bluuebunny/crossref_metadata_2025_split huggingface dataset:
Development of hematopoietic syndrome mice model for localized radiation exposure
Authors: Yashavarddhan M. H. , Sharma Ajay Kumar , Chaudhary Pankaj , Bajaj Sania , Singh Sukhvir , Shukla Sandeep Kumar 
Published: January 2021

AbstractCurrent models to study the hematopoietic syndrome largely rely on the uniform whole-body exposures. However, in the radio-nuclear accidents or terrorist events, exposure can be non-uniform. The data available on the non-uniform exposures is limited. Thus, we have developed a mice model for studying the hematopoietic syndrome in the non-uniform or partial body exposure scenarios using the localized cobalt60 gamma radiation exposure. Femur region of Strain ‘A’ male mice was exposed to doses ranging from 7 to 20 Gy. The 30 day survival assay showed 19 Gy as LD100 and 17 Gy as LD50. We measured an array of cytokines and important stem cell markers such as IFN-γ, IL-3, IL-6, GM-CSF, TNF-α, G-CSF, IL-1α, IL-1β, CD 34 and Sca 1. We found significant changes in IL-6, GM-CSF, TNF-α, G-CSF, and IL-1β levels compared to untreated groups and amplified levels of CD 34 and Sca 1 positive population in the irradiated mice compared to the untreated controls. Overall, we have developed a mouse model of the hematopoietic acute radiation syndrome that might be useful for understanding of the non-uniform body exposure scenarios. This may also be helpful in the screening of drugs intended for individuals suffering from radiation induced hematopoietic syndrome.
Targeting mTOR and DNA repair pathways in residual triple negative breast cancer post neoadjuvant chemotherapy
Authors: Anand Kartik , Patel Tejal , Niravath Polly , Rodriguez Angel , Darcourt Jorge , Belcheva Anna , Boone Toniva , Ensor Joe , Chang Jenny 
Published: January 2021

AbstractTriple-negative breast cancer (TNBC) patients who do not achieve pathologic complete response post neoadjuvant chemotherapy have a poor prognosis. Alteration in PI3K/mTOR plus DNA repair pathways are some of the major mechanisms of chemotherapy resistance. We designed an open-label phase II clinical trial to evaluate if the combination of everolimus (mTOR inhibitor) plus cisplatin (interferes with DNA function) will improve the rate of pathologic response, as assessed by residual cancer burden (RCB). Twenty-four Stage II/III TNBC patients with residual cancer > 1 cm post neoadjuvant anthracycline and taxane-based chemotherapy were enrolled. Patients received everolimus daily orally at 10 mg for 12 weeks and cisplatin IV at 20 mg/m2 weekly for 4 cycles (21-day cycle), until definitive surgery. The primary endpoint was the rate of RCB-0-I at the surgery. The median age of the whole cohort was 50.1 years, with 66.7% non-Hispanic Caucasians. Of the 24 patients enrolled, 22 were included in the efficacy analysis. Twenty-one patients underwent definitive surgery while one patient developed distant metastasis. Five patients had RCB-I at surgery, a response rate of 23% (5/22). Patients with germline PALB2 mutation or somatic PI3KCA mutation had a pathologic response, achieving RCB-I at the surgery. Three patients had metaplastic histology achieving RCB-I at the surgery. Estimated OS at 1 year was 100% in the RCB-I group vs. 76.5% in others, which was not statistically significant due to the small sample size. Certain cohorts including PALB2 germline mutation carrier and somatic PI3KCA mutations warrant further investigation.Trial registration: Clinicaltrials.gov identifier: NCT01931163. https://clinicaltrials.gov/ct2/show/NCT01931163.
FAK regulates IL-33 expression by controlling chromatin accessibility at c-Jun motifs
Authors: Griffith Billie G. C. , Upstill-Goddard Rosanna , Brunton Holly , Grimes Graeme R. , Biankin Andrew V. , Serrels Bryan , Byron Adam , Frame Margaret C. 
Published: January 2021

AbstractFocal adhesion kinase (FAK) localizes to focal adhesions and is overexpressed in many cancers. FAK can also translocate to the nucleus, where it binds to, and regulates, several transcription factors, including MBD2, p53 and IL-33, to control gene expression by unknown mechanisms. We have used ATAC-seq to reveal that FAK controls chromatin accessibility at a subset of regulated genes. Integration of ATAC-seq and RNA-seq data showed that FAK-dependent chromatin accessibility is linked to differential gene expression, including of the FAK-regulated cytokine and transcriptional regulator interleukin-33 (Il33), which controls anti-tumor immunity. Analysis of the accessibility peaks on theIl33gene promoter/enhancer regions revealed sequences for several transcription factors, including ETS and AP-1 motifs, and we show that c-Jun, a component of AP-1, regulatesIl33gene expression by binding to its enhancer in a FAK kinase-dependent manner. This work provides the first demonstration that FAK controls transcription via chromatin accessibility, identifying a novel mechanism by which nuclear FAK regulates biologically important gene expression.
Drivers use active gaze to monitor waypoints during automated driving
Authors: Mole Callum , Pekkanen Jami , Sheppard William E. A. , Markkula Gustav , Wilkie Richard M. 
Published: January 2021

AbstractAutomated vehicles (AVs) will change the role of the driver, from actively controlling the vehicle to primarily monitoring it. Removing the driver from the control loop could fundamentally change the way that drivers sample visual information from the scene, and in particular, alter the gaze patterns generated when under AV control. To better understand how automation affects gaze patterns this experiment used tightly controlled experimental conditions with a series of transitions from ‘Manual’ control to ‘Automated’ vehicle control. Automated trials were produced using either a ‘Replay’ of the driver’s own steering trajectories or standard ‘Stock’ trials that were identical for all participants. Gaze patterns produced during Manual and Automated conditions were recorded and compared. Overall the gaze patterns across conditions were very similar, but detailed analysis shows that drivers looked slightly further ahead (increased gaze time headway) during Automation with only small differences between Stock and Replay trials. A novel mixture modelling method decomposed gaze patterns into two distinct categories and revealed that the gaze time headway increased during Automation. Further analyses revealed that while there was a general shift to look further ahead (and fixate the bend entry earlier) when under automated vehicle control, similar waypoint-tracking gaze patterns were produced during Manual driving and Automation. The consistency of gaze patterns across driving modes suggests that active-gaze models (developed for manual driving) might be useful for monitoring driver engagement during Automated driving, with deviations in gaze behaviour from what would be expected during manual control potentially indicating that a driver is not closely monitoring the automated system.
Mercury accumulation in vegetable Houttuynia cordata Thunb. from two different geological areas in southwest China and implications for human consumption
Authors: Wang Qingfeng , Li Zhonggen , Feng Xinbin , Wang Ao , Li Xinyu , Wang Dan , Fan Leilei 
Published: January 2021

AbstractHouttuynia cordata Thunb. (HCT) is a common vegetable native to southwest China, and grown for consumption. The results suggested that THg contents in all parts and MeHg in underground parts of HCT in Hg mining areas were much higher than those in non-Hg mining areas. The highest THg and MeHg content of HCT were found in the roots, followed by the other tissues in the sequence: roots > leaves > rhizomes > aboveground stems (THg), and roots > rhizomes > aboveground stems > leaves (MeHg). The average THg bioaccumulation factor (BCF) of HCT root in the Hg mining area and in non-Hg mining areas could reach 1.02 ± 0.71 and 0.99 ± 0.71 respectively, indicating that HCT is a Hg accumulator. And the THg and MeHg contents in all tissues of HCT, including the leaves, were significantly correlated with THg and MeHg content in the soil. Additionally, preferred dietary habits of HCT consumption could directly affect the Hg exposure risk. Consuming the aboveground parts (CAP) of HCT potentially poses a high THg exposure risk and consuming the underground parts (CUP) may lead to a relatively high MeHg exposure risk. Only consuming the rhizomes (OCR) of the underground parts could significantly reduce the exposure risk of THg and to some extent of MeHg. In summary, HCT should not be cultivated near the Hg contaminated sites, such as Hg tailings, as it is associated with a greater risk of Hg exposure and high root Hg levels, and the roots should be removed before consumption to reduce the Hg risk.
miR299a-5p promotes renal fibrosis by suppressing the antifibrotic actions of follistatin
Authors: Mehta Neel , Li Renzhong , Zhang Dan , Soomro Asfia , He Juehua , Zhang Ivan , MacDonald Melissa , Gao Bo , Krepinsky Joan C. 
Published: January 2021

AbstractCaveolin-1 (cav-1), an integral protein of the membrane microdomains caveolae, is required for synthesis of matrix proteins by glomerular mesangial cells (MC). Previously, we demonstrated that the antifibrotic protein follistatin (FST) is transcriptionally upregulated in cav-1 knockout MC and that its administration is protective against renal fibrosis. Here, we screened cav-1 wild-type and knockout MC for FST-targeting microRNAs in order to identity novel antifibrotic therapeutic targets. We identified that miR299a-5p was significantly suppressed in cav-1 knockout MC, and this was associated with stabilization of the FST 3′UTR. Overexpression and inhibition studies confirmed the role of miR299a-5p in regulating FST expression. Furthermore, the profibrotic cytokine TGFβ1 was found to stimulate the expression of miR299a-5p and, in turn, downregulate FST. Through inhibition of FST, miR299a-5p overexpression augmented, while miR299a-5p inhibition diminished TGFβ1 profibrotic responses, whereas miR299a-5p overexpression re-enabled cav-1 knockout MC to respond to TGFβ1. In vivo, miR299a-5p was upregulated in the kidneys of mice with chronic kidney disease (CKD). miR299a-5p inhibition protected these mice against renal fibrosis and CKD severity. Our data demonstrate that miR299a-5p is an important post-transcriptional regulator of FST, with its upregulation an important pathogenic contributor to renal fibrosis. Thus, miR299a-5p inhibition offers a potential novel therapeutic approach for CKD.
Stimulus-evoked phase-locked activity along the human auditory pathway strongly varies across individuals
Authors: Gransier Robin , Hofmann Michael , van Wieringen Astrid , Wouters Jan 
Published: January 2021

AbstractPhase-locking to the temporal envelope of speech is associated with envelope processing and speech perception. The phase-locked activity of the auditory pathway, across modulation frequencies, is generally assessed at group level and shows a decrease in response magnitude with increasing modulation frequency. With the exception of increased activity around 40 and 80 to 100 Hz. Furthermore, little is known about the phase-locked response patterns to modulation frequencies ≤ 20 Hz, which are modulations predominately present in the speech envelope. In the present study we assess the temporal modulation transfer function (TMTFASSR) of the phase-locked activity of the auditory pathway, from 0.5 to 100 Hz at a high-resolution and by means of auditory steady-state responses. Although the group-averaged TMTFASSR corresponds well with those reported in the literature, the individual TMTFASSR shows a remarkable intersubject variability. This intersubject variability is especially present for ASSRs that originate from the cortex and are evoked with modulation frequencies ≤ 20 Hz. Moreover, we found that these cortical phase-locked activity patterns are robust over time. These results show the importance of the individual TMTFASSR when assessing phase-locked activity to envelope fluctuations, which can potentially be used as a marker for auditory processing.
A novel immune prognostic index for stratification of high-risk patients with early breast cancer
Authors: Lee Hannah , Kwon Mi Jeong , Koo Beom-Mo , Park Hee Geon , Han Jinil , Shin Young Kee 
Published: January 2021

AbstractThe prognostic value of current multigene assays for breast cancer is limited to hormone receptor-positive, human epidermal growth factor receptor 2-negative early breast cancer. Despite the prognostic significance of immune response-related genes in breast cancer, immune gene signatures have not been incorporated into most multigene assays. Here, using public gene expression microarray datasets, we classified breast cancer patients into three risk groups according to clinical risk and proliferation risk. We then developed the immune prognostic index based on expression of five immune response-related genes (TRAT1, IL2RB, CTLA4, IGHM and IL21R) and lymph node status to predict the risk of recurrence in the clinical and proliferation high-risk (CPH) group. The 10-year probability of disease-free survival (DFS) or distant metastasis-free survival (DMFS) of patients classified as high risk according to the immune prognostic index was significantly lower than those of patients classified as intermediate or low risk. Multivariate analysis revealed that the index is an independent prognostic factor for DFS or DMFS. Moreover, the C-index revealed that it is superior to clinicopathological variables for predicting prognosis. Its prognostic significance was also validated in independent datasets. The immune prognostic index identified low-risk patients among patients classified as CPH, regardless of the molecular subtype of breast cancer, and may overcome the limitations of current multigene assays.
Effect of ball collision direction on a wet mechanochemical reaction
Authors: Kozawa Takahiro , Fukuyama Kayo , Kushimoto Kizuku , Ishihara Shingo , Kano Junya , Kondo Akira , Naito Makio 
Published: January 2021

AbstractMechanochemical reactions can be induced in a solution by the collision of balls to produce high-temperature and high-pressure zones, with the reactions occurring through a dissolution–precipitation mechanism due to a change in solubility. However, only a fraction of the impact energy contributes to the mechanochemical reactions, while the rest is mainly consumed by the wear of balls and the heat generation. To clarify whether the normal or tangential component of collisions makes a larger contribution on the reaction, herein we studied the effect of collision direction on a wet mechanochemical reaction through combined analysis of the experimental reaction rates and simulated ball motion. Collisions of balls in the normal direction were found to contribute strongly to the wet mechanochemical reaction. These results could be used to improve the synthesis efficiency, predict the reaction, and lower the wear in the wet mechanochemical reactions.
Urban life promotes delayed dispersal and family living in a non-social bird species
Authors: Luna Álvaro , Lois Nicolás A. , Rodríguez-Martinez Sol , Palma Antonio , Sanz-Aguilar Ana , Tella José L. , Carrete Martina 
Published: January 2021

AbstractIn some vertebrate species, family units are typically formed when sexually mature individuals delay dispersal and independent breeding to remain as subordinates in a breeding group. This behaviour has been intensively studied in gregarious species but has also been described in non-social species where ecological and evolutionary drivers are less known. Here, we explore factors that favour delayed dispersal and family living and potential benefits associated with this strategy in a non-social, monogamous species (the burrowing owl,Athene cunicularia) occupying urban and rural habitats. Our results show that family units arise when first-year individuals, mainly males, delay their dispersal to stay in their natal nests with their parents. This delayed dispersal, while still uncommon, was more prevalent in urban (7%) than in rural (3%) habitats, and in areas with high conspecific density and productivity. Birds delaying dispersal contributed to the genetic pool of the offspring in 25% of the families analysed, but did not increase the productivity of the nests where they remained. However, their presence was related to an improvement in the body condition of chicks, which was ultimately linked to a slightly positive effect in offspring future survival probabilities. Finally, delayed dispersers were recruited as breeders in high-quality urban territories and closer to their natal nests than individuals dispersing during their first year of life. Thus, our results suggest that delaying dispersal may be mainly related to opportunities to inheriting a good quality territory, especially for males. Our study contributes to understanding the role played by habitat quality in promoting delayed dispersal and family living, not only in social but also non-social species, highlighting its impact in the ecology and evolution of animal populations.
Assessing ZNF154 methylation in patient plasma as a multicancer marker in liquid biopsies from colon, liver, ovarian and pancreatic cancer patients
Authors: Miller Brendan F. , Petrykowska Hanna M. , Elnitski Laura 
Published: January 2021

AbstractOne epigenetic hallmark of many cancer types is differential DNA methylation occurring at multiple loci compared to normal tissue. Detection and assessment of the methylation state at a specific locus could be an effective cancer diagnostic. We assessed the effectiveness of hypermethylation at the CpG island of ZNF154, a previously reported multi-cancer specific signature for use in a blood-based cancer detection assay. To predict its effectiveness, we compared methylation levels of 3698 primary tumors encompassing 11 solid cancers, 724 controls, 2711 peripheral blood cell samples, and 350 noncancer disease tissues from publicly available methylation array datasets. We performed a single-molecule high-resolution DNA melt analysis on 71 plasma samples from cancer patients and 20 noncancer individuals to assess ZNF154 methylation as a candidate diagnostic metric in liquid biopsy and compared results to KRAS mutation frequency in the case of pancreatic carcinoma. We documented ZNF154 hypermethylation in early stage tumors, which did not increase in most noncancer disease or with respect to age or sex in peripheral blood cells, suggesting it is a promising target in liquid biopsy. ZNF154 cfDNA methylation discriminated cases from healthy donor plasma samples in minimal plasma volumes and outperformed KRAS mutation frequency in pancreatic cancer.
A novel simple risk model to predict the prognosis of patients with paraquat poisoning
Authors: Gao Yanxia , Liu Liwen , Li Tiegang , Yuan Ding , Wang Yibo , Xu Zhigao , Hou Linlin , Zhang Yan , Duan Guoyu , Sun Changhua , Che Lu , Li Sujuan , Sun Pei , Li Yi , Ren Zhigang 
Published: January 2021

AbstractTo identify risk factors and develop a simple model to predict early prognosis of acute paraquat (PQ) poisoning patients, we performed a retrospective cohort study of acute PQ poisoning patients (n = 1199). Patients (n = 913) with PQ poisoning from 2011 to 2018 were randomly divided into training (n = 609) and test (n = 304) samples. Another two independent cohorts were used as validation samples for a different time (n = 207) and site (n = 79). Risk factors were identified using a logistic model with Markov Chain Monte Carlo (MCMC) simulation and further evaluated using a latent class analysis. The prediction score was developed based on the training sample and was evaluated using the testing and validation samples. Eight factors, including age, ingestion volume, creatine kinase-MB [CK-MB], platelet [PLT], white blood cell [WBC], neutrophil counts [N], gamma-glutamyl transferase [GGT], and serum creatinine [Cr] were identified as independent risk indicators of in-hospital death events. The risk model had C statistics of 0.895 (95% CI 0.855–0.928), 0.891 (95% CI 0.848–0.932), and 0.829 (95% CI 0.455–1.000), and predictive ranges of 4.6–98.2%, 2.3–94.9%, and 0–12.5% for the test, validation_time, and validation_site samples, respectively. In the training sample, the risk model classified 18.4%, 59.9%, and 21.7% of patients into the high-, average-, and low-risk groups, with corresponding probabilities of 0.985, 0.365, and 0.03 for in-hospital death events. We developed and evaluated a simple risk model to predict the prognosis of patients with acute PQ poisoning. This risk scoring system could be helpful for identifying high-risk patients and reducing mortality due to PQ poisoning.
Soil gross nitrogen transformations in forestland and cropland of Regosols
Authors: Ren Xiao , Zhang Jinbo , Bah Hamidou , Müller Christoph , Cai Zucong , Zhu Bo 
Published: January 2021

AbstractSoil gross nitrogen (N) transformations could be influenced by land use change, however, the differences in inherent N transformations between different land use soils are still not well understood under subtropical conditions. In this study, an 15N tracing experiment was applied to determine the influence of land uses on gross N transformations in Regosols, widely distributed soils in Southwest China. Soil samples were taken from the dominant land use types of forestland and cropland. In the cropland soils, the gross autotrophic nitrification rates (mean 14.54 ± 1.66 mg N kg−1 day−1) were significantly higher, while the gross NH4+ immobilization rates (mean 0.34 ± 0.10 mg N kg−1 day−1) were significantly lower than those in the forestland soils (mean 1.99 ± 0.56 and 6.67 ± 0.74 mg N kg−1 day−1, respectively). The gross NO3− immobilization and dissimilatory NO3− reduction to NH4+ (DNRA) rates were not significantly different between the forestland and cropland soils. In comparison to the forestland soils (mean 0.51 ± 0.24), the cropland soils had significantly lower NO3− retention capacities (mean 0.01 ± 0.01), indicating that the potential N losses in the cropland soils were higher. The correlation analysis demonstrated that soil gross autotrophic nitrification rate was negatively and gross NH4+ immobilization rate was positively related to the SOC content and C/N ratio. Therefore, effective measures should be taken to increase soil SOC content and C/N ratio to enhance soil N immobilization ability and NO3− retention capacity and thus reduce NO3− losses from the Regosols.
Distribution, toxicity load, and risk assessment of dissolved metal in surface and overlying water at the Xiangjiang River in southern China
Authors: Huang Zhifeng , Zheng Saisai , Liu Yan , Zhao Xingru , Qiao Xiaocui , Liu Chengyou , Zheng Binghui , Yin Daqiang 
Published: January 2021

AbstractMetal pollution in drinking water source has been under scrutiny as it seriously affects human health. This work examined 12 dissolved metals in the surface and overlying water of the Xiangjiang River, an important drinking water source in southern China, and characterized their distribution, identified their possible sources, assessed their toxicity load, and determined their potential ecological and health risk. No significant difference was found in the metal concentration between surface and overlying water. The average metal concentration fell in the order of Mg > Mn > Ba > Fe > Zn > As > Sb > Ni > Cd > V > Cr > Co, and all was lower than the safety threshold in the drinking water guideline of China. Anthropogenic activities were found to be the main source of metals from correlation analysis, principal component analysis (PCA), and cluster analysis (CA). According to the total heavy metal toxicity load (HMTL), 98.20%, 71.54%, 68.88%, and 7.97% of As, Cd, Sb, and Mn should be removed from the surface water to ensure safety. Most water samples from the surveyed area were found to have high ecological risk as was measured by the ecological risk index (RI). Health risk assessment showed that children are more susceptible than adults to the non-carcinogenic risk of dissolved metals, and the potential carcinogenic risk (CR) of As and Cd should be addressed. The results provide guidance for controlling the metal pollution of the Xiangjiang River and improving its quality as a drinking water source.