bluuebunny/crossref_metadata_2025_split huggingface dataset:
Design and simulation of a semiconductor detector-based Compton imaging system with efficiency analysis
Authors: Niknami Mostafa , Hosseini Seyed Abolfazl , Loushab Mahdy Ebrahimi 
Published: November 2022

Abstract
In recent years, Compton cameras that use electronic collimators have become common. One or more scatterer detectors and an absorber detector make up the Compton camera, which is sensitive to the energy and location of scattered gamma rays. It predicts the distribution of gamma-ray sources by reflecting all valid events in the image space using conical surfaces. Compton cameras are designed for specific applications and image reconstruction using various methods.
Based on studies on the efficiency of the Compton camera, the current work provides a novel detector design that includes scatterer and absorber detectors. This design includes eight scatterer detectors spaced 1 mm apart and an absorber detector 30 mm from the last scatterer detector. The distance between the source and the first scatterer detector was 5 mm. The scatterer and absorber detector plates were 70x70x2.125mm3 and 70x70x10mm3, respectively. The Compton imaging system is simulated using the GEANT4 toolkit.
In addition, this study uses an analytical method to reconstruct Compton camera images. The method used for analytical reconstruction in the Compton imaging system differs slightly from simple restoration methods used in other imaging systems. In the analytical method, the equation related to the data reflected by the image must be solved to reconstruct the image directly. This method, the C + + code was developed to reconstruct Compton camera images.
According to the results, using the analytical method to identify the best circumstances and the parameters impacting efficiency, the value of FWHM achieved was 3.7 mm with an angular uncertainty of about 2.7 at an energy of 0.662 MeV. Furthermore, the FWHM value decreased by 0.7 mm, compared to another (experimental) design that employed the analytical image reconstruction approach.
First non-covalent inhibitors of thioredoxin glutathione reductase with schistosomicidal activity in vivo
Authors: Petukhova Valentina , Aboagye Samuel , Ardini Matteo , Lullo Rachel , Byrne Margaret , Martin Lucy , Fata Francesca , Gabriele Federica , Ippoliti Rodolfo , Ling Wai Li , Effantin Grégory , Harding Luke , Nikolic Dejan , Lantvit Daniel , Dangi Bikash , Gone Vamshikrishna , Johnson Jeremy , Thatcher Gregory , Angelucci Francesco , Williams David , Petukhov Pavel 
Published: November 2022

Abstract
Only one drug, praziquantel, is available for treating schistosomiasis, a disease affecting more than 200 million people. Laboratory studies have shown that schistosome worms can develop resistance to praziquantel and low cure rates from mass drug administration programs suggest that resistance is evolving in the field. Previous studies have identified thioredoxin glutathione reductase (TGR), a selenoprotein, as essential for schistosome survival, and therefore, a target for much-needed new therapeutics for schistosomiasis. Compounds targeting TGR identified to date are irreversible and/or covalent inhibitors. Both potassium antimonial tartrate and oltipraz inhibit TGR and were used clinically for schistosomiasis treatment but their use was discontinued due to unacceptable side effects. These findings highlight the importance of the development of non-covalent, metabolically stable, and druglike TGR inhibitors. To identify TGR inhibitors for clinical use, small molecule fragments obtained by X-ray crystallography screening were ligated and partially optimized as first-in-class non-covalent inhibitors of TGR. A first cryo-EM structure of TGR demonstrated that these inhibitors bind at a secondary site preventing the NADPH oxidation steps. These compounds display schistosomicidal activity against different parasite-life cycle stages reaching the nanomolar range. Most importantly, novel druglike and orally bioavailable TGR inhibitors demonstrated efficacy against schistosome infections in mice, meeting the criteria for lead progression indicated by WHO and significantly outperformed praziquantel against juvenile worms. These findings open a new avenue for the development of therapeutics for the treatment of schistosomiasis.
A Dual-Population Cooperative Water Wave Optimization Algorithm with Knowledge-Driven Learning Mechanism and Its Performance Analysis
Authors: Zhao Fuqing , Shao Dongqu , Wang Ling , Cao Jie , Tang Jianxin 
Published: November 2022

Abstract
The water wave optimization algorithm (WWO), which is inspired by the shallow water wave theory, is a promising meta-heuristic in continuous optimization problems. However, the canonical WWO algorithm has proved to fall into the local optimum as lacking the guidance of the search direction and iteration step sizes in the search process. In this paper, a dual-population cooperative WWO with a knowledge-driven learning mechanism (DCLWWO) is proposed to relieve the drawback. The improved learning mechanism of WWO with the searching operations of different types of the population is combined to strengthen the self-learning and self-adapting capabilities of the algorithm. The wavelength [[EQUATION]] was redefined with a fixed external archive to further control the size of the search step during the iterations. DCLWWO is compared with the existing variants of WWO and several well-established algorithms to substantiate the performance of the algorithm. Meanwhile, DCLWWO is applied to solve the blocking flow shop scheduling problem (BFSP), which has been widely studied in artificial intelligence manufacturing. Experimental results and systematic analysis indicate the effectiveness of DCLWWO in solving complex optimization problems.
Residual behavior and risk assessment of fluopyram, acetamiprid and chlorantraniliprole used individually or in combination on strawberry
Authors: Li Yanjie , Luo Yuqin , Jiang Jinhua , He Hongmei , Zhang Changpeng , Zhao Xueping 
Published: November 2022

Abstract
In this study, fluopyram (FOR), acetamiprid (ATP) and chlorantraniliprole (CAP) were used individually or in combination at the maximum recommended dose in greenhouse strawberries to research the dissipation dynamics and dietary risks. A multi-residue analytical method for FOR, ATP and CAP in strawberries using UPLC-MS/MS integrated with QuEChERS approach was develop with a strong linearity (R2 ≧ 0.9990), accuracy (recoveries of 82.62–107.79%), and precision (relative standard deviations of 0.58–12.73%). The limits of quantification were 0.01 mg kg− 1. Field results showed that the half-lives of FOR, ATP and CAP in strawberry fruits were 11.6–12.4 days, 6.1–6.7 days and 10.9–11.7 days, respectively. The half-lives of the three investigated pesticides showed no significant difference when used individually or in combination. A risk assessment indicated that the dietary intake risks of the three pesticides in grown strawberries were 0.0041–7.63% whether applied alone or joint, which demonstrated that the dietary intake risks of three pesticides in grown strawberries could be negligible for Chinese male and female consumers, and even though pesticides were used in combination, there was no need to be concerned about the safety. This paper serves as a guide for the safe use of FOR, ATP and CAP on greenhouse strawberries.
Biomphalaria alexandrina snail as a bio-indicator of pollution with Manganese metal and its effect on physiological, immunological, histopathological parameters and larvicidal potencies
Authors: Ibrahim Amina , Abdel-Haleem Ahmed , Taha Rania Gamal 
Published: November 2022

Abstract
Metal pollution results in many dangerous consequences to the environment and human health due to the bioaccumulation in their tissues. The present study aims to measure the bioaccumulation factor of the Manganese (Mn) heavy metal in Biomphlaria alexandrina snails' tissues and water samples. The present results showed the concentration of Mn heavy metal in water (87.5 mg/l) and its bioaccumulation factor in Helisoma duryi tissue was higher than that in tissues of Physa acuta and B. alexandrina snails. Results showed that 87.5 mg/l Mn concentration had miracidial and cercaricidal activities. Also, this concentration decreased the mean total number of the hemocytes after exposure for 24h or 48h, while increased both the mean mortality and phagocytic indices of the hemocytes of exposed snails. It caused alterations in the cytomorphology of the hemocytes of exposed snails after 24 or 48h, where, the granulocytes had irregular cell membrane, and forming pseudopodia. Besides, both levels of Testosterone (T) and Estradiol (E) were increased after exposure to 87.5mg/l Mn metal compared to the control group. Also, it increased MDA (Malonaldehyde) and TAC (Total antioxidant capacity) contents, while, decreased SOD (superoxide dismutase). Besides, it caused great histopathological damages in both hermaphrodite and digestive glands, represented in the degeneration of the gonadal, digestive, secretory cells and the connective tissues. Therefore, B. alexandrina might be used as sensitive bio-indicator of pollution with Mn heavy metal to avoid ethics rules; beside they are easily available and large in number.
Improvement of 5-Fluorouracil Chemosensitivty In Colorectal Cancer Cells by siRNA-Mediated Silencing of STAT6 Oncogene
Authors: Farzam Omid Rahbar , Baradaran Behzad , Najafi Souzan , Amini Mohammad , Kaleybar Vahid Pourabdollah , Dabbaghipour Reza , Khosroshahi Shiva Ahdi , akbari bahman 
Published: November 2022

Abstract
Background: One of the cancers that occur most frequently around the world is colorectal cancer (CRC). STAT6 transcription factor is involved in cellular multipotency, tumor cell growth, drug resistance, stemness, and migration, showing potential as a cancer therapy target for a variety of cancers, including CRC. In this regard, the current study aimed to investigate the effect of STAT6 silencing via small interference RNA (siRNA) in combination with 5-FU on CRC development.
Methods: The MTT assay and the Annexin V/PI staining were used to examine cell proliferation and apoptosis induction, respectively. Flow cytometry was performed to investigate cell cycle progression. Wound healing assays were also used to examine HT-29 cell migration. A colony formation assay was used to examine cell stemness features of HT-29 cells. The qRT-PCR was used to measure the gene expression levels in the samples.
Results: Apoptosis induction by STAT6 inhibition significantly improved the HT-29 cell chemosensitivity to 5-FU. Both caspase-9 apoptotic gene and Bax/Bcl-2 ratio were upregulated when STAT6 suppression and 5-FU were combined. Additionally, combination therapy led to cell cycle arrest at the sub-G1 phase in CRC cells. The combined therapy also significantly reduced MMP9 expression, which in turn reduced the migration of HT-29 cells. Furthermore, STAT6 knockdown inhibited HT-29 cell colony formation by reducing the expression of the Sox2 and CD44 genes, either alone or in combination with 5-FU.
Conclusions: The findings show that combination therapy of 5-FU and STAT6 silencing may be an effective treatment for patients with CRC.
Aberrant somatic L- and T-type calcium channel function in cNurr1 and LRRK2-G2019S mice
Authors: Chergui Karima , Skiteva Olga , Yao Ning , Mantas Ioannis , Zhang Xiaoqun , Perlmann Thomas , Svenningsson Per 
Published: November 2022

Abstract
In Parkinson’s disease (PD), axons of dopaminergic (DA) neurons in the substantia nigra pars compacta (SNc) degenerate before their cell bodies. Calcium influx during pacemaker firing is suggested to contribute to neuronal loss, but it is not known if, and at which stage of the disease, dysfunctions of voltage-gated calcium channels (VGCCs) occur in DA neurons somata and axon terminals. We investigated T-type and L-type calcium channels in the somata and axon terminals of SNc-DA neurons of mice with a deletion of the Nurr1 gene in DA neurons from an adult age (cNurr1 mice) and mice bearing the G2019S mutation in the gene coding for LRRK2 (G2019S mice). Adult cNurr1 mice displayed motor and DA deficits (symptomatic stage), while middle-aged G2019S mice did not (prodromal stage). We found that the number and morphology of DA neurons as well as most of their intrinsic membrane properties and pacemaker firing were unaltered in cNurr1 and G2019S mice. However, in G2019S mice, but not cNurr1 mice, the function of somatic L-type VGCCs was increased. In cNurr1 mice, the function of somatic T-type VGCCs was reduced, and somatic dopamine-D2 autoreceptors desensitized more. These changes were reversed by a LRRK2 kinase inhibitor in G2019S mice, and by kaempferol, a flavonoid with antioxidant activity, in both G2019S and cNurr1 mice. The role of L-type and T-type calcium channels in controlling dopamine release from axon terminals in the striatum was unaltered in cNurr1 and G2019S mice. Our findings uncover opposite changes, linked to oxidative stress, in the function of two calcium channels in DA neurons somata, but not axon terminals, in symptomatic and prodromal experimental PD models.
Remimazolam tosilate has a lower incidence of hypotension than propofol in painless colonoscopy
Authors: Li Sitong , Zhang Yi , Wang Hongbai , Ye Gang , Yao Nana , Xiang Jun , Mou Junying , Zhu Xianlin 
Published: November 2022

Abstract
Background: Remimazolam tosilate is an ultra-short-acting sedative drug with the advantages of rapid onset, rapid recovery, and mild respiratory and circulatory inhibition. We aim to compare the incidence of hypotension of remimazolam with propofol in patients undergoing painless colonoscopy and explore the stability of remimazolam in circulation.
Methods: This is a randomized, double-blind trial. 116 patients with outpatient appointment for painless colonoscopy in our hospital from December 2020 to March 2021 were randomly divided into the remimazolam group and the propofol group. The modified observer’s assessment of alert/sedative (MOAA/S) was used to evaluate the depth of the patient's sedation. The Narcotrend score was monitored throughout the whole process. Taking the incidence of hypotension as the primary outcome indicators, records the incidence of respiratory depression, nausea, vomiting and other adverse events during sedation in the two groups of patients, and record the effective time of anesthesia, awakening time, sedative success rate, etc. to evaluate the effect of remimazolam on circulation.
Results：The incidence of hypotension during sedation (13.8%) in the remimazolam group was significantly lower than that in propofol (37.9%), and the success rate of remimazolam (98.3%) was slightly lower than propofol (100.0%), but the awakening time was significantly shorter (P<0.001); The incidence of respiratory inhibition, nausea, vomiting and other adverse events during colonoscopy, remimazolam was significantly lower than that of propofol (P<0.05).
Conclusion：Remimazolam tosilate has higher circulatory stability in patients undergoing painless colonoscopy.
Trial registration:
The trial was registered at the Chinese Clinical Trial Registry (ChiCTR2000040398), data of registration: 28/11/2020.
Application of weighted gene co-expression network analysis to explore potential prognostic markers of head and neck squamous cell carcinoma
Authors: He Liming , Zeng Yiyu , Gao Yijun , Xie Xiaoyan 
Published: November 2022

Abstract
Currently, there are no specific head and neck squamous cell carcinoma (HNSCC) prognostic markers. We explored the potential HNSCC prognostic markers using weighted gene co-expression network analysis (WGCNA). We obtained raw datasets of HNSCC and matched normal mucosal tissues and screened out differentially expressed genes (DEGs), then analyzed DEG enrichment. DEG co-expression network modules for both tumor and normal tissues were constructed using WGCNA, then hub genes in tumor set-specific modules were selected. Key genes underwent survival analysis using the HNSCC dataset in The Cancer Genome Atlas database. The key gene expression profiles in the clinical samples were verified with RT-qPCR and western blotting. We identified 893 DEGs: 518 were upregulated (mainly distributed in the exogenous metabolic processes, epidermal development, regulation of inflammatory mediators of TRP channels, and tyrosine metabolism) and 375 were downregulated (mainly related to cell adhesion, osteoblast and adipocyte lipolysis regulation, and the RIG-I-like receptor signaling pathway). The WGCNA constructs of the HNSCC co-expression module uncovered 10 hub genes. Survival analysis determined that EOMES (eomesodermin) and SPRYD3 (SPRYD domain-containing protein 3) were closely related to HNSCC prognosis and differentially expressed in oral cancer clinical tissues. EOMES and SPRYD3 might be potential HNSCC prognostic markers and therapeutic targets.
Significance of immunogenic cell death-related prognostic gene signature in cervical cancer prognosis and anti-tumor immunity
Authors: Jiang Shan , Cui Zhaolei , Zheng Jianfeng , Wu Qiaoling , Yu Haijuan , You Yiqing , Zheng Chaoqiang , Sun Yang 
Published: November 2022

Abstract
BACKGROUND
Immunogenic cell death (ICD) can reshape the tumor immune microenvironment, and ICD, as a type of regulated cell death, activates the adaptive immunity of the body to achieve better therapeutic results through direct tumor cell killing. ICD has never been associated with cervical cancer (CC), hence the purpose of this research was to find and evaluate ICD-related genetic characteristics as cervical cancer prognostic ators.
METHODS
Data of CC patients from The Tumor Genome Atlas (TCGA) was used as the basis to obtain immunogenic cell death-related prognostic genes (IPGs) in patients with CC, using the least absolute shrinkage and selection operator and Cox regression screening, and the IPGs scoring system was constructed to classify patients into high- and low-risk groups, with the Gene Expression Omnibus (GEO) dataset as the validation group. Finally, the difference analysis of single-sample gene set enrichment analysis, tumor microenvironment (TME), immune cells, tumor mutational burden, and chemotherapeutic drug sensitivity between the high-risk and low-risk groups was investigated. The PDIA3 gene was identified as the major gene in immunogenic death-related genes (IRG) with the greatest hazard ratio (HR), and in vitro experiments were performed to confirm its expression in colorectal cancer (CC) and its influence on the prognosis of the patient.
RESULTS
A prognostic model with four IPGs (PDIA3, CASP8, IL1 and LY96) was developed, and it was found that the group of CC patients with a higher risk score of IPG expression had a lower survival rate. Multiple regression analysis also showed that this risk score was a reliable predictor of overall survival (HR = 1.058, P 0.01). In comparison to the low-risk group, the high-risk group had lower TME scores and immune cell infiltration, and gene set variation analysis showed that immune-related pathways were more enriched in the high-risk group. Chemotherapeutic drug sensitivity analysis revealed that IC50 value of common chemotherapeutic agents for CC was lower in the high-risk compared with that in the low-risk group. In addition, high expression of the PDIA3 gene, a key gene in IPGs, was linked to worse patient prognosis.
CONCLUSION
A risk model constructed from four IPGs can independently predict the prognosis of CC patients and recommend more appropriate immunotherapy strategies for patients.
Skewed X-chromosome Inactivation in Unsolved Neurodevelopmental Disease Cases Can Guide Re-evaluation for X-linked Genes
Authors: Brusco Alfredo , Giovenino Chiara , Trajkova Slavica , Pavinato Lisa , Cardaropoli Simona , Pullano Verdiana , Sukarova-Angelovska Elena , Carestiato Silvia , Salmin Paola , Rinninella Antonina , Battaglia Anthony , Bertoli Luca , Fadda Antonio , Palermo Flavia , Carli Diana , Mussa Alessandro , Dimartino Paola , Bruselles Alessandro , froukh Tawfiq , Mandrile Giorgia , Pasini Barbara , De Rubeis Silvia , Buxbaum Joseph , Pippucci Tommaso , Tartaglia Marco , Rossato Marzia , Delledonne Massimo , Ferrero Giovanni Battista 
Published: November 2022

Abstract
Despite major technical and genetic advances, more than half of the neurodevelopmental disorders (NDDs) cases remain undiagnosed.
We explored the frequency of non-random XCI in the mothers of male patients and in affected females from a clinically heterogeneous cohort of unsolved NDD cases, negative at FRAXA, chromosomal microarray analysis and Trio Exome Sequencing. We hypothesize that an unbalanced XCI could unmask previously discarded genetic variants on the X chromosome connected both to XCI and NDD.
A multiplex fluorescent-PCR-based assay was used to screen the XCI pattern after methylation sensitive HhaI digestion. Trio-based ES re-analysis was performed in families with skewed XCI occurrence. Linkage analysis and RT-PCR were used to further study the X-chromosome inactive allele. X-drop was used to define the chromosome deletion boundaries.
We found a skewed XCI (>90%) in 16/186 mothers of affected NDD males (8.6%) and 12/90 female patients (13.3%), far beyond the expected XCI in normal population (3.6%, OR=4.10; OR=2.51). Reanalyzing ES and clinical data, we solved 7/28 cases (25%). These included variants in the KDM5C, PDZD4, PHF6, TAF1, OTUD5, and ZMYM3, and a genomic deletion spanning exons 3-4 of the ATRX gene.
The identification of a skewed XCI is an easy assay that can help selecting a subgroup of patients for the re-evaluation of X-linked variants, improving the diagnostic yield in NDD patients, and allowing the identification of new X-linked disorders.
Genome-wide analysis of bHLH57 and functional identification of the involvement of BcbHLH57 in abiotic stress in wucai (Brassica campestris L.)
Authors: Zhang Liting , Zhang Bingsheng , Lan Tian , Zhu Shidong , Hou Jinfeng , Chen Guohu , Tang Xiaoyan , Gan Defang , Wang Chenggang , Yuan Lingyun 
Published: November 2022

Abstract
Wucai (Brassica campestris L. ssp. chinensis var. rosularis Tsen), a variety of Brassica cabbage in the Cruciferous family, is a kind of cold-tolerant vegetable widely cultivated in the Jianghuai River Basin of China. To breed new varieties of resistance to stress, it is necessary to study the tolerance of Resistance to different stresses. Transcriptomic data showed that exogenous application of 2, 4-epbrassinolide (EBR) significantly increased bHLH genes in wucai at low temperature, and bHLH57 was up regulated significantly. BHLH (Basic helix-loop-helix) TFs (transcription factor) is a superfamily of TFs with complex functions and related to various plant life activities. In this study, a total of 239 bHLH genes were identified, and their amino acid physicochemical properties, chromosome location, gene structure, phylogeny and cis-acting elements were analyzed by bioinformatics. Phylogenetic analysis showed that bHLH gene families in Chinese cabbage and Arabidopsis were divided into six groups, and the distribution of bHLH genes in Chinese cabbage was uneven. Cis-acting elements analysis showed that the promoter region of bHLH family genes in Chinese cabbage had more responsive elements related to light, hormone and abiotic stress. The BcbHLH57 overexpressing Arabidopsis thaliana lines were subjected to different stress treatments, and the seed germination rate, root growth, survival rate and various plant physiological indexes were determined. The results showed that the transgenic lines were more tolerant to salt, heat and drought stress. In this study, the response of BcbHLH57 gene to salt, heat and drought stress was reported for the first time, which provided a basis for further research on the function of BcbHLH57 in abiotic stress.