bluuebunny/crossref_metadata_2025_split huggingface dataset:
Arterial Doppler Waveforms Are Independently Associated With Maximal Walking Distance in Suspected Peripheral Artery Disease Patients
Authors: Miossec Annaïg , Tollenaere Quentin , Lanéelle Damien , Guilcher Antoine , Métairie Antoine , Le Pabic Estelle , Carel Awenig , Le Faucheur Alexis , Mahé Guillaume 
Published: April 2021

Objective: Arterial Doppler waveform recordings are commonly used to assess lower extremity arterial disease (LEAD) severity. However, little is known about the relationship between arterial Doppler waveform profiles and patients' walking capacity. The purpose of this study was to assess whether arterial Doppler waveforms are independently associated with maximal walking distance (MWD) in patients experiencing exertional limb symptoms.Materials and Methods: This cross-sectional study included suspected LEAD patients experiencing exertional limb symptoms. In both lower extremities, arterial Doppler waveforms and ankle-brachial index (ABI) values were obtained from the pedis and tibial posterior arteries. Each arterial flow measurement was ranked using the Saint-Bonnet classification system. Treadmill stress testing (3.2 km/h, 10% slope) coupled with exercise oximetry (Exercise-TcPO2) were used to determine MWD. Delta from rest oxygen pressure (DROP) was calculated. Following treadmill stress testing, post-exercise ABI values were recorded. Univariate and multivariate analyses were used to determine the clinical variables associated with MWD.Results: 186 patients experiencing exertional limb symptoms (62 ± 12 years and 26.8 ± 4.5 kg/m2) were included between May 2016 and June 2019. Median [25th; 75th] treadmill MWD was 235 [125;500]m. Better arterial Doppler waveforms were associated with better walking distance (p = 0.0012). Whereas, median MWD was 524 [185;525]m in the group that yielded the best Doppler waveforms, it was 182 [125,305]m in the group with the poorest Doppler waveforms (p = 0.0012). MWD was significantly better (p = 0.006) in the patients with the best ABIs. However, arterial Doppler waveforms alone were significantly associated with MWD (p = 0.0009) in the multivariate model. When exercise variables (post-exercise ABI or DROP) were incorporated into the multivariate model, these were the only variables to be associated with MWD.Conclusion: Of the various clinical parameters at rest, Doppler flow waveform profiles were associated with MWD in suspected LEAD patients. A stronger link was however found between exercise variables and MWD.
AMPA-Type Glutamate Receptors Associated With Vascular Smooth Muscle Cell Subpopulations in Atherosclerosis and Vascular Injury
Authors: Gallina Alessandro L. , Rykaczewska Urszula , Wirka Robert C. , Caravaca April S. , Shavva Vladimir S. , Youness Mohamad , Karadimou Glykeria , Lengquist Mariette , Razuvaev Anton , Paulsson-Berne Gabrielle , Quertermous Thomas , Gisterå Anton , Malin Stephen G. , Tarnawski Laura , Matic Ljubica , Olofsson Peder S. 
Published: April 2021

Objectives and Aims: Vascular smooth muscle cells (VSMCs) are key constituents of both normal arteries and atherosclerotic plaques. They have an ability to adapt to changes in the local environment by undergoing phenotypic modulation. An improved understanding of the mechanisms that regulate VSMC phenotypic changes may provide insights that suggest new therapeutic targets in treatment of cardiovascular disease (CVD). The amino-acid glutamate has been associated with CVD risk and VSMCs metabolism in experimental models, and glutamate receptors regulate VSMC biology and promote pulmonary vascular remodeling. However, glutamate-signaling in human atherosclerosis has not been explored.Methods and Results: We identified glutamate receptors and glutamate metabolism-related enzymes in VSMCs from human atherosclerotic lesions, as determined by single cell RNA sequencing and microarray analysis. Expression of the receptor subunits glutamate receptor, ionotropic, α-amino-3-hydroxy-5-methyl-4-isoxazolepropionic (AMPA)-type subunit 1 (GRIA1) and 2 (GRIA2) was restricted to cells of mesenchymal origin, primarily VSMCs, as confirmed by immunostaining. In a rat model of arterial injury and repair, changes of GRIA1 and GRIA2 mRNA level were most pronounced at time points associated with VSMC proliferation, migration, and phenotypic modulation. In vitro, human carotid artery SMCs expressed GRIA1, and selective AMPA-type receptor blocking inhibited expression of typical contractile markers and promoted pathways associated with VSMC phenotypic modulation. In our biobank of human carotid endarterectomies, low expression of AMPA-type receptor subunits was associated with higher content of inflammatory cells and a higher frequency of adverse clinical events such as stroke.Conclusion: AMPA-type glutamate receptors are expressed in VSMCs and are associated with phenotypic modulation. Patients suffering from adverse clinical events showed significantly lower mRNA level of GRIA1 and GRIA2 in their atherosclerotic lesions compared to asymptomatic patients. These results warrant further mapping of neurotransmitter signaling in the pathogenesis of human atherosclerosis.
Body Adiposity, But Not Elements of Objectively Measured Sedentary Behavior or Physical Activity, Is Associated With Circulating Liver Enzymes in Adults With Overweight and Obesity
Authors: Laine Saara , Sjöros Tanja , Vähä-Ypyä Henri , Garthwaite Taru , Löyttyniemi Eliisa , Sievänen Harri , Vasankari Tommi , Knuuti Juhani , Heinonen Ilkka H. A. 
Published: April 2021

ObjectiveWe studied the associations between accelerometer-measured sedentary behavior (SB) and habitual physical activity (PA) as well as markers of body adiposity and other cardiometabolic risk factors with liver enzymes alanine aminotransferase (ALT), aspartate aminotransferase (AST) and γ-glutamyltransferase (GGT).MethodsA total of 144 middle-aged adults (mean age 57 (SD 6.5) years) with overweight or obesity (mean body mass index [BMI] 31.8 [SD 3.9] kg/m2) participated. Different components of SB (sitting, lying) and PA (standing, breaks in SB, daily steps, light PA, moderate-to-vigorous PA and total PA) were measured with validated hip-worn accelerometers for four consecutive weeks (mean 25 days, [SD 4]). Fasting venous blood samples were analysed using standard assays. The associations were examined with Pearson’s partial correlation coefficient test and linear mixed model.ResultsAmong 102 women and 42 men accelerometer measured SB or the elements of PA were not associated with circulating liver enzymes. When adjusted for age and sex, liver enzymes correlated positively with BMI and waist circumference (WC) (ALT r=0.34, p&lt;0.0001, r=0.41, &lt; 0.0001, AST r=0.17, p=0.049, r=0.26, p=0.002, GGT r=0.29, p=0.0005, r=0.32, p &lt; 0.0001, respectively). SB proportion associated positively with BMI (r=0.21, p=0.008) and WC (r=0.27, p=0.001). Components of PA associated negatively with BMI (MVPA r=-0.23, p=0.005, daily steps r=-0.30, p&lt;0.0001 and breaks in sedentary time r=-0.32, p&lt;0.0001), as well as with WC (breaks in SB r=-0.35, p&lt;0.0001, MVPA r=-0.26, p=0.002, daily steps r=-0.31, p&lt;0.0001, standing time r=-0.27, p=0.001). Liver enzymes associated positively with common cardiometabolic markers such as resting heart rate (ALT; β=0.17, p=0.03, AST; β=0.25, p=0.002, GGT; β=0.23, p=0.004) and systolic/diastolic blood pressure (ALT β=0.20, p=0.01, β=0.22, p=0.005, AST (only diastolic) β=0.23, p=0.006, GGT β=0.19, p=0.02, = 0.23, p=0.004, respectively), fasting insulin (ALT β=0.41, p&lt;0.0001, AST β=0.36, p=0.0003, GGT β=0.20, p=0.04) and insulin resistance index (ALT β=0.42, p&lt;0.0001, AST β=0.36, p=0.0003, GGT β=0.21, p=0.03), even after adjustment with BMI.ConclusionsLiver enzymes correlate with body adiposity and appear to cluster with other common cardiometabolic risk factors, even independently of body adiposity. SB and PA appear not to be essential in modulating the levels of circulating liver enzymes.
Circulating Adaptive Immune Cells Expressing the Gut Homing Marker α4β7 Integrin Are Decreased in COVID-19
Authors: Müller Tanja M. , Becker Emily , Wiendl Maximilian , Schulze Lisa Lou , Voskens Caroline , Völkl Simon , Kremer Andreas E. , Neurath Markus F. , Zundler Sebastian 
Published: April 2021

BackgroundInfection with the novel severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) causes a wide range of symptoms including gastrointestinal manifestations, and intestinal epithelial cells are a target of the virus. However, it is unknown how the intestinal immune system contributes to systemic immune responses in coronavirus disease 2019 (COVID-19).MethodsWe characterized peripheral blood lymphocytes from patients with active COVID-19 and convalescent patients as well as healthy controls by flow cytometry.ResultsThe frequency and absolute number of circulating memory T and B cells expressing the gut homing integrin α4β7 integrin was reduced during COVID-19, whether gastrointestinal symptoms were present or not. While total IgA-expressing B cells were increased, gut-imprinted B cells with IgA expression were stable.ConclusionCOVID-19 is associated with a decrease in circulating adaptive immune cells expressing the key gut homing marker α4β7 suggesting that these cells are preferentially recruited to extra-intestinal tissues independently of α4β7 or that the systemic immune response against SARS-CoV-2 is at least numerically dominated by extraintestinal, particularly pulmonary, immune cell priming.
Opposing Trends in Total Knee and Hip Arthroplasties for Patients With Rheumatoid Arthritis vs. the General Population—A 14-Year Retrospective Study in Taiwan
Authors: Tung Kuan-Kai , Lee Yung-Heng , Lin Chuan-Chao , Lee Cheng-Hung , Lin Mei-Chen , Wei James Cheng-Chung 
Published: April 2021

Objective: To determine the trend of incidence rate of total knee arthroplasty (TKA), total hip arthroplasty (THA), and TKA or THA (major joint arthroplasty, MJA) among rheumatoid arthritis (RA) population and compared them with general population (GP) in Taiwan.Methods: Incidence rates and trends of TKA, THA, and MJA were determined over a 14-year period (2000–2013) among RA patients and compared them with GP. RA of patients was diagnosed based on the ACR 1987 criteria and extracted from GP. Subanalyses of incidences of TKA, THA, and MJA by year, 10-year age group, and gender were further conducted for demographic analysis. Patient profiles were extracted from the National Health Insurance Research Database (NHIRD) for interrupted time-series analysis and cohort studies.Results: Patients enrolled were 168,457 receiving TKA, 64,543 receiving THA, and 228,191 receiving MJA surgery. Incidences of TKA, THA, and MJA in RA patients were significantly lower by 49.0, 41.5, and 41.0% compared with concomitantly rises in GP by 131.0, 25.1, and 90.0% among the GP during the study period. The dominant age population for TKA, THA, and MJA were those aged 70–79 years in both GP and RA groups.Conclusions: We found an opposing trend in incidence of TKA, THA, and MJA between RA patients and the GP. The possible influence of pharmacological treatment is implicated for the lower incidence rates of TKA, THA, and MJA surgeries among RA patients.
Fibrin-Platelet Clots in Acute Ischemic Stroke. Predictors and Clinical Significance in a Mechanical Thrombectomy Series
Authors: Hernández-Fernández Francisco , Ramos-Araque María E. , Barbella-Aponte Rosa , Molina-Nuevo Juan David , García-García Jorge , Ayo-Martin Oscar , Pedrosa-Jiménez María José , López-Martinez Lorena , Serrano-Heras Gemma , Julia-Molla Enrique , Segura Tomás 
Published: April 2021

Introduction: The histological composition of the clot influences its mechanical properties, affects the efficacy of endovascular treatment (EVT), and could determine the clinical outcome of patients with acute ischemic stroke (AIS). Insights into clot composition may guide therapeutic decision-making prior to EVT and facilitate revascularization therapies.Material and Methods: Consecutive patients with AIS recorded in a prospective single-center reperfusion registry from December 2015 to December 2019 and treated with EVT were included. Baseline, laboratory [including post-procedural C-reactive protein (CRP)], radiological, and angiographic variables were analyzed. We aimed to study the relationship between histological composition of the clot with basal neuroimaging, laboratory markers, and recanalization technique. The secondary outcome was to analyze the correlation between clot composition and functional outcome at 3 months assessed by the modified Rankin scale (mRS).Results: From the study period, 360 AIS patients treated with EVT were included, of whom 189 (53%) fulfilled the inclusion criteria. One hundred (53%) cases of fibrin-predominant clot (FPC) were recorded. Full recanalization in FPC cases was achieved with higher probability when stent retrievers (SR) were selected as the first-line device (68.2%, p = 0.039). Patients with FPC had higher levels of CRP (p = 0.02), lower frequency of the hyperdense middle cerebral artery (HMCA) in baseline imaging (p = 0.039), and higher rates of mortality (p = 0.012). The multivariate analysis showed that the absence of HMCA (OR = 0.420; 95% CI 0.197–0.898; p = 0.025) and higher levels of CRP (OR = 1.01; 95% CI 1.003–1.019; p = 0.008) were predictors of FPC. Leukocytes and platelet counts were not associated with clot histology.Conclusions: The absence of HMCA and higher levels of CRP were markers of FPC. In patients with FPC, complete recanalization was most likely to be achieved when a SR was selected as first line of treatment. Mortality was higher in patients within this histologic group.
Analysis of the EGFR Amplification and CDKN2A Deletion Regulated Transcriptomic Signatures Reveals the Prognostic Significance of SPATS2L in Patients With Glioma
Authors: Wang Haiwei , Wang Xinrui , Xu Liangpu , Zhang Ji , Cao Hua 
Published: April 2021

Purpose: This study was conducted in order to analyze the prognostic effects of epidermal growth factor receptor (EGFR) and CDKN2A alterations and determine the prognostic significance of EGFR and CDKN2A alterations on regulated genes in patients with glioblastoma (GBM) or lower grade glioma (LGG).Methods: The alteration frequencies of EGFR and CDKN2A across 32 tumor types were derived from cBioPortal based on The Cancer Genome Atlas (TCGA) datasets. The Kaplan–Meier analysis was used to determine the prognostic significance of EGFR and CDKN2A alterations. EGFR and CDKN2A alterations on regulated expression signatures were identified from RNA-seq data in the TCGA GBM datasets. The prognostic significance of EGFR and CDKN2A alterations on regulated genes in patients with glioma was determined using the TCGA and the Chinese Glioma Genome Atlas (CGGA) datasets.Results: Compared with the other 31 tumor types, EGFR amplification and CDKN2A deletion particularly occurred in patients with GBM. GBM patients with EGFR amplification or CDKN2A deletion demonstrated poor prognosis. Statistical analysis showed the coexistence of EGFR alteration and CDKN2A deletion in GBM patients. We identified 864 genes which were commonly regulated by EGFR amplification and CDKN2A deletion, and those genes were highly expressed in brain tissues and associated with the cell cycle, EBRR2, and MAPK signaling pathways. Spermatogenesis-associated serine-rich 2-like gene (SPATS2L) was upregulated in GBM patients with EGFR amplification or CDKN2A alteration. Higher expression levels of SPATS2L were associated with worse prognosis in patients with GBM in both TCGA and CGGA datasets. Moreover, the expression levels of SPATS2L were higher in patients with a mesenchymal subtype of GBM. Statistical analysis also showed that the coexistence of EGFR alteration and CDKN2A deletion was significant in patients with LGG. SPATS2L was upregulated in LGG patients with EGFR amplification or CDKN2A alteration. Furthermore, higher expression levels of SPATS2L were associated with worse prognosis in patients with LGG in both TCGA and CGGA datasets. The expression levels of SPATS2L were higher in patients with an astrocytoma subtype of LGG. Finally, the coexistence and unfavorable prognostic effects of EGFR amplification and CDKN2A alteration were validated using the Memorial Sloan Kettering Cancer Center (MSKCC) glioma datasets.Conclusions: EGFR amplification and CDKN2A deletion of the regulated gene SPATS2L have significant prognostic effects in patients with GBM or LGG.
STAM Prolongs Clear Cell Renal Cell Carcinoma Patients' Survival via Inhibiting Cell Growth and Invasion
Authors: Deng Tuo , He Zihao , Duan Xiaolu , Gu Di , Cai Chao , Wu Wenqi , Liu Yongda , Zeng Guohua 
Published: April 2021

Background: Signal transducing adaptor molecule 1 (STAM1) was considered to mediate cell growth and be involved in multiple signaling pathways; however, no research on the role of STAM1 in any tumors has been published yet. Our study aimed to investigate the prognostic value of STAM1 for clear cell renal cell carcinoma (ccRCC) and its role in modulating cancer cell function.Methods: Data from The Cancer Genome Atlas (TCGA) in December 2019 were used to examine the role of STAM1 in indicating ccRCC patients' survival. A purchased tissue microarray (TM) and fresh ccRCC renal tissues were used for further validation. Then, STAM1 was overexpressed in human ccRCC cell lines for in vitro assays. Finally, bioinformatics was performed for STAM1 protein–protein interaction (PPI) network construction and functional analyses.Results: A total of 539 ccRCC and 72 control samples were included for the TCGA cohort, and 149 ccRCC and 29 control slices were included for the TM cohort. In the TCGA and TM cohorts, we found that STAM1 expression was lower in ccRCC compared with normal adjacent non-cancerous renal tissues (P &lt; 0.0001 for both cohorts). STAM1 downregulation was also related to significantly shorter overall survival (OS) (P &lt; 0.0001 for both cohorts). In the TCGA cohort, reduced STAM1 expression was also associated with aggressive features of the tumor. Under multivariate analyses, STAM1 was demonstrated to be an independent prognostic factor for ccRCC survival in both TCGA (HR = 0.52, 95% CI: 0.33–0.84, P = 0.007) and TM cohorts (HR = 0.12, 95% CI: 0.04–0.32, P &lt; 0.001). Our in vitro experiments showed that STAM1 inhibited cell viability, invasion, and migration in ccRCC cell lines. In PPI network, 10 candidate genes categorized into five biological processes were found to be closely related to STAM1.Conclusion: STAM1 is a promising prognostic biomarker for predicting ccRCC survival outcomes. Preliminary pathogenesis is demonstrated by our in vitro experiments. Further pathological mechanisms of STAM1 in modulating ccRCC require comprehensive laboratory and clinical studies.
Efficacy, Safety, and Cost-Minimization Analysis of Continuous Infusion of Low-Dose Gemcitabine Plus Cisplatin in Patients With Unresectable Malignant Pleural Mesothelioma
Authors: Arrieta Oscar , Muñoz-Montaño Wendy , Muñiz-Hernández Sae , Campos Saul , Catalán Rodrigo , Soto-Molina Herman , Guzmán Vázquez Silvia , Díaz-Álvarez Osvaldo , Martínez-Pacheco Victor , Turcott Jenny G. , Ramos-Ramírez Maritza , Cabrera-Miranda Luis , Barrón Feliciano , Cardona Andrés F. 
Published: April 2021

BackgroundMalignant pleural mesothelioma (MPM) is rare and aggressive neoplasia, with a poor prognosis; furthermore, the monetary cost of its treatment represents a major challenge for many patients. The economic burden this malignancy imposes is underscored by the fact that asbestos exposure, which is the most frequent risk factor, is much more prevalent in the lower socioeconomic population of developing countries. The aims of the present study were to evaluate the efficacy, safety, and cost of continuous infusion of low-dose Gemcitabine plus Cisplatin (CIGC) as a treatment strategy for patients with unresectable MPM.MethodsWe performed a prospective cohort study to determine efficacy and safety of continuous infusion gemcitabine at a dose of 250 mg/m2 in a 6-h continuous infusion plus cisplatin 35 mg/m2 on days 1 and 8 of a 21-day cycle in patients with unresectable MPM. We also performed a cost-minimization analysis to determine if this chemotherapy regimen is less expensive than other currently used regimens.ResultsThe median number of chemotherapy cycles was six (range 1–11 cycles); objective response rate was documented in 46.2%, and disease control rate was seen in 81.2%. Median PFS was 8.05 months (CI 95% 6.97–9.13); median OS was 16.16 months (CI 95% 12.5–19.9). The cost minimization analysis revealed savings of 66.4, 61.9, and 97.7% comparing CIGC with short-infusion gemcitabine plus cisplatin (SIGC), cisplatin plus pemetrexed (CP), and cisplatin plus pemetrexed and bevacizumab (CPB), respectively. Furthermore, this chemotherapy regimen proved to be safe at the administered dosage.ConclusionCIGC is an effective and safe treatment option for patients with unresectable MPM; besides, this combination is a cost-saving option when compared with other frequently used chemotherapy schemes. Therefore, this treatment scheme should be strongly considered for patients with unresectable MPM and limited economic resources.
A Novel Clinical Nomogram for Predicting Cancer-Specific Survival in Adult Patients After Primary Surgery for Epithelial Ovarian Cancer: A Real-World Analysis Based on the Surveillance, Epidemiology, and End Results Database and External Validation in a Tertiary Center
Authors: Li Xianli , Xu Haoya , Yan Limei , Gao Jian , Zhu Liancheng 
Published: April 2021

BackgroundThe present study aimed to construct and validate a nomogram that can be used to predict cancer-specific survival (CSS) in patients with epithelial ovarian cancer (EOC).MethodsA total of 7,129 adult patients with EOC were extracted from the Surveillance, Epidemiology, and End Results database between 2010 and 2015. Patients were randomly divided into the training and validation cohorts (7:3). Cox regression was conducted to evaluate prognostic factors of CSS. The internal validation of the nomogram was performed using concordance index (C-index), AUC, calibration curves, and decision curve analyses (DCAs). Data from 53 adult EOC patients at Shengjing Hospital of China Medical University from 2008 to 2012 were collected for external verification. Kaplan–Meier curves were plotted to compare survival outcomes among risk subgroups.ResultsAge, grade, histological types, stage, residual lesion size, number of regional lymph nodes resected, number of positive lymph nodes, and chemotherapy were independent risk factors for CSS. Based on the above factors, we constructed a nomogram. The C-indices of the training cohort, internal validation cohort, and external verification group were 0.763, 0.750, and 0.920, respectively. The calibration curve indicated good agreement between the nomogram prediction and actual survival. AUC and DCA results indicated great clinical usefulness of the nomogram. The differences in the Kaplan–Meier curves among different risk subgroups were statistically significant.ConclusionsWe constructed a nomogram to predict CSS in adult patients with EOC after primary surgery, which can assist in counseling and guiding treatment decision making.