization (WHO) grade, IDH gene status, 1p19q deletion, histological type, and immune cell infiltration in glioma. UBA2 expression in carcinomas also correlated with drug sensitivity. Kaplan-Meier analysis revealed that high expression of UBA2 predicted poorer survival in glioma patients. A nomogram model containing UBA2 expression was constructed for clinical practice. Knockdown of UBA2 was observed to suppress glioma cell progression and sensitize glioma cells to irradiation in vitro. Conclusion: Overall, this research showed that UBA2 might be involved not only in the development of glioma but also in the regulation of immunity, drug sensitivity, and radiosensitivity. Therefore, UBA2 may be a potential target for therapy and a candidate biomarker for glioma diagnosis and prognosis.
Progenitor Cell Function and Cardiovascular Remodelling Induced by SGLT2 Inhibitors
Authors: Stougiannou Theodora M. , Christodoulou Konstantinos C. , Koufakis Theocharis , Mitropoulos Fotios , Mikroulis Dimitrios , Mazer Cyril David , Karangelis Dimos
Published: April 2024

Sodium-glucose cotransporters 2 (SGLT2) are high-capacity, low-affinity transporters, expressed mainly in the early portion of the proximal renal tube, mediating up to 90% of renal glucose uptake, while SGLT1 receptors are found mainly in the small intestine, facilitating glucose absorption. SGLT2 inhibitors (SGLT2i) originally emerged as agents for the treatment of type 2 diabetes mellitus; however, they soon demonstrated remarkable cardio- and renoprotective actions that led to their licensed use for the treatment of heart failure and chronic kidney disease, regardless of the diabetic status. Cardiovascular remodelling represents an umbrella term that encompasses changes that occur in the cardiovascular system, from the molecular and cellular level, to tissue and organs after local injury, chronic stress, or pressure. SGLT modulation has been shown to positively affect many of these molecular and cellular changes observed during pathological remodelling. Among the different pathophysiological mechanisms that contribute to adverse remodelling, various stem and progenitor cells have been shown to be involved, through alterations in their number or function. Recent studies have examined the effects of SGLT2i on stem and progenitor cell populations and more specifically on endothelial progenitor cells (EPCs). Although some found no significant effect, others showed that SGLT2i can modulate the morphology and function of EPCs. These preliminary observations of the effect of SGLT2i on EPCs may be responsible for some of the beneficial effects of gliflozins on pathological remodelling and, by extension, on cardiovascular disease. The purpose of this narrative review is to critically discuss recent evidence on the cardioprotective effects of SGLT2is, in the context of cardiac remodelling.
Profiles, Distribution, and Functions of Gamma Delta T Cells in Ocular Surface Homeostasis and Diseases
Authors: Sun Zhengze , Ji Haolan , Zhou Yifan , Duan Hongyu , Ma Baikai , Qi Hong
Published: April 2024

The ocular surface microenvironment, containing the cornea, conjunctiva, and lacrimal gland, constitutes the mucosal frontline of the eye and houses a myriad of immune cells. As a part of unconventional T cells, gamma delta (γδ) T cells differ in the development and functions from canonical alpha beta (αβ) T cells. They are predominantly situated in mucosal sites throughout the body, including ocular surface tissues. Recent research has elucidated that γδ T cells serve as the primary interleukin-17A (IL-17A) source in the conjunctiva. They play a pivotal role in preserving ocular surface homeostasis and exhibit both protective and pathogenic roles in ocular surface diseases. This review delves into the general profiles of γδ T cells, their distribution in ocular surface tissues, and consolidates current insights into their functions in different conditions including dry eye disease, infectious keratitis, corneal wound healing, anterior chamber-associated immune deviation, allergic conjunctival disease, and diabetic ocular surface disease. The aim is to provide a systemic perspective on γδ T cells in the ocular surface microenvironment and outline potential directions for future studies.
Whole Genome Analysis of Tibetan Kefir-Derived Lactiplantibacillus Plantarum 12-3 Elucidates Its Genomic Architecture, Antimicrobial and Drug Resistance, Potential Probiotic Functionality and Safety
Authors: Aziz Tariq , Naveed Muhammad , Shabbir Muhammad Aqib , Sarwar Abid , Khan Ayaz Ali , Hasnain Ammarah , Haq Taqweem Ul , Yang Zhennai , Zinedine Abdellah , Rocha João Miguel , Alharbi Metab
Published: April 2024

Background: Lactiplantibacillus plantarum 12-3 holds great promise as a probiotic bacterial strain, yet its full potential remains untapped. This study aimed to better understand this potential therapeutic strain by exploring its genomic landscape, genetic diversity, CRISPR-Cas mechanism, genotype, and mechanistic perspectives for probiotic functionality and safety applications. Methods: L. plantarum 12-3 was isolated from Tibetan kefir grains and, subsequently, Illumina and Single Molecule Real-Time (SMRT) technologies were used to extract and sequence genomic DNA from this organism. After performing pan-genomic and phylogenetic analysis, Average Nucleotide Identity (ANI) was used to confirm the taxonomic identity of the strain. Antibiotic resistance gene analysis was conducted using the Comprehensive Antibiotic Resistance Database (CARD). Antimicrobial susceptibility testing, and virulence gene identification were also included in our genomic analysis to evaluate food safety. Prophage, genomic islands, insertion sequences, and CRISPR-Cas sequence analyses were also carried out to gain insight into genetic components and defensive mechanisms within the bacterial genome. Results: The 3.4 Mb genome of L. plantarum 12-3, was assembled with 99.1% completeness and low contamination. A total of 3234 genes with normal length and intergenic spacing were found using gene prediction tools. Pan-genomic studies demonstrated gene diversity and provided functional annotation, whereas phylogenetic analysis verified taxonomic identity. Our food safety study revealed a profile of antibiotic resistance that is favorable for use as a probiotic. Analysis of insertional sequences, genomic islands, and prophage within the genome provided information regarding genetic components and their possible effects on evolution. Conclusions: Pivotal genetic elements uncovered in this study play a crucial role in bacterial defense mechanisms and offer intriguing prospects for future genome engineering efforts. Moreover, our findings suggest further in vitro and in vivo studies are warranted to validate the functional attributes and probiotic potential of L. plantarum 12-3. Expanding the scope of the research to encompass a broader range of L. plantarum 12-3 strains and comparative analyses with other probiotic species would enhance our understanding of this organism’s genetic diversity and functional properties.
Exosomal CircRNAs in Circulation Serve as Diagnostic Biomarkers for Acute Myocardial Infarction
Authors: Liu Xiaoyan , Zhang Yeping , Yuan Wen , Han Ruijuan , Zhong Jiuchang , Yang Xinchun , Zheng Meili , Xie Boqia
Published: April 2024

Background: The diagnostic potential of circular RNAs (circRNAs) in circulating exosomes for acute myocardial infarction (AMI) is not well understood, despite existing research indicating their role in cardiovascular diseases. This study aimed to clarify the significance of exosomal circular RNAs as indicators for AMI. Methods: We examined 120 individuals diagnosed with AMI and 83 individuals with non-cardiogenic chest pain (NCCP), all previously enrolled in a conducted study. High-throughput sequencing to identify differentially expressed circRNAs in the circulating exosomes of AMI patients. To validate, we employed Real-Time polymerase chain reaction (RT-PCR) targeting five circRNAs that exhibited notable increase. Results: The sequencing identified 893 exosomal circRNAs with altered expression in AMI patients, including 118 up-regulated and 775 down-regulated circRNAs. Genes linked to these circRNAs were enriched in crucial Kyoto Encyclopedia of Genes and Genomes (KEGG) pathways, highlighting their direct relevance to AMI pathophysiology. Three exosomal circRNAs (hsa_circ_0001558, hsa_circ_0001535, and hsa_circ_0000972) showed significant up-regulation in AMI patients during the initial validation cohort. The corresponding area under the curve (AUC) values were 0.79, 0.685, and 0.683, respectively. Further validation of hsa_circ_0001558 in a second cohort showed a 4.45-fold increase in AMI patients, with AUC = 0.793. The rise was particularly noticeable in patients with non-ST-elevation myocardial infarction (NSTEMI) (2.80 times, AUC = 0.72) and patients with ST-elevation myocardial infarction (STEMI) (5.27 times, AUC = 0.831) compared to patients with NCCP. Conclusions: Our findings demonstrate significant differences in the expression patterns of circRNAs in plasma exosomes between AMI patients and NCCP patients. Specifically, hsa_circ_0001558 appears as a promising indicator for AMI diagnosis. Further research is necessary to fully evaluate the diagnostic potential of exosomal circRNAs in the context of AMI, emphasizing the importance of these findings.
Salt Tolerance Assessment in Triticum Aestivum and Triticum Durum
Authors: Vasilik Mikhail P. , Belova Natalia I. , Lazareva Elena M. , Kononenko Neonila V. , Fedoreyeva Larisa I.
Published: April 2024

Background: Salt stress is a multicomponent phenomenon; it includes many processes that directly or indirectly affect the plant. Attempts have been made to comprehensively consider the processes of salt stress in plants Triticum aestivum (variety Orenburgskaya 22) and Triticum durum (variety Zolotaya). Methods: The study used methods of light and fluorescence microscopy, methods of immunofluorodetection, expression of DNA methyltransferase genes, genes of the ion transporter and superoxide dismutase families, as well as biochemical determination of total antioxidant activity using the 2,2-diphenyl-1-picrylhydrazyl (DPPH) reagent. Results: According to morphometric indicators, the Orenburgskaya 22 variety showed greater tolerance to the action of 150 mM NaCl than the Zolotaya variety. The level of expression of genes of the HKT ion transporter family in the Orenburgskaya 22 variety is higher than in the Zolotaya variety. It was found that the expression of the DNA methyltransferase gene DRM2.1, which post-translationally methylates cytosine residues, is 22.3 times higher in Zolotaya compared to Orenburg 22 when exposed to salt. The accumulation of toxic ions is accompanied by an increase in reactive oxygen species (ROS) and increased damage to root tissue, especially in the Zolotaya variety. Using fluorescence microscopy using the Carboxy-H2DFF marker in the Orenburgskaya 22 variety at high NaCl concentrations, the highest fluorescence intensity was determined in the cap zone; in the Zolotaya variety—in the zones of the cap and root meristem. Excess ROS is more successfully removed in the Orenburgskaya 22 variety, which has a higher level of antioxidant activity (AOA), as well as the level of expression of the Cu/ZnSOD and MnSOD superoxide dismutase genes. Using programmed cell death (PCD) markers based on the release of cytochrome c from mitochondria into the cytoplasm, DNA breakage and the release of phosphatidylserine from mitochondria, the degree of damage to root cells was assessed in both wheat varieties. It has been proven that wheat cell death occurs through the mitochondrial pathway. It was noted that the salt-sensitive variety Zolotaya had a significant number of necrotic cells. Conclusion: Based on the data obtained, it was concluded that the Orenburgskaya 22 variety exhibits greater resistance to salinity than the Zolotaya variety. These data may be of practical importance for enhancing protective mechanisms under abiotic stress.
Multi-Omics Pan-Cancer Analysis of Procollagen N-Propeptidase Gene Family of ADAMTS as Novel Biomarkers to Associate with Prognosis, Tumor Immune Microenvironment, Signaling Pathways, and Drug Sensitivities
Authors: Chen Yuxing , Xiao Chaoyu , Fan Qingxin , Zhang Ye , Huang Qiu , Ou Yunsheng
Published: April 2024

Background: The extracellular matrix (ECM) modeling induced by the metalloproteinases is a vital characteristic for tumor progression. Previous studies mainly focus on the functions of two subgroups of metalloproteinases: matrix metalloproteinases (MMPs) and a disintegrin and metalloproteases (ADAMs) in tumors. The roles of another important group: the ADAMs with thrombospondin motifs (ADAMTS) remain unclear. This study aimed to perform a pan-cancer analysis of procollagen N-propeptidase subgroup of ADAMTS (PNPSA). Methods: We systematically analyzed expression landscape, genomic variations, prognostic value, and cell expression clusters of PNPSA in pan-cancer based on the multiple integrated open databases. Besides, we also analyzed the impacts of expressions and genomic variations of PNPSA members on tumor immune microenvironment (TIME) and immune-related molecules in pan-cancer based on the immune-related open databases. The Gene Set Variation Analysis (GSVA) was performed to evaluate the associations of the whole PNPSA with prognosis, tumor indicators, TIME, and drug sensitivities. Meanwhile, the Kyoto Encyclopedia of Genes and Genomes (KEGG) was performed to reveal related signaling pathways. Finally, immunohistochemical staining was used to validate the differential analysis results. Results: We found a dual prognostic role of PNPSA members in pan-cancer and they were significantly correlated with TIME and immune-related molecules. Interestingly, the copy number variations (CNVs) of all PNPSA members were revealed to be negatively correlated with NK cell infiltration in most cancers. Single-cell sequencing analysis reveals expressions of PNPSA gene family members on some specific tumor and immune cells in addition to the fibroblasts. The GSVA score was found to have some predictive value for survival status in Brain Lower Grade Glioma (LGG), Mesothelioma (MESO), and Uveal Melanoma (UVM) and to be significantly correlated with tumorigenesis-related pathways such as PI3K-Akt, AGE-RAGE, etc. The GSVA score also shows some predictive value for chemotherapy and immunotherapy efficacy in some tumors. Conclusions: PNPSA was correlated with tumor development and might be potential tumor biomarker and therapeutic target.
Association between Lipid-Lowering Drugs and Traumatic Subdural Hemorrhage: A Mendelian Randomization Study
Authors: Chen Kaiqin , Li He , Chen Yongtai , Huang Hesen , Wei Liangfeng
Published: April 2024

Background: There are current clinical observations that atorvastatin may promote subdural hematoma resorption. We aimed to assess the causal effects of lipid-lowering agents 3-hydroxy-3-methylglutaryl coenzyme A reductase (HMGCR) inhibitors, Proproteinconvertase subtilisin/kexin type 9 (PCSK9) inhibitors and Niemann-Pick C1-like protein 1 (NPC1L1) inhibitors on traumatic subdural hematomas. Methods: We used genetic instruments to proxy lipid-lowering drug exposure, with genetic instruments being genetic variants within or near low-density lipoprotein (LDL cholesterol)-associated drug target genes. These were analyzed by using a two-sample Mendelian randomization (MR) study. Results: A causal relationship was found between HMGCR inhibitors and traumatic subdural hematoma (Inverse variance weighted (β = –0.7593341 (Odds Ratio (OR) = 0.4679779), p = 0.008366947 < 0.05)). However, no causal relationship was found between PCSK9 inhibitors and NPC1L1 inhibitors and traumatic subdural hematoma (PCSK9 inhibitors: Inverse variance weighted (β = 0.23897796 (OR = 1.2699505), p = 0.1126327), NPC1L1 inhibitors: Inverse variance weighted (β = –0.02118558 (OR = 0.9790373), p = 0.9701686)). Sensitivity analysis of the data revealed good stability of the results. Conclusions: This two-sample MR study suggests a potential causal relationship between HMGCR inhibition (atorvastatin) and traumatic subdural hemorrhage.
Thalamic Alterations in Motor Neuron Diseases: A Systematic Review of MRI Findings
Authors: Mohammadi Sana , Ghaderi Sadegh , Mohammadi Mahdi , Najafi Asli Pashaki Zahra , Khatyal Rahim , Mohammadian Fatemeh , Mohammadjani Sahar
Published: April 2024

Background: Motor neuron diseases (MNDs) are progressive neurodegenerative disorders characterized by motor impairment and non-motor symptoms. The involvement of the thalamus in MNDs, especially in conditions such as amyotrophic lateral sclerosis (ALS), and its interaction with frontotemporal dementia (FTD), has garnered increasing research interest. This systematic review analyzed magnetic resonance imaging (MRI) studies that focused on thalamic alterations in MNDs to understand the significance of these changes and their correlation with clinical outcomes. Methods: Following PRISMA 2020 guidelines, the PubMed and Scopus databases were searched from inception to June 2023 for studies related to MRI findings in the thalamus of patients with MNDs. Eligible studies included adult patients diagnosed with ALS or other forms of MND who underwent brain MRI, with outcomes related to thalamic alterations. Studies were evaluated for risk of bias using the Newcastle-Ottawa scale. Results: A total of 52 studies (including 3009 MND patients and 2181 healthy controls) used various MRI techniques, including volumetric analysis, diffusion tensor imaging, and functional MRI, to measure thalamic volume, connectivity, and other alterations. This review confirmed significant thalamic changes in MNDs, such as atrophy and microstructural degradation, which are associated with disease severity, progression, and functional disability. Thalamic involvement varies across different MND subtypes and is influenced by the presence of cognitive impairment and mutations in genes including chromosome 9 open reading frame 72 (C9orf72). The synthesis of findings across studies indicates that thalamic pathology is a prevalent early biomarker of MNDs that contributes to motor and cognitive deficits. The thalamus is a promising target for monitoring as its dysfunction underpins a variety of clinical symptoms in MNDs. Conclusions: Thalamic alterations provide valuable insights into the pathophysiology and progression of MNDs. Multimodal MRI techniques are potent tools for detecting dynamic thalamic changes, indicating structural integrity, connectivity disruption, and metabolic activity.
Immune Ataxias: The Continuum of Latent Ataxia, Primary Ataxia and Clinical Ataxia
Authors: Manto Mario , Mitoma Hiroshi
Published: April 2024

The clinical category of immune-mediated cerebellar ataxias (IMCAs) is now recognized after 3 decades of clinical and experimental research. The cerebellum gathers about 60% of neurons in the brain, is enriched in numerous plasticity mechanisms, and presents a large variety of antigens at the neuroglial level: ion channels and related proteins, synaptic adhesion/organizing proteins, transmitter receptors, and glial cells. Cerebellar circuitry is especially vulnerable to immune attacks. After the loss of immune tolerance, IMCAs present in an acute or subacute manner with various combinations of a vestibulocerebellar syndrome (VCS), a cerebellar motor syndrome (CMS), and a cerebellar cognitive affective syndrome/Schmahmann’s syndrome (CCAS/SS). IMCAs include gluten ataxia (GA), post-infectious cerebellitis (PIC), Miller Fisher syndrome (MFS), paraneoplastic cerebellar degeneration (PCD), opsoclonus myoclonus syndrome (OMS), anti-glutamic acid decarboxylase (anti-GAD) ataxia, and glial fibrillary acidic protein (GFAP) astrocytopathy (GFAP-A). In addition, multiple sclerosis (MS), acute disseminated encephalomyelitis (ADEM), Behçet disease, and collagen-vascular disorders may also present with cerebellar symptoms when lesions involve cerebellar afferences/efferences. Patients whose clinical profiles do not fit with IMCAs are now gathered in the group of primary autoimmune cerebellar ataxias (PACAs). Latent auto-immune cerebellar ataxia (LACA) refers to a clinical stage with a slow progressive course and a lack of obvious auto-immune background. At a pre-symptomatic stage, patients remain asymptomatic, whereas at the prodromal stage aspecific symptoms occur, announcing the symptomatic neuronal loss. LACA corresponds to a time-window where an intervention could lead to preservation of plasticity mechanisms. Patients may evolve from LACA to PACA and typical IMCAs, highlighting a continuum. Immune ataxias represent a model to elucidate the sequence of events leading to destruction of cerebellar neuronal reserve and develop novel strategies aiming to restore plasticity mechanisms.
Role and Mechanism of cGAS-STING Pathway in Cardiovascular System
Authors: Yu Xianqiang , Pan Silin
Published: April 2024

The cyclic guanosine monophosphate-adenosine monophosphate (GMP-AMP) synthase (cGAS)-stimulator of interferon genes (STING) pathway is a part of the innate immune system that plays a role in the cardiovascular system. It acts as a surveillance system, detecting and responding to cytosolic DNA, viral DNA, and other intracellular DNA species. Activation of the cGAS-STING pathway leads to the production of inflammatory cytokines and type I interferons, which are involved in the immune response. In the cardiovascular system, the cGAS-STING pathway has been implicated in various physiological and pathological processes. It contributes to vascular inflammation, atherosclerosis, endothelial dysfunction and cardiac remodeling and heart failure. In this review, we will elaborate on the research progress of the role of cGAS-STING in cardiovascular system.
Pulsed Field Ablation for Atrial Fibrillation: Mechanisms, Advantages, and Limitations
Authors: Jiang Shali , Qian Frank , Ji Shuting , Li Luohong , Liu Qiming , Zhou Shenghua , Xiao Yichao
Published: April 2024

Pulsed field ablation with irreversible electroporation for the treatment of atrial fibrillation involves tissue-specific and non-thermal energy-induced cell necrosis, which helps avoid complications, such as pulmonary vein stenosis, atrial collateral tissue damage, and extensive atrial structural damage, often encountered with traditional thermal ablation. In existing clinical trials, pulsed field ablation has shown excellent effects on pulmonary vein isolation in patients with paroxysmal and persistent atrial fibrillation. Pulsed field ablation is easy, simple, and quick and can reduce iatrogenic injury. Therefore, the application of pulsed field ablation technology in the treatment of atrial fibrillation has a promising future. Notably, the adjustment of parameters in pulsed field ablation with different ablation catheter systems can strongly affect the area and depth of the necrotic myocardium, which greatly affects the likelihood of atrial fibrillation recurrence and incidence of adverse complications after ablation. In this paper, we review the mechanisms, advantages, and limitations of pulsed field ablation based on the results of a series of previous studies and provide ideas and directions for future research.
Effects of Exercise Interventions on Estimated Pulse Wave Velocity and Mean Arterial Pressure in Overweight Adults: The Role of Modality
Authors: Alghanim Sara , Alablani Maha F. , Alqutami Ali , Alotaibi Rawan T. , Jung Hyun Chul , Stoner Lee , Alansare Abdullah B.
Published: April 2024

Background: Estimated pulse wave velocity (ePWV) is mathematically calculated from age and mean arterial pressure (MAP). We examined the effects of high-intensity interval training (HIIT) vs. moderate-intensity continuous training (MICT) on ePWV and MAP in insufficiently active overweight adults. Methods: Using the randomized controlled trial design, thirteen males (27.46 ± 3.80 years old; body mass index (BMI) = 29.61 ± 5.52) randomly completed either two-week HIIT (n = 7) or MICT (n = 6). HIIT consisted of 8 sessions of cycling, 20 min/session with an exercise-to-rest ratio of 10/50 s at ≥90% peak heart rate (HRpeak). MICT consisted of 8 cycling sessions, 40 min/session at 60–75% HRpeak. Oscillometric brachial MAP was measured pre- and post-intervention, and ePWV was calculated. Two-way repeated measure analysis of variance examined the effects of time, intervention, and their interactions on ePWV and MAP. Results: Significant time effects were observed for ePWV and MAP, where both measures comparably decreased over time in HIIT and MICT groups (p < 0.05 for all). However, no significant intervention or interaction effects were detected, indicating no superiority of either exercise modality for ePWV or MAP improvements. Conclusions: This study uniquely revealed that two weeks of HIIT or MICT resulted in significant, comparable, and clinically meaningful decreases in ePWV and MAP among insufficiently active overweight adults. As such, overweight adults who have time as a constraint to engage in traditional exercise (i.e., MICT) can accomplish comparable vascular benefits by performing HIIT.
An Updated Review of the Management of Chronic Heart Failure in Patients with Chronic Kidney Disease
Authors: Tumelty Ella , Chung Isaac , Hussain Sabba , Ali Mahrukh Ayesha , Addada Harshavardhani , Banerjee Debasish
Published: April 2024

Chronic kidney disease (CKD) is common in patients with heart failure (HF) and is associated with high morbidity and mortality. There has been remarkable progress in the treatment of HF over recent years with the establishment of guideline-directed medical therapies including: (1) Beta-blockers, (2) renal angiotensin aldosterone system (RAAS) inhibition (i.e., angiotensin-converting enzyme inhibitor [ACEi], aldosterone receptor blocker [ARB] or angiotensin receptor-neprilysin inhibitor [ARNI]); (3) mineralocorticoid receptor antagonists (MRA), and (4) sodium-glucose cotransporter-2 inhibitors (SGLT2i). However, there are challenges to the implementation of these medications in patients with concomitant CKD due to increased vulnerability to common side-effects (including worsening renal function, hyperkalaemia, hypotension), and most of the pivotal trials which provide evidence of the efficacy of these medications excluded patients with severe CKD. Patients with CKD and HF often have regular healthcare encounters with multiple professionals and can receive conflicting guidance regarding their medication. Thus, despite being at higher risk of adverse cardiovascular events, patients who have both HF and CKD are more likely to be under-optimised on evidence-based therapies. This review is an updated summary of the evidence available for the management of HF (including reduced, mildly reduced and preserved left ventricular ejection fraction) in patients with various stages of CKD. The review covers the evidence for recommended medications, devices such as implantable cardioverter-defibrillator (ICD), cardiac resynchronization therapy (CRT), intravenous (IV) iron, and discusses how frailty affects the management of these patients. It also considers emerging evidence for the prevention of HF in the cohort of patients with CKD. It synthesises the available evidence regarding when to temporarily stop, continue or rechallenge medications in this cohort. Chronic HF in context of CKD remains a challenging scenario for clinicians to manage, which is usually complicated by frailty, multimorbidity and polypharmacy. Treatment should be tailored to a patients individual needs and management in specialised cardio-renal clinics with a multi-disciplinary team approach has been recommended. This review offers a concise summary on this expansive topic.
Hacla İlgili Âyetlerin Tedrîcilik Açısından Değerlendirilmesi
Authors: Arslan Yahya
Published: April 2024

Kur’an-ı Kerim, Levh-i Mahfûz’dan Beytü’l-İzze’ye toptan indirildikten sonra buradan Hz. Peygamber’e (s.a.v.) peyderpey vahyedilmiştir. Takriben 23 yıllık bir zaman dilimini kapsayan vahyin gelişi, insanların ihtiyacı ve maslahatlarına göre, alışkanlıkları ve davranışlarındaki bağımlılık oranları, psikolojik ve sosyolojik algıları dikkate alınarak tedrîcî bir yöntem neticesinde tamamlanmıştır. Allah Teâlâ Kur’an’da emir ve yasaklarını bildirirken kullarının maslahatlarını gözeterek tedrîcilik metodunu kullanmıştır. Kur’an’ın bir anlatım üslûbu olan bu metot içki, faiz gibi yasaklarda; savaş, namaz gibi emirlerde ve ahlakî ilkeler bağlamında yanlış davranışların kaldırılıp doğrularının yerleştirilmesinde en etkili yöntemlerden birisi olmuştur. Tedrîcilik metodunun uygulandığı alanlardan birisi de hac ibadetidir. Hac ibadetiyle ilgili âyetler incelendiğinde hac farz kılınıncaya kadar birkaç aşamanın zikredildiği ortaya çıkmaktadır. Bu meyanda vahyin başlangıcından itibaren uygulanan ve Üslûbü’l-Kur’an’ın bir parçası olan tedrîcilik metodu önem arz etmektedir. Önemine binaen bu çalışmada tedrîciliğin hac ibadetinin farz kılınmasında da uygulandığını dikkatlere sunmak amaçlanmaktadır. Çalışmada literatür tarama yöntemi kullanılmış, hac ibadetiyle ilgili âyetler esas alınmış, bu âyetlerin tefsiri bağlamında klasik ve modern tefsirler taranmıştır. Aynı şekilde hac ibadetine dair yazılmış diğer çalışmalar incelenmiştir. Çalışma; Üslûbü’l-Kur’an, tedrîcilik, hac kavramları ve hacla ilgili âyetlerin hac ibadetinde tedrîcilik bağlamında izahını kapsamaktadır. Neticede tedrîcilik metodunun önemi ve hacla ilgili âyetlerde tedrîcilik metodunun nasıl uygulandığı ortaya konulmaya. Böylece hac ibadetinin tedrîcî bir şekilde meşru kılındığı ispatlanmaya çalışılmıştır.
Ending the Epidemic of Malaria in Nigeria Towards Attaining SDG Target 3.3.3: A Systematic Review of the Progress in Intervention Coverage
Authors: Egharevba Henry Omoregie , Ekpenyong Margaret Idongesit
Published: April 2024

Background: Meeting SDG 3, ‘healthy lives and well-being for all,’ is one of the bedeviling challenges of low-/medium income countries like Nigeria whose health index is adversely impacted by the burden of malaria, an epidemic that seems to have defied all interventions aimed at eliminating it and achieving the SDG target. A confounding problem in the efforts so far is the apparent inability to expand and sustain interventions coverage. This review systematically examines available evidence to determine if the current level of malaria intervention coverage in Nigeria could help achieve the SDG target 3.3.3. Methods: Data were systematically extracted through online search of ProQuest databases and BioMed Central website for publication between 1st January 2015 and 3rd February 2024. Of the 26 potential articles that met the inclusion criteria, 12 were selected for quality assessment using the CASP checklist. Seven of the studies reported coverage for seasonal malaria chemoprevention (SMC), while coverage for insecticide-treated nets (ITNs) or long-lasting insecticide-treated nets (LLINs) interventions was reported by 6 of the publications. One study each reported coverage for indoor-residual spraying (IRS) and rapid diagnostic tests (RDTs). The findings were thematically discussed. Findings: The included studies were 1 systematic review (SR), 7 randomized controlled trials (RCTs) and 4 household or community campaigns/surveys. Apart from one study, all the others raised questions of external validity due to the small sample size. The descriptive statistics of the evidence showed that the mean intervention coverages for SMC, ITNs/LLINs, IRS, and RDTs, were 40.31%, 50.02%, 51.1% and 39.67%, respectively. Conclusion: The current intervention coverage is not adequate to meet the National Malaria Elimination Programme (NMEP) vision/goal of 0:10:5:80:80 and the SDG targets 3.3.3 set for the elimination of malaria by 2025 and 2030, respectively. An incremental minimum annual coverage of about 6.3% is needed over the next 6 years to meet 80% coverage for SMC. The same trajectory is estimated for other intervention components.
Did you say brain or brave? Event-related potentials reveal the central role of phonological prediction in false hearing
Authors: Silcox Jack , Payne Brennan
Published: April 2024

Relying on predictions can help listeners better comprehend acoustically challenging speech. However, when the speech signal does not match what is predicted, a listener can occasionally experience false hearing (e.g., hearing the word “brain” when “brave” was presented). In the current paper, we report two event-related brain potential (ERP) experiments to examine the time-course of false hearing. Target words of three types—semantically congruent/predictable words, semantically incongruent baseline words, or semantically incongruent phonological lures—were presented either in a cue-target pair (Exp. 1) or in a lexically constraining sentence context (Exp. 2). Phonological lures and incongruent baseline words were equally semantically incongruent but phonological lures shared a similar phonological onset with congruent words. Across both experiments, participants routinely experienced false hearing, reporting the congruent word when the phonological lure was presented. In both experiments, we saw that the N400 to words that would go on to be falsely heard more closely resembled the response to congruent words than to correctly identified phonological lures. Additionally, the N400 response to correctly identified phonological lures was significantly delayed compared to the response to incongruent words that shared no phonological relation to congruent words, suggesting the listeners engaged in phonological prediction. Altogether, the findings from the current study provide evidence that listeners’ engagement in phonological prediction can, in some cases, lead to misperception.
Robust Bellman State Prediction with Learning and Model Preferences
Authors: Estey Clayton
Published: April 2024

I contribute to stochastic modeling methodology in a theoretical framework spanning core decisions in the model's lifetime. These are predicting an out-of-sample unit's latent state even from non-series data, deciding when to start and stop learning about the state variable, and choosing models from important trade-offs. States evolve from linear dynamics with time-varying predictors and coefficients (drift) and generalized continuous noise (diffusion). Coefficients must address misprediction costs, data complexity, and distributional uncertainty (ambiguity) about the state's diffusion and stopping time. I exactly solve a stochastic dynamic program robust to worst-case costs from both uncertainties. The Bellman optimal coefficients extend generalized ridge regression by out-of-sample components impacting value changes given state changes. Performance issues trigger sequential analysis whether learning alternative models, given the effort, is better than keeping baseline. Learning is method-general and stops in fewest average attempts within decision errors. I derive preference functions for comparing models with state and cost-change constraints to decide a model, joint-time state and value distributions, and other properties beneficial to modelers.
Changes in Dangerous and Competitive Worldviews During the Coronavirus Epidemic: Evidence from a Large-Scale U.S. Panel Study
Authors: Syropoulos Stylianos , Mah Andrea , Dixon-Gordon Katherine L. , Markowitz Ezra , Nteta Tatishe M. , Reid Allecia , Ginn Joel , Suh Se Min , Ames Daniel Robert , Lickel Brian
Published: April 2024

Extant psychological research has highlighted that perceiving the world as a dangerous or as a competitive place influences major sociopolitical attitudes and ideologies. However, considerably less emphasis has been placed on how these perceptions change over time. We hypothesized that such perceptions of the world might be particularly susceptible to changes during a time of high uncertainty such as the early onset of the COVID-19 pandemic. In a large (N = 1600) and nationally representative sample of the American population, results show that across the span of one year (i.e., the first year of the COVID-19 pandemic), dangerous but not competitive worldviews significantly increased. Results highlight that this increase was significantly larger for conservatives, whites and older Americans. Further, those who endorsed both worldviews highly at T1 (April 2020) reported significantly smaller increases on average at T2 (August 2021), suggesting that the world was perceived as more dangerous and more competitive one year later particularly for those who saw it as safer and more cooperative at the onset of the COVID-19 pandemic. These findings highlight that worldviews are malleable, and that specific demographic characteristics and existing worldview beliefs could influence the degree to which worldviews change across time.
Superordinate referring expressions in abstraction: Introducing the concept-level reference game
Authors: Kobrock Kristina , Uhlemann Charlotte , Gotzner Nicole
Published: April 2024

We study referential communication about concepts at different levels of abstraction in an interactive concept-level reference game. To better understand processes of abstraction, we investigate superordinate referring expressions (animal). Previous work identified two main factors that influence speakers’ choice of referring expressions for concepts: the immediate context and the basic-level effect, i.e. a preference for basic-level terms such as dog. Here we introduce a new concept-level reference game that allows us to study differences in the basic-level effect between comprehension and production and to elicit superordinate referring expressions experimentally. We find that superordinate referring expressions become relevant for groups of objects. Further, we reproduce the basic-level effect in production but not in comprehension. In conclusion, even though basic-level terms are most readily accessible, speakers tailor their expressions to the context, allowing the listener to identify the target concept
A Fair Go? How Belief in a Just World Shaped Attitudes, Intentions, and Behaviours Before and After the Australian Referendum on a First Nations Voice to Parliament
Authors: Bartholomaeus Jonathan , Strelan Peter
Published: April 2024

In October 2023 Australia voted on whether to enshrine in the constitution an Aboriginal and Torres Strait Islander ‘Voice’ to Parliament. Debate around the Voice raised questions of justice and deservingness for a marginalised group within Australian society. The belief in a just world, the perception of fairness in this world for others (BJW-other) and the self (BJW-self), was, therefore, central to how people formed and expressed their opinions. In this longitudinal study (N=253), we examined associations between BJW-other, BJW-self, and attitudes, intentions, and actions towards the Voice before and after the vote. Analysis indicated broadly negative associations between T1 BJW-other and pro Voice outcomes (at both timepoints), while BJW-self was positively related. Findings were, however, inconsistent when controlling for a broad range of socio-political covariates. These findings make an important contribution to justice motive theory by illustrating the role of justice beliefs in the political context.
How explainable AI affects human performance: A systematic review of the behavioural consequences of saliency maps
Authors: Müller Romy
Published: April 2024

Saliency maps can explain how deep neural networks classify images. But are they actually useful for humans? The present systematic review of 68 user studies found that while saliency maps can enhance human performance, null effects or even costs are quite common. To investigate what modulates these effects, the empirical outcomes were organised along several factors related to the human tasks, AI performance, XAI methods, images to be classified, human participants and comparison conditions. In image-focused tasks, benefits were less common than in AI-focused tasks, but the effects depended on the specific cognitive requirements. Moreover, benefits were usually restricted to incorrect AI predictions in AI-focused tasks but to correct ones in image-focused tasks. XAI-related factors had surprisingly little impact. The evidence was limited for image- and human-related factors and the effects were highly dependent on the comparison conditions. These findings may support the design of future user studies.
Bargaining between the sexes: outside options and leisure time in hunter-gatherer households
Authors: Deb Angarika , Saunders Daniel , Major-Smith Daniel , Dyble Mark , Page Abigail Emma , Salali Gul Deniz , Migliano Andrea , Heintz Christophe , Chaudhary Nikhil
Published: April 2024

We discuss gendered division of labour in nuclear households as a bargaining problem, where male and female partners bargain over labour inputs and resulting leisure time. We hypothesize that outside options - an individual’s fallback options for welfare outside their household, such as kin support - affects this bargaining process, providing those with greater outside options more leverage to bargain for leisure time. In two hunter-gatherer populations, the BaYaka and Agta, we take social capital as the determinant of outside options, using a generative model of the Nash bargaining problem and Bayesian multilevel logistic regression to test our hypothesis. We find no evidence for an association between social capital and division of leisure in either population. Instead, we find remarkable equality in the division of leisure time within households. We suggest the potential role of sex-egalitarian norms, non-substitutability of subsistence labour, bilocality and behaviors which maintain gender equality in immediate-return hunter-gatherers.