bluuebunny/crossref_metadata_2025_split huggingface dataset:
The Orbitofrontal Cortex Represents Advantageous Choice in the Iowa Gambling Task
Authors: Zha Rujing , Li Peng , Li Ying , Li Nan , Gao Meijun , Fan Yiyang , Aili Ruhuiya , Liu Ying , Zhang Xiaochu , Li Jun 
Published: May 2021

Abstract
A good-based model proposes that the orbitofrontal cortex (OFC) represents binary choice outcome, i.e., the chosen good. Previous studies have found that the OFC represents the binary choice outcome in decision-making tasks involving commodity type, cost, risk, and delay. Real-life decisions are often complex and involve uncertainty, rewards, and penalties; however, whether the OFC represents binary choice outcomes in a such decision-making situation, e.g., Iowa gambling task (IGT), remains unclear. Here, we propose that the OFC represents binary choice outcome, i.e., advantageous choice versus disadvantageous choice, in the IGT. We propose two hypotheses: first, the activity pattern in the human OFC represents an advantageous choice; and second, choice induces an OFC-related functional network. Using functional magnetic resonance imaging and advanced machine learning tools, we found that the OFC represented an advantageous choice in the IGT. The OFC representation of advantageous choice was related to decision-making performance. Choice modulated the functional connectivity between the OFC and the superior medial gyrus. In conclusion, the OFC represents an advantageous choice during the IGT. In the framework of a good-based model, the results extend the role of the OFC to complex decision-making when making a binary choice.
Capparis Spinosa Improves Non-Alcoholic Steatohepatitis Through Down-Regulating SREBP-1c and a PPARα-Independent Pathway in High-Fat Diet-Fed Rats
Authors: Akbari Rasoul , Yaghooti Hamid , Jalali Mohammad Taha , Khorsandi Laya Sadat , Mohammadtaghvaei Narges 
Published: May 2021

Abstract
Background: Non-alcoholic steatohepatitis (NASH) has become a global medical problem. Currently, there is no approved pharmacologic treatment for this condition. This study aimed to evaluate the ameliorative effects of Capparis spinosa (CS) on NASH in comparison to fenofibrate.Methods: An animal model of NASH was developed using a high-fat (HF) emulsion. Fatty liver rats were treated with aqueous extract of CS fruit or fenofibrate in parallel to the HF for six weeks. Animals were examined for weight gain, serum biochemistry, insulin sensitivity, hepatic triglyceride (TG) content, histopathological changes as well as gene expression of sterol regulatory element-binding protein-1c (SREBP-1c), acetyl-CoA carboxylase (ACC), peroxisome proliferator-activated receptor α (PPARα) and Carnitine palmitoyltransferase I (CPT1) in liver.Results: Fasting blood sugar, insulin level, body and liver weight, activities of liver enzymes, hepatic triglyceride (TG) content as well as serum lipids were decreased following six weeks CS and fenofibrate treatments compared to the HF administration alone. Histopathological examinations also showed that liver steatosis, inflammation and hepatic fibrosis were markedly attenuated in response to CS and fenofibrate interventions. At the molecular level, CS treatment down-regulated SREBP1c, ACC and up-regulated CPT1 expression, but did not show a significant effect on PPARα. In contrast, fenofibrate treatment induced the expression of all studied genes in fatty liver rats.Conclusions: These findings indicated the favorable therapeutic effects of CS fruit extract on liver damages associated with NASH. The beneficial effects of CS on lipid accumulation and steatosis were comparable to those of fenofibrate.
Exploring Dynamic Metabolomics Data With Multiway Data Analysis: a Simulation Study
Authors: Li Lu , Hoefsloot Huub , Graaf Albert A. , Acar Evrim , Smilde Age K. 
Published: May 2021

Abstract
Background: Analysis of dynamic metabolomics data holds the promise to improve our understanding of underlying mechanisms in metabolism. For example, it may detect changes in metabolism due to the onset of a disease. Dynamic or time-resolved metabolomics data can be arranged as a three-way array with entries organized according to a subjects mode, a metabolites mode and a time mode. While such time-evolving multiway data sets are increasingly collected, revealing the underlying mechanisms and their dynamics from such data remains challenging. For such data, one of the complexities is the presence of a superposition of several sources of variation: induced variation (due to experimental conditions or inborn errors), individual variation, and measurement error. Multiway data analysis (also known as tensor factorizations) has been successfully used in data mining to find the underlying patterns in multiway data. In this paper, we study the use of multiway data analysis to reveal the underlying patterns and dynamics in time-resolved metabolomics data. Results: We focus on simulated data arising from different dynamic models of increasing complexity, i.e., a simple linear system, a yeast glycolysis model, and a human cholesterol model. We generate data with induced variation as well as individual variation. Systematic experiments are performed to demonstrate the advantages and limitations of multiway data analysis in analyzing such dynamic metabolomics data and their capacity to disentangle the different sources of variations. We choose to use simulations since we want to understand the capability of multiway data analysis methods which is facilitated by knowing the ground truth. Conclusion: Our numerical experiments demonstrate that despite the increasing complexity of the studied dynamic metabolic models, tensor factorization methods CANDECOMP/PARAFAC(CP) and Parallel Profiles with Linear Dependences (Paralind) can disentangle the sources of variations and thereby reveal the underlying mechanisms and their dynamics.
ADP/ATP Translocase 1 Protects Against an A-Synuclein-Associated Neuronal Cell Damage in Parkinson's Disease Model
Authors: Ding Wenyong , Qi Minghua , Ma Li , Xu Xuefei , Chen Yingfei , Zhang Wenli 
Published: May 2021

Abstract
Background: ADP/ATP translocase 1 (ANT1) is involved in the exchange of cytosolic ADP and mitochondrial ATP, and its defection plays an important role in mitochondrial pathogenesis. To reveal an etiological implication of ANT1 for Parkinson’s disease (PD), a neurodegenerative disorder, a mouse model treated with 1-Methyl-4-phenyl-1,2,3,6-tetrahydropyridine and neuroblasma cell model induced by 1-methyl-4-pehny1-pyridine were utilized in this study. Results: The tissue-specific abundance in ANT1 in mouse brains was accessed using the analysis of Western blot and immunohistochemistry. Down-regulated soluble ANT1 was found to be correlated with PD, and ANT1 was associated with PD pathogenesis via forming protein aggregates with α-synuclein. This finding was confirmed at cellular level using neuroblasma cell models. Protein interaction assay, coupled with the analysis of LC-MS/MS, silver-stained SDS-PAGE and Western blot against anti-ANT1 antibody respectively, illustrated the interaction of ANT1 with α-synuclein using the expressed α-synuclein as a bite. Additionally, a significant increasing ROSs was detected in PD-like cells. Conclusions: his study indicated that ANT1 was a potentially causative factor of PD, and led to neuropathogenic injury via promoting the formation of protein aggregates with α-synuclein. This investigation potentially promotes an innovative understanding of ANT1 on the etiology of PD and provides valuable information on developing potential drug targets in PD treatment or reliable biomarkers in PD prognostication.
Potential of Enterococcus Faecium LM5.2 for Lipopeptide Biosurfactant Production and Its Effect on the Growth of Maize (Zea Mays L.)
Authors: Chaurasia Lalit K. , Tirwa Ranjan K. , Tamang Buddhiman 
Published: May 2021

Abstract
The lipopeptide biosurfactants' chemical characteristics from the lactic acid bacteria isolated from milk and milk products were studied and their effect on maize plant growth. The oil displacement test was performed as a primary screening method to select the BS producing bacteria. Enterococcus faecium LM5.2 had the maximum emulsification index of 45.1±3 and reduced the surface tension to 32.98 ± 0.23% among all the isolates. E. faecium LM5.2 efficiently produced 945.26 ± 4.62 mg/l biosurfactants within 48 hours in MRS broth under the optimum conditions. The confirmation of the identity of the isolate LM5.2 was done with physiochemical tests and 16S rRNA gene sequencing. The molecular phylogenetic relationship was evaluated by the Neighbour-Joining phylogenetic method. The biosurfactant was purified by TLC and identified as lipopeptide-like iturines and surfactins based on Rf values. Mass spectroscopy, NMR, and FTIR analysis also confirmed the biosurfactant's identity as the derivatives of iturin and surfactin. Both the biosurfactant and its producer bacterium were evaluated for their plant growth-promoting activity, and it was found that the biosurfactant and the bacterium could enhance plant growth. To the best of our knowledge, this is the first report of lipopeptide biosurfactant production from Enterococcus faecium. Moreover, the study also showed that the biosurfactant and biosurfactant producing E. faecium LM5.2 could be an eco-friendly plant growth-promoting agent.
Clinical Characteristics, Prognostic Factors, and Real-World Practice of Abnormal Liver Function Tests in Children with Acute Infectious Diseases: A Multicenter Study
Authors: Lee Kyung Jae , Yi Dae Yong , Lee Yoo Min , Choi So Yoon , Choi You Jin , Lee Yoon 
Published: May 2021

Abstract
Background Abnormal liver function tests (LFTs) are commonly seen in pediatric patients with acute infectious diseases; few studies and no definite clinical guidelines for these conditions are available. This study aimed to elucidate the causes and factors associated with prolongation of liver enzyme elevation. We also investigated actual real-world practices in Korea.Methods A retrospective study was performed on all patients younger than 18 years, who visited six tertiary teaching hospitals around Korea in 2018 for acute infectious diseases and showed alanine aminotransferase (ALT) levels above 60 IU/L. We categorized the infections that cause LFT elevation into six groups: respiratory infection, gastrointestinal infection, urinary tract infection, other febrile disease, Epstein-Barr virus infection, and cytomegalovirus infection. We collected data on the medical specialty of the attending physician who followed up the subject, follow-up duration, percentage of follow-up loss, and their investigation.ResultsA total of 613 patients were enrolled in this study, half of whom (50.7%) were younger than 12 months. The mean initial aspartate aminotransferase and ALT values were 171.2±274.1 and 194.9±316.1 IU/L (range 23~2881, 60~2949 IU/L), respectively; however, other LFTs were within the normal range. Respiratory infection was the most common diagnosis (45.0%), and rhinovirus was the most commonly identified pathogen (9.8%). The follow-up rate was higher with pediatric gastroenterologists (90.5%) and non-gastroenterology pediatricians (76.4%) than with pediatric residents and emergency doctors. Older age was related to better ALT recovery (odds ratio [OR] of age for month was 1.003, with 95% confidence interval [CI] 1.001-1.004, p=0.004), while the number of infection episodes (OR=0.626, 95% CI 0.505-0.777, p<0.001) was associated with poor ALT recovery. Abdominal sonography was the most commonly used diagnostic tool (36.9%), followed by the hepatotropic virus workup. The modalities of hepatitis workup were significantly differently applied by physicians based on their specialties and institutions.Conclusions An LFT abnormality after a systemic infection was common in respiratory infection and under the age of 1 year. Age, number of infections, and initial results of LFTs were related to ALT recovery time. Inter-physician, inter-institution, and inter-specialty variances were observed in real-world practice.
Potential Probiotic Lactobacillus Rhamnosus (MTCC-5897) Attenuates Escherichia Coli Induced Inflammatory Response in Intestinal Cells
Authors: Gupta Taruna , Kaur Harpreet , Kapila Suman , Kapila Rajeev 
Published: May 2021

Abstract
Probiotics are microbes having tremendous potential to prevent gastrointestinal disorders. In current investigation, immunomodulatory action of probiotic Lactobacillus rhamnosus (LR:MTCC-5897) was studied during exclusion, competition and displacement of Escherichia coli on intestinal epithelial (Caco-2) cells. The incubation of intestinal cells with E. coli, enhanced downstream signalling and activated nuclear factor kappa B (NF-κB). This significantly increased (p<0.01) the pro-inflammatory cytokines (IL-8, TNF-α and IFN-ϒ) expression. While, incubation of epithelial cells with L. rhamnosus during exclusion and competition with E. coli, counteracted these enhanced expressions. The immunomodulatory feature of L rhamnosus was also highlighted with increased (p<0.05) transcription of toll like receptor-2 (TLR-2) and single Ig IL-1-related receptor (SIGIRR) along with diminished expression of TLR-4. Likewise, attenuation (p<0.05) of E.coli-mediated enhanced nuclear translocation of NF-κB p-65 subunit by L. rhamnosus during exclusion was confirmed with western blotting. Thus, present finding establishes the prophylactic potential of L. rhamnosus against exclusion of E. coli in intestinal cells.
A Microservice Regression Testing Selection Approach Based on Belief Propagation
Authors: Chen Lizhe , Wu Ji , Yang Haiyan , Zhang Kui 
Published: May 2021

Abstract
Regression testing is required in each iteration of microservice systems. Regression testing selection, which reduces testing costs by selecting a subset from the original test cases, is one of the main techniques to optimize regression testing. Existing techniques mainly rely on the information retrieved from artifacts such as code files and system models. For microservice systems with service autonomy, development method diversity and a large amount of services, such artifacts are too difficultly obtained and costly processed to apply those approaches. This paper presents a regression testing selection approach called MRTS-BP, which needs the API gateway layer logs instead of code files and system models as inputs. By parsing the API gateway layer logs, our approach establishes the service dependency matrix, which in further is transformed into a directed graph with the services as nodes. Then, to find out which test cases are affected by service changes, an algorithm based on belief propagation is presented to compute the quantitative results of service-change propagation from the directed graph. Finally, the relationships between original test cases and service-change propagation results are established to select test cases with three strategies. To evaluate the efficiency of MRTS-BP, the empirical study based on four microservice systems is presented. A typical technique RTS-CFG is compared with MRTS-CFG and four experiments are setup to investigate four research questions. The results show that MRTS-BP can not only reduce the number of test cases by half compared with the retest-all strategy while ensuring the safety, but also save at least 20% testing time costs more than that of RTS-CFG. MRTS-BP is more practical than the techniques relying on the artifacts when the latter cannot be implemented due to the artifacts are difficult to obtain and process.
Link ER ion homeostasis maintained by an ER anion channel to ALS
Authors: Jia Yichang , Guo Liang , Mao Qionglei , He Ji , LIU Xiaoling , Piao Xuejiao , Luo Li , Hao Xiaoxu , Xiao Bailong , Fan Dongsheng , Gao Zhaobing 
Published: May 2021

Abstract
Although anion channel activities have been demonstrated in sarcoplasmic reticulum/endoplasmic reticulum (SR/ER), their molecular identities and functions remain unclear. Here, we link rare variants of CLCC1 (Chloride Channel CLIC Like 1) to ALS (amyotrophic lateral sclerosis). We demonstrate that CLCC1 is a pore-forming component of an ER anion channel and that ALS-associated mutations impair the channel activity. CLCC1 unitary conductance is inhibited by luminal Ca2+ but facilitated by phosphatidylinositol 4,5-bisphosphate (PIP2). We identified a conserved lysine 298 (K298) in CLCC1 intraluminal loop as the critical PIP2-sensing residue. CLCC1 maintains steady-state [Cl-]ER and morphology and regulates ER Ca2+ homeostasis including steady-state [Ca2+]ER and efficiency of internal Ca2+ release. ALS-associated mutant CLCC1 increase steady-state [Cl-]ER and impair ER Ca2+ homeostasis. Phenotypic comparisons of multiple Clcc1 mutant alleles, including ALS-associated mutations, reveal a CLCC1 dosage-dependence in severity of disease phenotypes in vivo. Conditional knockout of Clcc1 cell-autonomously causes motor neuron loss and ER stress, misfolded protein accumulation, and characteristic ALS pathologies in the spinal cord. Thus, we argue that disruption of ER ion homeostasis maintained by CLCC1 underlies etiology of neurodegenerative diseases.
Hallux Rigidus: Prevalence and Risk Factors
Authors: Senga Yoshiyuki , Nishimura Akinobu , Ito Naoya , Kitaura Yukie , Sudo Akihiro 
Published: May 2021

Abstract
Background: Hallux rigidus (HR) is a common degenerative arthritis of the first metatarsophalangeal joint. However, the epidemiology and risk factors of this pathology have yet to be clarified.Methods: This cohort study estimated the prevalence of and clarified risk factors for radiographic HR in individuals over 50 years old.Results: The prevalence of HR was 26.7% (161/604). Rates of grade 0, 1, 2, and 3 HR according to the Hattrup and Johnson classification were 73.3% (443/604), 16.4% (99/604), 8.0% (48/604), and 2.3% (14/604), respectively. Overall ratio of symptomatic HR was 8.1%. Univariate analysis revealed knee osteoarthritis (KOA), gout attack (GA), and hallux valgus (HV) as significantly associated with HR. The same factors were confirmed as independent risk factors for HR in multivariate analysis. All parameters were significantly associated with HR. Odds ratios of KOA, HV, and GA for HR were 1.73, 3.98, and 3.86, respectively. The presence or absence of KOA was significantly associated with severity of HR.Conclusion: Our study revealed the prevalence of HR in the elderly (≥50 years) was 26.7%, and KOA, HV, and GA were independent risk factors for HR. KOA was associated with severity of HR.
Efficacy of Cetuximab and 4-PBA Combination Therapy in Human Oral Squamous Cell Carcinoma Cells
Authors: Noguchi Akira , Nishida Takeshi , Hatta Hideki , Takagi Kohji , Kakiuchi Toshiko , Tanaka Shinichi , Minamisaka Takashi , Nakajima Takahiko , Imura Johji 
Published: May 2021

Abstract
Background: Cetuximab is a powerful anti-neoplastic agent that can inhibit cell growth in oral squamous cell carcinomas (OSCCs). Unfortunately, there are cases with unfavorable outcomes. Because few studies have focused on the combined effects of cetuximab and histone deacetylase (HDAC) inhibitors, we aimed to evaluate the antitumor effect of cetuximab in combination with HDAC inhibitors in human OSCC cell lines, and investigate the mechanism of apoptosis enhancing activity thereof.Methods: We used human OSCC cell lines treated with cetuximab (500 mg/ml) and several HDAC inhibitors. The WST assay and ApoToxGlo™ Triplex Assay determined cell survival. We employed the TdT-mediated dUTP-biotin nick end labeling method to detect apoptosis. We used western blotting to examine the histone acetylation status, ER stress markers, and epidermal growth factor receptor (EGFR) signaling pathways.Results: Cetuximab in combination with 4-phenyl butyric acid (4-PBA) remarkably decreases cell growth in vitro. In addition, the combined treatment resulted in increased EGFR mRNA expression, and it promoted the activation of ERK. The combination treatment induced apoptosis at a significantly higher frequency than did either agent alone.Conclusions: The combination of cetuximab and 4-PBA is more effective against human OSCC cells than either agent alone, suggesting a potential clinical applicability of combination treatment in OSCC therapies.
Natural selection drives genome-wide evolution via chance genetic associations
Authors: Gompert Zachariah , Feder Jeffrey , Nosil Patrik 
Published: May 2021

Abstract
Understanding selection's impact on the genome is a major theme in biology. Functionally-neutral genetic regions can be affected indirectly by natural selection, via their statistical association with genes under direct selection. The genomic extent of such indirect selection, particularly across loci not physically linked to those under direct selection, remains poorly understood, as does the time scale at which indirect selection occurs. Here we use field experiments and genomic data to show that widespread statistical associations with genes known to affect fitness in stick insects, deer mice and stickleback fish cause many genetic loci across the genome to be impacted indirectly by selection. We then show that statistical associations with other, unknown causal variants make aspects of evolution more predictable in stick insects. Thus, natural selection combines with chance genetic associations to affect genome-wide evolution across linked and unlinked loci and even in modest-sized populations.
Intravitreal Injection of Mitochondrial DNA Induces Cell Damage and Retinal Dysfunction in Rats
Authors: Guo Yue , Gan Dekang , Hu Fangyuan , Cheng Yun , Yu Jian , Lei Boya , Shu Qinmeng , Gu Ruiping , Xu Gezhi 
Published: May 2021

Abstract
Background: Retinal neurodegeneration is induced by a variety of environmental insults and stresses, but the exact mechanisms are unclear. In the present study, we explored the involvement of cytosolic mitochondrial DNA (mtDNA), resulting in the cGAS-STING dependent inflammatory response and apoptosis in retinal damage in vivo.Methods: Retinal injury was induced by white light or intravitreal injection of lipopolysaccharide (LPS). After light- or LPS-induced injury, the amount of cytosolic mtDNA in the retina was detected by PCR. The mtDNA was isolated and used to transfect retinas in vivo. WB and real-time PCR were used to evaluated the activation of cGAS-STING pathway and the levels of apoptosis-associated protein at different times after mtDNA stimulation. Retinal cell apoptosis rate was detected by TUNEL staining. Full-field electroretinography (ERG) was used to assess the retinal function.Results: Light injury and the intravitreal injection of LPS both caused the leakage of mtDNA into the cytoplasm in retinal tissue. After the transfection of mtDNA in vivo, the levels of cGAS, STING, and IFN-β mRNAs and the protein levels of STING, phosph-TBK1, phospho-IRF3, and IFN-β were upregulated. mtDNA stimulation also induced the phosphorylation of caspase 3 and caspase 9. BAX and BAK were increased at both the mRNA and protein levels. The release of cytochrome c from the mitochondria to the cytosol was increased after mtDNA stimulation. The wave amplitudes on ERG decreased and retinal cell apoptosis was detected after mtDNA stimulation.Conclusion: Cytosolic mtDNA triggers an inflammatory response. It also promotes apoptosis and the dysfunction of the retina.