bluuebunny/crossref_metadata_2025_split huggingface dataset:
Dual pathway inhibition as compared to acetylsalicylic acid monotherapy in relation to endothelial function in peripheral artery disease, a phase IV clinical trial
Authors: Willems Loes H. , Thijssen Dick H. J. , Groh Laszlo A. , Kooijman Nina I. , Ten Cate Hugo , Spronk Henri M. H. , Donders A. Rogier T. , van der Vijver-Coppen Rozemarijn J. , van Hoek Frank , Nagy Magdolna , Reijnen Michel M. P. J. , Warlé Michiel C. 
Published: October 2022

ObjectiveDual pathway inhibition (DPI) by combining acetylsalicylic acid (ASA) with low-dose rivaroxaban has been shown to reduce cardiovascular events in patients with peripheral arterial disease (PAD) when compared to ASA monotherapy. A potential explanation is that inhibition of factor Xa improves endothelial function through crosstalk between coagulation and inflammatory pathways, subsequently attenuating the occurrence of cardiovascular events. We hypothesize that the addition of rivaroxaban to ASA in PAD patients leads to improved endothelial function.DesignAn investigator-initiated, multicentre trial investigating the effect of DPI on endothelial function.MethodsPatients, diagnosed with PAD, were enrolled in two cohorts: cohort A (Rutherford I-III) and cohort B (Rutherford IV-VI). Participants received ASA monotherapy for a 4-weeks run-in period, followed by 12 weeks of DPI. Macro- and microvascular endothelial dysfunction were studied by measuring carotid artery reactivity upon sympathetic stimulus and by measuring plasma endothelin-1 concentrations, respectively. All measurements were performed during the use of ASA (baseline) and after 12 weeks of DPI.Results159 PAD patients (111 cohort A, 48 cohort B) were enrolled. Twenty patients discontinued study drugs early. Carotid artery constriction upon sympathetic stimulation at baseline (ASA) and after 12 weeks of DPI was similar in the total group, 22.0 vs. 22.7% (p = 1.000), and in the subgroups (Cohort A 22.6 vs. 23.7%, p = 1.000; cohort B 20.5 vs. 20.5%, p = 1.000), respectively. The mean concentration of plasma endothelin-1 at baseline and after 12 weeks of DPI did not differ, 1.70 ± 0.5 vs. 1.66 ± 0.64 pmol/L (p = 0.440) in the total group, 1.69 ± 0.59 vs. 1.62 ± 0.55 pmol/L in cohort A (p = 0.202), and 1.73 ± 0.53 vs. 1.77 ± 0.82 pmol/L in cohort B (p = 0.682), respectively.ConclusionMacro- and microvascular endothelial dysfunction, as reflected by carotid artery reactivity and plasma endothelin-1 concentrations, are not influenced in PAD patients by addition of low-dose rivaroxaban to ASA monotherapy for 12 weeks.Trial registrationhttps://clinicaltrials.gov/ct2/show/NCT04218656.
Teaching faculty perceptions, attitudes, challenges, and satisfaction of online teaching during COVID-19 pandemic in Saudi Arabia: A national survey
Authors: Alqahtani Jaber S. , Aldhahir Abdulelah M. , Al Ghamdi Shouq S. , Aldakhil Ahmad M. , Al-Otaibi Hajed M. , AlRabeeah Saad M. , Alzahrani Eman M. , Elsafi Salah H. , Alqahtani Abdullah S. , Al-maqati Thekra N. , Alnasser Musallam , Alnaam Yaser A. , Alzahrani Eidan M. , Alwafi Hassan , Almotairi Wafi , Oyelade Tope 
Published: October 2022

BackgroundThe COVID-19 pandemic and associated preventative measures introduced a shock to the teaching paradigm in Saudi Arabia and the world. While many studies have documented the challenges and perceptions of students during the COVID-19 pandemic, less attention has been given to higher education staff. The aim of the present investigation is to evaluate the staff’s perception and experiences of online teaching during the COVID-19 pandemic.Materials and methodsA validated survey was conducted between December 2021 and June 2022 in Saudi Arabian Universities to assess the status of online teaching during the COVID-19 pandemic among faculty members. The collected responses were exploratively and statistically analyzed.ResultsA total of 1117 response was received. About 66% of the respondents were male and 90% of them hold postgraduate degree. Although rarely or occasionally teach online pre-COVID-19, only 33% of the respondents think the transition was difficult and 55% of them support the move. Most respondents received adequate training (68%) and tools (80%) and 88% of the respondents mentioned that they did not accrue additional workload in online study design. While the perception of online teaching was mostly positive (62%) with high satisfaction (71%). However, 25% of the respondents reported that a poor internet bandwidth was an obstacle and 20% was unable to track students’ engagement. Respondents with more years of experience, previous training, support, or perceived online transition as easy were also more likely to be satisfied with the process. Also, older respondents, those who support the transition and those with previous training were less likely to report barriers (allp&lt; 0.001).ConclusionThe perception and experience of transition to online teaching during the COVID-19 pandemic in Saudi Arabia were positive. Low internet bandwidth and inability to track students’ limited effective online teaching. Work experience, previous training, and positive perception are the main factors that influence staff online teaching satisfaction.
Diabetic kidney disease progression is associated with decreased lower-limb muscle mass and increased visceral fat area in T2DM patients
Authors: Lin Xiaopu , Chen Zhenguo , Huang Haishan , Zhong Jingyi , Xu Lingling 
Published: October 2022

AimThis study aimed to explore the relationship between lower-limb muscle mass/visceral fat area and diabetic kidney disease (DKD) progression in patients with type 2 diabetes mellitus (T2DM).MethodsA total of 879 participants with T2DM were divided into 4 groups according to the prognosis of CKD classification from Kidney Disease: Improving Global Outcomes (KDIGO). Rectus femoris cross-sectional area (RFCSA) was measured through ultrasound, and visceral fat area (VFA) was evaluated with bioelectric impedance analysis (BIA).ResultsT2DM patients with high to very high prognostic risk of DKD showed a reduced RFCSA (male P &lt; 0.001; female P &lt; 0.05), and an enlarged VFA (male P &lt; 0.05; female P &lt; 0.05). The prognostic risk of DKD was negatively correlated with RFCSA (P &lt; 0.05), but positively correlated with VFA (P &lt; 0.05). Receiver-operating characteristic analysis revealed that the cutoff points of T2DM duration combined with RFCSA and VFA were as follows: (male: 7 years, 6.60 cm2, and 111 cm2; AUC = 0.82; 95% CI: 0.78–0.88; sensitivity, 78.0%; specificity, 68.6%, P &lt; 0.001) (female: 9 years, 5.05 cm2, and 91 cm2; AUC = 0.73; 95% CI: 0.66–0.81; sensitivity, 73.9%; specificity, 63.3%, P &lt; 0.001).ConclusionA significant association was demonstrated between reduced RFCSA/increased VFA and high- to very high-prognostic risk of DKD. T2DM duration, RFCSA, and VFA may be valuable markers of DKD progression in patients with T2DM.Clinical trial registrationhttp://www.chictr.org.cn, identifier ChiCTR2100042214
Outcome of CRH stimulation test and overnight 8 mg dexamethasone suppression test in 469 patients with ACTH-dependent Cushing’s syndrome
Authors: Detomas Mario , Ritzel Katrin , Nasi-Kordhishti Isabella , Wolfsberger Stefan , Quinkler Marcus , Losa Marco , Tröger Viola , Kroiss Matthias , Fassnacht Martin , Vila Greisa , Honegger Jürgen Bernd , Reincke Martin , Deutschbein Timo 
Published: October 2022

ObjectiveTo evaluate diagnostic accuracy of the corticotropin-releasing hormone (CRH) stimulation test and the overnight 8 mg dexamethasone suppression test (DST) for the differentiation of Cushing’s disease (CD) and ectopic Cushing’s syndrome (ECS).MethodsRetrospective study in 6 European centers. Inclusion criteria: patients with a) overt adrenocorticotropin (ACTH)-dependent Cushing’s syndrome at the time of dynamic testing, b) histopathological confirmed tumors and/or c) postoperative biochemical remission and/or adrenal insufficiency. Optimal cut-offs were calculated via receiver operating characteristic (ROC) analysis using CD as reference.Results469 patients were analyzed [78% females; median age 43 years (IQR 19)]. CRH test and overnight 8 mg DST were performed in 420 [CD, n=394 (94%); ECS, n=26 (6%)] and 237 patients [228 CD (96%), 9 ECS (4%)]. Both tests were performed in 205 patients (44%). The post-CRH %-increase at 30 minutes of both ACTH (cut-off ≥31%, sensitivity 83%, specificity 85%, AUC 0.81) and cortisol (cut-off ≥12%, sensitivity 82%, specificity 89%, AUC 0.86) discriminated best between CD and ECS. A test duration of &gt;60 minutes did not improve diagnostic performance of the CRH test. The optimal cortisol cut-off for the %-suppression during the 8 mg DST was ≥55% (sensitivity 80%, specificity 78%, AUC 0.75).ConclusionThe CRH test has equivalent sensitivity but higher specificity than the 8 mg DST and is therefore the test of first choice. The diagnostic outcome of ACTH and cortisol is well comparable, however, sampling beyond 60 minutes post-CRH does not provide diagnostic benefits.
Supply-demand bilateral energy structure optimization and carbon emission reduction in Shandong rural areas based on long-range energy alternatives planning model
Authors: Wang Jing , Liu Mohan 
Published: October 2022

To solve the problem of large carbon emissions in rural area, this paper conducts field research in rural areas of Shandong and embarks on supply-demand bilateral energy structure optimization which combines local resource endowments, the latest rural energy application technologies and energy consumption preference. The study uses long-range energy alternatives planning (LEAP) model to analyze the trend of energy consumption and CO2 emission from 2020 to 2050 under four different scenarios. The results of Tanzhuang show that residents in rural areas still rely on traditional biomass for energy consumption, especially for winter heating. Energy structure optimization has a significant impact on energy saving and emission reduction. Energy consumption and generation are projected steadily up to 2050 under all scenarios while the carbon emissions show a downward trend with a rapid decline from 2021 to 2030 and a relatively stable state for the next 20 years. Combining policy advancement and marginal carbon abatement cost (MACC) of different energy technologies, energy structure optimization-low cost (ESO-LOW) scenario shows a higher emission reduction benefits than the others. Six other villages in Shandong are analyzed in order to demonstrate the effectiveness of supply-demand bilateral energy structure optimization, sensitivity results show that the optimization is significant to the carbon neutrality target and carbon emission reduction.
The concentrations and sources of PAHs and PCBs in soil from an oil field and estuary in the Yellow River Delta, China
Authors: Jianrong Cao , Yanjun Liu , Sujie Yu 
Published: October 2022

The occurrence of organic pollutants [i.e. polycyclic aromatic hydrocarbons (PAHs) and polychlorinated biphenyls (PCBs)] had been assessed in the soil samples collected from two sub-regions (an oil field and the Yellow River Estuary) in the Yellow River Delta (YRD), China. The concentrations of PAHs and PCBs in the soil were in the range of 157.8–481.7 μg kg−1 (dry weight) and 5.6–56.6 μg kg−1 (dry weight), respectively. The average concentration of PAHs in the soil samples from the oil field were 274.0 μg kg−1, and that in the estuary soil samples were 244.4 μg kg−1. The average concentration of PCBs in the soil samples from the oil field and the estuary were 24.2 μg kg−1 and 10.8 μg kg−1, respectively. The contribution of low molecular weight PAHs (two-ring and three-ring PAHs) was larger in the soil samples from the oil field than that in the estuary soil samples. Both PAHs and PCBs contaminations in the estuary area were lower than that in the oil field area. By using diagnostic ratios analysis, the main source of PAHs was attributed to petroleum input caused by the fuel oil or light refined petroleum products in the Gudong Oilfield. The amount of low-chlorine congeners (three to four chlorine atoms) PCBs in soil samples from the oil field were higher than that in the estuary soil samples. The congeners analysis of PCBs and the correlation analysis between the concentrations of PAHs and PCBs were employed. The results indicated that the emission of PCBs in YRD were influenced by both Gudong oilfield and other industrial sources.
Association of PM2.5 With blood lipids and dyslipidaemia in a rural population of north-western china
Authors: Wang Kairong , Zhao Yi , Wang Qingan , Zhang Yajuan , Zhang Yuhong 
Published: October 2022

Background: Evidence regarding the association between particulate matter with aerodynamic diameter ≤2.5 μm (PM2.5) and blood lipid levels is insufficient in the rural areas of developing countries. Few studies have estimated the role of PM2.5 in blood lipid levels. We investigated the relationship between long-term exposure to PM2.5, blood lipids, and dyslipidaemia in rural Chinese adults.Methods: Baseline data of 15,802 participants (aged 35–74 years) in the China Northwest Cohort-Ningxia Project were used in this study. PM2.5 levels were assessed using satellite remote sensing data in accordance with each participant’s home address. Personally exposed PM2.5 was defined as the 3-year mean concentration prior to the baseline survey. Logistic and linear models were utilised to quantify the associations of PM2.5 with the prevalence of dyslipidaemia and with blood lipids, including total cholesterol (TC), triglyceride (TG), high-density lipoprotein cholesterol (HDL-C), and low-density lipoprotein cholesterol (LDL-C).Results: The 3-year mean level of PM2.5 was 35.36 ± 4.21 μg/m3. Every 1-μg/m3 increase in PM2.5 was related to an increase of 0.04% (95% CI: −0.44–0.53%) in TG and decreases of 0.37% (95% CI: 0.16–0.90%) in TC, 5.76% (95% CI: 5.32–6.21%) in LDL-C, and 0.89% (95% CI: 0.72–1.05%) in HDL-C. Every 1-μg/m3 increment in PM2.5 was related with a 4% (95% CI:3–5%) and 18% (95% CI:16–20%) higher risk of dyslipidaemia and hypoalphalipoproteinemia, respectively, and a decrease of 11% (95% CI:10–13%) in hyperbetalipoproteinemia. Sex, age, and BMI were adjusted for the relationships between PM2.5, blood lipids, and dyslipidaemia.Conclusion: Greater PM2.5 exposure was related to harmful changes in blood lipids and dyslipidaemia. Male, elderly, and overweight individuals may be more vulnerable to the negative effects of PM2.5.
Overexpression of LncRNA SNHG14 as a biomarker of clinicopathological and prognosis value in human cancers: A meta-analysis and bioinformatics analysis
Authors: Liu Bin , Lu Tingting , Wang Yongfeng , Zhang Guangming , Fu Liangyin , Yu Miao , Yang Kehu , Cai Hui 
Published: October 2022

Background: SNGH14 is a newly discovered long non-coding RNA (lncRNA) highly associated with tumorigenesis. However, whether the level of SNHG14 is related to the prognosis of patients with different cancer types is unclear.Methods: PubMed, Web of Science, Cochrane Library, and Embase were searched to identify eligible studies from inception to November 2021. The odds ratio (OR) and 95% confidence interval (CI) were utilized to analyze dichotomous variables, while the hazard ratio (HR) and 95% CI were used for survival outcomes. We also included trial sequential analysis (TSA) to assess whether the current evidence was sufficiently conclusive. Stata 15.0 and TSA 0.9 software were used for data analyses.Results: A total of 21 studies involving 1,080 patients, mainly from China, were included. Our results revealed that high SNHG14 expression was associated significantly with poor overall survival (OS) [HR = 1.39; 95% CI: (1.06–1.83); p = 0.017]. In addition, elevated SNHG14 expression was related to tumor size (&gt; 3.5 cm) [OR = 1.60; 95% CI: (1.20–2.14); p = 0.001], TNM staging [OR = 0.54; 95% CI: (0.40–0.71); p &lt; 0.001], lymph node metastasis [OR = 1.86; 95% CI: (1.35–2.55); p &lt; 0.001], differentiation grade [OR = 1.95; 95% CI: (1.36–2.80); p &lt; 0.001], and distant metastasis [OR = 2.44; 95% CI: (1.30–4.58); p = 0.005]. However, no significant difference was observed between age [OR = 0.98; 95% CI: (0.72–1.35); p = 0.915] and gender [OR = 0.98; 95% CI: (0.72–1.35); p = 0.915] from the enhanced expression of SNHG14.Conclusion: The current study revealed that overexpression of SNGH14 is associated with low OS rate and clinicopathological characteristics. SNGH14 can be a novel tumor marker that aids in tumor diagnosis, thereby improving patient prognosis.
Clinical neutrophil-associated genes as reliable predictors of hepatocellular carcinoma
Authors: Song Lishan , Xu Chaojie , Zhang Tong , Chen Shengyang , Hu Shuiquan , Cheng Bingbing , Tong Hao , Li Xiaoyong 
Published: October 2022

Background: Growing evidence suggests that infiltrating neutrophils are key players in hepatocellular carcinoma (HCC) tumor progression. However, a comprehensive analysis of the biological roles of neutrophil infiltration and related genes in clinical outcomes and immunotherapy is lacking.Methods: HCC samples were obtained from the TCGA and GEO databases. The CIBERSORT algorithm was used to reveal the TIME landscape. Gene modules significantly associated with neutrophils were found using weighted gene co-expression network analysis (WGCNA), a “dynamic tree-cut” algorithm, and Pearson correlation analysis. Genes were screened using Cox regression analysis and LASSO and prognostic value validation was performed using Kaplan-Meier curves and receiver operating characteristic (ROC) curves. Risk scores (RS) were calculated and nomograms were constructed incorporating clinical variables. Gene set variation analysis (GSVA) was used to calculate signaling pathway activity. Immunophenoscore (IPS) was used to analyze differences in immunotherapy among samples with different risk scores. Finally, the relationship between RS and drug sensitivity was explored using the pRRophetic algorithm.Results: 10530 genes in 424 samples (50 normal samples, 374 tumor samples) were obtained from the TCGA database. Using WGCNA, the “MEbrown” gene module was most associated with neutrophils. Nine genes with prognostic value in HCC (PDLIM3, KLF2, ROR2, PGF, EFNB1, PDZD4, PLN, PCDH17, DOK5) were finally screened. Prognostic nomograms based on RS, gender, tumor grade, clinical stage, T, N, and M stages were constructed. The nomogram performed well after calibration curve validation. There is an intrinsic link between risk score and TMB and TIME. Samples with different risk scores differed in different signaling pathway activity, immunopharmaceutical treatment and chemotherapy sensitivity.Conclusion: In conclusion, a comprehensive analysis of neutrophil-related prognostic features will help in prognostic prediction and advance individualized treatment.
Bet v 1-displaying elastin-like polypeptide nanoparticles induce a strong humoral and weak CD4+ T-cell response against Bet v 1 in a murine immunogenicity model
Authors: van Strien Jolinde , Warmenhoven Hans , Logiantara Adrian , Makurat Max , Aglas Lorenz , Bethanis Athanasios , Leboux Romain , van Rijt Leonie , MacKay J. Andrew , van Schijndel Johannes W. , Schneider Gregory , Olsthoorn René , Jiskoot Wim , van Ree Ronald , Kros Alexander 
Published: October 2022

There is growing concern about the toxicity of colloidal aluminum salts used as adjuvants in subcutaneous allergen immunotherapy (SCIT). Therefore, alternative adjuvants and delivery systems are being explored to replace alum in SCIT. We applied micellar elastin-like polypeptides (ELPs), a type of self-assembling protein, to replace alum as vaccine adjuvant in birch pollen SCIT. ELP and an ELP-Bet v 1 fusion protein were expressed inE. coliand purified by immuno-affinity chromatography and inverse-transition cycling (ITC). Nanoparticles self-assembled from ELP and a 9:1 ELP/ELP-Bet v 1 mixture were characterized by using dynamic light scattering and atomic force microscopy. Allergenicity was assessed by measuring mediator release from rat basophilic leukemia cells transformed with the human FcϵR1 and sensitized with sera derived from human birch pollen allergic patients. Humoral and T-cell immunity were investigated by immunizing naïve mice with the ELP/ELP-Bet v 1 nanoparticles or alum-adsorbed Bet v 1, both containing 36 µg Bet v 1. ELP and ELP/ELP-Bet v 1 self-assembled at 37°C into spherically shaped micelles with a diameter of ~45 nm. ELP conjugation made Bet v 1 hypo-allergenic (10-fold). Compared to alum-adsorbed Bet v 1, ELP/ELP-Bet v 1 nanoparticles induced stronger IgG responses with an earlier onset. Additionally, ELP/ELP-Bet v 1 did not induce Th2 skewing cytokines and IgE. The hypoallergenic character and strong humoral immune response in the absence of a Th2-skewing T-cell response make ELP-based nanoparticles a promising candidate to replace alum in SCIT.
Cytokine levels associated with favorable clinical outcome in the CAPSID randomized trial of convalescent plasma in patients with severe COVID-19
Authors: Körper Sixten , Schrezenmeier Eva Vanessa , Rincon-Arevalo Hector , Grüner Beate , Zickler Daniel , Weiss Manfred , Wiesmann Thomas , Zacharowski Kai , Kalbhenn Johannes , Bentz Martin , Dollinger Matthias M. , Paul Gregor , Lepper Philipp M. , Ernst Lucas , Wulf Hinnerk , Zinn Sebastian , Appl Thomas , Jahrsdörfer Bernd , Rojewski Markus , Lotfi Ramin , Dörner Thomas , Jungwirth Bettina , Seifried Erhard , Fürst Daniel , Schrezenmeier Hubert 
Published: October 2022

ObjectivesTo determine the profile of cytokines in patients with severe COVID-19 who were enrolled in a trial of COVID-19 convalescent plasma (CCP).MethodsPatients were randomized to receive standard treatment and 3 CCP units or standard treatment alone (CAPSID trial, ClinicalTrials.gov NCT04433910). The primary outcome was a dichotomous composite outcome (survival and no longer severe COVID-19 on day 21). Time to clinical improvement was a key secondary endpoint. The concentrations of 27 cytokines were measured (baseline, day 7). We analyzed the change and the correlation between serum cytokine levels over time in different subgroups and the prediction of outcome in receiver operating characteristics (ROC) analyses and in multivariate models.ResultsThe majority of cytokines showed significant changes from baseline to day 7. Some were strongly correlated amongst each other (at baseline the cluster IL-1ß, IL-2, IL-6, IL-8, G-CSF, MIP-1α, the cluster PDGF-BB, RANTES or the cluster IL-4, IL-17, Eotaxin, bFGF, TNF-α). The correlation matrix substantially changed from baseline to day 7. The heatmaps of the absolute values of the correlation matrix indicated an association of CCP treatment and clinical outcome with the cytokine pattern. Low levels of IP-10, IFN-γ, MCP-1 and IL-1ß on day 0 were predictive of treatment success in a ROC analysis. In multivariate models, low levels of IL-1ß, IFN-γ and MCP-1 on day 0 were significantly associated with both treatment success and shorter time to clinical improvement. Low levels of IP-10, IL-1RA, IL-6, MCP-1 and IFN-γ on day 7 and high levels of IL-9, PDGF and RANTES on day 7 were predictive of treatment success in ROC analyses. Low levels of IP-10, MCP-1 and high levels of RANTES, on day 7 were associated with both treatment success and shorter time to clinical improvement in multivariate models.ConclusionThis analysis demonstrates a considerable dynamic of cytokines over time, which is influenced by both treatment and clinical course of COVID-19. Levels of IL-1ß and MCP-1 at baseline and MCP-1, IP-10 and RANTES on day 7 were associated with a favorable outcome across several endpoints. These cytokines should be included in future trials for further evaluation as predictive factors.