bluuebunny/crossref_metadata_2025_split huggingface dataset:
Myocardial Perfusion Imaging After Severe COVID-19 Infection Demonstrates Regional Ischemia Rather Than Global Blood Flow Reduction
Authors: Thornton George D. , Shetye Abhishek , Knight Dan S. , Knott Kris , Artico Jessica , Kurdi Hibba , Yousef Souhad , Antonakaki Dimitra , Razvi Yousuf , Chacko Liza , Brown James , Patel Rishi , Vimalesvaran Kavitha , Seraphim Andreas , Davies Rhodri , Xue Hui , Kotecha Tushar , Bell Robert , Manisty Charlotte , Cole Graham D. , Moon James C. , Kellman Peter , Fontana Marianna , Treibel Thomas A. 
Published: December 2021

Background: Acute myocardial damage is common in severe COVID-19. Post-mortem studies have implicated microvascular thrombosis, with cardiovascular magnetic resonance (CMR) demonstrating a high prevalence of myocardial infarction and myocarditis-like scar. The microcirculatory sequelae are incompletely characterized. Perfusion CMR can quantify the stress myocardial blood flow (MBF) and identify its association with infarction and myocarditis.Objectives: To determine the impact of the severe hospitalized COVID-19 on global and regional myocardial perfusion in recovered patients.Methods: A case-control study of previously hospitalized, troponin-positive COVID-19 patients was undertaken. The results were compared with a propensity-matched, pre-COVID chest pain cohort (referred for clinical CMR; angiography subsequently demonstrating unobstructed coronary arteries) and 27 healthy volunteers (HV). The analysis used visual assessment for the regional perfusion defects and AI-based segmentation to derive the global and regional stress and rest MBF.Results: Ninety recovered post-COVID patients {median age 64 [interquartile range (IQR) 54–71] years, 83% male, 44% requiring the intensive care unit (ICU)} underwent adenosine-stress perfusion CMR at a median of 61 (IQR 29–146) days post-discharge. The mean left ventricular ejection fraction (LVEF) was 67 ± 10%; 10 (11%) with impaired LVEF. Fifty patients (56%) had late gadolinium enhancement (LGE); 15 (17%) had infarct-pattern, 31 (34%) had non-ischemic, and 4 (4.4%) had mixed pattern LGE. Thirty-two patients (36%) had adenosine-induced regional perfusion defects, 26 out of 32 with at least one segment without prior infarction. The global stress MBF in post-COVID patients was similar to the age-, sex- and co-morbidities of the matched controls (2.53 ± 0.77 vs. 2.52 ± 0.79 ml/g/min, p = 0.10), though lower than HV (3.00 ± 0.76 ml/g/min, p&lt; 0.01).Conclusions: After severe hospitalized COVID-19 infection, patients who attended clinical ischemia testing had little evidence of significant microvascular disease at 2 months post-discharge. The high prevalence of regional inducible ischemia and/or infarction (nearly 40%) may suggest that occult coronary disease is an important putative mechanism for troponin elevation in this cohort. This should be considered hypothesis-generating for future studies which combine ischemia and anatomical assessment.
Predictors and Long-Term Outcome of Ablation of Discrete Pre-potentials in Patients With Idiopathic Ventricular Arrhythmias Originating From the Aortic Sinuses of Valsalva
Authors: Wei Hui-Qiang , Guo Xiao-Gang , Zhou Gong-Bu , Sun Qi , Yang Jian-Du , Xie Hai-Yang , Liang Jackson , Zhang Shu , Wu Shulin , Ma Jian 
Published: December 2021

Background: The predictability and long-term outcome of the discrete pre-potential (DPP) of idiopathic ventricular arrhythmias (VAs) arising from the aortic sinuses of Valsalva (ASV) have not been fully identified.Methods: Of 687 consecutive patients undergoing ablation of outflow tract VAs, there were 105 (15.3%) patients with VAs originating from the ASV region who were included. Detailed mapping was performed within the ASV in all patients. Electrocardiographic, electrophysiological parameters, and long-term success rate were compared between patients with and without the DPPs.Results: A DPP was recorded in 67 of 105 (63.8%) patients, including 38 left sinus of Valsalva (LSV)-VAs (38/105, 36.2%) and 29 right sinus of Valsalva (RSV)-VAs (29/105, 27.6%). The patients with DPPs had wider QRS duration (152 ± 17 vs. 145 ± 14 ms, p &lt; 0.001). The average of earliest activation time was significantly earlier in patients with DPPs (−38.6 ± 8.5 vs. −27.7 ± 5.7 ms, p &lt; 0.001). Mean time from the first lesion to elimination of VAs was shorter in patients with DPPs (2.3 ± 2.1 s vs. 4.9 ± 1.0 s, p &lt; 0.001). A stepwise logistic multivariable analysis identified only younger age as a significant predictor of DPP (age ≤ 35.5 years predicted DPP with 92.9% positive predictive value). During a follow-up duration of 42.5 ± 22.3 months, 63 (94.0%) patients with DPPs and 30 (78.9%) patients without DPPs remained free of recurrent VAs (p = 0.027).Conclusion: Discrete pre-potentials were observed in 63.8% of patients with VAs arising from the ASV. Ablation in patients with DPPs was associated with higher long-term success. DPPs were seen more commonly in younger (age ≤ 35.5 years) patients.
Myocardial Extracellular Volume Fraction and T1 Mapping by Cardiac Magnetic Resonance Compared Between Patients With and Without Type 2 Diabetes, and the Effect of ECV and T2D on Cardiovascular Outcomes
Authors: Laohabut Issarayus , Songsangjinda Thammarak , Kaolawanich Yodying , Yindeengam Ahthit , Krittayaphong Rungroj 
Published: December 2021

Background: To investigate the difference in myocardial extracellular volume fraction (ECV) by cardiac magnetic resonance (CMR) T1 mapping between patients with and without type 2 diabetes (T2D), and the effect of ECV and T2D on cardiovascular (CV) outcomes.Methods: All patients aged &gt; 18 years with known or suspected coronary artery disease who underwent CMR for assessment of myocardial ischemia or myocardial viability at the Department of Cardiology of the Faculty of Medicine Siriraj Hospital, Mahidol University, Bangkok, Thailand from September 2017 to December 2018 were screened for inclusion eligibility. Left ventricular ejection fraction (LVEF), late gadolinium enhancement, and T1 mapping were performed. ECV values were derived from myocardial native T1 and contrast-enhanced T1 values that were obtained using modified Look-Locker inversion recovery at the septum of the mid-cavity short-axis map. Demographic data, clinical characteristics, and CV outcomes were collected by retrospective chart review. Composite CV outcomes included CV death, acute coronary syndrome, heart failure hospitalization, or ventricular tachycardia (VT)/ventricular fibrillation.Results: A total of 739 subjects (mean age: 69.5 ± 14.0 years, 49.3% men) were included. Of those, 188 subjects had T2D (25.4%). ECV was significantly higher in T2D than in non-T2D (30.0 ± 5.9% vs. 28.8 ± 4.7%, p = 0.004). During the mean follow-up duration of 26.2 ± 8.5 months, 43 patients (5.8%) had a clinical composite outcome, as follows: three CV death (0.4%), seven acute coronary syndrome (0.9%), 33 heart failure hospitalization (4.5%), and one VT (0.1%). T2D, low LVEF, and high ECV were all identified as independent predictors of CV events. Patients with T2D and high ECV had the highest risk of CV events.Conclusion: Among patients with known or suspected coronary artery disease, patients with T2D had a higher ECV. T2D and high ECV were both found to be independent risk factors for adverse CV outcomes.
Clinical Relevance of Right Atrial Functional Response to Treatment in Pulmonary Arterial Hypertension
Authors: Richter Manuel J. , Zedler Daniel , Berliner Dominik , Douschan Philipp , Gall Henning , Ghofrani Hossein A. , Kimmig Lucas , Kremer Nils , Olsson Karen M. , Brita da Rocha Bruno , Rosenkranz Stephan , Seeger Werner , Yogeswaran Athiththan , Rako Zvonimir , Tello Khodr 
Published: December 2021

Background: Right atrial (RA) function has emerged as an important determinant of outcome in pulmonary arterial hypertension (PAH). However, studies exploring RA function after initiation of specific pulmonary vascular treatment and its association with outcome in patients with incident PAH are lacking.Methods: RA peak longitudinal strain (PLS), passive strain (PS), and peak active contraction strain (PACS) were retrospectively assessed in 56 treatment-naïve patients with PAH at baseline and during follow-up after initiation of specific monotherapy or combination therapy. Patients were grouped according to their individual RA functional response to treatment, based on change from baseline (Δ): worsened (first Δ-tertile), stable (second Δ-tertile), and improved (third Δ-tertile). The Spearman's rho correlation and linear regression analysis were used to determine associations. Time to clinical worsening (defined as deterioration of functional class or 6-min walking distance, disease-related hospital admission, or death) was measured from the follow-up assessment. The association of RA functional treatment response with time to clinical worsening was assessed using the Kaplan–Meier and the Cox regression analyses.Results: Median (interquartile range) time to echocardiographic follow-up was 11 (9–12) months. Of the 56 patients, 37 patients (66%) received specific dual or triple combination therapy. Δ RA PLS during follow-up was significantly associated with changes in key hemodynamic and echocardiographic parameters. The change of pulmonary vascular resistance, right ventricular (RV) end-systolic area, and global longitudinal strain were independently associated with Δ RA PLS. The median time to clinical worsening after echocardiographic follow-up was 6 (2–14) months [17 events (30%)]. In the multivariate Cox regression analysis, worsening of RA PLS was significantly associated with clinical deterioration (hazard ratio: 4.87; 95% CI: 1.26–18.76; p = 0.022). Patients with worsened RA PLS had a significantly poorer prognosis than those with stable or improved RA PLS (log-rank p = 0.012). By contrast, PS and PACS did not yield significant prognostic information.Conclusion: Treatment-naïve patients with PAH may show different RA functional response patterns to PAH therapy. These functional patterns are significantly associated with clinically relevant outcome measures. Improvements of RA function are driven by reductions of afterload, RV remodeling, and RV dysfunction.
Left Ventricular Myocardial Septal Pacing in Close Proximity to LBB Does Not Prolong the Duration of the Left Ventricular Lateral Wall Depolarization Compared to LBB Pacing
Authors: Curila Karol , Jurak Pavel , Vernooy Kevin , Jastrzebski Marek , Waldauf Petr , Prinzen Frits , Halamek Josef , Susankova Marketa , Znojilova Lucie , Smisek Radovan , Karch Jakub , Plesinger Filip , Moskal Pawel , Heckman Luuk , Mizner Jan , Viscor Ivo , Vondra Vlastimil , Leinveber Pavel , Osmancik Pavel 
Published: December 2021

Background: Three different ventricular capture types are observed during left bundle branch pacing (LBBp). They are selective LBB pacing (sLBBp), non-selective LBB pacing (nsLBBp), and myocardial left septal pacing transiting from nsLBBp while decreasing the pacing output (LVSP). Study aimed to compare differences in ventricular depolarization between these captures using ultra-high-frequency electrocardiography (UHF-ECG).Methods: Using decremental pacing voltage output, we identified and studied nsLBBp, sLBBp, and LVSP in patients with bradycardia. Timing of ventricular activations in precordial leads was displayed using UHF-ECGs, and electrical dyssynchrony (e-DYS) was calculated as the difference between the first and last activation. The durations of local depolarizations (Vd) were determined as the width of the UHF-QRS complex at 50% of its amplitude.Results: In 57 consecutive patients, data were collected during nsLBBp (n = 57), LVSP (n = 34), and sLBBp (n = 23). Interventricular dyssynchrony (e-DYS) was significantly lower during LVSP −16 ms (−21; −11), than nsLBBp −24 ms (−28; −20) and sLBBp −31 ms (−36; −25). LVSP had the same V1d-V8d as nsLBBp and sLBBp except for V3d, which during LVSP was shorter than sLBBp; the mean difference −9 ms (−16; −1), p = 0.01. LVSP caused less interventricular dyssynchrony and the same or better local depolarization durations than nsLBBp and sLBBp irrespective of QRS morphology during spontaneous rhythm or paced QRS axis.Conclusions: In patients with bradycardia, LVSP in close proximity to LBB resulted in better interventricular synchrony than nsLBBp and sLBBp and did not significantly prolong depolarization of the left ventricular lateral wall.
Evidence of the Storegga Tsunami 8200 BP? An Archaeological Review of Impact After a Large-Scale Marine Event in Mesolithic Northern Europe
Authors: Nyland Astrid J. , Walker James , Warren Graeme 
Published: December 2021

Around 8,200 years ago, the Storegga tsunami hit the coasts of the Norwegian and North Seas. This event is well known from wide ranging geological and palaeobotanical work undertaken over the last 30 years. Outside of attempts at palaeodemographic models, however, exploration of the social impact of the wave on Mesolithic hunter-gatherer societies living on the coasts of west Norway, the north and east British Isles, and around the southern North Sea basin have been less common. It has been widely assumed that the tsunami was a disaster–but what constituted a disaster for the Mesolithic peoples who lived through this event? What can we learn about life after natural hazards by considering the archaeological material from regions with distinct Mesolithic histories? This paper presents a review of evidence of the Storegga tsunami at Mesolithic sites from western Norway, the Northeast UK, and elsewhere around the southern North Sea basin. We consider the ways in which the social impact of the Storegga tsunami has been studied up till now and suggest an alternative way forward.
Trace Element and Isotope Systematics in Vent Fluids and Sulphides From Maka Volcano, North Eastern Lau Spreading Centre: Insights Into Three-Component Fluid Mixing
Authors: Klose Lukas , Keith Manuel , Hafermaas Daniel , Kleint Charlotte , Bach Wolfgang , Diehl Alexander , Wilckens Frederike , Peters Christian , Strauss Harald , Klemd Reiner , van Geldern Robert , Haase Karsten Matthias , Koschinsky Andrea 
Published: December 2021

Back-arc spreading centres and related volcanic structures are known for their intense hydrothermal activity. The axial volcanic edifice of Maka at the North Eastern Lau Spreading Centre is such an example, where fluids of distinct composition are emitted at the Maka hydrothermal field (HF) and at Maka South in 1,525–1,543 m water depth. At Maka HF black smoker-type fluids are actively discharged at temperatures of 329°C and are characterized by low pH values (2.79–3.03) and a depletion in Mg (5.5 mmol/kg) and SO4 (0.5 mmol/L) relative to seawater. High metal (e.g., Fe up to ∼6 mmol/kg) and rare Earth element (REE) contents in the fluids, are indicative for a rock-buffered hydrothermal system at low water/rock ratios (2–3). At Maka South, venting of white smoke with temperatures up to 301°C occurs at chimneys and flanges. Measured pH values range from 4.53 to 5.42 and Mg (31.0 mmol/kg), SO4 (8.2 mmol/L), Cl (309 mmol/kg), Br (0.50 mmol/kg) and Na (230 mmol/kg) are depleted compared to seawater, whereas metals like Li and Mn are typically enriched together with H2S. We propose a three-component mixing model with respect to the fluid composition at Maka South including seawater, a boiling-induced low-Cl vapour and a black smoker-type fluid similar to that of Maka HF, which is also preserved by the trace element signature of hydrothermal pyrite. At Maka South, high As/Co (&gt;10–100) and Sb/Pb (&gt;0.1) in pyrite are suggested to be related to a boiling-induced element fractionation between vapour (As, Sb) and liquid (Co, Pb). By contrast, lower As/Co (&lt;100) and a tendency to higher Co/Ni values in pyrite from Maka HF likely reflect the black smoker-type fluid. The Se/Ge ratio in pyrite provides evidence for fluid-seawater mixing, where lower values (&lt;10) are the result of a seawater contribution at the seafloor or during fluid upflow. Sulphur and Pb isotopes in hydrothermal sulphides indicate a common metal (loid) source at the two vent sites by host rock leaching in the reaction zone, as also reflected by the REE patterns in the vent fluids.
Soil Fertility Changes With Climate and Island Age in Galápagos: New Baseline Data for Sustainable Agricultural Management
Authors: Strahlhofer Matthias , Gerzabek Martin H. , Rampazzo Nicola , Couenberg Paulina M. , Vera Evelyn , Salazar Valenzuela Xavier , Zehetner Franz 
Published: December 2021

While the extended absence of human influence has led to matchless natural conditions on the Galápagos archipelago, agricultural activities on the inhabited islands are increasingly affecting soil health and functioning. However, a systematic assessment of the agricultural soils on the Galápagos Islands is still absent. Plate tectonics and hotspot volcanism cause an eastward drift of the archipelago and result in a west-to-east soil age gradient from approx. 1 to 1,000 ka. In addition, precipitation regimes change from arid to humid with elevation on the higher-standing islands. The objective of this study was to investigate differences in soil fertility parameters and Mehlich (III)-extractable nutrient levels along these gradients in order to provide baseline information for sustainable agricultural management. Topsoil samples (0–20 cm) from 125 farms of the islands Isabela, Santa Cruz and San Cristóbal were analyzed. Gravel and sand content, pH, electrical conductivity, cation exchange capacity, base saturation, soil organic C and total N content tended to decrease with increasing island age, while clay content, soil macroaggregate stability, plant-available water and bulk density increased. Mehlich (III)-extractable base cations Ca, K, Mg and Na as well as P, Fe and Zn showed a decreasing tendency from the youngest to the oldest island, while Mn increased with island age. Mehlich (III)-extractable Cu and Na reached their highest levels on the most intensively farmed, intermediate-aged island Santa Cruz, likely related to anthropogenic inputs and irrigation with brackish water, respectively. Changes along the altitudinal climate gradient within the studied islands were most significant for soil pH, base saturation, and Mehlich (III)-extractable Ca and Mn. Our results highlight the importance of site-specific agricultural management to account for the strong heterogeneity in soil parameters among and within the Galápagos archipelago. The data provided herein shall serve as a baseline for targeted future management strategies to avoid soil degradation, restore and maintain soil functioning and, hence, sustain the soils’ provision of ecosystem services in this unique archipelago.
Circulating miRNAs as Potential Biomarkers for Celiac Disease Development
Authors: Tan Ineke L. , Coutinho de Almeida Rodrigo , Modderman Rutger , Stachurska Anna , Dekens Jackie , Barisani Donatella , Meijer Caroline R. , Roca María , Martinez-Ojinaga Eva , Shamir Raanan , Auricchio Renata , Korponay-Szabó Ilma R. , Castillejo Gemma , Szajewska Hania , Koletzko Sibylle , Zhernakova Alexandra , Kumar Vinod , Li Yang , Visschedijk Marijn C. , Weersma Rinse K. , Troncone Riccardo , Mearin M. Luisa , Wijmenga Cisca , Jonkers Iris , Withoff Sebo 
Published: December 2021

Background &amp; AimsCeliac disease (CeD), an immune-mediated disease with enteropathy triggered by gluten, affects ~1% of the general European population. Currently, there are no biomarkers to predict CeD development. MicroRNAs (miRNAs) are short RNAs involved in post-transcriptional gene regulation, and certain disease- and stage-specific miRNA profiles have been found previously. We aimed to investigate whether circulating miRNAs can predict the development of CeD.MethodsUsing next-generation miRNA-sequencing, we determined miRNAs in &gt;200 serum samples from 53 participants of the PreventCD study, of whom 33 developed CeD during follow-up. Following study inclusion at 3 months of age, samples were drawn at predefined ages, diagnosis (first anti-transglutaminase antibody (TGA) positivity or diagnostic biopsy) and after the start of a gluten-free diet (GFD). This allowed identification of circulating miRNAs that are deregulated before TGA positivity. For validation of the biomarkers for CeD and GFD response, two additional cohorts were included in subsequent meta-analyses. Additionally, miRNAs were measured in duodenal biopsies in a case-control cohort.Results53 circulating miRNAs were increased (27) or decreased (26) in CeD versus controls. We assessed specific trends in these individual miRNAs in the PreventCD cohort by grouping the pre-diagnostic samples of the CeD patients (all had negative TGA) by how close to seroconversion (first sample positive TGA) the samples were taken. 8/53 miRNAs differed significantly between controls and samples taken &lt;1 year before TGA positivity: miR-21-3p, miR-374a-5p, 144-3p, miR-500a-3p, miR-486-3p let-7d-3p, let-7e-5p and miR-3605-3p. 6/26 downregulated miRNAs reconstituted upon GFD, including miR-150-5p/-3p, whereas no upregulated miRNAs were downregulated upon GFD. 15/53 biomarker candidates also differed between CeD biopsies and controls, with a concordant direction, indicating that these circulating miRNAs might originate from the intestine.ConclusionsWe identified 53 circulating miRNAs that are potential early biomarkers for CeD, of which several can be detected more than a year before TGA positivity and some start to normalize upon GFD.
Identification and Clinical Validation of Key Extracellular Proteins as the Potential Biomarkers in Relapsing-Remitting Multiple Sclerosis
Authors: Li Meng , Chen Hongping , Yin Pengqi , Song Jihe , Jiang Fangchao , Tang Zhanbin , Fan Xuehui , Xu Chen , Wang Yingju , Xue Yang , Han Baichao , Wang Haining , Li Guozhong , Zhong Di 
Published: December 2021

BackgroundMultiple sclerosis (MS) is a demyelinating disease of the central nervous system (CNS) mediated by autoimmunity. No objective clinical indicators are available for the diagnosis and prognosis of MS. Extracellular proteins are most glycosylated and likely to enter into the body fluid to serve as potential biomarkers. Our work will contribute to the in-depth study of the functions of extracellular proteins and the discovery of disease biomarkers.MethodsMS expression profiling data of the human brain was downloaded from the Gene Expression Omnibus (GEO). Extracellular protein-differentially expressed genes (EP-DEGs) were screened by protein annotation databases. GO and KEGG were used to analyze the function and pathway of EP-DEGs. STRING, Cytoscape, MCODE and Cytohubba were used to construct a protein-protein interaction (PPI) network and screen key EP-DEGs. Key EP-DEGs levels were detected in the CSF of MS patients. ROC curve and survival analysis were used to evaluate the diagnostic and prognostic ability of key EP-DEGs.ResultsWe screened 133 EP-DEGs from DEGs. EP-DEGs were enriched in the collagen-containing extracellular matrix, signaling receptor activator activity, immune-related pathways, and PI3K-Akt signaling pathway. The PPI network of EP-DEGs had 85 nodes and 185 edges. We identified 4 key extracellular proteins IL17A, IL2, CD44, IGF1, and 16 extracellular proteins that interacted with IL17A. We clinically verified that IL17A levels decreased, but Del-1 and resolvinD1 levels increased. The diagnostic accuracy of Del-1 (AUC: 0.947) was superior to that of IgG (AUC: 0.740) with a sensitivity of 82.4% and a specificity of 100%. High Del-1 levels were significantly associated with better relapse-free and progression-free survival.ConclusionIL17A, IL2, CD44, and IGF1 may be key extracellular proteins in the pathogenesis of MS. IL17A, Del-1, and resolvinD1 may co-regulate the development of MS and Del-1 is a potential biomarker of MS. We used bioinformatics methods to explore the biomarkers of MS and validated the results in clinical samples. The study provides a theoretical and experimental basis for revealing the pathogenesis of MS and improving the diagnosis and prognosis of MS.