bluuebunny/crossref_metadata_2025_split huggingface dataset:
The RNA-binding protein RGGA is a sugar-responsive cofactor of the 5'-3' exonuclease XRN4 that post-transcriptionally meditates plant growth
Authors: Liu Hongmei , Yu Ru , Zhang Hong , Gao Xinlei , Zhu Changxiang , Wu Changai , Geng Liwei , Du Jinwen , Ma Haoran , Song Yunzhi , Zhou Shumei 
Published: January 2021

Abstract
Sugar-regulated gene expression is a ubiquitous mechanism for carbohydrate allocation and utilization by keeping a balance among source and sink organs in plants. Previous studies have shown that excess sugar represses the expression of the genes implicated in photosynthesis and sugar metabolism. However, the mechanism is still largely unknown. Here, we found that the mutant of Arabidopsis RGGA, RGG repeats RNA-binding protein A coding gene, grew faster than wild type (Col-0) in MS medium. In rgga, mRNA half-live of the genes related to sucrose transport and metabolism, chlorophyll synthesis, root development as well as certain transcription factors was obviously longer than those of Col-0. Further study revealed that AtRGGA could interact with 5'-3' exonuclease AtXRN4, and guide it to the target mRNAs for their degradation. When AtRGGA is absent or its interaction domain is deleted, AtXRN4 self can't recognize the target mRNAs, which leads to a dramatically increase in transcript levels of the above gene subsets, and thus promotes the growth of Arabidopsis with exogenous sucrose supply. And only 5-day sucrose supply could trigger the vigorous growth of rgga. These findings suggest that the regulation of mRNA stability mediated by RGGA plays a critical role in sugar suppression, and implicates a possibility to unlock the growth potential by modulating sugar utilization at post-transcriptional level in plants.
Multiplexed Imaging Analysis of the Tumor-Immune Microenvironment Reveals Predictors of Outcome in Triple-Negative Breast Cancer
Authors: Patwa Aalok , Yamashita Rikiya , Long Jin , Keren Leeat , Angelo Michael R. , Rubin Daniel 
Published: January 2021

Abstract
Triple-negative breast cancer (TNBC), the poorest-prognosis breast cancer subtype, lacks clinically approved biomarkers for patient risk stratification, treatment management, and immunotherapies. Prior literature has shown that interrogation of the tumor-immune microenvironment (TIME) may be a promising approach for the discovery of novel biomarkers that can fill these gaps. Recent developments in high-dimensional tissue imaging technology, such as multiplexed ion beam imaging (MIBI), provide spatial context to protein expression in the TIME, opening doors for in-depth characterization of cellular processes. We developed a computational pipeline for the robust examination of the TIME using MIBI. We discover that profiling the functional proteins involved in cell-to-cell interactions in the TIME predicts recurrence and overall survival in TNBC. The interactions between CD45RO and Beta Catenin and CD45RO and HLA-DR were the most relevant for patient stratification. We demonstrated the clinical relevance of the immunoregulatory proteins PD-1, PD-L1, IDO, and Lag3 by tying their interactions to recurrence and survival. Multivariate analysis revealed that our methods provide additional prognostic information compared to clinical variables. Our novel computational pipeline produces interpretable results, and is generalizable to other cancer types.
The Effect of Kuchala (Arum Korolkowii Regel, 1873) Tuber Tincture to Increase of the Serum Testosterone in the Adult Male Guinea Pigs (Cavia Porcellus Linnaeus, 1758)
Authors: Aldayarov Nurbek , Jumabekova Jarkinay , Kurmanbekova Gulbubu , Omurzakova Nurjamal , Kydyralieva Bermet , Sharshenalieva Gulnara , Borkoev Bakyt , Salieva Kalipa , Tulobaev Askarbek , Salykov Ruslan , Chekirov Kadyrbay 
Published: January 2021

Abstract
Background: Kuchala (Arum korolkowii Regel) is a medicinal plant often used in folk medicine in the Kyrgyz Republic. As a medicinal raw material, the tuber’s tincture is used in small doses to increase human sexual potency. However, there is no scientific evidence in support of the medicinal effects of kuchala. For these reasons, we decided to study the pharmacological effect of kuchala tuber tincture on the sexual potency of adult male guinea pigs. We analyzed the effect of kuchala at the age of ±48-months, in 12 male guinea pigs. A preparation of 10% tuber tincture of kuchala in 70% ethanol was administered perorally to the male guinea pigs in the form of a once-daily dose of 150 µl for 30 days. The study data were obtained by ethological, hematological and serum biochemistry, gross anatomical, histological and statistical methods.Results: The hematological and serum biochemistry parameters were significantly different between the control and the experimental group. The neutrophils’ percentage in the experimental group was significantly lower (dР < 0.001) than in the control group. On the other hand, the lymphocyte counts were significantly higher in the experimental group (dР < 0.001). The RBC counts, Hgb, Hct, MCH and MCHC were significantly higher in the experimental group (dР < 0.001; dР < 0.001; cР < 0.01; dР < 0.001; dР < 0.001 respectively) than in the control group. In contrast, the color indicator and the mean platelet volume were higher (bР < 0.05) and significantly higher (dР < 0.001) respectively in the control group than in the experimental group. The ALT and AST levels were lower in the experimental than in the control group (both dР < 0,001). The testosterone concentration in serum was much higher (dР < 0,001) in the experimental group. Microscopically, some structural damages were found in the liver of the experimental animals indicating a metabolic disorder. However, the testes showed an improvement in spermatogenesis in the experimental compared with the control group.Conclusions: The 10% kuchala tuber tincture in 70% ethanol has a positive effect in terms of improving the sexual potency of adult guinea pigs by increasing the production of testosterone and increasing spermatogenesis.
LDL delivery of microbial small RNAs drives atherosclerosis through macrophage TLR8
Authors: Allen Ryan , Michell Danielle , Cavnar Ashley , Zhu Wanying , Makhijani Neil , Contreras Danielle , Raby Chase , Semler Elizabeth , DeJulius Carlisle , Castleberry Mark , Zhang Youmin , Ramirez Marisol , Zhao Shilin , Duvall Craig , Doran Amanda , Sheng Quanhu , Linton MacRae , Vickers Kasey 
Published: January 2021

Abstract
Macrophages present a spectrum of phenotypes that mediate both the pathogenesis and resolution of atherosclerotic lesions. Inflammatory macrophage phenotypes are pro-atherogenic, but the natural factors that instigate this polarization are largely unknown. Here, we demonstrate that microbial small RNAs (msRNA) are enriched on LDL and drive pro-inflammatory macrophage polarization and cytokine secretion via activation of the ribonucleic acid sensor toll-like receptor 8 (TLR8). Removal of msRNA cargo during LDL re-constitution yields particles that readily promote sterol loading but fail to stimulate inflammatory activation. Competitive antagonism of TLR8 with non-targeting locked nucleic acids (nt-LNA) was found to prevent nLDL-induced macrophage polarization in vitro, and re-organize lesion macrophage phenotypes in vivo, as determined by single-cell RNA sequencing. Critically, this was associated with reduced disease burden in distinct mouse models of atherosclerosis. These results identify LDL-msRNA as instigators of atherosclerosis-associated inflammation and support alternative functions of LDL beyond cholesterol transport.
Estimating genetic variability among diverse lentil collections through novel multivariate techniques
Authors: Iqbal Muhammad Sajjad , Hussain Syed Atiq , Akbar Muhammad , Ilyas Kashif , Ghafoor Abdul , Arshad Noshia , Munir Saba , Ali Muhammad Azhar , Masood Hajra , Zafar Samina , Ahmad Tahira , Shaheen Nazra , Mashooq Rizwana , Sajjad Hifsa , Zahoor Munaza , Bashir Faiza , Shahbaz Khizra , Arshad Hamna , Fatima Noor , Nasir Faiza , Hashmi Aysha Javed , Chaudhary Sofia , Islam Muhammad 
Published: January 2021

Abstract
Lentil is a significant legume crop throughout the world where Pakistan stands at 18th position with 8610 tons from 17457 hectares. It is nutritionally rich in protein, carbohydrates, mineral, fat and fiber that can potentially meet food security resolving malnutrition issues. Lentil 220 collections representing Pakistan 184, Syria 14, USA 22 and 04 of unknown origin were studied for high yield, yield contributing traits and early cooking time. Results revealed high variability, 6122 (Pakistan) was considered as best during both years due to its performance as seed yield (68 ± 1.7), biological yield (264 ± 2.8), pod size (0.61 ± 0.01), seed per pod (2), cooking time (11 minutes) and hard seed (0). Comparatively 6122 (Pakistan) and 6042 (Syria) produced the highest biological yield which could also be an efficient source for fodder. 5698 (Pak) and 6015 (USA) took 161–172 days in 2018 while 24783 (unknown) and 5561 (Pak) were matured early in 2019. Lowest cooking time 10 minutes was observed in 6074 and 5745 of Pakistani origin. Lentil with the lowest cooking time saves energy and resources, develops adequate flavor, texture and improves protein digestibility. Pearson correlation matrix, Principal component analysis, structural equational model, cluster analysis, heritability showed promising results. In conclusion 12 genotypes were selected on high yield potential and recommended for lentils breeding including 5664, 5687, 6084, 6062, 6122, 6058, 6087, 5689, 6042, 6074, Markaz 2009 & Punjab 2009.
A Novel Survival Model Based on Ferroptosis-related Gene Signature for Overall Survival Prediction in Bladder Cancer
Authors: Liang Yingchun , Ye Fangdie , Xu Chenyang , Zou Lujia , Hu Yun , Jiang Haowen 
Published: January 2021

Abstract
Background: The effective treatment and prognosis prediction of bladder cancer(BLCA) remains a medical problem. Ferroptosis is an iron-dependent form of programmed cell death. Ferroptosis are closely related to tumor occurrence and progression, but the prognostic value of ferroptosis-related genes (FRGs) in BLCA remains to be further clarified. In this study, we identified a FRGs signature with potential prognostic value for patients with BLCA. Methods: The corresponding clinical data and the mRNA expression profile of BLCA patients were downloaded from The Cancer Genome Atlas (TCGA). Univariate Cox regression was used to extract FRGs related to survival time, Cox regression model was applied to construct a multigene signature. Both principal component analysis (PCA) and single-sample gene set enrichment analysis (ssGSEA) were performed for functional annotation. Results: Clinical traits were combined with FRGs, so that 15 prognostic-related FRGs were identified by Cox regression. High expression of CISD1, GCLM, CRYAB, SLC7A11, TFRC, ACACA, ZEB1, SQLE, FADS2, ABCC1, G6PD and PGD are related to poor survival rates of BLCA patients. Multivariate Cox regression constructed a prognostic model with 7 FRGs and divided patients into two risk groups. Compared with the low-risk group, the overall survival(OS) of patients in the high-risk group was significantly lower (P <0.001). In multivariate regression analysis, the risk score was shown to be an independent predictor of OS (HR> 1, P <0.01). ROC curve analysis verified the predictive ability of the model. In addition, the two risk groups displayed different immune statuses in the ssGSEA and different distributed patterns in PCA. Conclusion: Our research suggests that a new gene model related to ferroptosis can be applied for the prognosis prediction of BLCA. Targeting FRGs may be a treatment option for BLCA.
The Effects of Working Hours on Health Based on China’s Observations
Authors: Chu Liming 
Published: January 2021

Abstract
Background: At a time of rapid economic development, the quality of the labor force is an issue worthy of attention, and health is an important factor in the quality of the labor force. In recent years, the working hours of the workers have been continuously extended, and excessive labor has gradually become a common phenomenon, directly affect the health level of workers, but also not conducive to social stability and economic development.To understand the relationship between labor market performance and health is of great significance to expand the factors influencing the health level of labor force.Method: From the perspective of working hours, this study uses China Family Panel Studies(CFPS) data and order probit model to explore the impact of working hours on labor health, further analyze the heterogeneity of whether to participate in medical insurance, and explore the difference of education level.Result: First, the depreciation rate of healthy capital increases, and the increment of healthy capital decreases, thus lowering the health level of the labor force. Second, working hours have a more significant impact on the self-rated health of the labor force who does not participate in medical insurance. Thirdly, the work time of junior high school and below has more significant impact on self-rated health, and the work time of labor who is not in the 41-50 age stage has more significant impact on health.Conclusion: This paper focuses on the relationship between working hours on workforce health using the oprobit model. Based on the literature on the impact of workforce health levels, the variables are tightly controlled to address estimation bias caused by omitted variables and to ensure the credibility of the results.
Microarray Profiling in Fibrogenesis Imperfecta Ossium
Authors: Dhiman Vandana , Saini Samarth , Bhadada Sanjay , Bhasin Manoj , Rao Sudhaker 
Published: January 2021

Abstract
Fibrogenesis imperfecta ossium (FIO) is a rare, metabolic bone disease clinically characterized by generalized bone pain and fragility fractures in both the axial and appendicular skeleton. The etiology of the disease is unknown and the pathogenesis is poorly understood. In this disorder, collagen arrangement in the bone is disorganized , and causes abnormalities in the organic bone matrix. Genetic cues causing this defect in collagen arrangement are largely undetermined. Microarray analysis showed remarkable changes in gene expression , when we compared gene expression of FIO with the control. Differential gene expression analysis revealed 50 gene signatures, which can be used to organize novel ways to diagnose and treat FIO patients.
A study of the Relationship between Human Capital Accumulation and Economic Growth: A case of Liberia
Authors: Dukuly Faliku S. , Huang Kun 
Published: January 2021

Abstract
The neutral of this study is to examine the human capital effect on Liberia’s economic growth and empirically estimates the contribution of human capital accumulation within the Liberian economy from 2000 to 2019. We used a time-series data of linear regression (OLS) model where data is taken from the World Bank Development Indicators to test our observed variables using the Eviews7 statistical tool. The final linear regression model displayed Population (POP) growth rate as a positive and significant factor for GNI accumulation, while the model predicates government HEALTH expenditure, LIFE expectancy at birth, and foreign AID to be negative and not significant statistically. The result raises a concern that low expenditure on health could cause limited life expectancy and also hinder the attainment of human capital while placing the overall labor force at risk in the Liberian economy.
Chinese Herbal Preparation SaiLuoTong Alleviates Brain Ischemia Via Nrf2 Antioxidation Pathway Dependent Cerebral Microvascular Protection
Authors: Fan Xiao-Di , Yao Ming-Jiang , Yang Bin , Han Xiao , Wang Guang-Rui , Li Peng , Xu Li 
Published: January 2021

Abstract
Background: Stroke is one of the most devastating diseases worldwide. Chinese herbal preparation SaiLuoTong capsule (SLT) showed outstanding therapeutic effects over stroke and its sequelae. This study is to elucidate the mechanism. Methods: We duplicated cerebral ischemia model in rats by permanent MCAO, and simulated ischemia injury in cultured hCMEC/D3 cells with oxygen and glucose deprivation/reoxia (OGD/R); we treated them with SLT. Brain infarction volumes and micromorphology were examined with TTC and HE stainings, respectively; neurological function injuries were valued with deficits scoring; brain water contents were measured with the wet-dry method; and expressions of claudin-1, occludin, Nrf2 and HO-1 were examined with western blot assay and immunohistochemstry or immunocytofluorescnce stainings; activities of SOD and contents of GSH were measured by colorimetric method; cell viabilities were measured by CCK8 method; cell monolayer permeabilities were assessed by FITC-dextran diffusion method. Results: SLT (33 mg/kg) significantly decreased infarction volumes, relieved neuron degenerations and neuron loss, and ameliorated neurological functions; SLT also significantly inhibited elevations in brain water content and decreases of claudin-1 and occludin expressions; additionally SLT significantly increased the nucleus translocation of Nrf2, elevated expression of HO-1, and raised activity of SOD and content of GSH (p<0.05 or 0.01, compared with the model group, in quantitative data). These testified SLT’s anti-stroke effect, and hint the possible key role of cerebral blood vascular endothelial cells (CBVEC) protection and Nrf2 pathway in SLT’s therapy. In hCMEC/D3 cells, SLT significantly inhibited the drop in cell viabilities; SLT also significantly facilitated the nucleus translocation of Nrf2, and increased the expression of HO-1, the activity of SOD, and the content of GSH (in comparison to the model group, p<0.05 or 0.01). Lastly, the anti-OGD/R effects of SLT in hCMEC/D3 cells, including raising cell viabilities, inhibiting the elevation in cell monolayer permeabilities, and preserving the expressions of claudin-1 and occludin, were all abolished by Nrf2 siRNA interference. These undoubtedly confirmed SLT’s protective effect on CBVEC and the obligatory role of Nrf2 pathway in it. Conclusion: SLT’s therapeutic effect on brain ischemia is related to its protection on CBVEC, which is dependent on the activation of Nrf2 pathway.
Use of Vasopressors Increases the Risk of Mortality in Severe Traumatic Brain Injury: A Nationwide Retrospective Cohort Study in Japan
Authors: Hosomi Sanae , Sobue Tomotaka , Kitamura Tetsuhisa , Hirayama Atsushi , Ogura Hiroshi , Shimazu Takeshi 
Published: January 2021

Abstract
Background: Pharmacological elevation of blood pressure is frequently incorporated in severe traumatic brain injury (TBI) management algorithms. However, there is limited evidence on prevalent clinical practices regarding resuscitation for severe TBI using vasopressors. We conducted a nationwide retrospective cohort study to determine the association between the use of vasopressors and mortality following discharge from hospital in patients with severe TBI, and to determine whether the use of vasopressors affects emergency department mortality or the occurrence of cognitive dysfunction.Methods: Data were collected between January 2004 and December 2018 by the Japanese Trauma Data Bank, which includes data from 272 emergency hospitals in Japan. Adults aged ≥ 16 years with severe TBI, without other major injuries, were examined. A severe TBI was defined based on the Abbreviated Injury Scale code and a Glasgow Coma Scale score of 3–8 on admission. Multivariable and propensity score matching analyses were performed. Statistical significance was assessed using a 95% CI.Results: In total, 10,284 patients were eligible for analysis, with 650 patients (6.32%) included in the vasopressor group and 9,634 patients (93.68%) included in the non-vasopressor group. The proportion of deaths on hospital discharge was higher in the vasopressor group than in the non-vasopressor group (81.69% [531/650] vs. 40.21% [3,874/9,634]). This finding was confirmed by multivariable logistic regression analysis (adjusted odds ratio [OR], 5.71; 95% confidence interval [CI]: 4.56–7.16). Regarding propensity score-matched patients, the proportion of deaths on hospital discharge remained higher in the vasopressor group than in the non-vasopressor group (81.66% [530/649] vs. 50.69% [329/649]) (OR, 4.33; 95% CI: 3.37–5.57). The vasopressor group had a higher emergency department mortality rate than the non-vasopressor group (8.01% [52/649] vs. 2.77% [18/649]) (OR, 3.05; 95% CI: 1.77–5.28). There was no reduction in complications of cognitive disorders in the vasopressor group (5.39% [35/649] vs. 5.55% [36/649]) (OR, 0.97; 95% CI: 0.60–1.57).Conclusions: In this population, the use of vasopressors for severe TBI was associated with higher mortality on hospital discharge. Our results suggest that vasopressors should be avoided in most cases of severe TBI.
Negative Drift of Sedation Depth In Critically Ill Patients Receiving Constant Minimum Alveolar Concentration of Isoflurane, Sevoflurane, or Desflurane: A Randomized Controlled Trial
Authors: Georgevici Adrian Iustin , Kyprianou Theodoros , Herzog-Niescery Jennifer , Procopiuc Livia , Loganathan Sivakkanan , Weber Thomas Peter , Bellgardt Martin 
Published: January 2021

Abstract
Background: Intensive care unit (ICU) physicians have extended the minimum alveolar concentration (MAC) to deliver and monitor long-term volatile sedation in critically ill patients. There is limited evidence of MAC’s reliability in controlling sedation depth in this setting. We hypothesized that sedation depth, measured by the electroencephalography (EEG)-derived Narcotrend-Index (burst-suppression N_Index 0 – awake N_Index 100), might drift downward over time despite constant MAC values.Methods: This prospective single-centre randomized clinical study was conducted at a University Hospital Surgical Intensive Care Unit and included consecutive, postoperative ICU patients fulfilling the inclusion criteria. Patients were randomly assigned to receive uninterrupted inhalational sedation with isoflurane, sevoflurane, or desflurane. The end-expiratory concentration of the anaesthetics and the EEG-derived index were measured continuously in time-stamped pairs. Sedation depth was also monitored using Richmond-Agitation-Sedation-Scale (RASS). The paired t-test and linear models (bootstrapped or multilevel) have been employed to analyze MAC, N_Index and RASS across the three groups. Results: Thirty patients were recruited (female/male: 10/20, age 64±11, Simplified Acute Physiology Score II 30±10). In the first 24 hours, 21.208 pairs of data points (N_Index and MAC) were recorded. The median MAC of 0.58±0.06 remained stable over the sedation time in all three groups. The t-test indicated in the isoflurane and sevoflurane groups a significant drop in RASS and EEG-derived N_Index in the first versus last two sedation hours. We applied a multilevel linear model on the entire longitudinal data, nested per patient, which produced the formula N_Index=43−0.7·hours (R2=0.76), showing a strong negative correlation between sedation’s duration and the N_Index. Bootstrapped linear models applied for each sedation group produced: N_Index of 43–0.9, 45–0.8, and 43–0.4·hours for isoflurane, sevoflurane, and desflurane, respectively. The regression coefficient for desflurane was almost half of those for isoflurane and sevoflurane, indicating a less pronounced time-effect in this group.Conclusions: Maintaining constant MAC does not guarantee stable sedation depth. Thus, the patients necessitate frequent clinical assessments or, when unfeasible, continuous EEG monitoring. The differences across different volatile anaesthetics regarding their time-dependent negative drift requires further exploration.Trial registration: NCT03860129.