bluuebunny/crossref_metadata_2025 huggingface dataset:
Risk Factors Associated with Low Apgar Scores in Pregnancies Complicated by Severe Preeclampsia: A Case–Control Study
Authors: Wang Yunxia , Cui Bihong , Zhou Jiuju , Yue Shuang , Wang Chun , Gu Yongzhong , Meng Jinlai
Published: December 2024

Background: Neonates born to women with severe preeclampsia (PE) exhibited lower Apgar scores. The purpose of this study was to evaluate the association between low Apgar scores and maternal, prenatal, and intrapartum variables in patients with severe PE. Methods: A retrospective case–control study was conducted in a public teaching hospital from January 2016 to June 2022. Cases included patients with severe PE and an Apgar score below 7 at 1 or 5 minutes, while controls had severe PE with an Apgar score of 7 or higher. A total of 125 cases and 303 controls were included. Fisher's exact test, logistic regression and receiver operating characteristic (ROC) analysis were used as appropriated. Results: 22 potential risk factors were assessed, of which 12 were significantly associated with changes in outcome. Multivariate analysis identified gestational age at delivery (GAD) (odds ratio [OR], 0.570; 95% confidence interval [CI], 0.420–0.774; p < 0.001), intravenous anesthesia (OR, 12.889; 95% CI, 3.820–43.486; p < 0.001) and PE onset weeks (OR, 0.937; 95% CI, 0.879–0.999; p = 0.047) as independent risk factors for low Apgar scores in neonates with severe PE. The accuracy of predicting low Apgar scores in newborns of PE patients was high based on GAD (area under the curve [AUC], 0.868; 95% CI, 0.832–0.905; p < 0.001) and PE onset weeks (AUC, 0.785; 95% CI, 0.741–0.828; p < 0.001). Conclusion: The GAD (<30.5 weeks) and PE onset weeks (<28.5 weeks) are identified as risk factors for low Apgar scores in newborns of patients with severe PE, and general anesthesia is suggested to be avoided during delivery.
Clinical Significance of Abnormalities in Fetal Kidney Location or Number Diagnosed by Prenatal Ultrasound
Authors: He Lihong , Zhao Jing , Wang Hongli , Wei Rong , Liu Yun , Zha Xiaoxia , Zhang Chunguo
Published: December 2024

Background: The abnormal position or number of fetal kidneys accounts for 15%–20% of congenital abnormalities in the fetus, often resulting in oligo amniotic fluid or no amniotic fluid, thus affecting the development of fetal lung and resulting in a significant increase in the perinatal mortality of children. Therefore, detailed prenatal examination and evaluation of fetal kidneys should be carried out. Methods: We retrospectively analyzed data on fetuses with abnormal kidney location or number, as diagnosed by prenatal ultrasound in our hospital from January 2014 to December 2021. And analysis of the image characteristics, combined with intracardiac and extracardiac malformations, abnormal appendage and pregnancy outcomes, and statistical analysis of the ratio of each type of combined intracardiac malformation, combined with extracardiac malformation, abnormal appendage and induced labor rate respectively. Results: (1) A total of 7953 fetal cases were systematically screened, of which 391 had an abnormal fetal kidney location or number. These included 50 cases of horseshoe kidney, 169 cases of pelvic ectopic kidney, 12 cases of crossed ectopic kidney, and 160 cases of renal absence. (2) The 391 fetuses included 35 cases with intracardiac malformation, 163 cases with extracardiac malformation, and 85 cases with abnormal appendages. (3) With regard to pregnancy outcomes, 324 fetuses were born healthy and showed no significant abnormalities up to 2 years after birth, whereas 67 pregnancies were terminated due to severe fetal malformations. (4) There was no statistical significance in the ratio of intracardiac malformations among the four groups of horseshoe kidney, pelvic ectopic kidney, crossed ectopic kidney, and renal absence (p > 0.05); there was statistical significance in the ratio of the four groups with extracardiac malformations (p < 0.05); there was statistical significance in the ratio of the four groups with abnormal appendage (p < 0.05). The ratio of induced labor rate of the four groups was compared, and the difference was statistically significant (p < 0.05). Conclusions: Detailed prenatal ultrasonography can accurately diagnose fetal kidney location or number abnormalities, as well as fetal complications such as intra- and extra-cardiac malformations and abnormal appendages, providing important imaging information for subsequent clinical and eugenic care.
Assessment of the Impact of Assisted Reproductive Technology on the Incidence of Vacuum-Assisted Delivery
Authors: Arakaki Ryosuke , Isono Wataru , Fukuda Hiroaki , Tanaka Junya , Minamino Arisa , Hayash Shiko
Published: December 2024

Background: In Japan, the rising number of nulliparous women of advanced maternal age (AMA) conceiving via assisted reproductive technology (ART) is anticipated to lead to an increase in adverse labor outcomes, even when the progression of labor appears to be favorable. Therefore, by examining the likelihood of vacuum-assisted delivery (VaD), our aim was to confirm the potential adverse impact of AMA and a history of ART treatment on labor outcomes. Methods: In this retrospective cohort study, the medical records of 542 nulliparous pregnant women aged 30 years or older who delivered at our hospital between April 1, 2017 and March 31, 2024, were reviewed with the approval of the institutional review board. First, we compared the characteristics, including labor conditions and delivery outcomes, of 417 patients who underwent spontaneous vaginal delivery (SVD) with those of 125 patients who underwent VaD. Next, we performed multivariate analysis to assess the effect of various representative factor, including AMA and a history of ART treatment, in order to confirm their actual impact on the likelihood of VaD. Results: In the simple comparison, maternal age, history of ART treatment, the amount of blood loss, and Apgar scores differed significantly between the two groups. However, in the multivariate analysis, only two factors, including history of ART treatment and uterine leiomyoma status, were found to significantly affect the likelihood of VaD. Conclusions: We detected a clear effect of both uterine leiomyoma status and a history of ART treatment on the likelihood of VaD, while AMA did not emerge as a significant factor. Further studies are needed to confirm the adverse impact of a history of ART treatment on labor progression.
Gestational Diabetes and Type 1 Diabetes Affects Gustatory Sense but not Saccadic Eye Movements—A Prospective Cohort Study
Authors: Kania Michał , Wilk Magdalena , Kwiatkowska Magdalena , Kopka Marianna , Witek Przemysław , Krawczyk Magdalena , Cyganek Katarzyna , Szopa Magdalena
Published: December 2024

Background: Nutritional therapy is the basis of diabetes treatment. Non-compliance with dietary recommendations is a common obstacle in the treatment of diabetes, with attenuated taste perception being one of many potential responsible factors. We investigated the impact of gestational diabetes mellitus (GDM) and type 1 diabetes (T1D) on two sensory modalities—saccadic eye movement and gustatory sense. Methods: In this prospective cohort study, we included 91 participants—28 women with GDM, 26 nonpregnant women with T1D and 37 non-diabetic non-pregnant women. We performed gustatory sense examination (GSE) with test strips for taste modalities and saccadic eye movement examination (SEME) and compared obtained results between study groups. This study was started prior to the requirement for registration of interventional cohort studies. Results: The mean age of participants was 29.4 ± 5.2 years. Women from the GDM group were older (31.0 [interquartile ranges (IQR): 29.0–35.8] vs. 28.0 [IQR: 22.5–34.8] and 28.0 [IQR: 25.3–30.0] years, p = 0.003) and had higher pre-pregnancy body mass index (BMI) compared to women with T1D and controls (26.2 [IQR: 20.8–28.5] vs. 22.6 [IQR: 20.9–24.4] and 20.9 [IQR: 19.1–22.3] kg/m2, p = 0.001). The total gustatory score was lower in women with GDM and T1D than controls with no significant difference between the GDM and T1D groups (68.8% [56.3%–75.0%], 67.5% [55.0%–76.3%], and 80.0% [70.0%–85.0%], respectively, p < 0.001). Saccadic latency was borderline higher in GDM than in the control group (189.5 ms [162.8–214.3] vs. 167.5 ms [154.5–186.3], p = 0.054) and duration was shorter in GDM than in T1D group (50.0 ms [47.0–53.0] vs. 54.5 ms [48.0–60.3], p = 0.041), with no differences in saccadic amplitude, mean and peak velocity between the studied groups. Conclusions: The gustatory sense was attenuated to a similar degree in nonpregnant women with T1D and those with GDM, when compared to non-diabetic non-pregnant women. This partially explains the phenomenon of cravings and affects compliance to dietary recommendations. Gustatory testing could be a potential measure to improve the metabolic control of diabetes and reducing the risk of maternal and neonatal complications of pregnancy. More studies in diverse populations of T1D patients are needed to assess the effectiveness of saccadometry in screening for diabetic neuropathy.
The Warburg Effect: Is it Always an Enemy?
Authors: Papaneophytou Christos
Published: December 2024

The Warburg effect, also known as ‘aerobic’ glycolysis, describes the preference of cancer cells to favor glycolysis over oxidative phosphorylation for energy (adenosine triphosphate-ATP) production, despite having high amounts of oxygen and fully active mitochondria, a phenomenon first identified by Otto Warburg. This metabolic pathway is traditionally viewed as a hallmark of cancer, supporting rapid growth and proliferation by supplying energy and biosynthetic precursors. However, emerging research indicates that the Warburg effect is not just a strategy for cancer cells to proliferate at higher rates compared to normal cells; thus, it should not be considered an ‘enemy’ since it also plays complex roles in normal cellular functions and/or under stress conditions, prompting a reconsideration of its purely detrimental characterization. Moreover, this review highlights that distinguishing glycolysis as ‘aerobic’ and ‘anaerobic’ should not exist, as lactate is likely the final product of glycolysis, regardless of the presence of oxygen. Finally, this review explores the nuanced contributions of the Warburg effect beyond oncology, including its regulatory roles in various cellular environments and the potential effects on systemic physiological processes. By expanding our understanding of these mechanisms, we can uncover novel therapeutic strategies that target metabolic reprogramming, offering new avenues for treating cancer and other diseases characterized by metabolic dysregulation. This comprehensive reevaluation not only challenges traditional views but also enhances our understanding of cellular metabolism’s adaptability and its implications in health and disease.
Identification and Characterisation of Potential Targets for N6-methyladenosine (m6A) Modification during Intervertebral Disc Degeneration
Authors: Shen Jianlin , Zhang Qiang , Lan Yujian , Peng Qingping , Ji Ziyu , Wu Yanjiao , Liu Huan
Published: December 2024

Background: The mechanism for RNA methylation during disc degeneration is unclear. The aim of this study was to identify N6-methyladenosine (m6A) markers and therapeutic targets for the prevention and treatment of intervertebral disc degeneration (IDD). Methods: Methylated RNA immunoprecipitation sequencing (MeRIP-seq) and quantitative reverse transcription PCR (RT-qPCR) were employed to analyze m6A modifications of IDD-related gene expression. Bioinformatics was used to identify enriched gene pathways in IDD. m6A-RIP-qPCR was used to validate potential targets and markers. Results and Conclusion: Human IDD samples exhibited a distinct m6A modification pattern that allowed associated genes and pathways to be identified. These genes had functions such as “nuclear factor kappa-B (NF-κB) binding” and “extracellular matrix components”, which are crucial for IDD pathogenesis. ANXA2 showed increased m6A modification in IDD, while SLC3A2 and PBX3 showed decreased m6A methylation. The results of this study offer novel insights for the prevention and treatment of IDD.
Differential Response to Cisplatin between Co-cultured Cells and Pure Cultured Cells Based on Single-cell RNA Sequencing of Three-dimensional-cultured Breast Cancer Cells
Authors: Yang Shuqing , Chen Peixian , Mao Xiaofan , Lin KaiRong , Li Wei , He Tiancheng , Huang Huiqi , Wu AiGuo , Luo Wei , Ye Guolin , Yao Guangyu , Zhou Dan
Published: December 2024

Objective: The current study aimed to develop an experimental approach for the direct co-culture of three-dimensional breast cancer cells using single-cell RNA sequencing (scRNA-seq). Methods: The following four cell culture groups were established in the Matrigel matrix: the untreated Michigan Cancer Foundation (MCF)-7 cell culture group, the MCF-7 cell culture plus cisplatin group, the untreated co-culture group, and the cell co-culture plus cisplatin group. For cell co-culture, MCF-7 cells, human mammary fibroblasts, and human umbilical vein endothelial cells were mixed at a ratio of 1:1:1. Cisplatin was applied at a concentration of 1.25 μg/mL, and the cells were harvested after 2 days and subjected to scRNA-seq. Data were analyzed using a single-cell RNA sequencing data analysis pipeline with R language. Results: The response of MCF-7 cells to cisplatin differed among the four groups. The transcriptomic response of MCF-7 cells to cisplatin in the co-culture model was not as significant as that in the mono-culture model. Moreover, the pathways related to apoptosis, DNA damage, hypoxia, and metastasis in the co-culture groups were enriched in the genes that were differentially expressed based on cisplatin treatment. Conclusion: scRNA-seq analysis revealed that the response of MCF-7 cells to cisplatin in the co-culture model was lower than that in the mono-culture model. Therefore, the three-dimensional cell co-culture model can be applied to tumor research to better mimic the pathophysiological environment in vivo and can be a well-modified research method.
Dexmedetomidine Mitigates Acute Lung Injury by Enhancing M2 Macrophage Polarization and Inhibiting RAGE/Caspase-11-Mediated Pyroptosis
Authors: Zhao Yisi , Li Kefeng , Wang Liuyang , Kuang Gang , Xie Ke , Lin Shihui
Published: December 2024

Background: Acute lung injury (ALI) significantly impacts the survival rates in intensive care units (ICU). Releasing a lot of pro-inflammatory mediators during the progression of the disease is a core feature of ALI, which may lead to uncontrolled inflammation and further damages the tissues and organs of patients. This study explores the potential therapeutic mechanisms of Dexmedetomidine (Dex) in ALI. Methods: In present study, cecal ligation puncture (CLP)-established ALI model mice and lipopolysaccharide (LPS)-stimulated RAW264.7 cell line were established to discover the influence of Dex. The evaluation of lung injury in vivo using histopathology, TUNEL assay, and analysis of inflammatory factors in bronchoalveolar lavage fluid (BALF) and serum. The receptor for advanced glycation end products (RAGE)/Caspase-11-dependent pyroptosis-related proteins and macrophage polarization markers were analyzed using western blot, immunofluorescence, and flow cytometry. Finally, the mechanism of Dex in macrophages was further verified in vitro. Results: In vivo, Dex alleviated lung injury and decreased TUNEL-positive cell expression in CLP group. Dex decreased tumor necrosis factor-alpha (TNF-α), interleukin (IL)-6 and IL-17A levels in BALF and serum, while increasing IL-10 expression. Dex treatment decreased the protein levels of RAGE, caspase-11, IL-1β and Gasdermin-D (GSDMD) in both in cells and in mice. Dex also down-regulated the synthesis of inducible nitric oxide synthase (iNOS) of classical activation phenotype (M1) markers, and up-regulated the synthesis of CD206 and Arg-1 of alternate activation phenotype (M2) markers. Conclusions: Dex treatment can inhibit inflammation and reduce lung injury caused by CLP. It could be associated with mediating M1 and M2 polarization and suppressing RAGE/Caspase-11-depended pyroptosis.
Indoleamine-2,3-dioxygenase (IDO) Mediates the Suppression of T Cells by IFN-γ Primed Mesenchymal Stromal Cells in the Treatment of Psoriasis-Like Inflammation
Authors: Zhu Weidong , Qi Chang , Shi Chenxi , Yang Hongli , Shi Feng , Ding Yayun
Published: December 2024

Background: Psoriasis is a chronic and incurable skin inflammation driven by an abnormal immune response. Our study aims to investigate the potential of interferon-γ (IFN-γ) primed mesenchymal stem cells (IMSCs) in targeting T cells to attenuate psoriasis-like inflammation, and to elucidate the underlying molecular mechanism involved. Methods: Mesenchymal stem cells (MSCs) were isolated from the umbilical cord and identified based on their surface markers. Psoriasis models were established and then treated with IMSCs. Flow cytometry analysis was used to examine cell surface markers and T cell percentages. Indoleamine-2,3-dioxygenase (IDO) was knocked down by small interfering RNA (siRNA) and examined with western blot assay. The proliferative capacity of T cells was assessed using water-soluble tetrazolium salt-1(WST-1). Additionally, an immunohistochemical assay was used to determine epidermal thickness. The psoriasis area and severity index (PASI) scores were also assessed. Results: We observed significant therapeutic efficacy of IMSCs against psoriasis-like inflammation in mice. Treatment with IMSCs resulted in a notable reduction in T cell infiltration within psoriatic lesions. Furthermore, we demonstrated that the therapeutic efficacy was mediated by the upregulation of IDO through IFN-γ stimulation. In vitro, IDO inhibited T cell proliferation, and in vivo, the therapeutic efficacy was eliminated when MSCs were transfected with IDO siRNA. Conclusion: IMSCs can treat psoriasis by suppressing T cell infiltration and the suppression is mediated by IDO.
Gene Fusion Detection in Long-Read Transcriptome Datasets from Multiple Cancer Cell Lines
Authors: Masuda Keigo , Sota Yoshiaki , Matsuda Hideo
Published: December 2024

Background: Fusion genes are important biomarkers in cancer research because their expression can produce abnormal proteins with oncogenic properties. Long-read RNA sequencing (long-read RNA-seq), which can sequence full-length mRNA transcripts, facilitates the detection of such fusion genes. Several tools have been proposed for detecting fusion genes in long-read RNA-seq datasets derived from cancer cells. However, the high sequencing error rate in long-read RNA-seq makes fusion gene detection challenging. Methods: To address this issue, additional steps were incorporated into the fusion detection tool to improve detection accuracy. These steps include anchoring breakpoints to exon boundaries, realigning unaligned regions, and clustering breakpoints. To evaluate the accuracy of our tool in detecting fusion genes, we compared its detection accuracy with two representative existing tools, JAFFAL and FusionSeeker. Results: Our tool outperformed the two existing tools in detecting fusion genes, as demonstrated in long-read RNA-seq datasets. We also identified potentially novel fusion genes consistently detected across multiple tools or datasets. Conclusions: The application of our tool to the detection of fusion genes in long-read RNA-seq datasets from two different cancer cell lines demonstrated the detection effectiveness of this tool.
Role of Hypoxia Induced by Medicinal Plants; A Revolutionary Era of Cellular and Molecular Herbal Medicine in Neuroblastoma Treatment
Authors: Rahimi Samin , Shirin Fatemeh , Moassesfar Mahdi , Zafari Hossein , Bahmaie Nazila , Baghebani Kimia , Bidmeshki Yasna , Sajjadi Manesh Seyede Masoumeh , Rasoulzadeh Darabad Kasra , Bahmaie Massoud , Nouri Elham , Kilic Ahmet , Ansarin Melika , Özışık Pınar , Simsek Ender , Ozensoy Guler Ozen
Published: December 2024

As one of the most common solid pediatric cancers, Neuroblastoma (NBL) accounts for 15% of all of the cancer-related mortalities in infants with increasing incidence all around the world. Despite current therapeutic approaches for NBL (radiotherapies, surgeries, and chemotherapies), these approaches could not be beneficial for all of patients with NBL due to their low effectiveness, and some severe side effects. These challenges lead basic medical scientists and clinical specialists toward an optimal medical interventions for clinical management of NBL. Regardingly, taking molecular and cellular immunopathophysiology involved in the hypoxic microenvironment of NBL into account, it can practically be a contributing approach in the development of “molecular medicine” for treatment of NBL. Interestingly, pivotal roles of “herbal medicine” in the hypoxic microenvironment of NBL have been extensively interrogated for treating a NBL, functionally being served as an anti-cancer agent via inducing a wide range of molecular and cellular signaling, like apoptosis, cell cycle arrest, and inhibiting angiogenesis. Hence, in this review study, the authors aim to summarize the anti-tumor effects of some medicinal plants and their phytoconstituents through molecular immunopathophysiological mechanisms involved in the hypoxic microenvironment of NBL. In addition, they try to open promising windows to immune gene-based therapies for NBL “precision medicine” through clinical advantages of herbal and molecular medicine. An interdisciplinary collaboration among translation and molecular medicine specialists, immunobiologists, herbal medicine specialists, and pediatric neuro-oncologists is highly recommended.
VPO1 Promotes Programmed Necrosis of Cardiomyocytes in Rats with Chronic Heart Failure by Upregulating CYLD
Authors: Zhang Yinzhuang , Shen Zhijie , Mao Zhuoni , Huang Dan , Lou Chengyu , Fang Li
Published: December 2024

Background: Chronic heart failure (CHF) is a serious cardiovascular condition. Vascular peroxidase 1 (VPO1) is associated with various cardiovascular diseases, yet its role in CHF remains unclear. This research aims to explore the involvement of VPO1 in CHF. Methods: CHF was induced in rats using adriamycin, and the expression levels of VPO1 and cylindromatosis (CYLD) were assessed. In parallel, the effects of VPO1 on programmed necrosis in H9c2 cells were evaluated through cell viability assays, lactate dehydrogenase (LDH) level measurements, and analysis of receptor-interacting protein kinase 1/receptor-interacting protein kinase 3/mixed lineage kinase domain-like protein (RIPK1/RIPK3/MLKL) pathway-related proteins. The impact of CYLD on RIPK1 protein stability and ubiquitination was also investigated, along with the interaction between VPO1 and CYLD. Additionally, cardiac structure and function were assessed using echocardiography, Hematoxylin-eosin (HE) staining, Masson staining, and measurements of myocardial injury-related factors, including N-terminal prohormone of brain natriuretic peptide (NT-proBNP), Aspartate aminotransferase (AST), LDH, and creatine kinase-myocardial band (CK-MB). Results: VPO1 expression was upregulated in CHF rats and in H9c2 cells treated with adriamycin. In cellular experiments, VPO1 knockdown improved cell viability, inhibited necrosis and the expression of proteins associated with the RIPK1/RIPK3/MLKL pathway. Mechanistically, VPO1 promoted cardiomyocyte programmed necrosis by interacting with the deubiquitinating enzyme CYLD, which enhanced RIPK1 ubiquitination and degradation, leading to activation of the RIPK1/RIPK3/MLKL signaling pathway. At animal level, overexpression of CYLD counteracted the cardiac failure, cardiac hypertrophy, myocardial injury, myocardial fibrosis, and tissue necrosis caused by VPO1 knockdown. Conclusions: VPO1 exacerbates cardiomyocyte programmed necrosis in CHF rats by upregulating CYLD, which activates the RIPK1/RIPK3/MLKL signaling pathway. Thus, VPO1 may represent a potential therapeutic target for CHF.
Conservation Genetics and Breeding using Molecular Genetic Markers in Japanese Quail (Coturnix japonica)
Authors: Romanov Michael N. , Ameen Questan Ali , Shaker Ahmed Sami , Al-Obaidi Rana Mohammed , Griffin Darren K.
Published: December 2024

Background: The Japanese quail (Coturnix japonica) is a small migratory bird whose main habitats are located in East Asia, Russia, China, Japan, Korea, and India. The Japanese quail was first introduced into the Iraqi research sector in the early 1980s. This investigation aimed to identify the genetic divergence between the available genetic lines of the Japanese quail in Iraq as a first step to conducting further conservation and breeding, benefiting from studying the genetic diversity related to productivity, adaptation, and immune susceptibility. Methods: In this study, we harnessed the random amplified polymorphic DNA (RAPD)-polymerase chain reaction (PCR) protocol to investigate the genetic structure, diversity, and differentiation of seven distinct genetic lines of these birds with white, brown, wild grey, and yellow plumage guided by 20 molecular genetic markers. Results: Our findings showed a relatively high polymorphism level of these 20 markers, which was adequate for describing genetic variation within and between the quail lines under study. Overall, the pairs of the White male and Brown male, Brown female and Grey male, and Grey female and Grey male lines were the most genetically distant. Conversely, the White male and Grey male lines were the most similar. Conclusions: The genetic differences established between these lines can enable us to suggest recommendations for further conservation genetics and breeding of this species. In particular, we propose that choosing animals (lines) with the greatest genetic distances, i.e., the least genetic similarities, can help preserve the highest genetic variability within the population. This proposed approach mirrors many contemporary conservation strategies, and information derived directly from this study can potentially be used to improve breeder selection regimes for additional conservation initiatives ex situ.
GWAS-Significant Loci and Uterine Fibroids Risk: Analysis of Associations, Gene-Gene and Gene-Environmental Interactions
Authors: Ponomareva Liubov , Kobzeva Ksenia , Bushueva Olga
Published: December 2024

Background: Uterine fibroids (UF) is the most common benign tumour of the female reproductive system. We investigated the joint contribution of genome-wide association studies (GWAS)-significant loci and environment-associated risk factors to the UF risk, along with epistatic interactions between single nucleotide polymorphisms (SNPs). Methods: DNA samples from 737 hospitalised patients with UF and 451 controls were genotyped using probe-based PCR for seven common GWAS SNPs: rs117245733 LINC00598, rs547025 SIRT3, rs2456181 ZNF346, rs7907606 STN1, SLK, rs58415480 SYNE1, rs7986407 FOXO1, and rs72709458 TERT. Results: We observed an association between rs547025 SIRT3 and the decreased risk of UF in overall group (effect allele C, odds ratio (OR) = 0.61, 95% confidence interval (CI) = 0.43–0.866, p = 0.005). SNP rs547025 exhibits protective effects against UF exclusively in patients with normal fruit and vegetable intake (OR = 0.39, 95% CI = 0.21–0.75, p = 0.002), no history of spontaneous abortions (OR = 0.48, 95% CI = 0.33–0.70, p = 0.0001), no pelvic inflammatory diseases (PID) in anamnesis (OR = 0.55, 95% CI = 0.38–0.80, p = 0.0016), and in smokers (OR = 0.20, 95% CI = 0.06–0.65, p = 0.006). In addition, rs7907606 STN1, SLK was associated with the risk of UF in patients without a history of pelvic inflammatory diseases (PID) (OR = 1.34, 95% CI = 1.03–1.74, p = 0.028). SNPs rs547025 SIRT3 and rs7907606 STN1, SLK, displayed the strongest mono-effects (0.71% and 0.52% contribution to UF entropy) and were characterized by the most pronounced gene-gene (G×G) effects when interacting with each other (0.60% contribution to entropy). The interaction Medical abortion×rs547025 SIRT3 served as the base for all the best gene-environment (G×E) models. Medical abortions have the most pronounced mono-effect (1.15% contribution to the entropy of UF), exceeding the mono-effects of SNPs involved in the most significant G×E-models (0.01%–0.49% contribution to entropy) and spontaneous abortions (0.48% of UF entropy) and exceeding the effects of G×E interactions (0.05–0.46% of UF entropy). Conclusions: Bioinformatics analysis showed that GWAS SNPs are involved in the molecular mechanisms of UF mainly through the regulation of vasculogenesis, cell proliferation, apoptosis, DNA damage, inflammation, hypoxia, steroid hormone metabolism, cell signaling, organ formation.
Interferon Gamma Gene Polymorphisms in Greek Primary Breast Cancer Patients
Authors: Kuol Nyanbol , Yan Xu , Karakkat Jimsheena , Vassilaros Stamatis , Fyssas Ioannis , Tsibanis Anastasios , Fraser Sarah , Nurgali Kulmira , Apostolopoulos Vasso
Published: December 2024

Background: Breast cancer is a heterogeneous disease with distinct clinical subtypes, categorized by hormone receptor status, which exhibits different prognoses and requires personalized treatment approaches. These subtypes included luminal A and luminal B, which have different prognoses. Breast cancer development and progression involve many factors, including interferon-gamma (IFNG). Moreover, single nucleotide polymorphisms (SNPs) in IFNG have been associated with cancer risk. However, the functional role of IFNG polymorphisms in primary breast cancer subtypes, luminal A and luminal B, is unclear. Methods: A total of 138 breast cancer tissues were acquired: 81 had luminal A, 42 had luminal B, 10 had triple-negative, and 3 had human epidermal growth factor receptor 2 (HER2) subtypes, while 2 had missing data. The tissues were evaluated in relation to luminal A and luminal B primary breast cancer subtypes. DNA was extracted from freshly frozen samples, and three SNPs (rs1861493 (chr12:68157416 (GRCh38.p13)), rs1861494 (chr12:68157629 (GRCh38.p13)) and rs2430561 (chr12:68158742 (GRCh38.p13))) in the IFNG gene were selected and evaluated based on previously published associations with cancer or other diseases. Results: The data showed that IFNG polymorphisms rs1861493 and rs1861494 were associated with breast cancer risk, with the A allele of rs1861493 and T allele of rs1861494 being noted as the risk alleles. Furthermore, the IFNG polymorphism rs2430561 was associated with breast cancer risk, with the A allele being the risk allele. In addition, the risk alleles were more prevalent in the more aggressive subtype, luminal B breast cancer, compared to luminal A. Similarly, the rs2430561 AA genotype was associated with the breast cancer severity. Conclusion: IFNG polymorphisms rs1861493, rs1861494, and rs2430561, with their respective risk alleles, are associated with increased breast cancer risk and severity. These risk alleles are more prevalent in the aggressive luminal B subtype compared to luminal A, indicating their role in both the prevalence and prognosis of breast cancer in a Greek population.
Coherent Changes in Neural Motor Network Activity during Levodopa-Induced Dyskinesia in a Rat Model of Parkinson’s Disease
Authors: Brazhnik Elena S. , Mysin Ivan E. , Popova Lyudmila B. , Minaychev Vladislav V. , Novikov Nikolay I.
Published: December 2024

Background: Long-term use of levodopa, a metabolic precursor of dopamine (DA) for alleviation of motor symptoms in Parkinson’s disease (PD), can cause a serious side effect known as levodopa-induced dyskinesia (LID). With the development of LID, high-frequency gamma oscillations (~100 Hz) are registered in the motor cortex (MCx) in patients with PD and rats with experimental PD. Studying alterations in the activity within major components of motor networks during transition from levodopa-off state to dyskinesia can provide useful information about their contribution to the development of abnormal gamma oscillations and LID. Methods: Freely moving rats with unilateral 6-hydroxydopamine hydrobromide (6-OHDA)-induced nigral DA cell lesions were administered a high dose of levodopa for 7 days. Local field potentials (LFPs) and neuronal activity were recorded from electrodes implanted in the motor cortex (MCx), ventromedial nucleus of the thalamus (VM), and substantia nigra pars reticulata nucleus (SNpr). Results: Levodopa reduced the power of beta oscillations (30–36 Hz) associated with bradykinesia in PD rats in three divisions of the motor neural network (MCx, VM, and SNpr) and prompted subsequent emergence of robust high-frequency gamma oscillations (80–120 Hz) in VM and MCx, but not SNpr, LFPs. Gamma oscillations were strongly associated with the occurrence of abnormal involuntary movements (AIMs) and accompanied by an increase in spiking rates in the VM and MCx and enlarged spike-LFP synchronization with cortical gamma oscillations (68% in the VM and 34% in the MCx). In contrast, SNpr LFPs did not exhibit gamma oscillations during LID, and neuronal activity in most recordings (87%) was largely decreased and not synchronized with VM or MCx LFPs. Administration of the antidyskinetic drug 8-hydroxy-2-(dipropylamino)-tetraline hydrobromide (8-OH-DPAT) restored the initial characteristics of LFPs (30–36 Hz oscillations), rates of neuronal activity, and bradykinesia. Inhibition of VM neurons by the gamma-aminobutyric acid (GABA-A)-agonist muscimol during LID eliminated high gamma oscillations in the MCx and VM, but not dyskinesia, suggesting that gamma oscillations are not critical for the expression of AIMs. In contrast, chemogenetic activation of SNpr neurons during LID eliminated both gamma oscillations and dyskinesia. Conclusions: These findings suggest that levodopa treatment leads to crucial reduction of inhibitory control over motor networks due to a large decline in spiking of most SNpr GABAergic projecting neurons, which causes persistent hyperactivity in motor circuits, leading to the appearance of thalamocortical gamma oscillations and LID.
Characterizing Vericiguat Treatment in Heart Failure: A Multicenter Real-World Study in China
Authors: Wang Qi , Wang Guangchuan , Peng Jiecheng , Li Jingjing , Ju Changlin , Pan Lingxin , Xu Zhiwei , Qian Jun , Liu Zhiquan , Wu Guohong , Wei Xueping , Yan Ji , Xiang Xuejun , Chen Kangyu ,   on behalf of the HCDCG
Published: December 2024

Background: Real-world data on the clinical benefit of vericiguat are currently limited. This multicenter, real-world study was conducted to evaluate the clinical characteristics and therapeutic effects of vericiguat in real-world settings. Methods: This study analyzed heart failure (HF) patients who initiated vericiguat treatment from September 2022 to August 2023 across nine hospitals in the Anhui Province, China. The clinical data were retrospectively collected and cases were prospectively followed to assess changes from baseline in N-terminal pro-B type natriuretic peptide (NT-proBNP) at 12 months. Baseline characteristics were compared with those in the VICTORIA trial. Results: Of the 285 patients enrolled, the mean age was 64.8 ± 12.9 years. Of these, 22.8% were female, and 94.7% were classified as New York Heart Association class III–IV. Additionally, 66.4% had a reduced ejection fraction with a median NT-proBNP level of 2915 pg/mL. Vericiguat therapy was initiated during hospitalization in 223 patients (78.2%), with 105 (37.1%) receiving quadruple anti-HF therapy. Only 44.9% met the VICTORIA trial inclusion criteria. Conclusions: In this multicenter, real-world study of vericiguat in Anhui Province, only 44.9% of vericiguat users met the inclusion criteria for the VICTORIA trial. This suggests that vericiguat is being applied more broadly by physicians to treat HF in real clinical settings.
Prognostic Value of Serum Neutrophil Gelatinase-Associated Lipocalin in Acute Heart Failure: A Meta-Analysis
Authors: Cheng Zhendong , Lin Xiaoxin , Xu Chaoxiang , Zhang Zhilong , Lin Naping , Cai Kefeng
Published: December 2024

Background: Neutrophil gelatinase-associated lipocalin (NGAL) is not only a sensitive marker of acute kidney injury but may also be a prognostic marker of acute heart failure (AHF). This study aimed to investigate the relationship between serum NGAL and all-cause death (ACD) and the composite outcome of ACD or AHF readmissions in patients with AHF. Methods: The Embase, Cochrane Library, and PubMed databases were searched for articles focusing on serum NGAL and ACD and the composite outcome of ACD or AHF readmissions in patients with AHF. The hazard ratios (HRs) were pooled with random-effects models. Results: The results from 2428 patients from seven studies were pooled in this article. Higher NGAL was relevant to an increased risk of ACD (HR, 1.89; 95% CI, 1.38 to 2.61) and the composite outcome of ACD or AHF readmissions (HR, 2.92; 95% CI, 1.62 to 5.27) in patients with AHF. Conclusions: Serum NGAL has prognostic value for ACD and the composite outcome of ACD or AHF readmissions in AHF. The PROSPERO registration: CRD42022322057, https://www.crd.york.ac.uk/prospero/display_record.php?ID=CRD42022322057.
Exploring the Prognostic Role of Red Blood Cell Distribution Width in Aortic Valve Calcification Evaluations via Multi-Slice Computed Tomography
Authors: Zeng Yiyao , Jin Fulu , Wang Li , Wang Peiyu , Xiong Hui , Zhou Yafeng , Jiang Yufeng , Zhao Liangping
Published: December 2024

Background: Previous reports have indicated an association between red blood cell distribution width (RDW) and cardiovascular disease. However, few relevant studies exist on the relationship between RDW and aortic valve calcification (AVC). Explore the correlation and predictive value of RDW concerning the occurrence and severity of aortic valve calcification. Methods: Blood examination results were analyzed from 1720 hospitalized patients at the Second Affiliated Hospital of Soochow University. Logistic regression analysis and the Cox proportional hazards model examined the relationship between RDW and the incidence and severity of AVC. Results: The RDW value in cases with AVC was significantly higher than in the control group. Red cell distribution width-standard deviation (RDW–SD) and red cell distribution width-coefficient of variation (RDW–CV) increased with calcification severity. Both RDW–SD and RDW–CV demonstrated high predictive values for the occurrence of aortic valve calcification. Conclusions: Red blood cell distribution width significantly correlated with the occurrence and severity of aortic valve calcification.
Progress in the Clinical Application of Artificial Intelligence for Left Ventricle Analysis in Cardiac Magnetic Resonance
Authors: Le Yinghui , Zhao Chongshang , An Jing , Zhou Jiali , Deng Dongdong , He Yi
Published: December 2024

Cardiac magnetic resonance (CMR) imaging enables a one-stop assessment of heart structure and function. Artificial intelligence (AI) can simplify and automate work flows and improve image post-processing speed and diagnostic accuracy; thus, it greatly affects many aspects of CMR. This review highlights the application of AI for left heart analysis in CMR, including quality control, image segmentation, and global and regional functional assessment. Most recent research has focused on segmentation of the left ventricular myocardium and blood pool. Although many algorithms have shown a level comparable to that of human experts, some problems, such as poor performance of basal and apical segmentation and false identification of myocardial structure, remain. Segmentation of myocardial fibrosis is another research hotspot, and most patient cohorts of such studies have hypertrophic cardiomyopathy. Whether the above methods are applicable to other patient groups requires further study. The use of automated CMR interpretation for the diagnosis and prognosis assessment of cardiovascular diseases demonstrates great clinical potential. However, prospective large-scale clinical trials are needed to investigate the real-word application of AI technology in clinical practice.
Spontaneous Coronary Dissection Review: A Complex Picture
Authors: Bollati Mario , Ercolano Vincenzo , Mazzarotto Pietro
Published: December 2024

Spontaneous coronary artery dissection (SCAD) represents a quite rare event but with potentially serious prognostic implications. Meanwhile, SCAD typically presents as an acute coronary syndrome (ACS). Despite the majority of SCAD presentation being characterized by typical ACS signs and symptoms, young age at presentation with an atypical atherosclerotic risk factor profile is responsible for late medical contact and misdiagnosis. The diagnostic algorithm is similar to that for ACS. Low-risk factors prevalence and young age would push toward non-invasive imaging (such as coronary computed tomography (CT)); instead, the gold standard diagnostic exam for SCAD is an invasive coronary angiography (ICA) due to its increased sensitivity and disease characterization. Moreover, intravascular imaging (IVI) improves ICA diagnostic performance, confirming the diagnosis and clarifying the disease mechanism. A SCAD–ICA classification recognizes four angiographic appearances according to lesion extension and features (radiolucent lumen, long and diffuse narrowing, focal stenosis, and vessel occlusion). Concerning its management, the preferred approach is conservative due to the high rates of spontaneous healing in the first months and the low rate of revascularization success (high complexity percutaneous coronary intervention (PCI) with dissection/hematoma extension risk). Revascularization is recommended in the presence of high-risk features (such as left main or multivessel involvement, hemodynamic instability, recurrent chest pain, or ST elevation). The first choice is PCI; coronary artery bypass graft (CABG) is considered only if PCI is not feasible or too hazardous according to the operators’ and centers’ experience. Medical therapy includes beta blockers in cases of ventricular dysfunction; however, no clear data are available about antiplatelet treatment because of the supposed risk of intramural hematoma enlargement. Furthermore, screening for extracardiac arthropathies or connective tissue diseases is recommended due to the hypothesized association with SCAD. Eventually, SCAD follow-up is important, considering the risk of SCAD recurrence. Considering the young age of patients with SCAD, subsequent care is essential (including psychological support, also for relatives) with the aim of safe and complete reintegration into a non-limited everyday life.
A Two-Way Mendelian Randomization Analysis on the Link between Thyroid Activity Function and Coronary Atherosclerosis
Authors: Li Le-tai , Leng Jia-jie , Luo Yu-xiang , Liu Rong-jia , Song Zhuo-xuan , Ye Meng , Li Zhen-han , Cao Zhen-rui , Jiang Ying-jiu , Tie Hong-tao
Published: December 2024

Introduction: Coronary atherosclerosis serves as the primary pathological etiology underlying coronary artery disease (CAD). Thyroid hormones show potential as risk factors, aside from the main standard modifiable cardiovascular risk factors (SMuRFs). This research seeks to elucidate the link between thyroid activity and coronary atherosclerosis. Methods: Single nucleotide polymorphisms (SNPs) linked to hypothyroidism (N = 213,990), Graves’ disease (GD) (N = 190,034), other hyperthyroidism types (N = 190,799), thyroid-stimulating hormone (TSH) (N = 271,040), free thyroxine (FT4) (N = 119,120), and coronary atherosclerosis (N = 360,950) were retrieved from the IEU OpenGWAS, Finngen R9, and ThyroidOmics Consortium databases. Following the application of strict criteria to eliminate linkage disequilibrium, palindromic sequences, and heterozygous alleles, a bidirectional Mendelian Randomization (MR) analysis was conducted between the thyroid gland and coronary atherosclerosis using inverse variance weighting (IVW), weighted median (WM), and MR-Egger techniques. For sensitivity analysis, Cochran’s Q test, leave-one-out method, and MR-Egger regression analysis were employed. Results: The forward MR analysis indicates that genetic predispositions such as hypothyroidism (OR = 1.07; 95% CI 1.01–1.12; IVW-p = 0.021), Graves’ disease (OR = 1.04; 95% CI 1.01–1.07; IVW-p = 0.002), and other forms of hyperthyroidism (OR = 1.05; 95% CI 1.01–1.10; IVW-p = 0.021) elevate the likelihood of developing coronary atherosclerosis. Additionally, no discernible evidence of a causality between FT4 or TSH, and coronary atherosclerosis (IVW-p > 0.05) was found. Coronary atherosclerosis is not related to increased risk of five thyroid function phenotypes in reverse MR analysis. The sensitivity analysis provided relatively reliable evidence to reinforce the validity of our findings. Conclusions: Our findings are an investigation of the causality between thyroid function and coronary atherosclerosis. This study pinpointed potential heart disease risks linked to coronary atherosclerosis and offered additional understanding for defining SMuRFs in CAD.
The Effects of Seasonal Variation on the Outcomes of Patients Undergoing Off-Pump Coronary Artery Bypass Grafting
Authors: Wu Ling , Lin Pei-shuang , Yao Yun-tai ,   on behalf of the Evidence in Cardiovascular Anesthesia (EICA) Group
Published: December 2024

Background: The impact of seasonal patterns on the mortality and morbidity of surgical patients with cardiovascular diseases has gained increasing attention in recent years. However, whether this seasonal variation extends to cardiovascular surgery outcomes remains unknown. This study sought to evaluate the effects of seasonal variation on the short-term outcomes of patients undergoing off-pump coronary artery bypass grafting (OPCABG). Methods: This study identified all patients undergoing elective OPCABG at a single cardiovascular center between January 2020 and December 2020. Patients were divided into four groups according to the season of their surgery. The primary outcome was the composite incidence of mortality and morbidity during hospitalization. Secondary outcomes included chest tube drainage (CTD) within 24 h, total CTD, chest drainage duration, mechanical ventilation duration, and postoperative length of stay (LOS) in the intensive care unit (ICU) and hospital. Results: Winter and spring surgeries were associated with higher composite incidence of mortality and morbidities (26.8% and 18.0%) compared to summer (15.7%) and autumn (11.1%) surgeries (p < 0.05). Spring surgery had the highest median CTD within 24 hours after surgery (640 mL), whereas it also exhibited the lowest total CTD (730 mL) (p < 0.05). Chest drainage duration was longer in spring and summer than in autumn and winter (p < 0.05). While no significant differences were observed in mechanical ventilation duration and hospital stay among the four seasons, the LOS in the ICU was longer in summer than in autumn (88 h vs. 51 h, p < 0.05). Conclusions: The OPCABG outcomes might exhibit seasonal patterns in patients with coronary heart disease.
Plaque Stabilization and Regression, from Mechanisms to Surveillance and Clinical Strategies
Authors: Zhang Xi , Feng Huanhuan , Han Yan , Yuan Xiaohang , Jiang Mengting , Wang Wei , Gao Lei
Published: December 2024

With advances in therapies to reduce cardiovascular events and improvements in coronary imaging, an increasing number of clinical trials have demonstrated that treatments to reduce cardiovascular events in coronary artery disease are associated with favorable effects on atherosclerotic plaque size and characteristics. It has been observed that various drugs may induce plaque regression and enhance plaque stability after plaque formation. Numerous clinical trials have been conducted to verify the occurrence of plaque stabilization and regression and their beneficial effects on cardiovascular events. Using invasive imaging techniques such as intravascular ultrasound (IVUS) and optical coherence tomography (OCT), researchers have been able to gather evidence supporting the existence of coronary plaque stabilization and regression. In this review, we explore the possible mechanisms of plaque stabilization and regression, summarize the imaging features of plaque stabilization and regression, and assemble the evidence from clinical studies that have used different features as observational endpoints.