bluuebunny/crossref_metadata_2025_split huggingface dataset:
Theoretical analyses and experimental validation of the effects caused by the fluorinated substituent modification of DNA
Authors: Koseki Jun , Konno Masamitsu , Asai Ayumu , Horie Naohiro , Tsunekuni Kenta , Kawamoto Koichi , Obika Satoshi , Doki Yuichiro , Mori Masaki , Ishii Hideshi 
Published: January 2020

AbstractHalogen-modified nucleic acid molecules, such as trifluorothymidine (FTD) and 5-fluorouracil, are widely used in medical science and clinical site. These compounds have a very similar nucleobase structure. It is reported that both of these compounds could be incorporated into DNA. The incorporation of FTD produces highly anti-tumor effect. However, it is not known whether to occur a significant effect by the incorporation of 5-fluorouracil. Nobody knows why such a difference will occur. To understand the reason why there is large differences between trifluorothymidine and 5-fluorouracil, we have performed the molecular dynamics simulations and molecular orbital calculations. Although the active interaction energy between Halogen-modified nucleic acids or and complementary adenine was increased, in only FTD incorporated DNA, more strongly dispersion force interactions with an adjacent base were detected in many thermodynamic DNA conformations. As the results, the conformational changes occur even if it is in internal body temperature. Then the break of hydrogen bonding between FTD and complementary adenine base occur more frequently. The double helix structural destabilization of DNA with FTD is resulted from autoagglutination caused by the bonding via halogen orbitals such as halogen bonding and the general van der Waals interactions such as CH–$${\rm{\pi }}$$π, lone pair (LP)–$${\rm{\pi }}$$π, and $${\rm{\pi }}$$π–$${\rm{\pi }}$$π interactions. Therefore, it is strongly speculated that such structural changes caused by trifluoromethyl group is important for the anti-tumor effect of FTD alone.
Adaptive Landscape Shaped by Core Endogenous Network Coordinates Complex Early Progenitor Fate Commitments in Embryonic Pancreas
Authors: Wang Junqiang , Yuan Ruoshi , Zhu Xiaomei , Ao Ping 
Published: January 2020

AbstractThe classical development hierarchy of pancreatic cell fate commitments describes that multipotent progenitors (MPs) first bifurcate into tip cells and trunk cells, and then these cells give rise to acinar cells and endocrine/ductal cells separately. However, lineage tracings reveal that pancreatic progenitors are highly heterogeneous in tip and trunk domains in embryonic pancreas. The progenitor fate commitments from multipotency to unipotency during early pancreas development is insufficiently characterized. In pursuing a mechanistic understanding of the complexity in progenitor fate commitments, we construct a core endogenous network for pancreatic lineage decisions based on genetic regulations and quantified its intrinsic dynamic properties using dynamic modeling. The dynamics reveal a developmental landscape with high complexity that has not been clarified. Not only well-characterized pancreatic cells are reproduced, but also previously unrecognized progenitors—tip progenitor (TiP), trunk progenitor (TrP), later endocrine progenitor (LEP), and acinar progenitors (AciP/AciP2) are predicted. Further analyses show that TrP and LEP mediate endocrine lineage maturation, while TiP, AciP, AciP2 and TrP mediate acinar and ductal lineage maturation. The predicted cell fate commitments are validated by analyzing single-cell RNA sequencing (scRNA-seq) data. Significantly, this is the first time that a redefined hierarchy with detailed early pancreatic progenitor fate commitment is obtained.
Conversion of partial restorer Swarna into restorer by transferring fertility restorer Rf gene(s) through marker assisted back cross breeding (MABB) in rice
Authors: Ponnuswamy Revathi , Singh Arun Kumar , Raman Meenakshi Sundaram , Subbarao Lella venkata , C.N. Neeraja 
Published: January 2020

AbstractThe major constraints in hybrid rice breeding are availability of limited number of parental lines with specific desirable traits and lower frequency of restorers among elite breeding lines. The popular, high-yielding mega-rice variety Swarna, has been identified to be a partial restorer (as it has only one of major fertility restorer genes, Rf4) and hence cannot be utilized directly in the hybrid rice breeding. To convert the partial restorer to complete restorer, a cross was made between Swarna and a stable restorer KMR3R possessing Rf3 and Rf4 genes and developed BC1F5 and BC2F4 populations by marker-assisted back cross breeding (MABB). The SSR marker DRRM-RF3-10 linked to Rf3 gene located on chromosome 1, clearly distinguished restorers from partial restorers. All the improved lines of Swarna possessing Rf3 and Rf4 genes showed complete fertility restoration in test crosses with higher grain yield heterosis. Few rice hybrids developed by using converted restorers were evaluated in multi location testing under the All India Co-ordinated Rice Improvement Project (AICRIP). The results indicated that new rice hybrids expressed higher heterosis with matching grain quality attributes like Swarna. This study provides significantly novel and relevant restorers to enhance and economize future hybrid rice breeding programs.
Benchmarking Deep Learning Architectures for Predicting Readmission to the ICU and Describing Patients-at-Risk
Authors: Barbieri Sebastiano , Kemp James , Perez-Concha Oscar , Kotwal Sradha , Gallagher Martin , Ritchie Angus , Jorm Louisa 
Published: January 2020

AbstractTo compare different deep learning architectures for predicting the risk of readmission within 30 days of discharge from the intensive care unit (ICU). The interpretability of attention-based models is leveraged to describe patients-at-risk. Several deep learning architectures making use of attention mechanisms, recurrent layers, neural ordinary differential equations (ODEs), and medical concept embeddings with time-aware attention were trained using publicly available electronic medical record data (MIMIC-III) associated with 45,298 ICU stays for 33,150 patients. Bayesian inference was used to compute the posterior over weights of an attention-based model. Odds ratios associated with an increased risk of readmission were computed for static variables. Diagnoses, procedures, medications, and vital signs were ranked according to the associated risk of readmission. A recurrent neural network, with time dynamics of code embeddings computed by neural ODEs, achieved the highest average precision of 0.331 (AUROC: 0.739, F1-Score: 0.372). Predictive accuracy was comparable across neural network architectures. Groups of patients at risk included those suffering from infectious complications, with chronic or progressive conditions, and for whom standard medical care was not suitable. Attention-based networks may be preferable to recurrent networks if an interpretable model is required, at only marginal cost in predictive accuracy.
Beneficial bile acid metabolism from Lactobacillus plantarum of food origin
Authors: Prete Roberta , Long Sarah Louise , Gallardo Alvaro Lopez , Gahan Cormac G. , Corsetti Aldo , Joyce Susan A. 
Published: January 2020

AbstractBile acid (BA) signatures are altered in many disease states. BA metabolism is an important microbial function to assist gut colonization and persistence, as well as microbial survival during gastro intestinal (GI) transit and it is an important criteria for potential probiotic bacteria. Microbes that express bile salt hydrolase (BSH), gateway BA modifying enzymes, are considered to have an advantage in the gut. This property is reported as selectively limited to gut-associated microbes. Food-associated microbes have the potential to confer health benefits to the human consumer. Here, we report that food associated Lactobacillus plantarum strains are capable of BA metabolism, they can withstand BA associated stress and propagate, a recognised important characteristic for GIT survival. Furthermore, we report that these food associated Lactobacillus plantarum strains have the selective ability to alter BA signatures in favour of receptor activation that would be beneficial to humans. Indeed, all of the strains examined showed a clear preference to alter human glycol-conjugated BAs, although clear strain-dependent modifications were also evident. This study demonstrates that BA metabolism by food-borne non-pathogenic bacteria is beneficial to both microbe and man and it identifies an evolutionary-conserved characteristic, previously considered unique to gut residents, among food-associated non-pathogenic isolates.
Evaluation of capsular contracture following immediate prepectoral versus subpectoral direct-to-implant breast reconstruction
Authors: Sobti Nikhil , Weitzman Rachel E. , Nealon Kassandra P. , Jimenez Rachel B. , Gfrerer Lisa , Mattos David , Ehrlichman Richard J. , Gadd Michele , Specht Michelle , Austen William G. , Liao Eric C. 
Published: January 2020

AbstractCapsular contracture is a common adverse outcome following implant breast reconstruction, often associated with radiation treatment. The authors hypothesize that muscle fibrosis is the main contributor of breast reconstruction contracture after radiation. Retrospective chart review identified patients that underwent DTI reconstruction with pre-or post-operative breast irradiation. Signs of capsular contracture were assessed using clinic notes and independent graders reviewing two-dimensional images and anatomic landmarks. Capsular contracture rate was greater in the subpectoral vs. prepectoral group (n = 28, 51.8% vs. n = 12, 30.0%, p = 0.02). When compared to prepectoral DTI reconstruction in irradiated patients, subpectoral implant placement was nearly 4 times as likely to result in capsular contracture (p < 0.01). Rates of explantation, infection, tissue necrosis, and hematoma were comparable between groups. We also found that when subpectoral patients present with breast contracture, chemoparalysis of the muscle alone can resolve breast asymmetry, corroborating that muscle is a key contributor to breast contracture. As prepectoral breast reconstruction is gaining popularity, there have been questions regarding outcome following radiation treatment. This study suggest that prepectoral breast reconstruction is safe in an irradiated patient population, and in fact compares favorably with regard to breast contracture.
PDZRN3 protects against apoptosis in myoblasts by maintaining cyclin A2 expression
Authors: Honda Takeshi , Inui Makoto 
Published: January 2020

AbstractPDZRN3 is a PDZ domain-containing RING-finger family protein that functions in various developmental processes. We previously showed that expression of PDZRN3 is induced together with that of MyoD during the early phase of skeletal muscle regeneration in vivo. We here show that PDZRN3 suppresses apoptosis and promotes proliferation in myoblasts in a manner dependent on cyclin A2. Depletion of PDZRN3 in mouse C2C12 myoblasts by RNA interference reduced the proportion of Ki-67-positive cells and the level of Akt phosphorylation, implicating PDZRN3 in regulation of both cell proliferation and apoptosis. Exposure of C2C12 cells as well as of C3H10T1/2 mesenchymal stem cells and NIH-3T3 fibroblasts to various inducers of apoptosis including serum deprivation resulted in a greater increase in the amount of cleaved caspase-3 in PDZRN3-depleted cells than in control cells. The abundance of cyclin A2 was reduced in PDZRN3-depleted C2C12 myoblasts, as was that of Mre11, which contributes to the repair of DNA damage. Overexpression of cyclin A2 restored the expression of Mre11 and Ki-67 as well as attenuated caspase-3 cleavage in PDZRN3-depleted cells deprived of serum. These results indicate that PDZRN3 suppresses apoptosis and promotes proliferation in myoblasts and other cell types by maintaining cyclin A2 expression.
Transcriptome analysis of potato shoots, roots and stolons under nitrogen stress
Authors: Tiwari Jagesh Kumar , Buckseth Tanuja , Zinta Rasna , Saraswati Aastha , Singh Rajesh Kumar , Rawat Shashi , Dua Vijay Kumar , Chakrabarti Swarup Kumar 
Published: January 2020

AbstractPotato crop requires high dose of nitrogen (N) to produce high tuber yield. Excessive application of N causes environmental pollution and increases cost of production. Hence, knowledge about genes and regulatory elements is essential to strengthen research on N metabolism in this crop. In this study, we analysed transcriptomes (RNA-seq) in potato tissues (shoot, root and stolon) collected from plants grown in aeroponic culture under controlled conditions with varied N supplies i.e. low N (0.2 milli molar N) and high N (4 milli molar N). High quality data ranging between 3.25 to 4.93 Gb per sample were generated using Illumina NextSeq500 that resulted in 83.60–86.50% mapping of the reads to the reference potato genome. Differentially expressed genes (DEGs) were observed in the tissues based on statistically significance (p ≤ 0.05) and up-regulation with ≥ 2 log2 fold change (FC) and down-regulation with ≤ −2 log2 FC values. In shoots, of total 19730 DEGs, 761 up-regulated and 280 down-regulated significant DEGs were identified. Of total 20736 DEGs in roots, 572 (up-regulated) and 292 (down-regulated) were significant DEGs. In stolons, of total 21494 DEG, 688 and 230 DEGs were significantly up-regulated and down-regulated, respectively. Venn diagram analysis showed tissue specific and common genes. The DEGs were functionally assigned with the GO terms, in which molecular function domain was predominant in all the tissues. Further, DEGs were classified into 24 KEGG pathways, in which 5385, 5572 and 5594 DEGs were annotated in shoots, roots and stolons, respectively. The RT-qPCR analysis validated gene expression of RNA-seq data for selected genes. We identified a few potential DEGs responsive to N deficiency in potato such as glutaredoxin, Myb-like DNA-binding protein, WRKY transcription factor 16 and FLOWERING LOCUS T in shoots; high-affinity nitrate transporter, protein phosphatase-2c, glutaredoxin family protein, malate synthase, CLE7, 2-oxoglutarate-dependent dioxygenase and transcription factor in roots; and glucose-6-phosphate/phosphate translocator 2, BTB/POZ domain-containing protein, F-box family protein and aquaporin TIP1;3 in stolons, and many genes of unknown function. Our study highlights that these potential genes play very crucial roles in N stress tolerance, which could be useful in augmenting research on N metabolism in potato.
Discrimination of rosé wines using shotgun metabolomics with a genetic algorithm and MS ion intensity ratios
Authors: Gil Mélodie , Reynes Christelle , Cazals Guillaume , Enjalbal Christine , Sabatier Robert , Saucier Cédric 
Published: January 2020

AbstractA rapid Ultra Performance Liquid Chromatography coupled with Quadrupole/Time Of Flight Mass Spectrometry (UPLC-QTOF-MS) method was designed to quickly acquire high-resolution mass spectra metabolomics fingerprints for rosé wines. An original statistical analysis involving ion ratios, discriminant analysis, and genetic algorithm (GA) was then applied to study the discrimination of rosé wines according to their origins. After noise reduction and ion peak alignments on the mass spectra, about 14 000 different signals were detected. The use of an in-house mass spectrometry database allowed us to assign 72 molecules. Then, a genetic algorithm was applied on two series of samples (learning and validation sets), each composed of 30 commercial wines from three different wine producing regions of France. Excellent results were obtained with only four diagnostic peaks and two ion ratios. This new approach could be applied to other aspects of wine production but also to other metabolomics studies.
A misprocessed form of Apolipoprotein A-I is specifically associated with recurrent Focal Segmental Glomerulosclerosis
Authors: Jacobs-Cachá Conxita , Puig-Gay Natàlia , Helm Dominic , Rettel Mandy , Sellarès Joana , Meseguer Anna , Savitski Mikhail M. , Moreso Francesc J. , Soler Maria José , Seron Daniel , Lopez-Hellin Joan 
Published: January 2020

AbstractApolipoprotein A-Ib (ApoA-Ib) is a high molecular weight form of Apolipoprotein A-I (ApoA-I) found specifically in the urine of kidney-transplanted patients with recurrent idiopathic focal segmental glomerulosclerosis (FSGS). To determine the nature of the modification present in ApoA-Ib, we sequenced the whole APOA1 gene in ApoA-Ib positive and negative patients, and we also studied the protein primary structure using mass spectrometry. No genetic variations in the APOA1 gene were found in the ApoA-Ib positive patients that could explain the increase in its molecular mass. The mass spectrometry analysis revealed three extra amino acids at the N-Terminal end of ApoA-Ib that were not present in the standard plasmatic form of ApoA-I. These amino acids corresponded to half of the propeptide sequence of the immature form of ApoA-I (proApoA-I) indicating that ApoA-Ib is a misprocessed form of proApoA-I. The description of ApoA-Ib could be relevant not only because it can allow the automated analysis of this biomarker in the clinical practice but also because it has the potential to shed light into the molecular mechanisms that cause idiopathic FSGS, which is currently unknown.
Quality of life in people with ongoing symptoms of coeliac disease despite adherence to a strict gluten-free diet
Authors: Harnett Joanna E. , Myers Stephen P. 
Published: January 2020

AbstractPeople with Coeliac disease who suffer persistent symptoms despite adherence to a gluten-free diet are at a greater risk of a reduced health related quality of life. The purpose of this paper is to report the quality of life experienced by this specific group of patients in Australia. A Coeliac Disease Specific Questionnaire (CDQ) was administered to 45 people who were enrolled in a clinical trial and reported persistent symptoms of Coeliac disease despite adherence to a strict gluten free diet. The clinical trial was based in New South Wales, Australia. The instrument used was a subscale and total scores of a CDQ measuring health related quality of life. At baseline the overall mean CDQ score was 147 ± 3.31 (optimum 196) consisting of 4 subscales; gastrointestinal 33 ± 0.88, emotional 32.9 ± 0.99, worries 39.8 ± 0.79 and social 41 ± 6.12 each with a potential score of 49. The health related quality of life of people reporting persistent symptoms of Coeliac disease despite adherence to a gluten free diet is sub-optimal with concerningly low scores for emotional quality.
A simple and rapid pipeline for identification of receptor-binding sites on the surface proteins of pathogens
Authors: Mertinková Patrícia , Kulkarni Amod , Káňová Evelína , Bhide Katarína , Tkáčová Zuzana , Bhide Mangesh 
Published: January 2020

AbstractLigand-receptor interactions play a crucial role in the plethora of biological processes. Several methods have been established to reveal ligand-receptor interface, however, the majority of methods are time-consuming, laborious and expensive. Here we present a straightforward and simple pipeline to identify putative receptor-binding sites on the pathogen ligands. Two model ligands (bait proteins), domain III of protein E of West Nile virus and NadA of Neisseria meningitidis, were incubated with the proteins of human brain microvascular endothelial cells immobilized on nitrocellulose or PVDF membrane, the complex was trypsinized on-membrane, bound peptides of the bait proteins were recovered and detected on MALDI-TOF. Two peptides of DIII (~916 Da and ~2003 Da) and four peptides of NadA (~1453 Da, ~1810 Da, ~2051 Da and ~2433 Da) were identified as plausible receptor-binders. Further, binding of the identified peptides to the proteins of endothelial cells was corroborated using biotinylated synthetic analogues in ELISA and immunocytochemistry. Experimental pipeline presented here can be upscaled easily to map receptor-binding sites on several ligands simultaneously. The approach is rapid, cost-effective and less laborious. The proposed experimental pipeline could be a simpler alternative or complementary method to the existing techniques used to reveal amino-acids involved in the ligand-receptor interface.
Deep learning interpretation of echocardiograms
Authors: Ghorbani Amirata , Ouyang David , Abid Abubakar , He Bryan , Chen Jonathan H. , Harrington Robert A. , Liang David H. , Ashley Euan A. , Zou James Y. 
Published: January 2020

AbstractEchocardiography uses ultrasound technology to capture high temporal and spatial resolution images of the heart and surrounding structures, and is the most common imaging modality in cardiovascular medicine. Using convolutional neural networks on a large new dataset, we show that deep learning applied to echocardiography can identify local cardiac structures, estimate cardiac function, and predict systemic phenotypes that modify cardiovascular risk but not readily identifiable to human interpretation. Our deep learning model, EchoNet, accurately identified the presence of pacemaker leads (AUC = 0.89), enlarged left atrium (AUC = 0.86), left ventricular hypertrophy (AUC = 0.75), left ventricular end systolic and diastolic volumes ($${R}^{2}$$R2 = 0.74 and$${R}^{2}$$R2 = 0.70), and ejection fraction ($${R}^{2}$$R2 = 0.50), as well as predicted systemic phenotypes of age ($${R}^{2}$$R2 = 0.46), sex (AUC = 0.88), weight ($${R}^{2}$$R2 = 0.56), and height ($${R}^{2}$$R2 = 0.33). Interpretation analysis validates that EchoNet shows appropriate attention to key cardiac structures when performing human-explainable tasks and highlights hypothesis-generating regions of interest when predicting systemic phenotypes difficult for human interpretation. Machine learning on echocardiography images can streamline repetitive tasks in the clinical workflow, provide preliminary interpretation in areas with insufficient qualified cardiologists, and predict phenotypes challenging for human evaluation.
Catalytically-active porous assembly with dynamic pulsating motion for efficient exchange of products and reagents
Authors: Wu Shanshan , Huang Liping , Hou Yu , Liu Xin , Kim Jehan , Liang Yongri , Zhao Jiong , Zhang Liwei , Ji Hongbing , Lee Myongsoo , Huang Zhegang 
Published: January 2020

AbstractDespite recent advances in the use of porous materials as efficient heterogeneous catalysts which operate through effectively trapping reagents in a well-defined space, continuously uptaking reagents to substitute products in the cavity for efficient product turnover still remains challenging. Here, a porous catalyst is endowed with ‘breathing’ characteristics by thermal stimulus, which can enable the efficient exchange of reagents and products through reversible stacking from inflated aromatic hexamers to contracted trimeric macrocycles. The contracted super-hydrophobic tubular interior with pyridine environment exhibits catalytic activity towards a nucleophilic aromatic substitution reaction by promoting interactions between concentrated reagents and active sites. Subsequent expansion facilitates the exchange of products and reagents, which ensures the next reaction. The strategy of mesoporous modification with inflatable transition may provide a new insight for construction of dynamic catalysts.