bluuebunny/crossref_metadata_2025 huggingface dataset:
Effect of serum starvation on rheology of cell monolayers
Authors: Kiran Abhimanyu , Shekhar Chandra , Sabapathy Manigandan , Mishra Manoranjan , Kumar Lalit , Kumar Navin , Mehandia Vishwajeet
Published: July 2021

The rheological properties of cells and tissues are central to embryonic development and homeostasis in adult tissues and organs and are closely related to their physiological activities. This work presents our study of rheological experiments on cell monolayer under serum starvation compared to healthy cell monolayer with full serum. Serum starvation is one of the most widely used procedures in cell biology. However, the effect of deprivation of serum concentration on the material properties of cells is still unknown. Therefore, we performed macro-rheology experiments to investigate the effect of serum starvation on a fully confluent Madin–Darby Canine Kidney cell monolayer. The material properties, such as linear and non-linear viscoelastic moduli, of the monolayer, were measured using oscillatory shear experiments under serum-free [0% fetal bovine serum (FBS)] and full serum (10% FBS) conditions. Our results indicate that a serum-starved cell monolayer shows a different rheological behavior than a healthy cell monolayer. The loss and storage moduli decrease for the step-change in oscillatory strain amplitude experiments for a serum-starved cell monolayer and do not recover fully even after small deformation. In comparison, a healthy cell monolayer under full serum condition remains flexible and can fully recover even from a large deformation at higher strain. The effect of adhesion due to fibronectin was also studied in this work, and we found a significant difference in slip behavior for cell monolayer with and without serum.
Effective-medium-clad Bragg grating filters
Authors: Gao Weijie , Lee Wendy S. L. , Fumeaux Christophe , Withayachumnankul Withawat
Published: July 2021

We propose a series of integrated Bragg grating filters with performance enhancement via the concept of effective medium. The bandstop filters are built in a high-resistivity silicon wafer and operated over the WR-3.4 band (220–330 GHz) with in-plane polarization. The proposed designs use an additional degree of freedom in controlling the effective refractive index so as to fully use the potential of the Bragg grating structures. As a result, the high insertion loss typically observed at the low-frequency bound of the filters due to weak wave confinement can be reduced, while radiation caused by the leaky-wave effect at the high-frequency bound is minimized, allowing for a 40% operation fractional bandwidth. These features are not achievable with conventional waveguide Bragg grating filters. All-silicon prototypes of filter samples are experimentally validated, demonstrating promising performance for a wide range of terahertz applications. The techniques to improve the filter characteristics by controlling the effective medium can be adopted in both microwave and optics domains.
Real-time low-frequency oscillations monitoring
Authors: Hu Bin , Gharavi Hamid
Published: July 2021

A major concern for interconnected power grid systems is low-frequency oscillation, which limits the scalability and transmission capacity of power systems. Undamped or poorly damped oscillations will lead to undesirable conditions or even a catastrophic system blackout. Real-time synchrophasor data can be used to reliably detect and control these low-frequency oscillations in order to mitigate their catastrophic impact. In this paper, two low complexity tracking algorithms are proposed to identify and monitor low-frequency oscillations; namely, a fast subspace tracking algorithm and a gradient descent based fast recursive algorithm. Initially, both methods perform a one-time matrix pencil method on the power spectrum matrix of real-time Phasor Measurement Unit (PMU) data to detect low-frequency oscillations. This is then followed by two different low-complexity algorithms to fast track the low-frequency oscillations. While the first method uses a recursive fast data projection method-based algorithm, the latter runs a gradient-descent based fast recursive algorithm on every PMU to track and monitor low-frequency oscillations. Both methods have been compared to other state-of-the-art techniques, such as matrix pencil method, frequency domain decomposition, and TLS-ESPRIT. We have shown that the proposed approaches are capable of achieving performance with high accuracy, especially in terms of computational complexity for a large system with many PMUs.
Recent progress in stabilizing perovskite solar cells through two-dimensional modification
Authors: Zhi Chongyang , Li Zhen , Wei Bingqin
Published: July 2021

Tremendous progress has been made in lead halide perovskite solar cells (PSCs) with the record power conversion efficiency exceeding 25%. However, poor stability is the most significant obstacle hindering their practical applications. Therefore, improving stability becomes the primary focus of PSC research. Recently, a strategy of modifying the three-dimensional perovskite structures with hydrophobic organic cations for two-dimensional (2D) perovskites has been explored and proven beneficial for both PSC efficiency and stability. Herein, multi-dimensional tuning of the bulk and interfaces of perovskite materials and their influences on device performance and stability are reviewed. In addition, the effects of defect passivation and interface functionalization are discussed. Finally, the mechanisms of stability improvement through 2D modifications are discussed.
Electrical admittance-based evaluation of piezoelectric active sensor condition using k-nearest neighbors and least-squares regression
Authors: Jiang Xie , Zhang Xin , Zhang Yuxiang
Published: July 2021

In the electromechanical impedance-based health monitoring of structures, partial failure of piezoelectric lead zirconate titanate will result in signal changes, which may cause misjudgment of the structure state. Therefore, this paper proposes an evaluation method of the sensor condition based on k-nearest neighbors (kNNs) and least-squares regression (LSR) to make monitoring more reliable. After the analysis of the signal characteristics of three structural changes and four sensor faults, the principal components (PCs) of three indices are extracted by principal component analysis. Next, the kNN classifier is trained with the data represented by PCs and then tested by tenfold cross-validation. To determine the degree of sensor faults, LSR is used to fit the damage degree laws with multivariate nonlinear equations. The results show that the kNN model trained with three PCs has higher classification accuracy than the one trained with two PCs. The accuracy of the former reaches 100%. The R2 values of damage degree regressions of four sensor faults are all greater than 0.85, and the p-values are far less than 0.05, which denotes the effectiveness of the regression in the prediction of damage degree. This method has great application potential in evaluating sensor conditions accurately and quickly.
Microbe-dependent heterosis in maize
Authors: Wagner Maggie R. , Tang Clara , Salvato Fernanda , Clouse Kayla M. , Bartlett Alexandria , Vintila Simina , Phillips Laura , Sermons Shannon , Hoffmann Mark , Balint-Kurti Peter J. , Kleiner Manuel
Published: July 2021

Significance

Almost all grain crops grown on commercial farms are hybrid cultivars because these hybrid plants are reliably healthier, larger, and more productive than their inbred parent lines. The widespread and valuable phenomenon of hybrid superiority is called heterosis. Despite over a century of intensive research into heterosis, it is unclear how or why hybrid genomes give rise to superior phenotypes. Most hypotheses and research thus far have focused on genetic and physiological mechanisms of heterosis. In contrast, this article presents evidence for a microbe-driven mechanism of heterosis, whereby the activity of live soil microbes affects the expression of heterosis. This finding will open lines of research that could advance our understanding of heterosis.
Reward-specific satiety affects subjective value signals in orbitofrontal cortex during multicomponent economic choice
Authors: Pastor-Bernier Alexandre , Stasiak Arkadiusz , Schultz Wolfram
Published: July 2021

Significance

Ongoing consumption reduces the subjective value of rewards to different degrees depending on their individual properties, a phenomenon referred to as sensory-specific satiety. Such value change should be manifested in economic choices, and neuronal signals for subjective economic reward value should be sensitive to reward-specific satiety. We tested monkeys during the choice between two options that each contained two different rewards (“bundles”); the two rewards were prone to different degrees of satiety. Ongoing reward consumption affected choices in a way that indicated satiety-induced reward-specific change of subjective economic value. Neuronal responses in the monkey orbitofrontal cortex (OFC) followed the differential reduction of subjective economic value. These results satisfy a crucial requirement for subjective reward value coding in OFC neurons.
Active liquid crystals powered by force-sensing DNA-motor clusters
Authors: Tayar Alexandra M. , Hagan Michael F. , Dogic Zvonimir
Published: July 2021

Significance

Single-molecule techniques have elucidated how isolated molecular motors generate piconewton forces with unprecedented detail. However, in diverse biological and synthetic settings, force-generating proteins collectively power nonequilibrium dynamics, including continuous large-scale rearrangements and persistent fluid flows. Characterizing motor-generated forces in these dense and dynamical environments remains a challenge. We assembled a reversible DNA-based force-sensing probe that, by an optical readout, reveals the molecular arrangements and the force loads experienced by kinesin motors. These probes provide insight into motor-generated forces that collectively power the unique dynamics of microtubule-based active nematics, a noteworthy example of an internally driven active matter system. DNA-based force probes can be extended to study forces and stresses in various synthetic systems as well as diverse cellular environments.
Grain boundary formation through particle detachment during coarsening of nanoporous metals
Authors: Elder Kate L. M. , Andrews W. Beck , Ziehmer Markus , Mameka Nadiia , Kirchlechner Christoph , Davydok Anton , Micha Jean-Sébastien , Chadwick Alexander F. , Lilleodden Erica T. , Thornton Katsuyo , Voorhees Peter W.
Published: July 2021

Significance

Nanoporous metals are prototypical bicontinuous structures that have a large surface area and many applications. We demonstrate that an in-grain orientation spread develops during coarsening in nanoporous metals, leading to the formation of a nanocrystalline–nanoporous structure. The process of particles detaching and reattaching as the structure coarsens is identified as a mechanism of grain boundary formation. Coarsening the structure results in significant particle detachment with detachment rates that vary drastically with changes in the volume fraction and volume fraction inhomogeneities in the nanostructure. These results demonstrate that particle detachment must be understood to have full control of the nanocrystalline–nanoporous structure and improve material properties.
Corrigendum: A Simple Monte Carlo Simulation For the Two Dimensional Attractive Hubbard Model (2020 Journal of Physics: Conf. Series 1483 012002)
Authors: Correa Eberth , Rodrigues R. G. M. , Mόl L. A. S. , Costa B. V.
Published: July 2021

Please see Article PDF for corrigendum text.
Effects of lightning strokes on underground gravitational waves observatories
Authors: Washimi T. , Yokozawa T. , Nakano M. , Tanaka T. , Kaihotsu K. , Mori Y. , Narita T.
Published: July 2021

For ground-based gravitational wave (GW) detectors, lightning strokes in the atmosphere are sources of environmental noise.
Some GW detectors are built or planned in underground facilities, and knowledge of how lightning strokes affect them is of interest.
In this paper, the lightning detection system in KAGRA is introduced, and the properties of the magnetic field measured inside and outside the KAGRA tunnel are shown.
One lightning-induced event in the GW channel of the KAGRA main interferometer is also showed.
Finally, possible applications of lightning events for the GW experiments are discussed.
Quenching factor measurements of sodium nuclear recoils in NaI:Tl determined by spectrum fitting
Authors: Bignell L.J. , Mahmood I. , Nuti F. , Lane G.J. , Akber A. , Barberio E. , Baroncelli T. , Coombes B.J. , Dix W. , Dowie J.T.H. , Eriksen T. , Gerathy M.S.M. , Gray T.J. , McCormick B.P. , Mitchell A.J. , Rahman M.S. , Scutti F. , Spinks N.J. , Stuchbery A.E. , Timmers H. , Urquijo P. , Wang L. , Zhong Y.Y. , Zurowski M.J.
Published: July 2021

We have performed measurements of sodium nuclear recoils in NaI:Tl crystals, following scattering by neutrons produced in a 7Li(p,n)7Be reaction. Understanding the light output from such recoils, which is reduced relative to electrons of equivalent energy by the quenching factor, is critical to interpret dark matter experiments that search for nuclear scattering interactions. We have developed a spectrum-fitting methodology to extract the quenching factor from our measurements, and report quenching factors for nuclear recoil energies between 36 and 401 keV. Our results agree with other recent quenching factor measurements that use quasi-monoenergetic neutron sources. The new method will be applied in the future to the NaI:Tl crystals used in the SABRE experiment.
Preparation and properties of MDA-BAPP-BTDA copolyimide/18-crown ether-6 supramolecular films with inclusion structure and ultralow dielectric constants
Authors: Xiao Chunguang , Li Duxin , Lang Feng , Xiang Yu , Lin Yi , Ou Baoli
Published: July 2021

In order to obtain polyimide composites with ultra-low dielectric constant, a series of MDA-BAPP-BTDA copolyimides/18-crown ether-6 (CPI/18-CE) supramolecular films with inclusion structure were prepared. The effects of 18-CE on CPI’s thermal, mechanical, dielectric and water absorption properties were investigated. The inclusion rate of 18-CE to CPI backbone was ∼50%. The introduction of 18-CE slightly reduced the thermal properties of CPI/18-CE supramolecular films, but greatly improved their mechanical, dielectric and hydrophobic properties. The tensile strength, young’s modulus and elongation at break of CPI/18-CE supramolecular films were maximally increased by 21.8%, 34.1% and 92.9% respectively. Meanwhile their dielectric constant, dielectric loss and water absorption were as low as 2.10, 0.007 and 0.63%, respectively. In summary, CPI/18-CE supramolecular films possess excellent dielectric properties and broad application prospect in the field of microelectronics.
Algebraic degree in spatial matricial numerical ranges of linear operators
Authors: Bernik J. , Livshits L. , MacDonald G. , Marcoux L. , Mastnak M. , Radjavi H.
Published: July 2021

We study the maximal algebraic degree of principal ortho-compressions of linear operators that constitute spatial matricial numerical ranges of higher order. We demonstrate (amongst other things) that for a (possibly unbounded) operator

L
L

on a Hilbert space, every principal

m
m

-dimensional ortho-compression of

L
L

has algebraic degree less than

m
m

if and only if

r
a
n
k
(
L
−
λ
I
)
≤
m
−
2

rank(L-\lambda I)\le m-2

for some

λ
∈

C

\lambda \in \mathbb {C}

.
SPOT: a web-tool enabling swift profiling of transcriptomes
Authors: Farr Elias B , Sattler Julia M , Frischknecht Friedrich
Published: July 2021

The increasing number of single cell and bulk RNAseq datasets describing complex gene expression profiles in different organisms, organs or cell types calls for an intuitive tool allowing rapid comparative analysis. Here, we present Swift Profiling Of Transcriptomes (SPOT) as a web tool that allows not only differential expression analysis but also fast ranking of genes fitting transcription profiles of interest. Based on a heuristic approach the spot algorithm ranks the genes according to their proximity to the user-defined gene expression profile of interest. The best hits are visualized as a table, bar chart or dot plot and can be exported as an Excel file. While the tool is generally applicable, we tested it on RNAseq data from malaria parasites that undergo multiple stage transformations during their complex life cycle as well as on data from multiple human organs during development and cell lines infected by SARS-CoV-2. SPOT should enable non-bioinformaticians to easily analyse their own and any available dataset.

Availability and implementation

SPOT is freely available for (academic) use at: https://frischknechtlab.shinyapps.io/SPOT/ and https://github.com/EliasFarr/SPOT.

Supplementary information

Supplementary data are available at Bioinformatics online.
Systematic reporting of medical kidney biopsies
Authors: Leh Sabine , Dendooven Amélie
Published: July 2021

The medical kidney biopsy has an important added value in patient care in nephrology. In order to facilitate communication between the pathologist and the nephrologist and optimize patient care, both the content and form of the medical kidney biopsy report matter. With some exceptions, current guidelines in nephropathology focus on content rather than form and, not surprisingly, medical kidney biopsy reports mostly consist of unformatted and often lengthy free text. In contrast, in oncology, a more systematic reporting called synoptic reporting has become the dominant method. Synoptic formats enable complete, concise and clear reports that comply with agreed upon standards. In this review we discuss the possibilities of systematic reporting in nephropathology (including synoptic reporting). Furthermore, we explore applications of electronic formats with structured data and usage of international terminologies or coding systems. The benefits include the timely collection of high-quality data for benchmarking between centres as well as for epidemiologic and other research studies. Based on these developments, a scenario for future medical kidney biopsy reporting is drafted.
Orientation of the right superior pulmonary vein affects outcome after pulmonary vein isolation
Authors: Vecsey-Nagy M , Szegedi N , Simon J , Szilveszter B , Kolossvary M , Boussoussou M , Vattay B , Delgado V , Jeroen B , Maurovich-Horvat P , Merkely B , Geller L
Published: July 2021

Funding Acknowledgements

Type of funding sources: None.

Aims

Controversial results have been published regarding the influence of pulmonary vein (PV) anatomical variations on outcomes after pulmonary vein isolation (PVI). However, no data is available on the impact of PV orientation on the long-term success rates of point-by-point PVI. We sought to determine the impact of PV anatomy and orientation on atrial fibrillation (AF)-free survival in patients undergoing PVI using the radiofrequency point-by-point technique.

Methods and results

We retrospectively included 448 patients who underwent initial point-by-point radiofrequency ablation for AF at our department. Left atrial CT-angiography (CTA) was performed before each procedure. PV anatomical variations, ostial parameters (area, effective diameter and eccentricity), orientation and their associations with 24-month AF-free survival were analyzed. PV anatomical variations and ostial parameters were not predictive for AF-free survival (all p > 0.05). Univariate analysis showed that female sex (p = 0.025) was associated with higher rates of AF recurrence, ventral-caudal (p = 0.002), dorsal-cranial (p = 0.034) and dorsal-caudal (p = 0.042) orientation of the right superior PV (RSPV), on the other hand, showed an association with lower rates of AF recurrence, as compared to the reference ventral-cranial orientation. On multivariate analysis, both female sex [odds ratio(OR) 1.83, 95% CI 1.15-2.93, p = 0.011] and ventral-caudal RSPV orientation, compared with ventral-cranial orientation, proved to be independent predictors of 24-month AF recurrence (OR 0.37, 95% CI 0.19-0.71, p = 0.003).

Conclusion

  Female sex and ventral-caudal RSPV orientation have an impact on long-term arrhythmia-free survival. Assessment of PV orientation may be a useful tool in predicting AF-free survival and may contribute to a more personalized management of AF.
Characterization of apolipoprotein E-deficient rats as novel model for atherosclerosis imaging
Authors: Sijbesma JWA , Van Waarde A , Kristensen S , Kion I , Tietge UJF , Hillebrands JL , Buikema H , Nakladal D , Liu F , Boersma HH , Dierckx RAJO , Slart RHJA
Published: July 2021

Funding Acknowledgements

Type of funding sources: None.

Background

The apolipoprotein E-deficient (apoE-/-) mouse is a well-established atherosclerotic model with impaired lipoprotein clearance and development of vessel plaques. However, the small size of the mouse limits its use as an animal model in longitudinal positron emission tomography (PET) imaging studies of atherosclerosis. Recently, apoE-/- rats have become available. This study addresses the suitability of the apoE-/- rat as model for atherosclerotic PET imaging.

Methods

Ten male apoE-/- rats and ten male control rats (apoE+/+) (age 10+/-1 weeks), each fed with a Western diet, were injected at baseline week 4, 12, 26 and 51, with 60 MBq of [18F]2-fluoro-2-deoxy-D-glucose. Plasma cholesterol, body weight and fat were measured. 3h after injection, a computed tomography (CT) and a 20-min PET scan were made. After the final scan, aortic tissue was collected for histological staining.

Results

Cholesterol levels started to increase after 4 weeks in the apoE-/- rats, whereas in the apoE+/+ rats levels stayed stable. Body weight and body fat increased more rapidly in the apoE-/- rats but were similar in both strains at the end of the study. SUVmean and max in the aortic arch and abdominal aorta were significantly higher (p < 0.001) in apoE-/- versus apoE+/+ rats at weeks 12, 26 and 51. Oil red O staining showed lesions in 20.0 % of the surface of the aortic arch in the apoE-/- rats. Hardly no fatty streaks were detected in the apoE+/+ rats (2.29%). More histology data is being analyzed.

Conclusion

Plasma cholesterol levels were elevated in apoE-/- rats. PET imaging demonstrated differences in [18F]-FDG uptake in the aortic arch and abdominal aorta after 12, 26 and 51 weeks. Combined, these data demonstrate that apoE-/- rats represent a useful preclinical model for the non-invasive assessment of atherosclerosis in longitudinal studies.
Inter-operator reliability of an onsite machine learning-based prototype to estimate CT angiography-derived fractional flow reserve
Authors: Han Y , Ahmed AI , Schwemmer C , Cocker M , Alnabelsi T , Ramirez-Giraldo JC , Al Rifai M , Nabi F , Chang SM , Al-Mallah MH
Published: July 2021

Funding Acknowledgements

Type of funding sources: None.

Background

Advances in computed tomography (CT) and machine learning have enabled on-site non-invasive assessment of fractional flow reserve (ML-FFRCT). However, reproducibility of measurements across operators is not well demonstrated.

Purpose

This study was designed to measure the inter-operator variability and reproducibility of Coronary CT Angiography–derived fractional flow reserve values using a post-processing prototype based on a machine learning algorithm (ML-FFRCT).

Methods

We included 60 symptomatic patients who underwent coronary CT angiography. FFRCT was calculated by 2 independent operators after training using a machine learning based on-site prototype. FFRCT was measured 1 cm distal to the coronary plaque or in the middle of the segments if no coronary lesions were present.  Intraclass correlation coefficient (ICC) and Bland-Altman analysis were used to evaluate inter-operator variability effect in FFRCT estimates. Sensitivity analysis was done by cardiac risk factors, degree of stenosis and image quality.

Results

A total of 535 coronary segments in 60 patients were assessed. The overall ICC was 0.986 per patient (95% CI: 0.977 - 0.992) and 0.972 per segment (95% CI: 0.967 - 0.977). The absolute mean difference in FFRCT estimates was 0.012 per patient (95% CI for limits of agreement: -0.035 - 0.039) and 0.02 per segment (95% CI for limits of agreement: -0.077 - 0.080). Tight limits of agreement were seen on Bland-Altman analysis. Distal segments had greater variability compared to proximal/mid segments (absolute mean difference 0.011 vs 0.025, p < 0.001). Sensitivity analysis showed similar results across degrees of stenosis, image quality and those with cardiac risk factors such as hypertension, diabetes and dyslipidemia.

Conclusion

A high degree of inter-operator reproducibility can be achieved by onsite machine learning based ML-FFRCT assessment. Future research is required to evaluate the physiological relevance and prognostic value of ML-FFRCT.
Stress only myocardial perfusion imaging - comparison of hospitalized and outpatient patients
Authors: Stalc M , Dolenc Novak M , Saric S , Strojnik M , Guzic Salobir B
Published: July 2021

Funding Acknowledgements

Type of funding sources: None.

Background

In selected patients, stress-only myocardial perfusion imaging (MPI) has been proposed as an alternative to rest-stress MPI to reduce radiation exposure and enhance laboratory efficiency. The use of attenuation correction improves the diagnostic accuracy of stress-only imaging.  However, criteria for selecting appropriate patients for stress-first imaging protocol are not uniform. There is limited data about stress-only MPI in hospitalized patients. 

The purpose of this study was to compare the proportion of suitable hospitalized and outpatient patients with normal MPI on a routine two-day protocol for stress-only MPI.

Methods

In a retrospective longitudinal cohort study, stress scintigrams (with and without attenuation correction) of consecutive hospitalized and outpatient patients who underwent MPI at our department by a routine two-day protocol and had a normal MPI were visually and semi-quantitatively re-examined. Patients with summed stress score 0 or 1 were considered as candidates for stress-only MPI. We also obtained data on the patients" clinical characteristics and their treatment.

Results

We studied 178 patients (mean age 68.8 ± 13.4 years, 89 hospitalized, 89 outpatient patients, 55.6 % female). Hospitalized patients were significantly older than outpatient participants (72.4 ± 13.0 vs. 65 ± 12.9 years, p < 0.001) with no significant differences in risk factors and clinical characteristics. Proportion of inpatients and outpatients suitable for stress-only MPI with and without attenuation correction is shown on Figure 1. There was no significant difference in stress-only MPI with and without attenuation correction between hospitalized and outpatient patients (Figure 1). 9.1% of patients in whom stress only MPI was possible had known coronary artery disease, whereas it was present in 25.0% of patients in whom stress-only MPI was not possible (p = 0.004). By using attenuation correction stress-only MPI could be performed in 54% of patients without known coronary artery disease. There was no difference between hospitalized patients and outpatients (52% vs. 56%, p = 0.700). Absence of coronary artery disease turned out as the only independent prognostic factor for application of stress-only MPI (odds ratio 3.433, 95% confidence interval 1.44-8.17, p = 0.003). There was no influence of hospitalization on the application of stress-only MPI.

Conclusions

When we choose the right patients (especially those without a known coronary artery disease) and use modern cameras that enable attenuation correction, we can perform stress-only MPI in 50% of patients with a normal MPI result. The same approach can be used for outpatients and inpatients.
INOCA: Unraveling the pathophysiological mechanisms, non-invasively
Authors: Gobbo MY , Meretta AH , Sciancalepore MA , Rosa D , Corneli M , Blanco N , Retamozo E , Beber E , Coronel DS , Perez Balino NA , Masoli OH
Published: July 2021

Funding Acknowledgements

Type of funding sources: None.

Introduction

INOCA syndrome (Ischemia with Non-Obstructive Coronary Arteries) is an increasingly frequent finding. One of the proposed causes is microvascular dysfunction (MVD). CZT-SPECT systems quantifies myocardial blood flow (MBF) during rest and after hyperemia. Dipyridamole induced hyperemia is considered endothelium independent whereas cold pressor test (CPT) endothelium dependent. Using both stimuli vasomotor response of endothelium can be evaluated through the analysis of MBF relationship (MBFR): MBF during induced hyperemia/MBF rest.

Objectives

To determine the prevalence of microvascular dysfunction in patients with INOCA, through the analysis of non-invasive evaluation MBFR with dipyridamole and CPT.

Methods

Dynamic and myocardial perfusion imaging at rest, after dipyridamole (0,56 mg/kg i.v. in 4 minutes) and CPT (hand immersion during 2 minutes in 4ºC cold water) were performed in 45 patients with INOCA history of using CZT-SPECT system.  

A MBFR less than 2 was considered abnormal to dipyridamole induced hyperemia and less than 1.5 to CPT induced hyperemia.

The presence of an abnormal dipyridamole or CPT MBFR was considered as MVD.

Patients with MVD were divided into two groups

Group 1: normal dipyridamole MBFR and abnormal CPT MBFR.

Group 2: abnormal dipyridamole MBFR and abnormal CPT MBFR.

Comparison between variables were made with Wilcoxon signed rank test.

Results

The median age was 59 (32-78) years. Thirty-two patients (71%) were women and the majority (n = 29) were in the menopausal period. The cardiovascular risk factors present were: type 2 diabetes mellitus (n = 4), arterial hypertension (n = 21), smoking (n = 18) and dyslipidemia (n = 25).

All patients had normal myocardial perfusion at rest and with both stresses.

Thirty-nine patients (87%) presented MVD, 24 (54%) were in the group 1 and 15 (33%) in group 2. (Table 1)

Conclusion

The prevalence of MVD was 87 % in patients with INOCA.The use of both stresses made it possible to evaluate different pathophysiological mechanisms of MVD, dependent on smooth muscle and dependent on the endothelium.

Evaluation with CPT should be included in INOCA patients because MVD may be present even with preserved MBFR using dipyridamole.
Scintigraphic and echocardiographic evaluation of patients with cardiac transthyretin amyloidosis and first-degree relatives
Authors: Holcman K , Rubis P , Szot W , Graczyk K , Stepien A , Lesniak-Sobelga A , Hlawaty M , Wisniowska-Smialek S , Dziewiecka E , Karabinowska A , Mroz K , Podolec P , Kostkiewicz M
Published: July 2021

Funding Acknowledgements

Type of funding sources: Other. Main funding source(s): Pfizer Research Grant (ID#57165999)

Background

Misfolding of transthyretin (TTR) is the source of two distinct forms of amyloidosis (ATTR): acquired or wild-type (ATTRwt) and hereditary (ATTRm), which is transmitted in an autosomal dominant inheritance with a variable penetrance.  Types of transthyretin (TTR) gene mutations display genetic and ethnic variability.

Purpose

The aim of this prospective study was to assess the TTR gene variants, echocardiographic parameters and regional left ventricle 99mTc-DPD uptake among patients with ATTR and first-degree relatives.

Methods

We present data based on evaluation of first 25 patients (13 (52%) females), including 10 (40%) index patients with ATTR (age 66.4 ± 13 years) and 15 (60%) first-degree relatives who were studied between June 2020 and February 2021. Analysis included clinical data, free light chain blood immunoglobulins and urine immunofixation, transthoracic echocardiography (TTE) with global longitudinal strain (GLS) analysis, single-photon emission computed tomography (SPECT) with 3,3-disphono-1,2-propanodicarboxylic acid (DPD), genetic testing by an amplicon-based next-generation TTR sequencing approach, and in selected cases cardiac or soft tissue biopsy.

Results

Overall, 6 index patients were diagnosed with ATTRm and 4 with ATTRwt presenting mixed, cardiac or neuropathic phenotype. There were detected following types of TTR variants - Phe53Leu, Ala101Val, Glu112Lys, Glu109Lys. Nine out of 10 index patients were diagnosed with amyloid cardiomyopathy (CA) with grade 2-3 tracer uptake in SPECT and symptomatic heart failure (NYHA 2.2 ± 1.1; NT-proBNP value 2224 ± 2799 pg/ml). In both ATTRm and ATTRwt there were patients presenting with either focal or diffuse tracer pattern evaluated by SPECT technique. In TTE there was marked left ventricle (LV) hypertrophy with maximum wall thickness of 22 ± 5 mm and LV mass value index value of 382 ± 111 g/m2. All patients with CA had abnormal global longitudinal strain (GLS, -14.5 ± 5%) and diastolic dysfunction (EA 1.56 ± 0.76, E/E’ 16 ± 11). None of relatives expressed tracer uptake in scintigraphy. Overall, 5 first-degree relatives were diagnosed with Phe53Leu variant, among them two patients presented with decreased GLS value.

Conclusions

Patients with ATTR presented in TTE with LV hypertrophy, decreased GLS value, diastolic dysfunction and grade 2-3 in scintigraphy with either focal or diffuse tracer uptake in SPECT technique. None of first-degree relatives expressed increased tracer uptake in scintigraphy. However, some of relatives who were diagnosed with pathogenic TTR variant presented with decreased GLS value.
A 7-year warranty period for chest pain patients with a non-ischaemic [15O]H2O positron emission tomography: a follow-up of 273 individuals
Authors: Jukema RA , Diemen Van PA , Driessen RS , Stuijfzand J , Raijmakers PG , Winter De RW , Ven Van De PM , Rossum Van AC , Knaapen P , Danad I
Published: July 2021

Funding Acknowledgements

Type of funding sources: None.

Background

  A normal perfusion scan is associated with a favourable outcome. The aim of the present study is to determine the warranty period of normal hyperemic myocardial blood flow (MBF) derived with quantitative [15O]H2O positron emission tomography (PET) in symptomatic individuals with cardiovascular risk factors. 

Methods

A total of 539 patients referred for baseline adenosine [15O]H2O PET MBF imaging because of suspected coronary artery disease (CAD) were investigated. A PET scan was considered normal if the hyperemic MBF  was > 2.3 ml/min/g.  The warranty period was predefined as < 2% annual event rate. The primary endpoint was a composite of late revascularizations, myocardial infarction and all-cause mortality.  

Results

In a total of 273 patients (mean age 57.2 ± 9.1; 34.4% male) with a normal PET scan, 19 events occurred during a median follow-up of 6.8 years (interquartile range 4.9-7.7).  Events included 10 late revascularizations, 2 myocardial infarctions and 7 deaths. The annual event rate exceeded 2% in the 8th year of follow-up, resulting in a warranty period of 7 years  (see Figure 1). 

Conclusion

In patients referred for suspected CAD a normal hyperemic perfusion derived by [15O]H2O PET confers a 7-year warranty period against late revascularization, myocardial infarction and all-cause mortality.
[18F]FDG hypermetabolisms of the spleen and/or bone marrow: indirect signs of bacteremia
Authors: Zanca R , Bartoli F , Lazzeri E , Sollini M , Slart RHJA , Erba PA
Published: July 2021

Funding Acknowledgements

Type of funding sources: None.

Aim

Recently hypermetabolisms of the spleen and/or bone marrow has been proposed as an indirect sign of infective endocarditis (IE), useful to reinforce the suspicion of IE in the absence of any other infectious, inflammatory, or malignant disease. The purpose of this study is to determine whether hypermetabolisms of the spleen and/or bone marrow are indirect signs of bacteremia rather than of IE, specifically.

Materials and Method

In this work we retrospectively evaluated a series 240 patients who performed between January 2015 to December 2020 [18F]FDG PET/CT (Discovery 710 GE) for suspected infection. In particular, 80 pts had infections from different origin and a positive blood culture (PBC), 80 pts presented localized infection, but negative blood culture (IDBCN) and 80 pts were classified as definite IE (IED) according to the 2015 ESCcriteria. [18F]FDG SUVmax SUVmean in bone marrow, spleen and liver were measured drawind a 14 cm3 regions of interest (ROIs) positioned close to the centers of the spleen and of the right liver lobe, but excluding abscess and/or ischemic lesions., as previously described (Caroline Boursier et al. ; Jordy P.Pijl et al.). BM SUVmax and SUVmean was obtained from ROIs placed on the bodies of each of the five lumbar vertebrae, excluding any damaged vertebra. BM to liver SUV ratios (BLR) and spleen to liver SUV ratios (SLR) were calculated. Kruskal-Wallis tests and the Dunn’s test procedure for multiple comparison were performed using JMP Statistical Discoverytm.

Results

No significant difference among the three groups of SUVmax/mean or in SLR were found. Nevertheless, by grouping patients for the presence of positive blood culture (142 pts) or negative blood culture (98 pts), irrespectively from the final diagnosis a significant associations of SLR was found (p = 0.0070). No significant associations were found with BLR.

Conclusions

Based on our data SLR in seems to represent an indirect signs of bacteremia, rather than IE.
Longitudinal Associations Between Discrimination, Neighborhood Social Cohesion, and Telomere Length: The Multi-Ethnic Study of Atherosclerosis
Authors: Hailu Elleni M , Lewis Tené T , Needham Belinda L , Lin Jue , Seeman Teresa E , Mujahid Mahasin S
Published: July 2021

Background

We aimed to examine if neighborhood social cohesion moderated longitudinal associations between baseline reports of discrimination and 10-year changes in leukocyte telomere length (LTL).

Methods

Data are from the Multi-Ethnic Study of Atherosclerosis (N = 1064; age range 45–84 years). Baseline discrimination was measured using the Major Experiences of Discrimination Scale (MDS; none, 1 domain, ≥2 domains) and the Experiences of Discrimination Scale (EDS; none, moderate, high). Neighborhood social cohesion at baseline was assessed via a community survey within census tract–defined neighborhoods. 10-year change in LTL was defined as regression to the mean-corrected 10-year difference in the ratio of telomeric DNA to a single-copy gene (T/S).

Results

In linear mixed-effects models, we found that neighborhood social cohesion modified the effect of baseline reports of MDS on 10-year changes in LTL, independent of sociodemographic characteristics, health behaviors, and health conditions (p(χ 2) = .01). Among those residing in neighborhoods with low social cohesion, experiencing major discrimination in ≥2 domains was associated with faster LTL attrition over 10 years, compared to reporting no discrimination (β = −0.03; 95% confidence interval: −0.06, −0.003). We found no main associations for either discrimination measure and no interaction between EDS and neighborhood social cohesion.

Conclusions

Results indicate that neighborhood social cohesion is an important dimension of the neighborhood context that may moderate the impact of major experiences of discrimination on telomere length attrition. These findings help advance our understanding of the integral role that neighborhood environments play in attenuating the effect of discrimination on accelerated cell aging.
Accelerated deciphering of the genetic architecture of agricultural economic traits in pigs using a low-coverage whole-genome sequencing strategy
Authors: Yang Ruifei , Guo Xiaoli , Zhu Di , Tan Cheng , Bian Cheng , Ren Jiangli , Huang Zhuolin , Zhao Yiqiang , Cai Gengyuan , Liu Dewu , Wu Zhenfang , Wang Yuzhe , Li Ning , Hu Xiaoxiang
Published: July 2021

Background

Uncovering the genetic architecture of economic traits in pigs is important for agricultural breeding. However, high-density haplotype reference panels are unavailable in most agricultural species, limiting accurate genotype imputation in large populations. Moreover, the infinitesimal model of quantitative traits implies that weak association signals tend to be spread across most of the genome, further complicating the genetic analysis. Hence, there is a need to develop new methods for sequencing large cohorts without large reference panels.

Results

We describe a Tn5-based highly accurate, cost- and time-efficient, low-coverage sequencing method to obtain 11.3 million whole-genome single-nucleotide polymorphisms in 2,869 Duroc boars at a mean depth of 0.73×. On the basis of these single-nucleotide polymorphisms, a genome-wide association study was performed, resulting in 14 quantitative trait loci (QTLs) for 7 of 21 important agricultural traits in pigs. These QTLs harbour genes, such as ABCD4 for total teat number and HMGA1 for back fat thickness, and provided a starting point for further investigation. The inheritance models of the different traits varied greatly. Most follow the minor-polygene model, but this can be attributed to different reasons, such as the shaping of genetic architecture by artificial selection for this population and sufficiently interconnected minor gene regulatory networks.

Conclusions

Genome-wide association study results for 21 important agricultural traits identified 14 QTLs/genes and showed their genetic architectures, providing guidance for genetic improvement harnessing genomic features. The Tn5-based low-coverage sequencing method can be applied to large-scale genome studies for any species without a good reference panel and can be used for agricultural breeding.
M2aia—Interactive, fast, and memory-efficient analysis of 2D and 3D multi-modal mass spectrometry imaging data
Authors: Cordes Jonas , Enzlein Thomas , Marsching Christian , Hinze Marven , Engelhardt Sandy , Hopf Carsten , Wolf Ivo
Published: July 2021

Background

Mass spectrometry imaging (MSI) is a label-free analysis method for resolving bio-molecules or pharmaceuticals in the spatial domain. It offers unique perspectives for the examination of entire organs or other tissue specimens. Owing to increasing capabilities of modern MSI devices, the use of 3D and multi-modal MSI becomes feasible in routine applications—resulting in hundreds of gigabytes of data. To fully leverage such MSI acquisitions, interactive tools for 3D image reconstruction, visualization, and analysis are required, which preferably should be open-source to allow scientists to develop custom extensions.

Findings

We introduce M2aia (MSI applications for interactive analysis in MITK), a software tool providing interactive and memory-efficient data access and signal processing of multiple large MSI datasets stored in imzML format. M2aia extends MITK, a popular open-source tool in medical image processing. Besides the steps of a typical signal processing workflow, M2aia offers fast visual interaction, image segmentation, deformable 3D image reconstruction, and multi-modal registration. A unique feature is that fused data with individual mass axes can be visualized in a shared coordinate system. We demonstrate features of M2aia by reanalyzing an N-glycan mouse kidney dataset and 3D reconstruction and multi-modal image registration of a lipid and peptide dataset of a mouse brain, which we make publicly available.

Conclusions

To our knowledge, M2aia is the first extensible open-source application that enables a fast, user-friendly, and interactive exploration of large datasets. M2aia is applicable to a wide range of MSI analysis tasks.
From clinical trials to clinical practice: How long are drugs tested and then used by patients?
Authors: Yuan Chi , Ryan Patrick B , Ta Casey N , Kim Jae Hyun , Li Ziran , Weng Chunhua
Published: July 2021

Objective

Evidence is scarce regarding the safety of long-term drug use, especially for drugs treating chronic diseases. To bridge this knowledge gap, this research investigated the differences in drug exposure between clinical trials and clinical practice.

Materials and Methods

We extracted drug follow-up times from clinical trials in ClinicalTrials.gov and compared the difference between clinical trials and real-world usage data for 914 drugs taken by 96 645 927 patients.

Results

A total of 17.5% of drugs had longer median exposure in practice than in trials, 6% of patients had extended exposure to at least 1 drug, and drugs treating nervous system disorders and cardiovascular diseases were the most common among drugs with high rates of extended exposure.

Conclusions

For most of patients, the drug use length is shorter than the tested length in clinical trials. Still, a remarkable number of patients experienced extended drug exposure, particularly for drugs treating nervous system disorders or cardiovascular disorders.
Determination of β-Galactooligosaccharides (GOS) in Infant Formula and Adult Nutritionals: Single-Laboratory Validation, First Action 2021.01
Authors: Cuany Denis , Andetsion Fikrey , Fontannaz Xavier , Bénet Thierry , Spichtig Véronique , Austin Sean
Published: July 2021

Background

β-Galactooligosaccharides (GOS) are typically used in infant formula and adult nutritionals as a source of nondigestible oligosaccharides, which may bring beneficial effects through modulation of the gut microbiota. However, suitable methods for the determination of GOS in products with a high background of lactose do not exist.

Objective

The aim of this work was to develop a method suitable for the determination of GOS in infant formula and adult nutritionals and demonstrate suitability through single laboratory validation.

Methods

Reducing oligosaccharides are labeled with 2-aminobenzamide (2AB), separated by hydrophilic interaction LC, and determined assuming that all oligosaccharides give an equimolar response in the detector. The same sample is analyzed a second time after treatment with β-galactosidase to remove GOS. The difference in the determined oligosaccharides between the two measurements will be the GOS content of the sample. The method was validated in a single laboratory on infant formula and adult nutritionals.

Results

Recoveries were in the range 91.5–102%, relative standards of deviation (RSDr) were in the range 0.7–5.99%, and one sample had an RSDr of 8.30%. Except for the one sample with an RSDr of 8.30%, the performance is within the requirements outlined in the Standard Method Performance Requirements, which specifies recoveries in the range 90–110% and RSDr of below 6%.

Conclusions

The method is suitable for the determination of GOS in infant formula and adult nutritionals.

Highlights

A method has been developed which is suitable for the determination of GOS in products with a high background concentration of lactose (infant fromula and adult nutritionals). The method does not require access to the GOS ingredient used for the production of the finished product. It is also possible to separately quantify the amount of GOS containing three or more monomeric units in order to support dietary fibre analysis.