bluuebunny/crossref_metadata_2025_split huggingface dataset:
FGF21 restores hippocampual mitochondrial dysfunction via enhancing Nrf2/HO-1 and AMPK/SirT1/PGC-1α signaling pathways to alleviate chronic unpredictable mild stress induced depressive like behaviors in mice
Authors: Zhao Yun-Tao , Shen Ling , Zhang Yong-Ping , Zhang Lulu , Jin Leigang , Chen Shaohong , Song Cai , Hu Chuanyin , Liu You 
Published: October 2021

Abstract
Mitochondrial dysfunction plays a key role in the pathogenesis of depression. Ample research proves mitochondria are a promising target for depression. Fibroblast growth factor 21 (FGF21) exerts roles in neuroprotection and could enhance mitochondria function. Here, the anti-depressive effect of FGF21 was evaluated on a chronic unpredictable mild stress (CUMS)- induced model of depression. The depressive-like behaviors were assessed using sucrose preference test (SPT), forced swim test (FST) and tail suspension test (TST). The results showed that treatment of FGF21 significantly attenuated the decrease in SPT, and dramatically reduced the immobility time in the TST and FST. These effects were associated with enhanced hippocampal mitochondrial function, reflected by FGF21-induced increases in mitochondrial ATP concentration, mitochondrial membrane potential (MMP), and decrease of reactive oxygen species (ROS) levels. At the same time, FGF21 ameliorated oxidative stress in CUMS-exposed mice by enhancing superoxide dismutase (SOD), glutathione peroxidase (GSH-Px) and catalase activities, and reducing malondialdehyde (MDA) level in the hippocampus. Mechanistically, we found that CUMS treatment decreased expression level of mitochondrial fusion protein 1 (MFN1), and increased expression level of mitochondrial dynamin-related protein 1 (DRP1). FGF21 administration increased expression of MFN1, and reduced expression of DRP1. Meanwhile, FGF21 treatment promoted the expression levels of Nrf2, HO-1, phosphorylated AMPK, SirT1, PGC-1a in the hippocampus. This study revealed that FGF21 alleviates CUMS induced depressive like behaviors by restoring mitochondria function via enhancing Nrf2/HO-1 and AMPK/SirT1/PGC-1α signaling pathways. It suggested that FGF21 would be a potential therapeutic agent in the management of depression.
Frequency Spectra and the Color of Cellular Noise
Authors: Gupta Ankit , Khammash Mustafa 
Published: October 2021

Abstract
The invention of the Fourier integral in the 19th century laid the foundation for modern spectral analysis methods. By decomposing a (time) signal into its essential frequency components, these methods uncovered deep insights into the signal and its generating process, precipitating tremendous inventions and discoveries in many fields of engineering, technology, and physical science. In systems and synthetic biology, however, the impact of frequency methods has been far more limited despite their huge promise. This is in large part due to the difficulties encountered in connecting the underlying stochastic reaction network in the living cell, whose dynamics is typically modelled as a continuous-time Markov chain (CTMC), to the frequency content of the observed, distinctively noisy single-cell trajectories. Here we draw on stochastic process theory to develop a spectral theory and computational methodologies tailored specifically to the computation and analysis of frequency spectra of noisy cellular networks. Specifically, we develop a generic method to obtain accurate Padé approximations of the spectrum from a handful of trajectory simulations. Furthermore, for linear networks, we present a novel decomposition result that expresses the frequency spectrum in terms of its sources. Our results provide new conceptual and practical methods for the analysis and design of noisy cellular networks based on their output frequency spectra. We illustrate this through diverse case studies in which we show that the single-cell frequency spectrum facilitates topology discrimination, synthetic oscillator optimization, cybergenetic controller design, systematic investigation of stochastic entrainment, and even parameter inference from single-cell trajectory data.
Effects of Dedifferentiated Fat Cells on Neurogenic Differentiation and Cell Proliferation in Neuroblastoma Cells
Authors: Hidaka Ayano , Uekusa Shota , Hosokawa Takashi , Kaneda Hide , Kazama Tomohiko , Hagikura Kazuhiro , Uehara Shuichiro , Koshinaga Tsugumichi , Matsumoto Taro 
Published: October 2021

Abstract
Recent reports demonstrated that mesenchymal stem cells (MSCs) can induce differentiation of neuroblastoma (NB) cells. Dedifferentiated fat cells (DFAT) and MSCs have similar properties. The present study investigated whether DFAT can induce NB cell differentiation and suppress cell proliferation. DFAT was obtained from mature adipocytes isolated from adipose tissue from a ceiling culture. NB cells were cultured in a medium with/without DFAT, and subsequently in a DFAT-conditioned medium (CM) with/without phosphatidylinositol 3 kinase (PI3K) inhibitor. Length of neurites was measured, and the mRNA expression levels of the neurofilament (NF) and tubulin beta III (TUBβ3) were assessed using quantitative real-time reverse transcription polymerase chain reaction. Cell viability was assessed by the water-soluble tetrazolium salt-1 assay. NB cells cultured with DFAT elongated the neurites and upregulated the expression of NF and Tubβ3 compared with the control. However, NB cells cultured in DFAT-CM demonstrated increased cell viability compared with the control. NB cells cultured with DFAT-CM and PI3K inhibitor suppressed cell viability and demonstrated increased neurite length and expression and upregulation of Tubβ3. Therefore, the combined use of DFAT-CM and PI3K inhibitors suppresses the proliferation of NB cells and induces their differentiation. DFAT may offer new insights into therapeutic approaches in NB.
Determinants of Birth Asphyxia At Public Hospitals in Ilu Aba Bor Zone Southwest, Ethiopia: A Case Control Study
Authors: Wolde Tarekegn Fekede , Bekele Firomsa , Fufa Abeya 
Published: October 2021

Abstract
Despite birth asphyxia is one of the important causes of morbidity and mortality in newborn; its determinants were not investigated according to local context especially in this area. Thus, this study aims to investigate the determinants of birth asphyxia at Illu Aba Bor zone public health facilities. Study Design: An Institution based a case-control study. Methods: Systematic random sampling technique was used to select 308 (103 cases and 205 controls) newborn. Data were collected using checklist for record review & interviewer administered questionnaire and entered in to Epi-data version 3.1 and analyzed using SPSS version 24. Variables with P-value <0.25 were taken to multi-variable regression. Backward likelihood ratio with 0.1 probability removal was used to develop the model. Collinearity, goodness fit of final model using Hosmer Lemeshow test considering good fit at P-value ≥ 0.05 (0.208), omnibus likelihood test <0.05(0.000) and model classification of accuracy (77.9%) were checked. Odds Ratio estimated with 95% CI was used to show strength of association and P-value < 0.05 was used to declare statistical significance. Results: A total of 308 (103 cases and 205 controls) mothers of newborns were interviewed yielding a response rate of 100%. The mean age (±Standard deviation) of mothers for the cases and the controls were 25.97 (SD: ±4.47) and 25.52(SD: ±4.17), respectively. Being not educated (non-formal education) [AOR=2.44; (95%CI:1.37, 4.34)], having antenatal care follow up <4 [AOR=2.30; (95% CI:1.17, 4.53)], Prolonged duration of labour [AOR=4.12; (95% CI:1.78, 9.50)], non-cephalic fetal presentation [AOR=4.35; (95%CI:1.77, 10.67)] and being primi-gravida [AOR=2.14; (95%CI:1.20, 3.83)] were the predictors of birth asphyxia. Whereas, neonatal factor such as: being preterm [AOR=5.77; (l95%:2.62, 12.69)] and low birth weight [AOR=4.43; (95% CI: 1.94, 10.13)] were also the predictors of birth asphyxia Conclusion: Predictors were maternal and newborn related characteristics. Therefore, interventions focusing in this area should give priority for these identified determinants.
WITHDRAWN: Patent landscape of Chinese Classical Formulas
Authors: Shi Ruipeng , Luo Hua , Zhao Yi , Tang Yuyang , Zhong Zhangfeng , Wang Shengpeng , Hu Yuanjia 
Published: October 2021

Abstract
BackgroundChinese Classical Formulas (經典名方, CCFs) are clinically employed formulas that have been documented in the literature since before the Ming era. In 2010, China began focusing on the development and product transformation of CCFs and issued a list of 100 CCFs as a reference. Patents are key components of the process for transferring technology to product; however, they are rarely employed in current CCF research. Therefore, the present study aims to explore the current situation of CCFs based on the China National Intellectual Property Administration (CNIPA) and provide a reference for researchers, investors, and policymakers to make relevant decisions. MethodsInformation on CCF publication numbers was obtained from the CNIPA, and data for patent applications made before June 30, 2021, on inventors, titles, and abstracts were searched in the patent database, Derwent Innovation. Duplicate application numbers were removed, applications were standardized, and inventors were categorized. The processed data were then used for subsequent analyses. ResultsA total of 287 patents were included in this analysis, and 61 CCFs were patented. Two major policies regarding CCFs in 2011 and 2019 greatly stimulated related patent applications, but lacked sustainability, followed by a relatively large decline in 2012 and 2020. Among the granted patents, 42.59% are analytical methods-related inventions and 24.07% for preparation methods. The percentage of core patents on substance basis and mechanism of action is relatively small. ConclusionPolicies have a significant impact on CCF R&D. The number of CCF patent applications is increasing every year and there is an increasing number of companies as patent applicants, which indicates that CCF is considered to have a good market potential. However, the lack of high quality patents may create difficulties for future development and this will be an important issue to be addressed. Keywords Chinese classical formulations, Chinese medicine, patent, product transformation
Beyond the Scales: A physics-informed machine learning approach for more efficient modeling of SARS-CoV-2 spike glycoprotein
Authors: Liang David , Zhang Ziji , Rafailovich Miriam , Simon Marcia , Deng Yuefan , Zhang Peng 
Published: October 2021

Abstract
This paper presents a physics-informed machine learning approach to the derivation of a bottom-up coarse-grained model of the SARS-CoV-2 spike glycoprotein from all-atomic molecular dynamics simulations. The machine learning procedure employs a force-matching scheme in the optimization of interaction parameters, where the force-matching scheme is combined in methodology with the initialization of the interaction parameters by the traditional iterative Boltzmann inversion method. The force-matched machine learning procedure is constructed based on two physics-informed layers: one is the Harmonic layer consisting of bond, angle, and dihedral terms as bonded potentials; the other is the Lennard-Jones layer consisting of the non-bonded Lennard-Jones potential. Coarse-grained validation simulations are performed with the learned parameters to test the derived bottom-up coarse-grained model. The simulations are able to reach the microsecond time scale with stability. The physics-informed learning approach yields simulation speeds nearly 40,000 times faster than conventional all-atomic simulations while maintaining comparable simulation accuracy. Additionally, through examination of the non-bonded Lennard-Jones parameters and the radial distribution function analysis, the learning approach matches pairwise distances of the ground-truth data with greater accuracy than the conventional iterative approach method.
The Ecological Responses of Bacterioplankton During a Phaeocystis Globosa Bloom in Beibu Gulf, China Highlighted by Integrated Metagenomics and Metatranscriptomics
Authors: xu sha , He Cheng , Kang Zhenjun , Song Shuqun , Li Caiwen 
Published: October 2021

Abstract
The interaction between bacteria and phytoplankton during bloom events are complicated throughout the developmental processes of algal blooms. The detailed ecological roles of bacterioplankton during algal blooms still need to be investigated comprehensively. With the assistance of omics techniques, the composition and function of bacterioplankton were studied during the blooming and recession periods of Phaeocystis globosa in the Beibu Gulf, China. The transcriptionally active taxa of Vibrio, which correlated with most functional genes, were enriched in the blooming period, whereas the active microbial groups, such as Erythrobacter and Candidatus puniceispirillum, increased significantly in the recession period of the P. globosa bloom. The transcriptional analyses indicated the blooming and recession periods of P. globosa had different impacts on the function of bacterioplankton, including shifts in expression of specific metabolic pathways for variable nutritional utilization and their advantage in bacterial motility, quorum sensing, and extracellular secretion. Overall, the integrated field investigation and in-depth analysis of molecular data highlighted the difference of bacterial community during the outbreak and collapse stages of P. globosa bloom, and provided fundamental data for better understanding of the bacterial community in response to blooming and recession of the P. globosa bloom.
DeepAmp: A Convolutional Neural Network Based Tool for Predicting Protein AMPylation Sites From Binary Profile Representation
Authors: Azim Sayed Mehedi , Sharma Alok , Shatabda Swakkhar , Dehzangi Abdollah 
Published: October 2021

Abstract
AMPylation is an emerging post-translational modification that occurs on the hydroxyl group of threonine, serine, or tyrosine via a phosphodiester bond. AMPylators catalyze this process as covalent attachment of adenosine monophosphate to the amino acid side chain of a peptide. Recent studies have shown that this post-translational modification is directly responsible for regulation of neurodevelopment and neurodegeneration and also involved in many physiological processes. Despite the importance of this post-translational modification, there is no peptide sequence dataset available for conducting computational analysis. Therefore, so far, no computational approach has been proposed for predicting AMPylation. In this study, we introduce a new dataset of this distinct post-translational modification and develop a new machine learning tool using a deep convolutional neural network called DeepAmp to predict AMPylation sites in proteins. DeepAmp achieves 77.7%, 79.1%, 76.8%, and 0.55 in terms of Accuracy, Sensitivity, Specificity, and Matthews Correlation Coefficient (MCC) for AMPylation site prediction task, respectively. As the first machine learning model, DeepAmp demonstrate promising results which highlight its potential to solve this problem. Our presented dataset and DeepAmp as a standalone predictor are publicly available at https://github.com/MehediAzim/DeepAmp
Adipose Derived Stem Cells Ameliorate Atopic Dermatitis by Down-regulating IL-17 Secretion of Th17 Cells in an Ovalbumin-induced Mouse Model
Authors: Guan Jingyan , Li Yibao , Lu Feng , Feng Jingwei 
Published: October 2021

Abstract
Background: Mesenchymal stem cells (MSCs) has therapeutic potential for Atopic dermatitis (AD) due to their immunoregulatory effects. However, the underlying mechanisms for therapeutic efficacy of ADSCs on AD is still unclear. Objectives: We sought to investigate the therapeutic effect and mechanisms of adipose-derived stem cells (ADSCs) on AD using an ovalbumin-induced AD mouse model. Methods: AD mice were treated with mice-derived ADSCs, cortisone, or PBS. The therapeutic effect was determined via gross examination and additional in vitro assays using skin samples and blood. To further explore the underlying mechanisms, RNA sequencing analyses and co-culture assays were conducted.Results: ADSCs treatment attenuated the symptoms associated with AD, decreased the serum IgE level and mast cells infiltration. Tissue levels of T-cell relevant pro-inflammatory cytokine production, including IL-4R and IL-17A, were suppressed in both ADSCs and cortisone treatment groups. Genomics and bioinformatics analyses demonstrated a significant enrichment of certain of inflammation related pathway in the down regulated genes after the application of ADSCs and cortisone, specifically the IL-17 signaling pathway. Co-culture experiments revealed that ADSCs significantly suppressed the expression of pro-inflammation cytokines IL-17A and RORγT, as well as the proliferation of Th17 cells. Moreover, the expression of PD-L1, TGF-β, PGE2 was significantly upregulated in the co-cultured ADSCs compare to monocultured ADSCs. Conclusion: Taken together, our data may demonstrate that ADSCs ameliorate OVA- induced AD in mice by down-regulating IL-17 secretion of Th17 cells.
Hypoxia Promotes Metastasis of Gastric Cancer Through ANXA1 Pathway
Authors: Liu Qing-Hua , Xia Lei , Wu Xiao-Yue , Lu Chen-Chen , Song Jing-Yuan , Bao Shisan , Liu Ying 
Published: October 2021

Abstract
Background: To determinethe involvement of hypoxia inducible factor1α (HIF) pathway inmetastasis of gastric cancer (GC). Method: It was determined that the expression of HIF and annexin A1 (ANXA1) in human GC (n=76),using immunohis to chemistry, as well as,the involvement of HIF pathway in GC cell migration and invasion in vitro. The correlation between HIF/ANXA1 and the prognosis wasalso evaluated.Results: HIF1αwas substantiallyupregulatedin GC tissues, compared to that of non-cancer. HIF1α was positively correlated withlymph node metastasis, but inversely correlated with survival in GC patients. HIF1αwas an independent prognostic factor in GC patients, and the combination of HIF1α and ANXA1 might serve asuseful prognostic markers in GCpatients.Furthermore,HIF-1αseems topromote GC migration and invasion through HIF1α/ANXA1/MMP-2 pathway. Conclusions: Our findings suggestthat HIF-1αmay serve as a promising prognostic biomarkerand therapeutic target for inhibiting GC metastasis.
Making implementation programmes better. Mixed-m​ethods case study of an implementation process for two evidence-based brief psychotherapies
Authors: Lindholm Lars H. , Komulainen Jorma , Lassila Antero , Kampman Olli 
Published: October 2021

Abstract
Background

The Ostrobothnia Depression Programme (ODP) had a hybrid-design incorporating an implementation programme for two evidence-based treatments (EBTs), behavioural activation and motivational interviewing, and a study on their effectiveness. It was carried out regionally in secondary psychiatric care in a Finnish district. We evaluated the ODP through a mixed-methods analysis to extract organization- and programme-related knowledge to make future programmes more effective in terms of sustaining and scaling up the desired programme outcomes.
Methods

A cross-sectional mixed-methods survey was conducted with the programme addressees 4-5 months after the end of the ODP. The realization of case consultation groups analysed further by interviewing those responsible for them and making use of attendance lists.
Results

Out of 72 original programme addressees 33 completed the survey. The results showed that the ODP succeeded in initiating the desired change in clinical practices. Case consultations and training videos intended as reinforcers were underutilized. Deficits in the implementation plan and the hybrid design of the ODP jeopardized the maintenance of the implementation outcomes in the long term.
Conclusions

We discuss our results in light of the Normalization Process Theory (NPT) related sub-processes ‘implementation’, ‘embedding’ and ‘integration’. The complete training intervention in the target EBTs should comprise both workshops and non-optional case consultations. Access to case consultations should be made as convenient as possible. Means to decentralize the clinical support in everyday work should be elaborated in collaboration with the teams. Coaching team leaders to employ evidence-based active managerial practices that are connected e.g. to the concept of ‘transformational leadership’ would likely be fruitful. The original programme plan should be checked for means to sustain and scale up the implementation outcomes after the active programme phase.
Changes in Left Ventricular Global Longitudinal Strain Before and After Balloon Mitral Valvuloplasty
Authors: Soesanto Amiliana Mardiani , Syah Pangeran Akbar , Ariani Rina , Firman Doni , Kurniawati Yovi , Rudiktyo Estu 
Published: October 2021

Abstract
Background: Several studies have reported left ventricular systolic dysfunction as measured by the global longitudinal strain (GLS) in patients with mitral stenosis. This study aims to determine left ventricular systolic function changes using global longitudinal strain early after balloon mitral valvuloplasty (BMV) and on long-term observation.Methods: Baseline echocardiography data and GLS were taken before BMV, followed up early after (2 to 7 days), and in the long-term (6 months to 1 year) after BMV.Result: Among 36 patients, the mean age was 43.41±10.04 y.o, female dominant (72%); the majority have atrial fibrillation (56%), with a median mitral valve area (MVA) before BMV of 0.6 (0.2-1.3) cm2 and mean mitral valve gradient before BMV of 12.95 ± 5.29 mmHg. GLS increased from -14.34 ± 3.05% to 15.84 ±3.11% and increased further to -17.29 ± 2.80% (p<0.05), at pre-BMV- early post-BMV, and long-term follow up, respectively. Conclusions: There is a significant improvement in LV GLS early after BMV compare to baseline. The GLS improved further at long-term evaluation (six months until one year) after BMV.