bluuebunny/crossref_metadata_2025_split huggingface dataset:
Uric acid is associated with increased risk of myocardial infarction: results from NHANES 2009-2018 and bidirectional two-sample Mendelian randomization analysis
Authors: Deng Ting , Liu Xiaoying 
Published: October 2024

AimAlthough a growing number of studies have shown that elevated uric acid (UA) levels are associated with multiple cardiovascular risk factors and progression of coronary artery disease, the causal relationship between UA and the occurrence of myocardial infarction (MI) remains uncertain. The aim of this study was to investigate the relationship between UA and the risk of MI.MethodsWe screened 23,080 patients in the National Health and Nutrition Examination Survey (NHANES) database for 2009-2018 and explored the association between UA and MI risk using multivariate logistic regression model. In addition, a two-way two-sample Mendelian randomization (TSMR) analysis was performed to examine the causal relationship of UA on MI, and inverse variance-weighted (IVW) results were used as the primary outcome in this study. Sensitivity analysis and horizontal multiple validity test were also performed to verify the reliability of the results.ResultsAfter multivariable adjustment, individuals with the severe elevation of UA levels have a significantly increased risk of MI (OR=2.843, 95%CI: 1.296-6.237, P=0.010). In TSMR analysis, the IVW method demonstrated a significant association between UA and increased risk of MI (OR=1.333, 95%CI: 1.079-1.647, P=0.008). Results from the MR-Egger intercept test, Cochran’s Q test, and MR-PRESSO test all suggest the reliability of the IVW analysis. Reverse TSMR analysis did not indicate a causal relationship between genetic susceptibility to MI and UA levels (IVW: OR=1.001, 95%CI: 0.989-1.012, P=0.922).ConclusionBased on cross-sectional study and Mendelian randomization analysis, it has been demonstrated that UA is an independent risk factor for MI. Elevated levels of UA increase the risk of MI, particularly in cases of severe elevation.
Analyzing research trends in glioblastoma metabolism: a bibliometric review
Authors: Dai Jiaxin , Song Siyun , Chen Pengyu , Huang Qixuan , Duan Hubin 
Published: October 2024

BackgroundA bibliometric and visual analysis of articles related to glioblastoma metabolism was conducted to reveal the dynamics of scientific development and to assist researchers in gaining a global perspective when exploring hotspots and trends.MethodsThe Web of Science Core Collection (WoSCC) was employed to search, screen, and download articles about glioblastoma metabolism published between 2014 and 2024. The relevant literature was analyzed using CiteSpace, VOSviewer and Microsoft Excel.ResultsA total of 729 articles were included for bibliometric analysis between 2014 and 2024, and the number of articles published each year showed an overall increasing trend, except for a decrease in the number of articles published in 2018 compared to 2017. Collaboration network analysis showed that the United States, Germany and China are influential countries in this field, with a high number of articles published, citations and collaborations with other countries. The journal with the largest number of published articles is the International Journal of Molecular Sciences. Mischel PS is the most prolific author with 14 articles, and Guo DL received the most citations with 104 citations. Keyword analysis of the literature showed that the “Warburg effect” achieved the highest burst intensity, and “central nervous system”, “classification” and “fatty acids” showed stronger citation bursts in 2024, indicating that they are still popular topics so far.ConclusionThis article elucidates the research trends and focal points in the field of glioblastoma metabolism, furnishes invaluable insights into the historical and contemporary status of this field, and offers guidance for future research. Further research into glioblastoma metabolism will undoubtedly yield new insights that will inform the diagnosis and treatment of this disease.
Age-specific changes in the serum proteome of female anadromous, hilsa Tenualosa ilisha: a comparative analysis across developmental stages
Authors: Chakraborty Hena , Chakraborty Hirak Jyoti , Das Basanta Kumar , Maity Joydev 
Published: October 2024

IntroductionThe proteome profile of the female Tenualosa ilisha (Hamilton, 1822), a species of great ecological and economic importance, across various age groups was investigated to comprehend the functional dynamics of the serum proteome for conservation and aquaculture, as well as sustain the population.MethodsAdvanced liquid chromatography-tandem mass spectrometry LC-MS/MS-based proteomic data were analysed and submitted to the ProteomeXchange Consortium via PRIDE (PRoteomics IDEntifications database). Bioinformatics analysis of serum proteome have been done and it showed different proteins associated with GO Gene Ontology () terms, and the genes associated with enriched KEGG (Kyoto Encyclopedia of Genes and Genomes) pathways (such as phagosome, mTOR, Apelin signalling pathways, herpes simplex virus) implicated in immune responses.ResultsThe expression levels of important immunological proteins, such as those involved in cellular defence and inflammatory responses, were significantly different age-dependently. In this study, we annotated 952, 494, 415, and 282 proteins in year classes IV, III, II, and I Hilsa, respectively, and analysed their Protein–Protein Interaction (PPI) networks based on their functional characteristics. From year classes I to IV, new proteins appeared and were more than three-fold. Notably, class I hilsa displayed a lower abundance of proteins than class IV hilsa.DiscussionThis is the first study, to the best of our knowledge, to report the analysis of the serum proteome of hilsa at different developmental stages, and the results can help improve the understanding of the mechanisms underlying the different changes in protein enrichment during migration in hilsa. This analysis also offers crucial insights into the immune system for hilsa conservation and management.
Exploring and comparing renal adverse effects between PARP inhibitors based on a real-world analysis of post-marketing surveillance data
Authors: Xu Qiuyu , Jiang Lin , Chen Gang , Ai Sanxi , Fan Xiaohong , Wang Gangan , Jia Chunyu , Wang Jiahui , Zheng Ke , Zhao Bin , Qin Yan , Li Xuemei 
Published: October 2024

ObjectivePoly (ADP-ribose) polymerase inhibitors (PARPis) are emerging targeted therapeutic agents in oncology, primarily indicated for ovarian and metastatic breast cancer. Acute kidney injury (AKI) has been observed in patients undergoing PARPi treatment, while there is still a lack of comprehensive comparisons of AKI associated with different PARPis. Our study aimed to extensively characterize the renal adverse effects (RAEs) of PARPi using real-world data.MethodsDisproportionality analysis and Bayesian analysis were employed for data mining to identify suspected RAE cases after different PARPis use within the Food and Drug Administration’s Adverse Event Reporting System from January 2004 to September 2023. The time to onset, fatality, and hospitalization rates of PARPi-related RAEs were also investigated.ResultsWe identified 1,696 PARPi-related RAEs, predominantly affecting patients over 85 (56.31%). Veliparib exhibited a more pronounced association with RAEs compared to others, as indicated by the highest reporting odds ratio (ROR = 29.20, 95% CI = 8.79–96.97), proportional reporting ratio (PRR = 19.80, χ2 = 72.62), and empirical Bayes geometric mean (EBGM = 19.80, the lower 90% one-sided CI = 7.25). The median time to RAEs onset was 15 (interquartile range: 6–55.75) days following the initiation of PARPi therapy. PARPi-related RAEs generally led to a 28.15% hospitalization rate and a 4.34% fatality rate.ConclusionAlthough the majority present with reversible creatinine elevation, PARPi-related RAEs merits broader attention, given its potential for clinical consequences. We should strive to early identify those individuals who may have irreversible kidney damage. The focus should be directed toward monitoring renal function in individuals receiving PARPi, especially in senile people and those with a predisposition to AKI.
Safety and efficacy of plasmapheresis in treatment of acute fatty liver of pregnancy—a systematic review and meta-analysis
Authors: Siwatch Sujata , De Arka , Kaur Bandhanjot , Lamba Divjot Singh , Kaur Simarpreet , Singh Virendra , Periyasamy Aravind Gandhi 
Published: October 2024

IntroductionAcute fatty liver of pregnancy (AFLP) is a fatal disease occurring in 3rd trimester. The safety and efficacy of plasmapheresis/plasma exchange (PP/PE) as an adjunctive treatment in patients of AFLP has been studied. We performed systematic review and meta-analysis to estimate the clinical parameters that included mortality rates and improvement of the biochemical parameters including Liver and Renal function enzymes, coagulopathy factors of AFLP patients.MethodsWe searched PubMed, Ovid MEDLINE, Cochrane, CINAHL and Scopus, ClinicalTrials.gov. RevMan statistical software was used for meta-analysis.ResultsPooled survival proportion for AFLP patients treated with PP/PE was 87.74% (95% CI: 82.84 to 91.65). Efficacy of PP/PE was studied by its effect on mortality. PE/PP was associated with the reduction in the mortality with pooled odds ratio of 0.51 (95% CI: 0.08 to 3.09) with I2 = 86%. Sensitivity analysis after excluding outlier study, yielded a pooled odds ratio of 0.19 (95% CI: 0.02 to 1.52) with reduced heterogeneity (I2 = 63%). Biochemical parameter analysis demonstrated significant improvement post-PP/PE treatment, including decreased bilirubin (MD: 8.30, 95% CI: 6.75 to 9.84), AST (MD: 107.25, 95% CI: 52.45 to 162.06), ALT (MD: 111.08, 95% CI: 27.18 to 194.97), creatinine (MD: 1.66, 95% CI: 1.39 to 1.93), and Prothrombin time (MD: 5.08, 95% CI: 2.93 to 7.22).DiscussionDespite some heterogeneity, PP/PE shows promise in improving biochemical parameters in AFLP patients. PE can serve as a therapeutic approach for AFLP particularly in severe or refractory cases. PE provides the time for organ to recover and helps in creating a homeostatic environment for liver. Large RCTs and propensity matched studies are needed to better understand the safety and efficacy of the treatment.Systematic review registrationhttps://www.crd.york.ac.uk/prospero/display_record.php?ID=CRD42022315698.
Association of glymphatic system dysfunction with cognitive impairment in temporal lobe epilepsy
Authors: Wang Jiajia , Xia Xiaona , Zhang Bin , Ma Xiaotian , Shi Feng , Wei Ying , Li Ling , Meng Xiangshui 
Published: October 2024

ObjectivesTo explore the relationship between glymphatic dysfunction and cognitive impairment in unilateral temporal lobe epilepsy (TLE).MethodsThis study retrospectively included 38 patients with unilateral TLE and 26 age- and gender-matched healthy controls (HCs). The diffusion tensor image analysis along the perivascular space (DTI-ALPS) index, choroid plexus volume (CPV), and cognitive assessment were obtained for each participant. Neuropsychological test batteries included Montreal Cognitive Assessment (MoCA), Minimum Mental State Examination, Arithmetic Test (AT), Digit Symbol Substitution Test (DSST), Digit Span Test (DST), Boston Naming Test, Block design, Phonological Fluency Test (PFT), and Semantic Verbal Fluency (SVF).ResultsCompared to HCs, TLE patients had lower scores of MoCA, AT, DSST, DST, Block design, PFT and SVF (all p &lt; 0.05) and lower values of mean DTI-ALPS index (1.491 ± 0.142 vs. 1.642 ± 0.123, p &lt; 0.001). Significantly lower DTI-ALPS index values were observed in the ipsilateral hemisphere than in the contralateral hemisphere (1.466 ± 0.129 vs. 1.517 ± 0.175, p = 0.013) for patients with unilateral TLE. Correlation analyses found that SVF performance was significantly or borderline significantly associated with glymphatic function (FDR-corrected p &lt; 0.05 for all DTI-ALPS index and FDR-corrected p = 0.057 for CPV) in TLE patients. Linear regression analyses showed that increased CPV and decreased DTI-ALPS index were independent risk factors for semantic fluency impairment (all p &lt; 0.05). Furthermore, mediation analyses found the mediator role of the mean DTI-ALPS index in the relationship between choroid plexus enlargement and semantic fluency impairment (indirect effect: β = −0.182, 95%CI = −0.486 to −0.037).ConclusionThese findings reveal the important role of the DTI-ALPS index and CPV in SVF performance in unilateral TLE. Decreased DTI-ALPS index and increased CPV are the independent risk factors for semantic fluency impairment. The DTI-ALPS index may fully mediate the relationship between CP enlargement and SVF performance. These insights provide a radiological foundation for further investigations into the mechanism of the glymphatic system in TLE pathophysiology.
Inside CKD: a microsimulation modelling study projects the clinical and economic burden of chronic kidney disease in Hungary
Authors: Szabó Lilla , Halmai Luca Adél , Ladányi Erzsébet , Garcia Sanchez Juan Jose , Barone Salvatore , Cabrera Claudia , Retat Lise , Webber Laura , Wittmann István , Laczy Boglárka 
Published: October 2024

ObjectivesThe Inside CKD programme implemented a microsimulation modelling approach to project the clinical and economic burden of chronic kidney disease (CKD) between 2024 and 2027 in Hungary.MethodsUsing the peer-reviewed Inside CKD microsimulation, a virtual Hungarian population was generated that was derived from national records, local demographic data and published epidemiological data. These inputs defined the likelihood of a change in health state for each individual as they progressed through the model in annual increments. Individual CKD status, including disease progression, cardiorenal complications and associated costs, was tracked annually to generate the population-level projections of the clinical and economic burden of CKD.ResultsBy 2027, people with CKD were projected to constitute 13.3% of the Hungarian national population. The prevalence of heart failure, myocardial infarction and stroke in people with CKD were projected to remain consistently high, reaching 323 447, 69 188 and 120 118 by 2027, respectively. Kidney replacement therapy cases were predicted to remain high at 20 515 in 2024 and 22 325 in 2027, with associated costs increasing from 71.4 billion HUF in 2024 to 79.6 billion HUF in 2027. Total annual healthcare costs associated with treating CKD were projected to constitute 5.4% of the overall national healthcare budget in 2027.ConclusionsInside CKD demonstrates that the future burden of CKD in Hungary will be substantial unless current management strategies change. The high prevalence of undiagnosed CKD and associated cardiorenal complications highlight the urgent need for policy interventions focused on early diagnosis and timely intervention to mitigate the future burden of CKD.
The effect of lipidomes on the risk of endometrioid endometrial cancer: a Mendelian randomization study
Authors: Lou Yaochen , Jiang Feng , Guan Jun 
Published: October 2024

ObjectiveThis study aimed to explore the potential effects between various human plasma lipidomes and endometrioid endometrial cancer (EEC) by using Mendelian randomization (MR) methods.MethodsThis study designated a total of 179 human plasma lipidomes from the genome-wide association study (GWAS) database as the exposure variable. An EEC-related dataset from the GWAS (GCST006465) served as the outcome variable. MR analyses used the inverse variance-weighted method (IVW), MR-Egger, weighted median, simple mode, and weighted mode methods for regression calculations, accounting for possible biases induced by linkage disequilibrium and weak instrument variables. Any lipidomes failing to pass heterogeneity and horizontal pleiotropy tests were deemed to lack significant causal impact on the outcome.ResultsThe results of IVW analysis disclosed that a variety of human plasma lipidomes (n = 15) exhibited a significant causal effect on EEC (p &lt; 0.05). A subset of these lipidomes (n = 13) passed heterogeneity and horizontal pleiotropy tests, which demonstrated consistent and viable causal effects (p &lt; 0.05) including glycerophospholipids, glycerolipids, and sterols. Specifically, phosphatidylcholine (odds ratio [OR]: 1.065-1.129, p &lt; 0.05) exhibited a significant positive causal effect on the occurrence of EEC. Conversely, sterol ester (OR = 0.936, p = 0.007), diacylglycerol (OR = 0.914, p = 0.036), phosphatidylcholine (OR: 0.903-0.927, p &lt; 0.05), phosphatidylethanolamine (OR = 0.907, p = 0.046) and triacylglycerol (OR: 0.880-0.924, p &lt; 0.05) showed a notable negative causal association with EEC, suggesting their inhibitory effects on the EEC occurrence.ConclusionsThe study revealed that human plasma lipidomes have complex impacts on EEC through Mendelian randomization. This indicated that the diversity of structural changes in lipidomes could show different effects on subtypes and then affect EEC occurrence. Although these lipids had the potential to be promising biomarkers, they needed to be further clinically validated nevertheless.
Antiphospholipid syndrome onset with hemolytic anemia and accompanied cardiocerebral events: a case report
Authors: Zheng Jie , Wei Zhao-Yu , Lin Shi-Chao , Wang Yong , Fang Xin 
Published: October 2024

BackgroundAntiphospholipid syndrome (APS) is a systemic autoimmune disorder that can manifest as thrombosis in the pediatric population, characterized by persistently positive antiphospholipid antibodies. APS is infrequently observed in children and could represent non-criteria manifestations.Case presentationA six-year-old Chinese female presented with jaundice and dark urine, leading to a diagnosis of hemolytic anemia. Prednisone therapy initially improved her complexion, but she later developed neurological symptoms. Further laboratory tests showed intravascular hemolysis, coagulation abnormalities, and a positive lupus anticoagulant (LA) test result. Magnetic resonance imaging (MRI) scan revealed abnormal signals in the pons and cerebellar hemispheres, and an occluded part of the basilar artery. She was subsequently diagnosed with autoimmune encephalitis and received IG(immunoglobulin) and high-dose glucocorticoid (GC) treatment, leading to improvement in her clinical symptoms. However, the symptoms of hemolytic anemia worsened after two years. Subsequent laboratory assessments demonstrated the presence of intravascular hemolysis, coagulation abnormalities, and positive tests of anticardiolipin, LA, and anti-beta2 glycoprotein I antibodies. Elevated troponin I and N-terminal pro-brain natriuretic peptide levels, along with electrocardiogram and echocardiogram findings, indicated a myocardial infarction and a thrombus-like mass in the left auricle. Brain MRI showed multifocal infarction and cerebrovascular obstruction. She was diagnosed with APS accompanied by hemolytic anemia, cerebrovascular obstruction, and myocardial infarction. After several weeks of treatment with GC, IG, rituximab, hydroxychloroquine alone with low-molecular-weight heparin sodium, and warfarin, there was a marked improvement in the patient's condition.ConclusionPediatricians should be familiar with various presentations of pediatric APS to promptly detect possible aPL-related complications and initiate appropriate management strategies early on.
Comparison of sGC activator and sGC stimulator in 5/6 nephrectomized rats on high-salt-diet
Authors: Chen Xin , Xiong Yingquan , Zeng Shufei , Delić Denis , Gaballa Mohamed , Kalk Philipp , Klein Thomas , Krämer Bernhard K. , Hocher Berthold 
Published: October 2024

IntroductionSoluble guanylate cyclase (sGC) stimulators and activators are known to enhance kidney function in various models of chronic kidney disease (CKD) by increasing cyclic guanosine monophosphate (cGMP). Their differential effects on CKD progression, particularly under conditions of oxidative stress, remain unexplored by direct comparative studies.MethodsWe conducted a side-by-side comparison using 5/6 nephrectomized rats on a high salt diet (5/6Nx+HSD) to evaluate the efficacy of the sGC stimulator BAY 41–8543 and the sGC activator BAY 60–2770 in CKD progression. BAY 41–8543 (1 mg/kg; twice daily) and BAY 60–2770 (1 mg/kg; once daily) were administered by gavage for 11 weeks.ResultsThe 5/6Nx+HSD model led to increased plasma creatinine, proteinuria, and blood pressure. Both BAY 41–8543 and BAY 60–2770 significantly reduced systolic and diastolic blood pressure to a similar extent but did not improve renal function parameters. Notably, BAY 60–2770 reduced renal fibrosis, including interstitial fibrosis and glomerulosclerosis, whereas BAY 41–8543 did not. These antifibrotic effects of BAY 60–2770 were independent of blood pressure reduction. Proteomic analysis revealed that BAY 60–2770 corrected the upregulation of 9 proteins associated with apoptosis and fibrosis, including Caspase-3, MKK6 (Mitogen-Activated Protein Kinase Kinase 6), Prdx5 (Peroxiredoxin-5), in the 5/6Nx+HSD group.DiscussionIn contrast, BAY 41–8543 had no significant impact on these proteins. sGC activators were more effective than sGC stimulators in reducing renal fibrosis in 5/6 nephrectomized rats on a high salt diet, and this effect was due to modulation of apoptosis-associated proteins beyond the control of blood pressure.
A novel missense mutation in ISCA2 causes aberrant splicing and leads to multiple mitochondrial dysfunctions syndrome 4
Authors: Al-Hassnan Zuhair , AlDosary Mazhor , AlHargan Aljouhra , AlQudairy Hanan , Almass Rawan , Alahmadi Khaled Omar , AlShahrani Saif , AlBakheet Albandary , Almuhaizea Mohammad A. , Taylor Robert W. , Colak Dilek , Kaya Namik 
Published: October 2024

BackgroundIron–sulfur cluster assembly 2 (ISCA2) deficiency is linked to an autosomal recessive disorder known as multiple mitochondrial dysfunctions syndrome 4 (MMDS4). This disorder is characterized by leukodystrophy and neuroregression. Currently, most of the reported patients are from Saudi Arabia. All these patients carry a homozygous founder variant (NM_194279.2:c.229G&gt;A:p.Gly77Ser) in ISCA2.MethodsWe describe a patient who underwent full clinical evaluation, including metabolic, neurological, and radiological examinations. Standard genetic testing, including whole exome sequencing coupled with autozygome analysis, was undertaken, as were assessments of mitochondrial DNA (mtDNA) copy number and mtDNA sequencing on DNA extracted from blood and cultured fibroblasts. Functional workup consisted of splicing assessment of ISCA2 using RT-PCR, biochemical assessment of complex I status using dipstick assays, and mitochondrial respiration measurements using a Seahorse XFp analyzer.ResultsWe present the clinical and functional characterization of a novel homozygous ISCA2 missense variant (NM_194279.3:c.70A&gt;G:p.Arg24Gly), leading to aberrant splicing in a patient presenting with neuroregression, generalized spasticity with exaggerated deep tendon reflexes and head lag, and progressive loss of acquired milestones. The novel variant was fully segregated in a wider family and was absent in a large control cohort, ethnically matching in-house exomes, local databases such as CGMdb and Saudi Human Genome Program, and ClinVar.ConclusionsOur analyses revealed that the variant is pathogenic, disrupting normal ISCA2 splicing and presumably leading to a truncated protein that disturbs metabolic pathways in patient-derived cells.