bluuebunny/crossref_metadata_2025_split huggingface dataset:
Structural and stereochemical determinants for hGAT3 inhibition: development of novel conformationally constrained and substituted analogs of (S)-isoserine.
Authors: Bavo Francesco , Kickinger Steffanie , Lie Maria E.K. , avgerinos Christos , Xu Yue , Wilhelmsen Kristine Sloth , Wellendorph Petrine , Frølund Bente 
Published: May 2023

Abstract

The GABA transporter 3 (GAT3) is a member of the GABA transporter (GAT) family proposed to have a role in regulating tonic inhibition. The GAT3-preferring substrate (S)-isoserine has shown beneficial effects in a mouse model of stroke accompanied by an increased GAT3 expression, indicating a molecular mechanism mediated by GAT3. However, (S)-isoserine is not ideally suited for in vivo studies due to a lack of selectivity and brain permeability. To elucidate the structural determinants of (S)-isoserine for GAT3 inhibition, and to optimize and inform further ligand development, we here present the design, synthesis and pharmacological evaluation of a series of conformationally constrained isoserine analogues with defined stereochemistry. Using [3H]GABA uptake assays at recombinant human GAT3, we identified the azetidine and pyrrolidine analogs ((S,S)-6a and (S,S)-7a) as the most potent inhibitors. To further elaborate on the selectivity profile both compounds were tested at all GATs, the taurine transporter (TauT) and GABAA receptors. Although (S,S)-6a and (S,S)-7a are comparable to (S)-isoserine with respect to potency, the selectivity versus the taurine transporter was significantly improved (at least 6 and 53 times more activity at hGAT3, respectively). A subsequent comprehensive structure-activity study showed that different connectivity approaches, stereochemical variations, simple or larger α- and N- substituents, and even minor size enlargement of the alicyclic ring all abrogated GAT3 inhibition, indicating very strict stereochemical and size requirements. The observed structure activity relationships may guide future ligand optimization and the novel ligands ((S,S)-6a and (S,S)-7a) can serve as valuable tools to validate the proposed GAT3-mediated effect of (S)-isoserine such as in functional recovery after stroke and thus help corroborate the relevance of targeting GAT3 and tonic inhibition in relevant brain pathologies.
Getting Closer or Keeping Distance? The Role of Prefrontal Cortex and Temporoparietal Junction in Interpersonal Comfort and Emotional Approach
Authors: Nejati Vahid , Mardanpour Aylin , Zabihzadeh Abbas , Estaji Reza , Shahidi Shahriar 
Published: May 2023

Abstract
Our perception of physical distance to individuals and stimuli is influenced by our mental distance and relatedness. The present study aimed to investigate the role of the dorsolateral prefrontal cortex (dlPFC), ventromedial prefrontal cortex (vmPFC), and right temporoparietal junction (rTPJ) in interpersonal comfortable distance and approach behaviors towards emotional stimuli. Twenty healthy volunteers received brain stimulation in four separate sessions with a one-week interval, including anodal left dlPFC, anodal right vmPFC, anodal rTPJ, and sham condition, with an extracranial return electrode. Our results revealed an increase in interpersonal distance during anodal rTPJ stimulation and a decrease in distance to positive pictures during anodal vmPFC stimulation. These findings suggest that the rTPJ plays a role in the perceptual component of self-other distancing, while the vmPFC is involved in approaching positive emotions.
TRPA1 promotes cisplatin-induced acute kidney injury by regulating the endoplasmic reticulum stress-mitochondrial damage
Authors: Deng Fei , Zhang Heping , Zhou Wei , Ma Shijie , Kang Yuwei , Yang Wei , Zhao Liangbin , Qin Wei 
Published: May 2023

AbstractBackground Cisplatin (DDP) is a widely used and effective chemotherapeutic agent against cancer. However, nephrotoxicity is one of the most common side effects of DDP, and it can proceed to acute kidney injury (AKI). The aim of this study was to investigate the mechanism of TRPA1 in promoting DDP-induced AKI through modulation of the endoplasmic reticulum stress (ERS)-mitochondrial damage. Methods A DDP-induced HK-2 cell model in vitro and mouse model in vivo were established and treated with the TRPA1 antagonist (HC-030031). We also used TRPA1 agonists, and treated with ERS inhibitors or GRP75 inhibitors. Renal function, histopathological changes, apoptosis, ERS and mitochondria-related proteins expression, mitochondrial changes, calcium ion concentration, cell proliferative activity, mitochondrial membrane potential (MMP), ATP, and ROS levels were also evaluated. Result DDP increased Scr and BUN levels, caused renal tissue injury and cell apoptosis, decreased ERS-related proteins GRP78, CHOP, and GRP75. The mitochondrial fusion-related proteins OPA1, MFN1, and MFN2, and mitochondrial division-related proteins p-DRP1 and MFF were elevated, DDP lead to mitochondrial dysfunction, and increased calcium ion concentration. In addition, DDP inhibited cell proliferation activity, decreased MMP and ATP levels, and increased ROS levels. In contrast, HC-030031 had protective effects against DDP-induced ERS and mitochondrial dysfunctionin vivoandin vitro. Futhermore, TRPA1 agonists promoted mitochondrial dysfunction via mitochondria-associated endoplasmic reticulum membrane. ERS inhibitors and GRP75 inhibitors increased cell proliferation activity, reduced cell apoptosis, and modulated ERS-mitochondrial damage and calcium overload to improve cell injury. Conclusion TRPA1 promotes DDP-induced AKI by regulating the ERS-mitochondrial damage.
The impact of changing exposure to PM 2.5 on mortality for US diplomats with multiple international relocations: A modelling study
Authors: Edwards Leslie , Milner James , Wilkinson Paul , Milojevic Ai 
Published: May 2023

Abstract
Background Current evidence linking fine particulate matter (PM2.5) exposure and mortality is primarily based on long-term exposure for persons that live in the same residence, city and/or country throughout the study, with few residential moves or relocations. We propose a novel method to quantify the health impacts of PM2.5 for United States (US) diplomats who regularly relocate to international cities with different PM2.5 levels.Methods Life table methods were applied at an individual-level to US mortality statistics using the World Health Organization’s database of city-specific PM2.5 annual mean concentrations. Global Burden of Disease concentration-response (C-R) functions were used to estimate cause-specific mortality and days of life lost (DLL) for a range of illustrative 20-year diplomatic assignments for three age groups. Time lags between exposure and exposure-related mortality risks were applied. Sensitivity analysis of baseline mortality, exposure level, C-R functions and lags was conducted. The effect of mitigation measures, including the addition of air purifiers, was examined.Results DLL due to PM2.5 exposure for a standard 20-year assignment ranged from 0.3 days for diplomats’ children to 84.1 days for older diplomats. DLL decreased when assignments in high PM2.5 cities were followed by assignments in low PM2.5 cities: 162.5 DLL when spending 20 years in high PM2.5 cities compared to 62.6 DLL when spending one of every four years (5 years total) in a high PM2.5 city for older male diplomats. Use of air purifiers and improved home tightness in polluted cities may halve DLL due to PM2.5 exposure. The results were highly sensitive to lag assumptions: DLL increased by 68% without inception lags and decreased by 59% without cessation lags for older male diplomats.Conclusion We developed a model to quantify health impacts of changing PM2.5 exposure for a population with frequent relocations. Our model suggests that alternating assignments in high and low PM2.5 cities may help reduce PM2.5-related mortality burdens. Adding exposure mitigation at home may help reduce PM2.5 related mortality. Further research on outcome-specific lag structures is needed to improve the model.
Circulating biomarkers at diagnosis correlate with distant metastases of early luminal-like breast cancer
Authors: Lambrechts Yentl , Garg Abhishek , Floris Giuseppe , Punie Kevin , Neven Patrick , Nevelsteen Ines , Govaerts Jannes , Richard François , Laenen Annouschka , Desmedt Christine , Wildiers Hans , Hatse Sigrid 
Published: May 2023

Abstract
There is an urgent need for new and better biomarker modalities to estimate the risk of recurrence within the luminal-like breast cancer (BC) population. Molecular diagnostic tests used in the clinic lack accuracy in identifying patients with early luminal BC who are likely to develop metastases. This study provides proof-of-concept that various liquid biopsy read-outs could serve as valuable candidates to build a multi-modal biomarker model distinguishing, already at diagnosis, between early metastasizing and non-metastasizing patients. All these blood biomarkers (chemokines, microRNAs, leukemia-inhibitory factor, osteopontin, and serum-induced functional myeloid signaling responses) can be measured in baseline plasma/serum samples and could be added to the existing prognostic factors to improve risk stratification and more patient-tailored treatment in early luminal BC.
Half-cost array-based genotyping of SNPs in bread wheat from pooled experiments and imputation
Authors: Clouard Camille , Nettelblad Carl 
Published: May 2023

Abstract

The plant breeding industry has shown growing interest in using the genotype data of relevant markers for performing selection of new competitive varieties. The selection usually benefits from large amounts of marker data and it is therefore crucial to dispose of data collection methods that are both cost-effective and reliable.Computational methods such as genotype imputation have been proposed earlier in several plant science studies for addressing the cost challenge.Genotype imputation methods have though been used more frequently and investigated more extensively in human genetics research.The various algorithms that exist have shown lower accuracy at inferring the genotype of genetic variants occurring at low frequency, while these rare variants can have great significance and impact in the genetic studies that underlie selection.In contrast, pooling is a technique that can efficiently identify low-frequency items in a population and it has been successfully used for detecting the samples that carry rare variants in a population.In this study, we propose to combine pooling and imputation with microarray data for genotyping a population of recombinant inbred lines in a cost-effective and accurate manner, even for rare variants.We show that with an adequate imputation model, it is feasible to accurately predict the individual genotypes at half the cost of sample-wise genotyping and time-effectively. Moreover, we provide code resources for reproducing the results presented in this study in the form of a containerized workflow.
Genetic Diversity of bottle gourd [Lagenaria siceraria (Mol.) Standl.] genotypes of Eastern India through agro-morphological traits and ISSR markers: Implication for future breeding
Authors: Kumar Rajesh , Kumar Randhir , Prasad Bishun Deo , Kumar Jitesh , Bamaniya Bahadur Singh 
Published: May 2023

AbstractGenetic characterization of plant genetic resources is a pre-requisite for a strategic breeding program. Bottle gourd is an important cucurbit grown throughout India for its tender fruits used for culinary purpose. For the present investigation twenty-four genotypes of bottle gourd were collected from Eastern India to examine the magnitude of genetic diversity based upon 16 quantitative traits and seven ISSR (Inter simple sequence repeats) markers. In morphological study genotypes performed significantly in all traits, however BRBG-65 (591.10 q/ha) was proved to be high yielder with other attributing traits in pooled analysis of two growing seasons than compare to the all three check varieties of the region. Almost all the traits under study showed high percentage of genotypic coefficient of variation, phenotypic coefficient of variation and heritability with genetic advancement. Quantitative traits like fruit weight, number of fruits per vine and yield of marketable fruits per vine shown strong character association with yield per hectare. Principal component analysis on quantitative traits depicted six principal components, accounted for 79.33% of the total variations. The first two components accounted for 44.92 cumulative percent of the total variation, which signifies a high degree of correlation between the analyzed traits. In the molecular study, average polymorphism percentage was obtained by ISSR marker pattern studied by seven primers. Total 48 reproducible amplicons were generated of an average around 6.85 amplicon per primer. The values of average polymorphic information content, major allele frequency and major gene diversity were obtained in wide range. Wide range of value regarding Jaccard’s similarity coefficient was also ensured through ISSR markers. Dendrogram and similarity matrix produced from ISSR data then compared and concluded the discrimination among genotypes within these clusters. Most genotypes studied in the present experiment differed with their geographic origin. The investigation highlights the potential utilization of these germplasm for further genetic analysis.
A Tolerance Evaluation and Genetic Relationship Analysis Among Some Economically Important Chestnut Cultivars in Turkey Using Drought Associated SSR and EST-SSR Markers
Authors: KARA Didem , ORHAN Emine 
Published: May 2023

Abstract
In this study, it was aimed to evaluate drought tolerance and genetic relationship analyzes among some important chestnut cultivars for Turkey by using drought related genomic SSR markers and genic EST-SSR markers. The values such as average and total number of alleles, number of polymorphic alleles, polymorphism ratio, heterozygosity, polymorphism information content, discriminating power and marker index for these primers were determined. All microsatellite markers used in this study showed 100% polymorphism among chestnut cultivars. In UPGMA dendograms obtained with both SSR and EST-SSR markers, Erfelek and Hacıömer chestnut cultivars were determined as the most similar cultivars. As a result of the use of EST SSR markers named GOT045, GOT021, GOT004, FIR094 and VIT033, some preliminary information was obtained for the determination of drought tolerance in 11 chestnut cultivars. Marigoule cultivar which is known to be drought resistant, was taken as a basis in evaluating the drought tolerance of other chestnut cultivars. As a result, high accuracy molecular analyzes were carried out for chestnut breeding. It has been revealed that drought related genomic and genic markers will be useful in marker assisted selection studies. Thus, early selection will be ensured and breeding studies will be carried out more effectively.
The Turkish Tsunami of 6 February 2023 in the Northeastern Mediterranean
Authors: Medvedeva Alisa , Vydrin Danil , Krylov Artem , Shiryborova Arina , Smirnova Daria , Tsukanova Elizaveta , Kânoğlu Utku , Medvedev Igor 
Published: May 2023

Abstract
Two powerful earthquakes struck southeastern Turkey on 6 February 2023 with the magnitudes of Mw = 7.8 and Mw = 7.5 in nine hours. In addition, a storm surge caused by the passage of a cyclone over the area coincided with the first earthquake. Field observations showed that the fault planes did not extend to the Mediterranean Sea; however, a weak tsunami was observed on several tide gauges in the northeastern Mediterranean. Historically, there were tsunamis in the Levantine Sea region caused by earthquakes on land within the East Anatolian Fault Zone and the Dead Sea, having a complex cause, i.e., earthquakes and associated landslides. Hence, we studied the origin of the generated waves. We separated and estimated various components of sea level oscillations from 1 to 8 February 2023, using spectral and f-t analyses and sets of narrow-band and high-frequency filters. The earthquake Mw = 7.8 on 6 February 2023 caused a weak tsunami with maximum amplitudes 15‒17 cm in Erdemli and Arsuz. We identified that the increase in sea level oscillations in Arsuz after 7 February was associated with the impact of the cyclone. The maximum amplitude of sea level oscillations, 22 cm, in Arsuz was observed on 7 February and is associated with infragravity waves caused by the influence of storm surge during the passage of the cyclone. In Erdemli, on the contrary, the influence of high-frequency waves of atmospheric origin is significantly lower, i.e., the amplitude of the sea level oscillations after 7 February was less than 10 cm.
Identification and Validation of Targets of Swertiamarin on Idiopathic Pulmonary Fibrosis Through Bioinformatics and Molecular Docking-based Approach
Authors: Chang Jun , Xu Subo , Zou Shaoqing , Xiao Yiwen , Zhu Du 
Published: May 2023

Abstract
Purpose
the main purpose is to identify the potential targets of swertiamarin, a new anti-idiopathic pulmonary fibrosis traditional Chinese medicine that was previously screened out with machine learning, on idiopathic pulmonary fibrosis.
Methods
GEO2R was used to analyze the differentially expressed genes of GSE10667, GSE110147, and GSE71351 datasets that were downloaded from the Gene Expression Omnibus database, the differentially expressed genes were enriched with GO and KEGG analysis for their biological functions and annotated terms, then the protein-protein interaction network was constructed to screen the hub genes. The selected hub genes were predicted for their capabilities of binding swertiamarin with molecular docking and finally validated as the targets of swertiamarin on idiopathic pulmonary fibrosis with in vitro experiments.
Results
76 upregulated and 27 downregulated differentially expressed genes were screened out, and these genes were found to be enriched in tissue development and cancer signaling pathways. Three top hub genes, i.e., LOX, COL5A2, and CTGF were selected as the hub genes for experimental validation.
Conclusion
LOX, COL5A2, and CTGF were identified as the targets of swertiamarin on idiopathic pulmonary fibrosis.
Acidity reduction receiving long-term pig manure application in red soil
Authors: Luo Peisang , Sun Mei , Feng Qiufen , Zeng Xibai , Shi Lihong , Wang Hua , Luo Zunchang , Long Zedong , Sun Geng 
Published: May 2023

Abstract
While the application of manure to improve soil quality has attracted attention, the effect of pig manure application rates on soil fertility and acidity remains poorly understood. This study analyzed the changes in and correlations between soil acidity, pH buffer capacity (pHBC), soil chemical properties and crop yields after 8 years of pig manure application at different rates (i.e., 0, 7.5, 15, 30, and 45 t·ha-1) in red soil. Crop yield, soil nutrients, pH, pHBC, iron activation, and exchangeable base cations increased with increased pig manure application rates. Soil fertility and pHBC were significantly enhanced when the application rate was larger than 15 t·ha-1. At 30 and 45 t·ha-1, pH values increased significantly while exchangeable acid decreased (41.3% and 52.8%) compared to no pig manure input. Crop yields were positively related to soil pH, but negatively correlated with soil exchangeable hydrogen and exchangeable aluminum. Redundancy analysis revealed pH and pHBC to be positively correlated with exchangeable base cations, total phosphorus, total nitrogen, soil organic carbon, and amorphous iron oxide. In conclusion, crop yield could be improved by adjusting soil acidity characteristics, and the application of pig manure reduced soil acidity, with an optimal application rate of 15–30 t·ha-[1].
[1]Hunan Soil and Fertilizer Institute, Changsha, 410125, China. 2Institute of Environment and Sustainable Development in Agriculture, Chinese Academy of Agricultural Sciences/ Key Laboratory of Agricultural Environment, Ministry of Agriculture and Rural Affairs of P.R.China, 100081, Beijing, China. 3Hunan Agricultural University, Changsha, 410128, China. *email: longzd313@hunaas.cn; sungeng@hunaas.cn.
Machine learning for differentiation of lipid-poor adrenal adenoma and subclinical pheochromocytoma based on multiphase CT imaging radiomics
Authors: xiao dao-xiong , Peng Ji-dong , Fan Cun-geng , Wang Xiao-chun , Wen Xing-lin , Zhong Jian-ping , Liao Wei-wei , Wan Jun , Yin Xiao-feng 
Published: May 2023

Abstract
Objective The aim of this study was to use radiomics analysis of multiphase computed tomography (CT) imaging to develop and validate machine learning models that can accurately differentiate between lipid-poor adrenal adenoma (LPA) and subclinical pheochromocytoma (sPHEO) to improve the accuracy of preoperative diagnosis of the two.Methods A retrospective analysis was performed on 134 patients who underwent abdominal multiphase spiral CT scans in three local tertiary hospitals between March 2015 and November 2022. The analysis included 74 cases of LPA (52 at our hospital and 22 at other hospitals) and 60 cases of sPHEO (44 at our hospital and 16 at other hospitals), all of which were surgically and pathologically confirmed. Tumors were delineated using 3D Slicer and radiomics were extracted using PyRadiomics, a plug-in to the software. Cases from internal hospital were randomly split into training and test sets in a 7:3 ratio, while all cases from external hospitals were used as the validation set. The T-test and the minimum absolute contraction and selection operator (LASSO) were used to reduce the dimensionality of the data. Then six dichotomous models were developed, including k-nearest neighbor (KNN), logistic regression (LR), decision tree (DT), random forest (RF), support vector machine (SVM), and multi-layer perceptron (MLP). The diagnostic performance of each model was evaluated using the receiver operating characteristic (ROC) curve and the area under the curve (AUC). The ROC curves of the test and validation sets were compared using DeLong's method to determine the most effective model for distinguishing between LPA and sPHEO.Results A total of 902 rows and 112 columns of radiomic feature data were extracted from multiple phases and slice-thickness CT data. After dimensionality reduction processing, 13 - dimensional radiomic feature data was obtained. The six binary models demonstrated good diagnostic performance for each phase and slice thickness, as well as for the entire CT data, with AUC values ranging from 0.706 to 1. Among these models, RF, SVM, and MLP showed particularly good diagnostic performance. The ROC curves of RF, SVM, and MLP did not show a statistically significant difference (p < 0.05) for different phase, slice-thicknesses, as well as the entire test and validation sets, except for the thick slice-thickness data sets. The AUC value of the MLP model for the non-contrast CT validation set was 0.979, which is quite high. Furthermore, there was no significant difference in the ROC curves when compared to other phases and the entire validation sets (p < 0.05).Conclusions The CT radiomics-based machine learning model was able to differentiate between LPA and sPHEO well, even using non-contrast CT data alone to efficiently discriminate between the two.