bluuebunny/crossref_metadata_2025_split huggingface dataset:
Dynamic Homogenization of Internal Strain via High-concentration Doping of Oxygen with Large Mobility
Authors: Song Yajing , Zhang Bozhao , Li Tianxin , Fu Xiaoqian , Zou Jiawei , Chen Yujie , Fang Yan , Zhang Qinghua , GU Lin , Lu Yiping , Yang Guang , Liu Suya , Wang Haifeng , Ding Jun , Yu Qian 
Published: June 2022

Abstract
Internal strain and its distribution in crystal lattice play important roles in tuning dislocation activities, which would affect the mechanical properties of materials consequently. Here, by combing integrated differential phase contrast, in situ transmission electron microscope characterizations and computer simulations, we revealed a way of homogenizing dislocation pinning by doping high concentration of oxygen atoms with high diffusion mobility into NiCoCr medium entropy alloy. The doping of massive oxygen atoms introduces high density of strong local pinning points for dislocation motion. Moreover, the oxygen interstitials can easily diffuse and move between different octahedral and tetrahedral sites in the distorted crystal lattice of NiCoCr alloy at even room temperature, based on which severe stress concentrations produced by dislocation tangling can be released and strong local dislocation pinning points can be re-built at other sites towards a uniform way, enabling the material with high strength and outstanding deformability. Our results indicate that the interstitial atoms may become highly mobile at even ambient temperature in complex multi-elements alloys with spreading lattice distortion, which may open a new branch of dislocation engineering.
Completely diverted tube ileostomy versus conventional loop ileostomy
Authors: Bulut Alisina , Attaallah Wafi 
Published: June 2022

Abstract
Purpose
Diverting ileostomies are commonly performed to prevent morbidity and mortality caused by colorecta lanastomotic leakage. However, many complications may develop due to loop ileostomy itself and its reversal. In this study, we aimed to compare the outcomes ofcompletely diverted tube ileostomy and conventional loopileostomy.
Methods
The study was designed prospectively, and operations were performed by the same surgeon at a single center. Completely diverted tube ileostomy with the rubber strip was performed in 20 consecutive patients and loop ileostomy was performed in the next 20 consecutive patients who needed diverting stoma. Theprimary outcome of the study is to compare the overall complication rates in both techniques. Length of hospital stay, achieving complete diversion, and length of time with a stoma were evaluated as secondary outcomes.
Results
There were no significant differences in the demographic characteristics between the two groups. Complete diversion was achieved in both groups. The number of patients who developed any kind ofcomplications during the observation period was significantly higher in the loopileostomy group in comparison with tube ileostomy group [13 (65%) vs 3 (15%)respectively, p = 0.002].Median time with stoma was significantly higherin loop ileostomy group compared to tube ileostomy group [270 days (56–443)vs 21 days (14–28) respectively, p < 0.001].
Conclusion
Completely diverted tube ileostomy is superior to loop ileostomy for reasons such as lack of need for reversal surgery and fewer complications.
Dimethyl Fumarate attenuates Di-(2-ethylhexyl) phthalate-induced Nephrotoxicity, Crosstalk between Nrf2 and NFκB Signaling Pathways
Authors: Ashari Sorour , Barghi Nasrin Ghassemi , Bagheri Abouzar 
Published: June 2022

Abstract
Introduction: Dimethyl fumarate (DMF), the methyl ester of fumaric acid, exhibited various pharmacological effects. The aim of this study was to clarify the potential nephroprotective effect of DMF against DEHP-induced nephrotoxicity. Methods: HEK-293 cells were exposed to different concentrations of DMF plus IC50 concentrations of monoethylhexyl phthalate (MEHP) to evaluate possible cytoprotective effect of DMF. For more evaluation, rats were divided into 7 groups (n=6 per group). Corn oil group, DEHP group (200 mg/kg dissolved in corn oil by gavage). DMF (15, 30, and 60 mg/kg) plus DEHP (200 mg/kg) groups, vitamin E (20 mg/kg) plus DEHP (200 mg/kg) group and DMF (60 mg/kg) alone (45 days). Results: DMF significantly decrease MEHP-induced cytotoxicity DMF improved BUN and creatinine levels compared to DEHP in a dose-dependent manner. Furthermore, DEHP-induced mitochondrial dysfunction was reduced by DMF. To determine the molecular signaling involved in the nephroprotective effects of DMF, the expression of the p65 nuclear factor kappa B (NFκB), tumor necrosis factor alpha (TNFα), nuclear factor E2-related factor 2 (Nrf2), and heme oxygenase-1 (HO-1) genes was measured by real-time PCR. p65NFκB and TNFα expression was increased, whereas Nrf2 and HO-1 expression was decreased in the DEHP group compared to the control group. These effects were reversed by using DMF. Conclusions: The findings of the current study revealed that DMF can act as a nephroprotective agent against kidney damage induced by DEHP partly through inhibiting NFκB and improving Nrf2 signaling pathways.
Rational Design and Development of Novel NAE inhibitors for the treatment of pancreatic cancer
Authors: Lu Cheng , Lu Peng , Gong Lei , Zhu Li-Juan , An Yuanyuan , Wang Yubin 
Published: June 2022

Abstract
Pancreatic cancer remains clinically challenging because of the lack of efficient targeted therapies and high aggressiveness. NEDD8 activating enzyme (NAE) plays a critical role in various cellular functions in cancers. Herein, we report the synthesis, optimization, and evaluation of a new series of pyrido[2,3-d]pyrimidin-7(8H)-one derivative as highly selective and efficacious NAE inhibitors, enabling rapid degradation of related substrates and potent inhibition of BxPC-3 cell proliferation. Moreover, western blot assays demonstrated that compound 51 could inhibit NAE activity, resulting in apoptosis in BxPC-3 cells. Furthermore, compound 51 induced cell apoptosis in vitro and inhibited tumor growth in BxPC-3 xenograft models. Our work established that 51 was a highly potent and efficacious NAE inhibitor, representing an effective strategy and great potential as a new targeted therapy for pancreatic cancer.
Synthetic control of the surface area in nickel cobalt oxide for glucose detection via additive- assisted wet chemical method
Authors: Jang Kyu-bong , Park Kyoung Ryeol , Mo Chan Bin , Kim Seongtak , Jeon Jaeeun , Lim Sung-chul , Ahn Chisung , Han HyukSu , Kim Dongju , Kim Kang min , Mhin Sungwook 
Published: June 2022

Abstract
We investigated the effect of specific surface area on the electrochemical properties of NiCo2O4 (NCO) for glucose detection. NCO nanomaterials with controlled specific surface areas were prepared by additive-assisted hydrothermal synthesis, and self-assembled nanostructures with urchin-, pine-needle-, tremella-, and flower-like morphologies were obtained. The novelty of this method is the systematic control of chemical reaction routes assisted by the addition of different additives during synthesis, which results in the spontaneous formation of various morphologies without any difference in the crystal structure and chemical states of the constituent elements. Such morphological control of NCO nanomaterials leads to considerable changes in the electrochemical performance for glucose detection. Combined with materials characterization, the relationship between the specific surface area and the electrochemical performance is discussed for glucose detection. This work can provide scientific insights for tailoring the surface area of nanostructures, which determines their functionality for potential applications in glucose biosensors.
Characterization of Cassava brown streak virus proteins draw their sides during mixed infections and reveal P1 as a silencing suppressor
Authors: Pablo-Rodríguez José Luis , Bailey Andy M. , Foster Gary D. 
Published: June 2022

Abstract
Cassava brown streak disease (CBSD) is currently one of the major constraints on cassava production in Africa. CBSD is estimated to cause annual economic losses of over $100 million USD. CBSD is caused by at least two viral species: Cassava brown streak virus (CBSV) and the Uganda cassava brown streak virus (UCBSV). In field, CBSV and UCBSV occur in single and mixed infections with the potential to be found in mixed infections with other viruses. The interactions between CBSV and other viruses are poorly understood and many functions of CBSV genes are not fully characterised. In this study we analysed the interaction of CBSV with non-related viruses, for potential synergistic interactions, namely tobacco mosaic virus (TMV), and potato virus Y (PVY), both very well characterised for their infection and symptomatology in Nicotiana species. These interactions demonstrated to be synergistic with TMV and antagonistic with PVY. Then P1, P3, 6k1, CI, 6k2, VPg, NIa, NIb, Ham1-like and CP from CBSV were analysed separately, to determine which genes from CBSV were responsible for the direction of these interactions. For this analysis, transgenic lines expressing single CBSV genes were used, providing information about the importance of Ham1. Further functional analysis of these CBSV genes was carried out, analysing silencing suppression activity through agroinfiltration assays. This confirmed silencing suppression activity for the CBSV P1 protein and demonstrated that a functional LRRA domain is required for this activity.
Exosomal miR-140-5p inhibits osteogenesis by targeting IGF1R and regulating mTOR pathway in ossification of the posterior longitudinal ligament
Authors: Tang Yifan , Sun Yanqing , Zeng Junkai , Yuan Bo , Zhao Yin , Geng Xiangwu , Jia Lianshun , Zhou Shengyuan , Chen Xiongsheng 
Published: June 2022

Abstract
Background
Ossification of the posterior longitudinal ligament (OPLL) is a disabling disease, of which the pathogenesis is still unclear, and there are no effective cure or prevention methods. Exosomal miRNA play an important role in osteogenesis of the ectopic bone. Therefore, we focused on the down-regulation miR-140-5p from OPLL cell-derived exosomes in order to explore the mechanism of exosomal miR-140-5p in inhibiting osteogenesis in OPLL.
Results
Exosomes were isolated by differential centrifugation and identified by transmission electron microscopy, nanoparticle tracking analysis, and exosomal markers. Exosomal RNA was extracted to perform miRNA sequencing and disclose the differentially expressed miRNAs, among which miR-140-5p was significantly down-regulated. The confocal microscopy was used to trace the exosomal miR-140-5p delivered from OPLL cells to human mesenchymal stem cells (hMSCs). In vitro, we verified exosomal miR-140-5p inhibited osteoblast differentiation of hMSCs by targeting IGF1R and suppressing the phosphorylation of IRS1/PI3K/Akt/mTOR pathway. In vivo, we verified that exosomal miR-140-5p inhibited the ectopic bone formation in mice assessed by micro-CT and immunohistochemistry.
Conclusions
We found that exosomal miR-140-5p could inhibit the osteogenic differentiation of hMSCs by targeting IGF1R and regulating the mTOR pathway, prompting a further potential means of drug treatment and a possible target for molecular therapy of OPLL.
Establishment of Cryogenic Constitutive Model for Ti-6Al-2Zr-1Mo-1V Titanium Alloy
Authors: LIU Kuo , Yu Qingbo , Gan Yongquan , Yang Yuebing , Zhang Yu , Wang Yongqing , Liu Haibo 
Published: June 2022

Abstract
Ti-6Al-2Zr-1Mo-1V (TA15) titanium alloy is widely used in aerospace and other key fields because of its excellent properties such as specific strength, specific stiffness, and corrosion resistance. TA15 titanium alloy has low thermal conductivity and high cutting temperature, which is a typical difficult-to-machine material. The cryogenic machining technology can effectively improve the problems of high cutting temperature and poor machining quality during the machining of titanium alloy. Many researchers have studied the constitutive model of TA15 titanium alloy in order to reveal the machining mechanism, but there has been no research on the cryogenic constitutive model of TA15 titanium alloy. In this paper, a series of tensile tests at low temperature were conducted with TA15 titanium alloy as the research target; The cryogenic constitutive model was established, and the accuracy of the cryogenic constitutive model was verified based on the unequal shear zone model. The test results show that the strength of TA15 titanium alloy increases and the plasticity decrease at low temperatures. the strengthened stage of TA15 titanium alloy was significantly shortened at − 196°C; The maximum error of shear force calculated by orthogonal cutting tests is less than 20% compared with that predicted by cryogenic constitutive model.
Aluminum induced oxidative mitochondrial DNA release mediated by HIF-1α-related pathway to activate NLRP3 inflammasome in astrocytes
Authors: Liu Ziyue , Hao Chenyu , Zhu Xiaoying , Song Yushuai , Hao Wudi , Wu Shengwen , Yang Jinghua , Lu Xiaobo , Jin Cuihong 
Published: June 2022

Abstract
Aluminum compounds are widely distributed in nature and applied frequently in daily life, which are considered as environmental pathogenic factor of neurodegenerative diseases. Previous studies have suggested that aluminum can cause neuroinflammation, but whether astrocytes could play an important role is still obscure. Here, the rat model of subchronic aluminum exposure was established by drinking water containing AlCl3 for 12 w. Primary astrocytes were isolated and treated with AlCl3. YC-1 was adopted as an inhibitor of HIF-1α in vitro experiments. In this study, aluminum exposure could activate astrocytes, decrease α-KGDH activity while increase SDH activity, which stabilized HIF-1α to enhance HIF-1α level and its colocalization with PKM2 in nucleus. Further, PKM2 was activated to phosphorylate C-Myc at Ser62 to prevent its degradation, which upregulated CLIC4 protein level to reduce mitochondrial membrane potential and OX-mt DNA was released. In the cytoplasm, OX-mt DNA could bind to and stimulate NLRP3 inflammasome, resulting in more IL-1β release to trigger neuroinflammation, and the intervention of YC-1 could rescue these impairments. That is, astrocytes play an important role in aluminum-induced neuroinflammation.
Healthier but Wasteful? Changing food loss and waste along global
food supply chains with healthier diets
Authors: Gatto Alessandro , Kuiper Marijke , Meijl Hans 
Published: June 2022

Abstract
Bridging economic and technical modelling of food loss and waste (FLW), we trace physical quantities of FLW along food supply chains (FSC) in a global economic model, building on a newly compiled FLW database. Imposing the EAT-Lancet diet provides changes in FLW magnitude, composition, and geographical location by 2030. By decreasing global food consumption FLW reduces along each stage of the FSC despite a shift to higher FLW foods. Shares of less-processed and plant-based FLW increase, improving reuse possibilities. While food trade decreases, high-income region (HIC) imports still generate substantial losses in low- and mid-income regions (LMIC) with limited scope for reuse. As import-embedded FLW is not captured in SDGs this eases HICs ability to meet SDG12.3, hampering LMICs. While the healthy diet generates less FLW, farm-level loss policies in LMIC need to be complemented by FLW reuse strategies to not let potential inputs for nutritious foods go to waste.
Effective natural inhibitors targeting IL-2 receptor by computational study
Authors: Hou Yuanyuan , Mou Yanhao , Xie Haoqun , Dou Gaojing , Ge Junliang , Zhong Sheng 
Published: June 2022

Abstract
Objective: This study aims to screen ideal lead compounds and potential candidate drugs with inhibitory effect on IL-2R from the drug library (ZINC database).Methods: Computer Aided virtual technology was used to identify the potential inhibitors of IL-2R. Libdock is used for structure based screening, followed by ADME (absorption, distribution, metabolism and excretion) and toxicity prediction. Molecular docking was performed to demonstrate the binding affinity mechanism between ligand and IL-2R. Molecular dynamics simulations were used to evaluate the stability of ligand receptor complexes.Results: Two effective natural compounds ZINC00044361247 and ZINC0028882432 were found in ZINC database to bind to IL-2R, showing high binding affinity. In addition, they were predicted to have low rodent carcinogenicity, Ames mutagenicity, developmental toxicity potential and high tolerance to cytochrome P4502D6. Molecular dynamics simulation shows that ZINC00044361247 and ZINC0028882432 and IL-2R have more favorable potential energy and can exist stably in the natural environment.Conclusion: This study shows that ZINC00044361247 and ZINC0028882432 are ideal IL-2R targeted inhibitors. These compounds are safe potential drug candidates and are of great significance in inhibiting T cell-mediated immune response and allogeneic transplantation.
Prognostic Nomograms for Patients with Metastatic Gastric Cancer: A Large Population-Based Cohort Study and External Validation
Authors: Wang Zhengguang , Chen Mengding , Hou Huanan , Dao Qianze , Chen Ke 
Published: June 2022

Abstract
Purpose
This study aimed to identify the prognostic variables in patients with metastatic gastric cancer (MGC) and to establish a nomogram based on the number of organs for metastasis (NOM) to predict the survival of MGC patients.
Methods
Data of 3,909 patients (training cohort) were collected from the Surveillance, Epidemiology, and End Results Program (SEER) database and that of 312 patients (validation cohort) were collected from two Chinese hospitals. Univariate and multivariate Cox regression analyses were performed to identify the significant prognostic variables. A predictive nomogram was built based on SEER cohort and validated in the Chinese cohort. The discrimination and calibration abilities were assessed by concordance index (C-index), calibration plot, and area under the (time-dependent receiver operating characteristic) curve (AUC).
Results
Race, surgery, chemotherapy, radiotherapy, tumor grade, number of organs affected by metastasis (NOM) were identified by univariate and multivariate Cox regression models. A predictive nomogram was constructed based on the SEER cohort. Excellent C-index, calibration plots, and AUC were obtained using the nomogram in the Chinese cohort. An online version was built based on the nomogram.
Conclusion
Our nomogram provides a reliable tool for predicting the prognosis of MGC patients.
Gene expression profiles associated with molecular subtypes and pathological response to neoadjuvant treatment in surgical breast cancer.
Authors: Baulies Sonia , Molina Miguel Ángel , Tresserra Francisco , Rodríguez Ignacio , Giménez-Capitán Ana , Ara Carmen , Fábregas Rafael 
Published: June 2022

Abstract
Purpose
The association between mRNA expression of 13 candidate genes in surgical breast cancer, molecular tumor subtypes and response to neoadjuvant chemotherapy has been investigated in order to identify potential markers with predictive and prognostic value.
Methods
Tumor pretreatment core biopsies of 92 breast cancer patients treated with neoadjuvant chemotherapy were submitted to gene expression profiling. Medians and percentiles of mRNA expression for each gene were calculated and correlated to molecular tumor subtype and pathological response.
Results
Positive-hormone receptor (HR) tumors showed significantly higher mRNA levels of AXL (p = 0.006), FGFR1 (p = 0.006), RAP80 (p = 0.007), GAS6 (p = 0.05), BTRCP (p = 0.003) and ZNF217 (p = 0.005). A significant association between gene expression and pathological complete response (pCR) was observed for four genes; AXL (p = 0.03), FGFR1 (p = 0.018), YAP (p = 0.023), BRCA1 (p = 0.027). Multivariate analysis identified low levels of AXL and BRCA1 mRNA as independent factors associated with pCR, with an OR 14.03 (CI95% 1.44-136.61) in AXL and 7.07 (CI95% 1.41–35.43) in BRCA1. The expression signature combining BRCA1 and AXL low levels associated with pCR in 100% of the cases (p < 0.001).
Conclusion
A two-gene mRNA expression signature including AXL and BRCA1 associates with pCR to neoadjuvant chemotherapy and can have predictive value.
Clinical observation of menopause hormone therapy in euthyroid and mild subclinical hypothyroidism postmenopausal women
Authors: Xu Wenxian , Huang Yizhou , Ma Linjuan , Chen Peiqiong , Li Saisai , Chu Ketan , Lan Yibing , Li Chunming , Song Yang , Ying Qian , Zhou Jianhong 
Published: June 2022

Abstract
Objective:
To evaluate the endocrine hormone and metabolic indexes in euthyroid and mild subclinical hypothyroidism postmenopausal women after menopause hormone therapy (MHT).
Methods:
A retrospective study was conducted including 587 postmenopausal women received MHT, whose median (25-75th percentile) age was 52.00 (49.00–54.00) years. According to the state of thyroid stimulating hormone (TSH) level at the initial diagnosis, the patients were divided into three groups: I (euthyroid with low normal TSH range, n = 460), II (euthyroid with upper normal TSH range, n = 106) and III (mild subclinical hypothyroidism, n = 21). After continuous oral MHT regimen used same potency of estradiol for 6–18 month cycles, serum endocrine hormone and metabolic indexes were reassessed.
Results:
Compared with baseline, serum TSH level in group I and II changed with significant difference, but all values were within the normal range, no significant difference was found of serum TSH level in group III. After treatment, all serum free triiodothyronine and free thyroxine levels were within the normal range. Serum total cholesterol, triglyceride, fasting plasma glucose, fasting insulin levels and homeostasis model assessment of insulin resistance index were decreased in group I with significant differences. All lipid and glucose parameters were found no significant differences in group III before and after treatment.
Conclusions:
MHT did not affect thyroid function in euthyroid and mild subclinical hypothyroidism women. MHT led to an improvement of lipid and glucose indicators in euthyroid women with low normal TSH range.
Machine learning for clinical decision support in intrahepatic cholangiocarcinoma based on a population study of the US SEER database and a Chinese single-center registry
Authors: Zhou Shuang-nan , Jv Da-Wei , Meng Xiang-Fei , Zhang Jing-Jing , Liu Chun , Wu Zeyi , Hong Na , Lu Yin-Ying , Zhang Ning 
Published: June 2022

Abstract
Background and aims To date, there is still a lack of consensus on the treatment of intrahepatic cholangiocarcinoma (iCCA). This study aims to build a clinical decision support tool based on machine learning of the Surveillance, Epidemiology, and End Results (SEER) database and the Fifth Medical Center of PLA General Hospital in China. Methods A total of 4,398 eligible patients with pathology-proven iCCA from the SEER database and 504 from the hospital data were enrolled for modeling by cross-validation based on the method of machine learning. All models were trained by the open-source Python library 4scikit-survival version 0.16.0 and explained by SHapley Additive exPlanations. Permutation importance was calculated using the library ELI5. Results All of the involved treatment modalities can contribute to a better prognosis. Three models were derived and tested among different data sources with the concordance index in the test datasets of 0.67, 0.69, and 0.73 respectively. The prediction was also consistent with the actual situation in randomly selected real patients. Model 2 trained by the hospital data was selected to develop an online tool because of the advantage of predicting the short-term prognosis.Conclusion The prediction model and tool of this study can be applied to predicting patients’ prognosis after treatment by inputting the patient’s clinical parameters or TNM stages and the treatment option and thus contribute to the optimal clinical decision.