bluuebunny/crossref_metadata_2025_split huggingface dataset:
STYK1/NOK Promotes Metastasis and Epithelial-Mesenchymal Transition in Non-small Cell Lung Cancer by Suppressing FoxO1 Signaling
Authors: Lai Yuanyang , Lin Fang , Wang Xuejiao , Zhang Jiao , Xia Jinghua , Sun Ying , Wen Miaomiao , Li Xiaofei , Zhang Zhipei , Zhao Jinbo 
Published: July 2021

AimsSerine/threonine/tyrosine kinase 1 (STYK1) has been previously shown to have oncogenic properties, and emerging evidence suggests that STYK1 expression correlates with epithelial-mesenchymal transition (EMT). However, the mechanism of STYK1 involvement in oncogenesis remains unknown. The present study aimed to elucidate how STYK1 expression level relates to the metastasis, migration, invasion, and EMT in non-small cell lung cancer (NSCLC) and to determine the molecular mechanism of STYK1 effects.MethodsSerine/threonine/tyrosine kinase 1 (STYK1) expression level and its relationship with the prognosis of NSCLC were determined using the ONCOMINE database and clinical cases. Non-small cell lung cancer cell lines with the overexpression or knockdown of STYK1 were established to determine whether STYK1 promotes cell migration, invasion, and EMT in vitro and in vivo. In addition, a constitutively active FoxO1 mutant (FoxO1AAA) was used to examine the role of FoxO1 in the STYK1-mediated upregulation of metastasis and EMT in NSCLC.ResultsSerine/threonine/tyrosine kinase 1 (STYK1) was upregulated in NSCLC tissues and cell lines, and its overexpression correlated with poor prognosis in patients with NSCLC after surgery. Enhanced expression of STYK1 potentiated the migration, invasion, and EMT in SW900 cells, thereby promoting metastasis, whereas knockdown of STYK1 inhibited these cellular phenomena in Calu-1 cells. Furthermore, STYK1 expression was positively related to the level of phosphorylated-FoxO1, whereas the constitutively active FoxO1 mutant protected against the positive effect of STYK1 overexpression on cell migration, invasion, and EMT.ConclusionSerine/threonine/tyrosine kinase 1 (STYK1) was upregulated in NSCLC and correlated with poor clinical outcomes. In addition, STYK1 suppressed FoxO1 functions, thereby promoting metastasis and EMT in NSCLC.
Dihydropyrimidinase Like 2 Promotes Bladder Cancer Progression via Pyruvate Kinase M2-Induced Aerobic Glycolysis and Epithelial–Mesenchymal Transition
Authors: Zou Jun , Huang Ruiyan , Chen Yanfei , Huang Xiaoping , Li Huajun , Liang Peng , Chen Shan 
Published: July 2021

BackgroundAerobic glycolysis and epidermal–mesenchymal transition (EMT) play key roles in the development of bladder cancer. This study aimed to investigate the function and the underlying mechanism of dihydropyrimidinase like 2 (DPYSL2) in bladder cancer progression.MethodsThe expression pattern of DPYSL2 in bladder cancer and the correlation of DPYSL2 expression with clinicopathological characteristics of bladder cancer patients were analyzed using the data from different databases and tissue microarray. Gain- and loss-of-function assays were performed to explore the role of DPYSL2 in bladder cancer progression in vitro and in mice. Proteomic analysis was performed to identify the interacting partner of DPYSL2 in bladder cancer cells.FindingsThe results showed that DPYSL2 expression was upregulated in bladder cancer tissue compared with adjacent normal bladder tissue and in more aggressive cancer stages compared with lower stages. DPYSL2 promoted malignant behavior of bladder cancer cells in vitro, as well as tumor growth and distant metastasis in mice. Mechanistically, DPYSL2 interacted with pyruvate kinase M2 (PKM2) and promoted the conversion of PKM2 tetramers to PKM2 dimers. Knockdown of PKM2 completely blocked DPYSL2-induced enhancement of the malignant behavior, glucose uptake, lactic acid production, and epithelial–mesenchymal transition in bladder cancer cells.InterpretationIn conclusion, the results suggest that DPYSL2 promotes aerobic glycolysis and EMT in bladder cancer via PKM2, serving as a potential therapeutic target for bladder cancer treatment.
Stable Water Isotope Assessment of Tundra Wetland Hydrology as a Potential Source of Arctic Riverine Dissolved Organic Carbon in the Indigirka River Lowland, Northeastern Siberia
Authors: Takano Shinya , Yamashita Youhei , Tei Shunsuke , Liang Maochang , Shingubara Ryo , Morozumi Tomoki , Maximov Trofim C. , Sugimoto Atsuko 
Published: July 2021

Arctic tundra wetlands may be an important source of dissolved organic carbon (DOC) in Arctic rivers and the Arctic Ocean under global warming. We investigated stable water isotopes and DOC concentration in wetlands, tributaries, and the mainstream at the lower reaches of the Indigirka River in northeastern Siberia during the summers of 2010–2014 to assess the complex hydrology and role of wetlands as sources of riverine DOC. The wetlands had higher values of δ18O and DOC concentration than the tributaries and mainstream of the Indigirka River. A relationship between the two parameters was observed in the wetlands, tributaries, and mainstream, suggesting the wetlands can be a source of DOC for the mainstream through the tributaries. The combined temporal variations in riverine δ18O and DOC concentration indicate the mainstream water flowed into the tributaries during relatively high river-level periods in summer, whereas high DOC water in the downstream wetlands could be discharged to the mainstream through the tributaries during the low river-level periods. A minor fraction (7–13%) of riverine and wetland DOC was degraded during 40 days of dark incubation. Overall, the downstream wetlands potentially provide relatively less biodegradable DOC to the Arctic river and costal ecosystem during the low river-level periods—from late summer to autumn.
GAS1: A New β-Glucan Immunostimulant Candidate to Increase Rainbow Trout (Oncorhynchus mykiss) Resistance to Bacterial Infections With Aeromonas salmonicida achromogenes
Authors: Cornet Valérie , Khuyen Trinh Dinh , Mandiki Syaghalirwa. N. M. , Betoulle Stéphane , Bossier Peter , Reyes-López Felipe E. , Tort Lluis , Kestemont Patrick 
Published: July 2021

β-glucans are prebiotic and/or food additives used by the aquaculture industry to enhance the immune response of fish. Their efficiency may vary according to their origin and structure. In this study, the immunostimulant effects of two β-glucan types extracted from wild-type baker’s yeast (Saccharomyces cerevisiae) and its null-mutant Gas1 were investigated. Gas1 has a beta-1,3-glucanosyltransferase activity necessary for cell wall assembly. Using a positive (commercial product MacroGard®) and a negative control (a diet without glucans), we evaluated the immune responses and disease resistance of rainbow trout juveniles (mean weight, ~44 g) fed control, low (0.2%) and high (0.5%) doses of Macrogard®, Gas1, and Wild type-β-glucan after a short-term (15 days, D15) or mid-term (36 days, D36) feeding periods. We found that β-glucan supplemented diets did not affect growth performance, mortality, splenic index, or leukocyte respiratory burst activity on D15 nor D36. However, each β-glucan triggered different immune effectors, depending of the doses or length of exposure compared to others and/or the negative control. Indeed, high dose of MacroGard® significantly increased lysozyme activities at D15 compared with the control and other diets (p&lt;0.05). At D36, MacroGard β-glucan enhanced the production of lymphocytes in comparison with the control diet (p&lt;0.05). Regarding WT β-glucan, at D36, WT-β-glucan, especially the high dose, provided the highest enzymatic activities (lysozyme and ACH50) and Ig level (p&lt;0.01). Furthermore, on D36, Gas1 also increased lysozyme activity, Ig proportion, and some immune genes (mcsfra, hepcidin) compared with MacroGard® (p&lt;0.05). Besides, both doses of Gas1-β-glucans increased the resistance of juveniles to bacterial infection highlighted by a higher survival rate at 14 days post-challenge compared with the control and other types and doses of β-glucans (p&lt;0.05). In conclusion, our results suggest that Gas1-β-glucan could represent a promising immunostimulant that would help to prevent diseases in aquaculture even more efficiently than other β-glucans already in use. Mode of action and particular efficiency of this new Gas1 mutant are debated.
Investigation into Microstructure Evolution of Co–Ni–Cr–W–Based Superalloy During Hot Deformation
Authors: Zhang Wei , Zhu Baohong , Wu Shuaishuai , Tao Shutian 
Published: July 2021

Hot compression tests were conducted using a Gleeble 3500 thermomechanical simulator at temperatures ranging from 1,000 to 1,200°C with the strain rate ranging from 0.1 to 10 s−1. Electron backscatter diffraction (EBSD) technique was employed by investigating the microstructure evolution during hot deformation. Microstructure observations reveal that deformation temperatures and strain rates have a significant effect on the DRX process. It is found that the fraction and grain size of DRX increase with the decreasing deformation temperature, along with the increasing high-angle grain boundaries (HAGBs). The fraction of DRX first decreases and then increases with the increase of strain rates. It is noted that there are both the nucleation mechanisms of discontinuous dynamic recrystallization (DDRX) and continuous dynamic recrystallization (CDRX) during the DRX process for Co–Ni–Cr–W–based superalloys. DDRX and CDRX are the primary and subsidiary nucleation mechanisms of DRX, respectively. It is also found that deformation temperatures and strain rates have almost no effect on the primary and subsidiary nucleation mechanisms of DRX. At the temperature above 1,150°C, the complete DRX occurred with the average grain sizes of about 25.32–29.01 μm. The homogeneity and refinement of microstructure can be obtained by selecting the suitable hot deformation parameters.
The Impact of Age on Mortality and Disability in Patients With Ischemic Stroke Who Underwent Cerebral Reperfusion Therapy: A Brazilian Cohort Study
Authors: Furlan Natália Eduarda , Luvizutto Gustavo José , Hamamoto Filho Pedro Tadao , Zanati Bazan Silméia Garcia , Modolo Gabriel Pinheiro , Ferreira Natalia Cristina , Miranda Luana Aparecida , de Souza Juli Thomaz , Winckler Fernanda Cristina , Vidal Edison Iglesias de Oliveira , de Freitas Carlos Clayton Macedo , Martin Luis Cuadrado , Bazan Rodrigo 
Published: July 2021

Introduction: The main driver for increased stroke prevalence is the aging of the population; however, the best evidenced-based strategies for stroke treatment and prevention are not always followed for older patients. Therefore, the aim was studying the association of age with clinical outcomes (mortality and functional disability) in stroke patients who underwent cerebral reperfusion therapy at hospital discharge and 90 days after ictus.Methods: This was a retrospective (stroke databank analysis) cohort study of participants who had been diagnosed with ischemic stroke and undergone intravenous cerebral reperfusion therapy or mechanical thrombectomy. The variable of interest was patient age, which was categorized into four groups: (1) up to 59 years; (2) 60 to 69 years; (3) 70 to 79 years old; and (4) above 79 years. The primary outcome was mortality at hospital discharge and 90 days after stroke, and the secondary outcome was functional capacity at hospital discharge and 90 days after stroke.Results: A total of 281 patients was included in the study (235 treated by thrombolysis alone, and 46 treated with mechanical thrombectomy). The mean age of the total sample was 67 ± 13.1 years. The oldest patients had the most unfavorable outcomes, except for mortality rate, at hospital discharge (mRS &gt; 2; OR: 1.028; 95% CI 1.005 to 1.051; p = 0.017; mRS &gt; 3; OR: 1.043, 95% CI 1.018 to 1.069; p = 0.001) and 90 days after stroke (mRS &gt; 2; OR: 1.028; 95% CI 1.005 to 1.051; p = 0.017; mRS &gt; 3; OR: 1.043, 95% CI 1.018 to 1.069; p = 0.001).Conclusion: Cerebral reperfusion was a viable treatment for ischemic stroke in both elderly and very elderly patients, as it did not increase mortality. However, it was observed that older individuals had worse functional outcomes at hospital discharge and 90 days after stroke.
Load Auditory Feedback Boosts Crutch Usage in Subjects With Central Nervous System Lesions: A Pilot Study
Authors: Tamburella Federica , Lorusso Matteo , Tagliamonte Nevio Luigi , Bentivoglio Francesca , Bigioni Alessandra , Pisotta Iolanda , Lancini Matteo , Pasinetti Simone , Ghidelli Marco , Masciullo Marcella , Saraceni Vincenzo Maria , Molinari Marco 
Published: July 2021

Background:Crutches are the most common walking aids prescribed to improve mobility in subjects with central nervous system (CNS) lesions. To increase adherence to the appropriate level of crutch usage, providing load-related auditory feedback (aFB) may be a useful approach. We sensorized forearm crutches and developed a custom software to provide aFB information to both user and physical therapist (PhT).Aim:Evaluate aFB effects on load control during gait by a self-controlled case series trial.Methods:A single experimental session was conducted enrolling 12 CNS lesioned participants. Load on crutch was recorded during 10 Meter Walk Test performed with and without aFB. In both cases, crutch load data, and gait speed were recorded. Usability and satisfaction questionnaires were administered to participants and PhTs involved.Results:Reliable data were obtained from eight participants. Results showed that compared to the no FB condition, aFB yielded a significant reduction in the mean load on the crutches during gait (p= 0.001). The FB did not influence gait speed or fatigue (p&gt; 0.05). The experience questionnaire data indicated a positive experience regarding the use of aFB from both participants' and PhTs' perspectives.Conclusion:aFB significantly improves compliance with crutch use and does not affect gait speed or fatigue by improving the load placed on crutches. The FB is perceived by users as helpful, safe, and easy to learn, and does not interfere with attention or concentration while walking. Furthermore, the PhTs consider the system to be useful, easy to learn and reliable.
Previous History of Migraine Is Associated With Fatigue, but Not Headache, as Long-Term Post-COVID Symptom After Severe Acute Respiratory SARS-CoV-2 Infection: A Case-Control Study
Authors: Fernández-de-las-Peñas César , Gómez-Mayordomo Víctor , García-Azorín David , Palacios-Ceña Domingo , Florencio Lidiane L. , Guerrero Angel L. , Hernández-Barrera Valentín , Cuadrado María L. 
Published: July 2021

ObjectiveTo investigate the association of pre-existing migraine in patients hospitalised and who recovered from severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection with the presence of post-coronavirus disease (COVID) symptoms.BackgroundNo study has investigated the role of migraine as a risk factor for development of post-COVID symptoms.MethodsA case-control study including individuals hospitalised during the first wave of the pandemic (from February 20 to May 31, 2020) was conducted. Patients with confirmed previous diagnosis of migraine were considered cases. Two age- and sex-matched individuals without a history of headache per case were also recruited as controls. Hospitalisation/clinical data were collected from hospital medical records. Patients were scheduled for a telephone interview. A list of post-COVID symptoms was systematically evaluated, but participants were invited to freely report any symptom. The Hospital Anxiety and Depression Scale and the Pittsburgh Sleep Quality Index were used to assess anxiety/depressive symptoms and sleep quality. Multivariable conditional logistic regression models were constructed.ResultsOverall, 57 patients with confirmed diagnosis of migraine and 144 non-migraine controls who had recovered from COVID-19 were assessed at 7.3 months (SD 0.6) after hospital discharge. The number of post-COVID symptoms in the migraine group was significantly greater (OR 1.70, 95% CI 1.29–2.25, P &lt; 0.001) than in the non-migraine group. Fatigue was significantly more prevalent (OR 2.89, 95% CI 1.32–6.32, P = 0.008) in the migraine group. However, no between-groups difference in the prevalence of headache as a post-COVID symptom was detected.ConclusionPatients with a history of migraine who recovered from COVID-19 exhibited more long-term fatigue as post-COVID sequelae than those without migraine. Some of the pathophysiological changes associated with migraine could predispose to the occurrence of post-COVID symptoms.
Diet Data Collected Using 48-h Dietary Recall: Within—and Between-Person Variation
Authors: Rossato Sinara Laurini , Fuchs Sandra Costa 
Published: July 2021

Background and Aims: Forty-eight-hour dietary recall is a valuable source of information regarding food consumption in a population-based sample. This method covers 2 consecutive days in a single interview. Nevertheless, the number of assessments and the sample size necessary to estimate usual intake are unknown. We aimed to assess sources of variation, sample sizes, and numbers of days necessary to estimate usual nutrient intake using the 48-h dietary recall.Methods: This was a population-based cross-sectional study including 237 participants, 11–90 years old, selected using multistage probabilistic sampling to obtain data using 48-h dietary recall. Analysis of variance was used to calculate within- and between-person variation and determine the statistical parameters necessary to calculate sample size and the number of days required to calculate the usual energy and nutrient intake.Results: Within-person variation was generally lower than between-person variation, except for calcium (CVw2 = 40.8; CVb2 = 38.4%), magnesium (CVw2 = 27.4; CVb2 = 18.7%), and monounsaturated fat (CVw2 = 20.0; CVb2 = 17.3%) for the entire group and magnesium for women (CVw2 = 28.3; CVb2 = 91.8%). The number of days and sample size required to determine usual energy and nutrient intake varied substantially with gender and age (e.g., vitamin C in women N = 9, in men N = 1,641).Conclusions: Energy and nutrient intake assessment using the 48-h dietary recall misrepresents within-person variation but can generate acceptable results for between-person variation. The calculation of sample size and number of days required to determine usual energy and nutrient intake might have been affected by inadequate assessment of the within-person variation.
Development and Validation of a Radiomic Nomogram for Predicting the Prognosis of Kidney Renal Clear Cell Carcinoma
Authors: Gao Ruizhi , Qin Hui , Lin Peng , Ma Chenjun , Li Chengyang , Wen Rong , Huang Jing , Wan Da , Wen Dongyue , Liang Yiqiong , Huang Jiang , Li Xin , Wang Xinrong , Chen Gang , He Yun , Yang Hong 
Published: July 2021

PurposeThe present study aims to comprehensively investigate the prognostic value of a radiomic nomogram that integrates contrast-enhanced computed tomography (CECT) radiomic signature and clinicopathological parameters in kidney renal clear cell carcinoma (KIRC).MethodsA total of 136 and 78 KIRC patients from the training and validation cohorts were included in the retrospective study. The intraclass correlation coefficient (ICC) was used to assess reproducibility of radiomic feature extraction. Univariate Cox analysis and least absolute shrinkage and selection operator (LASSO) as well as multivariate Cox analysis were utilized to construct radiomic signature and clinical signature in the training cohort. A prognostic nomogram was established containing a radiomic signature and clinicopathological parameters by using a multivariate Cox analysis. The predictive ability of the nomogram [relative operating characteristic curve (ROC), concordance index (C-index), Hosmer–Lemeshow test, and calibration curve] was evaluated in the training cohort and validated in the validation cohort. Patients were split into high- and low-risk groups, and the Kaplan–Meier (KM) method was conducted to identify the forecasting ability of the established models. In addition, genes related with the radiomic risk score were determined by weighted correlation network analysis (WGCNA) and were used to conduct functional analysis.ResultsA total of 2,944 radiomic features were acquired from the tumor volumes of interest (VOIs) of CECT images. The radiomic signature, including ten selected features, and the clinical signature, including three selected clinical variables, showed good performance in the training and validation cohorts [area under the curve (AUC), 0.897 and 0.712 for the radiomic signature; 0.827 and 0.822 for the clinical signature, respectively]. The radiomic prognostic nomogram showed favorable performance and calibration in the training cohort (AUC, 0.896, C-index, 0.846), which was verified in the validation cohort (AUC, 0.768). KM curves indicated that the progression-free interval (PFI) time was dramatically shorter in the high-risk group than in the low-risk group. The functional analysis indicated that radiomic signature was significantly associated with T cell activation.ConclusionsThe nomogram combined with CECT radiomic and clinicopathological signatures exhibits excellent power in predicting the PFI of KIRC patients, which may aid in clinical management and prognostic evaluation of cancer patients.
A Novel Post-Operative ALRI Model Accurately Predicts Clinical Outcomes of Resected Hepatocellular Carcinoma Patients
Authors: Liao Minjun , Sun Jiarun , Zhang Qifan , Tang Cuirong , Zhou Yuchen , Cao Mingrong , Chen Tao , Hu Chengguang , Yu Junxiong , Song Yangda , Li Meng , Liao Weijia , Zhou Yuanping 
Published: July 2021

BackgroundHepatocellular carcinoma (HCC) is one of the leading malignant tumors worldwide. Prognosis and long-term survival of HCC remain unsatisfactory, even after radical resection, and many non-invasive predictors have been explored for post-operative patients. Most prognostic prediction models were based on preoperative clinical characteristics and pathological findings. This study aimed to investigate the prognostic value of a newly constructed nomogram, which incorporated post-operative aspartate aminotransferase to lymphocyte ratio index (ALRI).MethodsA total of 771 HCC patients underwent radical resection from three medical centers were enrolled and grouped into the training cohort (n = 416) and validation cohort (n = 355). Prognostic prediction potential of ALRI was assessed by receiver operating curve (ROC) analysis. The Cox regression model was used to identify independent prognostic factors. Nomograms for overall survival (OS) and disease-free survival (DFS) were constructed and further validated externally.ResultsThe ROC analysis ranked ALRI as the most effective prediction marker for resected HCC patients, with the cut-off value determined at 22.6. Higher ALRI level positively correlated with larger tumor size, higher tumor node metastasis (TNM) stage, and inversely with lower albumin level and shorter OS and DFS. Nomograms for OS and DFS were capable of discriminating HCC patients into different risk-groups.ConclusionsPost-operative ALRI was of prediction value for HCC prognosis. This novel nomogram may categorize HCC patients into different risk groups, and offer individualized surveillance reference for post-operative patients.