bluuebunny/crossref_metadata_2025_split huggingface dataset:
Doxorubicin Impacts the Chromatin Binding of Hmgb1, Histone H1 and Retinoic Acid Receptor
Authors: Bosire Rosevalentine , Fadel Lina , Mocsár Gábor , Nánási Péter , Sen Pialy , Sharma Anshu Kumar , Naseem Muhammad Umair , Kovács Attila , Kugel Jennifer , Kroemer Guido , Vámosi György , Szabó Gábor 
Published: January 2022

Abstract
Doxorubicin (Dox), a widely used anticancer DNA-binding drug, affects chromatin in multiple ways, and these effects contribute to both its efficacy and dose-limiting side-effects, especially cardiotoxicity. Here we studied the Dox effects on the chromatin binding of the architectural proteins high mobility group B1 (HMGB1) and the linker histone H1, and the transcription factor retinoic acid receptor (RARα) by fluorescence recovery after photobleaching (FRAP) and fluorescence correlation spectroscopy (FCS), in live cells. At lower drug concentrations, Dox increased the binding of HMGB1 to DNA while decreasing the binding of the linker histone H1. At higher doses that correspond to the peak plasma concentrations reached in chemotherapy, Dox reduced the binding of HMGB1 as well. This biphasic effect is interpreted in terms of a hierarchy of competition between the ligands involved and Dox-induced local conformational changes of nucleosome-free DNA. When combined, FRAP and FCS mobility data suggest that Dox decreases the overall binding of RARα to DNA, an effect that was only partially overcome by agonist binding. The intertwined interactions described likely contribute to the effects as well as side-effects of Dox.
Locomotive Syndrome Associated With Daily Moderate to Vigorous Physical Activity in Community‐dwelling Older Adults: A Cross-sectional Analysis
Authors: Ishihara Yoshihiko , Ozaki Hayao , Nakagata Takashi , Yoshihara Toshinori , Natsume Toshiharu , Kitada Tomoharu , Ishibashi Masayoshi , Deng Pengyu , Yamada Yasuyuki , Kobayashi Hiroyuki , Machida Shuichi , Naito Hisashi 
Published: January 2022

Abstract
Background: Locomotive syndrome (LS) is associated with weakness and loss of function in the musculoskeletal organs. To evaluate the association between LS and daily physical activities (PA) in community-dwelling older adults using a three-axis accelerometer. Methods: This cross-sectional study included healthy 80 older adults (40 men and 40 women; age: 60-79 years). Three functional tests, the two-step test, the stand-up test, and the 25-question geriatric locomotive function scale (GLFS) were used to assess the risk of LS. Maximal isometric muscle strengths of the knee extensors were examined, and the weight bearing index (knee extension strength/body weight) was calculated. Habitual daily PA was evaluated using a three-axis wrist accelerometer. Results: Of the 80 participants, 41 (51.3%) fulfilled the diagnostic criteria for LS (including a two-step test score < 1.3, difficulty with one-leg standing from 40 cm in the stand-up test, and a 25-question GLFS score ≥ 7) We found that step count and time spent performing moderate to vigorous PA (MVPA) were significantly higher in women participants without LS compared to those with LS (p = 0.01); no significant difference was found in men. Logistic regression analyses indicated a longer time spent performing MVPA (> 47.26 min/day) was associated with a lower risk of LS compared to only performing for 21.11 min/day. Conclusions: Our data showed that daily MVPA using a three-axis accelerometer was associated with LS in community-dwelling older adult women, but not in men.
Retinal Development and The Expression Profiles of Opsins Genes During Larvae Development in Takifugu Rubripes
Authors: Zhang Qi , Wu Yumeng , Li Weiyuan , Wang Jia , Zhou Huiting , Zhang Lei , Liu Qi , Ying Liu , Yan Hongwei 
Published: January 2022

Abstract
Vision is the dominant sensory modality in fish and critical for the survival of fish larvae to detect predators or capture prey. The visual capacity of fish larvae is determined by the structure of the retina and the opsins expressed in the retinal and non-retinal photoreceptors. In this study, the retinal structure and opsin expression patterns during the early development stage of Takifugu rubripes larvae were investigated. At around two days after hatching days (dah), the yolk sac of T. rubripes disappeared, the mouth was clearly visible and the larvae started swimming and feeding on rotifers. Histological examination showed that at 1 dah, six layers were observed in the retina of T. rubripes larva, including the pigment epithelial layer (RPE), photoreceptor layer (PRos/is), outer nuclear layer (ONL), inner nuclear layer (INL), inner plexiform layer (IPL) and ganglion cell layer (GCL). At 2 dah, all eight layers were visible in the retina in T. rubripes larva, including RPE, PRos/is, ONL, outer plexiform layer (OPL), INL, IPL, GCL and optic fiber layer (OFL). By measuring the thickness of each layer, opposing developmental trends were found in the thickness of ONL, OPL, INL and IPL, GCL and OFL. The nuclear density of ONL, INL and GCL and ratio of ONL/INL, ONL/GCL and INL/GCL were also measured and the ratio of ONL/GCL ranged from 1.9 at 2 dah to 3.4 at 8 dah and no significant difference was observed between the different developmental stages (p > 0.05). No significant difference was observed for the INL/GCL ratio between the different developmental stages, which ranged from 1.2 at 2 dah to 2.0 at 18 dah (p > 0.05). The results of quantitative real-time PCR showed that the expression of rhodopsin, LWS, SWS2, green opsin, rod opsin, opsin3 and opsin5 could be detected from 1 dah. These results suggested that the maturation of eye of T. rubripes occurred during the period of transition from endogenous to mixed feeding, explaining the need for vision-based survival skills during the early life stages after hatching and for the overall ecology and fitness of T. rubripes.
Astragalin Ameliorates Cognitive Dysfunction Through Inhibiting PI3K/Akt-MTOR-Mediated Autophagic Flow in Hippocampal Neurons of APP/PS1 Mice
Authors: Yang Cuizhu , Zhang Runheng , Wang Shuhan , Tian Yinghong , Yang Yaqi , Liu Jing , MA YUXIN 
Published: January 2022

Abstract
Astragalin (AST), a natural small molecule flavonoid, can exert anti-oxidant, anti-inflammatory and anti-cancer impacts by regulating autophagy. However, the potential mechanism of the neuroprotective effect of AST on neurological disorders such as Alzheimer’s disease (AD) is still not clear. In the present study, we firstly screened AST for the treatment of AD from the ingredients of Chinese medicines such as Acori tataninowii Rhizoma, Eucommiae Cortex, Paeoniae Radix Alba through the traditional Chinese medicine systems pharmacology database and analysis platform (TCMSP) database. And then we found that AST could improve the cognitive abilities of APP/PS1 mice by Step-down passive avoidance (SDA) and Morris Water Maze (MWM) Test. Further, we identified that AST diminished Aβ plaques deposition in the brains of APP/PS1 mice and Aβ as well as Aβ42 levels in the serum of APP/PS1 mice. Next, microtubule-associated protein 1 light chain 3B (LC3B), p62, Beclin-1, ATG5, ATG12, LAMP-1 were observed to be co-expressed with NeuN in the hippocampus of APP/PS1 mice by immunofluorescent multiplex staining, while AST was able to activate autophagy and maintain autophagic flow in hippocampal neurons of APP/PS1 mice by western blot (WB) analysis. Finally, AST reduced the expressions of p-PI3K, p-Akt, p-mTOR by WB analysis. Taken together, we confirmed that AST may play key neuroprotective effects on APP/PS1 mice by inhibiting the PI3K/Akt-mTOR signaling pathway to activate autophagy and keep autophagic flow smooth.
Treatment Outcomes and Relative Dose Intensity of Chemotherapy in Slovene Patients With Advanced Hodgkin Lymphoma
Authors: Rozman Samo , Gorenjec Nina Ružić , Novaković Barbara Jezeršek 
Published: January 2022

Abstract
This retrospective study was undertaken to investigate the association of relative dose intensity (RDI) with the outcome of Hodgkin lymphoma (HL) patients with advanced stage disease receiving ABVD (doxorubicin, bleomycin, vinblastine, dacarbazine) and escalated BEACOPP regimen (bleomycin, etoposide, doxorubicin, cyclophosphamide, vincristine, procarbazine, prednisone). A total of 114 HL patients treated between 2004 and 2013 were enrolled for evaluation. RDI calculations were based on a Hryniuk's model. The association of variables with overall survival (OS) and progression-free survival (PFS) was analysed using univariate and multivariate Cox proportional hazards models. The median age of patients was 39 years, majority of patients were males and had stage IV disease. Fifty-four patients received ABVD and 60 received BEACOPP chemotherapy with 24 and 4 deaths, respectively. Patients in BEACOPP group were significantly younger with lower Charlson comorbidity index (CCI) in comparison with ABVD group, making the comparison of groups impossible. In ABVD group, RDI was not significantly associated with OS (p=0.590) or PFS (p=0.354) in a multivariate model where age was controlled. The low number of events prevented the analysis in the BEACOPP group. Patients' age was strongly associated with both OS and PFS: all statistically significant predictors for OS and PFS from univariate analyses (chemotherapy regimen, CCI, RDI) lost its effect in multivariate analyses where age was controlled. Based on our observations, we can conclude that RDI is not associated with the OS or PFS after the age is controlled, neither in all patients combined nor in individual chemotherapy groups.
A Fluorescence System Composed of Nitrogen-doped Graphene Quantum Dots and Gold Nanoparticles Coated With Phenylalanine for Selective and Sensitive Quantification of Piroxicam in Biological Samples
Authors: Bahmani Maryam Moallemi , Shabani Ali Mohammad Haji , Dadfarnia Shayessteh , Afsharipour Roya 
Published: January 2022

Abstract
In this study, a sensitive fluorimetric method is proposed for the determination of piroxicam using nitrogen graphene quantum dots (N-GQDs) and gold nanoparticles coated with phenylalanine. The fluorescence emission of N-GQDs at 440 nm decreases with the increase of gold nanoparticles coated with phenylalanine. However, the addition of piroxicam causes the release of gold nanoparticles from the surface of quantum dots followed by the retrieval of the fluorescence emission of N-GQDs. Under the optimum conditions, the calibration graph was linear in the concentration range of 2.0-35.0 nmol L-1 for piroxicam with a limit of detection of 0.11 nmol L-1. The developed method was successfully applied for the determination of piroxicam in urine and serum samples.
Mouse Mesenchymal Stem Cell-derived Exosomal Mir-466f-3p Reverses Emt Process Through Inhibiting Akt/gsk3β Pathway via C-met in Radiation-induced Lung Injury
Authors: Li Yi , Shen Zhufu , Jiang Xiao , Wang Yuanyuan , Yang Zuozhang , Mao Yuchi , Wu Zhixian , Li Gaofeng , Chen Hong 
Published: January 2022

Abstract
Background: Radiation-induced lung fibrosis (RILF) is a common complication of thoracic radiotherapy. Alveolar epithelial cells play a crucial role in lung fibrosis via epithelial-mesenchymal transition (EMT). Exosomes derived from mesenchymal stem cells own the beneficial properties to repair and regeneration of damaged tissues, however the underlying mechanisms remain poorly understood. Methods: Mouse mesenchymal stem cells-derived exosomes (mMSCs-Exo) were isolated by differential centrifugation, and their protective effects were assessed in vivo and in vitro , respectively. EMT-associated proteins were measured via western blot assay and/or immunofluorescence staining. The miRNA expression was measured by microarray assay and qPCR. Furthermore, bioinformatics prediction with KEGG analysis, luciferase assay, and rescue experiments were performed to explore the molecular mechanism underlying miR-466f-3p. Results: mMSCs-Exos were efficiently isolated ranging from 90-150 nm with high expression of exosomal markers (CD63, TSG101, and CD9). mMSCs-Exos administration efficiently relieved radiation-induced lung injury with less collagen deposition and lower levels of IL-1β and IL-6. Meanwhile, in vitro results showed mMSCs-Exos treatment obviously reversed EMT process induced by radiation. Among enriched miRNA cargo in exosomes, miR-466f-3p was primarily responsible for the protective effects via inhibition of AKT/GSK3β pathway. Our mechanistic study further demonstrated that c-MET was the direct target of miR-466f-3p, whose restoration partially abrogated mMSCs-Exo-mediated inhibition in both EMT process and AKT/GSK3β signaling activity induced by radiation. Conclusions: Our findings indicated that exosomal miR-466f-3p derived from mMSCs may possess anti-fibrotic properties and prevent radiation-induced EMT through inhibition of AKT/GSK3β via c-MET, providing a promising therapeutic modality for radiation-induced lung fibrosis.
Matched Queues with Flexible Customers and Impatient Customers
Authors: liu hengli 
Published: January 2022

Abstract
This paper studies a double-ended queue with four Poisson inputs and flexible customers, and its stability is guaranteed by customers’ impatient behavior. We show that such a queue can be expressed as a quasi birth-and-death (QBD) process with infinitely many phases. For this purpose, we provide a detailed analysis for the QBD process, including the system stability, the stationary probability vector, the sojourn time, and so forth. Finally, numerical examples are employed to verify the correctness of our theoretical results, and demonstrate how the performance measures of this queue are influenced by key system parameters. We believe that the methodology and results described in this paper can be applied to analyze many practical issues, such as those encountered in sharing economy, organ transplantation, employee recruitment, onlinedating, and so on.
WITHDRAWN: Edible Mushroom significantly ameliorated Hepatorenal Toxicity of Butyl Paraben (BP) in Albino Rats.
Authors: berhane Kassahun 
Published: January 2022

Abstract
Introduction: Parabens are used commonly as preservatives in a range of cosmetics applied to the under arm and breast area as well as popular preservatives because of their cost.Aim of the work: This study was done to evaluate the neprohepatic toxicity of parabens. Materials and methods: Thirty adult female rats were used and given paraben orally for six months at parabens at dose of 10 % of the LD50 equal to 4.6mg\kg.bw. Mushroom was given orally to at dose of 10 mg/kg/day for six months too. Results: Oral administration of BP induced biochemical and histopathological changes. Biochemical changes: BP toxicity manifested by changes in the liver and kidney function tests manifested by increase AST, ALT, Bilirubin, urea and createnine with decreases to plasma proteins in comparison to control group. Giving mushroom caused amelioration to the nephrohepatic toxicity by inducing recovery in liver and kidney functions in comparison to paraben treated group. For histopathological findings: BP induced vascular congestion in liver and kidney in association with necrotic changes in the hepatorenal epithelium which improved after mushroom treatment. Conclusion: BP induced hepatorenal toxicity which improved by mushroom treatment.
Revisiting regulatory decoherence: Accounting for temporal bias in a co-expression analysis reveals novel candidates controlling environmental response
Authors: Cai Haoran , Des Marais David 
Published: January 2022

Abstract
Transcriptional Regulatory Networks (TRNs) orchestrate the timing, magnitude, and rate of organismal response to many environmental perturbations. Regulatory interactions in TRNs are dynamic but exploiting temporal variation to understand gene regulation requires a careful appreciation of both molecular biology and confounders in statistical analysis. Seeking to exploit the abundance of RNASequencing data now available, many past studies have relied upon population-level statistics from cross-sectional studies, estimating gene co-expression interactions to capture transient changes of regulatory activity. We show that population-level co-expression exhibits biases when capturing transient changes of regulatory activity in rice plants responding to elevated temperature. An apparent cause of this bias is regulatory saturation, the observation that detectable co-variance between a regulator and its target may be low as their transcript abundances are induced. This phenomenon appears to be particularly acute for rapid onset environmental stressors. However, exploiting temporal correlations appears to be a reliable means to detect transient regulatory activity following rapid onset environmental perturbations such as temperature stress. Such temporal correlation may lose information along a more gradual-onset stressor (e.g., dehydration). We here show that rice plants exposed to a dehydration stress exhibit temporal structure of coexpression in their response that can not be unveiled by temporal correlation alone. Collectively, our results point to the need to account for the nuances of molecular interactions and the possibly confounding effects that these can introduce into conventional approaches to study transcriptome datasets.
The Employment in Innovative Enterprises in Europe
Authors: Laureti Lucio , Alberto Costantiello , Matarrese Marco Maria , Leogrande Angelo 
Published: January 2022

Abstract

In this article we evaluate the determinants of the Employment in Innovative Enterprises in Europe. We use data from the European Innovation Scoreboard of the European Commission for 36 countries in the period 2000-2019 with Panel Data with Fixed Effects, Panel Data with Random Effects, Dynamic Panel, WLS and Pooled OLS. We found that the “Employment in Innovative Enterprises in Europe” is positively associated with “Broadband Penetration in Europe”, “Foreign Controlled Enterprises Share of Value Added”, “Innovation Index”, “Medium and High-Tech Product Exports” and negatively associated to “Basic School Entrepreneurial Education and Training”, “International Co-Publications”, and “Marketing or Organizational Innovators”. Secondly, we perform a cluster analysis with the k-Means algorithm optimized with the Silhouette Coefficient and we found the presence of four different clusters. Finally, we perform a comparison among eight different machine learning algorithms to predict the level of “Employment in Innovative Enterprises” in Europe and we found that the Linear Regression is the best predictor.
Impact of ageing on female metabolic flexibility: a cross-sectional pilot study in over-60 active women
Authors: Monferrer-Marín Jordi , Roldán Ainoa , Monteagudo Pablo , Chulvi-Medrano Iván , Blasco-Lafarga Cristina 
Published: January 2022

Abstract
Background
Ageing influences the metabolic flexibility, albeit the physical status could determine this relationship. This cross-sectional study aims to describe and analyse the metabolic flexibility/inflexibility in a group of active older women, together with the impact of ageing and physical status on their oxidation rates and maximal fat oxidation (MFO).
Methods
Fifteen volunteers (69.00±6.97 years) from 24 women, completed an incremental cycling test until the second ventilatory threshold. Intensity increased 10W each 3min–15sec, starting at 30W. Gas exchange, heart rate, rate of perceived effort, pain scale and muscle power were registered, together with lactate. VO2 and VCO2 were considered for Fat and CHO oxidation (FATox & CHOox; Frayn’s equation) at the intensities 60%, 80% and 100% from the peak of power in the test (P100). Psychophysiological parameters were compared at MFO/FATmax and P100, together with the main correlation analyses, with and without P100 and VO2 as covariates.
Results
FATox was low at MFO (0.13; 95%CI [0.09-0.17] g·min−1·kg; 5.61 [3.59-7.63] g·min−1·kg FFM), with a shifting down and leftward of a short oxidation-rate curves. CHOox and FATox were both low for a reduced power with age (77.14±18.58 W & 39.29±9.17 W at P100 and MFO respectively), pointing to metabolic inflexibility in older women despite being active. Notwithstanding, the negative correlation between age and MFO (r=-0.54, p=0.04; R2=0.29) disappeared when normalized with P100 (r=-0.17, p=0.53), which was in turn strongly and negatively associated to age (r=-0.85, p<0.005; R2=0.72). P100 was also positive and moderately associated to MFO (r=0.71, p=0.01; R2=0.50).
Conclusions
Despite the inflexibility with age, physical status (i.e., larger muscular power) suggest a key role in the preservation of the metabolic health with aging in active women.
The complete genome sequences of Erythroxylum coca and Erythroxylum novogranatense
Authors: White Dawson , Meinhardt Lyndel , Bailey Bryan , Pirro Stacy 
Published: January 2022

Abstract
The flowering plant genus Erythroxylum contains approximately 300 species, including the economically and socially consequential crops called coca. We present the genome sequences of Erythroxylum coca and E. novogranatense, two cultigens produced for medicinal and quotidian use in the Andes and Amazon regions of South America, as well as the international cocaine industry. Sequencing was performed on an Illumina X-Ten platform, and reads were assembled by a de novo method followed by finishing via comparison with several species from the same genus. The BioProject, raw and assembled data can be accessed in GenBank for E. coca (PRJNA676123; JAJMLV000000000) and E. novogranatense (PRJNA675212; JAJKBF000000000)
Electronic gadgets use and sleep quality among medical students during COVID-19 Lockdown
Authors: Upreti Manish , Dawadi Ambika 
Published: January 2022

Abstract
BACKGROUND: The Nepal Government imposed two national-level lockdowns to curtail the spread of coronavirus. Schools, colleges, and universities were briefly shut leading students to stay indoors. Change in daily routine, online education and plenty of free time has ultimately led to an increase in use of electronic gadgets like smartphones, laptops, etc. There have not been enough studies to evaluate the usage pattern of electronic gadgets and sleep quality among undergraduate medical students of Nepal before and during the COVID-19 lockdown. Our study aims to evaluate the usage pattern of electronic gadgets and sleep quality among undergraduate medical students before and during the COVID-19 lockdown in Nepal.METHODOLOGY: This cross-sectional study was conducted among 208 undergraduate medical students of Lumbini Medical College, Tansen, Palpa. Participants were requested to fill up an online questionnaire circulated via Viber and Facebook messenger. Gadget usage pattern and sleep quality before and during COVID-19 lockdown were evaluated using Smartphone addiction score-short version (SAS-SV) and Pittsburgh Sleep Quality Index (PSQI) respectively.RESULTS: Of 208 responses which met the inclusion criteria, smartphone addiction was seen 94 (46.30%) respondents with higher number of male addicts (27.59%). Mean time spent in electronic gadgets raised significantly during lockdown compared to pre-COVID phase. 99 (48.77%) respondents had impaired sleep according to PSQI global sleep score. Significant relation was present between most of the components of PSQI with addicts and non-addicts.CONCLUSION: This study is merely a partial snapshot of the present scenario and provides preliminary understanding on smartphone use pattern and sleep quality among medical students from Nepal. It is critical to decrease total screen time and promote sleep quality for the betterment of physical and mental health of the future health care professionals.