bluuebunny/crossref_metadata_2025_split huggingface dataset:
Rapid combinatorial rewiring of metabolic networks for enhanced poly(3- hydroxybutyrate) production in Corynebacterium glutamicum
Authors: Yim Sung Sun , Choi Jae Woong , Lee Yong Jae , Jeong Ki Jun 
Published: October 2022

Abstract
Background: The disposal of plastic waste is a major environmental challenge. With recent advances in microbial genetic and metabolic engineering technologies, microbial polyhydroxyalkanoates (PHAs) are being used as next-generation biomaterials to replace petroleum-based synthetic plastics in a sustainable future. However, the relatively high production cost of bioprocesses hinders the production and application of microbial PHAs on an industrial scale.
Results: Here, we describe a rapid strategy to rewire metabolic networks in an industrial microorganism, Corynebacterium glutamicum, for the enhanced production of poly(3-hydroxybutyrate) (PHB). A three-gene PHB biosynthetic pathway in Rasltonia eutropha was refactored for high-level gene expression. A fluorescence-based quantification assay for cellular PHB content using BODIPY was devised for the rapid fluorescence-activated cell sorting (FACS)-based screening of a large combinatorial metabolic network library constructed in C. glutamicum. Rewiring metabolic networks across the central carbon metabolism enabled highly efficient production of PHB up to 29% of dry cell weight, which is the highest PHB content ever reported in C. glutamicumusing a sole carbon source.
Conclusions: We successfully constructed a heterologous PHB biosynthetic pathway and rapidly optimized metabolic networks across central metabolism in C. glutamicum for enhanced production of PHB using glucose or fructose as the sole carbon source in minimal medium. We expect that this FACS-based metabolic rewiring framework will accelerate strain engineering processes for the production of diverse biochemicals and biopolymers.
Combined Non-convex Second-order Total Variation with Overlapping Group Sparsity for Full Waveform Inversion
Authors: fu Hongsun , Qi Hongyu , Gu Ruixue 
Published: October 2022

Abstract
Full Waveform Inversion (FWI) can provide an accurate velocity modelby matching observed and simulated seismograms. Mathematically, FWIis a highly ill-posed inverse problem that the inversion results lackdependence on the observed data. For a stable and reasonable inversion,proper regularization methods have to be taken into account.We proposea novel composite regularization for frequency-domain FWI problem,which uses a non-convex second-order total variation (TV) term and anoverlapping group sparse TV (OGS-TV) regularization term. Comparedwith the conventional TV regularization, our method has better accuracyand robustness, and could effectively make use of the structuralsparsity in the velocity model. Furthermore, the alternating directionmultiplier algorithm with the adaptive selection of the penalty parametersis developed to solve this composite constraint problem, which canimprove the stability of the FWI process. To illustrate the superior performanceof the proposed FWI method both visually and quantitatively,we present several numerical examples through the comparison betweenour FWI method and conventional FWI method with TV regularization.
Phosphoethanolamine reverses aberrant DNA methylation in non-alcoholic steatohepatitis caused by Pcyt2 deficiency
Authors: Grapentine Sophie , Agarwal Prasoon , Dolinsky Vern , Bakovic Marica 
Published: October 2022

Abstract

Background Accumulating evidence links disruptions in phospholipid homeostasis to obesity, type 2 diabetes, and fatty liver diseases. Mice with a heterozygous ablation of the phosphatidylethanolamine (PE) synthesizing enzymePcyt2+/−show reduced PE synthesis and turnover and develop an age-dependent metabolic syndrome that is characterized by impaired fatty acid and glucose metabolism, hypertriglyceridemia, insulin resistance, obesity, and all characteristics of NASH. Aberrant DNA methylation can lead to the onset of pathological phenotypes and is increasingly being implicated in age-related metabolic diseases, including NASH. The methylation of PE to phosphatidylcholine (PC) is a major consumer of liver S-adenosyl methionine (SAM) and thus, alterations in PE metabolism have the potential to influence DNA methylation by modulating SAM availability. Here, we hypothesize that abnormal DNA methylation patterns underly the development ofPcyt2+/−NASH. We conduct an epigenome-wide methylation analysis to determine differential methylation and investigate whether treatment with the Pcyt2 substrate phosphoethanolamine (PEtn) for 8 weeks can reverse aberrant DNA methylation through the stimulation PE synthesis. ResultsPcyt2+/−NASH liver experiences significant alterations in DNA hypo- and hypermethylation relative toPcyt2+/+. Differentially methylated genes belong to pathways including PI3K-Akt signalling pathway, Foxo signalling pathway, oxidative phosphorylation and insulin signalling/secretion indicating that epigenetic regulation underlies many of our previously established pathological mechanisms ofPcyt2+/−NASH. Previously unidentified pathways during Pcyt2 deficiency are highlighted such as cell cycle regulation and cellular senescence that may contribute to NASH development. Treatment with PEtn dramatically reverses aberrant total and protein-coding DNA methylation patterns by 96%. PEtn treatment restored the methylation status of key genes involved in epigenetic modifications and induced differential methylation of genes associated with obesity and T2DM such asAdyc3, Celsr2, Fam63b.Conclusion ThePcyt2+/−liver methylome and transcriptome is altered and likely underlies much of the pathology inPcyt2+/−NASH phenotype. PEtn significantly attenuates aberrant DNA methylation inPcyt2+/−liver by stimulating the CDP:Ethanolamine Kennedy pathway and corrects the epigenetic regulation of genes involved in the pathogenesis of NASH, showing its therapeutic potential. This analysis provides critical insight into the epigenetic basis of NASH pathophysiology and suggests diagnostic markers and therapeutic targets.
Diagnostic performance of total PSA an its derivatives for clinically significant prostate cancer and high-grade prostate cancer
Authors: Wang Changming , Zhang Bin , Zhang Qi , Wang Lei , Wang Ling , Xu Siqin , Tao Tao , Xiao Jun 
Published: October 2022

Abstract
Background: Diagnostic value of total PSA an its derivatives for prostate cancer is still controversial. Our aim is to explore the diagnostic performance of total prostate-specific antigen (tPSA) and its derivatives for clinically significant prostate cancer (csPCa) and high-grade prostate cancer (hgPCa).
Methods: Data of qualified 423 patients who received prostate biopsy from October 2020 to July 2022 was used to accomplish this study. Patient’s clinical characteristics were compared by Mann Whitney U test. Spearman rank correlation analysis was performed to calculate correlation coefficients. Univariate logistic regression analysis was used to screen the related variables of csPCa and hgPCa. Receiver-operating characteristic (ROC) curves and diagnostic tests were performed for assessing the diagnostic value of clinical variables.
Results: Of these 423 patients, 131/423 (31.0%) were diagnosed with csPCa and 103/423 (24.3%) were diagnosed with hgPCa. By plotting ROC curves, PSAD had highest diagnostic accuracy for both csPCa (AUC: 0.840, 95%CI: 0.802-0.874) and hgPCa (AUC: 0.825, 95%CI: 0.785-0.860), tPSA and prostate volume had fair diagnostic value after PSAD, then, f/t PSA only had mediocre performance, but fPSA alone had very low diagnostic value. After stratifying patients into different subgroups of tPSA, prostate volume, PSA density (PSAD) and free/total PSA (f/t PSA). We found the detection rate will obvious rise following by increased tPSA, PSAD and decreased prostate volume, f/tPSA. The results of diagnostic tests found the sensitivity and negative predictive value were 79.4%, 83.0% for tPSA<10ng/ml, 80.8%, 76.2% for f/tPSA>0.20, 95.4%, 93.2% for prostate volume≥70ml and 96.9%, 96.0% for PSAD<0.15 ng/ml2 respectively.
Conclusions: In this study, we evaluated the diagnostic value of tPSA and its derivatives for identification of prostate cancer. For patients with suspected prostate cancer, lower tPSA and PSAD, bigger prostate volume and higher f/tPSA value may mean smaller probability of csPCa.
Aerobic biodegradation of untreated polyester-polyether urethanes by newly isolated yeast strains Exophilia sp. NS-7 and Rhodotorula sp. NS-12
Authors: Giyahchi Minoo , Moghimi Hamid 
Published: October 2022

Abstract
In this study, two polyester-polyether urethane degrading yeasts were isolated from forest soil and wastewater. These isolates were identified through ITS region gene sequencing as two new strains of Exophilia sp. NS-7 and Rhodotorula sp. NS-12. The polyurethanes (PUs) biodegradation ability of two strains was evaluated by urease, protease, esterase, and Impranil® degradation activity assays, Fourier transformed infra-red spectroscopy (FT-IR), scanning electron microscopy (SEM), Sturm test, and Proton nuclear magnetic resonance (H-NMR) spectroscopy. The results showed that Exophilia sp. NS-7 is esterase, protease, and urease positive, and Rhodotorula sp. NS-12 can produce esterase and urease. Both strains can degrade Impranil® as the sole source of carbon with the highest growth rate in 4–6 and 8–12 days, respectively. SEM micrograph revealed PU degradation ability in both strains by showing so many pits and holes in treated films. The Sturm test showed that these two isolates can mineralize PU to CO2, and significant decreases in N-H stretching, C-H stretching, C = O stretching, and N-H/ C = O bending absorption in the molecular structure of PU were revealed by the FT-IR spectrum. The detection of new signals in the H-NMR spectrum after the treatment also confirmed the destructive effects of both strains on PU films.
Renewable Composite Quantile Method and Algorithm for Nonparametric Models with Streaming Data
Authors: Chen Yan , Fang Shuixin , Lin Lu 
Published: October 2022

Abstract
We are interested in renewable estimations and algorithms for nonparametric models with streaming data. In our method, the nonparametric function of interest is expressed through a functional depending on a weight function and a conditional distribution function (CDF). The CDF is estimated by renewable kernel estimations combined with function interpolations, based on which we propose the method of renewable weighted composite quantile regression (WCQR). Then we fully use the model structure and obtain new selectors for the weight function, such that the WCQR can achieve asymptotic unbiasness when estimating specific functions in the model. We also propose practical bandwidth selectors for streaming data and find the optimal weight function minimizing the asymptotic variance. The asymptotical results show that our estimator is almost equivalent to the oracle estimator obtained from the entire data together. Besides, our method also enjoys adaptiveness to error distributions, robustness to outliers, and efficiency in both estimation and computation. Simulation studies and real data analyses further confirm our theoretical findings.
Novel Ultra-Energy-Efficient Reversible Designs of Sequential Logic Quantum-Dot Cellular Automata Flip-Flop Circuits
Authors: Alharbi Mohammed , Edwards Gerard , Stocker Richard 
Published: October 2022

Abstract
Quantum-dot cellular automata (QCA) is a technological approach to implement digital circuits with exceptionally high integration density, high switching frequency, and low energy dissipation. QCA circuits are a potential solution to the energy dissipation issues created by shrinking microprocessors with ultra-higher integration densities. Current QCA circuit designs are nonreversible, yet reversible circuits are known to increase energy efficiency. Thus, the development of reversible QCA circuits will further reduce energy dissipation. This paper presents novel reversible and nonreversible sequential QCA set/reset (SR), data (D), Jack Kilby (JK), and toggle (T) flip-flop designs based on the majority gate that utilizes the universal, standard, and efficient (USE) clocking scheme, which allows the implementation of feedback paths and easy routing for sequential QCA-based circuits. The simulation results confirm that the proposed reversible QCA USE sequential flip-flop circuits exhibit energy dissipation less than the Landauer energy limit. Nonreversible QCA USE flip-flop designs, although having higher energy dissipation, sometimes have floorplan areas and delay times less than those of reversible designs; therefore, they are also explored. The trade-offs between the energy dissipation versus the area cost and delay time for the reversible and nonreversible QCA circuits are examined comprehensively.
CD146+ umbilical cord mesenchymal stem cells exhibit higher immunomodulatory activity and therapeutic efficacy in septic mice
Authors: Zhang Lin , Zhang Xiaoxu , Liu Yubin , Zhang Weiyuan , Wu Chu-Tse , Wang Lisheng 
Published: October 2022

Abstract
Background
Several animal studies have shown that MSCs can significantly improve the survival of sepsis. CD146 + MSCs, a subpopulation of mesenchymal stem cell (MSCs), correlate with high therapeutic and secretory potency. However, their therapeutic effect on sepsis and detail mechanisms about regulation of macrophage have not been explored.
Methods
The effect of CD146+/-MSCs on differentiation of Treg,Th1,Th17 subsets was evaluated by flow cytometry. The paracrine effects of CD146+/-MSCs on RAW264.7 phagocytosis and LPS-stimulated polarization were studied using a co-culture protocol. In addition, we employed Luminex bead array and RNA sequencing analysis to determine the mechanisms of MSCs on LPS-stimulated RAW264.7. The Arg1 protein was detected by Western blot. CD146+/-MSCs were injected into LPS-induced sepsis mice by tail vein. The treatment effect was assessed by organ HE staining, T-cell subsets, cytokine in plasma, peritoneal macrophages, infiltrating monocytes subpopulations.
Results
In vitro, CD146 + MSCs could significantly increase the Treg cells proportion in PBMCs stimulated by PHA. Both CD146+/-MSCs can reduce the proportion of Th1 and Th17 subsets. CD146 + MSCs can increase the phagocytic rate of raw264.7. The RNA sequencing data indicated that UC-MSCs therapy improved LPS-induced raw264.7 through PPAR and cytokine receptor pathways. The differences between the CD146 + and CD146- groups were clustered in arginine metabolism. CD146 + MSCs decreased NO production and increased agr1 expression. CD146 + MSCs secreted higher IL15,IFNγ, VEGF and lower IL1β, IL8 under LPS. In vivo, CD146+/-MSCs treatment can improve the pathological damage of organs caused by LPS. CD146+/-MSCs therapy significantly decreased CD4 expression, increased CD8 expression, and decreased CD4/CD8 ratios, which was similar to that in the normal group. CD146+/-MSCs can reduce IL1β,IL6 content in plasma. The level of IL10 at 24h and CXCL1 at 12h in CD146 + MSCs group was the highest. The phagocytic capacity of peritoneal macrophages in CD146 + MSCs group was better than that in CD146- group and LPS group at 12h. The CD146+/-MSCs had significantly reduced numbers of monocytes in the peritoneal cavity. CD146 + MSCs enhanced the ratios of CD11b + Ly6Clo reparative monocytes and CD11b + Ly6Chi inflammatory monocytes until 24h.
Conclusions
Compared with CD146-MSCs, CD146 + MSCs can accelerates the end of the inflammatory response and have robust anti-inflammatory effects, by increasing the Treg cells, promoting macrophage phagocytosis, enhancing the reparative macrophage, secreting more VEGF, etc.
De novo transcriptome analysis and development of novel EST-SSR markers in Bergenia ciliata (Haw.) Sternb. (Saxifragaceae) through Illumina sequencing
Authors: Singh Harish Chandra , Tiwari Vandana , Tiwari Avinash , Rana Tikam Singh 
Published: October 2022

Abstract
Bergenia ciliata (Haw.) Sternb. is an important herb predominantly found in Indian Himalayan Region (IHR). It is widely used in medicines and healthcare system, cosmetics, food, fodder, and ornamental purposes. Illumina sequencing and de novo transcriptome assembly were carried out in B. ciliata to develop and identify simple sequence repeat markers for genetic diversity and conservation studies. The assembled data generated a total of 65,010 unigenes that showed significant similarities when compared with seven functional databases including 53,577 (Non-Redundant Protein Sequence Database: 82.41%), 44,297 (Nucleotide Sequence Database: 68.14%), 42,287 (Swiss Prot: 65.05%), 15,027 (Eukaryotic Orthologous Groups: 23.11%), 22,540 (KEGG Orthology: 34.67%), 29,477 (Gene Ontology: 45.34%) and 20,609 (Pfam: 31.7%) unigenes. In this study, a total of 18,226 SSRs and 14,497 SSR containing sequences were identified. Dinucleotides were found to be abundant (47.88%) in B. ciliata followed by mononucleotides (35.04%), and trinucleotides repeat (15.90%). AG/CT was the most common di-nucleotide repeat (40.33%). A total of 11,839 EST-SSR primers were designed, of which 96 primer pairs were synthesized randomly. Finally, 18 primer pairs were selected that revealed clear, distinct polymorphic bands when examined in eight diverse B. ciliata accessions. Furthermore, the transcriptome data and the EST-SSR markers will be an important resource for investigating genetic diversity in B. ciliata and other species of the family Saxifragaceae.
Treatment of herpes zoster with brivudin in immunocompromised children
Authors: Vogel Clara , Wetzel Laura , Wutzler Peter , Gruhn Bernd 
Published: October 2022

Abstract
Purpose: Herpes zoster (HZ) is caused by endogenous reactivation of latent varicella-zoster virus (VZV) that persists in sensory ganglia after primary infection. The incidence and severity of HZ increases during immunosuppression. Especially immunocompromised patients are at high risk of developing a cutaneous rash and suffering from delayed healing of lesions. Bromovinyl deoxyuridine (brivudin), one of the most potent oral inhibitors of VZV replication, is widely used in therapy of HZ in adult patients, particularly in Europe. In this study, we investigated the efficacy of brivudin in immunocompromised children to provide an outpatient treatment option.
Methods: In this prospective study, we included 64 immunocompromised pediatric patients with a median age of 14 years. Forty-seven patients received immunosuppressive therapy as part of hematopoietic stem cell transplantation and 17 patients as part of chemotherapy. Primary diagnosis was made clinically by examining the nature and the localization of the skin lesions. Laboratory confirmation was conducted based on the detection of VZV DNA in vesicle fluid and blood samples. Brivudin was administered orally at a single dose of 2-5 mg/kg per day. We monitored the patients’ response for the full time of treatment and observed the time of full crusting of lesions, loss of crusts, and any adverse effects that occurred.
Results: Patients received medication for 7-21 days (median: 14 days). All children responded promptly to antiviral treatment and recovered completely from their HZ infections without complications.Crusting of lesions was reached after 3-14 days (median: 6 days). Full healing of skin lesions was ascertained within 7-21 days (median: 12 days). Overall, brivudin therapy was well tolerated. No clinical side effects during or after the treatment were observed. High compliance was achieved due to the once-daily dosing regimen. All patients were treated in an outpatient manner.
Conclusion: Oral brivudin was a very effective and well-tolerated therapy in immunocompromised children with HZ infection. The oral administration offers potential for outpatient treatment of HZ in these patients.
Optimization of job shop scheduling problem based on deep reinforcement learning
Authors: Qiao Dongping , Duan Lvqi , Li HongLei , Xiao Yanqiu 
Published: October 2022

Abstract
Aiming at the optimization problem of minimizing the maximum completion time in job shop scheduling, a deep reinforcement learning optimization algorithm is proposed. First, a deep reinforcement learning scheduling environment is built based on the disjunctive graph model, and three channels of state characteristics are established. The action space consists of 20 designed combination scheduling rules. The reward function is designed based on the proportional relationship between the total work of the scheduled operation and the current maximum completion time. The deep convolutional neural network is used to construct action network and target network, and the state features are used as inputs to output the Q value of each action. Then, the action is selected by using the action validity exploration and exploitation strategy. Finally, the immediate reward is calculated and the scheduling environment is updated. Experiments are carried out using benchmark instances to verify the algorithm. The results show that it can balance solution quality and computation time effectively, and the trained agent has good generalization ability to the scheduling problem in the non-zero initial state.
Keywords
Deep reinforcement learning · Job shop scheduling · Scheduling rules · Agent
Introducing the E100: Will the improvement make a significant difference? Financial analysis based on sleeve gastrectomy
Authors: Guevara Oriana , Lam Victoria , Sanchez Alexis , Arias Simon , Teixeira Andre , Ghanem Muhammad 
Published: October 2022

Abstract
Robotic Assisted surgery has proven to show significant advantages in surgery, for patients and surgeons alike. Nontheless the elevated cost remains a barrier to its acceptance in the medical field. Strategies to reduce cost should be implemented as a way to ensure cost-effectiveness in robotic-assisted procedures. The aim of this article was to compared the performance of the new generator E100 (Intuitive Surgical, Inc.) vs. VIO dV 2.0 (Erbe Elektromedizin GmbH) by analyzing the number of times the generators were activated, the average time per seal, total sealing time, and console time. Financial impact based on annual volume was determined. A total of 1,457 sleeves gastrectomies (Erbe:746, E100:711) were analyzed, the average activation per case was similar in both groups. The sealing time dropped by 42.3% and the average console time dropped by 8 minutes in cases with the E100. The financial analysis concluded that transitioning to the E100, will in fact save $33K to $34K/year. Proving that Introducing the new generator is a successful strategy to reduce costs.
Group decision-making with hesitant fuzzy linguistic preference relations in view of worst and average indexes
Authors: Li Jian , Niu Li-li , Chen Qiongxia , Li Feilong 
Published: October 2022

Abstract
To address the situation where Multi-criteria decision-making (MCDM) problems with hesitant fuzzy linguistic preference relations (HFLPRs), this study introduces a group decision-making method in view of worst and average indexes simultaneously. First, several optimization models for deriving the worst and average additive consistency indexes of HFLPRs are proposed. The main characteristic of the constructed optimization models is that the personalized individual semantics (PISs) model is taken into accounted. And then the concept of acceptable additive consistent HFLPRs is developed, which takes into accounted the worst consistency index (WCI) and average consistency index (ACI). Second, several optimization models are constructed for improving the consistency of HFLPRs. The main characteristic of the constructed optimization models is that two predefined thresholds for the WCI and ACI are considered. It requires the consistency level of all the linguistic preference relations (LPRs) derived from original HFLPR meet the threshold of WCI, and the average consistency level of all LPRs reaches the threshold of ACI. Third, an algorithm is designed for deriving priority weights from acceptable consistent HFLPRs. Finally, the presented models are validated using a numerical example and extensive comparative analyses.