bluuebunny/crossref_metadata_2025 huggingface dataset:
Identification of core genes in intervertebral disc degeneration using bioinformatics and machine learning algorithms
Authors: Zhang Hao , Shi Shengbo , Huang Xingxing , Gong Changsheng , Zhang Zijing , Zhao Zetian , Gao Junxiao , Zhang Meng , Yu Xiaobing
Published: July 2024

Background

Intervertebral Disc Degeneration (IDD) is a major cause of lower back pain and a significant global health issue. However, the specific mechanisms of IDD remain unclear. This study aims to identify key genes and pathways associated with IDD using bioinformatics and machine learning algorithms.

Methods

Gene expression profiles, including those from 35 LDH patients and 43 healthy volunteers, were downloaded from the GEO database (GSE124272, GSE150408, GSE23130, GSE153761). After merging four microarray datasets, differentially expressed genes (DEGs) were selected for GO and KEGG pathway enrichment analysis. Weighted Gene Co-expression Network Analysis (WGCNA) was then applied to the merged dataset to identify relevant modules and intersect with DEGs to discover candidate genes with diagnostic value. A LASSO model was established to select appropriate genes, and ROC curves were drawn to elucidate the diagnostic value of genetic markers. A Protein-Protein Interaction (PPI) network was constructed and visualized to determine central genes, followed by external validation using qRT-PCR.

Results

Differential analysis of the preprocessed dataset identified 244 genes, including 183 upregulated and 61 downregulated genes. WGCNA analysis revealed the most relevant module intersecting with DEGs, yielding 9 candidate genes. The lasso-cox method was used for regression analysis, ultimately identifying 6 genes: ASPH, CDC42EP3, FOSL2, IL1R1, NFKBIZ, TCF7L2. A Protein-Protein Interaction (PPI) network created with GENEMANIA identified IL1R1 and TCF7L2 as central genes.

Conclusion

Our study shows that IL1R1 and TCF7L2 are the core genes of IDD, offering new insights into the pathogenesis and therapeutic development of IDD.
Overlap of membranous nephropathy and IgA nephropathy in a patient with Kimura’s disease: a case report and literature review
Authors: Barbosa Géssica Sabrine Braga , Neves Precil Diego Miranda de Menezes , Mohrbacher Sara , Abdo André Néder Ramires , Cavalcante Lívia Barreira , Menezes Yara de , Sato Victor Augusto Hamamoto , Oliveira Érico de Souza , Pereira Leonardo Victor Barbosa , Bales Alessandra Martins , Frediani Marcella Martins , Chocair Pedro Renato , Cuvello-Neto Américo Lourenço
Published: July 2024

Introduction

Kimura’s disease (KD) is a rare chronic inflammatory disorder characterized by subcutaneous lymphoid hyperplasia with peripheral eosinophilia. Kidney involvement is reported in 15%–18% of adult patients with KD, in many cases as nephrotic syndrome. We present a case of overlapping membranous nephropathy and IgA nephropathy associated with KD.

Case report

A 27-year-old man was admitted with a history of bilateral leg edema for the last 2 months and concomitant progressive increase of cervical mass and fever. Laboratory findings were as follows: peripheral leukocyte count, 10,080/mm³; eosinophils, 3,200/mm³ (31.7%); serum creatinine, 0.83 mg/dL; and eGFR: 140 mL/min per 1.73 m2. Urinalysis revealed the presence of hematuria and proteinuria and the following results: 24-h proteinuria, 12.9 g; serum albumin, 1.3 g/dL; and elevated IgE level, 750 kU/L. Serologies for hepatitis B, hepatitis C, HIV, and VDRL were all negative. Complement C3 and C4 levels were normal. No monoclonal protein was detected in blood and urine. Parasite infestation was discarded. A biopsy of the cervical lymph node revealed eosinophilic lymphoid hyperplasia, suggesting KD. A kidney biopsy revealed findings consistent with the overlapping of membranous nephropathy with IgA nephropathy. The patient was treated for KD with prednisone 1 mg/kg/d with progressive dose tapering and posterior association of methotrexate 15 mg/week. A renin–angiotensin system inhibitor was prescribed for nephrotic syndrome. The cervical mass regressed, and proteinuria achieved partial remission, with an increase in serum albumin level and normalization of eosinophils and IgE levels.

Conclusion

Although uncommon, kidney involvement must be considered in patients with KD. Glomerular diseases are the most frequent form of kidney injury.
Patient-reported assessment of compassion in Spanish: a systematic review
Authors: Soto-Rubio Ana , Picazo Carmen , Gil-Juliá Beatriz , Andreu-Vaillo Yolanda , Pérez-Marín Marian , Sinclair Shane
Published: July 2024

Aims and objectives

This systematic review aims to: (1) explore which tools have been used in Spanish to measure compassion; (2) know which of these tools could be used to assess compassion in healthcare settings from the perspective of patients; (3) evaluate the quality of these patient-reported measures in Spanish contexts; and (4) determine which of these instruments would be best suited to be used in healthcare settings.

Background

Compassion has been recognized as a fundamental dimension of quality healthcare.

Methods

Several scientific databases were consulted for relevant records published up to December 16th, 2021. In accordance with PRISMA guidelines, 64 studies were included.

Results and conclusions

while existing instruments, validated in Spanish, allow for the measurement of self-compassion or compassion to others, there are no valid and reliable measures currently available in Spanish to measure patient-reported compassion.

Relevance to clinical practice

In order to ensure and promote compassion in the health care context, it is essential to have a valid and reliable tool to measure this construct in a patient-informed way, and this is currently not possible in the Spanish-speaking context because of the lack of such an instrument in Spanish.
Neuroimmune cell interactions and chronic infections in oral cancers
Authors: D’Silva Nisha J. , Pandiyan Pushpa
Published: July 2024

Inflammation is a process that is associated with the activation of distal immunosuppressive pathways that have evolved to restore homeostasis and prevent excessive tissue destruction. However, long-term immunosuppression resulting from systemic and local inflammation that may stem from dysbiosis, infections, or aging poses a higher risk for cancers. Cancer incidence and progression dramatically increase with chronic infections including HIV infection. Thus, studies on pro-tumorigenic effects of microbial stimulants from resident microbiota and infections in the context of inflammation are needed and underway. Here, we discuss chronic infections and potential neuro-immune interactions that could establish immunomodulatory programs permissive for tumor growth and progression.
Impact of alternate partial root-zone irrigation on the rhizosphere microbiota of alfalfa plants inoculated with rhizobia
Authors: Zou Junhong , Xin Jianhui , Wang Tiemei , Song Qing
Published: July 2024

Water is an important constraint on alfalfa (Medicago sativa) production in arid and semiarid areas, and alternate irrigation in root areas has water-saving potential for alfalfa production. To investigate the impact of alternate partial root-zone irrigation (APRI) on the rhizosphere soil microorganisms of alfalfa, this study subjected alfalfa plants to different irrigation methods and irrigation levels. The growth status and rhizosphere soil microbial community diversity of alfalfa plants under alternate root-zone watering treatment were analyzed through laboratory experiments and high-throughput sequencing. The results showed that at soil moisture levels of 80% field moisture capacity (FMC) and 60% FMC, APRI had no significant impact on the biomass or nodule number of alfalfa. However, 40% FMC significantly reduced the individual plant dry weight, chlorophyll content, and nodule number of the alfalfa plants. APRI increased the relative abundance of Actinomycetes in the alfalfa rhizosphere soil. Moreover, at 60% FMC, the MBC and MBN of rhizosphere, relative abundance of Actinobacteria and unclassified K fungi and Chao 1 index of bacteria significantly increased under APRI treatment. While relative abundance of Ascomycetes and Proteobacteria in the alfalfa rhizosphere significantly reduced under 60% FMC + APRI treatment. In summary, under the same irrigation conditions, APRI did not significantly affect the growth of alfalfa in the short term. And 60%FMC + APRI treatment did significantly affect the groups, structure and diversity of the rhizosphere soil microbial communities.
Exploring prebiotic properties and its probiotic potential of new formulations of soy milk-derived beverages
Authors: Rana Ananya , Taneja Neetu Kumra , Raposo António , Alarifi Sehad N. , Teixeira-Lemos Edite , Lima Maria João , Gonçalves João Carlos , Dhewa Tejpal
Published: July 2024

Introduction

The food and beverage industry has shown a growing interest in plant-based beverages as alternatives to traditional milk consumption. Soy milk is derived from soy beans and contains proteins, isoflavones, soy bean oligosaccharides, and saponins, among other ingredients. Because of its high nutritive value and versatility, soy milk has gained a lot of attention as a functional food.

Methods

The present work aims to explore the prebiotic properties and gastrointestinal tolerance potential of new formulations of soy milk-derived drinks to be fermented with riboflavin-producing probiotic Lactiplantibacillus plantarum MTCC (Microbial Type Culture Collection and Gene Bank) 25432, Lactiplantibacillus plantarum MTCC 25433, and Lactobacillus acidophilus NCIM (National Collection of Industrial Microorganisms) 2902 strains.

Results and discussion

The soy milk co-fermented beverage showed highest PAS (1.24 ± 0.02) followed by soy milk beverages fermented with L. plantarum MTCC 25433 (0.753 ± 0.0) when compared to the commercial prebiotic raffinose (1.29 ± 0.01). The findings of this study suggested that the soy milk beverages exhibited potent prebiotic activity, having the ability to support the growth of probiotics, and the potential to raise the content of several bioactive substances. The higher prebiotics activity score showed that the higher the growth rate of probiotics microorganism, the lower the growth of pathogen. For acidic tolerance, all fermented soy milk managed to meet the minimal requirement of 106 viable probiotic cells per milliliter at pH 2 (8.13, 8.26, 8.30, and 8.45 logs CFU/mL, respectively) and pH 3.5 (8.11, 8.07, 8.39, and 9.01 log CFU/mL, respectively). The survival rate of soy milk LAB isolates on bile for 3 h ranged from 84.64 to 89.60%. The study concluded that lactobacilli could thrive in gastrointestinal tract. The sensory evaluation scores for body and texture, color, flavor, and overall acceptability showed a significant difference (p < 0.05) between the fermented probiotic soy milk and control samples. Soy milk fermented with a combination of L. plantarum MTCC 25432 & MTCC 25433 demonstrated the highest acceptability with the least amount of beany flavor. The findings of the study suggest soy milk’s potential in plant-based beverage market.
The impact of oxygen content on Staphylococcus epidermidis pathogenesis in ocular infection based on clinical characteristics, transcriptome and metabolome analysis
Authors: Lv Hongling , Zhang Wenjia , Zhao Zhu , Wei Yingpu , Bao Zhengyilin , Li Yizheng , Hu Zhulin , Deng Deyao , Yuan Wenli
Published: July 2024

Introduction

This study aims to delineate the etiology and prevalence of isolated pathogens, along with the clinical characteristics of endophthalmitis patients over a 9-year period at hospital in Southwest of China. Additionally, we investigating the metabolic and cellular processes related to environmental factors may offer novel insights into endophthalmitis.

Methods

We analyzed data pertaining to endophthalmitis patients treated at the Affiliated Hospital of Yunnan University from 2015 to 2023. According to our clinical data, we conducted an experiment based on transcriptomics and metabolomics analysis to verify whether environmental factors affect behavior of S. epidermidis by culturating S. epidermidis under oxic and microoxic condition.

Results

In this study, 2,712 fungi or bacteria strains have been analyzed, gram-positive bacteria constituted 65.08%, with S. epidermidis being the most predominant species (25.55%). Ophthalmic trauma was the primary pathogenic factor for S. epidermidis ocular infections. Regarding fluoroquinolones, S. epidermidis exhibited the higher resistance rate to levofloxacin than moxifloxacin. Moreover, our investigation revealed that S. epidermidis in microoxic environment increase in energy metabolism, amino acid metabolism, and membrane transport.

Conclusion

Our findings underscore the significance of S. epidermidis as a crucial pathogen responsible for infectious endophthalmitis. It is crucial to exercise vigilance when considering Levofloxacin as the first-line drug for empiric endophthalmitis treatment. The metabolites alteration observed during the commensal-to-pathogen conversion under microoxic condition serve as a pivotal environmental signal contributing to S. epidermidis metabolism remodeling, toward more pathogenic state.
Structure-guided discovery of novel AflG inhibitors for aflatoxin contamination control in aspergillus flavus
Authors: Wang Fenghua , Zhou Weijie , Yang Maohua , Niu Jinlu , Huang Wenjie , Chen Zhaofu , Chen Yuanyuan , Wang Dongdong , Zhang Jun , Wu Shaowen , Yan Shijuan
Published: July 2024

Aflatoxins (AFs) are highly carcinogenic metabolites produced by Aspergillus species that can contaminate critical food staples, leading to significant health and economic risks. The cytochrome P450 monooxygenase AflG catalyzes an early step in AF biosynthesis, resulting in the conversion of averantin (AVN) to 5′-hydroxy-averantin. However, the molecular mechanism underlying the AflG-AVN interaction remains unclear. Here, we sought to understand the structural features of AflG in complex with AVN to enable the identification of inhibitors targeting the AflG binding pocket. To achieve this goal, we employed a comprehensive approach combining computational and experimental methods. Structural modeling and microsecond-scale molecular dynamics (MD) simulations yielded new insights into AflG architecture and unveiled unique ligand binding conformations of the AflG-AVN complex. High-throughput virtual screening of more than 1.3 million compounds pinpointed specific subsets with favorable predicted docking scores. The resulting compounds were ranked based on binding free energy calculations and evaluated with MD simulations and in vitro experiments with Aspergillus flavus. Our results revealed two compounds significantly inhibited AF biosynthesis. Comprehensive structural analysis elucidated the binding sites of competitive inhibitors and demonstrated their regulation of AflG dynamics. This structure-guided pipeline successfully enabled the identification of novel AflG inhibitors and provided novel molecular insights that will guide future efforts to develop effective therapeutics that prevent AF contamination.
Prion protein E219K polymorphism: from the discovery of the KANNO blood group to interventions for human prion disease
Authors: Wang Si-Si , Meng Zhao-Li , Zhang Yi-Wen , Yan Yi-Shuang , Li Ling-Bo
Published: July 2024

KANNO is a new human blood group that was recently discovered. The KANNO antigen shares the PRNP gene with the prion protein and the prion protein E219K polymorphism determines the presence or absence of the KANNO antigen and the development of anti-KANNO alloantibodies. These alloantibodies specifically react with prion proteins, which serve as substrates for conversion into pathological isoforms in some prion diseases and may serve as effective targets for resisting prion infection. These findings establish a potential link between the KANNO blood group and human prion disease via the prion protein E219K polymorphism. We reviewed the interesting correlation between the human PRNP gene’s E219K polymorphism and the prion proteins it expresses, as well as human red blood cell antigens. Based on the immune serological principles of human blood cells, the prion protein E219K polymorphism may serve as a foundation for earlier molecular diagnosis and future drug development for prion diseases.
Gender effect in human–machine communication: a neurophysiological study
Authors: Ding Yi , Guo Ran , Lyu Wei , Zhang Wengang
Published: July 2024

Purpose

This study aimed to investigate the neural mechanism by which virtual chatbots' gender might influence users' usage intention and gender differences in human–machine communication.

Approach

Event-related potentials (ERPs) and subjective questionnaire methods were used to explore the usage intention of virtual chatbots, and statistical analysis was conducted through repeated measures ANOVA.

Results/findings

The findings of ERPs revealed that female virtual chatbots, compared to male virtual chatbots, evoked a larger amplitude of P100 and P200, implying a greater allocation of attentional resources toward female virtual chatbots. Considering participants' gender, the gender factors of virtual chatbots continued to influence N100, P100, and P200. Specifically, among female participants, female virtual chatbots induced a larger P100 and P200 amplitude than male virtual chatbots, indicating that female participants exhibited more attentional resources and positive emotions toward same-gender chatbots. Conversely, among male participants, male virtual chatbots induced a larger N100 amplitude than female virtual chatbots, indicating that male participants allocated more attentional resources toward male virtual chatbots. The results of the subjective questionnaire showed that regardless of participants' gender, users have a larger usage intention toward female virtual chatbots than male virtual chatbots.

Value

Our findings could provide designers with neurophysiological insights into designing better virtual chatbots that cater to users' psychological needs.
Robust gesture recognition based on attention-deep fast convolutional neural network and surface electromyographic signals
Authors: Lin Chuang , Wang Yuhao , Dai Ming
Published: July 2024

The surface electromyographic (sEMG) signals reflect human motor intention and can be utilized for human-machine interfaces (HMI). Comparing to the sparse multi-channel (SMC) electrodes, the high-density (HD) electrodes have a large number of electrodes and compact space between electrodes, which can achieve more sEMG information and have the potential to achieve higher performance in myocontrol. However, when the HD electrodes grid shift or damage, it will affect gesture recognition and reduce recognition accuracy. To minimize the impact resulting from the electrodes shift and damage, we proposed an attention deep fast convolutional neural network (attention-DFCNN) model by utilizing the temporary and spatial characteristics of high-density surface electromyography (HD-sEMG) signals. Contrary to the previous methods, which are mostly base on sEMG temporal features, the attention-DFCNN model can improve the robustness and stability by combining the spatial and temporary features. The performance of the proposed model was compared with other classical method and deep learning methods. We used the dataset provided by The University Medical Center Göttingen. Seven able-bodied subjects and one amputee involved in this work. Each subject executed nine gestures under the electrodes shift (10 mm) and damage (6 channels). As for the electrodes shift 10 mm in four directions (inwards; onwards; upwards; downwards) on seven able-bodied subjects, without any pre-training, the average accuracy of attention-DFCNN (0.942 ± 0.04) is significantly higher than LSDA (0.910 ± 0.04, p < 0.01), CNN (0.920 ± 0.05, p < 0.01), TCN (0.840 ± 0.07, p < 0.01), LSTM (0.864 ± 0.08, p < 0.01), attention-BiLSTM (0.852 ± 0.07, p < 0.01), Transformer (0.903 ± 0.07, p < 0.01) and Swin-Transformer (0.908 ± 0.09, p < 0.01). The proposed attention-DFCNN algorithm and the way of combining the spatial and temporary features of sEMG signals can significantly improve the recognition rate when the HD electrodes grid shift or damage during wear.
Causal relationships involving brain imaging-derived phenotypes based on UKB imaging cohort: a review of Mendelian randomization studies
Authors: Wang Mengdong , Wang Zirui , Wang Yaoyi , Zhou Quan , Wang Junping
Published: July 2024

The UK Biobank (UKB) has the largest adult brain imaging dataset, which encompasses over 40,000 participants. A significant number of Mendelian randomization (MR) studies based on UKB neuroimaging data have been published to validate potential causal relationships identified in observational studies. Relevant articles published before December 2023 were identified following the PRISMA protocol. Included studies (n = 34) revealed that there were causal relationships between various lifestyles, diseases, biomarkers, and brain image-derived phenotypes (BIDPs). In terms of lifestyle habits and environmental factors, there were causal relationships between alcohol consumption, tea intake, coffee consumption, smoking, educational attainment, and certain BIDPs. Additionally, some BIDPs could serve as mediators between leisure/physical inactivity and major depressive disorder. Regarding diseases, BIDPs have been found to have causal relationships not only with Alzheimer’s disease, stroke, psychiatric disorders, and migraine, but also with cardiovascular diseases, diabetes, poor oral health, osteoporosis, and ankle sprain. In addition, there were causal relationships between certain biological markers and BIDPs, such as blood pressure, LDL-C, IL-6, telomere length, and more.
Transcutaneous auricular vagus nerve stimulation modulates masseter muscle activity, pain perception, and anxiety levels in university students: a double-blind, randomized, controlled clinical trial
Authors: Ferreira Luciano Maia Alves , Brites Ricardo , Fraião Gonçalo , Pereira Gonçalo , Fernandes Henrique , de Brito José Américo Almeida , Pereira Generoso Laura , Maziero Capello Maria Gabriela , Pereira Gabrielly Santos , Scoz Robson Dias , Silva Josie Resende Torres , Silva Marcelo Lourenço
Published: July 2024

Introduction

Chronic anxiety is a statemarked by sustained activation of the masseter muscle, manifesting in both mental and physical strain. This prolonged tension can significantly impact mental wellbeing and cognitive abilities, posing a risk for a range of health complications. This double-blind, randomized, controlled clinical trial investigated the impact of transcutaneous auricular vagus nerve stimulation (TAVNS) on masseter muscle activity, pressure pain threshold (PPT), and anxiety levels in university students with elevated anxiety.

Methods

Forty-two participants meeting inclusion criteria were randomly assigned to either active TAVNS or sham TAVNS groups. Various parameters, including masseter muscle electromyographic (EMG) signals, PPT, and Beck Anxiety Inventory (BAI) scores, were assessed before pretreatment, immediately after the intervention week, and 2 weeks follow-up.

Results

Active TAVNS significantly reduced both left and right masseter activation during resting mandibular position, persisting for 2 weeks post-intervention. Additionally, TAVNS induced a lasting decrease in both left and right masseter PPT, indicative of altered pain perception. Notably, BAI scores showed a substantial reduction, emphasizing TAVNS as a potential intervention for anxiety, with effects maintained at the 2-week follow-up.

Discussion

This study provides comprehensive insights into the multifaceted effects of TAVNS on physiological and psychological aspects associated with anxiety in university students. The promising results underscore TAVNS as a potential neuromodulatory intervention for anxiety-related conditions, warranting further research and clinical exploration.

Clinical Trial Registration

https://ensaiosclinicos.gov.br/rg/RBR-4s4kt2r.
Lupeol protect against LPS-induced neuroinflammation and amyloid beta in adult mouse hippocampus
Authors: Choe Kyonghwan , Park Jun Sung , Park Hyun Young , Tahir Muhammad , Park Tae Ju , Kim Myeong Ok
Published: July 2024

Neuroinflammation includes the activation of immune glial cells in the central nervous system, release pro-inflammatory cytokines, which disrupt normal neural function and contribute to various neurological disorders, including Alzheimer’s disease (AD), Parkinson’s disease, multiple sclerosis, and stroke. AD is characterized by various factors including amyloidogenesis, synaptic dysfunction, memory impairment and neuroinflammation. Lipopolysaccharide (LPS) constitutes a vital element of membrane of the gram-negative bacterial cell, triggering vigorous neuroinflammation and facilitating neurodegeneration. Lupeol, a naturally occurring pentacyclic triterpene, has demonstrated several pharmacological properties, notably its anti-inflammatory activity. In this study, we evaluated the anti-inflammatory and anti-Alzheimer activity of lupeol in lipopolysaccharide (LPS)-injected mice model. LPS (250ug/kg) was administered intraperitoneally to C57BL/6 N male mice for 1 week to induce neuroinflammation and cognitive impairment. For biochemical analysis, acetylcholinesterase (AChE) assay, western blotting and confocal microscopy were performed. AChE, western blot and immunofluorescence results showed that lupeol treatment (50 mg/kg) along with LPS administration significantly inhibited the LPS-induced activation of neuroinflammatory mediators and cytokines like nuclear factor (NF-κB), tumor necrosis factor (TNF-α), cyclooxygenase (COX-2) and interleukin (IL-1β). Furthermore, we found that LPS-induced systemic inflammation lead to Alzheimer’s symptoms as LPS treatment enhances level of amyloid beta (Aβ), amyloid precursor protein (APP), Beta-site APP cleaving enzyme (BACE-1) and hyperphosphorylated Tau (p-Tau). Lupeol treatment reversed the LPS-induced elevated level of Aβ, APP, BACE-1 and p-Tau in the hippocampus, showing anti-Alzheimer’s properties. It is also determined that lupeol prevented LPS-induced synaptic dysfunction via enhanced expression of pre-and post-synaptic markers like SNAP-23, synaptophysin and PSD-95. Overall, our study shows that lupeol prevents memory impairment and synaptic dysfunction via inhibition of neuroinflammatory processes. Hence, we suggest that lupeol might be a useful therapeutic agent in prevention of neuroinflammation-induced neurological disorders like AD.
Molecular characteristics and immune microenvironment of gastrointestinal stromal tumours: targets for therapeutic strategies
Authors: Yu Yang , Yu Mengdie , Luo Lijie , Zhang Zijing , Zeng Haiping , Chen Yan , Lin Zeyu , Chen Mengnan , Wang Wei
Published: July 2024

Gastrointestinal stromal tumours (GISTs) are the most common mesenchymal tumours, arising mainly from the interstitial cells of Cajal (ICCs) of the gastrointestinal tract. As radiotherapy and chemotherapy are generally ineffective for GISTs, the current primary treatment is surgical resection. However, surgical resection is not choice for most patients. Therefore, new therapeutic strategies are urgently needed. Targeted therapy, represented by tyrosine kinase inhibitors (TKIs), and immunotherapy, represented by immune checkpoint inhibitor therapies and chimeric antigen receptor T-cell immunotherapy (CAR-T), offer new therapeutic options in GISTs and have shown promising treatment responses. In this review, we summarize the molecular classification and immune microenvironment of GISTs and discuss the corresponding targeted therapy and immunotherapy options. This updated knowledge may provide more options for future therapeutic strategies and applications in GISTs.
A case for the study of native extracellular vesicles
Authors: Nambiar Dhanya , Le Quynh-Thu , Pucci Ferdinando
Published: July 2024

Three main areas of research revolve around extracellular vesicles (EVs): their use as early detection diagnostics for cancer prevention, engineering of EVs or other enveloped viral-like particles for therapeutic purposes and to understand how EVs impact biological processes. When investigating the biology of EVs, it is important to consider strategies able to track and alter EVs directly in vivo, as they are released by donor cells. This can be achieved by suitable engineering of EV donor cells, either before implantation or directly in vivo. Here, we make a case for the study of native EVs, that is, EVs released by cells living within a tissue. Novel genetic approaches to detect intercellular communications mediated by native EVs and profile recipient cells are discussed. The use of Rab35 dominant negative mutant is proposed for functional in vivo studies on the roles of native EVs. Ultimately, investigations on native EVs will tremendously advance our understanding of EV biology and open novel opportunities for therapy and prevention.
The role of cGAS in epithelial dysregulation in inflammatory bowel disease and gastrointestinal malignancies
Authors: Ramos Anna , Bizri Nazih , Novak Elizabeth , Mollen Kevin , Khan Sidrah
Published: July 2024

The gastrointestinal tract is lined by an epithelial monolayer responsible for selective permeability and absorption, as well as protection against harmful luminal contents. Recognition of foreign or aberrant DNA within these epithelial cells is, in part, regulated by pattern recognition receptors such as cyclic GMP-AMP synthase (cGAS). cGAS binds double-stranded DNA from exogenous and endogenous sources, resulting in the activation of stimulator of interferon genes (STING) and a type 1 interferon response. cGAS is also implicated in non-canonical pathways involving the suppression of DNA repair and the upregulation of autophagy via interactions with PARP1 and Beclin-1, respectively. The importance of cGAS activation in the development and progression of inflammatory bowel disease and gastrointestinal cancers has been and continues to be explored. This review delves into the intricacies of the complex role of cGAS in intestinal epithelial inflammation and gastrointestinal malignancies, as well as recent therapeutic advances targeting cGAS pathways.
Anti-hyperglycemic effects of Cissus quadrangularis extract via regulation of gluconeogenesis in type 2 diabetic db/db mice
Authors: Kim Jeong-Won , Jeong Ji-Soo , Kim Jin-Hwa , Chung Eun-Hye , Kim Chang-Yeop , Lee Dong-Ryung , Choi Bong-Keun , Lim Jong-Hwan , Ko Je-Won , Kim Tae-Won
Published: July 2024

Introduction:Cissus quadrangularis is a vining plant widely used as a traditional herbal remedy for various ailments. In this study, the therapeutic effects of C. quadrangularis extract (CQR-300) on type 2 diabetes mellitus (T2DM) were investigated in a leptin receptor-mutated db/db mouse model.

Methods: CQR-300 was orally administered to db/db mice (n = 6/group) at different doses (50, 100, and 200 mg/kg) for 8 weeks. Blood glucose levels and oral glucose tolerance were assessed using the AccuCheck glucometer. Enzyme-linked immunosorbent assay was performed to evaluate insulin and hemoglobin A1c (HbA1c) levels in the blood of db/db mice. Liver and pancreatic tissues from db/db mice were examined by hematoxylin and eosin (H&E) and immunohistochemical staining. The protein levels of gluconeogenesis-, lipogenesis-, and oxidative stress-related factors were evaluated using western blotting.

Results and discussion: CQR-300 treatment effectively reduced body weight, blood glucose, and insulin levels. HbA1c levels were increased by leptin receptor mutation. Additionally, in the oral glucose tolerance tests, the CQR-300 treated group had a faster blood glucose recovery rate than the db/db group. H&E and Oil red-O staining of the liver showed decreased lipid accumulation in the CQR-300 treated group than the db/db group. Western blot analysis confirmed that CQR-300 effectively inhibited gluconeogenesis, lipogenesis, and oxidative stress-related factors. Our findings suggest that CQR-300 has the potential to be used as a T2DM supplement.
COE targets EphA2 to inhibit vasculogenic mimicry formation induced by hypoxia in hepatocellular carcinoma
Authors: Chen Jue , Dai Shu-Ying , Wu Su , Wu Meng-Ke , Yu Ke-Ke , Liu Jun-Chi , Chang Jia-Yu , Liu Yan-Qing
Published: July 2024

Background

Vasculogenic Mimicry (VM) can reduce the efficacy of anti-angiogenesis and promote distant metastasis in hepatocellular carcinoma (HCC). Our previous studies have found that Celastrus orbiculatus extract (COE) can inhibit the VM formation in HCC by reducing EphA2 expression. However the underlying mechanism related to EphA2 in VM formation is unclear.

Purpose

This study aimed to confirm that EphA2 is one of the potential targets of COE, and to explore the effect of EphA2 in VM formation in hypoxia context in HCC.

Methods

TCM Systems Pharmacology database and proteomics analysis were used to explore the key targets of COE in HCC treatment. CD31-PAS double staining and VE-CAD staining were used to indicate vasculogenic mimicry. The localization of EphA2 and VE-CAD was examined through fluorescent microscopy. CCK8 assay, cell invasion assay, and tube formation assay were used to indicate the formation of VM under hypoxic conditions. The regulatory relationship of EphA2 upstream and downstream molecules were evaluated through COIP and Western Blot. The nude mouse xenograft tumor models were used to observe the VM formation after knocking down or overexpressing EphA2.

Results

EphA2 is identified to the target of COE, and the driving gene of HCC. In HCC surgical specimens, EphA2 expression is closely associated with the VM formation of HCC. COE-regulated EphA2 is involved in hypoxia-induced VM formation in HCC cells in vitro. EphA2 is regulated by HIF directly or indirectly by C-MYC. Overexpression of EphA2 can promote the VM formation of HCC in nude mice, while knocking down EphA2 can inhibit the VM formation.

Conclusion

EphA2, as a target of COE, plays a crucial regulatory role in the formation of vasculogenic mimicry in HCC, involving upstream HIF/MYC transcriptional promotion and downstream PI3K/FAK/VE-CAD expression regulation.
Predicting the impact of climate change and land use change on the potential distribution of two economic forest trees in Northeastern China
Authors: Lin Xiaokun , Chang Baoliang , Huang Yanqing , Jin Xin
Published: July 2024

Young shoots of Aralia elata and young leaves of Eleutherococcus senticosus are two major non-timber forest products in northeastern China. However, human activities and climate change have resulted in serious threats to the habitats of two trees, which greatly limits resource conservation and exploitation of economic forest trees. We used the MaxEnt model to predict the suitable habitats of the two economic trees and analyzed the dominant factors affecting their distribution. The results showed that the suitable habitat areas of A. elata and E. senticosus in the current period were 159950 km2 and 123449 km2, respectively, and the suitable habitats of both economic forest trees were located in the eastern part of the northeast region. Climate factors (Annual precipitation, Precipitation Seasonality) and land use factors are important variables influencing changes in suitable habitat for both trees. With the change of climate and land use in the future, the overall trend of suitable habitat for both economic forest trees shows a northward and then a southward migration. These results may provide assistance in developing strategies for resource conservation and sustainable use of A. elata and E. senticosus, and we suggest that stable and suitable habitats should be selected as areas for in situ conservation and breeding of the two economic forest trees.
Substantial parallel mediation contribution by cognitive domains in the relationship between adolescents’ physical fitness and academic achievements: the Cogni-Action Project
Authors: Cristi-Montero Carlos , Martínez-Flores Ricardo , Espinoza-Puelles Juan Pablo , Doherty Anya , Zavala-Crichton Juan Pablo , Aguilar-Farias Nicolas , Reyes-Amigo Tomas , Salvatierra-Calderon Vanessa , Ibáñez Romualdo , Sadarangani Kabir P.
Published: July 2024

Objective

To determine how cognitive domains mediate the link between fitness components, their global score (GFS), and adolescents’ academic achievement (ACA) across various school subjects.

Methods

In this study, 1,296 adolescents aged 10–14 participated. GFS was computed by three fitness components (strength, muscular, and cardiorespiratory fitness) through the ALPHA-fitness test battery. ACA was determined by five school subjects (Language, English, Mathematics, Science, and History) and two academic scores (a) “Academic Average” (five subjects) and (b) “Academic-PISA” (Language, Mathematics, and Science). A principal component analysis was performed to establish four factors (working memory [WM], cognitive flexibility [CF], inhibitory control [IC], and fluid reasoning [FR]). A parallel mediation approach was implemented with 5,000 bootstrapped samples controlled for sex, maturity, central obesity, having breakfast before cognitive tasks, schools, and school vulnerability. Total, direct, indirect effects, and mediation percentages were estimated.

Results

Overall, the finding showed a full parallel mediation effect for Language (92.5%) and English (53.9%), while a partial mediation for Mathematics (43.0%), Science (43.8%), History (45.9%), “Academic Average” (50.6%), and “Academic-PISA” (51.5%). In particular, WM, IC, and FR mediated all school subjects except mathematics, where IC was not significant. CF has not mediated any relationship between GF and academic performance.

Conclusion

This study underscores the pivotal role of cognitive domains, specifically WM, IC, and FR, in mediating the link between physical fitness and academic performance in adolescents. These insights have relevant implications for educational and public health policies.
Pre- and post-pandemic risk perceptions and worries
Authors: Wolff Katharina , Larsen Svein
Published: July 2024

Introduction

The present study is a cross-sectional investigation of worry and risk perceptions regarding various hazards and destinations, measured before, during, and after the COVID-19 pandemic.

Methods

Questionnaire data were collected from tourists in Norway during the summer seasons of 2012 (N = 2,669), 2019 (N = 1,666), and 2022 (N = 956), and from a representative sample of Norwegians in 2020 (N = 1,003).

Results

The results show a general decline in the level of worry and risk perceptions post-pandemic compared to those pre-pandemic, with the exception of infectious diseases, whose perceived risk slightly increased in 2022.

Conclusion

The results highlight the importance of employing cross-sectional or longitudinal data to investigate changes in risk perceptions over time. The findings also indicate that pessimistic predictions of a continued decline in tourism appear to be unwarranted.
Administrative regulation-informed analysis of the developmental path of national volume-based procurement to improve drug accessibility in China
Authors: Lu Songxin , Liu Xiangdong , Huang Zhengzong , Zhou Zhiheng , Feng Zehua
Published: July 2024

Introduction

The procurement of medicines via China’s national volume-based procurement (NVBP) necessitates collaboration among various entities. This paper highlights the legal significance of the engagement of pharmaceutical companies, hospitals, and the National Healthcare Security Administration (NHSA) in improving drug accessibility.

Methods

We conducted a numerical simulation using MATLAB to develop an evolutionary game model involving these three participants in NVBP.

Results

Our findings indicate that the final evolutionary stabilization strategies are pharmaceutical companies actively participating, hospitals using bid-winning medicines, and the NHSA implementing a low-intensity intervention. The study reveals that the evolutionary outcomes for hospitals and pharmaceutical companies are significantly affected by factors such as NHSA’s subsidy level and pharmaceutical companies’ level of participation. However, NHSA’s decision-making process is less influenced by these factors.

Discussion

From a legal perspective, the successful implementation of NVBP, ensuring fairness and legality, requires adherence to relevant policies and regulations. The NHSA should employ statutory incentives and regulatory methods in formulating and adjusting NVBP policy to enable pharmaceutical companies, hospitals, and the NHSA to exercise their rights rationally within the legal framework of the game process.
Race science without racists: how bigoted paradigms persist in allergy research
Authors: Myles Ian A.
Published: July 2024

In the wake of the murder of George Floyd and the massacre in Buffalo, the editorial boards of the prominent scientific publication companies formally apologized for their journals’ historical role in advancing race science and promised to improve their standards. However, flowery commentaries cannot undo the consistent pattern of endorsing biologic differences between ethnic groups, even when discussing diseases or traits that are not considered politically charged. In this report, an exemplar is made of a recent publication claiming to identify phenotypes of atopic dermatitis that are distinct between European Americans, Asians, and African Americans. The insufficiency of the evidence and logic underlying these claims are discussed. Although devoid of malice, numerous publications continue to demonstrate how claims of biological differences between races is mainstreamed in modern scientific publications. Overall, the goal of this work is to challenge the scientific community, particularly the publication companies, to evaluate how assumptions of innate biologic disadvantage have clouded assessments of racial disparities in disease beyond the topics that are more stereotypical of race science.
Serotype distribution of invasive pneumococcal disease from countries of the WHO Africa, Americas, Eastern Mediterranean, South-East Asia, and Western Pacific regions: a systematic literature review from 2010 to 2021
Authors: Fletcher Mark A. , Daigle Derek , Siapka Mariana , Baay Marc , Hanquet Germaine , del Carmen Morales Graciela
Published: July 2024

Background

Most publications on invasive pneumococcal disease (IPD) serotype distribution are from about 20 countries (Australia, Canada, China, European Union members, Japan, New Zealand, South Korea, and USA). Here, we reviewed the literature among underrepresented countries in the Americas (AMRO), Africa (AFRO), Eastern Mediterranean (EMRO), South-East Asia (SEARO), and Western Pacific (WPRO) WHO regions.

Methods

We performed a systematic review of the most recent IPD serotype surveillance publications (from 01/01/2010 to 31/12/2021, Medline/Embase) in those WHO regions. Selection criteria were delineated by contemporality, within-country geographical scope, and number of samples. Reported serotype distributions for each country were stratified by age group, pneumococcal conjugate vaccine (PCV) serotype category (considering undifferentiated serotypes), and PCV program period (pre-PCV, intermediate, or PCVhv [higher valency PCV formulation]). Pre-PCV period pooled data estimated PCV serotype category distribution by age group across WHO regions, while for the PCVhv period, country-level dataset tables were prepared.

Results

Of 2,793 publications screened, 107 were included (58 pediatric, 11 adult, 37 all ages, and one comprising every age group). One-third of eligible countries (51/135) published serotype distribution, ranging from 30 to 43% by WHO region. Considering number of samples per WHO region, a few countries prevailed: AMRO (Brazil), AFRO (South Africa, Malawi, and Burkina Faso), and WPRO (Taiwan). In the pre-PCV period, PCV13 formulation serotypes predominated: ranging from 74 to 85% in children and 58–86% in adults in the different WHO regions. The PCVhv period represented half of the most recent IPD surveillance by countries (26/51). Undifferentiated serotypes represented >20% of IPD from most countries (34/51).

Conclusion

Ubiquity of undifferentiated serotypes among the publications could constrain estimates of PCV program impact and of serotype coverage for newer PCVhv formulations; consequently, we recommend that countries favor techniques that identify serotypes specifically and, rather than reporting PCV formulation serotype distributions, provide serotype results individually.

Systematic review registration

The protocol has been prospectively registered at PROSPERO, identifier: CRD42021278501. https://www.crd.york.ac.uk/prospero/display_record.php?RecordID=278501.
One-year post-acute COVID-19 syndrome and mortality in South Korea: a nationwide matched cohort study using claims data
Authors: Won Jung-Hyun , Hong Yesol , Kim Siun , Lee Howard
Published: July 2024

Background

Current understanding of post-COVID-19 syndrome in South Korea is primarily based on survey studies or research targeting specific patient groups, such as those hospitalized. Moreover, the majority of relevant studies have been conducted in European and North American populations, which may limit their applicability to the South Korean context. To address this gap, our study explores the one-year outcomes of COVID-19, focusing on the potential post-acute syndrome and all-cause mortality in South Korea.

Methods

This retrospective cohort study used nationwide claims data in South Korea, including adults aged >18 with records between January 20, 2020, and February 25, 2021. Patients were classified into COVID-19 and non-COVID-19 groups and matched 1:1 based on propensity scores. Primary outcomes were 12-month post-acute COVID-19 syndrome and all-cause mortality.

Results

The study involved 34,802 matched patients. The COVID-19 group had significantly elevated risks of coagulopathies (OR = 2.70 [2.24, 3.28]; p < 0.001), chronic lower respiratory diseases (OR = 1.96 [1.80, 2.14]; p < 0.001), symptoms of the circulatory and respiratory systems (OR = 1.91 [1.80, 2.04]; p < 0.001), mood disorders (OR = 1.67 [1.51, 1.86]; p < 0.001), cardiac diseases (OR = 1.39 [1.21, 1.59]; p < 0.001), and symptoms of cognition, perception, emotional state, and behavior (OR = 1.15 [1.04, 1.27]; p = 0.005). All-cause mortality was higher in the COVID-19 group during the 6 months (OR = 1.34 [1.06, 1.69]; p = 0.015), but gradually decreased, reaching an OR of 0.996 ([0.83, 1.19]; p = 0.964) at 1 year.

Conclusion

In South Korea, the 12-month post-acute COVID-19 syndrome includes coagulopathies, respiratory issues, mood disorders, and cardiac diseases. The risk of all-cause mortality post-COVID-19 is heightened for up to 6 months, then significantly decreases and resolves within a year.