bluuebunny/crossref_metadata_2025_split huggingface dataset:
Prognostic value of growth differentiation factor-15 in patients with coronary artery disease: A meta-analysis and systematic review
Authors: Zhang Song , Hao Panpan , Li Jiaxin , Zhang Qi , Yin Xiaoying , Wang Jiali , Chen Yuguo 
Published: February 2023

Background and aimsThe predictive value of growth differentiation factor-15 (GDF-15) for individual cardiovascular outcomes remained controversial in patients with coronary artery disease (CAD). We aimed to investigate the effects of GDF-15 on all-cause death, cardiovascular death, MI and stroke in CAD patients.MethodsWe searched PubMed, EMBASE, Cochrane library and Web of Science till 30 December, 2020. Hazard ratios (HRs) were combined with fixed or random effect meta-analyses. Subgroup analyses were performed in different disease types. Sensitivity analyses were used to evaluate the stability of the results. Publication bias was tested using funnel plots.ResultsA total of 10 studies with 49,443 patients were included in this meta-analysis. Patients with the highest GDF-15 concentrations had significantly increased risk of all-cause death (HR 2.24; 95% CI: 1.95–2.57), cardiovascular death (HR 2.00; 95% CI: 1.66–2.42), MI (HR 1.42; 95% CI: 1.21–1.66) after adjusting clinical characteristics and prognostic biomarkers (hs-TnT, cystatin C, hs-CRP, and NT-proBNP) but except for stroke (HR 1.43; 95% CI: 1.01–2.03, p = 0.05). For the outcome of all-cause death and cardiovascular death, subgroup analyses revealed consistent results. Sensitivity analyses showed that the results were stable. Funnel plots showed that there was no publication bias.ConclusionIn CAD patients with elevated GDF-15 levels on admission, there were independently significant risks for all-cause death and cardiovascular death. The highest concentrations of GDF-15 had a lower predictive effect on MI than all-cause death and cardiovascular death. The association of GDF-15 with the outcome of stroke needs to be further studied.
HMM-based profiling identifies the binding to divalent cations and nucleotides as common denominators of suramin targets
Authors: Hauser Dennis A. , Mäser Pascal 
Published: February 2023

Introduction: Suramin is one of the pharmacopeia’s most promiscuous drugs. Originally developed for African trypanosomiasis, suramin was also used for onchocerciasis and it has been proposed as an anticancer agent, antiviral drug, therapy for arthritis, autism, and antidote for snake bites. Target proteins of suramin have been described from different species. Here we identify the common motifs among these various targets, aiming to explain the promiscuous nature of suramin.Methods: We have searched for suramin target proteins in the literature and in chemical databases. Applying rigorous inclusion criteria, a list of 44 diverse proteins was assembled with experimental evidence for direct interaction with, and inhibition by, suramin. Hidden Markov model-based target profiling was performed by running the full set of Pfam protein family domains against these proteins.Results: Common denominators were identified by mapping the identified Pfam domains to molecular function gene ontology terms. This in silico pipeline identified nucleotide binding, nucleic acid binding, and binding to divalent cations as the most common denominators of the suramin targets.Discussion: Our results suggest that the extraordinary polypharmacology of suramin may be caused by its ability to inhibit the interaction of proteins with nucleotides or nucleic acids and with divalent cations (Mg2+, Ca2+, Zn2+). Suramin is well known to inhibit nucleotide receptors and nucleic acid-binding enzymes. The association with divalent cations is new and might be key towards the design of better, more selective inhibitors.
Prognostic value of low-density lipoprotein cholesterol in IgA nephropathy and establishment of nomogram model
Authors: Tian Zhang-Yu , Li Ai-Mei , Chu Ling , Hu Jing , Xie Xian , Zhang Hao 
Published: February 2023

BackgroundDyslipidemia is closely related to kidney disease. We aimed to investigate the relationship between low-density lipoprotein cholesterol (LDL-C) and prognosis of IgA nephropathy (IgAN) and build a nomogram prognostic model.Methods519 IgAN patients with 61 months median follow-up were enrolled and divided into two groups based on the cut-off value of baseline LDL-C (2.60 mmol/L): the high group (n=253) and the low group (n=266). Renal survival was assessed by Kaplan⁃Meier (KM) survival curve. Risk factors were identified by COX regression analysis. The area under the receiver operating characteristic (ROC) curves (AUC), concordance index (C-index), and calibration curves were applied to evaluate the nomogram model.ResultsKM survival curve analysis showed that the high LDL-C group had worse renal survival than the low LDL-C group (χ2 = 8.555, p=0.003). After adjusting for confounding factors, Cox regression analysis showed the baseline LDL-C level was an independent risk factor of end-stage renal disease (ESRD) in IgAN (HR=3.135, 95% CI 1.240~7.926, p =0.016). LDL-C, segmental sclerosis, tubular atrophy/interstitial fibrosis, the prevalence of cardiovascular disease, 24-hour proteinuria were identified and entered into the nomogram models, with AUC of 0.864, 0.827, and 0.792 respectively to predict the 5-, 8-, and 10-year risk of ESRD in IgAN. The C-index of this prediction model was respectively 0.862, 0.838, and 0.800 and was well-calibrated.ConclusionElevated LDL-C level is a predictive factor for the prognosis of IgAN. We developed a nomogram model that can predict the risk of ESRD in IgAN by using LDL-C ≥ 2.60 mmol/L.
STRA6 regulates tumor immune microenvironment and is a prognostic marker in BRAF-mutant papillary thyroid carcinoma
Authors: He Weiman , Sun Yijia , Ge Jiawei , Wang Xuejie , Lin Bo , Yu Shuang , Li Yanbing , Hong Shubin , Xiao Haipeng 
Published: February 2023

BackgroundBRAF mutation is one of the most common genetic alterations contributing to the initiation and progression of papillary thyroid carcinoma (PTC). However, the prognostic value of BRAF mutation for PTC is limited. Novel markers are needed to identify BRAF-mutant patients with poor prognosis.MethodsTranscriptional expression data were downloaded from the Cancer Genome Atlas (TCGA) and Gene Expression Omnibus (GEO) datasets. Pathway enrichment was performed by Kyoto Encyclopedia of Genes and Genomes (KEGG) analysis and gene set enrichment analysis (GSEA). Protein-protein interaction networks were predicted by the GeneMANIA. The correlation between STRA6 expression and immune infiltration was analyzed by tumor immune estimation resource (TIMER) and tumor-immune system interaction database (TISIDB). Immunohistochemistry was used to detect the STRA6 protein expression level of PTC. Infiltration of regulatory T cells (Tregs) and CD8+ T cells in tumor samples were analyzed by fluorescent multiplex immunohistochemistry.ResultsIn BRAF-mutant PTC, STRA6 was extremely upregulated and predicted unfavorable survival, which was an independent risk factor for increased mortality risk. Bioinformatic analyses indicated that STRA6 might activate the MAPK pathway synergistically with BRAFV600E. The expression of STRA6 was associated with immune infiltrates and T cell exhaustion. Fluorescent multiplex immunohistochemistry showed that STRA6 increased Tregs abundance and decreased CD8+ T cells infiltration in PTC. Moreover, STRA6 promoted epithelial-mesenchymal transition via increased cancer-associated fibroblasts infiltration.ConclusionsOur study demonstrates STRA6 may serve as a prognostic marker for BRAF-mutated PTC, which may drive thyroid carcinogenesis via activation of oncogenic pathway and regulation of tumor immunosuppressive microenvironment.
A meta-analysis: Effect of androgens on reproduction in sows
Authors: Guo Zhenhua , Lv Lei , Liu Di , Ma Hong , Radovic Cedomir 
Published: February 2023

IntroductionThe mechanisms by which male hormones affect the development of ovaries and follicles has been studied by injecting exogenous androgens into sows. This may provide a reference for human polycystic ovary syndrome (PCOS), and can also provide guidance for improving the litter size of sows.MethodsWe present a meta-analysis of studies published in the past 30 years on the effect of androgens on the ovulation rate of sows. A total of 517 papers were analyzed.ResultsThe results showed that both testosterone (T) and dihydrotestosterone (DHT) injected into sows were positively related to the ovulation rate. T did not have a relevant effect on swine in vivo blastocyst survival rate. DHT had a negative phase with respect to blastocyst survival rate. Pig T-androgen receiver affinity was higher than the analogous affinity for DHT; this is different in humans. This suggests that sows are not suitable as human PCOS experimental animal models.DiscussionTo improve the litter size of sows, future research should focus on the mixed use of T and DHT, and the timing of use should be consistent with the periodic changes in androgen levels in sows. In addition, the welfare of experimental sows should be considered with reference to the clinical symptoms of PCOS.
Hyperprolactinaemia is common in Chinese premenopausal women with breast diseases
Authors: Zhu Jiang , Tang Yuyi , Lv Cuixia , Cong Han , Liu Jie , Zhao Song , Wang Yawen , Zhang Kai , Yu Wenbin , Cai Qian , Ma Rong , Wang Jianli 
Published: February 2023

Purpose: Hyperprolactinaemia has been proposed to play a role in breast lesions pathophysiology. Thus far, controversial results have been reported for the relationship between hyperprolactinaemia and breast lesions. Moreover, the prevalence of hyperprolactinaemia in a population with breast lesions is scarcely reported. We aimed to investigate the prevalence of hyperprolactinaemia in Chinese premenopausal women with breast diseases, and explore the associations between hyperprolactinaemia with different clinical characteristics.Methods: This was a retrospective cross-sectional study performed in the department of breast surgery of Qilu hospital of Shandong University. Overall, 1,461 female patients who underwent the serum prolactin (PRL) level assay before breast surgery from January 2019 to December 2020 were included. Patients were divided into two groups: before and after menopause. Data were analyzed using SPSS 18.0 software.Results: The results showed an elevated PRL level in 376 of the 1,461 female patients with breast lesions (25.74%). Furthermore, the proportion of hyperprolactinemia among premenopausal patients with breast disease (35.75%, 340/951) was significantly higher than among postmenopausal patients with breast disease (7.06%, 36/510). In premenopausal patients, the proportion of patients with hyperprolactinaemia and the mean serum PRL level were significantly higher in those diagnosed with fibroepithelial tumours (FETs) and in younger patients (aged &lt; 35 years) than in those with non-neoplastic lesions and in those aged ≥ 35 years (both p &lt; 0.05). Especially, the prolactin level exhibited steady ascending tendency for positive correlation with FET.Conclusion: Hyperprolactinaemia is prevalent in Chinese premenopausal patients with breast diseases, especially in those with FETs, which implies a potential association, to some extent, between the PRL levels in various breast diseases.
The prognostic value of the GPAT/AGPAT gene family in hepatocellular carcinoma and its role in the tumor immune microenvironment
Authors: Wen Peizhen , Wang Rui , Xing Yiqun , Ouyang Wanxin , Yuan Yixin , Zhang Shuaishuai , Liu Yuan , Peng Zhihai 
Published: February 2023

BackgroundLiver cancer is the sixth most commonly diagnosed cancer and the third leading cause of cancer-related death worldwide. Hepatocellular carcinoma accounts for an estimated 90% of all liver cancers. Many enzymes of the GPAT/AGPAT family are required for the synthesis of triacylglycerol. Expression of AGPAT isoenzymes has been reported to be associated with an increased risk of tumorigenesis or development of aggressive phenotypes in a variety of cancers. However, whether members of the GPAT/AGPAT gene family also influence the pathophysiology of HCC is unknown.MethodsHepatocellular carcinoma datasets were obtained from the TCGA and ICGC databases. Predictive models related to the GPAT/AGPAT gene family were constructed based on LASSO-Cox regression using the ICGC-LIRI dataset as an external validation cohort. Seven immune cell infiltration algorithms were used to analyze immune cell infiltration patterns in different risk groups. IHC, CCK-8, Transwell assay, and Western blotting were used for in vitro validation.ResultsCompared with low-risk patients, high-risk patients had shorter survival and higher risk scores. Multivariate Cox regression analysis showed that risk score was a significant independent predictor of overall survival (OS) after adjustment for confounding clinical factors (p &lt; 0.001). The established nomogram combined risk score and TNM staging to accurately predict survival at 1, 3, and 5 years in patients with HCC with AUC values of 0.807, 0.806, and 0.795, respectively. This risk score improved the reliability of the nomogram and guided clinical decision-making. In addition, we comprehensively analyzed immune cell infiltration (using seven algorithms), response to immune checkpoint blockade, clinical relevance, survival, mutations, mRNA expression-based stemness index, signaling pathways, and interacting proteins related to the three core genes of the prognostic model (AGPAT5, LCLAT1, and LPCAT1). We also performed preliminary validation of the differential expression, oncological phenotype, and potential downstream pathways of the three core genes by IHC, CCK-8, Transwell assay, and Western blotting.ConclusionThese results improve our understanding of the function of GPAT/AGPAT gene family members and provide a reference for prognostic biomarker research and individualized treatment of HCC.
Mid-titer human convalescent plasma administration results in suboptimal prophylaxis against SARS-CoV-2 infection in rhesus macaques
Authors: Beddingfield Brandon J. , Maness Nicholas J. , Spencer Skye , Rappaport Jay , Aye Pyone Pyone , Russell-Lodrigue Kasi , Doyle-Meyers Lara A. , Blair Robert V. , Gao HongMei , Montefiori David , Roy Chad J. 
Published: February 2023

IntroductionSARS-CoV-2 is a respiratory pathogen currently causing a worldwide pandemic, with resulting pathology of differing severity in humans, from mild illness to severe disease and death. The rhesus macaque model of COVID-19 was utilized to evaluate the added benefit of prophylactic administration of human post-SARS-CoV-2 infection convalescent plasma (CP) on disease progression and severity.MethodsA pharmacokinetic (PK) study using CP in rhesus monkeys preceded the challenge study and revealed the optimal time of tissue distribution for maximal effect. Thereafter, CP was administered prophylactically three days prior to mucosal SARS-CoV-2 viral challenge.ResultsResults show similar viral kinetics in mucosal sites over the course of infection independent of administration of CP or normal plasma, or historic controls with no plasma. No changes were noted upon necropsy via histopathology, although there were differences in levels of vRNA in tissues, with both normal and CP seemingly blunting viral loads.DiscussionResults indicate that prophylactic administration with mid-titer CP is not effective in reducing disease severity of SARS-CoV-2 infection in the rhesus COVID-19 disease model.
Global trends in research of fibroblasts associated with rheumatoid diseases in the 21st century: A bibliometric analysis
Authors: Huang Runzhi , Jin Minghao , Liu Yifan , Lu Yuwei , Zhang Mengyi , Yan Penghui , Xian Shuyuan , Wang Siqiao , Zhang Hao , Zhang Xinkun , Chen Shaofeng , Lu Bingnan , Yang Yiting , Huang Zongqiang , Liu Xin , Ji Shizhao 
Published: February 2023

BackgroundRheumatoid Diseases (RDs) are a group of systemic auto-immune diseases that are characterized by chronic synovitis, and fibroblast-like synoviocytes (FLSs) play an important role in the occurrence and progression of synovitis. Our study is the first to adopt bibliometric analysis to identify the global scientific production and visualize its current distribution in the 21st century, providing insights for future research through the analysis of themes and keywords.MethodsWe obtained scientific publications from the core collection of the Web of Science (WoS) database, and the bibliometric analysis and visualization were conducted by Biblioshiny software based on R-bibliometrix.ResultsFrom 2000 to 2022, a total of 3,391 publications were reviewed. China is the most prolific country (n = 2601), and the USA is the most cited country (cited 7225 times). The Center of Experimental Rheumatology at University Hospital Zürich supported the maximum number of articles (n = 40). Steffen Gay published 85 records with 6263 total citations, perhaps making him the most impactful researcher. Arthritis and Rheumatism, Annals of Rheumatic Diseases, and Rheumatology are the top three journals.ConclusionThe current study revealed that rheumatoid disease (RD)-related fibroblast studies are growing. Based on the bibliometric analysis, we summarized three important topics: activation of different subsets of fibroblasts; regulation of fibroblast function; and in vitro validation of existing discoveries. They are all valuable directions, which provide reference and guidance for researchers and clinicians engaged in the research of RDs and fibroblasts.
Association of GBA genotype with motor and cognitive decline in Chinese Parkinson’s disease patients
Authors: Ren Jingru , Zhou Gaiyan , Wang Yajie , Zhang Ronggui , Guo Zhiying , Zhou Hao , Zheng Huifen , Sun Yu , Ma Changyan , Lu Ming , Liu Weiguo 
Published: February 2023

ObjectiveVariants in the glucocerebrosidase (GBA) gene are the most common and significant risk factor for Parkinson’s disease (PD). However, the impact ofGBAvariants on PD disease progression in the Chinese population remains unclear. This study aimed to explore the significance ofGBAstatus on motor and cognitive impairment in a longitudinal cohort of Chinese patients with PD.MethodsThe entireGBAgene was screened by long-range polymerase chain reaction (LR-PCR) and next generation sequencing (NGS). A total of 43GBA-related PD (GBA-PD) and 246 non-GBA-mutated PD (NM-PD) patients with complete clinical data at baseline and at least one follow-up were recruited for this study. The associations ofGBAgenotype with rate of motor and cognitive decline, as measured by Unified PD Rating Scale (UPDRS) motor and Montreal Cognitive Assessment (MoCA), were assessed by linear mixed-effect models.ResultsThe estimated (standard error, SE) UPDRS motor [2.25 (0.38) points/year] and MoCA [−0.53 (0.11) points/year] progression rates in theGBA-PD group were significantly faster than those in the NM-PD group [1.35 (0.19); −0.29 (0.04) points/year; respectively]. In addition, theGBA-PD group showed significantly faster estimated (SE) bradykinesia [1.04 (0.18) points/year], axial impairment [0.38 (0.07) points/year], and visuospatial/executive [−0.15 (0.03) points/year] progression rates than the NM-PD group [0.62 (0.10); 0.17 (0.04); −0.07 (0.01) points/year; respectively].ConclusionGBA-PD is associated with faster motor and cognitive decline, specifically greater disability in terms of bradykinesia, axial impairment, and visuospatial/executive function. Better understanding ofGBA-PD progression may help predict prognosis and improve clinical trial design.
Microcatheter-guided compartment packing of acutely ruptured complex intracerebral aneurysms (ARCIAs): Preliminary experience and technical note
Authors: Zhang Yi-Bin , Xie Bing-Sen , Wang Hao-Jie , Huang Sheng-Xuan , Fan Wen-Jian , Zhu Mei , Chen Guo-Rong , Wang Deng-Liang , Yao Pei-Sen , Yu Liang-Hong , Dai Lin-Sun , Kang De-Zhi , Zheng Shu-Fa 
Published: February 2023

ObjectiveWe present our initial experience using the microcatheter-guided compartment packing (MCP) technique for endovascular embolization of acutely ruptured complex intracerebral aneurysms (ARCIAs) and evaluate the safety, feasibility, and efficiency of this technique.MethodsThis retrospective, single-center study included 28 patients who underwent coil embolization using the MCP technique for ARCIAs at our institution between January 2021 and January 2022. The MCP technique was the placement of microcatheters in different compartments within the aneurysm to deploy the coils simultaneously or sequentially. Patient demographics, aneurysm characteristics, procedural parameters, grade of occlusion, complications, and clinical results were analyzed. The clinical outcomes were evaluated with modified Rankin Scale (mRS) scores.ResultsOf the 28 patients successfully treated with the MCP technique, 24 (85.7%) aneurysms were considered as complete occlusions (Raymond I) based on the immediate postembolization angiogram results. Complications occurred in 2/28 treatments, including guidewire perforation with subarachnoid hemorrhage and cerebral vasospasm-related cerebral infarction. An angiography follow-up demonstrated complete occlusion in 25/28 aneurysms. Twenty-six (92.9%) patients had favorable 90-day outcomes (mRS 0-2) after the endovascular coil embolization.ConclusionThe MCP technique is simple, safe, and effective, achieving good packing density and initial occlusion rate when used to treat ARCIAs.
Behavioral and transcriptomic effects of the cancer treatment tamoxifen in mice
Authors: Galvano Elena , Pandit Harshul , Sepulveda Jordy , Ng Christi Anne S. , Becher Melanie K. , Mandelblatt Jeanne S. , Van Dyk Kathleen , Rebeck G. William 
Published: February 2023

IntroductionTamoxifen is a common treatment for estrogen receptor-positive breast cancer. While tamoxifen treatment is generally accepted as safe, there are concerns about adverse effects on cognition.MethodsWe used a mouse model of chronic tamoxifen exposure to examine the effects of tamoxifen on the brain. Female C57/BL6 mice were exposed to tamoxifen or vehicle control for six weeks; brains of 15 mice were analyzed for tamoxifen levels and transcriptomic changes, and an additional 32 mice were analyzed through a battery of behavioral tests.ResultsTamoxifen and its metabolite 4-OH-tamoxifen were found at higher levels in the brain than in the plasma, demonstrating the facile entry of tamoxifen into the CNS. Behaviorally, tamoxifen-exposed mice showed no impairment in assays related to general health, exploration, motor function, sensorimotor gating, and spatial learning. Tamoxifen-treated mice showed a significantly increased freezing response in a fear conditioning paradigm, but no effects on anxiety measures in the absence of stressors. RNA sequencing analysis of whole hippocampi showed tamoxifen-induced reductions in gene pathways related to microtubule function, synapse regulation, and neurogenesis.DiscussionThese findings of the effects of tamoxifen exposure on fear conditioning and on gene expression related to neuronal connectivity suggest that there may be CNS side effects of this common breast cancer treatment.