bluuebunny/crossref_metadata_2025_split huggingface dataset:
The relationship between autoimmune thyroid disease, thyroid nodules and sleep traits: a Mendelian randomization study
Authors: Wang Suijian , Wang Kui , Chen Xiaohong , Lin Shaoda 
Published: March 2024

BackgroundPrevious studies have suggested a potential association between Autoimmune thyroid disease Thyroid nodules and Sleep Traits, but the evidence is limited and controversial, and the exact causal relationship remains uncertain.ObjectiveTherefore, we employed a MR analysis to investigate the causal relationship between Autoimmune thyroid disease, Thyroid nodules and Sleep Traits.MethodsTo explore the interplay between Autoimmune thyroid disease Thyroid nodules and Sleep Traits, we employed MR studies utilizing summary statistics derived from GWAS in individuals of European ancestry. To ensure robustness, multiple techniques were employed to assess the stability of the causal effect, including random-effect inverse variance weighted, weighted median, MR-Egger regression, and MR-PRESSO. Heterogeneity was evaluated using Cochran’s Q value. Additionally, we investigated the presence of horizontal pleiotropy through MR-Egger regression and MR-PRESSO.ResultsThe IVW method indicates a significant causal relationship between “Getting up” and autoimmune hypothyroidism, as revealed by the IVW method (OR: 0.59, 95% CI: 0.45 to 0.78, P-value = 1.99e-4). Additionally, there might be a potential correlation between sleep duration and autoimmune hypothyroidism (OR: 0.76, 95% CI: 0.60 to 0.79, P-value = 0.024). Moreover, the observed potential positive link between daytime nap and thyroid nodules (OR: 1.66, 95% CI: 1.07 to 2.58, P-value = 0.023) is subject to caution, as subsequent MR PRESSO testing reveals the presence of horizontal pleiotropy, raising concerns about the reliability of the findings. The findings suggested a potential inverse association between Autoimmune hypothyroidism and Getting up (OR: 0.99, 95% CI: 0.98 to 1.00, P-value = 6.66e-3).As the results of MR-Egger method(OR: 1.00, 95% CI: 0.98 to 1.02, P-value = 0.742) exhibited an opposing trend to that observed with the IVW method and the results did not reach significance after P-value correction.ConclusionThe results of our study reveal a notable cause-and-effect relationship between Getting up and Autoimmune hypothyroidism, indicating its potential role as a protective factor against this condition. However, no causal connection was observed between sleep traits and Graves’ disease or Thyroid nodules
Risk factors associated with changes in serum anti-Müllerian hormone levels before and after laparoscopic cystectomy for endometrioma
Authors: Zhang Chenyu , Li Xiaoyan , Dai Yi , Gu Zhiyue , Wu Yushi , Yan Hailan , Li Qiutong , Shi Jinghua , Leng Jinhua 
Published: March 2024

BackgroundThe objective of our study was to investigate the risk factors for a decrease in ovarian reserve in patients with endometriomas after standardized laparoscopic procedures and evaluation to provide corresponding clinical guidance for patients with fertility requirements.MethodsAnti-Müllerian hormone (AMH) levels and other clinical data from 233 patients with endometriomas and 57 patients with non-endometrioma ovarian cysts admitted to the Peking Union Medical College Hospital between January 2018 and September 2023 were prospectively analysed. The pretreatment AMH levels of the study groups were compared to assess the impact of endometrioma on ovarian reserve, and the decrease in AMH after treatment was analysed to determine potential risk factors contributing to this change.ResultsPretreatment AMH levels did not significantly differ between patients with endometriomas and those with non-endometrioma ovarian cysts. Within the endometrioma group, older age, higher body mass index (BMI), and shorter menstrual cycles were found to be associated with decreased AMH levels prior to treatment (p&lt;0.05). Participants presenting with bilateral cysts, advanced surgical staging, or a completely enclosed Douglas pouch demonstrated significantly lower levels of AMH prior to treatment compared to those without these conditions (p&lt;0.05). Furthermore, their AMH levels further declined within one year after undergoing laparoscopic cystectomy (p&lt;0.05). However, there was no difference in AMH levels after surgery between patients who successfully became pregnant and those who did not (p&gt;0.05).ConclusionLaparoscopic removal of endometriomas can adversely affect ovarian reserve, especially during bilateral cysts removal and when patients are diagnosed as having a higher stage of endometriosis, further impacting ovarian function. It should be noted that a decrease in AMH levels may not necessarily indicate an absolute decline in fertility. Therefore, it is crucial to conduct thorough patient evaluations and provide comprehensive patient education to offer appropriate guidance for fertility preservation.
The role of random forest and Markov chain models in understanding metropolitan urban growth trajectory
Authors: Badshah Muhammad Tariq , Hussain Khadim , Rehman Arif Ur , Mehmood Kaleem , Muhammad Bilal , Wiarta Rinto , Silamon Rato Firdaus , Khan Muhammad Anas , Meng Jinghui 
Published: March 2024

IntroductionThis study delves into the spatiotemporal dynamics of land use and land cover (LULC) in a Metropolitan area over three decades (1991–2021) and extends its scope to forecast future scenarios from 2031 to 2051. The intent is to aid sustainable land management and urban planning by enabling precise predictions of urban growth, leveraging the integration of remote sensing, GIS data, and observations from Landsat satellites 5, 7, and 8.MethodsThe research employed a machine learning-based approach, specifically utilizing the random forest (RF) algorithm, for LULC classification. Advanced modeling techniques, including CA–Markov chains and the Land Change Modeler (LCM), were harnessed to project future LULC alterations, which facilitated the development of transition probability matrices among different LULC classes.ResultsThe investigation uncovered significant shifts in LULC, influenced largely by socio-economic factors. Notably, vegetation cover decreased substantially from 49.21% to 25.81%, while forest cover saw an increase from 31.89% to 40.05%. Urban areas expanded significantly, from 7.55% to 25.59% of the total area, translating into an increase from 76.31 km2 in 1991 to 258.61 km2 in 2021. Forest area also expanded from 322.25 km2 to 409.21 km2. Projections indicate a further decline in vegetation cover and an increase in built-up areas to 371.44 km2 by 2051, with a decrease in forest cover compared to its 2021 levels. The predictive accuracy of the model was confirmed with an overall accuracy exceeding 90% and a kappa coefficient around 0.88.DiscussionThe findings underscore the model’s reliability and provide a significant theoretical framework that integrates socio-economic development with environmental conservation. The results emphasize the need for a balanced approach towards urban growth in the Islamabad metropolitan area, underlining the essential equilibrium between development and conservation for future urban planning and management. This study underscores the importance of using advanced predictive models in guiding sustainable urban development strategies.
Single nucleotide variants in nuclear pore complex disassembly pathway associated with poor survival in osteosarcoma
Authors: Jacobs James E. , Davis Lara , McWeeney Shannon 
Published: March 2024

Introduction:The bone tumor, osteosarcoma, remains challenging to treat in children and young adults, especially when patients present with metastatic disease. Developing new therapies based on genomic data from sequencing projects has proven difficult given the lack of recurrent genetic lesions across tumors. MYC overexpression has been associated with poor outcomes in osteosarcoma. However, other genomic markers of disease severity are lacking.Materials and Methods:We utilized whole genome sequencing of 106 tumors and matched normal controls in order to define genomic characteristics that correlate with overall survival. Single nucleotide variants were overlaid onto annotated molecular pathways in order to define aberrant pathway signatures specific to aggressive osteosarcoma. Additionally, we calculated differential gene expression in a subsample of 71 tumors. Differentially expressed genes were then queried for known MYC-responsive genes.Results:Molecular pathways specific to nuclear pore complex disassembly (NPCD) show significant correlation with poor overall survival in osteosarcoma when mutations were present. Genes involved in immune response and immune regulation are enriched in the differential expression analysis of samples with and without NPCD pathway aberrations. Furthermore, neither MYC nor MYC-responsive genes show differential expression between NPCD-aberrant and non-aberrant groups. The NPCD pathway mutations are dominated by regulatory region variants rather than protein-altering mutations, suggesting that dysregulation of genetic regulatory networks may be the underlying mechanism for their relation to osteosarcoma phenotype.Discussion:Overall survival is significantly worse in patients whose tumors show aberrations in the NPCD pathway. Moreover, this difference in survival is not driven by MYC-overexpression, suggesting a novel mechanism for some aggressive osteosarcomas. These findings add light to the evolving understanding of the drivers of osteosarcoma and may aid in the search for new treatments based on patient-specific genetic data.
Predictive value of the neutrophil-to-lymphocyte ratio in the prognosis and risk of death for adult sepsis patients: a meta-analysis
Authors: Wu Hongsheng , Cao Tiansheng , Ji Tengfei , Luo Yumei , Huang Jianbin , Ma Keqiang 
Published: March 2024

BackgroundThe neutrophil-to-lymphocyte ratio (NLR) is a commonly used biomarker for acute inflammation that often rises during sepsis, making it a valuable diagnostic indicator for clinical practice. However, no consensus has been reached on the prognostic value of NLR for predicting the prognosis and mortality risk in adult sepsis patients. In light of this controversy, we conducted a meta-analysis to clarify the prognostic significance of NLR in adult sepsis patients. The meta-analysis was registered in the PROSPERO database (registration number CRD42023433143).MethodsWe performed a comprehensive literature search in PubMed, Cochrane Library, Ovid, and Springer databases, using retrieval terms “sepsis” or “septic shock” and “prognosis” or “mortality” for studies published between January 1, 2000, and May 31, 2023. Children and neonates with sepsis were excluded from our research. Two independent researchers conducted the literature search and data extraction. Consensus was reached when discrepancies occurred, and in case of persistent discrepancies, the final decision was made by the research supervisor. The hazard ratio (HR) and its corresponding 95% confidence interval (95% CI) were extracted from each study included in the analysis. A random-effects model was used to synthesize all HRs and their 95% CIs. Sensitivity analysis was performed to investigate heterogeneity. Sensitivity analysis was conducted to identify studies that had a significant impact on the overall results of the meta-analysis. Subgroup analysis and meta-regression were performed to explore sources of heterogeneity. Egger’s test was also used to investigate publication bias in this meta-analysis.ResultsAfter a comprehensive literature search and screening, we included 12 studies comprising 10,811 patients for the meta-analysis. The pooled results indicated that patients with a higher NLR level were associated with a poor prognosis (Random-effects model, HR: 1.6273, 95% CI: 1.3951-1.8981). Heterogeneity testing showed significant heterogeneity (I2 = 87.2%, 95% CI: 79.5-92, p&lt;0.0001). Sensitivity analysis was performed to investigate the sources of heterogeneity, which revealed that the omission of one highly sensitive study significantly reduced the I2 value. After removing this study, a strong association was found between a higher NLR level and poor prognosis and risk of death in adult sepsis patients (Random-effects model, HR: 1.6884, 95% CI: 1.4338-1.9882). Both subgroup analysis and meta-regression indicated that the study design and testing time of NLR were sources of heterogeneity. Egger’s test showed no obvious publication bias in this meta-analysis.ConclusionNLR is a reliable and valuable biomarker for predicting prognosis and the risk of death in adult sepsis patients.Systematic Review Registration[https://www.crd.york.ac.uk/prospero/display_record.php?ID=CRD42023433143] PROSPERO, identifier [CRD42023433143].
Causal effects of immune cell surface antigens and functional outcome after ischemic stroke: a Mendelian randomization study
Authors: Sun Weiming , Gui Jiawei , Wan Keqi , Cai Yize , Dong Xiangli , Yu Guohua , Zheng Chafeng , Feng Zhen , Shuai Lang 
Published: March 2024

ObjectiveWhile observational studies link immune cells with post-stroke functional outcome, the underlying immune mechanisms are not well understood. Immune cell surface antigens are actively involved in the biological behavior of immune cells, investigating immune cell surface antigens could deepen our comprehension of their role and biological processes in stroke recovery. Therefore, we aimed to investigate the immunological basis of stroke outcome by exploring the causal relationship between immune cell surface antigens and functional outcome after ischemic stroke in a Mendelian randomization study.MethodsGenetic variants related to immune cell surface antigens and post-stroke functional outcome were selected for two-sample Mendelian randomization (MR) analysis. 389 fluorescence intensities (MFIs) with surface antigens were included. Inverse variance weighted (IVW) modeling was used as the primary MR method to estimate the causal effect of exposure on the outcome, followed by several alternative methods and sensitivity analyses. Additional analysis of the association between immune cell surface antigens and risk of ischemic stroke for assessment of collider bias.ResultsWe found that suggestive associations between CD20 on switched memory B cell (OR = 1.16, 95% CI: 1.01-1.34, p = 0.036) and PDL-1 on monocyte (OR = 1.32, 95% CI: 1.04-1.66, p = 0.022) and poor post-stroke functional outcome, whereas CD25 on CD39+ resting Treg (OR = 0.77, 95% CI: 0.62-0.96, p = 0.017) was suggestively associated with good post-stroke functional outcome.ConclusionThe elevated CD20 on switched memory B cell, PDL-1 on monocyte, and CD25 on CD39+ resting Treg may be novel biomarkers and potential causal factors influencing post-stroke functional outcome.
Case report: Isolated axillary lymph node metastasis in high-risk endometrial cancer
Authors: Chen Yi-Ju Amy , Oo Myoe , Xu Yiqing 
Published: March 2024

IntroductionThere are risks of developing distant metastases over time for both early- and advanced-stage endometrial cancer. Axillary lymph node metastasis as the first site of recurrence, whether isolated or non-isolated, is uncommon, and there are currently no established treatment guidelines for such cases. This study highlights four cases of recurrent endometrial cancer that manifested axillary lymph node metastasis, providing a comprehensive review of their distinctive clinical behavior and the treatment strategies employed.MethodsWe reviewed and compared four cases of recurrent endometrial cancer that developed axillary lymph node metastasis following adjuvant treatment. Patients’ perspectives were also discussed.ResultsAll four patients had aggressive endometrial histology, including high-grade serous carcinoma and carcinosarcoma. The stages at presentation were stages I and III, with laparotomy or laparoscopy used as the initial surgical approach. Axillary lymph node metastasis was the primary site of recurrence in three cases. Of the three patients with isolated axillary lymph node metastasis, two had long-term survival after aggressive locoregional treatment comprising surgery and radiation.ConclusionAxillary lymph node metastasis as the first site of recurrence is rare, even in high-risk endometrial cancer. In addition to systemic chemotherapy, aggressive locoregional treatment can potentially maximize the chance of long-term disease control.
Isoquercitrin alleviates pirarubicin-induced cardiotoxicity in vivo and in vitro by inhibiting apoptosis through Phlpp1/AKT/Bcl-2 signaling pathway
Authors: Wang Lei , Ma Jiulong , Chen Chen , Lin Bin , Xie Sicong , Yang Weiwei , Qian Jiajia , Zhang Yang 
Published: March 2024

Introduction: Due to the cardiotoxicity of pirarubicin (THP), it is necessary to investigate new compounds for the treatment of THP-induced cardiotoxicity. Isoquercitrin (IQC) is a natural flavonoid with anti-oxidant and anti-apoptosis properties. Thus, the present study aimed to investigate the influence of IQC on preventing the THP-induced cardiotoxicity in vivo and in vitro.Methods: The optimal concentration and time required for IQC to prevent THP-induced cardiomyocyte damage were determined by an MTT assay. The protective effect was further verified in H9c2 and HCM cells using dichlorodihydrofluorescein diacetate fluorescent probes, MitoTracker Red probe, enzyme-linked immunosorbent assay, JC-1 probe, and real time-quantitative polymerase chain reaction (RT-qPCR). Rats were administered THP to establish cardiotoxicity. An electrocardiogram (ECG) was performed, and cardiac hemodynamics, myocardial enzymes, oxidative stress indicators, and hematoxylin-eosin staining were studied. Voltage-dependent anion channel 1 (VDAC1), adenine nucleotide translocase 1 (ANT1), and cyclophilin D (CYPD) were detected by qRT-PCR, and the Phlpp1/AKT/Bcl-2 axis proteins were detected by western blot, confirming that IQC markedly increased cell viability and superoxide dismutase (SOD) levels, diminished the levels of ROS and MDA, and elevated mitochondrial function and apoptosis in vivo and in vitro.Results: Results showed that IQC reduced THP-induced myocardial histopathological injury, electrocardiogram (ECG) abnormalities, and cardiac dysfunction in vivo. IQC also decreased serum levels of MDA, BNP, CK-MB, c-TnT, and LDH, while increasing levels of SOD and GSH. We also found that IQC significantly reduced VDAC1, ANT1, and CYPD mRNA expression. In addition, IQC controlled apoptosis by modulating Phlpp1/AKT/Bcl-2 signaling pathways. IQC markedly increased H9c2 and HCM cell viability and SOD levels, diminished the levels of ROS and MDA, and elevated mitochondrial function in H9c2 and HCM cells to defend against THP-induced cardiomyocyte apoptosis in vitro. The AKT inhibitor IMQ demonstrated that IQC lacked antioxidant and anti-apoptotic properties. Moreover, our data showed that IQC regulates Phlpp1 expression, thereby influencing the expression levels of p-AKT, cytochrome c, caspase-3, caspase-9, Bcl-2, and Bax.Discussion: In conclusion, our results indicate that IQC protects the changes in mitochondrial membrane permeability in cardiomyocytes by regulating the Phlpp1/AKT/Bcl-2 signaling pathway, inhibits the release of cytc from the mitochondrial inner membrane to the cytoplasm, forms apoptotic bodies, induces cell apoptosis, and reduces THP induced cardiotoxicity.
Examining the safety of mirabegron: an analysis of real-world pharmacovigilance data from the US FDA adverse event reporting system (FAERS) database
Authors: Wang Junwei , Zhang Aiwei , Ye Miaoyong , Zhang Cunming 
Published: March 2024

Background: Mirabegron, the first β-3 adrenergic receptor agonist, received approval from the Food and Drug Administration (FDA) in 2012 for the treatment of overactive bladder (OAB). This pharmacovigilance study investigated the safety profile of mirabegron treatment using the US FDA Adverse Event Reporting System (FAERS) database.Methods: This study employed disproportionality analyses, including the reporting odds ratio (ROR) and Bayesian Confidence Propagation Neural Network (BCPNN) algorithm, to quantify signals of adverse events associated with mirabegron.Results: From the first quarter of 2012 to the third quarter of 2023, a comprehensive total of 14,356,234 adverse event (AE) reports were submitted to the FDA Adverse Event Reporting System database. Within this dataset, encompassing 18,763 reports specifically associated with mirabegron, healthcare professionals notably contributed 2,902 of these reports. A total of 80 preferred terms (PTs) of interest were identified using both the ROR and information component algorithms. The most common AEs included blood pressure increased, urinary retention, atrial fibrillation, dry mouth, and tachycardia, which were consistent with the product instructions. Unexpected significant AEs, such as arrhythmia, palpitations, dementia, transient ischemic attack, Parkinson’s disease, anti-neutrophil cytoplasmic antibody positive vasculitis, lip swelling, and swollen tongue, were also identified. The study findings indicated that the majority of onset time occurred within 30 days (n = 358, 55.68%). However, AEs were still possible after 1 year of mirabegron treatment.Conclusion: This study provided valuable evidence for the real-world safety of mirabegron, helping clinical professionals enhance their understanding of mirabegron’s safety in clinical practice. It also contributed valuable evidence for further safety studies on mirabegron.
Fibrosis modeling choice affects morphology of ventricular arrhythmia in non-ischemic cardiomyopathy
Authors: Myklebust Lena , Maleckar Mary M. , Arevalo Hermenegild 
Published: March 2024

Introduction: Patients with non-ischemic cardiomyopathy (NICM) are at risk for ventricular arrhythmias, but diagnosis and treatment planning remain a serious clinical challenge. Although computational modeling has provided valuable insight into arrhythmic mechanisms, the optimal method for simulating reentry in NICM patients with structural disease is unknown.Methods: Here, we compare the effects of fibrotic representation on both reentry initiation and reentry morphology in patient-specific cardiac models. We investigate models with heterogeneous networks of non-conducting structures (cleft models) and models where fibrosis is represented as a dense core with a surrounding border zone (non-cleft models). Using segmented cardiac magnetic resonance with late gadolinium enhancement (LGE) of five NICM patients, we created 185 3D ventricular electrophysiological models with different fibrotic representations (clefts, reduced conductivity and ionic remodeling).Results: Reentry was induced by electrical pacing in 647 out of 3,145 simulations. Both cleft and non-cleft models can give rise to double-loop reentries meandering through fibrotic regions (Type 1-reentry). When accounting for fibrotic volume, the initiation sites of these reentries are associated with high local fibrotic density (mean LGE in cleft models: p< 0.001, core volume in non-cleft models: p = 0.018, negative binomial regression). In non-cleft models, Type 1-reentries required slow conduction in core tissue (non-cleftsc models) as opposed to total conduction block. Incorporating ionic remodeling in fibrotic regions can give rise to single- or double-loop rotors close to healthy-fibrotic interfaces (Type 2-reentry). Increasing the cleft density or core-to-border zone ratio in cleft and non-cleftc models, respectively, leads to increased inducibility and a change in reentry morphology from Type 2 to Type 1.Conclusions: By demonstrating how fibrotic representation affects reentry morphology and location, our findings can aid model selection for simulating arrhythmogenesis in NICM.