bluuebunny/crossref_metadata_2025_split huggingface dataset:
Exploring the relationship between lactate metabolism and immunological function in colorectal cancer through genes identification and analysis
Authors: Zhang Enkui , Zhou Xueliang , Fan Xiaodong , Li Shuchun , Ding Chengsheng , Hong Hiju , Aikemu Batuer , Yang Guang , Yesseyeva Galiya , Yang Xiao , Ma Junjun , Zheng Minhua 
Published: August 2023

Introduction: Metabolic dysregulation is a widely acknowledged contributor for the development and tumorigenesis of colorectal cancer (CRC), highlighting the need for reliable prognostic biomarkers in this malignancy.Methods: Herein, we identified key genes relevant to CRC metabolism through a comprehensive analysis of lactate metabolism-related genes from GSEA MsigDB, employing univariate Cox regression analysis and random forest algorithms. Clinical prognostic analysis was performed following identification of three key genes, and consistent clustering enabled the classification of public datasets into three patterns with significant prognostic differences. The molecular pathways and tumor microenvironment (TME) of these patterns were then investigated through correlation analyses. Quantitative PCR was employed to quantify the mRNA expression levels of the three pivotal genes in CRC tissue. Single-cell RNA sequencing data and fluorescent multiplex immunohistochemistry were utilized to analyze relevant T cells and validate the correlation between key genes and CD4+ T cells.Results: Our analysis revealed that MPC1, COQ2, and ADAMTS13 significantly stratify the cohort into three patterns with distinct prognoses. Additionally, the immune infiltration and molecular pathways were significantly different for each pattern. Among the key genes, MPC1 and COQ2 were positively associated with good prognosis, whereas ADAMTS13 was negatively associated with good prognosis. Single-cell RNA sequencing (scRNA-seq) data illustrated that the relationship between three key genes and T cells, which was further confirmed by the results of fluorescent multiplex immunohistochemistry demonstrating a positive correlation between MPC1 and COQ2 with CD4+ T cells and a negative correlation between ADAMTS13 and CD4+ T cells.Discussion: These findings suggest that the three key lactate metabolism genes, MPC1, COQ2, and ADAMTS13, may serve as effective prognostic biomarkers and support the link between lactate metabolism and the immune microenvironment in CRC.
Antimicrobial activity of dietary supplements based on bacterial lysate of Lactobacillus rhamnosus DV
Authors: Penchuk Yurii , Savytska Maryana , Kobyliak Nazarii , Ostapchenko Danylo , Kolodiy Igor , Onysenko Svitlana , Tsyryuk Olena , Korotkyi Oleksandr , Grygoriev Fedir , Falalyeyeva Tetyana 
Published: August 2023

IntroductionAccording to WHO, antibiotic resistance is increasing to hazardous levels worldwide. Candidiasis often occurs after taking antibiotics. Therefore, antibiotic resistance is a global problem and searching for antibacterial agents is necessary.AimTo determine the antimicrobial activity of bacterial lysate of Lactobacillus (L.) rhamnosus DV separately and with plant extracts against bacterial and yeast test cultures.Material and methodsAntimicrobial activity of Del-Immune V® (cell wall and DNA fragments from a L. rhamnosus DV) separately and with cinnamon, beetroot, and blackcurrant extracts was determined by the minimum inhibitory concentration (MIC). Twofold serial dilutions determined the MIC in previously prepared meat-peptone broth (MPB) for bacteria and liquid wort for yeast. In the study, gram-negative (Escherichia coli IEM-1, Proteus vulgaris PА-12, Pseudomonas sp. MI-2, L. rhamnosus 13/2) and gram-positive (Bacillus (B.) subtilis BТ-2, Staphylococcus aureus BМС-1) bacteria, as well as yeast (Candida (C.) albicans D-6, C. tropicalis PE-2, C. utilis BVS-65) were used as test cultures.ResultsThe MIC for the studied bacterial test cultures after application of L. rhamnosus DV bacterial lysates was from 1.0 ± 0.05 mg/mL to 12.5 ± 0.63 mg/mL, which was significantly less than that of the thermally inactivated control (MIC from 125.0 ± 6.25 mg/mL to 250.0 ± 12.5 mg/mL). B. subtilis BT-2 culture was the least sensitive to the action of the bacterial lysate (MIC—12.5 ± 0.63 mg/mL). It showed the best antibacterial and antifungal effect bacterial lysate with the phytonutrient blackcurrant.ConclusionsIt was demonstrated that bacterial lysate of lactic acid bacteria L. rhamnosus DV exhibits antibacterial and antifungal properties during direct contact with pathogenic agents.
Dismal prognosis of patients with operative indication without surgical intervention in active left-sided infective endocarditis
Authors: Van Hemelrijck Mathias , Sromicki Juri , Frank Michelle , Greutmann Matthias , Ledergerber Bruno , Epprecht Jana , Padrutt Maria , Vogt Paul R. , Carrel Thierry P. , Dzemali Omer , Mestres Carlos-A. , Hasse Barbara 
Published: August 2023

IntroductionAround 25% of patients with left-sided infective endocarditis and operative indication do not undergo surgery. Baseline characteristics and outcomes are underreported. This study describes characteristics and outcomes of surgical candidates with surgical intervention or medical treatment only.MethodsRetrospective analysis of ongoing collected data from a single-center from an observational cohort of patients with infective endocarditis (ENVALVE). Kaplan-Meier estimates for survival was calculated. Factors associated with survival were assessed using a bivariable Cox model. To adjust for confounding by indication, uni- and multivariable logistic regression for the propensity to receive surgery were adjusted.ResultsFrom January 2018 and December 2021, 154 patients were analyzed: 116 underwent surgery and 38 received medical treatment only. Surgical candidates without surgery were older (70 vs. 62 years, p = 0.001). They had higher preoperative risk profile (EuroSCORE II 14% (7.2–28.6) vs. 5.8% (2.5–20.3), p = 0.002) and more comorbidities. One patient was lost-to-follow-up. Survival analysis revealed a significant higher one-year survival rate among patients following surgery (83.7% vs. 15.3% in the non-surgical group; log-rank test &lt;0.0001). In the final multivariable adjusted model, surgery was less likely among patients with liver cirrhosis [OR = 0.03 (95% CI 0.00–0.30)] and with hemodialysis [OR = 0.014 (95% CI 0.00–0.47)].ConclusionPatients with left-sided infective endocarditis who do not undergo surgery despite an operative indication are older, have more comorbidities and therefore higher preoperative risk profile and a low 1-year survival. The role of the Endocarditis Team may be particularly important for the decision-making process in this specific group.
Impact of gender on left atrial low-voltage zones in patients with persistent atrial fibrillation: results of a voltage-guided ablation
Authors: Marzak Halim , Ringele Romain , Matsushita Kensuke , Marchandot Benjamin , Fitouchi Simon , Cardi Thomas , Kanso Mohamad , Schatz Alexandre , Hammann Justine , Ohlmann Patrick , Morel Olivier , Jesel Laurence 
Published: August 2023

BackgroundGender-related differences have been reported in atrial fibrotic remodeling and prognosis of atrial fibrillation (AF) patients after ablation. We assessed in persistent AF the regional distribution of left atrial (LA) bipolar voltage and the extent of low-voltage zones (LVZ) according to gender as well as the results of a voltage-guided substrate ablation.MethodsConsecutive patients who underwent a voltage-guided AF ablation were enrolled. LA endocardial voltage maps were obtained using a 3D electro-anatomical mapping system in sinus rhythm. LVZ was defined as &lt;0.5 mV.ResultsA total of 115 patients were enrolled (74 men, 41 women). The LA bipolar voltage amplitude was twice lower in the whole LA (p &lt; 0.01) and in each atrial region in women compared with men, whereas the LA indexed volume was similar. LVZ were found in 56.1% of women and 16.2% of men (p &lt; 0.01). LVZ were also more extensive in women (p = 0.01), especially in the anterior LA. Atrial voltage alteration occurred earlier in women than in men. In a multivariate analysis, the female sex (OR 12.99; 95% CI, 3.23–51.63, p = 0.0001) and LA indexed volume (OR 1.09; 95% CI, 1.04–1.16, p = 0.001) were predictive of LVZ. Atrial arrhythmia-free survival was similar in men and women 36 months after a single ablation procedure.ConclusionThe study reports a strong relationship between the female gender and atrial substrate remodeling. The female gender was significantly associated with higher incidence, earlier occurrence, and greater extent of LVZ compared with men. Despite the female-specific characteristics in atrial remodeling, LVZ-guided ablation may improve the AF ablation outcome in women.
Risk factors and drug discovery for cognitive impairment in type 2 diabetes mellitus using artificial intelligence interpretation and graph neural networks
Authors: Zhang Xin , Xie Jiajia , You Xiong , Gong Houwu 
Published: August 2023

BackgroundAmong the 382 million diabetic patients worldwide, approximately 30% experience neuropathy, and one-fifth of these patients eventually develop diabetes cognitive impairment (CI). However, the mechanism underlying diabetes CI remains unknown, and early diagnostic methods or effective treatments are currently not available.ObjectiveThis study aimed to explore the risk factors for CI in patients with type 2 diabetes mellitus (T2DM), screen potential therapeutic drugs for T2DM-CI, and provide evidence for preventing and treating T2DM-CI.MethodsThis study focused on the T2DM population admitted to the First Affiliated Hospital of Hunan College of Traditional Chinese Medicine and the First Affiliated Hospital of Hunan University of Chinese Medicine. Sociodemographic data and clinical objective indicators of T2DM patients admitted from January 2018 to December 2022 were collected. Based on the Montreal Cognitive Assessment (MoCA) Scale scores, 719 patients were categorized into two groups, the T2DM-CI group with CI and the T2DM-N group with normal cognition. The survey content included demographic characteristics, laboratory serological indicators, complications, and medication information. Six machine learning algorithms were used to analyze the risk factors of T2DM-CI, and the Shapley method was used to enhance model interpretability. Furthermore, we developed a graph neural network (GNN) model to identify potential drugs associated with T2DM-CI.ResultsOur results showed that the T2DM-CI risk prediction model based on Catboost exhibited superior performance with an area under the receiver operating characteristic curve (AUC) of 0.95 (specificity of 93.17% and sensitivity of 78.58%). Diabetes duration, age, education level, aspartate aminotransferase (AST), drinking, and intestinal flora were identified as risk factors for T2DM-CI. The top 10 potential drugs related to T2DM-CI, including Metformin, Liraglutide, and Lixisenatide, were selected by the GNN model. Some herbs, such as licorice and cuscutae semen, were also included. Finally, we discovered the mechanism of herbal medicine interventions in gut microbiota.ConclusionThe method based on Interpreting AI and GNN can identify the risk factors and potential drugs associated with T2DM-CI.
Proteomic analysis of diabetic retinas
Authors: Starr Christopher R. , Zhylkibayev Assylbek , Mobley James A. , Gorbatyuk Marina S. 
Published: August 2023

IntroductionAs a metabolic disease, diabetes often leads to health complications such as heart failure, nephropathy, neurological disorders, and vision loss. Diabetic retinopathy (DR) affects as many as 100 million people worldwide. The mechanism of DR is complex and known to impact both neural and vascular components in the retina. While recent advances in the field have identified major cellular signaling contributing to DR pathogenesis, little has been reported on the protein post-translational modifications (PTM) - known to define protein localization, function, and activity - in the diabetic retina overall. Protein glycosylation is the enzymatic addition of carbohydrates to proteins, which can influence many protein attributes including folding, stability, function, and subcellular localization. O-linked glycosylation is the addition of sugars to an oxygen atom in amino acids with a free oxygen atom in their side chain (i.e., threonine, serine). To date, more than 100 congenital disorders of glycosylation have been described. However, no studies have identified the retinal O-linked glycoproteome in health or disease. With a critical need to expedite the discovery of PTMomics in diabetic retinas, we identified both global changes in protein levels and the retinal O-glycoproteome of control and diabetic mice.MethodsWe used liquid chromatography/mass spectrometry-based proteomics and high throughput screening to identify proteins differentially expressed and proteins differentially O-glycosylated in the retinas of wildtype and diabetic mice.ResultsChanges in both global expression levels of proteins and proteins differentially glycosylated in the retinas of wild-type and diabetic mice have been identified. We provide evidence that diabetes shifts both global expression levels and O-glycosylation of metabolic and synaptic proteins in the retina.DiscussionHere we report changes in the retinal proteome of diabetic mice. We highlight alterations in global proteins involved in metabolic processes, maintaining cellular structure, trafficking, and neuronal processes. We then showed changes in O-linked glycosylation of individual proteins in the diabetic retina.
Tetra-ARMS PCR analysis of angiotensinogen AGT T174M (rs4762) genetic polymorphism in diabetic patients: a comprehensive study
Authors: Akash Muhammad Sajid Hamid , Shahid Momina , Suhail Shaleem , Rehman Kanwal , Nadeem Ahmed , Mir Tahir Maqbool 
Published: August 2023

Background and purposeHypertension (HTN) is a multifactorial chronic disease that poses a significant global health burden and is associated with increased mortality rates. It often coexists with other conditions, such as cardiovascular, liver, and renal diseases, and has a strong association with diabetes mellitus. Insulin resistance and endothelial dysfunction commonly occur in individuals with both HTN and type 2 diabetes mellitus (T2DM). Genetic factors, along with environmental and pathological factors, play a role in the development of HTN. Recent studies have revealed the influence of single nucleotide polymorphisms (SNPs) in various genes on HTN. In this study, we aimed to investigate the genetic polymorphism of angiotensinogen (AGT) T174M (rs4762) and its association with HTN in diabetic patients.MethodsA total of 300 participants were enrolled in this study and divided into three groups: control, hypertensive, and hypertensive diabetic. Blood samples were collected, and predetermined biochemical parameters were assessed. Genotyping of the AGT T174M (rs4762) gene was conducted using Tetra ARMS PCR with specific primers.ResultsThe study findings revealed a significant association between AGT T174M (rs4762) genotype and HTN in diabetic patients within the Pakistani population. The C/T genotype of AGT T174M (rs4762) was found to be significant in both the hypertensive and hypertensive diabetic participants compared to the control group. This genotype was identified as a risk factor for developing HTN in both the hypertensive and hypertensive diabetic participants.ConclusionThis study demonstrates a significant association between AGT T174M (rs4762) genetic polymorphism and HTN in diabetic patients. The C/T genotype of AGT T174M (rs4762) may serve as a potential marker for identifying individuals at risk of developing HTN, specifically in the hypertensive and hypertensive diabetic populations. Further research is warranted to elucidate the underlying mechanisms and validate these findings in larger cohorts.
Identification and characterization of ecdysis-related neuropeptides in the lone star tick Amblyomma americanum
Authors: Lyu Bo , Li Jingjing , Niemeyer Brigid , Stanley David , Song Qisheng 
Published: August 2023

IntroductionThe lone star tick, Amblyomma americanum, is an important ectoparasite known for transmitting diseases to humans and animals. Ecdysis-related neuropeptides (ERNs) control behaviors crucial for arthropods to shed exoskeletons. However, ERN identification and characterization in A. americanum remain incomplete.MethodsWe investigated ERNs in A. americanum, assessing their evolutionary relationships, protein properties, and functions. Phylogeny, sequence alignment, and domain structures of ERNs were analyzed. ERN functionality was explored using enrichment analysis, and developmental and tissue-specific ERN expression profiles were examined using qPCR and RNAi experiments.Results and discussionThe study shows that ERN catalogs (i.e., eclosion hormone, corazonin, and bursicon) are found in most arachnids, and these ERNs in A. americanum have high evolutionary relatedness with other tick species. Protein modeling analysis indicates that ERNs primarily consist of secondary structures and protein stabilizing forces (i.e., hydrophobic clusters, hydrogen bond networks, and salt bridges). Gene functional analysis shows that ENRs are involved in many ecdysis-related functions, including ecdysis-triggering hormone activity, neuropeptide signaling pathway, and corazonin receptor binding. Bursicon proteins have functions in chitin binding and G protein-coupled receptor activity and strong interactions with leucine-rich repeat-containing G-protein coupled receptor 5. ERNs were expressed in higher levels in newly molted adults and synganglia. RNAi-mediated knockdown of burs α and burs β expression led to a significant decrease in the expression of an antimicrobial peptide, defensin, suggesting they might act in signaling or regulatory pathways that control the expression of immune-related genes. Arthropods are vulnerable immediately after molting because new cuticles are soft and susceptible to injury and pathogen infections. Bursicon homodimers act in prophylactic immunity during this vulnerable period by increasing the synthesis of transcripts encoding antimicrobial peptides to protect them from microbial invasion. Collectively, the expression pattern and characterization of ERNs in this study contribute to a deeper understanding of the physiological processes in A. americanum.
Modeling and analysis of the LC filter-integrated quasi Z-source indirect matrix converter for the wind energy conversion system
Authors: Maheswari K. T. , Kumar C. , Balachandran Praveen Kumar , Senjyu Tomonobu 
Published: August 2023

A Quasi Z-Source Indirect Matrix Converter (QZSIMC) is proposed in this paper for Permanent Magnet Generator (PMG) based Direct Drive Wind Energy Conversion Systems (DDWECS) to enhance the voltage transfer ratio and also to control the output voltage under various loading conditions. The QZSIMC comprises three Quasi Z-Source (QZS) networks connected between PMG and load through a three-phase Indirect Matrix Converter (IMC). Two different PWM control techniques such as Carrier Based Pulse Width Modulation Technique and Modified Space Vector Pulse Width Modulation Technique are proposed to analyze the performance of QZSIMC. By changing the shoot through time period, the duty ratio of quasi Z-Source network can be increased which in turn increases the boost factor of both QZSIMC without affecting the efficiency of the converter. A closed-loop control system has also been designed to sustain constant parameters at the output. The proposed QZSIMC for PMG based DDWECS along with two different PWM Control Schemes are to be modeled using MATLAB/SIMULINK environment. To validate the simulation results, a 1 kW, 415 V, 50 Hz experimental setup with an FPGA SPARTAN-6 processor has been developed in the laboratory for QZSIMC and the results are investigated based on the parameters such as output voltage, output current, Switching Stress, Boost Factor, inductor current, capacitor voltage, Total Harmonic Distortion.
Pharmacogenetics and phenoconversion: the influence on side effects experienced by psychiatric patients
Authors: den Uil Manon G. , Hut Hannelotte W. , Wagelaar Kay R. , Abdullah-Koolmees Heshu , Cahn Wiepke , Wilting Ingeborg , Deneer Vera H. M. 
Published: August 2023

Introduction: Preventing side effects is important to ensure optimal psychopharmacotherapy and therapeutic adherence among psychiatric patients. Obtaining the pharmacogenetic profile of CYP2C19 and CYP2D6 can play an important role in this. When the genotype-predicted phenotype shifts because of the use of co-medication, this is called phenoconversion. The aim was to study the influence of the pharmacogenetic (PGx) profile and phenoconversion on side effects experienced by psychiatric patients.Methods: A retrospective cohort study was performed using data from 117 patients from a psychiatric outpatient clinic. Patients were genotyped with a psychiatric PGx panel and side effects were evaluated using the Udvalg for Kliniske Undersølgelser side effects rating scale (UKU).Results: Of all patients, 10.3% and 9.4% underwent phenoconversion (any shift in predicted phenotype) for CYP2C19 and CYP2D6 respectively. No significant associations were found between the phenotype and UKU-score. 75% of the patients with an Intermediate metabolizer (IM) or Poor metabolizer (PM) phenoconverted phenotype of CYP2C19 experienced nausea and vomiting compared to 9.1% of the Normal metabolizer (NM) and Ultrarapid metabolizer (UM) patients (p = 0.033). 64% of the patients with an IM or PM phenoconverted phenotype of CYP2D6 experienced the side effect depression compared to 30.4% NMs and UMs (p = 0.020). CYP2D6 IM and PM patients had a higher concentration-dose ratio than NM patients (p &lt; 0.05).Discussion: This study underlines the importance to consider phenoconversion when looking at a patient’s genotype. This is important for a better prediction of the phenotype and preventing possible side effects under a specific psychopharmacotherapy.
Potential causal association between aspirin use and the reduced risk of hayfever or allergic rhinitis: a Mendelian randomization study
Authors: Li Li , Zhang Yuanding , Liu Xiangliang , Li Junxin , Yang Qiuyu , Jiang Jiajia , Liu Hong , Fu Zhongying , Chen Weilun 
Published: August 2023

BackgroundThe evidence from observational studies on the association between the use of aspirin and the risk of hayfever or allergic rhinitis is conflicting, with a dearth of high-quality randomized controlled trials.ObjectiveThis study aims to investigate the causal relationship between aspirin use and the risk of hayfever or allergic rhinitis.MethodsWe conducted a two-sample Mendelian randomization (MR) analysis using the inverse-variance weighted (IVW), weighted median, and MR-Egger regression methods. We utilized publicly available summary statistics datasets from genome-wide association studies (GWAS) meta-analyses on aspirin use in individuals of European descent (n = 337,159) as the exposure variable, and a GWAS on doctor-diagnosed hayfever or allergic rhinitis in individuals from the UK Biobank (n = 83,529) as the outcome variable.ResultsWe identified 7 single nucleotide polymorphisms (SNPs) at genome-wide significance from the GWASs associated with aspirin use as instrumental variables (P&lt;5×10−8; linkage disequilibrium r2 &lt;0.1). The IVW method provided evidence supporting a causal association between aspirin use and reduced risk of hayfever or allergic rhinitis (β = -0.349, SE = 0.1356, P = 0.01008). MR-Egger regression indicated no causal association between aspirin use and hayfever or allergic rhinitis (β = -0.3742, SE = 0.3809, P = 0.371), but the weighted median approach yielded evidence of a causal association (β = -0.4155, SE = 0.1657, P = 0.01216). Cochran’s Q test and the funnel plot indicated no evidence of heterogeneity and asymmetry, indicating no directional pleiotropy.ConclusionThe findings of the MR analysis support a potential causal relationship between aspirin use and the reduced risk of hayfever or allergic rhinitis.