bluuebunny/crossref_metadata_2025 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< 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 < 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 < 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 < 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 > 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.
Change in Extreme Precipitation Over Indochina Under Climate Change From a Lagrangian Perspective of Water Vapor
Authors: Cheng Zelun , Xie Zuowei , Tang Wei , Bueh Cholaw , Gong Yuanfa , Yan Jie
Published: December 2021

The process of global warming has humidified the atmosphere and increased the occurrence of extreme-precipitation events over the Indochina Peninsula, which lies in the transition region from the South Asian monsoon to the East Asian monsoon. The annual occurrence number of days of extreme precipitation over the Indochina Peninsula exhibits a significant change in 2003, with an abnormally higher occurrence number during the period 2003–2015 than that during 1951–2002. The extreme precipitation and such decadal change are contributed by more moisture sources associated with an enhanced dipole circulation over the Indian Ocean, which could be linked to the Pacific Decadal Oscillation. The daily large-scale meteorological pattern directly associated with extreme precipitation is characterized by an enhanced dipole of the typical summer monsoon pattern, with a zonally elongated Mascarene high and a deepened monsoon trough from northern India to the South China Sea. Such an intensified dipole provides two major channels of water vapor: one along the low-level westerly jet over the Indian Ocean and the other along the gyre of monsoon trough over the South China Sea. Compared with that during the period 1951–2002, the dipole is enhanced from northern India to the Indian Ocean and weakened over the Indochina Peninsula during the period 2003–2015. Although the Lagrangian analysis shows that the trajectory of air masses is displaced southward to the Indian Ocean, the intensified low-level westerly jet increases the evaporation of water from the ocean and thus not only enhances the water channel over the Indian Ocean but also yields a parallel water channel over the Bay of Bengal. In contrast, in spite of the increased trajectory density of air masses over the South China Sea, the lingering of air mass suppresses the evaporation of water and thus provides a declined contribution to the extreme precipitation during 2003–2015.
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 (>10–100) and Sb/Pb (>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 (<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 (<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.
Ratio-Dependence in Predator-Prey Systems as an Edge and Basic Minimal Model of Predator Interference
Authors: Tyutyunov Yuri V. , Titova Lyudmila I.
Published: December 2021

The functional response (trophic function or individual ration) quantifies the average amount of prey consumed per unit of time by a single predator. Since the seminal Lotka-Volterra model, it is a key element of the predation theory. Holling has enhanced the theory by classifying prey-dependent functional responses into three types that long remained a generally accepted basis of modeling predator-prey interactions. However, contradictions between the observed dynamics of natural ecosystems and the properties of predator-prey models with Holling-type trophic functions, such as the paradox of enrichment, the paradox of biological control, and the paradoxical enrichment response mediated by trophic cascades, required further improvement of the theory. This led to the idea of the inclusion of predator interference into the trophic function. Various functional responses depending on both prey and predator densities have been suggested and compared in their performance to fit observed data. At the end of the 1980s, Arditi and Ginzburg stimulated a lively debate having a strong impact on predation theory. They proposed the concept of a spectrum of predator-dependent trophic functions, with two opposite edges being the prey-dependent and the ratio-dependent cases, and they suggested revising the theory by using the ratio-dependent edge of the spectrum as a null model of predator interference. Ratio-dependence offers the simplest way of accounting for mutual interference in predator-prey models, resolving the abovementioned contradictions between theory and natural observations. Depending on the practical needs and the availability of observations, the more detailed models can be built on this theoretical basis.
Fungal Diversity in Multiple Post-harvest Aged Red Pine Stumps and Their Potential Influence on Heterobasidion Root Rot in Managed Stands Across Minnesota
Authors: Otto Eric C. , Held Benjamin W. , Gould Trevor J. , Blanchette Robert A.
Published: December 2021

Thinning operations that occur in managed red pine (Pinus resinosa) stands, create tree stumps that can serve as a habitat for fungi, especiallyHeterobasidion irregulare, the cause of a serious root disease. Different fungi can colonize stumps early and the community of fungi can change over time as initial fungal species become replaced. Samples were collected from both the native and non-native range of red pine from stumps that were cut at different time periods. Stumps that were harvested at 0–1, 2–3, 5–6, and 10–12 years before sampling were used to provide data on the diversity of fungi that colonize tree stumps and how these communities can change over time as well as how they influence colonization ofH. irregulare. Traditional culturing methods and Illumina MiSeq sequencing were used to identify the fungi in the samples. Of particular interest wasPhlebiopsis gigantea, which can colonize cut stumps and preventH. irregularefrom becoming established. Overall,P. giganteawas the most abundant fungus isolated and sequenced via Illumina MiSeq. Results show thatPhlebiopsis giganteawas isolated from 90% of all stumps sampled for sites harvested within 3 years of sampling in the native range of red pine compared to 33% in the non-native range. For Illumina MiSeq, 5,940 total amplicon sequence variants (ASVs) were detected.P. gigantearepresented 14% of the total reads and composed 19% of the reads in the native range and 8% in non-native range of red pine. Furthermore,P. gigantearepresented 38% of the reads for stumps that were harvested within 3 years of sampling in the native range of red pine compared to 14% in the non-native range. These results help demonstrate that a higher amount ofP. giganteais present in the native range of red pine and could be acting as a native biological control agent. Additional fungi, includingResinicium bicolor, Hypochnicium cremicolor, Leptographiumspp., and others identified at different cutting times are also discussed. Finally, different diversity indices revealed similar, but slightly higher diversity for southern sites via Shannon and Simpson Diversity indices. Beta diversity demonstrated a similar species composition in stumps harvested at different times with these stumps being grouped together based on harvesting years.
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 & Aims

Celiac 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.

Methods

Using next-generation miRNA-sequencing, we determined miRNAs in >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.

Results

53 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 <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.

Conclusions

We 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

Background

Multiple 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.

Methods

MS 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.

Results

We 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.

Conclusion

IL17A, 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.
Long Non-Coding RNAs, Novel Offenders or Guardians in Multiple Sclerosis: A Scoping Review
Authors: Jalaiei Abbas , Asadi Mohammad Reza , Sabaie Hani , Dehghani Hossein , Gharesouran Jalal , Hussen Bashdar Mahmud , Taheri Mohammad , Ghafouri-Fard Soudeh , Rezazadeh Maryam
Published: December 2021

Multiple sclerosis (MS), a chronic inflammatory demyelinating disease of the central nervous system, is one of the most common neurodegenerative diseases worldwide. MS results in serious neurological dysfunctions and disability. Disturbances in coding and non-coding genes are key components leading to neurodegeneration along with environmental factors. Long non-coding RNAs (lncRNAs) are long molecules in cells that take part in the regulation of gene expression. Several studies have confirmed the role of lncRNAs in neurodegenerative diseases such as MS. In the current study, we performed a systematic analysis of the role of lncRNAs in this disorder. In total, 53 studies were recognized as eligible for this systematic review. Of the listed lncRNAs, 52 lncRNAs were upregulated, 37 lncRNAs were downregulated, and 11 lncRNAs had no significant expression difference in MS patients compared with controls. We also summarized some of the mechanisms of lncRNA functions in MS. The emerging role of lncRNAs in neurodegenerative diseases suggests that their dysregulation could trigger neuronal death via still unexplored RNA-based regulatory mechanisms. Evaluation of their diagnostic significance and therapeutic potential could help in the design of novel treatments for MS.
SARS-CoV-2 N Protein Induces Acute Lung Injury in Mice via NF-ĸB Activation
Authors: Xia Jie , Tang Wenqi , Wang Jiangmei , Lai Dengming , Xu Qi , Huang Ruoqiong , Hu Yaoqin , Gong Xiaojue , Fan Jiajie , Shu Qiang , Xu Jianguo
Published: December 2021

Background

Infection of SARS-CoV-2 may cause acute respiratory syndrome. It has been reported that SARS-CoV-2 nucleocapsid protein (N-protein) presents early in body fluids during infection. The direct involvement of N-protein in lung injury is poorly understood.

Methods

Recombinant N-protein was pretreated with polymyxin B, a lipopolysaccharide (LPS)-neutralizing agent. C57BL/6, C3H/HeJ (resistant to LPS), and C3H/HeN (control for C3H/HeJ) mice were exposed to N-protein via intratracheal administration to examine acute lung injury. In vitro, bone marrow–derived macrophages (BMDMs) were cultured with N-protein to study phosphorylation of nuclear factor kappa B (NF-ĸB) p65, macrophage polarization, and expression of proinflammatory cytokines.

Results

N-protein produced acute lung injury in C57BL/6 mice, with elevated protein permeability, total cell count, neutrophil infiltration, and proinflammatory cytokines in the bronchioalveolar lavage. N-protein also induced lung injury in both C3H/HeJ and C3H/HeN mice, indicating that the effect could not be attributed to the LPS contamination. N-protein triggered phosphorylation of NF-ĸB p65 in vitro, which was abolished by both N-protein denaturation and treatment with an antibody for N-protein, demonstrating that the effect is N-protein specific. In addition, N-protein promoted M1 macrophage polarization and the expression of proinflammatory cytokines, which was also blocked by N-protein denaturation and antibody for N-protein. Furthermore, N-protein induced NF-ĸB p65 phosphorylation in the lung, while pyrrolidine dithiocarbamate, an NF-ĸB inhibitor, alleviated the effect of N-protein on acute lung injury.

Conclusions

SARS-CoV-2 N-protein itself is toxic and induces acute lung injury in mice. Both N-protein and NF-ĸB pathway may be therapeutic targets for treating multi-organ injuries in Coronavirus disease 2019 (COVID-19).
Integrated Knowledge Translation in Non-Communicable Disease Research in Sub-Saharan Africa: A Comparison of Systematic and Ad Hoc Stakeholder Engagement
Authors: Mpando Talitha L. , Sell Kerstin , Delobelle Peter , Osuret Jimmy , Niyibizi Jean Berchmans , Ntawuyirushintege Seleman , Geremew Bezinash , Jessani Nasreen S.
Published: December 2021

Background

Low- and middle-income countries (LMICs) are currently experiencing an increasing prevalence of non-communicable diseases (NCDs). To address this as well as other health challenges, Integrated Knowledge Translation (IKT) approaches to build mutually beneficial relationships between researchers and decision-makers can concurrently inform research as well as enhance evidence use in policy and practice. The Collaboration for Evidence-Based Healthcare and Public Health in Africa (CEBHA+) is a research consortium which conducts research on NCDs and uses an IKT approach to facilitate the uptake of this research in five African countries: Ethiopia, Uganda, Rwanda, Malawi, and South Africa. Tailored IKT strategies were designed and implemented to plan and guide stakeholder engagement. This systematic approach contrasts with more commonly usedad hocapproaches to stakeholder engagement.

Methods

In this article, we explore the experiences of researchers engaged in the CEBHA+ IKT approach across the five African countries. Data sources included: 1) an informal document review of CEBHA+ country-specific IKT strategies, IKT team meeting minutes and activity reports, and 2) a semi-structured survey of IKT implementers to elicit country-specific experiences on actual implementation and adaptation of the IKT strategies. Results were collated and contrasted across all CEBHA+ countries with a focus on systematic versusad hocapproaches to engagement.

Results

South Africa, Malawi and Ethiopia country teams indicated that their engagements benefited from a systematic IKT strategy. This was especially the case in the early stages of the project as it allowed focused and intentional engagement. However,ad hocengagement was still required as new professional relationships developed, and contextual circumstances - including the SARS-CoV-2 pandemic - required responsive engagement with decision-makers and other stakeholders. In Rwanda and Uganda, continuous systematic engagement was found to bolster ownership of the research at both community and national levels.

Conclusion

Political and health climates are constantly shifting with a need to maintain flexibility in how IKT strategies are implemented. While strategic IKT can benefit from deliberate planning and stakeholder engagement, there is value in remaining flexible to respond to the needs of stakeholders and contextual circumstances. This paper highlights how IKT implementers in the five African CEBHA+ countries responded to this challenge.
Fish Assemblages in a Small Mangrove System on Príncipe Island, Gulf of Guinea
Authors: Cravo Mariana , Almeida Armando J. , Lima Hamilton , Azevedo e Silva João , Bandeira Salomão , Machava-António Vilma , Paula José
Published: December 2021

Mangroves are highly productive ecosystems with complex adaptations to the transition between freshwater and sea. Mangroves function as nursery habitats for many organisms, providing protection and food sources for early developmental stages of crustaceans and fish, helping to maintain adjacent marine stocks. Mangroves in São Tomé and Príncipe remain poorly studied. This study addresses the importance of a small mangrove stand to ichthyofauna. The main goal of the study was to describe the fish assemblages of the Praia Salgada mangrove stand on Príncipe Island, and assess if variations in the season, tide, and mangrove zone affected fish distribution. Fish assemblages were sampled with mosquito nets during the rainy and dry seasons, and neap and spring tides, while environmental parameters such as water depth, temperature, pH, and salinity measurements were taken. The characteristics of the water column were affected by a sandbank that developed between sampling seasons, impacting on the dynamics of the water and biological exchanges between the mangrove stand and the adjacent marine environment. The study identified 14 fish species occurring in the Praia Salgada mangrove stand from a total of 772 specimens caught. Five species were recorded for the first time as occurring in the country’s mangrove areas, namely Caranx latus, Ethmalosa fimbriata, Mugil curema, Gobioides cf. africanus, and Citharus cf. linguatula. Most of the reported species are of commercial interest, and were predominantly juveniles, suggesting that the mangrove ecosystem provides a nursery function for several species. Some species revealed preferences for either the upper or lower part of the mangrove forest. The size of fish sampled tended to be bigger during the dry season, especially for the Mugilidae, Aplocheilichthys spilauchen and Gobiidae groups. E. fimbriata and Eucinostomus melanopterus displayed similar sizes between seasons. The average quantity of fish caught per day in the rainy season was three times higher than in the dry season. The fish species distribution in the mangrove stand varied significantly according to the season and mangrove zone. The overall results suggest that the Praia Salgada mangrove stand provides a nursery function for several of the studied fish species.
Impact of Shifting Subpolar Front on Phytoplankton Dynamics in the Western Margin of East/Japan Sea
Authors: Kim Dongyoung , Ji Rubao , Park Hyun Je , Feng Zhixuan , Jang Jaebin , Lee Chung l , Kang Yun-Ho , Kang Chang-Keun
Published: December 2021

A subpolar front (SPF) generated between the East Korea Warm Current (EKWC) and the North Korea Cold Current (NKCC) in the western margin of the East/Japan Sea has shifted northward in recent decades. This study investigated the biomass and composition of the phytoplankton assemblage in relation to hydrological and biogeochemical features in the shallow shelf and slope off the Korean coast from January to June in 2016 and 2017, to determine the mechanistic effects of SPF on spring–summer phytoplankton bloom dynamics. Monthly average depth-integrated chlorophylla(Chla) levels and the contribution of phytoplankton classes revealed bimodal diatom blooms in early spring and summer in the frontal zone. Canonical correspondence analysis showed that the distribution of high Chlawas associated with cold, low-salinity NKCC water in March 2016. No Chlapeak was observed in March 2017 when the warm saline EKWC water mass invaded. These results suggest that the NKCC intrusion acts as a forcing mechanism leading to enhanced phytoplankton biomass in the frontal zone. In contrast, positive correlations of Chlaconcentration with water density and nutrient concentrations suggest that summer blooms were fed by the subsurface chlorophyll maximum (SCM) driven by shoaling of the pycnocline and nitracline. Varying water-column stratification determined the thickness of the SCM layer, driving year-to-year variability in the magnitude of diatom blooms. These findings further suggest that seasonal/interannual variability in the timing of algal blooms affects regional trophodynamics and hence could be an important factor in explaining ecosystem changes in this region.
A Review of SARS-CoV2: Compared With SARS-CoV and MERS-CoV
Authors: Zhou Huan , Yang Junfa , Zhou Chang , Chen Bangjie , Fang Hui , Chen Shuo , Zhang Xianzheng , Wang Linding , Zhang Lingling
Published: December 2021

The outbreak of coronavirus disease 2019 (COVID-19) has been spreading rapidly in China and the Chinese government took a series of policies to control the epidemic. Studies found that severe COVID-19 is characterized by pneumonia, lymphopenia, exhausted lymphocytes and a cytokine storm. Studies have showen that SARS-CoV2 has significant genomic similarity to the severe acute respiratory syndrome (SARS-CoV), which was a pandemic in 2002. More importantly, some diligent measures were used to limit its spread according to the evidence of hospital spread. Therefore, the Public Health Emergency of International Concern (PHEIC) has been established by the World Health Organization (WHO) with strategic objectives for public health to curtail its impact on global health and economy. The purpose of this paper is to review the transmission patterns of the three pneumonia: SARS-CoV2, SARS-CoV, and MERS-CoV. We compare the new characteristics of COVID-19 with those of SARS-CoV and MERS-CoV.
Observation of Peripapillary Choroidal Vascularity in Natural Disease Course and After Gene Therapy for Leber's Hereditary Optic Neuropathy
Authors: Jiang Jingwen , Sun Gongpeng , Miao Qingmei , Li Bin , Wang Dan , Yuan Jiajia , Chen Changzheng
Published: December 2021

Purpose: To compare peripapillary choroidal vascularity among Leber's Hereditary Optic Neuropathy (LHON) patients at different stages of natural course and healthy controls using optical coherence tomography (OCT), and to evaluate peripapillary choroidal vascularity changes in LHON patients before and after gene therapy.

Methods: 57 LHON patients and 15 healthy controls were enrolled in this prospective clinical study. LHON patients were divided into three duration groups based on stage of disease progression. Both patients and healthy controls underwent OCT scans focused on the optic disc at baseline with Heidelberg Spectralis, and patients underwent OCT at 1, 3, and 6 months after gene therapy. OCT images were converted and binarized using ImageJ software. Choroidal thickness (CT), total choroidal area (TCA), and choroidal vascularity index (CVI) in each quadrant of OCT images were measured to evaluate peripapillary choroidal vascularity.

Results: At baseline, the average CT was not significantly different between LHON patients at different stages and between healthy controls (P = 0.468). Although average TCA and average CVI were slightly higher in LHON patients at different stages than in healthy controls, the difference was not statistically significant (P = 0.282 and 0.812, respectively). After gene therapy, The average TCA at 1 month after gene therapy was significantly higher than that before gene therapy (P = 0.003), while no significant differences were found in the average CT or average CVI in LHON patients before and 1,3 and 6 months after gene therapy using pairwise comparisons (all P > 0.05).

Conclusions: No significant difference was found in choroidal vascularity of LHON patients at different stages and healthy controls. Choroidal vascularity seems to stay stable after gene therapy.
PD-1H Expression Associated With CD68 Macrophage Marker Confers an Immune-Activated Microenvironment and Favorable Overall Survival in Human Esophageal Squamous Cell Carcinoma
Authors: Chen Yuangui , Feng Rui , He Bailin , Wang Jun , Xian Na , Huang Gangxiong , Zhang Qiuyu
Published: December 2021

Esophageal squamous cell carcinoma (ESCC) is the most common type of esophageal carcinoma (EC) in China. Although the PD-1 inhibitor pembrolizumab has been approved to treat patients with EC, its therapeutic efficacy is limited. Thus, additional immunotherapeutic targets for EC treatment are needed. Programmed Death-1 Homolog (PD-1H) is a negative checkpoint regulator that inhibits antitumor immune responses. Here, PD-1H expression in 114 patients with ESCC was evaluated by immunohistochemistry. Next, 12 randomly selected tumor tissue sections were used to assess the colocalization of PD-1H protein and multiple immune markers by multiplex immunohistochemistry. Our results demonstrated that PD-1H was expressed at high frequency in ESCC tumor tissues (85.1%). PD-1H protein was predominantly expressed in CD68+ tumor-associated macrophages and expressed at low levels in CD4+ T cells and CD8+ T cells in ESCC tumor tissues. Furthermore, based on ESCC data in The Cancer Genome Atlas (TCGA), the gene expression levels of PD-1H were positively associated with the infiltration levels of immune-activated cells especially CD8+ cytotoxic T cells. In contrast, the gene expression levels of PD-1H were negatively correlated with myeloid-derived suppressor cells (MDSCs). Importantly, PD-1H expression in tumor sites was significantly correlated with favorable overall survival in patients with ESCC. Collectively, our findings first provided direct information on the PD-1H expression pattern and distribution in ESCC, and positive correlation of PD-1H expression with overall survival suggested PD-1H expression levels could be a significant prognostic indicator for patients with ESCC. Future studies need to explore the immunoregulatory of PD-1H in the tumor microenvironment of ESCC.