bluuebunny/crossref_metadata_2025_split huggingface dataset:
Proteomic profile of mesothelial exosomes isolated from peritoneal dialysis effluent of children with focal segmental glomerulosclerosis
Authors: Bruschi Maurizio , La Porta Edoardo , Panfoli Isabella , Candiano Giovanni , Petretto Andrea , Vidal Enrico , Kajana Xhuliana , Bartolucci Martina , Granata Simona , Ghiggeri Gian Marco , Zaza Gianluigi , Verrina Enrico 
Published: October 2021

AbstractPeritoneal dialysis (PD) is the worldwide recognized preferred dialysis treatment for children affected by end-stage kidney disease (ESKD). However, due to the unphysiological composition of PD fluids, the peritoneal membrane (PM) of these patients may undergo structural and functional alterations, which may cause fibrosis. Several factors may accelerate this process and primary kidney disease may have a causative role. In particular, patients affected by steroid resistant primary focal segmental glomerulosclerosis, a rare glomerular disease leading to nephrotic syndrome and ESKD, seem more prone to develop peritoneal fibrosis. The mechanism causing this predisposition is still unrecognized. To better define this condition, we carried out, for the first time, a new comprehensive comparative proteomic mass spectrometry analysis of mesothelial exosomes from peritoneal dialysis effluent (PDE) of 6 pediatric patients with focal segmental glomerular sclerosis (FSGS) versus 6 patients affected by other primary renal diseases (No FSGS). Our omic study demonstrated that, despite the high overlap in the protein milieu between the two study groups, machine learning allowed to identify a core list of 40 proteins, with ANXA13 as most promising potential biomarker, to distinguish, in our patient population, peritoneal dialysis effluent exosomes of FSGS from No FSGS patients (with 100% accuracy). Additionally, the Weight Gene Co-expression Network Analysis algorithm identified 17 proteins, with PTP4A1 as the most statistically significant biomarker associated to PD vintage and decreased PM function. Altogether, our data suggest that mesothelial cells of FSGS patients are more prone to activate a pro-fibrotic machinery. The role of the proposed biomarkers in the PM pathology deserves further investigation. Our results need further investigations in a larger population to corroborate these findings and investigate a possible increased risk of PM loss of function or development of encapsulating peritoneal sclerosis in FSGS patients, thus to eventually carry out changes in PD treatment and management or implement new solutions.
Earliest evidence of herd-living and age segregation amongst dinosaurs
Authors: Pol Diego , Mancuso Adriana C. , Smith Roger M. H. , Marsicano Claudia A. , Ramezani Jahandar , Cerda Ignacio A. , Otero Alejandro , Fernandez Vincent 
Published: October 2021

AbstractSauropodomorph dinosaurs dominated the herbivorous niches during the first 40 million years of dinosaur history (Late Triassic–Early Jurassic), yet palaeobiological factors that influenced their evolutionary success are not fully understood. For instance, knowledge on their behaviour is limited, although herding in sauropodomorphs has been well documented in derived sauropods from the Late Jurassic and Cretaceous. Here we report an exceptional fossil occurrence from Patagonia that includes over 100 eggs and skeletal specimens of 80 individuals of the early sauropodomorph Mussaurus patagonicus, ranging from embryos to fully-grown adults, with an Early Jurassic age as determined by high-precision U–Pb zircon geochronology. Most specimens were found in a restricted area and stratigraphic interval, with some articulated skeletons grouped in clusters of individuals of approximately the same age. Our new discoveries indicate the presence of social cohesion throughout life and age-segregation within a herd structure, in addition to colonial nesting behaviour. These findings provide the earliest evidence of complex social behaviour in Dinosauria, predating previous records by at least 40 My. The presence of sociality in different sauropodomorph lineages suggests a possible Triassic origin of this behaviour, which may have influenced their early success as large terrestrial herbivores.
Microwave-assisted photooxidation of sulfoxides
Authors: Matsukawa Yuta , Muranaka Atsuya , Murayama Tomotaka , Uchiyama Masanobu , Takaya Hikaru , Yamada Yoichi M. A. 
Published: October 2021

AbstractWe demonstrated microwave-assisted photooxidation of sulfoxides to the corresponding sulfones using ethynylbenzene as a photosensitizer. Efficiency of the photooxidation was higher under microwave irradiation than under conventional thermal heating conditions. Under the conditions, ethynylbenzene promoted the oxidation more efficiently than conventional photosensitizers benzophenone, anthracene, and rose bengal. Ethynylbenzene, whose T1 state is extremely resistant to intersystem crossing to the ground state, was suitable to this reaction because spectroscopic and related reported studies suggested that this non-thermal effect was caused by elongating lifetime of the T1 state by microwave. This is the first study in which ethynylbenzene is used as a photosensitizer in a microwave-assisted photoreaction.
The invasive cactus Opuntia stricta creates fertility islands in African savannas and benefits from those created by native trees
Authors: Novoa Ana , Foxcroft Llewellyn C. , Keet Jan-Hendrik , Pyšek Petr , Le Roux Johannes J. 
Published: October 2021

AbstractThe patchy distribution of trees typical of savannas often results in a discontinuous distribution of water, nutrient resources, and microbial communities in soil, commonly referred to as “islands of fertility”. We assessed how this phenomenon may affect the establishment and impact of invasive plants, using the invasion of Opuntia stricta in South Africa’s Kruger National Park as case study. We established uninvaded and O. stricta-invaded plots under the most common woody tree species in the study area (Vachellia nilotica subsp. kraussiana and Spirostachys africana) and in open patches with no tree cover. We then compared soil characteristics, diversity and composition of the soil bacterial communities, and germination performance of O. stricta and native trees between soils collected in each of the established plots. We found that the presence of native trees and invasive O. stricta increases soil water content and nutrients, and the abundance and diversity of bacterial communities, and alters soil bacterial composition. Moreover, the percentage and speed of germination of O. stricta were higher in soils conditioned by native trees compared to soils collected from open patches. Finally, while S. africana and V. nilotica trees appear to germinate equally well in invaded and uninvaded soils, O. stricta had lower and slower germination in invaded soils, suggesting the potential release of phytochemicals by O. stricta to avoid intraspecific competition. These results suggest that the presence of any tree or shrub in savanna ecosystems, regardless of origin (i.e. native or alien), can create favourable conditions for the establishment and growth of other plants.
Gene transfer of MRCKα rescues lipopolysaccharide-induced acute lung injury by restoring alveolar capillary barrier function
Authors: Liu Jing , Dean David A. 
Published: October 2021

AbstractAcute Lung Injury/Acute Respiratory Distress Syndrome (ALI/ARDS) is characterized by alveolar edema accumulation with reduced alveolar fluid clearance (AFC), alveolar-capillary barrier disruption, and substantial inflammation, all leading to acute respiratory failure. Enhancing AFC has long been considered one of the primary therapeutic goals in gene therapy treatments for ARDS. We previously showed that electroporation-mediated gene delivery of the Na+, K+-ATPase β1 subunit not only increased AFC, but also restored alveolar barrier function through upregulation of tight junction proteins, leading to treatment of LPS-induced ALI in mice. We identified MRCKα as an interaction partner of β1 which mediates this upregulation in cultured alveolar epithelial cells. In this study, we investigate whether electroporation-mediated gene transfer of MRCKα to the lungs can attenuate LPS-induced acute lung injury in vivo. Compared to mice that received a non-expressing plasmid, those receiving the MRCKα plasmid showed attenuated LPS-increased pulmonary edema and lung leakage, restored tight junction protein expression, and improved overall outcomes. Interestingly, gene transfer of MRCKα did not alter AFC rates. Studies using both cultured microvascular endothelial cells and mice suggest that β1 and MRCKα upregulate junctional complexes in both alveolar epithelial and capillary endothelial cells, and that one or both barriers may be positively affected by our approach. Our data support a model of treatment for ALI/ARDS in which improvement of alveolar-capillary barrier function alone may be of more benefit than improvement of alveolar fluid clearance.
Herbstzeitlose, Colchicum autumnale L.
Authors: Mo Zilin , Melzig Matthias F. 
Published: October 2021

ZusammenfassungColchicum autumnale L., die Herbstzeitlose, ist eine in Mitteleuropa verbreitete Pflanze, die v. a. Tropolonalkaloide wie Colchicin, Demecolcin sowie Colchicosid enthält. Der Hauptwirkstoff Colchicin verhindert die Ausbildung des zellulären Mikrotubuli-Apparates, was mit einer Entzündungshemmung verbunden ist. Trotz hoher Toxizität werden isoliertes Colchicin und Herbstzeitlosen-Extrakte zur Behandlung von Gicht eingesetzt. Weitere Anwendungsgebiete werden derzeit erforscht.
A rapidly reversible mutation generates subclonal genetic diversity and unstable drug resistance
Authors: Dan Lufeng , Li Yuze , Chen Shuhua , Liu Jingbo , Wang Yu , Li Fangting , He Xiangwei , Carey Lucas B. 
Published: October 2021

Significance
Mutations that confer drug resistance often confer a growth defect in the absence of drug. Mechanisms that enable temporary mutations—mutations that provide drug resistance but frequently revert back to the wild-type genomic DNA sequence—would therefore be advantageous for organisms forced to adapt in changing environments. Here, we show that rapidly reversible mutations are frequently generated by microhomology-mediated tandem duplications (MTDs) in the gene ssp1, causing rapamycin resistance and a growth defect, and reversal back to wild type restores fitness and drug sensitivity. We also found that genomes have evolved to minimize the number of potentially deleterious MTDs and used machine learning to determine the sequence-encoded rules that govern the formation and collapse of MTDs.
TDP-43 proteinopathy in oligodendrocytes revealed using an induced pluripotent stem cell model
Authors: Barton Samantha K , Magnani Dario , James Owen G , Livesey Matthew R , Selvaraj Bhuvaneish T , James Owain T , Perkins Emma M , Gregory Jenna M , Cleary Elaine , Ausems C Rosanne M , Carter Rod , Vasistha Navneet A , Zhao Chen , Burr Karen , Story David , Cardinali Alessandra , Morton Nicholas M , Hardingham Giles E , Wyllie David J A , Chandran Siddharthan 
Published: October 2021

Abstract
Oligodendrocytes are implicated in Amytrophic Lateral Sclerosis pathogenesis and display TDP-43 pathological inclusions. To investigate the cell autonomous consequences of TDP-43 mutations on human oligodendrocytes, we generated oligodendrocytes from patient-derived induced pluripotent stem cell lines harbouring mutations in the TARDBP gene, namely G298S and M337V. Through a combination of immunocytochemistry, electrophysiological assessment via whole-cell patch clamping, and three-dimensional cultures, no differences in oligodendrocyte differentiation, maturation or myelination were identified. Further, expression analysis for monocarboxylate transporter 1 (a lactate transporter) coupled with a glycolytic stress test showed no deficit in lactate export. However, using confocal microscopy, we report TDP-43 mutation dependent pathological mis-accumulation of TDP-43. Furthermore, using in vitro patch-clamp recordings, we identified functional Ca2+-permeable AMPA receptor dysregulation in oligodendrocytes. Together, these findings establish a platform for further interrogation of the role of oligodendrocytes and cellular autonomy in TDP-43 proteinopathy.
The role of cardiac magnetic resonance in MINOCA diagnosis
Authors: Dias Claudio F , Picarra B , Neves D , Trinca M 
Published: October 2021

Abstract

Introduction
Absence of obstructive coronary disease does not imply absence of acute myocardial infarction (AMI). Hence, it can be designated as Myocardial Infarction with Non-obstructive Coronary Arteries (MINOCA). Performing Cardiac Magnetic Resonance (CMR) can be essential for establishing a final diagnosis, according to the presence and pattern of late gadolinium enhancement (LGE).

Purpose
The aim of this study is to evaluate the diagnostic and prognostic impact of CMR in patients with a possible diagnosis of MINOCA.

Methods
A 7-year prospective study, which included all patients proposed to CMR with a presumptive diagnosis of MINOCA due to acute chest pain, troponin raise and absence of angiographically significant coronary disease (luminal stenosis of &lt;50%). All patients performed functional, anatomical evaluation and LGE assessment. We analysed clinical characteristics, electrocardiographic presentation, echocardiographic and invasive coronary angiography results. A presumptive diagnosis was elaborated after invasive coronary angiography and comparison was made with the definitive one after CMR.

Results
A total of 96 patients were included, 50% were male, with a mean age of 48±20 years old. Clinical history of hypertension was observed in 51.0% patients, 35.4% had dyslipidaemia, 7.3% with diabetes, obesity was present in 22.9% of patients and smoking habits in 30.2%. At admission, 44.8% had ST segment elevation, so emergent invasive coronary angiography was performed. The mean highest troponin I was 7.34±9.18 ng/mL. Late gadolinium enhancement was observed in 53 (55.2%) of patients. After CMR realization a final diagnosis of MINOCA was made in only 8 patients (8.4%) and in 51 patients (53.1%) CMR evaluation allowed a diagnosis modification, with impact on patients' management and prognosis. A definitive diagnosis of myocarditis was seen in 46.9% (n=45) of cases, of Takotsubo's myocardiopathy in 13.5% (n=13), and hypertrophic cardiomyopathy in 3.1% (n=3). In 27 (28.1%) of patients, late gadolinium enhancement was not found. This diagnosis adjustment had an impact on treatment in 34.4% (n=33).

Conclusion
CMR is a pivotal technique on MINOCA patients' management. Our study portrayed the importance of performing CMR, allowing initial diagnosis modification in half of the cases, with important therapeutic in one third of patients and prognostic implications, related to diagnosis and target treatment adverse effects.

Funding Acknowledgement
Type of funding sources: None.
Prognostic value of diastolic function parameters in significant aortic regurgitation. The role of the left atrial strain
Authors: Garcia Martin A , Abellas Sequeiros M , Rincon Diaz L M , Gonzalez Gomez A , Monteagudo Ruiz J M , Hinojar Baydes R , Moya Mur J L , Zamorano Gomez J L , Fernandez-Golfin C 
Published: October 2021

Abstract

Background
The management of patients with asymptomatic significant aortic regurgitation (sAR) is often challenging and appropriate timing of aortic valve surgery remains controversial. There are no strong indicators to recommend early surgery in patients with sAR, however delaying the time for the intervention could bring potential negative consequences, such as the risk of permanent left ventricular (LV) dysfunction. The prognostic value of diastolic parameters has been demonstrated in several cardiac diseases. In particular, left atrial (LA) function has been shown to be an important determinant of morbimortality.

Purpose
The purpose of this study was to analyze the prognostic significance of diastolic function parameters, included LA strain, in asymptomatic patients with sAR and to evaluate whether these parameters could help to identify patients at high risk of adverse events that could benefit from early cardiac surgery.

Methods
From February 2013 to November 2019 consecutive asymptomatic patients with chronic sAR evaluated in the Heart Valve Clinic with a comprehensive transthoracic echocardiogram (TTE) were included. Combined clinical endpoint included hospital admission due to heart failure, cardiovascular mortality, or indication for aortic valve surgery.

Results
A total of 126 patients were included. During a mean follow up of 33±19 month, 25 (19.8%) patients reached the combined end-point.
In a sub-group of 57 patients with TTE performed in the Philips stations, LA auto-strain analysis was obtained (figure 1).
Univariate analysis showed that LV volumes, LVEF, E wave, E/e' ratio, LA volume and LA reservoir strain (LASr) were significant predictors of events, whereas LA diameter, and LV diastolic diameters were not. Multivariate model 1 that tested all echocardiographic variables statistically significant in the univariate model showed that the LVEDV and E/e' ratio, were significant predictors of events. In the subgroup of patients with LA auto-strain analyzed, a second multivariable model was built, including the previous significant variables for the first model (LVEDV and E/e' ratio), as well as the LA volume and LASr. It showed that LVEDV and LASr were the most significant predictors of cardiovascular events (figure 2).

Conclusions
In this population of asymptomatic patients with sAR and normal LV systolic function, baseline diastolic parameters were prognostic markers of cardiovascular events; among them, LA reservoir strain played a strong independent predictor role. In addition, our results also showed that LV volumes had greater prognostic value that LV diameters in patients with asymptomatic sAR.

Funding Acknowledgement
Type of funding sources: None. Figure 1Figure 2
Aortic stenosis reexpanded – a novel approach to determine aortic valve area with phase contrast cardiovascular magnetic resonance imaging
Authors: Troger F , Lechner I , Reindl M , Tiller C , Holzknecht M , Pamminger M , Kremser C , Reinstadler S J , Bauer A , Metzler B , Mayr A , Klug G 
Published: October 2021

Abstract

Background
Transthoracic echocardiography (TTE) has become the diagnostic standard for evaluating aortic stenosis (AS) severity, mainly because of its advantages in comparison to the gold standard of cardiac catheterization. However, its inaccuracies in determining stroke volume (SV) and consequentially computing aortic valve area (AVA) call for a more precise and dependable method. Phase contrast cardiovascular magnetic resonance imaging (PC-CMR) is an aspiring tool to push these boundaries.

Purpose
The aim of this study was to validate a novel and simple approach based on PC-CMR against the invasive and echocardiographic determination of SV and AVA in patients with moderate and severe AS.

Methods
A total of 50 patients with moderate or severe AS underwent TTE, cardiac catheterization and CMR; AVA by PC-CMR was determined via plotting momentary flow across the valve against momentary flow velocity. SV via CMR was measured directly via PC-CMR and volumetrically using cine images. Invasive SV and AVA were determined via Fick principle and Gorlin formula, respectively. TTE yielded SV and AVA using the continuity equation. Finally, gradients were calculated via the modified Bernoulli equation.

Results
SV by PC-CMR showed a strong correlation with cine-CMR with no significant bias (r: 0.730, p&lt;0.001; SV by PC-CMR: 85±31ml; SV by cine-CMR: 85±19ml, p=0.829). Peak gradients determined by PC-CMR were 65±29mmHg and correlated inversely with AVA by PC-CMR (r: −0.371; p=0.008). Mean AVA during the whole systolic phase showed a moderate correlation (r: 0.544, p&lt;0.001) to invasive AVA with a small bias (AVA by CMR: 0.78±0.25cm2 versus invasive AVA: 0.70±0.23cm2, bias: 0.08cm2, p=0.017). Inter-methodical correlation and bias of AVA as measured by TTE and invasive AVA (AVA by TTE: 0.81±0.23cm2, r: 0.580, p&lt;0.001, bias 0.11cm2, p&lt;0.001) were similar to AVA by PC-CMR and invasive AVA.

Conclusion
PC-CMR provides a great option to yield reliable and solid SV values in patients with moderate and severe AS. Furthermore, continuous determination of flow volumes and flow velocities is able to determine AVA in these patients in an easy and reproducible manner. Our novel approach shines a light on the diagnostic potential of PC-CMR for non-invasive AS grading, especially in cases where echocardiography reaches its limits and where clinical findings appear inconclusive.

Funding Acknowledgement
Type of funding sources: None. Central IllustrationCine (l,r) and PC-CMR (m) images in AS
Normal values for paediatric atrial volumes assessed by steady-state free-precession cardiovascular magnetic resonance
Authors: Voges I , Hinz S , Caliebe A , Boroni Gracioli S , Wage R , Gabbert D , Uebing A , Krupickova S 
Published: October 2021

Abstract

Background
Measurement of atrial volumes by steady-state free precession (SSFP)cardiovascular magnetic resonance (CMR) is becoming increasingly important in the treatment and follow-up of paediatric congenital heart disease. It has prognostic value in terms of heart failure and cardiovascular death. However, CMR normal values for the clinically often used mono- and biplane area-length method in children are lacking.

Aims
We sought to create paediatric normal values for atrial volumes using the mono- and biplane area-length method.

Methods
In a retrospective study design, CMR data sets of 157 healthy children with an age range between 4 and 18 years from two centers in the UK and Germany were evaluated. In a four-chamber (4ch-) view, left and right atrial (LA, RA) endocardial borders were segmented during end-diastole and end-systole to calculate minimal and maximal atrial volumes (LAmin, LAmax, RAmin, RAmax) using the monoplane area-length method. Additionally, end-diastolic and end-systolic LA endocardial borders were segmented in a two-chamber (2ch-) view. Using the measurements from the 2ch- and 4ch-views, minimal and maximal LA volumes were calculated using the biplane area-length method. Atrial volumes were normalized for body surface area (BSA in m2). Sex-specific reference curves were created using the lambda mu sigma method.

Results
The median age was 13.8±2.81 years (53 girls).
In children from 4–10 years average atrial volumes measured: monoplane 4ch: LAmin 10.2±3.5 ml/m2, LAmax 28.8±7.4 ml/m2, RAmin 14.1±6.3 ml/m2, RAmax 27.0±11.4 ml/m2; monoplane 2ch: LAmin 10.9±4.1 ml/m2, LAmax 27.0±6.1 ml/m2; biplane: LAmin 10.2±3.3 ml/m2, LAmax 27.4±5.7 ml/m2.
In children from 11–18 years average atrial volumes measured: monoplane 4ch: LAmin 13.6±4.9 ml/m2, LAmax 34.1±9.1 ml/m2, RAmin 19.2±6.8 ml/m2, RAmax 34.2±9.6 ml/m2; monoplane 2ch: LAmin 13.2±4.9 ml/m2, LAmax 31.4±9.7 ml/m2; biplane: LAmin 12.9±4.4 ml/m2, LAmax 31.8±8.8 ml/m2.
Separate centile charts and centile tables for boys and girls for all volumetric parameters were created.

Conclusion
We provide paediatric CMR reference values for atrial volumes. They can be used in the diagnosis and follow-up of congenital or acquired heart disease in children and for research purposes.

Funding Acknowledgement
Type of funding sources: None.