bluuebunny/crossref_metadata_2025_split huggingface dataset:
Multi-objective parallel human-machine steering coordination control strategy of intelligent vehicles path tracking based on deep reinforcement learning
Authors: Wang Hongbo , Feng Lizhao , Li Shaohua , Chen Wuwei , Zhou Juntao 
Published: June 2023

Abstract
In the parallel steering coordination control strategy for path tracking, it is difficult to match the current driver steering model using the fixed parameters with the actual driver, and the designed steering coordination control strategy under a single objective and simple conditions is difficult to adapt to the multi-dimensional state variables’ input. In this paper, we propose a deep reinforcement learning algorithm-based multi-objective parallel human-machine steering coordination strategy for path tracking considering driver mis-operation and external disturbance. Firstly, the driver steering mathematical model is constructed based on the driver preview characteristics and steering delay response, and the driver characteristic parameters are fitted after collecting the actual driver driving data. Secondly, considering that the vehicle is susceptible to the influence of external disturbances during the driving process, the Tube MPC (Tube Model Predictive Control) based path tracking steering controller is designed based on vehicle system dynamics error model. After verifying that the driver steering model meets the driver steering operation characteristics, DQN (Deep Q-network), DDPG (Deep Deterministic Policy Gradient) and TD3 (Twin Delayed Deep Deterministic Policy Gradient) deep reinforcement learning algorithms are utilized to design a multi-objective parallel steering coordination strategy which satisfies the multi-dimensional state variables’ input of the vehicle. Finally, the tracking accuracy, lateral safety, human-machine conflict and driver steering load evaluation index are designed in different driver operation states and different road environments, and the performance of the parallel steering coordination control strategies with different deep reinforcement learning algorithms and fuzzy algorithms are compared by simulations and hardware in the loop experiments. The results show that the parallel steering collaborative strategy based on deep reinforcement learning algorithm can more effectively assist the driver in tracking the target path under lateral wind interference and driver misoperation, and the TD3 based coordination control strategy has better overall performance.
Industrial Sources of Per- and Polyfluoroalkyl Substances (PFAS) to a Sewershed in Ontario, Canada
Authors: Payne Mark , Kleywegt Sonya , Ng Chi-Fai 
Published: June 2023

Abstract
Per- and Polyfluoroalkyl Substances (PFAS) are ubiquitous in the environment despite global regulatory action to reduce or restrict their use in industrial processes and products. Fourteen PFAS were analyzed in effluents from four sectors; electroplaters (3), laundry and carpet cleaners (2), landfill leachate (2), and circuit board manufacturers (3) that (in)directly discharge to sewersheds and connected wastewater treatment plants. Circuit board manufacturers had relatively lower levels of total summed PFAS (∑PFAS14) concentrations (average 21.6 ng/L) than the other sectors; laundry and carpet cleaners > electroplaters > landfill leachate > circuit boarders. Maximum concentrations for individual PFAS were seen in carpet cleaning wastewater with values of 79,000 ng/L for perfluorohexane sulfonate (PFHxS); 26,000 ng/l perfluorooctane sulfate (PFOS) and 9,400, ng/l perfluorooctanoic acid (PFOA). These concentrations represent some of the highest measured PFAS concentrations in wastewater samples reported in the literature.
Reprogramming biocatalytic futile cycles through computational engineering of stereochemical promiscuity to create an amine racemase
Authors: Han Sang-Woo , Jang Youngho , Song Jimin , Kook Jihyun , Shin Jong-Shik 
Published: June 2023

Abstract
Repurposing the intrinsic properties of natural enzymes can offer a viable solution to current synthetic challenges through the development of novel biocatalytic processes. Although amino acid racemases are ubiquitous in living organisms, an amine racemase (AR) has not yet been discovered despite its synthetic potential for producing chiral amines. Here, we report the creation of an AR based on the serendipitous discovery that amine transaminases (ATAs) can perform stereoinversion of 2-aminobutane. Kinetic modeling revealed that the unexpected off-pathway activity results from stereochemically promiscuous futile cycles due to incomplete stereoselectivity for 2-aminobutane. This finding motivated us to engineer an S-selective ATA through in silico alanine scanning and empirical combinatorial mutations, creating an AR with broad substrate specificity. The resulting AR, carrying double point mutations, enables the racemization of both enantiomers of diverse chiral amines in the presence of a cognate ketone. This strategy may be generally applicable to a wide range of transaminases, paving the way for the development of new-to-nature racemases.
A Review of Automatic Generation of Test Cases from Use Case Specification
Authors: Asefa Surafiel Habib 
Published: June 2023

Abstract
Software testing is an integral phase in the software development life cycle (SDLC). It refers to the process of verifying and evaluating the function of a software product. Among the testing activities, test case generation affects the effectiveness and efficiency of the testing process and requires a significant amount of effort and time. To reduce the effort and time involved in the manual test case generation process, significant research effort has been dedicated to the automatic generation of test cases. Although the majority of the proposed approaches are based on UML models, some works have presented a test case generation approach based on specifications. This literature review (LR) discusses use case specification-based automatic test case generation approaches and the methods used to validate them. Additionally, the review shows how the approaches differ in addressing some current issues in software testing.
Selection an Effective Drug Regimen on the Tumor Microenvironment of Non-invasive to Invasive Human Retinoblastoma
Authors: TarvijEslami Saeedeh , Nasirian Hosain , Nasirian Alimohamad , Abouali Behdokht , Ivrigh Sina Rahmani , Arabi Maryam , Bereimipour Ahmad 
Published: June 2023

Abstract
Malignant retinoblastoma has a dismal prognosis for children under the age of 5, and we still don't understand what drives the growth of these tumors. The microenvironment of retinoblastoma cells can have a great impact on the metastasis of retinoblastoma. In this study, which was based on bioinformatics analysis, we evaluated the gene expression profile in non-invasive and invasive retinoblastoma using databases and Python programming. We investigated the signaling pathways, gene ontology, protein network and candidates for important drugs in the microenvironment of retinoblastoma. The results showed that hypoxia, TGFB, MAPK and metabolic pathways have an effect in this event. VTN, TF, TNF, VEGFA, UBC, SP1 and TGFB1 were observed as a hub proteins in tumor microenvironment. Then, indomethacin and daurobicin seleceted as a high significant drugs, relationship with invasive retinoblastoma microenvironment proteins. Finally, the evaluation of the microenvironment of retinoblastoma still needs further investigations, because this cancer, due to its difficult access to the tumor, can cause secondary tumors for children. Therefore, the use of strong and different drug regimens can have a better effect on the tumor microenvironment and reduce drug resistance.
De novo biosynthesis of the hops bioactive flavonoid xanthohumol in yeast
Authors: Yang Shan , Chen Ruibing , Cao Xuan , Wang Guodong , zhou Yongjin 
Published: June 2023

Abstract
The flavonoid xanthohumol is an important flavor substance in the brewing industry that has a wide variety of bioactivities. However, its unstable structure is easily oxidized during the brewing process, resulting in its low content in beer. Moreover, its extraction and purification from plants requires laborious and expensive procedures. Microbial biosynthesis is considered a sustainable and economically viable alternative to supply natural products. However, the complex structures of natural products and regulation of the biosynthetic pathways make it challenging to construct and optimize the xanthohumol pathway in microbes. Here, we harnessed the brewing yeast Saccharomyces cerevisiae for the de novo biosynthesis of xanthohumol from glucose by modular fine-tuning of the competitive metabolic pathways, prenyltransferase engineering, enhancing precursor supply, substrate channeling, and peroxisomal engineering. These strategies significantly improved the production of the key xanthohumol precursor demethylxanthohumol (DMX) by 83-fold and achieved the de novo biosynthesis of xanthohumol for the first time in a microbial cell factory. We also revealed that prenylation is the key limiting step in DMX biosynthesis and that enhancing the supply of dimethylallyl pyrophosphate (DMAPP) and substrate channeling helps to drive the metabolic flux toward DMX biosynthesis, which should be helpful for improving the production of prenylated natural products. Our work provides feasible approaches for systematically engineering yeast cell factories for the de novo biosynthesis of complex natural products.
Mitochondrial CISD1/Cisd accumulation blocks mitophagy and genetic or pharmacological inhibition rescues neurodegenerative phenotypes in Pink1/parkin models
Authors: Martinez Aitor , Sanchez-Martinez Alvaro , Pickering Jake T. , Twyning Madeleine J. , Terriente-Felix Ana , Chen Po-Lin , Chen Chun-Hong , Whitworth Alex J. 
Published: June 2023

Abstract
Background Mitochondrial dysfunction and toxic protein aggregates have been shown to be key features in the pathogenesis of neurodegenerative diseases, such as Parkinson’s disease (PD). Functional analysis of genes linked to PD have revealed that the E3 ligase Parkin and the mitochondrial kinase PINK1 are important factors for mitochondrial quality control. PINK1 phosphorylates and activates Parkin, which in turn ubiquitinates mitochondrial proteins priming them and the mitochondrion itself for degradation. However, it is unclear whether dysregulated mitochondrial degradation or the toxic build-up of certain Parkin ubiquitin substrates is the driving pathophysiological mechanism leading to PD. The iron-sulphur cluster containing proteins CISD1 and CISD2 have been identified as major targets of Parkin in various proteomic studies.Methods We employed in vivo Drosophila and human cell culture models to study the role of CISD proteins in cell and tissue viability as well as aged-related neurodegeneration, specifically analysing aspects of mitophagy and autophagy using orthogonal assays.Results We discovered that the Drosophila homolog Cisd accumulates during aging, as well as in Pink1 and parkin mutant flies. We observed that build-up of Cisd is particularly toxic in neurons, resulting in mitochondrial defects and Ser65-phospho-Ubiquitin accumulation. Age-related increase of Cisd blocks mitophagy and impairs autophagy flux. Importantly, reduction of Cisd levels upregulates mitophagy in vitro and in vivo, and ameliorates pathological phenotypes in locomotion, lifespan and neurodegeneration in Pink1/parkin mutant flies. In addition, we show that pharmacological inhibition of CISD1/2 by rosiglitazone and NL-1 induces mitophagy in human cells and rescues the defective phenotypes of Pink1/parkin mutants.Conclusion Altogether, our studies indicate that Cisd accumulation during aging and in Pink1/parkin mutants is a key driver of pathology by blocking mitophagy, and genetically and pharmacologically inhibiting CISD proteins may offer a potential target for therapeutic intervention.
Individualized dose of anti-thymocyte globulin based on weight and pre-transplantation lymphocyte counts in pediatric patients: A single center experience
Authors: Wietstruck Angelica , Schulze Clara , Catalan Paula , Sotomayor Cristian , Zuñiga PAmela , Aguirre Noemi , Vizcaya Cecilia , Barriga Francisco 
Published: June 2023

Abstract
Anti-Thymocyte Globulin (ATG) has become standard in preventing GvHD in related and unrelated donor transplantation. There needs to be a consensus on the best administration schedule. The PARACHUTE trial reported excellent CD4 immune reconstitution (CD4 IR) using a dosing schedule based on the patient's weight and pre-conditioning absolute lymphocyte count (ALC). In 2015 we introduced the PARACHUTE dosing schedule at our center. Patients received ATG doses according to weight and ALC starting day -9. One hundred one patients were transplanted for malignant and non-malignant diseases. CD4 IR+ was seen in 81% of patients. The incidence of grade II-IV and III to IV aGvHD was 26.6% and 15.3% and 5% for cGvHD with no severe cases. We found no difference in aGvHD between donor type and stem cell sources. Five-year EFS and OS were 77.5% and 83.5%. Grade III-IV GFRS was 75.2%. CD4 IR + patients had better EFS (93.1% vs. 77.7%, p=0.04) and lower non-relapse mortality (2.7% vs. 22.2%, p=0.002). The PARACHUTE ATG dosing schedule individualized by weight and ALC results in good early immune reconstitution, low incidence of cGvHD, and favorable survival for patients with different disease groups, donor types, and stem cell sources.
Costs of transitioning to net-zero emissions under future climates
Authors: Bilotto Franco , Christie-Whitehead Karen , Malcolm Bill , Barnes Nicoli , Cullen Brendan , Ayre Margaret , Harrison Matthew 
Published: June 2023

Abstract
Land managers are challenged with balancing priorities for agri-food production, greenhouse gas (GHG) abatement, natural conservation, social and economic license to operate. We co-designed pathways for transitioning farming systems to net-zero emissions under future climates. Few interventions enhanced productivity and profitability while also reducing GHG emissions. Seaweed (Asparagopsis) feed supplement and planting trees enabled the greatest mitigation (67–95%), while enterprise diversification (installation of wind turbines) and improved feed-conversion efficiency (FCE) were most conducive to improved profitability (17–39%). Mitigation efficacy was hampered by adoptability. Serendiptiously, the least socially acceptable option – business as usual and purchasing carbon credits to offset emissions – were also the most costly options. In contrast, stacking synergistic interventions enabling enteric methane mitigation, improved FCE and carbon removals entirely negated net emissions in a profitable way. We conclude that costs of transitioning to net-zero vary widely (-64% to + 30%), depending on whether interventions are stacked and/or elicit productivity co-benefits.
Neutrophils of MDSCs in ovarian cancer are negatively related to Immunotherapy and prognosis: a multi-omics-based consensus clustering
Authors: Li Liling , Yang Haolin , Bi Sheng , Zhang Weina , Huang Jinchang 
Published: June 2023

Abstract
Background:: A plateau has been reached for conventional therapies in ovarian cancer as there is no definitive increase in overall survival. It is necessary to distinguish molecular subtypes based on multi-omics integration to take more targeted strategies to improve prognosis and increase therapeutic efficacy.
Methods:: A total of 202 patients with mRNA, miRNA, DNA methylation, somatic mutation, and Reverse Phase Protein Array (RPPA) data were assembled into one multi-omics dataset and then developed a model via MOVICS. A total of 1028 OV samples with raw microarray data and clinicopathological information were obtained from the Gene Expression Omnibus (GEO) as a validation cohort. Then, a series of immune infiltration analyses were performed by GSVA, TIDE, EaSIeR, and ESTIMATE package. Lastly, Metascape was conducted to unravel activated signaling pathways, and the ChAMP package was used to identify potential biomarkers.
Results:: 202 OV samples retrieved from the multi-omics TCGA cohort were categorized into two subgroups by MOVICS. Drug sensitivity analysis revealed that targeted therapy and immunotherapy are possibly considered as preferable approaches to prolong the survival of such patients as C2 while platinum-based drugs to C1. Furthermore, immune infiltration analysis revealed that there is a negative correlation between myeloid and neutrophil cells (MDSC) and prognosis and response to immunotherapy in C1. Immune-associated pathways were mainly enriched in C1 and metabolic-related pathways in C2. CRISPLD2, SLC12A8, STARD8, and DCHS1 were considered as potential targets to possibly improve the outcome by disrupting the immunosuppressive immunocytes by integration of DNA methylation and transcriptome expression.
Conclusion:: The molecular subtypes based on integrated multi-omics provided novel insights into the molecular basis of immune recognition and immune regulation of cancer cells for predicting the prognosis of ovarian cancer and potential clinical therapeutic targets for OV.
Effects of Exercise Type on Core Symptoms of ADHD in Children：A Systematic Review
Authors: li liang , song Yi-ling , Zhang lingling , Wu xueping 
Published: June 2023

Abstract
Background
Attention-deficit/hyperactivity disorder (ADHD) is the most common neurodevelopmental disorder disease in children
Methods
Randomized controlled trials or crossover studies were identified in four databases (PubMed, Web of Science, EBSCO, and China Knowledge Network) from January 2000 to January 2022. A total of 27 interventional studies met the inclusion criteria.
Results
Interventions of various types of aerobic exercise performed at moderate intensity (45%-75% peak heart rate) for 20 minutes or more 2–3 times per week best improved executive function and attention deficits in children with ADHD.
conclusions
Integrating different types of aerobic exercise programs, comparing acute vs long-term effects of the same intervention and assessing gender differences may provide more evidence-based and precise intervention programs for children with ADHD and help exercise interventions to become more effective alternative or complementary non-pharmacological treatments for ADHD in children.
Detection of disease-associated microglia among various microglia phenotypes induced by West Nile virus infection in mice
Authors: Thammahakin Passawat , Maezono Keisuke , Maekawa Naoya , Kariwa Hiroaki , Kobayashi Shintaro 
Published: June 2023

Abstract
West Nile virus (WNV) has emerged as a significant cause of viral encephalitis in humans and horses. However, the pathogenesis of the West Nile encephalitis remains unclear. Microglia are activated by WNV infection, and the pathogenic involvement of their phenotypes is controversial. In this study, we examined the diversity of microglia phenotypes caused by WNV infection by assessing various microglia markers and identified disease-associated microglia in WNV-infected mouse brain tissue. Cells positive for general microglia markers such as Iba1, P2RY12, or TMEM119 were detected in the control and WNV-infected brain tissue. The morphology of the positive cells in brain tissue infected by WNV was different from that of control brain tissue, indicating that WNV infection induced activation of microglia. The activated microglia were classified into various phenotypes by investigation of specific marker expression. Among the activated microglia, disease-associated microglia that were positive for CD11c and weakly positive for TMEM119 were detected close to the WNV-infected cells. These results indicate that WNV infection induces activation of diverse microglia phenotypes and that disease-associated microglia may be associated with the pathogenicity of WNV infection in the mouse brain.
Flexible anchored mats of artificial seagrass for restoration: wave dynamics and agreement with contemporary models
Authors: Villanueva Raúl , Paul Maike , Schlurmann Torsten 
Published: June 2023

Abstract
Seagrass restoration requires a sound understanding of the hydrodynamics around established meadows. Present know-how primarily stems from idealized artificial seagrass (ASG) attached to a fixed bed. With the goal of accessible field deployment for restoration, anchored prototype scale ASG mats (coconut mesh) were tested under differing wave conditions to analyze hydrodynamic interaction and assess the suitability of contemporary predictive models. Velocity structure and wave propagation were measured around one and two ASG mats (separated by a 2-m gap). The mats reduced orbital velocities by up to 16% (2 mats), whereby the average reduction was low (< 10%) compared to the non-vegetated conditions. Velocities increased above the ASG, with the gap enhancing velocity (up to 11%) instead of attenuating it. Wave decay followed an exponential decrease, further enhanced by the second mat. Current models did not capture the induced hydrodynamics for the full range of wave conditions tested, with the second mat increasing uncertainties. Wave decay models generally overestimated wave attenuation (up to 30%), except for longer wave periods. Nevertheless, for the full range of conditions, the models provide accurate insight into the expected magnitude of attenuation under field conditions. It is speculated that mat flexibility affects the surrounding hydrodynamics through inherent motion, with the gap contributing to the uncertainties.
Oral cavity manifestations in COVID-19 patients: A cross-sectional study
Authors: Fernandes Tatiana , Ogrzewalska Maria , Martins Ezequias , Siqueira Marilda , Brasil Patrícia , Calvet Guilherme 
Published: June 2023

Abstract
Objective
To determine the prevalence of oral manifestations in symptomatic patients in the ambulatory setting with suspected COVID-19.
Methods
This cross-sectional study evaluated oral manifestations in adults (aged ≥ 18 years) with suspected and confirmed SARS-CoV-2 infection. Chi-square and Fisher’s exact tests were used to compare data between the groups (RT-PCR-positive and RT-PCR-negative patients).
Results
One hundred and thirty-sixparticipants were included. Mostwere female (n = 79; 58.1%), mean age of 39.53 (± 14.17) years. Of these, 54 (39.7%) had a positive RT-PCR test, and 82 (60.3%) had negative RT-PCR results. Oral manifestations were observed in 40 participants (74.1%)in the RT-PCR-positive group and in 67 participants (81.7%) in the RT-PCR-negative group. The most common oral manifestations were xerostomia (n = 85; 62.5%) and dysgeusia/ageusia (n = 57; 41.9%). Different rates of gingivitis (n = 12; 22.2% vs n = 5; 6.1%) and halitosis (n = 7; 13.0% vs n = 1; 1.2%) were observed between the RT-PCR-positive and negative groups, respectively. Mouth ulcers, glossitis, tongue coating, and petechiae were reported in both groups, without significant differences.
Conclusions
A high prevalence of oral manifestations was observed in symptomatic patients with suspected or confirmed COVID-19.
Clinical Relevance
This study highlights the importance of routine oral examinations by dentists as part of the multidisciplinary care of COVID-19 patients.