bluuebunny/crossref_metadata_2025_split huggingface dataset:
The association of plasma sortilin with essential hypertension and subclinical carotid atherosclerosis: A cross-sectional study
Authors: Chu Xinglin , Liu Rui , Li Chunli , Gao Tao , Dong Yongqi , Jiang Yi , Ke Dazhi 
Published: October 2022

BackgroundSortilin, a protein that regulates glucose and lipid metabolism, has recently been linked to cardiovascular diseases (CVDs) such as coronary heart disease and carotid artery stenosis. In this study, we measured circulating sortilin concentrations in essential hypertensive (EH) patients, and evaluated the association between sortilin, hypertension, and subclinical carotid atherosclerosis in hypertensive individuals.MethodsThis cross-sectional study included 336 individuals, including 186 newly diagnosed EH patients and 150 age-and-sex-matched normotensive healthy subjects (NT). Plasma sortilin and adiponectin (ADI) levels were measured using ELISA kits. In the EH group, high-resolution B-mode ultrasound was used to detect the existence of subclinical carotid atherosclerosis (subAS), which was defined as having a carotid intima–media thickness (cIMT) ≥ 1.0 mm and/or plaque on the carotid artery without any clinical manifestations.ResultsOur findings showed that plasma sortilin concentrations ranged from 3.34–11.34 ng/ml for all subjects. Sortilin levels were significantly higher in the EH group than in the NT group (8.10 ± 1.82 ng/ml vs. 6.37 ± 1.52 ng/ml, P &lt; 0.001) and were further upregulated in the EH with subclinical carotid atherosclerosis (EH + subAS) group compared to the EH without subclinical carotid atherosclerosis (EH-subAS) group (8.42 ± 1.75 ng/ml vs. 7.79 ± 1.84 ng/ml, P &lt; 0.05). In correlation analysis, sortilin was positively correlated with systolic blood pressure (SBP), diastolic blood pressure (DBP), triglyceride (TG), total cholesterol (TC), low-density lipoprotein cholesterol (LDL-C), white blood cell (WBC), endothelin-1 (ET-1), high-sensitivity C-reactive protein (hsCRP), interleukin-6 (IL-6), and cIMT (all P &lt; 0.05) and negatively associated with NO and ADI (P &lt; 0.001). Multiple linear regression analysis revealed that SBP, LDL-C, and ET-1 were independently associated with plasma sortilin levels. Increased sortilin levels were independently associated with the risk of EH (OR: 1.86, 95%CI: 1.56–2.20, P &lt; 0.001) and EH + subAS (OR: 1.33, 95%CI: 1.07–1.66, P = 0.011), after adjustment for multiple risk factors. Restricted spline curve showed that elevated sortilin levels increase the odds of having EH.ConclusionElevated sortilin levels are associated with an increased risk of essential hypertension and subclinical carotid atherosclerosis in hypertensive patients.
Comparing the associations of central venous pressure and pulmonary artery pulsatility index with postoperative renal injury
Authors: Wei Johnny , Houchin Abigail , Nazir Niaman , Leonardo Vincent , Flynn Brigid C. 
Published: October 2022

ObjectiveCardiac surgery-associated acute kidney injury (CS-AKI) is associated with significant morbidity and mortality. We investigated the association of postoperative central venous pressure (CVP) and pulmonary artery pulsatility index (PAPi) with the development of CS-AKI.MethodsThis was a single-center, retrospective cohort study of patients undergoing cardiac surgery. CVP and PAPi were acquired hourly postoperatively and averaged for up to 48 h. PAPi was calculated as [(Pulmonary Artery Systolic Pressure–Pulmonary Artery Diastolic Pressure) / CVP]. The primary aim was CS-AKI. Secondary aims were need for renal replacement therapy (RRT), hospital and 30-day mortality, total ventilator and intensive care unit hours, and hospital length of stay. Logistic regression was used to calculate odds of development of renal injury and need for RRT.ResultsOne thousand two hundred eighty-eight patients were included. The average postoperative CVP was 10.3 mmHg and average postoperative PAPi was 2.01. Patients who developed CS-AKI (n = 384) had lower PAPi (1.79 vs. 2.11, p &lt; 0.01) and higher CVP (11.5 vs. 9.7 mmHg, p &lt; 0.01) than those who did not. Lower PAPi and higher CVP were also associated with each secondary aim. A standardized unit decrease in PAPi was associated with increased odds of CS-AKI (OR 1.39, p &lt; 0.01) while each unit increase in CVP was associated with both increased odds of CS-AKI (OR 1.56, p &lt; 0.01) and postoperative RRT (OR 1.49, p = 0.02).ConclusionsBoth lower PAPi and higher CVP values postoperatively were associated with the development of CS-AKI but only higher CVP was associated with postoperative RRT use. When differences in values are standardized, CVP may be more associated with development of CS-AKI when compared to PAPi.
Machine learning methods for predicting major types of rheumatic heart diseases in children of Southern Punjab, Pakistan
Authors: Shahid Sana , Khurram Haris , Billah Baki , Akbar Atif , Shehzad Muhammad Ahmed , Shabbir Muhammad Farhan 
Published: October 2022

ObjectiveRheumatic heart disease (RHD) is a major health problem in the world, particularly in developing countries. This study aimed to predict mitral regurgitation (MR) and mitral stenosis (MS) RHD among children with RHD.MethodologyData was collected from the Pediatric Cardiology Department at Chaudhry Pervaiz Elahi Institute of Cardiology Multan, Pakistan from March to October 2019. A sample of 561 children aged 4–14 years, who were diagnosed with RHD of either MR or MS, were recruited from the hospital’s outpatient department. The presence of multivariate outliers was detected, and different machine learning methods, including subset logistic regression, subset logistic regression after deletion, stepwise winsorized logistic regression, robust logistic regression, subset deep neural network, and random forest models were compared using the area under receiver operating characteristics (ROC) curve, sensitivity, and specificity. Parsimony was also considered in model selection.ResultsOut of 561 patients in this study, 75.94% had RHD MR and 24.06% had RHD MS. The average age of study participants was 9.19 ± 2.45 years and of them 55.43% were male. Among the male participants, 58.6 and 45.2% had MR and MS, respectively; and among female participants, those were 70.4 and 29.6%, respectively. Subset logistic regression after deletion appeared as competitive with a discrimination power of 90.1% [95% CI 0.818–0.983]. The sensitivity and specificity of this model were 85.1 and 70.6%.ConclusionThe best predictive model was subset logistic regression after deletion. The predicted method will be used in the decision-making process, which helps early diagnosis of the disease and leads to prevention. The study findings provide the proper guideline for earlier diagnosis of the RHD MR and MS cases among children with RHD in Pakistan.
Micron- to atomic-scale investigation of rare earth elements in iron oxides
Authors: Cook Nigel J. , Ciobanu Cristiana L. , Ehrig Kathy , Slattery Ashley D. , Gilbert Sarah E. 
Published: October 2022

Hematite (α-Fe2O3) and magnetite (Fe3O4) readily accommodate a wide range of minor and trace elements from across the periodic table at up to wt.% concentrations. This prompts the question of whether these common minerals can also host rare earth elements (lanthanides, Y and Sc; REEs)? If so, what is the chemical and physical nature of the elements: are they incorporated into the oxide crystal structures, or do they occur as nanometer-to micron-sized inclusions of discrete REE-minerals? By combining micron-scale petrography and analysis by LA-ICP-MS with nanoscale imaging and energy-dispersive spectroscopy, the relationships between REEs and iron-oxides are addressed in samples from the world-class Olympic Dam Cu-U-Au-Ag deposit, South Australia. Spatially co-existing silician magnetite and hematite from the outer shell at Olympic Dam show stages of interconversion during which REEs are redistributed. REEs are shown to be preferentially incorporated into the magnetite structure, whereas hematite concentrates U, W, and Sn, and contains negligible structurally bound REEs. Abundant, &lt;20 nm-sized uraninite nanoparticles (NPs) are a key host for REEs in hematite. In contrast, hematite from mineralized breccias displays co-precipitation of Fe-oxides and REE-minerals facilitated by discharge of high-volatile fluids. Variation in the shape of chondrite-normalized REE fractionation trends, ranging from concave (hematite containing uraninite NPs) to steeply downwards-sloping (included LREE-dominant phases such as monazite, florencite, fluocerite and cerianite), reflect these differences. Evolving NP mineralogy in the breccias, from in-situ NP formation to an abundance of monazite reflects successive overprinting events and remobilization of elements from solid-solution and subsequent trapping as NPs via coupled dissolution replacement reaction. REE-minerals such as florencite can host nanoinclusions of hematite. Atomic-scale observations, including defects in magnetite and an O-deficient, two-fold hematite superstructure show crystal structural accommodation during Fe-oxide interconversion and inclusion nucleation. Both silician magnetite and hematite show nanoscale muscovite forming along planar defects. Understanding the mineralogical deportment of REEs at Olympic Dam carries potential implications for investigating the viability of REE extraction opportunities from any resource in which Fe-oxides are the dominant component.
Root exudate glycine synergistically promotes phytoremediation of petroleum-contaminated soil
Authors: He Mengfan , Li Zhongbao , Mei Ping 
Published: October 2022

The exploitation of petroleum, the production and use of petroleum products causes pollution that is harmful to the ecology and environment. At present, petroleum hydrocarbon pollution has become a universal concern in the world. As one of the bioremediation methods, plant root exudate repair has the effect of eliminating toxic substances in the environment. To explore the role of root exudates glycine in phytoremediation of petroleum-contaminated soil, seed germination and pot experiments were carried out to study the effects of glycine on the degradation of petroleum hydrocarbons in different plants and soil types. The results showed that when the concentration of petroleum pollutants was constant, the order of seed germination rate of the eight plants was ryegrass &gt; sudan grass &gt; white clover &gt; tall fescue &gt; alfalfa &gt; pennisetum &gt; canine root &gt; maize grass.1000 mg L−1 of glycine could effectively promote plant biomass and the petroleum hydrocarbons degradation rate. The degradation effect was ryegrass + glycine &gt; ryegrass &gt; sudan grass + glycine &gt; sudan grass &gt; white clover + glycine &gt; white clover. The degradation rate of ryegrass + glycine in 18,000 mg kg−1 petroleum-contaminated soil reached 55.7%. All plants had the highest biomass and plant height in loamy soil, while the highest degradation rate of petroleum hydrocarbons was observed in sandy soil, ranging from 50.36% to 59.36%. Among them, ryegrass combined with 1000 mg L−1 of glycine reached the highest petroleum hydrocarbons degradation rate of 59.36% in sandy soil. Ryegrass, sudan grass and white clover had the potential to remediate petroleum-contaminated soils. In the three types of soil, ryegrass had a strong remediation efficiency, and the degradation effect to petroleum hydrocarbons was more significant after the addition of glycine. Therefore, ryegrass can be planted with glycine as a priority for remediation in oil field areas contaminated by petroleum hydrocarbons.
Molecular subtypes based on cuproptosis-related genes and immune profiles in lung adenocarcinoma
Authors: Wang Yufei , Zhang Chen , Ji Chengyue , Jin Wenli , He Xin , Yu Shunzhi , Guo Renhua 
Published: October 2022

Background: Recent studies have identified several molecular subtypes of lung adenocarcinoma (LUAD) that have different prognoses to help predict the efficacy of immunotherapy. However, the prognostic prediction is less than satisfactory. Alterations in intracellular copper levels may affect the tumor immune microenvironment and are linked to cancer progression. Previous studies have identified some genes related to cuproptosis. The characteristics of the cuproptosis molecular subtypes have not been thoroughly studied in LUAD.Methods: The transcriptomic data and clinical information of 632 LUAD patients were used to investigate the LUAD molecular subtypes that are associated with the cuproptosis-related genes (CRGs), the tumor immune microenvironment, and stemness. The cuproptosis score was constructed using univariate Cox regression and the minor absolute shrinkage and selection operator (LASSO) to quantify the prognostic characteristics.Results: Three different molecular subtypes related to cuproptosis, with different prognoses, were identified in LUAD. Cluster A had the highest cuproptosis score and the worst prognosis. Patients in the high cuproptosis score group had a higher somatic mutation frequency and stemness scores. Patients in the low cuproptosis score group had more immune infiltration and better prognosis.Conclusion: Molecular subtypes of LUAD based on CRGs reflect the differences in LUAD patients. The cuproptosis score can be used as a promising biomarker, which is of great significance to distinguish the relationship between cuproptosis and the immune microenvironment. The cuproptosis signature based on the cuproptosis score and clinical characteristics of individual patients will be useful for guiding immunotherapy in LUAD.
The double-sided of human leukocyte antigen-G molecules in type 1 autoimmune hepatitis
Authors: Littera Roberto , Perra Andrea , Miglianti Michela , Piras Ignazio S. , Mocci Stefano , Lai Sara , Melis Maurizio , Zolfino Teresa , Balestrieri Cinzia , Conti Maria , Serra Giancarlo , Figorilli Francesco , Firinu Davide , Onali Simona , Matta Laura , Porcu Carmen , Pes Francesco , Fanni Daniela , Manieli Cristina , Vacca Monica , Cusano Roberto , Trucas Marcello , Cipri Selene , Tranquilli Stefania , Rassu Stefania , Cannas Federica , Carta Mauro Giovanni , Kowalik Marta Anna , Giuressi Erika , Faa Gavino , Chessa Luchino , Giglio Sabrina 
Published: October 2022

The immunomodulatory effects of HLA-G expression and its role in cancers, human liver infections and liver transplantation are well documented, but so far, there are only a few reports addressing autoimmune liver diseases, particularly autoimmune hepatitis (AIH).Method and materialsWe analyzed the genetic and phenotypic characteristics of HLA-G in 205 type 1 AIH patients (AIH-1) and a population of 210 healthy controls from Sardinia (Italy).ResultsAnalysis of the HLA-G locus showed no substantial differences in allele frequencies between patients and the healthy control population. The HLA-G UTR-1 haplotype was the most prevalent in both AIH-1 patients and controls (40.24% and 34.29%). Strong linkage was found between the HLA-G UTR-1 haplotype and HLA-DRB1*03:01 in AIH-1 patients but not controls (D’ = 0.92 vs D’ = 0.50 respectively; P = 1.3x10-8). Soluble HLA-G (sHLA-G) levels were significantly lower in AIH-1 patients compared to controls [13.9 (11.6 – 17.4) U/mL vs 21.3 (16.5 – 27.8) U/mL; P = 0.011]. Twenty-four patients with mild or moderate inflammatory involvement, as assessed from liver biopsy, showed much higher sHLA-G levels compared to the 28 patients with severe liver inflammation [33.5 (23.6 – 44.8) U/mL vs 8.8 (6.1 – 14.5) U/mL; P = 0.003]. Finally, immunohistochemistry analysis of 52 liver biopsies from AIH-1 patients did not show expression of HLA-G molecules in the liver parenchyma. However, a percentage of 69.2% (36/52) revealed widespread expression of HLA-G both in the cytoplasm and the membrane of plasma cells labeled with anti-HLA-G monoclonal antibodies.ConclusionThis study highlights the positive immunomodulatory effect of HLA-G molecules on the clinical course of AIH-1 and how this improvement closely correlates with plasma levels of sHLA-G. However, our results open the debate on the ambiguous role of HLA-G molecules expressed by plasma cells, which are pathognomonic features of AIH-1.
Factors influencing the SARS-CoV-2 infection and vaccination induced immune response in rheumatoid arthritis
Authors: Nemeth Dora , Vago Hajnalka , Tothfalusi Laszlo , Ulakcsai Zsuzsanna , Becker David , Szabo Zsofia , Rojkovich Bernadett , Merkely Bela , Nagy Gyorgy 
Published: October 2022

BackgroundTo investigate the factors that have significant impact on the Severe Acute Respiratory Syndrome Corona Virus 2 (SARS-CoV-2) infection and vaccination induced immune response in rheumatoid arthritis (RA).MethodsSerological response was measured by quantifying anti-SARS-CoV-2 specific antibodies, while the cell-mediated response was measured by a whole-blood test quantifying the interferon (IFN)-γ response to different SARS-CoV-2-specific domains.ResultsWe prospectively enrolled 109 RA patients and 43 healthy controls. The median time (IQR) between the confirmed infection or the last vaccination dose and the day when samples were taken (“sampling interval”) was 3.67 (2.03, 5.50) months in the RA group. Anti-Spike (anti-S) specific antibodies were detected in 94% of RA patients. Among the investigated patient related variables, age (p&lt;0.004), sampling interval (p&lt;0.001), the brand of the vaccine (p&lt;0.001) and targeted RA therapy (TNF-inhibitor, IL-6 inhibitor, anti-CD20 therapy) had significant effect on the anti-S levels. After covariate adjustment TNF-inhibitor therapy decreased the anti-S antibody concentrations by 80% (p&lt;0.001). The same figures for IL-6 inhibitor and anti-CD20 therapy were 74% (p=0.049) and 97% (p=0.002), respectively. Compared to subjects who were infected but were not vaccinated, the RNA COVID-19 vaccines increased the anti-S antibody levels to 71.1 (mRNA-1273) and 36.0 (BNT162b2) fold (p&lt;0.001). The corresponding figure for the ChAdOx1s vaccine is 18.1(p=0.037). Anti-CCP (anti-cyclic citrullinated peptides) positive patients had 6.28 times (p= 0.00165) higher anti-S levels, than the anti-CCP negative patients. Positive T-cell response was observed in 87% of the healthy volunteer group and in 52% of the RA patient group. Following vaccination or infection it declined significantly (p= 0.044) but more slowly than that of anti-S titer (6%/month versus 25%). Specific T-cell responses were decreased by 65% in patients treated with anti-CD20 therapy (p=0.055).ConclusionOur study showed that the SARS-CoV-2-specific antibody levels were substantially reduced in RA patients treated with TNF-α-inhibitors (N=51) and IL-6-inhibitor (N=15). In addition, anti-CD20 therapy (N=4) inhibited both SARS-CoV-2-induced humoral and cellular immune responses. Furthermore, the magnitude of humoral and cellular immune response was dependent on the age and decreased over time. The RNA vaccines and ChAdOx1s vaccine effectively increased the level of anti-S antibodies.
A mixed methods study of the awareness and management of familial hypercholesterolaemia in Irish general practice
Authors: Homeniuk Robyn , Gallagher Joseph , Collins Claire 
Published: October 2022

IntroductionFamilial Hypercholesterolemia (FH) is one of the most common genetic disorders, with an estimated global prevalence of 1:200-500, which leads to premature cardiovascular disease. Nevertheless, public and professional awareness of FH is often lacking, with an estimated 20,000 largely undiagnosed cases in Ireland.PurposeThe overall aim of the project was to test the feasibility of a model of care that would include electronic record screening, clinical assessment, and coding of possible FH patients across a network of general practices in Ireland. In addition, a secondary aim was to gauge the awareness and knowledge of FH across the network.MethodsThis study took part in multiple phases, employing a mixed methods design. The study included a validated questionnaire, tailored online educational resources, a retrospective chart review of patients with a history of elevated LDL cholesterol (LDLc) and an active review with a selection of those patients. Results were analyzed using SPSS V27, where descriptive statistics and relevant correlation tests were employed.ResultsEighteen general practices agreed to take part in the study. In the initial survey, respondents rated their personal and practice familiarity with FH as slightly below average. Around one-third of respondents were not aware of FH guidelines. Of over 55,000 adult patient records searched, only 0.2% had a recorded FH diagnosis and 3.9% had ever had an LDLc above 4.9 mmol/l. Eight practices completed 198 chart reviews. Among these, 29.8% of patients had a family history recorded, and 22.2% had a family history of CVD recorded. Female patients had higher averages for highest and recent LDLc. Seventy patients underwent a clinical review—with 27% of these patients identified as “probable” or “definite FH.” There was a statistically significant (p = 0.002) relationship between FH status and whether the patient had other CVD risk factors.ConclusionGeneral practitioners in Ireland had similar levels of awareness of FH compared to findings from elsewhere. The activities discussed encouraged clinicians to consider FH when talking to their patients, especially those with elevated LDLc at an early age. Broader awareness of the condition could increase conversations about FH and benefit patient outcomes.
Design and analysis of umbrella trials: Where do we stand?
Authors: Ouma Luke O. , Wason James M. S. , Zheng Haiyan , Wilson Nina , Grayling Michael 
Published: October 2022

BackgroundThe efficiencies that master protocol designs can bring to modern drug development have seen their increased utilization in oncology. Growing interest has also resulted in their consideration in non-oncology settings. Umbrella trials are one class of master protocol design that evaluates multiple targeted therapies in a single disease setting. Despite the existence of several reviews of master protocols, the statistical considerations of umbrella trials have received more limited attention.MethodsWe conduct a systematic review of the literature on umbrella trials, examining both the statistical methods that are available for their design and analysis, and also their use in practice. We pay particular attention to considerations for umbrella designs applied outside of oncology.FindingsWe identified 38 umbrella trials. To date, most umbrella trials have been conducted in early phase settings (73.7%, 28/38) and in oncology (92.1%, 35/38). The quality of statistical information available about conducted umbrella trials to date is poor; for example, it was impossible to ascertain how sample size was determined in the majority of trials (55.3%, 21/38). The literature on statistical methods for umbrella trials is currently sparse.ConclusionsUmbrella trials have potentially great utility to expedite drug development, including outside of oncology. However, to enable lessons to be effectively learned from early use of such designs, there is a need for higher-quality reporting of umbrella trials. Furthermore, if the potential of umbrella trials is to be realized, further methodological research is required.