bluuebunny/crossref_metadata_2025_split huggingface dataset:
Effectiveness of desertliving cistanche in managing hyperlipidemic osteoporosis in ovariectomized rats through the PI3K/AKT signaling pathway
Authors: Lin Jia-Yue , Kuang Hao-Ming , Rong Kuan , Peng Li , Kuang Jian-Jun , Yan Xu 
Published: July 2024

Abstract
Background
To aim of this study is to assess the mechanism through which Desertliving Cistanche modulates the PI3K/AKT signaling pathway in the treatment of hyperlipidemic osteoporosis in ovariectomized rats.

Methods
We randomly assigned specific-pathogen-free (SPF) rats into five groups (n = 10 per group). The normal control group received a standard diet, while the model group, atorvastatin group, diethylstilbestrol group, and treatment group were fed a high-fat diet. Four weeks later, bilateral ovariectomies were conducted, followed by drug interventions. After six weeks of treatment, relevant indicators were compared and analyzed.

Results
Compared to the normal control group, rats in the model group exhibited blurred trabecular morphology, disorganized osteocytes, significantly elevated levels of bone-specific alkaline phosphatase (BALP), bone Gla-protein (BGP), total cholesterol (TC), tumor necrosis factor-α (TNF-α), and receptor activator of NF-κB ligand (RANKL). Also, the model group revealed significantly reduced levels of ultimate load, fracture load, estradiol (E2), bone mineral density (BMD), osteoprotegerin (OPG), and phosphoinositide 3-kinase (PI3K) and protein kinase B (Akt) in femoral tissue. The atorvastatin group presented with higher TC and TNF-α levels compared to the normal control group. Conversely, the treatment group demonstrated enhanced trabecular morphology, denser structure, smaller bone marrow cavities, and reduced BALP, BGP, TC, TNF-α, and RANKL levels. Furthermore, the treatment group exhibited higher levels of E2, BMD, OPG, and PI3K and Akt in bone tissue compared to the model group. The treatment group also had lower TC and TNF-α levels than the atorvastatin group. Biomechanical analysis indicated that after administration of Desertliving Cistanche, the treatment group had reduced body mass, increased ultimate and fracture load of the femur, denser bone structure, smaller bone marrow cavities, and altered periosteal arrangement compared to the model group.

Conclusion
Our study revealed that Desertliving Cistanche demonstrated significant efficacy in preventing and treating postmenopausal hyperlipidemic osteoporosis in rats.
Different antithrombotic strategies after coronary artery bypass grafting to prevent adverse events: a retrospective analysis
Authors: Shi Yi , Chen Shenglong , Liu Gang , Lian Bo , Chen Yu , Zhang Lixue 
Published: July 2024

Abstract
Objective
Coronary artery bypass grafting (CABG) is associated with antithrombotic therapy in terms of postoperative adverse events; however, it is still unknown whether the early use of such drugs after CABG is safe and effective. In this study, we aim to evaluate the relationship between different postoperative antithrombotic strategies and in-hospital adverse events in patients undergoing isolated coronary artery bypass grafting surgery.

Methods
This was a single-center, retrospective cohort analysis of patients undergoing isolated CABG due to coronary artery disease (CAD) between 2001 and 2012. Data were extracted from the Medical Information Mart for Intensive Care III database. The patients involved were divided into the ASA (aspirin 81 mg per day only) or DAPT (aspirin plus clopidogrel 75 mg per day) group according to the antiplatelet strategy. Patients were also stratified into subgroups based on the type of anticoagulation. The in-hospital risk of bleeding and adverse events was investigated and compared between groups. Propensity score matching (PSM) was performed to reduce the potential effects of a selection bias.

Results
A total of 3274 patients were included in this study, with 2358 in the ASA group and 889 in the DAPT group. Following the PSM, no significant difference was seen in the risk of major bleeding between the two groups according to the PLATO, TIMI or GUSTO criteria. There was no difference in the postoperative mortality. In subgroup analysis, patients given anticoagulant therapy had an increased incidence of bleeding-related events. Multivariable analysis revealed that postoperative anticoagulant therapy and the early use of heparin, but not DAPT, were independent predictors of bleeding-related events.

Conclusions
Postoperative DAPT was not associated with an increased occurrence of bleeding-related events in patients undergoing isolated CABG and appears to be a safe antiplatelet therapy. The addition of anticoagulants to antiplatelet therapy increased the risk of bleeding and should be considered cautiously in clinical practice.
Positive feedback loop of c-myc/XTP6/NDH2/NF-κB to promote malignant progression in glioblastoma
Authors: Xiao Feng , Zhu Hong , Xiong Yaping , Guo Yun , Zhang Zhe , Zeng Jie , Xiao Yao , Liao Bin , Shang Xuesong , Zhao Siyi , Hu Guowen , Huang Kai , Guo Hua 
Published: July 2024

Abstract
Background
Recent studies have highlighted the significant role of the NF-κB signaling pathway in the initiation and progression of cancer. Furthermore, long noncoding RNAs (lncRNAs) have been identified as pivotal regulators in sustaining the NF-κB signaling pathway’s functionality. Despite these findings, the underlying molecular mechanisms through which lncRNAs influence the NF-κB pathway remain largely unexplored.

Methods
Bioinformatic analyses were utilized to investigate the differential expression and prognostic significance of XTP6. The functional roles of XTP6 were further elucidated through both in vitro and in vivo experimental approaches. To estimate the interaction between XTP6 and NDH2, RNA pulldown and RNA Immunoprecipitation (RIP) assays were conducted. The connection between XTP6 and the IκBα promoter was examined using Chromatin Isolation by RNA Purification (ChIRP) assays. Additionally, Chromatin Immunoprecipitation (ChIP) assays were implemented to analyze the binding affinity of c-myc to the XTP6 promoter, providing insights into the regulatory mechanisms at play.

Results
XTP6 was remarkedly upregulated in glioblastoma multiforme (GBM) tissues and was connected with adverse prognosis in GBM patients. Our investigations revealed that XTP6 can facilitate the malignant progression of GBM both in vitro and in vivo. Additionally, XTP6 downregulated IκBα expression by recruiting NDH2 to the IκBα promoter, which resulted in elevated levels of H3K27me3, thereby reducing the transcriptional activity of IκBα. Moreover, the progression of GBM was further driven by the c-myc-mediated upregulation of XTP6, establishing a positive feedback loop with IκBα that perpetuated the activation of the NF-κB signaling pathway. Notably, the application of an inhibitor targeting the NF-κB signaling pathway effectively inhibited the continuous activation induced by XTP6, leading to a significant reduction in tumor formation in vivo.

Conclusion
The results reveal that XTP6 unveils an innovative epigenetic mechanism instrumental in the sustained activation of the NF-κB signaling pathway, suggesting a promising therapeutic target for the treatment of GBM.
Neurobehavioral, neurotransmitter and redox modifications in Nauphoeta cinerea under mixed heavy metal (silver and mercury) exposure
Authors: Olagoke Olawande C. , Ogunsuyi Opeyemi B. , Mayokun Famutimi E. , Rocha João B.T. , Oboh Ganiyu 
Published: July 2024

AbstractHeavy metals are encountered in nature, and are used in several human endeavors, including in dental fillings. It is well known that the safety of metals depends on their chemical form, as well as the dose and route through which biological systems are exposed to them. Here, we used the Nauphoeta cinerea model to examine the mechanism by which salts of the heavy metals used in dental fillings – silver and mercury – exert their neurotoxicity. Nymphs exposed to heavy metals presented with reduced motor and exploratory abilities as they spent more time immobile, especially in the periphery of a novel object, and covered less distance compared with control nymphs. Exposure to AgNO3 and HgCl2 also exacerbated levels of oxidative stress markers (MDA & ROS) and the neurotransmitter regulators – AChE and MAO, while reducing antioxidant activity markers, both in biochemical (thiol & GST) and RT-qPCR (TRX, GST, SOD, Catalase) examinations, in neural tissues of the cockroach. The observed disruptions in neurolocomotor control, synaptic transmission and redox balance explain how heavy metal salts may predispose organisms to neurological disorders.
A systematic review on the contribution of DNA methylation to hearing loss
Authors: Patil Vibha , Perez-Carpena Patricia , Lopez-Escamez Jose A. 
Published: July 2024

Abstract
Background
DNA methylation may have a regulatory role in monogenic sensorineural hearing loss and complex, polygenic phenotypic forms of hearing loss, including age-related hearing impairment or Meniere disease. The purpose of this systematic review is to critically assess the evidence supporting a functional role of DNA methylation in phenotypes associated with hearing loss.

Results
The search strategy yielded a total of 661 articles. After quality assessment, 25 records were selected (12 human DNA methylation studies, 5 experimental animal studies and 8 studies reporting mutations in the DNMT1 gene). Although some methylation studies reported significant differences in CpG methylation in diverse gene promoters associated with complex hearing loss phenotypes (ARHI, otosclerosis, MD), only one study included a replication cohort that supported a regulatory role for CpG methylation in the genes TCF25 and POLE in ARHI. Conversely, several studies have independently confirmed pathogenic mutations within exon 21 of the DNMT1 gene, which encodes the DNA (cytosine-5)-methyltransferase 1 enzyme. This methylation enzyme is strongly associated with a rare disease defined by autosomal dominant cerebellar ataxia, deafness and narcolepsy (ADCA-DN). Of note, rare variants in DNMT1 and DNMT3A genes have also been reported in noise-induced hearing loss.

Conclusions
Evidence supporting a functional role for DNA methylation in hearing loss is limited to few genes in complex disorders such as ARHI. Mutations in the DNMT1 gene are associated with ADCA-DN, suggesting the CpG methylation in hearing loss genes deserves further attention in hearing research.
Macro and micro structural preservation of grey matter integrity after 24 weeks of rTMS in Alzheimer’s disease patients: a pilot study
Authors: Mencarelli Lucia , Torso Mario , Borghi Ilaria , Assogna Martina , Pezzopane Valentina , Bonnì Sonia , Di Lorenzo Francesco , Santarnecchi Emiliano , Giove Federico , Martorana Alessandro , Bozzali Marco , Ridgway Gerard R. , Chance Steven A. , Koch Giacomo 
Published: July 2024

AbstractAlzheimer’s Disease (AD) is characterized by structural and functional dysfunction involving the Default Mode Network (DMN), for which the Precuneus (PC) is a key node. We proposed a randomized double-blind pilot study to determine neurobiological changes after 24 weeks of PC-rTMS in patients with mild-to-moderate AD. Sixteen patients were randomly assigned to SHAM or PC-rTMS, and received an intensive 2-weeks course with daily rTMS sessions, followed by a maintenance phase in which rTMS has been applied once a week. Before and after the treatment structural and functional MRIs were collected. Our results showed macro- and micro-structural preservation in PC-rTMS compared to SHAM-rTMS group after 24 weeks of treatment, correlated to an increase of functional connectivity (FC) within the PC in the PC-rTMS group. Even if preliminary, these results trigger the possibility of using PC-rTMS to arrest atrophy progression by manipulating distributed network connectivity patterns.
Amino acid mutations PB1-V719M and PA-N444D combined with PB2-627K contribute to the pathogenicity of H7N9 in mice
Authors: Wang Xiaoquan , Tang Xin-en , Zheng Huafen , Gao Ruyi , Lu Xiaolong , Yang Wenhao , Zhou Le , Chen Yu , Gu Min , Hu Jiao , Liu Xiaowen , Hu Shunlin , Liu Kaituo , Liu Xiufan 
Published: July 2024

AbstractH7N9 subtype avian influenza viruses (AIVs) cause 1567 human infections and have high mortality, posing a significant threat to public health. Previously, we reported that two avian-derived H7N9 isolates (A/chicken/Eastern China/JTC4/2013 and A/chicken/Eastern China/JTC11/2013) exhibit different pathogenicities in mice. To understand the genetic basis for the differences in virulence, we constructed a series of mutant viruses based on reverse genetics. We found that the PB2-E627K mutation alone was not sufficient to increase the virulence of H7N9 in mice, despite its ability to enhance polymerase activity in mammalian cells. However, combinations with PB1-V719M and/or PA-N444D mutations significantly enhanced H7N9 virulence. Additionally, these combined mutations augmented polymerase activity, thereby intensifying virus replication, inflammatory cytokine expression, and lung injury, ultimately increasing pathogenicity in mice. Overall, this study revealed that virulence in H7N9 is a polygenic trait and identified novel virulence-related residues (PB2-627K combined with PB1-719M and/or PA-444D) in viral ribonucleoprotein (vRNP) complexes. These findings provide new insights into the molecular mechanisms underlying AIV pathogenesis in mammals, with implications for pandemic preparedness and intervention strategies.
Genomic variation induced by a low concentration of ethyl methanesulfonate (EMS) in quinoa ‘Longli-4’ variety
Authors: Li Xiaofeng , Cui Xiaoyun , Ran Ruilan , Chen Guoxiong , Zhao Pengshan 
Published: July 2024

AbstractQuinoa (Chenopodium quinoa, 2n = 4x = 36), a super pseudocereal crop, has been introduced into China nearly 60 years. Many excellent varieties have been developed through massive selection; however, few are developed through mutagenesis breeding. In this study, the ‘Longli-4’ variety, locally cultivated in Gansu province, Northwest China, was selected for experimentation. The grains of ‘Longli-4’ were treated with ethyl methanesulfonate (EMS) at a concentration of 0.8% for 8 h. Nine plants from independent M2 families were randomly selected to investigate the mutagenesis effect of EMS on the quinoa genome. The results indicated that the single nucleotide polymorphisms (SNPs) induced by EMS were unevenly distributed across all 18 chromosomes, with an average mutation frequency of 91.2 SNPs/Mb, ranging from 4.5 to 203.5 SNPs/Mb. A significant positive correlation between the number of SNPs and chromosome length was identified through linear model analysis. Transitions from G/C to A/T were the most predominated in all variant categories, accounting for 34.4–67.2% of the mutations, and SNPs were significantly enriched in intergenic regions, representing 69.2–75.1% of the total mutations. This study provides empirical support for the application of low concentration EMS treatment in quinoa breeding.
Lead and calcium crosstalk tempted acrosome damage and hyperpolarization of spermatozoa: signaling and ultra-structural evidences
Authors: Yadav Rajkumar Singh , Kushawaha Bhawna , Dhariya Rahul , Swain Dilip Kumar , Yadav Brijesh , Anand Mukul , Kumari Priyambada , Rai Pradeep Kumar , Singh Dipty , Yadav Sarvajeet , Garg Satish Kumar 
Published: July 2024

Abstract
Background
Exposure of humans and animals to heavy metals is increasing day-by-day; thus, lead even today remains of significant public health concern. According to CDC, blood lead reference value (BLRV) ranges from 3.5 µg/dl to 5 μg/dl in adults. Recently, almost 2.6% decline in male fertility per year has been reported but the cause is not well established. Lead (Pb2+) affects the size of testis, semen quality, and secretory functions of prostate. But the molecular mechanism(s) of lead toxicity in sperm cells is not clear. Thus, present study was undertaken to evaluate the adverse effects of lead acetate at environmentally relevant exposure levels (0.5, 5, 10 and 20 ppm) on functional and molecular dynamics of spermatozoa of bucks following in vitro exposure for 15 min and 3 h.

Results
Lead significantly decreased motility, viable count, and motion kinematic patterns of spermatozoa like curvilinear velocity, straight-line velocity, average path velocity, beat cross frequency and maximum amplitude of head lateral displacement even at 5 ppm concentration. Pb2+ modulated intracellular cAMP and Ca2+ levels in sperm cells through L-type calcium channels and induced spontaneous or premature acrosome reaction (AR) by increasing tyrosine phosphorylation of sperm proteins and downregulated mitochondrial transmembrane potential. Lead significantly increased DNA damage and apoptosis as well. Electron microscopy studies revealed Pb2+ -induced deleterious effects on plasma membrane of head and acrosome including collapsed cristae in mitochondria.

Conclusions
Pb2+ not only mimics Ca2+ but also affects cellular targets involved in generation of cAMP, mitochondrial transmembrane potential, and ionic exchange. Lead seems to interact with Ca2+ channels because of charge similarity and probably enters the sperm cell through these channels and results in hyperpolarization. Our findings also indicate lead-induced TP and intracellular Ca2+ release in spermatozoa which in turn may be responsible for premature acrosome exocytosis which is essential feature of capacitation for fertilization. Thus, lead seems to reduce the fertilizing capacity of spermatozoa even at 0.5 ppm concentrations.

Graphical Abstract
Perinatal mortality and its predictors in Beni City, Democratic Republic of Congo: a cross-sectional study
Authors: Kahiririaa Mathe Julien , Namyalo Josephine , Mubarak Nasur , Otieno Emmanuel 
Published: July 2024

Abstract
Background
Globally, perinatal mortality rates have decreased considerably in the last 30 years. However, in sub-Saharan African countries perinatal mortality remains a public health burden. Therefore, this study aimed to determine the Perinatal Mortality Rate and the factors associated with perinatal mortality in Beni City, Northeastern Democratic Republic of Congo.

Methods
A hospital-based retrospective cross-sectional study was conducted among 1394 deliveries that were documented in Beni General Referral Hospital from 2 January to May 31, 2022. The study was done in the conflict-ridden Beni city of the North Kivu Province. Analysis was done using Open Epi and SPSS version 22. Binary and Multivariate logistic regression analyses were performed. Odds ratio with 95% confidence interval was used to measure strength of association.

Results
Findings indicate that 60.7% of 1394 participants were below the age of 21 years, and 95.1% (1325) Beni residents. The Perinatal Mortality Rate was 42.3 per 1000 live births. Majority (51) of the postpartum women who experienced perinatal mortality didn`t have a history of perinatal mortality as compared to their counterparts. Multivariable analysis revealed that birth weight (AoR = 0.082, 95% CI 0.014–0.449, p < 0.05) and Apgar score in the 10th minute (AoR = 0.082, 95% CI 0.000- 0.043, p < 0.05) were significantly associated with Perinatal mortality.

Conclusion
The high perinatal mortality rate in Beni General Referral Hospital, approximately four in every 100 births remains a disturbing public health concern of which is attributable to low birth weight and Apgar score. This study may help policy-makers and healthcare providers to design preventive interventions.
Development of an HPLC method using relative molar sensitivity for the measurement of blood concentrations of nine pharmaceutical compounds
Authors: Ohtsuki Takashi , Huang Yi , Kamiya Ayane , Nakayama Yuki , Matsushita Miyuki , Morikawa Satoru , Matsufuji Hiroshi 
Published: July 2024

AbstractWe developed a reliable high-performance liquid chromatographic analysis method using a relative molar sensitivity (RMS) technique that does not require an authentic, identical reference analyte material to quantify blood serum carbamazepine, phenytoin, voriconazole, lamotrigine, meropenem, mycophenolic acid, linezolid, vancomycin, and caffeine levels for routine blood concentration measurements. Carbamazepine and caffeine were also used as non-analyte reference materials to calculate the RMS of each analyte. The RMS was calculated from the ratio of the slope of the calibration equation (analyte/non-analyte reference material), then used to quantify analytes in control serum samples spiked with carbamazepine, phenytoin, voriconazole, meropenem, mycophenolic acid, linezolid or vancomycin. In addition, the concentrations of these six drugs in control serum samples determined by the proposed RMS method agreed well with that obtained using a conventional method. The proposed RMS method is a promising tool for the clinical determination of nine drugs, given the accuracy, precision, and efficiency of quantifying these analytes.
Gamma knife radio surgery for cerebral arteriovenous malformation (AVM) in children: a systematic review and meta-analysis of clinical outcomes
Authors: Florez-Perdomo William Andrés , Reyes Bello Juan Sebastián , Moscote Salazar Luis Rafael , Agrawal Amit , Janjua Tariq , Chavda Vishal , García-Ballestas Ezequiel , Abdulla Ebtesam 
Published: July 2024

AbstractThis article aims to evaluate the safety and effectiveness of Gamma Knife radiosurgery as a treatment modality for pediatric cerebral arteriovenous malformations (AVMs) by assessing mortality rates, the rate of complete AVM obliteration, and the incidence of complications while exploring potential risk factors. A comprehensive search was conducted through multiple databases to identify relevant studies, including randomized controlled trials and observational studies. The studies were assessed for risk of bias using the ROBINS-I tool and methodological quality with the Newcastle–Ottawa Scale. Data on mortality, AVM obliteration rates, and complications were systematically extracted. Pooled rate analysis was performed to assess outcomes, and heterogeneity was evaluated. The analysis included 21 studies involving 2142 pediatric patients with cerebral AVMs. A low mortality rate of 0.75% (95% CI 0.09% to 2.71%) and a high rate of complete obliteration of AVMs was observed, with a rate of 71.64% (95% CI 65.716% to 77.211%). Complications, including new neurological deficits, post-radiosurgery intracranial hemorrhage, and other complications (such as seizures and radiation-related issues), were relatively low, with rates of 2.57%, 2.463%, and 4.784%, respectively. Gamma Knife radiosurgery demonstrates its potential as a safe and effective treatment option for pediatric cerebral AVMs. The low mortality rate and high rate of AVM obliteration suggest that this approach offers significant benefits. While some complications were observed, they were generally non-severe. However, further high-quality studies with extended follow-up periods are needed to better understand long-term efficacy and safety.