bluuebunny/crossref_metadata_2025_split huggingface dataset:
Diagnostic potential of the amniotic fluid cells transcriptome in deciphering mendelian disease: a proof-of-concept
Authors: Lee Mianne , Kwong Anna K. Y. , Chui Martin M. C. , Chau Jeffrey F. T. , Mak Christopher C. Y. , Au Sandy L. K. , Lo Hei Man , Chan Kelvin Y. K. , Yépez Vicente A. , Gagneur Julien , Kan Anita S. Y. , Chung Brian H. Y. 
Published: December 2022

AbstractRNA sequencing (RNA-seq) is emerging in genetic diagnoses as it provides functional support for the interpretation of variants of uncertain significance. However, the use of amniotic fluid (AF) cells for RNA-seq has not yet been explored. Here, we examined the expression of clinically relevant genes in AF cells (n = 48) compared with whole blood and fibroblasts. The number of well-expressed genes in AF cells was comparable to that in fibroblasts and much higher than that in blood across different disease categories. We found AF cells RNA-seq feasible and beneficial in prenatal diagnosis (n = 4) as transcriptomic data elucidated the molecular consequence leading to the pathogenicity upgrade of variants in CHD7 and COL1A2 and revising the in silico prediction of a variant in MYRF. AF cells RNA-seq could become a reasonable choice for postnatal patients with advantages over fibroblasts and blood as it prevents invasive procedures.
Regulation of stem cell fate by HSPGs: implication in hair follicle cycling
Authors: Colin-Pierre Charlie , El Baraka Oussama , Danoux Louis , Bardey Vincent , André Valérie , Ramont Laurent , Brézillon Stéphane 
Published: December 2022

AbstractHeparan sulfate proteoglycans (HSPGs) are part of proteoglycan family. They are composed of heparan sulfate (HS)-type glycosaminoglycan (GAG) chains covalently linked to a core protein. By interacting with growth factors and/or receptors, they regulate numerous pathways including Wnt, hedgehog (Hh), bone morphogenic protein (BMP) and fibroblast growth factor (FGF) pathways. They act as inhibitor or activator of these pathways to modulate embryonic and adult stem cell fate during organ morphogenesis, regeneration and homeostasis. This review summarizes the knowledge on HSPG structure and classification and explores several signaling pathways regulated by HSPGs in stem cell fate. A specific focus on hair follicle stem cell fate and the possibility to target HSPGs in order to tackle hair loss are discussed in more dermatological and cosmeceutical perspectives.
Mechanics of the cellular microenvironment as probed by cells in vivo during zebrafish presomitic mesoderm differentiation
Authors: Mongera Alessandro , Pochitaloff Marie , Gustafson Hannah J. , Stooke-Vaughan Georgina A. , Rowghanian Payam , Kim Sangwoo , Campàs Otger 
Published: December 2022

AbstractTissue morphogenesis, homoeostasis and repair require cells to constantly monitor their three-dimensional microenvironment and adapt their behaviours in response to local biochemical and mechanical cues. Yet the mechanical parameters of the cellular microenvironment probed by cells in vivo remain unclear. Here, we report the mechanics of the cellular microenvironment that cells probe in vivo and in situ during zebrafish presomitic mesoderm differentiation. By quantifying both endogenous cell-generated strains and tissue mechanics, we show that individual cells probe the stiffness associated with deformations of the supracellular, foam-like tissue architecture. Stress relaxation leads to a perceived microenvironment stiffness that decreases over time, with cells probing the softest regime. We find that most mechanical parameters, including those probed by cells, vary along the anteroposterior axis as mesodermal progenitors differentiate. These findings expand our understanding of in vivo mechanosensation and might aid the design of advanced scaffolds for tissue engineering applications.
An accurate deep learning model for wheezing in children using real world data
Authors: Kim Beom Joon , Kim Baek Seung , Mun Jeong Hyeon , Lim Changwon , Kim Kyunghoon 
Published: December 2022

AbstractAuscultation is an important diagnostic method for lung diseases. However, it is a subjective modality and requires a high degree of expertise. To overcome this constraint, artificial intelligence models are being developed. However, these models require performance improvements and do not reflect the actual clinical situation. We aimed to develop an improved deep-learning model learning to detect wheezing in children, based on data from real clinical practice. In this prospective study, pediatric pulmonologists recorded and verified respiratory sounds in 76 pediatric patients who visited a university hospital in South Korea. In addition, structured data, such as sex, age, and auscultation location, were collected. Using our dataset, we implemented an optimal model by transforming it based on the convolutional neural network model. Finally, we proposed a model using a 34-layer residual network with the convolutional block attention module for audio data and multilayer perceptron layers for tabular data. The proposed model had an accuracy of 91.2%, area under the curve of 89.1%, precision of 94.4%, recall of 81%, and F1-score of 87.2%. The deep-learning model proposed had a high accuracy for detecting wheeze sounds. This high-performance model will be helpful for the accurate diagnosis of respiratory diseases in actual clinical practice.
Endothelial dysfunction in Marfan syndrome mice is restored by resveratrol
Authors: Mieremet Arnout , van der Stoel Miesje , Li Siyu , Coskun Evrim , van Krimpen Tsveta , Huveneers Stephan , de Waard Vivian 
Published: December 2022

AbstractPatients with Marfan syndrome (MFS) develop thoracic aortic aneurysms as the aorta presents excessive elastin breaks, fibrosis, and vascular smooth muscle cell (vSMC) death due to mutations in the FBN1 gene. Despite elaborate vSMC to aortic endothelial cell (EC) signaling, the contribution of ECs to the development of aortic pathology remains largely unresolved. The aim of this study is to investigate the EC properties in Fbn1C1041G/+ MFS mice. Using en face immunofluorescence confocal microscopy, we showed that EC alignment with blood flow was reduced, EC roundness was increased, individual EC surface area was larger, and EC junctional linearity was decreased in aortae of Fbn1C1041G/+ MFS mice. This modified EC phenotype was most prominent in the ascending aorta and occurred before aortic dilatation. To reverse EC morphology, we performed treatment with resveratrol. This restored EC blood flow alignment, junctional linearity, phospho-eNOS expression, and improved the structural integrity of the internal elastic lamina of Fbn1C1041G/+ mice. In conclusion, these experiments identify the involvement of ECs and underlying internal elastic lamina in MFS aortic pathology, which could act as potential target for future MFS pharmacotherapies.
Multi-omics network model reveals key genes associated with p-coumaric acid stress response in an industrial yeast strain
Authors: Ciamponi F. E. , Procópio D. P. , Murad N. F. , Franco T. T. , Basso T. O. , Brandão M. M. 
Published: December 2022

AbstractThe production of ethanol from lignocellulosic sources presents increasingly difficult issues for the global biofuel scenario, leading to increased production costs of current second-generation (2G) ethanol when compared to first-generation (1G) plants. Among the setbacks encountered in industrial processes, the presence of chemical inhibitors from pre-treatment processes severely hinders the potential of yeasts in producing ethanol at peak efficiency. However, some industrial yeast strains have, either naturally or artificially, higher tolerance levels to these compounds. Such is the case ofS. cerevisiae SA-1, a Brazilian fuel ethanol industrial strain that has shown high resistance to inhibitors produced by the pre-treatment of cellulosic complexes. Our study focuses on the characterization of the transcriptomic and physiological impact of an inhibitor of this type,p-coumaric acid (pCA), on this strain under chemostat cultivation via RNAseq and quantitative physiological data. It was found that strain SA-1 tend to increase ethanol yield and production rate while decreasing biomass yield when exposed to pCA, in contrast to pCA-susceptible strains, which tend to decrease their ethanol yield and fermentation efficiency when exposed to this substance. This suggests increased metabolic activity linked to mitochondrial and peroxisomal processes. The transcriptomic analysis also revealed a plethora of differentially expressed genes located in co-expressed clusters that are associated with changes in biological pathways linked to biosynthetic and energetical processes. Furthermore, it was also identified 20 genes that act as interaction hubs for these clusters, while also having association with altered pathways and changes in metabolic outputs, potentially leading to the discovery of novel targets for metabolic engineering toward a more robust industrial yeast strain.
Variation between glaucous and non-glaucous near-isogenic lines of rye (Secale cereale L.) under drought stress
Authors: Laskoś Kamila , Myśków Beata , Dziurka Michał , Warchoł Marzena , Dziurka Kinga , Juzoń Katarzyna , Czyczyło-Mysza Ilona M. 
Published: December 2022

AbstractGlaucous (811, L35, and RXL10) and non-glaucous (811bw, L35bw, and RXL10bw) near-isogenic lines (NILs) of rye (Secale cereale L.) forming three pairs of inbred lines were the subject of the research. The research aimed to study the relationship between wax cover attributes and the physio-biochemical drought reactions and yield of rye NILs and to uncover the differences in drought resistance levels of these lines. The greatest differences between glaucous and non-glaucous NILs were observed in the RXL10/RXL10bw pair. Of particular note were the stable grain number and the thousand grain weight of the non-glaucous line RXL10bw under drought and the accompanying reactions, such as an approximately 60% increase in MDA and a two-fold increase in wax amount, both of which were significantly higher than in the glaucous line RXL10 and in other NILs. The surprisingly high level of MDA in the RXL10bw line requires further analysis. Moreover, additional wax crystal aggregates were found under drought conditions on the abaxial leaf surface of the glaucous lines 811 and RXL10. The use of rye NILs indicated that line-specific drought resistance could be associated with wax biosynthetic pathways involved in physiological and biochemical responses important for increased drought resistance.
Mechanism based therapies enable personalised treatment of hypertrophic cardiomyopathy
Authors: Margara Francesca , Psaras Yiangos , Wang Zhinuo Jenny , Schmid Manuel , Doste Ruben , Garfinkel Amanda C. , Repetti Giuliana G. , Seidman Jonathan G. , Seidman Christine E. , Rodriguez Blanca , Toepfer Christopher N. , Bueno-Orovio Alfonso 
Published: December 2022

AbstractCardiomyopathies have unresolved genotype–phenotype relationships and lack disease-specific treatments. Here we provide a framework to identify genotype-specific pathomechanisms and therapeutic targets to accelerate the development of precision medicine. We use human cardiac electromechanical in-silico modelling and simulation which we validate with experimental hiPSC-CM data and modelling in combination with clinical biomarkers. We select hypertrophic cardiomyopathy as a challenge for this approach and study genetic variations that mutate proteins of the thick (MYH7R403Q/+) and thin filaments (TNNT2R92Q/+,TNNI3R21C/+) of the cardiac sarcomere. Using in-silico techniques we show that the destabilisation of myosin super relaxation observed in hiPSC-CMs drives disease in virtual cells and ventricles carrying the MYH7R403Q/+variant, and that secondary effects on thin filament activation are necessary to precipitate slowed relaxation of the cell and diastolic insufficiency in the chamber. In-silico modelling shows that Mavacamten corrects the MYH7R403Q/+phenotype in agreement with hiPSC-CM experiments. Our in-silico model predicts that the thin filament variants TNNT2R92Q/+and TNNI3R21C/+display altered calcium regulation as central pathomechanism, for which Mavacamten provides incomplete salvage, which we have corroborated in TNNT2R92Q/+and TNNI3R21C/+hiPSC-CMs. We define the ideal characteristics of a novel thin filament-targeting compound and show its efficacy in-silico. We demonstrate that hybrid human-based hiPSC-CM and in-silico studies accelerate pathomechanism discovery and classification testing, improving clinical interpretation of genetic variants, and directing rational therapeutic targeting and design.
Evaluation of congenital and acquired heart diseases in a Spanish cohort of adults with Down syndrome
Authors: Rabes Laura , Adán-Lirola Laura , González-Molina María del Pilar , Galván-Román José María , Moldenhauer Fernando , Roy-Vallejo Emilia , Real de Asúa Diego 
Published: December 2022

AbstractTo describe congenital and acquired heart diseases in a Spanish cohort of adults with Down syndrome (DS), which could inform potential health recommendations for this population. Cross-sectional, observational study of adults with DS evaluated consecutively at a tertiary care, outpatient center between January 1 and December 31, 2019. The study population comprised 937 patients (51.8% men; median [IQR] age, 42 [18] years). An echocardiogram was available in the clinical chart of 420 patients (44.8%). The diagnosis of any form of heart disease was confirmed in 211 patients (22.5%): 101 (10.8%) had congenital heart defects, 80 (8.5%) simultaneous congenital and valvular heart diseases, and 30 (3.2%) isolated valvular heart disease. 111 patients (52.6% of those with congenital or valvular heart disease) had received corrective cardiac surgery. A total of 65 individuals were receiving medical management alone (30.8%), while 35 did not require any treatment because their cardiac disease was mild (16.6%). We found a high overall prevalence of heart disease in patients with DS, higher than previously reported for the pediatric population. Management of cardiovascular disease in adults with DS differs from that of the general population and should include universal echocardiography-based screening.
In situ transduction of cells in human corneal limbus using adeno-associated viruses: an ex vivo study
Authors: Son Hyeck-Soo , Jun Albert S. , Foster James W. , Wang Wei , Daoud Yassine , Auffarth Gerd U. , Roy Madhuparna 
Published: December 2022

AbstractThis study aimed to evaluate the efficacy of in situ adeno-associated virus (AAV)-mediated gene delivery into the human corneal limbal region via targeted sub-limbal injection technique. Human cadaveric corneal tissues were fixed on an artificial anterior chamber. Feasibility of sub-limbal injection technique was tested using trypan blue and black India ink. An enhanced green fluorescent protein (eGFP) encoding AAV DJ was injected into sub-limbal region. After AAV injection, corneal tissues were incubated in air-lift culture and prepared for immunohistochemical analysis. Cell survivial and expression of eGFP, stem cell markers (p63α and cytokeratin 19 (KRT19)), and differentiation marker cytokeratin 3 (KRT3) were evaluated using confocal microscopy. Both trypan blue and black India ink stained and were retained sub-limbally establishing specificity of the injection technique. Immunohistochemical analysis of corneas injected with AAV DJ-eGFP indicated that AAV-transduced cells in the limbal region co-express eGFP, p63α, and KRT19 and that these transduced cells were capable of differentiating to KRT3 postitive corneal epithelial cells. Our sub-limbal injection technique can target cells in the human limbus in a reproducible and efficient manner. Thus, we demonstrate that in situ injection of corneal limbus may provide a feasible mode of genetic therapy for corneal disorders with an epithelial etiology.
Bottom-hole pressure drawdown management of fractured horizontal wells in shale gas reservoirs using a semi-analytical model
Authors: Xu Yingying , Liu Xiangui , Hu Zhiming , Duan Xianggang , Chang Jin 
Published: December 2022

AbstractDue to strong stress sensitivity resulted from unconventional tight formationsit is of practical interest to formulate a reasonable pressure drawdown plan to improve gas extraction recovery. The impact of water-shale interactions on the reservoir permeability was previously ignored in the managed pressure drawdown optimization. The controlled-pressure production dynamic analysis was mostly conducted using numerical simulation, lack of rigorous theoretical support. Hence in this paper, a theoretical production prediction model was proposed and verified with HIS RTA 2015by incorporating multiple pressure drawdown mechanisms and various non-linear gas flow process. The on-site production effects dominated by two different pressure drop methods was further compared, indicating that compared to depressurization production, the production reversion can occur in the controlled pressure production process and the EUR of single well can be increased by about 30% under the control of managed pressure drawdown approach. Finally, the pressure drawdown optimization strategy was carried out on the field test from the both production effect and economic benefits, which demonstrated that the best economic solution can generally be obtained in the early stage of production. The research results can be closely linked to the on-site production practice of shale gas wells, providing insights into designing optimized production strategy scheme.
Development of a simple multiple mutation detection system using seed-coat flavonoid pigments in irradiated Arabidopsis M1 plants
Authors: Kitamura Satoshi , Hirata Shoya , Satoh Katsuya , Inamura Rie , Narumi Issay , Oono Yutaka 
Published: December 2022

AbstractIonizing radiation induces genetic variations in plants, which makes it useful for plant breeding. A theory that the induced mutations occur randomly in the genome has long been accepted, but is now controversial. Nevertheless, a comparative analysis of the mutations at multiple loci has not been conducted using irradiated M1 genomes that contain all types of mutations. In this study, we identified Arabidopsis mutants (pab2 and pab3) in a mutagenized population of an anthocyanin-positive seed mutant (ban). Both pab2 and pab3 were revealed to be double mutants (tt4 ban and tt8 ban, respectively) that produced similar anthocyanin-less immature seeds, but differentially colored mature seeds. These features enabled the seed color-based detection of de novo M1 mutations in TT4 or TT8 following the irradiation of double heterozygous plants (TT4/tt4 TT8/tt8 ban/ban). Most of the irradiated double heterozygous plants produced anthocyanin-positive immature seeds, but 19 plants produced anthocyanin-less immature seeds. Of these 19 mutants, 2 and 17 exhibited tt4- and tt8-type mature seed coloration, respectively. The molecular analysis of the seed coat DNA from randomly selected anthocyanin-less seeds detected mutations at the locus predicted on the basis of the phenotype. Thus, the simple system developed in this study can reliably detect radiation-induced mutations at multiple loci in irradiated Arabidopsis M1 plants.
Revelation of microcracks as tooth structural element by X-ray tomography and machine learning
Authors: Dumbryte Irma , Narbutis Donatas , Vailionis Arturas , Juodkazis Saulius , Malinauskas Mangirdas 
Published: December 2022

AbstractAlthough teeth microcracks (MCs) have long been considered more of an aesthetic problem, their exact role in the structure of a tooth and impact on its functionality is still unknown. The aim of this study was to reveal the possibilities of an X-ray micro-computed tomography ($$\mu$$
μ
CT) in combination with convolutional neural network (CNN) assisted voxel classification and volume segmentation for three-dimensional (3D) qualitative analysis of tooth microstructure and verify this approach with four extracted human premolars. Samples were scanned using a $$\mu$$
μ
CT instrument (Xradia 520 Versa; ZEISS) and segmented with CNN to identify enamel, dentin, and cracks. A new CNN image segmentation model was trained based on “Multiclass semantic segmentation using DeepLabV3+” example and was implemented with “TensorFlow”. The technique which was used allowed 3D characterization of all MCs of a tooth, regardless of the volume of the tooth in which they begin and extend, and the evaluation of the arrangement of cracks and their structural features. The proposed method revealed an intricate star-shaped network of MCs covering most of the inner tooth, and the main crack planes in all samples were arranged radially in two almost perpendicular directions, suggesting that the cracks could be considered as a planar structure.
Photo-oscillations in MgZnO/ZnO heterostructures
Authors: Iñarrea Jesús 
Published: December 2022

AbstractWe theoretically examine the characteristics of microwave-induced magnetoresistance (MIRO) and photovoltage oscillations in MgZno/ZnO heterostructures. We demonstrate that both kind of oscillations, although described with different physical properties, are intimately related sharing the same physical origin. We use the radiation driven electron orbit model showing that the interplay of radiation driven swinging Landau orbits and the scattering processes are at the heart of the oscillations in both scenarios. Thus, our simulations show that all photo-oscillations present the main features of MIRO: they are periodic with the inverse of the magnetic field and the oscillations minima are 1/4 cycle shifted.
Multi-objective steel plate cutting optimization problem based on real number coding genetic algorithm
Authors: Xu Jianqiao , Yang Wenguo 
Published: December 2022

AbstractThe rectangular packing problem is an NP-complete combinatorial optimization problem. This problem occurs widely in social production scenarios, with steel plate cutting being one example. The cutting scheme for the rectangular packing problem needs to be improved because, without the globally optimal solution, there are many unnecessary edges in the steel cutting process. Based on a practical roll-fed disc shearing steel plate optimization problem, this paper explores a generalized packing method for rectangles of special dimensions and abstractly condenses complex quantitative relationships to establish a multi-objective mixed-integer nonlinear programming model. An innovative algorithm design based on a genetic algorithm is established to plan the cutting scheme in a high-speed and efficient way. The outcome is a utilization rate of up to 92.73% for raw materials and a significant reduction in labor, providing a guide for practical production and processing tasks. The advantages and disadvantages of the model and algorithm are discussed, and it is concluded that this rectangular packing method has strong universality and generalization ability, allowing rectangular packing tasks with large data volumes to be completed within a short time.
AI in the hands of imperfect users
Authors: Kostick-Quenet Kristin M. , Gerke Sara 
Published: December 2022

AbstractAs the use of artificial intelligence and machine learning (AI/ML) continues to expand in healthcare, much attention has been given to mitigating bias in algorithms to ensure they are employed fairly and transparently. Less attention has fallen to addressing potential bias among AI/ML’s human users or factors that influence user reliance. We argue for a systematic approach to identifying the existence and impacts of user biases while using AI/ML tools and call for the development of embedded interface design features, drawing on insights from decision science and behavioral economics, to nudge users towards more critical and reflective decision making using AI/ML.