bluuebunny/crossref_metadata_2025_split huggingface dataset:
Case Report: Unmasking sustainable left ventricular recovery in chronic heart failure with axillary temporary mechanical circulatory support
Authors: Desai Aarti , Sharma Shriya , Luce Caitlyn , Ruiz Jose , Goswami Rohan 
Published: August 2024

BackgroundMechanical circulatory support (MCS), temporary or durable, is essential in patients with acute heart failure presenting in cardiogenic shock (CS). MCS is fundamental in patients with advanced heart failure when used as a bridge to decision, transplant or left ventricular recovery. Limited data on acute-on-chronic heart failure (HF) patients exists in the era of axillary mechanical circulatory support with the Impella 5.5. We describe a case of chronic ischemic cardiomyopathy, HF-CS, in a patient who underwent Impella placement, medical optimization, and explant, now with sustained normalization in ejection fraction.Case summaryA Caucasian female in her 50 s was referred to our center for evaluation for advanced therapies, including transplantation or durable left ventricular assist device placement. Her initial ejection fraction was 30% with comorbidities including multivessel coronary artery disease revascularized with 3 vessel bypass grafting ten years prior, type 2 diabetes (A1c 8.6%), and peripheral vascular disease. During her evaluation, she had acute decompensation leading to cardiogenic shock and required hospitalization with inotrope initiation, which was unable to be weaned. She was approved for organ transplant and listed; however, she required escalation of support and eventual placement of right axillary Impella 5.5. While on Impella support, her vasoactive needs reduced, and she was found to have left ventricular recovery and tolerated the initiation of guideline medical therapy. After three weeks of support, the Impella was weaned and explanted, and the patient was discharged. She remains stable with a sustained ejection fraction of greater than 50% with NYHA class 1 functional status at follow-up. One year later, the patient showed sustained myocardial recovery with guideline-directed medical therapy (GDMT).ConclusionOur case highlights a unique approach in patients with long-standing (&gt;5 years) heart failure who may benefit from early consideration for axillary support and concomitant optimization with guideline-directed medical therapy to assess for explant and native heart recovery.
Relationship of fibroblast growth factor 21, Klotho, and diabetic retinopathy: a meta-analysis
Authors: Jiang Yanhua , Zhang Weilai , Xu Yao , Zeng Xiandong , Sun Xin 
Published: August 2024

BackgroundDiabetic retinopathy (DR) is a serious microvascular complication of diabetes mellitus. Research has identified a close relationship between fibroblast growth factor 21 (FGF21) and DR. FGF21 is a member of the FGF subfamily, which is activated by the Klotho coenzyme involved in the occurrence of DR. However, the association between FGF21, Klotho, and DR remains controversial.AimTo assess FGF21 and Klotho levels in patients with DR.MethodsA literature search of the Web of Science, Wiley Online Library, PubMed, China National Knowledge Infrastructure and Wanfang databases was performed. The title or abstract search terms “diabetic retinopathy” and “DR” were used in combination with “fibroblast growth factor 21”, “FGF21”, and “Klotho”. Meta-analysis results are presented as standardized mean difference (SMD) with corresponding 95% confidence interval (CI).ResultsFifteen studies were included in this meta-analysis. FGF21 levels in patients with DR were significantly higher than in non-DR patients with diabetes (SMD: 2.12, 95% CI [1.40, 2.84]). Klotho levels in patients with DR were significantly lower than in non-DR patients with diabetes (SMD: –0.63, 95% CI [–1.22, – 0.04]).ConclusionsThis systematic review is the first to evaluate the relationship between FGF21, Klotho levels, and DR. FGF21 levels were significantly higher in patients with DR. Fully elucidating the role of FGF21 will significantly contribute to the treatment of DR.
Enhancing diagnostic precision in thyroid nodule assessment: evaluating the efficacy of a novel cell preservation technique in fine-needle aspiration cytology
Authors: Streinu Diana-Raluca , Neagoe Octavian Constantin , Borlea Andreea , Icma Ion , Derban Mihnea , Stoian Dana 
Published: August 2024

ObjectivesThis study aimed to evaluate the effectiveness of thyroid fine needle aspiration cytology (FNAC) using a novel-cell preserving matrix called Cytomatrix in improving diagnostic accuracy for thyroid nodules.Materials and methodsFifty patients undergoing thyroidectomy were enrolled and FNAC was performed on the excised thyroid glands, with the collected sample being placed on the Cytomatrix. The results were compared with histopathological analysis, and diagnostic performance was assessed statistically.ResultsCytomatrix demonstrated an accuracy of 96%, sensitivity of 84.61%, and specificity of 100%. Concordance between cytological and histopathological findings highlighted Cytomatrix’s potential to enhance thyroid FNAC accuracy.ConclusionFNAC using Cytomatrix shows promise in improving diagnostic accuracy for thyroid nodules. Its application, marked by faster processing and efficient resource utilization, coupled with the preservation of cellular architecture, holds considerable potential in enhancing cytological diagnosis, thus optimizing patient management strategies.
Walking away from depression: the mediating role of walking activity in depression impacting blood glucose levels of people with diabetes or prediabetes
Authors: Fundoiano-Hershcovitz Yifat , Breuer Asher Inbar , Kantor Halit , Rahmon Sandy , Ritholz Marilyn D. , Horwitz David L. , Manejwala Omar , Goldstein Pavel 
Published: August 2024

IntroductionDepression can exacerbate diabetes by impairing self-care behaviors and increasing the risk of complication; however, the underlying mechanism is still unclear. Given the suggested associations between walking activity, depression status, and blood glucose levels this study explores the intricate relationship between depression and blood glucose (BG) control, with a focus on walking activity as a behavioral mediator. The purpose of this study is to examine walking activity’s mediating role in depression’s impact on BG levels, investigating and validating the non-linear association between BG levels and walking activity. This retrospective real-world study demonstrates the potential of regular walking activity as a simple and accessible intervention to mitigate the negative effects of depression on BG levels in T2D and prediabetes.MethodsA cohort of 989 users with T2D and prediabetes, who regularly tracked their steps levels and BG levels for 12 months using the Dario digital health platform was evaluated. The mediating role of the monthly average number of steps on the relationship between the self-reported depression status and lagged monthly average BG was assessed. Additionally, the association between monthly walking activity and monthly average BG was tested using a piecewise linear mixed effects model.ResultsUsers with self-reported depression demonstrated increased BG levels compared to users without depression (B=8.00, P=.01). The association between depression and monthly average number of steps was significant (B=-.27, P&lt;.005) and monthly average number of steps significantly predicted the following months’ average BG (B=-.81, P=.001), adjusting for depression. The monthly average number of steps significantly mediated the effect of self-reported depression on the following month’s average BG (M=.22, P&lt;.005). Further sensitivity analysis demonstrated model robustness over various periods. Finally, non-linear dynamics of walking activity over time was validated using unseen data showing a decrease in monthly average BG for users with over an average of 400 steps per day (B=-1.87, P&lt;.01).DiscussionThis study shows how regular walking may reduce the negative impact of depression on BG levels in people with T2D. Our findings advocate for the integration of walking activity into treatment protocols as a cost-effective, accessible intervention strategy to improve glycemic management and depressive symptoms in this population.
The impact of China’s digital economy industry development and its structural indicators on carbon emission intensity
Authors: Wang Yitong , Yuan Yongke , Qian Xiao , Chi Yuanying 
Published: August 2024

IntroductionThe development of the digital economy has a profound impact on industrial economics. The article starts from the perspective of industrial organization theory. The thesis aims to analyze the industrial development of the digital economy and its three structural variables: digital manufacturing industry, digital service industry, and the development of industrial digitization on carbon emission intensity.MethodBased on the data of Input-output Tables with extended tables of 30 provinces, this paper analyzes the industrial development of digital economy and its three structural variables: digital manufacturing industry, digital service industry, and the development of industrial digitization on carbon emission intensity.Results and discussionThe empirical results show that: 1) at the national level, the development of China’s digital economy industries has a suppressive effect on carbon emission intensity; 2) in terms of spatial effects, the development of digital economy has significant carbon spillover effects, but digital industrialization and industrial digitization present different spatial effect results; 3) from the analysis of regional heterogeneity, in the northeast, central and western regions, the direction of influence of digital industrialization and industrial digitalization on carbon emission intensity is consistent; in the eastern region, the development of digital industrial service sector and industrial digitalization has a suppressive effect on carbon emission intensity, while digital industrial manufacturing sector presents a pro-increasing effect; 4) Non-linear relationship analysis shows that the development of the digital industrial manufacturing sector has a “promoting and then inhibiting” effect on carbon emission intensity. Overall, the impact of digital industry development on carbon intensity exhibits a “promoting increase, then suppressing, then promoting increase” trend. In conclusion, the findings suggest that China’s digital economy industry has entered the low-carbon development stage.
Lactylation signature identifies liver fibrosis phenotypes and traces fibrotic progression to hepatocellular carcinoma
Authors: Li Lin-na , Li Wen-wen , Xiao Lu-shan , Lai Wei-nan 
Published: August 2024

IntroductionPrecise staging and classification of liver fibrosis are crucial for the hierarchy management of patients. The roles of lactylation are newly found in the progression of liver fibrosis. This study is committed to investigating the signature genes with histone lactylation and their connection with immune infiltration among liver fibrosis with different phenotypes.MethodsFirstly, a total of 629 upregulated and 261 downregulated genes were screened out of 3 datasets of patients with liver fibrosis from the GEO database and functional analysis confirmed that these differentially expressed genes (DEGs) participated profoundly in fibrosis-related processes. After intersecting with previously reported lactylation-related genes, 12 DEGs related to histone lactylation were found and narrowed down to 6 core genes using R algorithms, namely S100A6, HMGN4, IFI16, LDHB, S100A4, and VIM. The core DEGs were incorporated into the Least absolute shrinkage and selection operator (LASSO) model to test their power to distinguish the fibrotic stage.ResultsAdvanced fibrosis presented a pattern of immune infiltration different from mild fibrosis, and the core DEGs were significantly correlated with immunocytes. Gene set and enrichment analysis (GSEA) results revealed that core DEGs were closely linked to immune response and chemokine signaling. Samples were classified into 3 clusters using the LASSO model, followed by gene set variation analysis (GSVA), which indicated that liver fibrosis can be divided into status featuring lipid metabolism reprogramming, immunity immersing, and intermediate of both. The regulatory networks of the core genes shared several transcription factors, and certain core DEGs also presented dysregulation in other liver fibrosis and idiopathic pulmonary fibrosis (IPF) cohorts, indicating that lactylation may exert comparable functions in various fibrotic pathology. Lastly, core DEGs also exhibited upregulation in HCC.DiscussionLactylation extensively participates in the pathological progression and immune infiltration of fibrosis. Lactylation and related immune infiltration could be a worthy focus for the investigation of HCC developed from liver fibrosis.
Single-cell and spatial transcriptome assays reveal heterogeneity in gliomas through stress responses and pathway alterations
Authors: He Zongze , Liu Zheng , Wang Qi , Sima Xingjian , Zhao Wei , He Chunmei , Yang Wenjie , Chen Han , Gong Bo , Song Siyuan , Wang Yi 
Published: August 2024

BackgroundGlioma is a highly heterogeneous malignancy of the central nervous system. This heterogeneity is driven by various molecular processes, including neoplastic transformation, cell cycle dysregulation, and angiogenesis. Among these biomolecular events, inflammation and stress pathways in the development and driving factors of glioma heterogeneity have been reported. However, the mechanisms of glioma heterogeneity under stress response remain unclear, especially from a spatial aspect.MethodsThis study employed single-cell RNA sequencing (scRNA-seq) and spatial transcriptomics (ST) to explore the impact of oxidative stress response genes in oligodendrocyte precursor cells (OPCs). Our analysis identified distinct pathways activated by oxidative stress in two different types of gliomas: high- and low- grade (HG and LG) gliomas.ResultsIn HG gliomas, oxidative stress induced a metabolic shift from oxidative phosphorylation to glycolysis, promoting cell survival by preventing apoptosis. This metabolic reprogramming was accompanied by epithelial-to-mesenchymal transition (EMT) and an upregulation of stress response genes. Furthermore, SCENIC (Single-Cell rEgulatory Network Inference and Clustering) analysis revealed that oxidative stress activated the AP1 transcription factor in HG gliomas, thereby enhancing tumor cell survival and proliferation.ConclusionOur findings provide a novel perspective on the mechanisms of oxidative stress responses across various grades of gliomas. This insight enhances our comprehension of the evolutionary processes and heterogeneity within gliomas, potentially guiding future research and therapeutic strategies.
Identification of novel PHGDH inhibitors based on computational investigation: an all-in-one combination strategy to develop potential anti-cancer candidates
Authors: Xu Yujing , Yang Zhe , Yang Jinrong , Gan Chunchun , Qin Nan , Wei Xiaopeng 
Published: August 2024

ObjectiveBiological studies have elucidated that phosphoglycerate dehydrogenase (PHGDH) is the rate-limiting enzyme in the serine synthesis pathway in humans that is abnormally expressed in numerous cancers. Inhibition of the PHGDH activity is thought to be an attractive approach for novel anti-cancer therapy. The development of structurally diverse novel PHGDH inhibitors with high efficiency and low toxicity is a promising drug discovery strategy.MethodsA ligand-based 3D-QSAR pharmacophore model was developed using the HypoGen algorithm methodology of Discovery Studio. The selected pharmacophore model was further validated by test set validation, cost analysis, and Fischer randomization validation and was then used as a 3D query to screen compound libraries with various chemical scaffolds. The estimated activity, drug-likeness, molecular docking, growing scaffold, and molecular dynamics simulation processes were applied in combination to reduce the number of virtual hits.ResultsThe potential candidates against PHGDH were screened based on estimated activity, docking scores, predictive absorption, distribution, metabolism, excretion, and toxicity (ADME/T) properties, and molecular dynamics simulation.ConclusionFinally, an all-in-one combination was employed successfully to design and develop three potential anti-cancer candidates.
Developing a predictive nomogram for mortality in patients with extrapulmonary acute respiratory distress syndrome: the prognostic value of serum soluble thrombomodulin, lung ultrasound score, and lactate
Authors: Yang Yang , Wang Yue , Zhu Guoguo , Xu Siya , Liu Jie , Tang Zhongzhi 
Published: August 2024

Objective: This study aimed to elucidate the prognostic significance of serum soluble thrombomodulin (sTM), lung ultrasound score (LUS), and lactate levels in patients with extrapulmonary acute respiratory distress syndrome (ARDS), with the goal of refining mortality risk prediction in this cohort.Methods: In a prospective cohort of 95 patients with extrapulmonary ARDS admitted to the intensive care unit, we investigated the primary endpoint of 28-day mortality. Utilizing Lasso-Cox regression analysis, we identified independent prognostic factors for mortality. A predictive nomogram was developed incorporating these factors, and its performance was validated through several statistical measures, including the consistency index, calibration plot, internal validation curve, decision curve analysis, interventions avoided analysis, receiver operating characteristic curve analysis, and Kaplan-Meier survival analysis. We further conducted a subgroup analysis to examine the impact of prone positioning on patient outcomes.Results: The study identified baseline serum sTM, LUS, and lactate levels as independent predictors of 28-day mortality in extrapulmonary ARDS patients. The predictive nomogram demonstrated superior prognostic accuracy compared to the use of sTM, LUS, or lactate levels alone, and outperformed traditional prognostic tools such as the Acute Physiology and Chronic Health Evaluation II score and the partial pressure of arterial oxygen to fractional inspired oxygen ratio. The subgroup analysis did not show a significant impact of prone positioning on the predictive value of the identified biomarkers.Conclusion: Our study results support the development and validation of a novel prognostic nomogram that integrates key clinical biomarkers and ultrasound imaging scores to predict mortality in patients with extrapulmonary ARDS. While our research is preliminary, further studies and validation are required.
Cannabidiol or ketamine for preventing the impact of adolescent early drug initiation on voluntary ethanol consumption in adulthood
Authors: Colom-Rocha Carles , Bis-Humbert Cristian , García-Fuster M. Julia 
Published: August 2024

BackgroundFew studies have previously evaluated the long-term impact of initiating the combined use of alcohol and cocaine early-in-life during adolescence. Our preclinical study characterized changes in affective-like behavior and/or voluntary ethanol consumption emerging later on in adulthood induced by a prior adolescent drug exposure, as well as tested therapeutical interventions (i.e., cannabidiol or ketamine) to prevent the observed effects.MethodsWe performed three independent studies with male and female Sprague-Dawley rats, treated in adolescence (postnatal days, PND 29–38) with non-contingent paradigms of ethanol, cocaine, their combination or vehicle. Later on, adult rats were (1) scored for their affective-like state (forced-swim, elevated-plus maze, novelty-suppressed feeding, sucrose preference), (2) allowed to freely drink ethanol for 6 weeks (two-bottle choice), or (3) treated with cannabidiol or ketamine before given access to ethanol in adulthood.ResultsNo signs of increased negative affect were observed in adulthood following the adolescent treatments. However, adolescent ethanol exposure was a risk-factor for later developing an increased voluntary ethanol consumption in adulthood, both for male and female rats. This risk was similar when ethanol was combined with adolescent cocaine exposure, since cocaine alone showed no effects on later ethanol intake. Finally, rats exposed to adolescent ethanol and pretreated in adulthood with cannabidiol (and/or ketamine, but just for females) reduced their ethanol voluntary consumption.ConclusionOur data provided two therapeutical options capable of preventing the impact of an early drug initiation during adolescence by decreasing voluntary ethanol consumption in adult rats
A mendelian randomisation study of the causal effect of exercise intensity on the development of type 2 diabetes
Authors: Yu Fengliang , Bi Haixiang , Qian Haonan , Li Shunji 
Published: August 2024

ObjectiveThis study examines the causal effects of varying exercise intensities on type 2 diabetes mellitus (T2D) through Mendelian randomization (MR) analysis, using genetic variants as instrumental variables.MethodsA two-sample MR analysis was performed, employing Inverse Variance Weighted (IVW) as the primary method, supported by weighted median, MR-Egger regression, MR-PRESSO, and MR robustness-adjusted contour scores. Data were obtained from the International Exercise Genetics Database (IEGD) and the Global Diabetes Research Consortium (GRC), encompassing over 150,000 individuals for exercise intensity and around 200,000 T2D patients and controls. SNPs linked to exercise intensity were selected based on genome-wide significance (P &lt; 5 × 10^-8) and linkage disequilibrium criteria (distance &gt;10,000 kb, r^2 &lt; 0.001).ResultsThe IVW analysis suggested that high-intensity exercise might reduce T2D risk, but the association was not statistically significant (OR = 0.667, 95% CI = 0.104–4.255, P = 0.667). The wide confidence interval indicates uncertainty in the effect estimate. Low-intensity exercise showed no significant effect on T2D risk (OR ∼ 1.0). Sensitivity analyses, including weighted median and MR-Egger regression, confirmed no significant association between high-intensity exercise and T2D risk. The MR-PRESSO analysis found no significant outliers, and the global test for pleiotropy was non-significant (P = 0.455). Cochran’s Q test for heterogeneity in the IVW analysis was non-significant (Q = 12.45, P = 0.234), indicating consistency among SNP-derived estimates.ConclusionHigh-intensity exercise potentially reduces T2D risk, but the association is not statistically significant. Further research is needed to understand the complex relationship between exercise intensity and T2D.