bluuebunny/crossref_metadata_2025_split huggingface dataset:
Proteomic and Biological Analysis of the Effects of Metformin Senomorphics on the Mesenchymal Stromal Cells
Authors: Acar Mustafa Burak , Ayaz-Güner Şerife , Gunaydin Zeynep , Karakukcu Musa , Peluso Gianfranco , Di Bernardo Giovanni , Özcan Servet , Galderisi Umberto 
Published: October 2021

Senotherapeutics are new drugs that can modulate senescence phenomena within tissues and reduce the onset of age-related pathologies. Senotherapeutics are divided into senolytics and senomorphics. The senolytics selectively kill senescent cells, while the senomorphics delay or block the onset of senescence. Metformin has been used to treat diabetes for several decades. Recently, it has been proposed that metformin may have anti-aging properties as it prevents DNA damage and inflammation. We evaluated the senomorphic effect of 6 weeks of therapeutic metformin treatment on the biology of human adipose mesenchymal stromal cells (MSCs). The study was combined with a proteome analysis of changes occurring in MSCs’ intracellular and secretome protein composition in order to identify molecular pathways associated with the observed biological phenomena. The metformin reduced the replicative senescence and cell death phenomena associated with prolonged in vitro cultivation. The continuous metformin supplementation delayed and/or reduced the impairment of MSC functions as evidenced by the presence of three specific pathways in metformin-treated samples: 1) the alpha-adrenergic signaling, which contributes to regulation of MSCs physiological secretory activity, 2) the signaling pathway associated with MSCs detoxification activity, and 3) the aspartate degradation pathway for optimal energy production. The senomorphic function of metformin seemed related to its reactive oxygen species (ROS) scavenging activity. In metformin-treated samples, the CEBPA, TP53 and USF1 transcription factors appeared to be involved in the regulation of several factors (SOD1, SOD2, CAT, GLRX, GSTP1) blocking ROS.
Identification of the Prognostic Signature Associated With Tumor Immune Microenvironment of Uterine Corpus Endometrial Carcinoma Based on Ferroptosis-Related Genes
Authors: Liu Jinhui , Wang Yichun , Meng Huangyang , Yin Yin , Zhu Hongjun , Ni Tingting 
Published: October 2021

Background: Uterine corpus endometrial carcinoma (UCEC) is the sixth most common cancer worldwide. Ferroptosis plays an important role in malignant tumors. However, the study of ferroptosis in the endometrial carcinoma remains blank.Methods: First, we constructed a ferroptosis-related signature based on the expression profiles from The Cancer Genome Atlas database. Then, patients were divided into the high-risk and low-risk groups based on this signature. The signature was evaluated by Kaplan–Meier analysis and receiver operating characteristic (ROC) analysis. We further investigated the relationship between this signature and immune microenvironment via CIBERSORT algorithm, ImmuCellAI, MAF, MSI sensor algorithm, GSEA, and GDSC.Results: This signature could be an independent prognostic factor based on multivariate Cox regression analysis. GSEA revealed that this signature was associated with immune-related phenotype. In addition, we indicated the different status of immune infiltration and response to the immune checkpoint between low-risk and high-risk groups. Patients in the low-risk group were more likely to present with a higher expression of immune checkpoint molecules and tumor mutation burden. Meanwhile, the low-risk patients showed sensitive responses to chemotherapy drugs.Conclusion: In summary, the six ferroptosis-related genes signature could be used in molecular subgrouping and accurately predict the prognosis of UCEC.
Combined the Photocatalysis and Fenton-like Reaction to Efficiently Remove Sulfadiazine in Water Using g-C3N4/Ag/γ-FeOOH: Insights Into the Degradation Pathway From Density Functional Theory
Authors: Zhu Yangchen , Zhao Furong , Wang Fei , Zhou Beihai , Chen Huilun , Yuan Rongfang , Liu Yuxin , Chen Yuefang 
Published: October 2021

Sulfadiazine (SDZ) is a common antibiotic pollutant in wastewater. Given that it poses a risk as an environmental pollutant, finding effective ways to treat it is important. In this paper, the composite catalytic material g-C3N4/Ag/γ-FeOOH was prepared, and its degradation performance was studied. g-C3N4/Ag/γ-FeOOH had a superior degradation effect on SDZ than g-C3N4 and γ-FeOOH. Compared with different g-C3N4 loadings and different catalyst dosages (5, 10, 25, and 50 mg/L), 2 mg/L g-C3N4/Ag/γ-FeOOH with a g-C3N4 loading of 5.0 wt% has the highest degradation promotion rate for SDZ, reaching up to 258.75% at 600 min. In addition, the photocatalytic enhancement mechanism of the catalyst was studied. Density functional theory (DFT) calculations indicated that the enhancement of photocatalytic activity was related to the narrowing of the forbidden band and the local electron density of the valence band. The bandgap of the catalyst was gradually narrowed from 2.7 to 1.05 eV, which can increase the light absorption intensity and expand the absorption edge. The density of states diagram showed that the local resonance at the interface could effectively improve the separation efficiency of e−-h+ pairs. Four degradation paths of SDZ were speculated based on DFT calculations. The analysis confirmed that the degradation path of SDZ primarily included Smiles-type rearrangement, SO2 extrusion, and S-N bond cleavage processes.
HATCH Score and Left Atrial Size Predict Atrial High-Rate Episodes in Patients With Cardiac Implantable Electronic Devices
Authors: Chen Ju-Yi , Chen Tse-Wei , Lu Wei-Da 
Published: October 2021

Background: Patients with sustained atrial high-rate episodes (AHRE) have a high risk of major adverse cardio/cerebrovascular events (MACCE). However, the prediction model and factors for the occurrence of AHRE are unknown. We aimed to identify independent factors and various risk models for predicting MACCE and AHRE.Methods: We retrospectively enrolled 314 consecutive patients who had cardiac implantable electronic devices (CIEDs). The primary endpoint was MACCE after AHRE ≥3, 6 min, and 6 h. Atrial high-rate episodes was defined as &gt;175 bpm (Medtronic®) lasting ≥30 s. Multivariate Cox and logistic regression analysis with time-dependent covariates were used to determine variables associated with independent risk of MACCE and occurrence of AHRE ≥3 min, respectively.Results: One hundred twenty-five patients (39.8%) developed AHRE ≥3 min, 103 (32.8%) ≥6 min, and 55 (17.5%) ≥6 h. During follow-up (median 32 months), 77 MACCE occurred (incidence 9.20/100 patient years, 95% CI 5.66–18.39). The optimal AHRE cutoff value was 3 min for MACCE, with highest Youden index 1.350 (AUC, 0.716; 95% CI, 0.638–0.793; p &lt; 0.001). Atrial high-rate episodes ≥3 min−6 h were independently associated with MACCE. HATCH score and left atrial diameter were independently associated with AHRE ≥3 min. The optimal cutoff for HATCH score was 3 and for left atrial diameter was 4 cm for AHRE ≥3 min.Conclusion: Patients with CIEDs who develop AHRE ≥3 min have an independently increased risk of MACCE. Comprehensive assessment using HATCH score and echocardiography of patients with CIEDs is warranted.
Prognostic Value of Preoperative Serum Calcitonin Levels for Predicting the Recurrence of Medullary Thyroid Carcinoma
Authors: Park Hyunju , Park So Young , Park Jun , Choe Jun Ho , Chung Man Ki , Woo Sook-Young , Choi Joon Young , Kim Sun Wook , Chung Jae Hoon , Kim Tae Hyuk 
Published: October 2021

BackgroundSerum calcitonin level is a useful biomarker for predicting primary tumor size, the extent of lymph node, and distant metastasis in patients with medullary thyroid carcinoma (MTC). However, the association between preoperative serum calcitonin levels and long-term oncologic outcomes has not yet been established. The aims of this study were to determine the preoperative serum calcitonin cut-off value for predicting disease recurrence and to evaluate its prognostic value.MethodsPatients with MTC (n = 169) who were treated at a tertiary referral hospital in Korea between 1995 and 2019 were enrolled. To determine the preoperative serum calcitonin cut-off value for predicting structural recurrence, the maximum of the standardized log-rank statistics of all possible cut-off values was used. Multivariable Cox regression analysis was used to determine prognostic factors for disease-free survival.ResultsThe overall disease-free survival rate was 75.7%. The preoperative serum calcitonin cut-off value that predicted structural recurrence was 309 pg/mL. Preoperative serum calcitonin levels of &gt; 309 pg/mL were the strongest independent predictor of disease recurrence (hazard ratio (HR) 5.33, 95% confidence interval (85% CI) 1.67–16.96; P = 0.005). Lateral lymph node metastasis (HR 3.70, 95% CI 1.61–8.51; P = 0.002) and positive resection margins (HR 3.57, 95% CI 1.44–8.88; P = 0.006) were also significant predictors of disease recurrence.ConclusionsThe preoperative serum calcitonin cut-off value is useful in clinical practice. It is also the best predictive factor for disease-free survival. Preoperative serum calcitonin levels may help determine the optimal postoperative follow-up strategy for patients with MTC.
Major Reorganization of Chromosome Conformation During Muscle Development in Pig
Authors: Marti-Marimon Maria , Vialaneix Nathalie , Lahbib-Mansais Yvette , Zytnicki Matthias , Camut Sylvie , Robelin David , Yerle-Bouissou Martine , Foissac Sylvain 
Published: October 2021

The spatial organization of the genome in the nucleus plays a crucial role in eukaryotic cell functions, yet little is known about chromatin structure variations during late fetal development in mammals. We performed in situ high-throughput chromosome conformation capture (Hi-C) sequencing of DNA from muscle samples of pig fetuses at two late stages of gestation. Comparative analysis of the resulting Hi-C interaction matrices between both groups showed widespread differences of different types. First, we discovered a complex landscape of stable and group-specific Topologically Associating Domains (TADs). Investigating the nuclear partition of the chromatin into transcriptionally active and inactive compartments, we observed a genome-wide fragmentation of these compartments between 90 and 110 days of gestation. Also, we identified and characterized the distribution of differential cis- and trans-pairwise interactions. In particular, trans-interactions at chromosome extremities revealed a mechanism of telomere clustering further confirmed by 3D Fluorescence in situ Hybridization (FISH). Altogether, we report major variations of the three-dimensional genome conformation during muscle development in pig, involving several levels of chromatin remodeling and structural regulation.
Sertraline for Functional Recovery After Acute Ischemic Stroke: A Prospective Observational Study
Authors: Stuckart Isabella , Siepmann Timo , Hartmann Christian , Pallesen Lars-Peder , Sedghi Annahita , Barlinn Jessica , Reichmann Heinz , Puetz Volker , Barlinn Kristian 
Published: October 2021

Background: Neuroprotective and neurorestorative effects have been postulated for selective serotonin-reuptake inhibitors (SSRI). We hypothesized that sertraline, which is characterized by less severe adverse effects and more stable pharmacokinetics than classic SSRI, is associated with improved functional recovery in acute ischemic stroke patients with motor deficits.Methods: Prospective observational study of consecutive acute ischemic stroke patients who received sertraline for clinically suspected post-stroke depression (PSD) or at high risk for PSD. Eligibility comprised acute motor deficit caused by ischemic stroke (≥2 points on NIHSS motor items) and functional independence pre-stroke (mRS ≤1). Decision to initiate treatment with SSRI during hospital stay was at the discretion of the treating stroke physician. Patients not receiving sertraline served as control group. Favorable functional recovery defined as mRS ≤2 was prospectively assessed at 3 months. Multivariable logistic regression analysis was used to explore the effects of sertraline on 3-months functional recovery. Secondary outcomes were frequency of any and incident PSD (defined by BDI ≥10) at 3 months.Results: During the study period (03/2017–12/2018), 114 patients were assigned to sertraline (n = 72, 62.6%) or control group (n = 42, 37.4%). At study entry, patients in sertraline group were more severely neurologically affected than patients in the control group (NIHSS: 8 [IQR, 5–11] vs. 5 [IQR, 4–7]; p = 0.002). Also, motor NIHSS scores were more pronounced in sertraline than in control group (4 [IQR 2–7] vs. 2 [IQR 2–4], p = 0.001). After adjusting for age and baseline NIHSS, multivariable regression analysis revealed a significant association between sertraline intake and favorable functional outcome at 3 months (OR 3.10, 95% CI 1.02–9.41; p = 0.045). There was no difference between both groups regarding the frequency of any depression at 3 months (26/53 [49.1%] vs. 14/28 [50.0%] patients, p = 0.643, BDI ≥10). However, fewer incident depressions were observed in sertraline group patients compared to patients in control group (0/53 [0%] vs. 5/28 [17.9%] patients, p = 0.004).Conclusions: In this non-randomized comparison, early treatment with sertraline tended to favor functional recovery in patients with acute ischemic stroke. While exploratory in nature, this hypothesis needs further investigation in a clinical trial.
Dynamic Network Connectivity Reveals Markers of Response to Deep Brain Stimulation in Parkinson’s Disease
Authors: Wu Chengyuan , Matias Caio , Foltynie Thomas , Limousin Patricia , Zrinzo Ludvic , Akram Harith 
Published: October 2021

Background: Neuronal loss in Parkinson’s Disease (PD) leads to widespread neural network dysfunction. While graph theory allows for analysis of whole brain networks, patterns of functional connectivity (FC) associated with motor response to deep brain stimulation of the subthalamic nucleus (STN-DBS) have yet to be explored.Objective/Hypothesis: To investigate the distributed network properties associated with STN-DBS in patients with advanced PD.Methods: Eighteen patients underwent 3-Tesla resting state functional MRI (rs-fMRI) prior to STN-DBS. Improvement in UPDRS-III scores following STN-DBS were assessed 1 year after implantation. Independent component analysis (ICA) was applied to extract spatially independent components (ICs) from the rs-fMRI. FC between ICs was calculated across the entire time series and for dynamic brain states. Graph theory analysis was performed to investigate whole brain network topography in static and dynamic states.Results: Dynamic analysis identified two unique brain states: a relative hypoconnected state and a relative hyperconnected state. Time spent in a state, dwell time, and number of transitions were not correlated with DBS response. There were no significant FC findings, but graph theory analysis demonstrated significant relationships with STN-DBS response only during the hypoconnected state – STN-DBS was negatively correlated with network assortativity.Conclusion: Given the widespread effects of dopamine depletion in PD, analysis of whole brain networks is critical to our understanding of the pathophysiology of this disease. Only by leveraging graph theoretical analysis of dynamic FC were we able to isolate a hypoconnected brain state that contained distinct network properties associated with the clinical effects of STN-DBS.
Mandibular Reconstruction With Fibula Flap and Dental Implants Through Virtual Surgical Planning and Three Different Techniques: Double-Barrel Flap, Implant Dynamic Navigation and CAD/CAM Mesh With Iliac Crest Graft
Authors: Antúnez-Conde Raúl , Salmerón José Ignacio , Díez-Montiel Alberto , Agea Marc , Gascón Dafne , Sada Ángela , Navarro Cuéllar Ignacio , Tousidonis Manuel , Ochandiano Santiago , Arenas Gema , Navarro Cuéllar Carlos 
Published: October 2021

IntroductionVertical discrepancy between the fibula flap and the native mandible results in difficult prosthetic rehabilitation. The aim of this study was to evaluate the outcomes of 3D reconstruction of the mandible in oncologic patients using three different techniques through virtual surgical planning (VSP), cutting guides, customized titanium mesh and plates with CAD/CAM technology, STL models and intraoperative dynamic navigation for implant placement. Material and methodsMaterial and MethodsThree different techniques for mandibular reconstruction and implant rehabilitation were performed in 14 oncologic patients. Five patients (36%) underwent VSP, cutting guides, STL models and a customized double-barrel titanium plate with a double-barrel flap and immediate implants. In six patients (43%), VSP, STL models and a custom-made titanium mesh (CAD/CAM) for 3D reconstruction with iliac crest graft over a fibula flap with deferred dental implants were performed. Three patients (21%) underwent VSP with cutting guides and customized titanium plates for mandibular reconstruction and implant rehabilitation using intraoperative dynamic navigation was accomplished. Vertical bone reconstruction, peri-implant bone resorption, implant success rate, effects of radiotherapy in vertical reconstruction, bone resorption and implant failure, mastication, aesthetic result and dysphagia were evaluated.ResultsSignificant differences in bone growth between the double-barrel technique and iliac crest graft with titanium mesh technique were found (p&lt;0.002). Regarding bone resorption, there were no significant differences between the techniques (p=0.11). 60 implants were placed with an osseointegration rate of 91.49%. Five implants were lost during the osseointegration period (8%). Peri-implant bone resorption was measured with a mean of 1.27 mm. There was no significant difference between the vertical gain technique used and implant survival (p&gt;0.385). Implant survival rates were higher in non-irradiated patients (p&lt;0.017). All patients were rehabilitated with a fixed implant-supported prosthesis reporting a regular diet (80%), normal swallowing (85.7%) and excellent aesthetic results.ConclusionsMulti-stage implementation of VSP, STL models and cutting guides, CAD/CAM technology, customized plates and in-house dynamic implant navigation for mandibular defects increases bone-to-bone contact, resolves vertical discrepancy and improves operative efficiency with reduced complication rates and minimal bone resorption. It provides accurate reconstruction that optimizes implant placement, thereby improving facial symmetry, aesthetics and function.
Prognostic Value of Pretreatment Prognostic Nutritional Index in Patients With Renal Cell Carcinoma: A Meta-Analysis
Authors: Mao Changqing , Xu Weixin , Ma Weina , Wang Chun , Guo Zhaojiao , Yan Jun 
Published: October 2021

BackgroundThe pretreatment prognostic nutritional index (PNI) is correlated with poor prognosis in several malignancies. However, the prognostic role of PNI in patients with renal cell carcinoma (RCC) remains unclear. Therefore, we performed a meta-analysis to investigate the prognostic significance of PNI in patients with RCC.MethodsWe searched the PubMed, Web of Science, Embase, Scopus, and Cochrane Library databases up to February 2021. Pooled hazard ratios (HRs) and 95% confidence intervals (CIs) were used to estimate correlation between PNI and survival endpoints in RCC.ResultsTen studies with 4,908 patients were included in the meta-analysis. The pooled results indicated that a low PNI associated with poor overall survival (HR = 2.10, 95% CI = 1.67–2.64, p&lt;0.001), shorter progression-free survival, disease-free survival, recurrence-free survival (HR = 1.99, 95% CI = 1.67–2.36, p&lt;0.001), and poor cancer-specific survival (HR = 2.95, 95% CI = 1.61–5.39, p&lt;0.001). Additionally, the prognostic ability of PNI was not affected by subgroup analysis factors.ConclusionThe meta-analysis indicated that low PNI associated with shorter survival outcomes in patients with RCC. Therefore, PNI could be used as an effective prognostic indicator in RCC.
Identification of a Somatic Mutation-Derived Long Non-Coding RNA Signatures of Genomic Instability in Renal Cell Carcinoma
Authors: Fang Xisheng , Liu Xia , Lu Lin , Liu Guolong 
Published: October 2021

BackgroundRenal cell carcinoma (RCC) is a malignant tumor with high morbidity and mortality. It is characterized by a large number of somatic mutations and genomic instability. Long non-coding RNAs (lncRNAs) are widely involved in the expression of genomic instability in renal cell carcinoma. But no studies have identified the genome instability-related lncRNAs (GInLncRNAs) and their clinical significances in RCC.MethodsClinical data, gene expression data and mutation data of 943 RCC patients were downloaded from The Cancer Genome Atlas (TCGA) database. Based on the mutation data and lncRNA expression data, GInLncRNAs were screened out. Co-expression analysis, Gene Ontology (GO) enrichment analysis and Kyoto Encyclopedia of Genes and Genomes (KEGG) enrichment analysis were conducted to explore their potential functions and related signaling pathways. A prognosis model was further constructed based on genome instability-related lncRNAs signature (GInLncSig). And the efficiency of the model was verified by receiver operating characteristic (ROC) curve. The relationships between the model and clinical information, prognosis, mutation number and gene expression were analyzed using correlation prognostic analysis. Finally, the prognostic model was verified in clinical stratification according to TCGA dataset.ResultsA total of 45 GInLncRNAs were screened out. Functional analysis showed that the functional genes of these GInLncRNAs were mainly enriched in chromosome and nucleoplasmic components, DNA binding in molecular function, transcription and complex anabolism in biological processes. Univariate and Multivariate Cox analyses further screened out 11 GInLncSig to construct a prognostic model (AL031123.1, AC114803.1, AC103563.7, AL031710.1, LINC00460, AC156455.1, AC015977.2, ‘PRDM16-dt’, AL139351.1, AL035661.1 and LINC01606), and the coefficient of each GInLncSig in the model was calculated. The area under the curve (AUC) value of the ROC curve was 0.770. Independent analysis of the model showed that the GInLncSig model was significantly correlated with the RCC patients’ overall survival. Furthermore, the GInLncSig model still had prognostic value in different subgroups of RCC patients.ConclusionOur study preliminarily explored the relationship between genomic instability, lncRNA and clinical characteristics of RCC patients, and constructed a GInLncSig model consisted of 11 GInLncSig to predict the prognosis of patients with RCC. At the same time, our study provided theoretical support for the exploration of the formation and development of RCC.