bluuebunny/crossref_metadata_2025_split huggingface dataset:
Prediction of radiation-induced acute skin toxicity in breast cancer patients using data encapsulation screening and dose-gradient-based multi-region radiomics technique: A multicenter study
Authors: Feng Huichun , Wang Hui , Xu Lixia , Ren Yao , Ni Qianxi , Yang Zhen , Ma Shenglin , Deng Qinghua , Chen Xueqin , Xia Bing , Kuang Yu , Li Xiadong 
Published: November 2022

PurposeRadiation-induced dermatitis is one of the most common side effects for breast cancer patients treated with radiation therapy (RT). Acute complications can have a considerable impact on tumor control and quality of life for breast cancer patients. In this study, we aimed to develop a novel quantitative high-accuracy machine learning tool for prediction of radiation-induced dermatitis (grade ≥ 2) (RD 2+) before RT by using data encapsulation screening and multi-region dose-gradient-based radiomics techniques, based on the pre-treatment planning computed tomography (CT) images, clinical and dosimetric information of breast cancer patients.Methods and Materials214 patients with breast cancer who underwent RT between 2018 and 2021 were retrospectively collected from 3 cancer centers in China. The CT images, as well as the clinical and dosimetric information of patients were retrieved from the medical records. 3 PTV dose related ROIs, including irradiation volume covered by 100%, 105%, and 108% of prescribed dose, combined with 3 skin dose-related ROIs, including irradiation volume covered by 20-Gy, 30-Gy, 40-Gy isodose lines within skin, were contoured for radiomics feature extraction. A total of 4280 radiomics features were extracted from all 6 ROIs. Meanwhile, 29 clinical and dosimetric characteristics were included in the data analysis. A data encapsulation screening algorithm was applied for data cleaning. Multiple-variable logistic regression and 5-fold-cross-validation gradient boosting decision tree (GBDT) were employed for modeling training and validation, which was evaluated by using receiver operating characteristic analysis.ResultsThe best predictors for symptomatic RD 2+ were the combination of 20 radiomics features, 8 clinical and dosimetric variables, achieving an area under the curve (AUC) of 0.998 [95% CI: 0.996-1.0] and an AUC of 0.911 [95% CI: 0.838-0.983] in the training and validation dataset, respectively, in the 5-fold-cross-validation GBDT model. Meanwhile, the top 12 most important characteristics as well as their corresponding importance measures for RD 2+ prediction in the GBDT machine learning process were identified and calculated.ConclusionsA novel multi-region dose-gradient-based GBDT machine learning framework with a random forest based data encapsulation screening method integrated can achieve a high-accuracy prediction of acute RD 2+ in breast cancer patients.
SKA1/2/3 is a biomarker of poor prognosis in human hepatocellular carcinoma
Authors: Song Guo-Qiang , He Tian-Li , Ji Ke-Jie , Duan Yi-Meng , Zhang Jia-Wen , Hu Guo-Qiang 
Published: November 2022

BackgroundSpindle and kinetochore-associated complex subunits 1–3 (SKA1–3) stabilize the kinetochore-attached spindle microtubules in metaphase. Due to the dysregulation in multiple cancers, SKA1–3 is considered a predictor for the prognosis of the patients. However, the potential clinical applications of SKA1–3, particularly in hepatocellular carcinoma (HCC) prognosis and progression, have completely unknown yet.MethodsFor the analysis of SKA1–3 expression and applications in clinics in HCC patients, several databases, such as STRING, UALCAN, GEO, and TCGA, were searched. In addition, the underlying mechanisms of SKA for the regulation of HCC occurrence, development, and progression were also explored.ResultsCompared to the normal controls, HCC patients showed dramatically elevated SKA1–3 expression at the mRNA level, and the values of the area under the curve (AUC) were 0.982, 0.887, and 0.973, respectively. Increased SKA1–3 expression levels were associated with the clinical stage, age, body mass index, tumor grade, tissue subtype, and Tp53 mutation status in HCC patients. The analyses of Kyoto Encyclopedia of Genes and Genome (KEGG) and Gene ontology (GO) demonstrated that SKA1–3 are enriched mainly in the Fanconi anemia, homologous recombination, spliceosome, DNA replication, and cell cycle signaling pathways. The hub genes, such as CDK1, CCNB1, CCNA2, TOP2A, BUB1, AURKB, CCNB2, BUB1B, NCAPG, and KIF11, were identified in protein–protein interactions (PPIs). The expression levels of hub genes were increased in HCC patients and predictive of a poor prognosis. Finally, the expression levels of SKA1–3 were determined using the GEO database.ConclusionsSKA1–3 are potential prognostic biomarkers of and targets for HCC. In addition, SKA1–3 may affect HCC prognosis via the Fanconi anemia pathway, homologous recombination, spliceosome, DNA replication, and cell cycle signaling pathway.
CRISPR Cas9-mediated ablation of pyruvate carboxylase gene in colon cancer cell line HT-29 inhibits growth and migration, induces apoptosis and increases sensitivity to 5-fluorouracil and glutaminase inhibitor
Authors: Ngamkham Jarunya , Siritutsoontorn Siraprapa , Saisomboon Saowaluk , Vaeteewoottacharn Kulthida , Jitrapakdee Sarawut 
Published: November 2022

Pyruvate carboxylase (PC) is an important anaplerotic enzyme that replenishes the tricarboxylic acid cycle (TCA) intermediates. It prevents the collapse of the TCA cycle upon its intermediates are removed during high anabolic demand. We have recently shown that overexpression of PC protein was associated with staging, metastasis and poor survival of colorectal cancer patients. Herein, we generated the PC knockout (PC KO) colon cancer cell lines, HT-29, by CRISPR-Cas9 technique, as a model to understand the role of this enzyme in colorectal cancer. The PC KO HT-29 cell lines had no detectable PC protein and did not show abnormal cellular or nuclear structures. However, PC KO HT-29 cells showed a 50-60% reduction in their growth rate and a 60-70% reduction in migration. The deficient growth phenotype of PC KO HT-29 cells was associated with apoptotic induction with no apparent cell cycle disruption following five days of growth. Down-regulation of key lipogenic enzymes, including acetyl-CoA carboxylase-1 and fatty acid synthase, was also associated with growth inhibition, suggesting that the de novo lipogenesis is impaired. Furthermore, PC KO HT-29 cells were 50% and 60% more sensitive to 5-fluorouracil and glutaminase inhibitor, CB-839, at their IC50 concentrations, respectively, following 48 h exposure. The increased cytotoxicity of CB-839 to PC KO HT-29 cells was associated with increased poly (ADP-ribose) polymerase cleavage. However, this was not observed with PC KO cells exposed to 5-fluorouracil, suggesting that PC KO HT-29 cells were prone to CB-839-induced apoptosis. Collectively, these findings indicate that ablation of PC expression in HT-29 cells disrupts the metabolic homeostasis of cells and inhibits proliferation and migration, accompanied by apoptotic induction. This study highlights the crucial role of PC in supporting the survival of HT-29 cells during exposure to chemotherapeutic drugs.
Prognostic values of the gross volume of metastatic lymph nodes in patients with esophageal squamous cell carcinoma treated with definitive concurrent chemoradiotherapy
Authors: Li Yang , Li Yanqi , Huang Hui , Guo Zhoubo , Zhang Kunning , Zhang Wencheng , Pang Qingsong , Wang Ping 
Published: November 2022

PurposeWe aim to explore whether the gross volume of metastatic lymph nodes (GTVnd) and the gross volume of primary tumor (GTVp) could be prognostic factors for esophageal squamous cell carcinoma (ESCC) patients treated with definitive concurrent chemoradiotherapy (dCCRT).MethodsWe retrospectively analyzed 252 ESCC patients treated with dCCRT in the era of intensity-modulated radiation therapy (IMRT) at our institution. The cut-off value for the GTVnd derived from the restricted cubic splines (RCS) was determined. Univariate and multivariate Cox proportional hazard models were performed to determine the association between GTVnd and prognosis. we performed recursive partitioning analysis (RPA) method using GTVnd to develop a new risk stratification (TGTVndM). Moreover, the linear trend χ2, likelihood ratio χ2, and akaike information criterion (AIC) were used to determine the prognostic value between the TNM and TGTVndM staging systems.ResultsThe five-year overall survival (OS) rate was 30.6%, with a median follow-up of 38 months. The cut-off value of GTVnd determined by the RCS was 4.35 cm3. GTVnd≥4.35 cm3 was an independent and significant negative prognostic factor for OS (HR=1.949, P&lt;0.001), progression free survival (PFS) (HR=1.425, P=0.048), and distance metastasis free survival (DMFS) (HR=2.548, P=0.001). In multivariable analysis, gender, clinical T stage, and GTVnd were independently associated with OS. RPA segregated patients into 3 prognostic groups: high risk (T1-4 GTVnd≥4.35, n=126, III stage), intermediate risk (T4 GTVnd&lt;4.35,n=38,II stage), and low risk(T1-3GTVnd&lt;4.35, n=88, I stage). The 5-year OS(P&lt;0.001), PFS (P=0.002), and DMFS (P=0.001) were significantly worse in high-risk group in comparison with the intermediate and low risk groups. Compared with the TNM staging system, the clinical T stage combined with GTVnd (TGTVndM) had a higher linear trend χ2 (26.38 versus 25.77), higher likelihood ratio χ2 (24.39 versus 20.69), and lower AIC (1255.07 versus 1260.06).ConclusionsGTVnd may serve as a good prognostic factor in predicting distant metastasis and death for ESCC patients treated with dCCRT. The TGTVndM staging system demonstrated superior accuracy for predicting OS and could serve as a more effective prognostic guidance for unresectable ESCC patients.
Potential safety signal of pregnancy loss with vascular endothelial growth factor inhibitor intraocular injection: A disproportionality analysis using the Food and Drug Administration Adverse Event Reporting System
Authors: Sakai Takamasa , Mori Chiyo , Ohtsu Fumiko 
Published: November 2022

Objectives: Intraocular administration of vascular endothelial growth factor (VEGF) inhibitors may be associated with pregnancy loss. However, little is known about intraocular anti-VEGF therapy during pregnancy. Here, we conducted a pharmacovigilance study using a spontaneous reporting database to evaluate the relationship between intraocular VEGF inhibitors and pregnancy loss.Methods: We used the JAPIC AERS database which is composed of the Food and Drug Administration Adverse Event Reporting System (FAERS) dataset preprocessed by the Japan Pharmaceutical Information Center (JAPIC) to investigate the VEGF inhibitors ranibizumab, aflibercept, and bevacizumab. Disproportionality analyses were conducted for VEGF inhibitors and pregnancy loss. The lower limit of the 95% confidence interval (CI) of the reporting odds ratio (ROR) &gt; 1 and a minimum of three reported cases of pregnancy loss were the detection criteria used in the current study.Results: In the FAERS, 19 pregnancy loss cases were reported for ranibizumab with an ROR of 4.44 (95% CI: 2.42–8.16), 6 for intraocular bevacizumab with an ROR of 32.25 (95% CI: 3.88–267.9), and 4 for intraocular aflibercept with an ROR of 5.37 (95% CI: 1.34–21.49). All these drugs met the detection criteria.Conclusion: Potential safety signals of pregnancy loss were obtained from intraocular administration of VEGF inhibitors during pregnancy. These signals should be validated using a causal design study.
GPER limits adverse changes to Ca2+ signalling and arrhythmogenic activity in ovariectomised guinea pig cardiomyocytes
Authors: Francis Alice J. , Firth Jahn M. , Sanchez-Alonso Jose L. , Gorelik Julia , MacLeod Kenneth T. 
Published: November 2022

Background: The increased risk of post-menopausal women developing abnormalities of heart function emphasises the requirement to understand the effect of declining oestrogen levels on cardiac electrophysiology and structure, and investigate possible therapeutic targets, namely the G protein-coupled oestrogen receptor 1 (GPER).Methods: Female guinea pigs underwent sham or ovariectomy (OVx) surgeries. Cardiomyocytes were isolated 150-days post-operatively. Membrane structure was assessed using di-8-ANEPPs staining and scanning ion conductance microscopy. Imunnohistochemistry (IHC) determined the localisation of oestrogen receptors. The effect of GPER activation on excitation-contraction coupling mechanisms were assessed using electrophysiological and fluorescence techniques. Downstream signalling proteins were investigated by western blot.Results: IHC staining confirmed the presence of nuclear oestrogen receptors and GPER, the latter prominently localised to the peri-nuclear region and having a clear striated pattern elsewhere in the cells. Following OVx, GPER expression increased and its activation reduced Ca2+ transient amplitude (by 40%) and sarcomere shortening (by 32%). In these cells, GPER activation reduced abnormal spontaneous Ca2+ activity, shortened action potential duration and limited drug-induced early after-depolarisation formation.Conclusion: In an animal species with comparable steroidogenesis and cardiac physiology to humans, we show the expression and localisation of all three oestrogen receptors in cardiac myocytes. We found that following oestrogen withdrawal, GPER expression increased and its activation limited arrhythmogenic behaviours in this low oestrogen state, indicating a potential cardioprotective role of this receptor in post-menopausal women.
The mechanosensitive Piezo1 channels contribute to the arterial medial calcification
Authors: Szabó László , Balogh Norbert , Tóth Andrea , Angyal Ágnes , Gönczi Mónika , Csiki Dávid Máté , Tóth Csaba , Balatoni Ildikó , Jeney Viktória , Csernoch László , Dienes Beatrix 
Published: November 2022

Vascular calcification (VC) is associated with a number of cardiovascular diseases, as well as chronic kidney disease. The role of smooth muscle cells (SMC) has already been widely explored in VC, as has the role of intracellular Ca2+ in regulating SMC function. Increased intracellular calcium concentration ([Ca2+]i) in vascular SMC has been proposed to stimulate VC. However, the contribution of the non-selective Piezo1 mechanosensitive cation channels to the elevation of [Ca2+]i, and consequently to the process of VC has never been examined. In this work the essential contribution of Piezo1 channels to arterial medial calcification is demonstrated. The presence of Piezo1 was proved on human aortic smooth muscle samples using immunohistochemistry. Quantitative PCR and Western blot analysis confirmed the expression of the channel on the human aortic smooth muscle cell line (HAoSMC). Functional measurements were done on HAoSMC under control and calcifying condition. Calcification was induced by supplementing the growth medium with inorganic phosphate (1.5 mmol/L, pH 7.4) and calcium (CaCl2, 0.6 mmol/L) for 7 days. Measurement of [Ca2+]i using fluorescent Fura-2 dye upon stimulation of Piezo1 channels (either by hypoosmolarity, or Yoda1) demonstrated significantly higher calcium transients in calcified as compared to control HAoSMCs. The expression of mechanosensitive Piezo1 channel is augmented in calcified arterial SMCs leading to a higher calcium influx upon stimulation. Activation of the channel by Yoda1 (10 μmol/L) enhanced calcification of HAoSMCs, while Dooku1, which antagonizes the effect of Yoda1, reduced this amplification. Application of Dooku1 alone inhibited the calcification. Knockdown of Piezo1 by siRNA suppressed the calcification evoked by Yoda1 under calcifying conditions. Our results demonstrate the pivotal role of Piezo1 channels in arterial medial calcification.
Novel candidate loci for morpho-agronomic and seed quality traits detected by targeted genotyping-by-sequencing in common bean
Authors: Ugwuanyi Samson , Udengwu Obi Sergius , Snowdon Rod J. , Obermeier Christian 
Published: November 2022

Phaseolus vulgaris L., known as common bean, is one of the most important grain legumes cultivated around the world for its immature pods and dry seeds, which are rich in protein and micronutrients. Common bean offers a cheap food and protein sources to ameliorate food shortage and malnutrition around the world. However, the genetic basis of most important traits in common bean remains unknown. This study aimed at identifying QTL and candidate gene models underlying twenty-six agronomically important traits in common bean. For this, we assembled and phenotyped a diversity panel of 200 P. vulgaris genotypes in the greenhouse, comprising determinate bushy, determinate climbing and indeterminate climbing beans. The panel included dry beans and snap beans from different breeding programmes, elite lines and landraces from around the world with a major focus on accessions of African, European and South American origin. The panel was genotyped using a cost-conscious targeted genotyping-by-sequencing (GBS) platform to take advantage of highly polymorphic SNPs detected in previous studies and in diverse germplasm. The detected single nucleotide polymorphisms (SNPs) were applied in marker-trait analysis and revealed sixty-two quantitative trait loci (QTL) significantly associated with sixteen traits. Gene model identification via a similarity-based approach implicated major candidate gene models underlying the QTL associated with ten traits including, flowering, yield, seed quality, pod and seed characteristics. Our study revealed six QTL for pod shattering including three new QTL potentially useful for breeding. However, the panel was evaluated in a single greenhouse environment and the findings should be corroborated by evaluations across different field environments. Some of the detected QTL and a number of candidate gene models only elucidate the understanding of the genetic nature of these traits and provide the basis for further studies. Finally, the study showed the possibility of using a limited number of SNPs in performing marker-trait association in common bean by applying a highly scalable targeted GBS approach. This targeted GBS approach is a cost-efficient strategy for assessment of the genetic basis of complex traits and can enable geneticists and breeders to identify novel loci and targets for marker-assisted breeding more efficiently.
Effects of agronomic traits and climatic factors on yield and yield stability of summer maize (Zea mays L) in the Huang-Huai-Hai Plain in China
Authors: Ren Hao , Liu Mingyu , Zhang Jibo , Liu Peng , Liu Cunhui 
Published: November 2022

Zhengdan 958 (ZD958) is the summer maize variety with the widest planting area in Huang-Huai-Hai plain in the past 20 years. Understanding the agronomic characteristics of maize and its adaptability to climatic factors is of great significance for breeding maize varieties with high yield and stability. In this study, the experimental data of 33 experimental stations from 2005 to 2015 were analyzed to clarify the effects of different agronomic traits on yield and the correlation between agronomic traits, and to understand the effects of different climatic factors on summer maize yield and agronomic traits. The results showed that the average yield of ZD958 was 9.20 t ha-1, and the yield variation coefficient was 13.41%. There was a certainly negative correlation between high yield and high stability. Plant heights, ear heights, double ear rate, ear length, ear rows, line grain number, grain number per ear, ear diameter, cob diameter, and 1000 grains weight were significantly positive correlation with maize yield. Solar radiation before and after silking were significantly positive correlation with maize yield. Path analysis showed that changes in agronomic traits accounted for 54% of the yield variation, and changes in climate factors accounted for 26% of the yield variation. Our study showed that higher plant height, ear height, grain number per ear and 1000-grain weight, lower lodging rate, pour the discount rate and shorter bald tip long were the main reasons for high yield. Among the climatic factors, solar radiation and the lowest temperature have significant effects on the yield.
Health-related quality of life of young academics: A cross-sectional survey of universities in Wuhan, China
Authors: Yao Qiang , Yang Fei , Li Hanxuan , Tang Kaiyue , Liu Chaojie 
Published: November 2022

ObjectiveThis study aimed to assess the health-related quality of life (HRQoL) of young academics in Wuhan, China, and its determinants.MethodsA multistage stratified cluster sampling strategy was employed to recruit study participants (young academics &lt;40 years old) from 12 universities in Wuhan. A total of 301 respondents returned a self-complete questionnaire that contained the EQ-5D-5L. Multivariate linear and Tobit regression models were established to determine the sociodemographic and job predictors of the visual analogue scale (VAS) score and the EQ-5D utility index, respectively.ResultsThe study participants reported a mean VAS value of 79.42 (SD = 10.51) and a mean EQ-5D utility index of 0.915 (SD = 0.090). Anxiety/depression was the most frequently reported problem (65.12%), followed by pain/discomfort (43.52%). Transitioning towards a full professorship in national key universities (p &lt; 0.001), lower income (p &lt; 0.05) and too much pressure for academic promotion (p &lt; 0.001) were significant predictors of lower HRQoL; whereas, maintaining routines in physical activities (p &lt; 0.001), sleep (p &lt; 0.001) and meals (p &lt; 0.001), a good relationship with colleagues and family members (p &lt; 0.001), and social activities (p &lt; 0.01) were significant predictors of higher HRQoL.ConclusionLow HRQoL of young academics in China is evident, as indicated by the 7.08 and 0.049 gap in VAS and utility index, respectively, compared to the general population at the same age. Work and career pressures are associated with the low HRQoL of young academics. The findings of this study highlight the importance of work-life balance in promoting HRQoL of young academics in universities in China.
Gender differences in major depressive disorders: A resting state fMRI study
Authors: Tu Zhaoyuan , Wu Feng , Jiang Xiaowei , Kong Lingtao , Tang Yanqing 
Published: November 2022

BackgroundMajor depressive disorder (MDD) has a high disability rate and brings a large disease burden to patients and the country. Significant sex differences exist in both the epidemiological and clinical features in MDD. The effect of sex on brain function in MDD is not clear now. Regional homogeneity (ReHo) and ALFF are widely used research method in the study of brain function. This research aimed to use ReHo and ALFF to explore gender differences in brain function images in MDD.MethodsEighty first-episode drug-naive patients (47 women and 30 men) with MDD and 85 age, education matched healthy volunteers (47 women and 31 men) were recruited in our study and participated in resting-state functional magnetic resonance imaging scans. ReHo and ALFF were used to assess brain activity, two-way ANOVA and post hoc analysis was conducted to explore the sex difference in MDD. Correlation analysis was used to explore the relationship between abnormal brain functioning and clinical symptoms.ResultsWe observed sex-specific patterns and diagnostic differences in MDD Patients, further post hoc comparisons indicated that women with MDD showed decreased ALFF value in the right superior occipital gyrus and decreased ReHo value in the left calcarine and left dorsolateral superior frontal gyrus compared with HC females and men with MDD. Men with MDD showed decreased ReHo value in the right median cingulate gyrus compared with HC males and increased ReHo value in the left dorsolateral superior frontal gyrus compared with HC males, we also found that HC males showed higher ReHo value in the right median cingulate gyrus than HC females.ConclusionsMen and women do have sex differences in brain function, the occipital lobe, calcarine, DLPFC, and DCG were the main different brain regions found between male and female in MDD, which may be the biomarker brain regions that can help diagnose and treat MDD in men and women.