bluuebunny/crossref_metadata_2025_split huggingface dataset:
The screening for marine fungal strains with high potential in alkaloids production by in situ colony assay and LC-MS/MS based secondary metabolic profiling
Authors: Lu Tiantian , Liu Yayue , Zhou Longjian , Liao Qingnan , Nie Yingying , Wang Xingyuan , Lei Xiaoling , Hong Pengzhi , Feng Yan , Hu Xueqiong , Zhang Yi 
Published: May 2023

BackgroundAlkaloids are the second primary class of secondary metabolites (SMs) from marine organisms, most of which have antioxidant, antitumor, antibacterial, anti-inflammatory, and other activities. However, the SMs obtained by traditional isolation strategies have drawbacks such as highly reduplication and weak bioactivity. Therefore, it is significantly important to establish an efficient strategy for screening strains and mining novel compounds.MethodsIn this study, we utilized in situ colony assay combined with liquid chromatography-tandem mass spectrometry (LC-MS/MS) to identify the strain with high potential in alkaloids production. The strain was identified by genetic marker genes and morphological analysis. The secondary metabolites from the strain were isolated by the combine use of vacuum liquid chromatography (VLC), ODS column chromatography, and Sephadex LH-20. Their structures were elucidated by 1D/2D NMR, HR-ESI-MS, and other spectroscopic technologies. Finally, these compounds bioactivity were assay, including anti-inflammatory and anti-β aggregation.ResultsEighteen marine fungi were preliminarily screened for alkaloids production by in situ colony assay using Dragendorff reagent as dye, and nine of them turned orange, which indicated abundant alkaloids. By thin-layer chromatography (TLC), LC-MS/MS, and multiple approaches assisted Feature-Based Molecular Networking (FBMN) analysis of fermentation extracts, a strain ACD-5 (Penicillium mallochii with GenBank accession number OM368350) from sea cucumber gut was selected for its diverse alkaloids profiles especially azaphilones. In bioassays, the crude extracts of ACD-5 in Czapek–dox broth and brown rice medium showed moderate antioxidant, acetylcholinesterase inhibitory, anti-neuroinflammatory, and anti-β aggregation activities. Three chlorinated azaphilone alkaloids, compounds 1–3 (sclerotioramine, isochromophilone VI, and isochromophilone IX, respectively), were isolated from the fermentation products of ACD-5 in brown rice medium guided by bioactivities and mass spectrometry analysis. Compound 1 had shown remarkable anti-neuroinflammatory activity in liposaccharide induced BV-2 cells.ConclusionIn summary, in situ colony screening together with LC-MS/MS, multi-approach assisted FBMN can act as an efficient screening method for strains with potential in alkaloids production.
Modeling the innate inflammatory cGAS/STING pathway: sexually dimorphic effects on microglia and cognition in obesity and prediabetes
Authors: Elzinga Sarah E. , Koubek Emily J. , Hayes John M. , Carter A. , Mendelson Faye E. , Webber-Davis Ian , Lentz Stephen I. , Feldman Eva L. 
Published: May 2023

IntroductionThe prevalence of obesity, prediabetes, and diabetes continues to grow worldwide. These metabolic dysfunctions predispose individuals to neurodegenerative diseases and cognitive impairment, including dementias such as Alzheimer’s disease and Alzheimer’s disease related dementias (AD/ADRD). The innate inflammatory cGAS/STING pathway plays a pivotal role in metabolic dysfunction and is an emerging target of interest in multiple neurodegenerative diseases, including AD/ADRD. Therefore, our goal was to establish a murine model to specifically target the cGAS/STING pathway to study obesity- and prediabetes-induced cognitive impairment.MethodsWe performed two pilot studies in cGAS knockout (cGAS-/-) male and female mice designed to characterize basic metabolic and inflammatory phenotypes and examine the impact of high-fat diet (HFD) on metabolic, inflammatory, and cognitive parameters.ResultscGAS-/- mice displayed normal metabolic profiles and retained the ability to respond to inflammatory stimuli, as indicated by an increase in plasma inflammatory cytokine production in response to lipopolysaccharide injection. HFD feeding caused expected increases in body weight and decreases in glucose tolerance, although onset was accelerated in females versus males. While HFD did not increase plasma or hippocampal inflammatory cytokine production, it did alter microglial morphology to a state indicative of activation, particularly in female cGAS-/- mice. However, HFD negatively impacted cognitive outcomes in male, but not female animals.DiscussionCollectively, these results suggest that cGAS-/- mice display sexually dimorphic responses to HFD, possibly based on differences in microglial morphology and cognition.
Altered coupling of resting-state cerebral blood flow and functional connectivity in Meige syndrome
Authors: Yang Aocai , Liu Bing , Lv Kuan , Luan Jixin , Hu Pianpian , Yu Hongwei , Shmuel Amir , Li Shijun , Tian Hong , Ma Guolin , Zhang Bing 
Published: May 2023

IntroductionMeige syndrome (MS) is an adult-onset segmental dystonia disease, mainly manifested as blepharospasm and involuntary movement caused by dystonic dysfunction of the oromandibular muscles. The changes of brain activity, perfusion and neurovascular coupling in patients with Meige syndrome are hitherto unknown.MethodsTwenty-five MS patients and thirty age- and sex-matched healthy controls (HC) were prospectively recruited in this study. All the participants underwent resting-state arterial spin labeling and blood oxygen level-dependent examinations on a 3.0 T MR scanner. The measurement of neurovascular coupling was calculated using cerebral blood flow (CBF)-functional connectivity strength (FCS) correlations across the voxels of whole gray matter. Also, voxel-wised analyses of CBF, FCS, and CBF/FCS ratio images between MS and HC were conducted. Additionally, CBF and FCS values were compared between these two groups in selected motion-related brain regions.ResultsMS patients showed increased whole gray matter CBF-FCS coupling relative to HC (t = 2.262, p = 0.028). In addition, MS patients showed significantly increased CBF value in middle frontal gyrus and bilateral precentral gyrus.ConclusionThe abnormal elevated neurovascular coupling of MS may indicate a compensated blood perfusion in motor-related brain regions and reorganized the balance between neuronal activity and brain blood supply. Our results provide a new insight into the neural mechanism underlying MS from the perspective of neurovascular coupling and cerebral perfusion.
Multiparametric MRI radiomics fusion for predicting the response and shrinkage pattern to neoadjuvant chemotherapy in breast cancer
Authors: Fan Ming , Wu Xilin , Yu Jiadong , Liu Yueyue , Wang Kailang , Xue Tailong , Zeng Tieyong , Chen Shujun , Li Lihua 
Published: May 2023

PurposeDuring neoadjuvant chemotherapy (NACT), breast tumor morphological and vascular characteristics are usually changed. This study aimed to evaluate the tumor shrinkage pattern and response to NACT by preoperative multiparametric magnetic resonance imaging (MRI), including dynamic contrast-enhanced MRI (DCE-MRI), diffuse weighted imaging (DWI) and T2 weighted imaging (T2WI).MethodIn this retrospective analysis, female patients with unilateral unifocal primary breast cancer were included for predicting tumor pathologic/clinical response to NACT (n=216, development set, n=151 and validation set, n=65) and for discriminating the tumor concentric shrinkage (CS) pattern from the others (n=193; development set, n=135 and validation set, n=58). Radiomic features (n=102) of first-order statistical, morphological and textural features were calculated on tumors from the multiparametric MRI. Single- and multiparametric image-based features were assessed separately and were further combined to feed into a random forest-based predictive model. The predictive model was trained in the testing set and assessed on the testing dataset with an area under the curve (AUC). Molecular subtype information and radiomic features were fused to enhance the predictive performance.ResultsThe DCE-MRI-based model showed higher performance (AUCs of 0.919, 0.830 and 0.825 for tumor pathologic response, clinical response and tumor shrinkage patterns, respectively) than either the T2WI or the ADC image-based model. An increased prediction performance was achieved by a model with multiparametric MRI radiomic feature fusion.ConclusionsAll these results demonstrated that multiparametric MRI features and their information fusion could be of important clinical value for the preoperative prediction of treatment response and shrinkage pattern.
The prognostic value of multiparametric cardiac magnetic resonance in patients with systemic light chain amyloidosis
Authors: Miao Fujia , Tang Chunxiang , Ren Guisheng , Guo Jinzhou , Zhao Liang , Xu Weiwei , Zhou Xiyang , Zhang Longjiang , Huang Xianghua 
Published: May 2023

BackgroundLate gadolinium enhancement (LGE) is a classic imaging modality derived from cardiac magnetic resonance (CMR), which is commonly used to describe cardiac tissue characterization. T1 mapping with extracellular volume (ECV) and native T1 are novel quantitative parameters. The prognostic value of multiparametric CMR in patients with light chain (AL) amyloidosis remains to be thoroughly investigated.MethodsA total of 89 subjects with AL amyloidosis were enrolled from April 2016 to January 2021, and all of them underwent CMR on a 3.0 T scanner. The clinical outcome and therapeutic effect were observed. Cox regression was used to investigate the effect of multiple CMR parameters on outcomes in this population.ResultsLGE extent, native T1 and ECV correlated well with cardiac biomarkers. During a median follow-up of 40 months, 21 patients died. ECV (hazard ratio [HR]: 2.087 for per 10% increase, 95% confidence interval [CI]: 1.379-3.157, P &lt; 0.001) and native T1 (HR: 2.443 for per 100 ms increase, 95% CI: 1.381-4.321, P=0.002) were independently predictive of mortality. A novel prognostic staging system based on median native T1 (1344 ms) and ECV (40%) was similar to Mayo 2004 Stage, and the 5-year estimated overall survival rates in Stage I, II, and III were 95%, 80%, and 53%, respectively. In patients with ECV &gt; 40%, receiving autologous stem cell transplantation had higher cardiac and renal response rates than conventional chemotherapy.ConclusionBoth native T1 and ECV independently predict mortality in patients with AL amyloidosis. Receiving autologous stem cell transplantation is effective and significantly improves the clinical outcomes in patients with ECV &gt; 40%.
Lipid metabolism marker CD36 is associated with 18FDG-PET/CT false negative lymph nodes in head and neck squamous cell carcinoma
Authors: Meng Xiaoyan , Sun Jingjing , Xu Feng , Liu Zhonglong , He Yue 
Published: May 2023

BackgroundLymph node metastasis frequently occurs in head and neck squamous cell carcinoma (HNSCC) patients, and [18F] fluorodeoxyglucose positron emission tomography with computed tomography (18FDG-PET/CT) examination for lymph node metastasis could result in false negativity and delay following treatment. However, the mechanism and resolution for 18FDG-PET/CT false negatives remain unclear. Our study was aim to found biomarkers for false negativity and true positivity from a metabolic perspective.MethodsNinety-two patients diagnosed with HNSCC who underwent preoperative 18FDG-PET/CT and subsequent surgery in our institution were reviewed. Immunohistochemistry (IHC) examinations of glucose metabolism (GLUT1 and GLUT5), amino acid metabolism4 (GLS and SLC1A5), and lipid metabolism (CPT1A and CD36) markers were conducted on their primary lesion and lymph node sections.ResultsWe identified specific metabolic patterns of the false-negative group. Significantly, CD36 IHC score of primary lesions was higher in false-negative group than true-positive group. Moreover, we validated pro-invasive biological effects of CD36 by bioinformatics analysis as well as experiments. Conclusion: IHC examination of CD36 expression, which is a lipid metabolism marker, in primary lesions could distinguish HNSCC patients’ lymph nodes false negatives in 18FDG-PET/CT.
Efficacy and safety of hepatic artery infusion chemotherapy combined with tyrosine kinase inhibitors plus programmed death-1 inhibitors for hepatocellular carcinoma refractory to transarterial chemoembolization
Authors: Lin Long-Wang , Ke Kun , Yan Le-Ye , Chen Rong , Huang Jing-Yao 
Published: May 2023

BackgroundThe subsequent therapy for hepatocellular carcinoma (HCC) patients with refractory to transarterial chemoembolization (TACE) is still controversial. This study was performed to evaluate the efficacy and safety of combination therapy comprising hepatic artery infusion chemotherapy (HAIC), lenvatinib, and programmed death-1 inhibitors relative to HAIC combined with lenvatinib.MethodsIn this single-center retrospective study, we analyzed data from HCC patients with refractory to TACE from June 2017 to July 2022. Primary study outcomes were overall survival (OS) and progression-free survival (PFS), while the secondary outcomes were the objective response rate (ORR), disease control rate (DCR), and treatment-related adverse events.ResultsWe enrolled 149 patients finally, including 75 patients who received HAIC combined with lenvatinib plus PD-1 inhibitors therapy (HAIC+L+P group) and 74 patients who received HAIC combined with lenvatinib therapy (HAIC+L group). The median OS in the HAIC+L+P group (16.0; 95% CI: 13.6~18.3 months) was significantly higher compared to the HAIC+L group (9.0; 95% CI: 6.5~11.4 months) (p = 0.002), while the median PFS in the HAIC+L+P group (11.0; 95% CI: 8.6~13.3 months) was significantly higher compared to the HAIC+L group (6.0; 95% CI: 5.0~6.9 months) (p &lt; 0.001). Significant between-group differences in DCR (p = 0.027) were found. Additionally, 48 pairs of patients were matched after propensity matching analysis. The survival prognosis between two groups before propensity matching is similar to that after propensity matching. Moreover, the percentage of patients with hypertension in the HAIC+L+P group was significantly higher compared to the HAIC+L group (28.00% vs. 13.51%; p = 0.029).ConclusionsA combination therapy of HAIC, lenvatinib, and programmed death-1 inhibitors significantly improved oncologic response and prolonged survival duration, showing a better survival prognosis for HCC patients with refractory toTACE.
Identification of prognostic cancer-associated fibroblast markers in luminal breast cancer using weighted gene co-expression network analysis
Authors: Xu An , Xu Xiang-Nan , Luo Zhou , Huang Xiao , Gong Rong-Quan , Fu De-Yuan 
Published: May 2023

BackgroundCancer-associated fibroblasts (CAFs) play a pivotal role in cancer progression and are known to mediate endocrine and chemotherapy resistance through paracrine signaling. Additionally, they directly influence the expression and growth dependence of ER in Luminal breast cancer (LBC). This study aims to investigate stromal CAF-related factors and develop a CAF-related classifier to predict the prognosis and therapeutic outcomes in LBC.MethodsThe Cancer Genome Atlas (TCGA) and Gene Expression Omnibus (GEO) databases were utilized to obtain mRNA expression and clinical information from 694 and 101 LBC samples, respectively. CAF infiltrations were determined by estimating the proportion of immune and cancer cells (EPIC) method, while stromal scores were calculated using the Estimation of STromal and Immune cells in MAlignant Tumors using Expression data (ESTIMATE) algorithm. Weighted gene co-expression network analysis (WGCNA) was used to identify stromal CAF-related genes. A CAF risk signature was developed through univariate and least absolute shrinkage and selection operator method (LASSO) Cox regression model. The Spearman test was used to evaluate the correlation between CAF risk score, CAF markers, and CAF infiltrations estimated through EPIC, xCell, microenvironment cell populations-counter (MCP-counter), and Tumor Immune Dysfunction and Exclusion (TIDE) algorithms. The TIDE algorithm was further utilized to assess the response to immunotherapy. Additionally, Gene set enrichment analysis (GSEA) was applied to elucidate the molecular mechanisms underlying the findings.ResultsWe constructed a 5-gene prognostic model consisting of RIN2, THBS1, IL1R1, RAB31, and COL11A1 for CAF. Using the median CAF risk score as the cutoff, we classified LBC patients into high- and low-CAF-risk groups and found that those in the high-risk group had a significantly worse prognosis. Spearman correlation analyses demonstrated a strong positive correlation between the CAF risk score and stromal and CAF infiltrations, with the five model genes showing positive correlations with CAF markers. In addition, the TIDE analysis revealed that high-CAF-risk patients were less likely to respond to immunotherapy. Gene set enrichment analysis (GSEA) identified significant enrichment of ECM receptor interaction, regulation of actin cytoskeleton, epithelial-mesenchymal transition (EMT), and TGF-β signaling pathway gene sets in the high-CAF-risk group patients.ConclusionThe five-gene prognostic CAF signature presented in this study was not only reliable for predicting prognosis in LBC patients, but it was also effective in estimating clinical immunotherapy response. These findings have significant clinical implications, as the signature may guide tailored anti-CAF therapy in combination with immunotherapy for LBC patients.
Oral vinorelbine and continuous low doses of cyclophosphamide in pediatric rhabdomyosarcoma: a real-world study
Authors: Lan Yingxia , Wu Liuhong , Hong Ye , Sun Xiaofei , Wang Juan , Huang Junting , Sun Feifei , Zhu Jia , Zhen Zijun , Zhang Yizhuo , Song Mengjia , Lu Suying 
Published: May 2023

Introduction: Metronomic maintenance therapy (MMT) has significantly improved the survival of patients with high-risk rhabdomyosarcoma in clinical trials. However, there remains a lack of relevant data on its effectiveness in real-world situations.Methods: We retrospectively retrieved data of 459 patients &lt; 18 years of age diagnosed with rhabdomyosarcoma at Sun Yat-sen University Cancer Center from January 2011 to July 2020 from our database. The MMT regimen was oral vinorelbine 25–40 mg/m2 for twelve 4-week cycles on days 1, 8, and 15, and oral cyclophosphamide 25–50 mg/m2 daily for 48 consecutive weeks.Results: A total of 57 patients who underwent MMT were included in the analysis. The median follow-up time was 27.8 (range: 2.9–117.5) months. From MMT to the end of follow-up, the 3-year PFS and OS rates were 40.6% ± 6.8% and 58.3% ± 7.2%, respectively. The 3-year PFS was 43.6% ± 11.3% in patients who were initially diagnosed as low- and intermediate-risk but relapsed after comprehensive treatment (20/57), compared with 27.8% ± 10.4% in high-risk patients (20/57) and 52.8% ± 13.3% in intermediate-risk patients who did not relapse (17/57). The corresponding 3-year OS for these three groups was 65.8% ± 11.4%, 50.1% ± 12.9%, and 55.6% ± 13.6%, respectively.Conclusion: We present a novel study of MMT with oral vinorelbine and continuous low doses of cyclophosphamide in real-world pediatric patients with RMS. Our findings showed that the MMT strategy significantly improved patient outcomes and may be an effective treatment for high-risk and relapsed patients.
Advanced lung cancer inflammation index is associated with long-term cardiovascular death in hypertensive patients: national health and nutrition examination study, 1999–2018
Authors: Tu Jiabin , Wu Bo , Xiu Jiaming , Deng Jiayi , Lin Shuqiong , Lu Jin , Yan Yanfang , Yu Pei , Zhu Jinlong , Chen Kaihong , Ding Shan , Chen Liling 
Published: May 2023

Background: Hypertension is one of the main causes of cardiovascular death. Inflammation was considered influential factors of cardiovascular (CVD) death in patients with hypertension. Advanced lung cancer inflammation index (ALI) is an index to assess inflammation, few studies have investigated the relationship between advanced lung cancer inflammation index and cardiovascular death in hypertensive patients.Objective: The aim of this study was to investigate the association between advanced lung cancer inflammation index and long-term cardiovascular death in hypertensive patients.Method: Data from the National Health and Nutrition Examination Survey (NHANES) 1999–2018 with mortality follow-up through 31 December 2019 were analyzed. Advanced lung cancer inflammation index was calculated as BMI (kg/㎡) × serum albumin level (g/dL)/neutrophil to lymphocyte ratio (NLR). A total of 20,517 participants were evaluated. Patients were divided into three groups based on tertiles of advanced lung cancer inflammation index as follows: T1 (n = 6,839), T2 (n = 6,839), and T3 (n = 6,839) groups. The relationship between advanced lung cancer inflammation index and long-term cardiovascular death was assessed by survival curves and Cox regression analysis based on the NHANES recommended weights.Results: The median advanced lung cancer inflammation index value in this study was 61.9 [44.4, 84.6]. After full adjustment, the T2 group (hazard ratio [HR]: 0.59, 95% confidence interval [CI]: 0.50–0.69; p &lt; 0.001) and T3 group (HR: 0.48, 95% CI: 0.39–0.58; p &lt; 0.001) were found to have a significantly lower risk of cardiovascular death compared to the T1 group.Conclusion: High levels of advanced lung cancer inflammation index were associated with reduced risk of cardiovascular death in hypertensive patients.
Energy cost differences between marathon runners and soccer players: Constant versus shuttle running
Authors: Padulo Johnny , Buglione Antonio , Larion Alin , Esposito Fabio , Doria Christian , Čular Dražen , di Prampero Pietro Enrico , Peyré-Tartaruga Leonardo Alexandre 
Published: May 2023

Purpose: In the last decades, the energy cost assessment provided new insight on shuttle or constant running as training modalities. No study, though, quantified the benefit of constant/shuttle running in soccer-players and runners. Therefore, the aim of this study was to clarify if marathon runners and soccer players present specific energy cost values related to their training experience performing constant and shuttle running.Methods: To this aim, eight runners (age 34 ± 7.30y; training experience 5.70 ± 0.84y) and eight soccer-players (age 18.38 ± 0.52y; training experience 5.75 ± 1.84y) were assessed randomly for 6’ on shuttle-running or constant-running with 3 days of recovery in-between. For each condition, the blood lactate (BL) and the energy cost of constant (Cr) and shuttle running (CSh) was determined. To assess differences for metabolic demand in terms of Cr, CSh and BL over the two running conditions on the two groups a MANOVA was used.Results:V·O2max were 67.9 ± 4.5 and 56.8 ± 4.3 ml·min−1 kg−1 (p = 0.0002) for marathon runners and soccer players, respectively. On constant running, the runners had a lower Cr compared to soccer players (3.86 ± 0.16 J kg−1m−1 vs. 4.19 ± 0.26 J kg−1 m−1; F = 9.759, respectively; p = 0.007). On shuttle running, runners had a higher CSh compared to soccer players (8.66 ± 0.60 J kg−1 m−1 vs. 7.86 ± 0.51 J kg−1 m−1; F = 8.282, respectively; with p = 0.012). BL on constant running was lower in runners compared to soccer players (1.06 ± 0.07 mmol L−1 vs. 1.56 ± 0.42 mmol L−1, respectively; with p = 0.005). Conversely, BL on shuttle running was higher in runners compared to soccer players 7.99 ± 1.49 mmol L−1 vs. 6.04 ± 1.69 mmol L−1, respectively; with p = 0.028).Conclusion: The energy cost optimization on constant or shuttle running is strictly related to the sport practiced.