bluuebunny/crossref_metadata_2025_split huggingface dataset:
CRISPR/Cas9 and Anther Culture for Precision Double Haploid Line Production in Controlled Environments
Authors: Sharma Avinash , Pandey Himanshu , Misra Varucha , Kumar Rajeev , Vashishth Amit , Devadas V. S. , Mall A. K. , Ashutosh  , Raghvan Megha , Kesavan Ajith Kumar , Chaturvedi Vishva Deepak 
Published: October 2024

ABSTRACTThe development of mapping populations and quantitative trait loci (QTL) analysis face constraints, in crops exhibiting male sterility and self‐incompatibility under field conditions. Addressing these challenges requires the integration of advanced techniques, including the temporal alteration or excision of centromere histone H3 (CENH3) protein and the use of gene editing tools such as MATRILINEAL (MTL) knockout. Specifically, this can be achieved through Cas9/gRNA‐mediated mutagenesis or Cas9/gRNA‐driven promoter expression systems. These technologies offer efficient means to advance mapping populations and QTL analysis in male sterile and self‐incompatible crops within controlled ecosystems. The doubled haploid (DH) mapping population, traditionally requiring 3 years of generation time via anther culture method, can now be expedited to 2–3 years of generation time using gene editing techniques within controlled environmental systems. Notably, DH mapping populations can be efficiently generated in various crops, including rice, wheat, maize, barley and oats by leveraging gene editing tools. Among these tools, the novel approach of CENH3 protein temporal alteration/excision emerges as highly efficient compared to MTL knockout using Cas9/gRNA‐mediated mutation or Cas9/gRNA promoter expression. However, further investigation is warranted to optimise the regeneration of double haploid populations and enhance QTL analysis in male sterile and self‐incompatible crops under controlled systems.
Astrophysical Tests of General Relativity
Authors: Zakharov A. F. 
Published: October 2024

Abstract
At the initial stage of its development, general relativity (GR) was verified and confirmed in a weak gravitational field limit. However, with the development of astronomical observation technologies, GR predictions in a strong gravitational field began to be discussed and confirmed, such as the profile of the X-ray iron $$K\alpha $$ line (in the case if the emission region is very close to the event horizon), the trajectories of stars near black holes and the shapes and sizes of shadows of supermassive black holes in M87* and Sgr A*. In 2005 it was predicted that a shadow formed near a supermassive black hole at the Galactic Center could be reconstructed from observations of ground based global VLBI system or ground—space interferometer acting in mm or sub-mm bands. In 2022 this prediction was confirmed since the Event Horizon Telescope (EHT) collaboration reported about a shadow reconstructions for Sgr A*. In 2019 the EHT collaboration presented the first image reconstruction around the shadow for the supermassive black hole in M87. In 2021 the EHT collaboration constrained parameters (“charges”) of spherical symmetrical metrics of black holes from an allowed interval for shadow radius. In 2022 the EHT collaboration constrained charges of metrics for the supermassive black hole at the Galactic Center. Earlier, we obtained analytical expressions for the shadow radius as a function of charge (including a tidal one) in the case of Reissner–Nordström metric. Based on results of the shadow size evaluation for M87* done by the EHT collaboration we constrained a tidal charge. We discussed opportunities to use shadows to test alternative theories of gravity and alternative models for galactic centers.
Quiescent optical solitons with Kudryashov’s generalized quintuple-power law and nonlocal nonlinearity having nonlinear chromatic dispersion with generalized temporal evolution by enhanced direct algebraic method and sub-ODE approach
Authors: Zayed Elsayed M. E. , El-Shater Mona , Arnous Ahmed H. , Yıldırım Yakup , Hussein Layth , Jawad Anwar Ja’afar Mohamad , Veni S. Saravana , Biswas Anjan 
Published: October 2024

AbstractRevisiting the study of quiescent optical solitons with quintuple-power-law self-phase modulation and nonlinear chromatic dispersion is the focus of the current paper. The soliton solutions to the model are revealed through the intermediary Jacobi’s elliptic functions using the enhanced direct algebraic method. The intermediary Weierstrass’ elliptic functions are used by the sub-ODE approach to reveal such quiescent soliton solutions.
Reflection and transmission amplitudes in a digital quantum simulation
Authors: Mussardo Giuseppe , Stampiggi Andrea , Trombettoni Andrea 
Published: October 2024

AbstractIn this paper we show how to measure in the setting of digital quantum simulations the reflection and transmission amplitudes of the one-dimensional scattering of a particle with a short-ranged potential. The main feature of the protocol is the coupling between the particle and an ancillary spin-1/2 degree of freedom. This allows us to reconstruct tomographically the scattering amplitudes, which are in general complex numbers, from the readout of one qubit. Applications of our results are discussed.
Abstract Mo105: End Systolic Pressure and Ejection Timing Correlate with Impaired Relaxation
Authors: Wagner Yoshio , Chung Charles 
Published: October 2024

Impaired relaxation is a common feature in most cases of diastolic dysfunction, including heart failure with preserved ejection fraction. Isovolumetric relaxation is typically characterized by τ, an exponential time constant, but may be broken into relaxation and stiffness-like parameters (µ and Ek). Recent in vitro work suggests that strain during late systole (protodiastolic period) modifies relaxation. We hypothesize that late systolic pressure and time indexes correlate with myocardial relaxation.
Thirty-four (34) simultaneous aortic and left ventricular micromanometric (Millar) pressure traces were obtained from a comprehensive database of clinical cardiac catheterization patients. These patients underwent coronary artery disease screening and presented but did not have arterial blockages. Pressure and time parameters were calculated over a five-minute interval.
Relaxation rate (1/τ), and stiffness (Ek) correlated to end systolic parameters in an orthogonal pattern to relaxation (µ). 1/τ showed strong correlations with time from peak pressure to aortic valve divided by ejection time (t54/t52, r = .675, p < .01) and moderate correlation to the pressure decline after peak pressure to aortic valve pressure divided by the pulse pressure (P45/P42, r = .577, p < .01). In parallel Ek showed moderate correlation with t54/t52 (r = .592, p < .01), and a moderate correlation with P45/P42 (r = .470, p < .01), the pressure at aortic valve closure (r = -.420, p < .05), and aortic augmentation index (AIx, r = -.360, p < .05). Finally, µ presented a moderate correlation to P45/P42 (r = .501, p < .05), the pressure at aortic valve closure (r = .404, p < .05), and AIx (r = -.357, p < .05).
As predicted, ventricular relaxation in patients correlates with late systolic hemodynamics. Parameters or combinations of parameters may predict relaxation rates or correlate to in vivo late systolic strain. Prospective studies evaluating end systolic strain and relaxation merit consideration. Overall, these observations are consistent with in vitro studies that suggest that impaired cessation of contraction is a regulator of relaxation.
Abstract Mo124: New Rho-kinase Inhibitor Reduces Diastolic Dysfunction induced by Estrogen Depletion in Spontaneously Hypertensive Rats
Authors: Zapata-Sudo Gisele , Carvalho Juliana , Montagnoli Tadeu , Dematte Bruno , Rocha Bruna , Cunha Rebeca , Tolomeu Heber , Fraga Carlos 
Published: October 2024

Heart failure with preserved ejection fraction (HFpEF) observed in women with estrogen depletion is a consequence of the reduction of cardioprotection and endothelial dysfunction. Rho-kinase (ROCK) signaling pathway plays a role in cardiac dysfunction consequent to female aging. This work investigated the effects of a new synthetic ROCK inhibitor (iROCK) after oral administration in spontaneously hypertensive rats (SHR) submitted to oophorectomy (OVX). Experimental protocols were approved Animal Care and Use Committee at Universidade Federal do Rio de Janeiro. Under ketamine (80 mg/kg, i.p.) and xylazine (15 mg/kg, i.p.) anesthesia, female SHR submitted to OVX had cardiac function assessed after 8 weeks and compared to SHR-Sham. Eight weeks after OVX, SHR were randomly divided in groups, which were orally treated with either vehicle (DMSO) or iROCK (10 mg/kg) during 2 weeks. Novel iROCK displays potent inhibitory activity for ROCK1 and ROCK2 isoforms, with IC50 of 1.3 μM and 1.7 μM, respectively. At the end of treatment, hemodynamic parameters were evaluated using echocardiography and LV catheterization. Cardiac tissues collected for determining the expression of mitogen-activated protein kinases p38MAPK and extracellular signal-regulated kinase (ERK-1/2) using Western blot technique. After 8 weeks of estrogen depletion, SHR displayed HFpEF because ejection fraction (EF) was 85.2 ± 0.9%, while a reduction in EF from 83.0 ± 2.7 to 64.9 ± 0.9% was only detected after 12 weeks of OVX. Altered filling pressure confirmed the diastolic dysfunction after OVX, because the ratio of rapid mitral flow (E) to rapid wave of mitral annulus tissue Doppler (e') increased from 12.1 ± 1.3 in SHR-Sham to 19.3 ± 0.5. LV end diastolic pressure (LVEDP) increased from 13.4 ± 1.3 to 21.1 ± 4.9 in SHR after 8 weeks post-OVX. Oral administration of iROCK (10 mg/kg) reduced both E/e’ to 16.2 ± 0.5 and LVEDP to 6.4 ± 0.7 mmHg. OVX in SHR increased cardiac p38 MAPK and ERK-1/2 contents by 2.3 and 1.3 fold from SHR-Sham values. In contrast, iROCK reduced p38 overexpression but not altered ERK-1/2 content. Since pro-inflammatory cytokines and oxidative stress activate p38, the recovery of its expression after treatment, indicates that iROCK could reduce the inflammatory component of HF.
In conclusion, the new iROCK recovered LV diastolic function induced by estrogen depletion in SHR, through the reduction of myocardial inflammation.
Abstract Tu024: Nitric oxide-dependent Vasodilation in Preeclampsia is impaired due to dysregulated L-arginine pathways and reduced cyclic Guanosine Monophosphate activity
Authors: Valdivia-Silva Julio 
Published: October 2024

To demonstrate the relationship between nitric oxide-dependent vasodilation and the expression of several enzymes from L-arginine pathway such as protein arginine N-methyltransferase-1, arginase-2, and nitric oxide synthase 2 -3, the cyclic guanosine monophosphate expression, and their activity in preeclamptic women, we employed a non-invasive technique to compare endothelial vasomotor function in 60 nonpregnant women, 60 healthy pregnant women, 55 preeclamptic women, and 40 pregnant women with essential hypertension. The concentrations of cGMP were measured in samples of platelets from all groups. RNA and protein expression for the enzymes were examined by reverse transcription-polymerase chain reaction and western blot analysis in umbilical vein endothelial cells that previously were isolated from all groups of women. Nitrite/nitrate in plasma levels were measured spectrophotometrically by Griess reaction.
The percentage increase of arterial diameter during reactive hyperemia in nonpregnant women, normal pregnant women, essential hipertensive pregnant women, and preeclamptic women was 7.8 ±2.2%; 16.93 ±2.86%; 9.94 ±1.51% and 6.48 ±1.96% respectively. Vasodilation in preeclampsia and essential hypertensive women was significantly less than that in normal pregnant women. The concentration of platelet cGMP was higher in the normotensive pregnant women than in nonpregnant and essential hypertensive women but did not differ from that in preeclamptic groups. Relative expressions of messenger RNA and protein for eNOS were decreased significantly in preeclamptic and essential hypertension endothelial cells compared with cells from normal pregnancies (P<0.001). Nevertheless, relative messenger RNA for iNOS, Arginase-2, and protein arginine N-methyltransferase-1 was significantly increased in cells from preeclampsia (P<0.001) versus cells from normal pregnancies. Preeclamptic women had significantly higher plasma levels of nitrite/nitrate (49.7 ±7.1 µmol/L) compared with normal pregnant, non-pregnant, and essential hypertensive women (34,2 ±3.1 µmol/L, 29.0 ±8.21 µmol/L, and 17,4 ±2.7 µmol/L respectively).
Our results indicate that reduced NO-dependent vasodilation in preeclampsia may be due to the dysregulated expression and activity of enzymes from L-arginine pathway rather than the reduction of cGMP production. Furthermore, increased production of nitrite/nitrate in preeclampsia might be a redirection of NOS 2 and 3 activities to the peroxinitrite production.
Abstract Tu065: The role of heavy metals in pulmonary arterial hypertension pathogenesis
Authors: Cathey Dakotah , Cai Lu , Cai Jun , TAN YI , Huang Jiapeng 
Published: October 2024

Pulmonary arterial hypertension (PAH) is a disease where chronic high pulmonary arterial pressure causes inflammation, remodeling, and dysfunctions of lung endothelial/smooth muscle cells, and right ventricle (RV) cardiomyocytes. Pathogenesis is caused by a mixture of genetic, epigenetic, and environmental factors. Our clinical studies found PAH patients had elevated cadmium (Cd) and antimony (Sb) levels in the blood and/or urine, which correlated with increased severity of PAH parameters. Thus, we hypothesize that environmental factors, specifically chronic heavy metal exposure, could contribute to PAH pathogenesis either directly or indirectly.
We tested if Cd could induce PAH or worsen PAH parameters in the mouse SU5416 and hypoxia (SuHx) PAH model. Forty male C57/6J mice were initially split in 2 groups: control and 5ppm Cd in drinking water (n=20/each) for 8 weeks (wks). Diastolic and systolic functions were evaluated with echocardiography (echo) at baseline, and 8ks. Then, half of these mice were subject to PAH induction, netting 4 subgroups (n=10/group): CTRL, Cd, PAH, and Cd+PAH. Echo was performed again 4 wks post-PAH induction, followed by RV systolic pressure (RVSP) measurement (n=3/group). The remaining 7 mice/group were euthanized for heart/lung histopathology focusing on fibrosis and hypertrophy, and protein western blot analyses. GraphPad Prism 8 software was used for statistical analysis with normality checked. When data did not follow normality, the non-parametric equivalence was used. Two-way and one-way ANOVA with Tukey were performed for echo/RVSP and histological/biochemical analyses respectively, with a p-value<0.05 being significant.
Results showed 12-wks Cd exposure alone caused: (1) significantly increased RV systolic function indicating systolic stimulation, and (2) significantly increased collagen contents in both ventricles and LV cardiomyocyte area when compared to CTRL. Twelve-wks Cd+PAH group demonstrated (1) significantly decreased RV cardiac output and RVSP measurements indicating RV failure; (2) no further RV changes in collagen contents or hypertrophy; (3) LV western blot analysis revealed significant upregulation of antioxidant proteins, including catalase and superoxide dismutase 2, when compared to PAH group. Further mechanistic experiments are being conducted, including whether Sb has similar results as Cd.
Abstract We103: Integration of deep learning assisted high-content screening and deep tissue-phenotyping to identify cardioprotective compounds in dilated cardiomyopathy
Authors: Wiest-Daessle Nicolas , Sharkova Krasimira , Weiss Amelie , Sommer Peter , Zimmermann Wolfram , Gkatzis Konstantinos 
Published: October 2024

With a prevalence of 4:10,000, dilated cardiomyopathy (DCM) is the most common hereditary heart disease, characterized by dilatation of one or both ventricles and impaired systolic and diastolic function. Numerous mutations have been identified to cause DCM. TITIN-truncating variants (TTNtv) are commonly observed in 20% of the genetic DCM cases. Progress in drug discovery for DCM has been hampered by the lack of robust high-throughput/high-content analysis pipelines of disease-specific cell and tissue platforms for deep structural and functional phenotyping.
To address this challenge, we have developed a two-tiered human induced pluripotent stem cell (iPSC)-based screening approach, comprised of high-content cardiomyocyte imaging with artificial intelligence (AI)-driven image and data analyses as well as deep tissue phenotyping in engineered heart muscle (EHM) models. As a DCM use case, we have developed several isogenic human iPSC-lines with and without a previously reported and pathologically relevant A-band-TTNtv mutation (c.70692_70693insAT; p.T23565SfsX5; Gerull et al. 11788824, Gramlich et al. 25759365, Fomin et al. 34731013)

Using fixed weights from a convolutional deep neural network trained on ImageNet, we generated unbiased deep embeddings from each 2D cell model and applied these to train machine learning (ML) models to detect morphological disease phenotypes. Our ML model is able to confidently separate healthy controls from
TTNtv
cells with high accuracy (>93%), specificity (WT >79%) across different batches/plate layouts and generate concentration-response curves, demonstrating platform robustness and sensitivity. Building upon this work, we will present our latest efforts applying the platform technology for a chemogenomic screening campaign to identify novel cardioprotective drugs using a library of 7,100 bioactive compounds and validation assays, including measuring functional changes in EHMs.

The phenotypic profiling platform, as presented here, can be readily adapted to other disease-relevant cell types and pathologies. Our results demonstrate the power of combining iPSC-CMs with cytological profiling and deep learning as well as tissue-level phenotyping to accelerate drug discovery for patients with DCM.
Abstract We121: Doxorubicin-Induced Cardiomyocyte Death is mediated by Lysosomal Membrane Permeabilization
Authors: Nasef Demarcus , Nasef Daniel , Hahn Younghee , Kobayashi Tamayo , Huang Yuan , Stout Randy , Liang Qiangrong , Kobayashi Satoru 
Published: October 2024

Doxorubicin (DOX) is a potent antineoplastic drug with broad-spectrum capabilities. However, its clinical use is hindered by dose-dependent cardiotoxicity, often leading to heart failure. This study investigates the connection between DOX-induced cardiotoxicity and lysosomal dysfunction, focusing on lysosomal membrane permeabilization (LMP) as a central mechanism in cardiomyocyte death. LMP occurs when there is a disruption in the integrity of the lysosomal membrane, releasing lysosomal enzymes into the cytoplasm. We tested the hypothesis that DOX induces LMP, contributing to cardiomyocyte death.
Utilizing a tfGalectin3 LMP reporter and Lysosensor staining, we verified LMP occurrence in DOX-treated H9C2 cardiomyoblast cells, as indicated by compromised lysosomal acidity and increased release of lysosomal protease Cathepsin D (CTSD). Western blot analysis showed elevated CTSD expression following DOX exposure, while DQRed BSA staining demonstrated diminished lysosomal proteolysis, signifying lysosomal dysfunction. Intriguingly, downregulating CTSD via siRNA aggravates cardiomyocyte death, whereas enhancing CTSD expression through adenoviral delivery exerts opposite effects, suggesting a protective role of CTSD in DOX cardiotoxicity. In vivo study using a tfGalectin3 LMP reporter mouse validated the ability of DOX to induce LMP in cardiac tissue. CTSD heterozygous knockout mice exhibited deteriorated heart function compared to the wild type, underscoring CTSD's protective role against DOX-induced cardiotoxicity. In summary, our findings highlight the critical impact of DOX on lysosomal stability and protease activity, leading to cardiomyocyte death and cardiac dysfunction. Further studies are warranted to explore potential interventions, such as imidazolines and apolipoproteins, to reinforce LMP stability and safeguard against DOX-induced cardiotoxicity.
Beading plot: a novel graphics for ranking interventions in network evidence
Authors: Chen Chiehfeng , Chuang Yu-Chieh , Chan Edwin Shih-Yen , Chen Jin-Hua , Hou Wen-Hsuan , Kang Enoch ,   Cochrane Taiwan
Published: October 2024

Abstract
Background
Network meta-analysis is developed to compare all available treatments; therefore it enriches evidence for clinical decision-making, offering insights into treatment effectiveness and safety when faced with multiple options. However, the complexity and numerous treatment comparisons in network meta-analysis can challenge healthcare providers and patients. The purpose of this study aimed to introduce a graphic design to present complex rankings of multiple interventions comprehensively.

Methods
Our team members developed a “beading plot” to summary probability of achieving the best treatment (P-best) and global metrics including surface under the cumulative ranking curve (SUCRA) and P-score. Implemented via the “rankinma” R package, this tool summarizes rankings across diverse outcomes in network meta-analyses, and the package received an official release on the Comprehensive R Archive Network (CRAN). It includes the `PlotBead()` function for generating beading plots, which represent treatment rankings among various outcomes.

Results
Beading plot has been designed based on number line plot, which effectively displays collective metrics for each treatment across various outcomes. Order on the -axis is derived from ranking metrics like P-best, SUCRA, and P-score. Continuous lines represent outcomes, and color-coded beads signify treatments.

Conclusion
The beading plot is a valuable graphic that intuitively displays treatment rankings across diverse outcomes, enhancing reader-friendliness and aiding decision-making in complex network evidence scenarios. While empowering clinicians and patients to identify optimal treatments, it should be used cautiously, alongside an assessment of the overall evidence certainty.
Post-viral symptoms and conditions are more frequent in COVID-19 than influenza, but not more persistent
Authors: Tesch Falko , Ehm Franz , Loser Friedrich , Bechmann Lars , Vivirito Annika , Wende Danny , Batram Manuel , Buschmann Tilo , Menzer Simone , Ludwig Marion , Roessler Martin , Seifert Martin , Margolis Giselle Sarganas , Reitzle Lukas , König Christina , Schulte Claudia , Hertle Dagmar , Ballesteros Pedro , Baßler Stefan , Bertele Barbara , Bitterer Thomas , Riederer Cordula , Sobik Franziska , Scheidt-Nave Christa , Schmitt Jochen 
Published: October 2024

Abstract
Background
Post-viral symptoms have long been known in the medical community but have received more public attention during the COVID-19 pandemic. Many post-viral symptoms were reported as particularly frequent after SARS-CoV-2 infection. However, there is still a lack of evidence regarding the specificity, frequency and persistence of these symptoms in comparison to other viral infectious diseases such as influenza.

Methods
We investigated a large population-based cohort based on German routine healthcare data. We matched 573,791 individuals with a PCR-test confirmed SARS-CoV-2 infection from the year 2020 to contemporary controls without SARS-CoV-2 infection and controls from the last influenza outbreak in 2018 and followed them up to 18 months.

Results
We found that post-viral symptoms as defined for COVID-19 by the WHO as well as tissue damage were more frequent among the COVID-19 cohort than the influenza or contemporary control cohort. The persistence of post-viral symptoms was similar between COVID-19 and influenza.

Conclusion
Post-viral symptoms following SARS-CoV-2 infection constitute a substantial disease burden as they are frequent and often persist for many months. As COVID-19 is becoming endemic, the disease must not be trivialized. Research should focus on the development of effective treatments for post-viral symptoms.