bluuebunny/crossref_metadata_2025_split huggingface dataset:
Inducing secondary metabolite production of Aspergillus sydowii through microbial co-culture with Bacillus subtilis
Authors: Sun Yu , Liu Wen-Cai , Shi Xuan , Zheng Hai-Zhou , Zheng Zhi-Hui , Lu Xin-Hua , Xing Yan , Ji Kai , Liu Mei , Dong Yue-Sheng 
Published: February 2021

Abstract
Background
The co-culture strategy which mimics natural ecology by constructing an artificial microbial community is a useful tool to activate the biosynthetic gene clusters to generate new metabolites. However, the conventional method to study the co-culture is to isolate and purify compounds separated by HPLC, which is inefficient and time-consuming. Furthermore, the overall changes in the metabolite profile cannot be well characterized.

Results
A new approach which integrates computational programs, MS-DIAL, MS-FINDER and web-based tools including GNPS and MetaboAnalyst, was developed to analyze and identify the metabolites of the co-culture of Aspergillus sydowii and Bacillus subtilis. A total of 25 newly biosynthesized metabolites were detected only in co-culture. The structures of the newly synthesized metabolites were elucidated, four of which were identified as novel compounds by the new approach. The accuracy of the new approach was confirmed by purification and NMR data analysis of 7 newly biosynthesized metabolites. The bioassay of newly synthesized metabolites showed that four of the compounds exhibited different degrees of PTP1b inhibitory activity, and compound N2 had the strongest inhibition activity with an IC50 value of 7.967 μM.

Conclusions
Co-culture led to global changes of the metabolite profile and is an effective way to induce the biosynthesis of novel natural products. The new approach in this study is one of the effective and relatively accurate methods to characterize the changes of metabolite profiles and to identify novel compounds in co-culture systems.
Identification and development of a novel invasion-related gene signature for prognosis prediction in colon adenocarcinoma
Authors: Liu Jiahua , Jiang Chunhui , Xu Chunjie , Wang Dongyang , Shen Yuguang , Liu Ye , Gu Lei 
Published: February 2021

AbstractThe overall survival of metastatic colon adenocarcinoma (COAD) remains poor, so it is important to explore the mechanisms of metastasis and invasion. This study aimed to identify invasion-related genetic markers for prognosis prediction in patients with COAD. Three molecular subtypes (C1, C2, and C3) were obtained based on 97 metastasis-related genes in 365 COAD samples from The Cancer Genome Atlas (TCGA). A total of 983 differentially expressed genes (DEGs) were identified among the different subtypes by using the limma package. A 6-gene signature (ITLN1, HOXD9, TSPAN11, GPRC5B, TIMP1, and CXCL13) was constructed via Lasso-Cox analysis. The signature showed strong robustness and could be used in the training, testing, and external validation (GSE17537) cohorts with stable predictive efficiency. Compared with other published signatures, our model showed better performance in predicting outcomes. Pan-cancer expression analysis results showed that ITLN1, TSPAN11, CXCL13, and GPRC5B were downregulated and TIMP1 was upregulated in most tumor samples, including COAD, which was consistent with the results of the TCGA and GEO cohorts. Western blot analysis and immunohistochemistry were performed to validate protein expression. Tumor immune infiltration analysis results showed that TSPAN11, GPRC5B, TIMP1, and CXCL13 protein levels were significantly positively correlated with CD4+ T cells, macrophages, neutrophils, and dendritic cells. Further, the TIMP1 and CXCL13 proteins were significantly related to the tumor immune infiltration of CD8+ T cells. We recommend using our signature as a molecular prognostic classifier to assess the prognostic risk of patients with COAD.
MSN, MWCNT and ZnO nanoparticle-induced CHO-K1 cell polarisation is linked to cytoskeleton ablation
Authors: Yadav Karmveer , Ali Syed Azmal , Mohanty Ashok Kumar , Muthusamy Eshwarmoorthy , Subaharan Kesavan , Kaul Gautam 
Published: February 2021

Abstract
Background
The cellular response to nanoparticles (NPs) for the mechanical clue and biochemical changes are unexplored. Here, we provide the comprehensive analysis of the Chinese Hamster Ovary (CHO-K1) cell line to study cell behaviour following the exposure of mesoporous silica nanoparticle (MSN), multiwall carbon nanotubes (MWCNTs), and zinc oxide (ZnO) NPs.

Results
Through the high-throughput proteomic study, we observed that the effect of NPs is alone not restricted to cell viability but also on cell polarisation. In the case of MSN, no drastic changes were observed in cellular morphology, but it upregulated chaperons that might prevent protein aggregation. However, MWCNT showed elongated cell appearance with numerous cytoplasmic vacuoles, and induce lamellipodia formation through actin polymerisation. The cytoskeleton remodelling was accompanied by the increased expression of Dlc-1, cofilin and Rac1 proteins. While ZnO NPs resulted in the rounded cell morphology along with nuclear abnormalities. The proteome analysis revealed that UBXN11 control cell roundness and DOCK3 leads to actin stress fibre formation and finally, loss of cell adhesion. It enhances the expression of catastrophic DNA damage and apoptotic proteins, which was unrecoverable even after 72 h, as confirmed by the colony formation assay. All three NPs trigger over-expression of the endocytic pathway, ubiquitination, and proteasomal complex proteins. The data indicate that ZnO and MSN entered into the cells through clathrin-mediated pathways; whereas, MWCNT invades through ER-mediated phagocytosis.

Conclusions
Based on the incubation and concentration of NPs, our work provides evidence for the activation of Rac-Rho signalling pathway to alter cytoskeleton dynamics. Our results assist as a sensitive early molecular readout for nanosafety assessment.
Novel fusion peptide‐mediated siRNA delivery using self‐assembled nanocomplex
Authors: Ryu Yeong Chae , Kim Kyung Ah , Kim Byoung Choul , Wang Hui-Min David , Hwang Byeong Hee 
Published: February 2021

Abstract
Background
Gene silencing using siRNA can be a new potent strategy to treat many incurable diseases at the genetic level, including cancer and viral infections. Treatments using siRNA essentially requires an efficient and safe method of delivering siRNA into cells while maintaining its stability. Thus, we designed novel synergistic fusion peptides, i.e., SPACE and oligoarginine.

Results
Among the novel fusion peptides and siRNAs, nanocomplexes have enhanced cellular uptake and gene silencing effect in vitro and improved retention and gene silencing effects of siRNAs in vivo. Oligoarginine could attract siRNAs electrostatically to form stable and self-assembled nanocomplexes, and the SPACE peptide could interact with the cellular membrane via hydrogen bonding. Therefore, nanocomplexes using fusion peptides showed improved and evident cellular uptake and gene silencing of glyceraldehyde 3-phosphate dehydrogenase (GAPDH) via the lipid raft-mediated endocytosis pathway, especially to the HDFn cells of the skin, and all of the fusion peptides were biocompatible. Also, intratumorally injected nanocomplexes had increased retention time of siRNAs at the site of the tumor. Finally, nanocomplexes demonstrated significant in vivo gene silencing effect without overt tissue damage and immune cell infiltration.

Conclusions
The new nanocomplex strategy could become a safe and efficient platform for the delivery of siRNAs into cells and tissues to treat various target diseases through gene silencing.
MDAKRLS: Predicting human microbe-disease association based on Kronecker regularized least squares and similarities
Authors: Xu Da , Xu Hanxiao , Zhang Yusen , Wang Mingyi , Chen Wei , Gao Rui 
Published: February 2021

AbstractBackgroundMicrobes are closely related to human health and diseases. Identification of disease-related microbes is of great significance for revealing the pathological mechanism of human diseases and understanding the interaction mechanisms between microbes and humans, which is also useful for the prevention, diagnosis and treatment of human diseases. Considering the known disease-related microbes are still insufficient, it is necessary to develop effective computational methods and reduce the time and cost of biological experiments.MethodsIn this work, we developed a novel computational method called MDAKRLS to discover potential microbe-disease associations (MDAs) based on the Kronecker regularized least squares. Specifically, we introduced the Hamming interaction profile similarity to measure the similarities of microbes and diseases besides Gaussian interaction profile kernel similarity. In addition, we introduced the Kronecker product to construct two kinds of Kronecker similarities between microbe-disease pairs. Then, we designed the Kronecker regularized least squares with different Kronecker similarities to obtain prediction scores, respectively, and calculated the final prediction scores by integrating the contributions of different similarities.ResultsThe AUCs value of global leave-one-out cross-validation and 5-fold cross-validation achieved by MDAKRLS were 0.9327 and 0.9023 ± 0.0015, which were significantly higher than five state-of-the-art methods used for comparison. Comparison results demonstrate that MDAKRLS has faster computing speed under two kinds of frameworks. In addition, case studies of inflammatory bowel disease (IBD) and asthma further showed 19 (IBD), 19 (asthma) of the top 20 prediction disease-related microbes could be verified by previously published biological or medical literature.ConclusionsAll the evaluation results adequately demonstrated that MDAKRLS has an effective and reliable prediction performance. It may be a useful tool to seek disease-related new microbes and help biomedical researchers to carry out follow-up studies.
Laparoscopic repair of hepatic herniation through a ventral incisional hernia: a case report
Authors: Misumi Toshihiro , Nishihara Masahiro , Sugino Keizo , Kawasaki Yukari 
Published: February 2021

Abstract
Background
Ventral incisional hernia is a common problem after abdominal surgery. Most patients with these hernias present with greater omentum and gastrointestinal prolapse. However, hepatic herniation through a ventral incisional hernia is a rare phenomenon that has been seldom reported in the literature. We report the case of a ventral incisional hernia with hepatic herniation treated with laparoscopic repair.

Case presentation
A 68-year-old Japanese women with a history of myocardial resection for hypertrophic cardiomyopathy 1 year earlier was admitted to our hospital with symptoms of vomiting and epigastric pain. Physical examination showed a 4-cm epigastric mass. Abdominal computed tomography revealed left hepatic lobe herniation through the lower edge of a mid-sternal incision. We diagnosed the patient with a ventral incisional hernia with hepatic herniation. The patient underwent laparoscopic hernia repair. During an 18-month follow-up, no recurrence or symptoms have been observed.

Conclusions
To the best of our knowledge, this is the first case report of laparoscopic repair of ventral incisional hernias with hepatic herniation. Laparoscopic repair was useful and suitable for this rare herniation due to its minimally invasive nature and ability to achieve sufficient visibility of the surgical field. Laparoscopic repair could be a potential treatment option for elective surgery for this disease, which is often treated conservatively.
UL28 and UL33 homologs of Marek’s disease virus terminase complex involved in the regulation of cleavage and packaging of viral DNA are indispensable for replication in cultured cells
Authors: Sun Aijun , Yang Shuaikang , Luo Jun , Teng Man , Xu Yijie , Wang Rui , Zhu Xiaojing , Zheng Luping , Wu Yanan , Yao Yongxiu , Nair Venugopal , Zhang Gaiping , Zhuang Guoqing 
Published: February 2021

AbstractProcessing and packaging of herpesvirus genomic DNA is regulated by a packaging-associated terminase complex comprising of viral proteins pUL15, pUL28 and pUL33. Marek’s disease virus (MDV) homologs UL28 and UL33 showed conserved functional features with high sequence identity with the corresponding Herpes simplex virus 1 (HSV-1) homologs. As part of the investigations into the role of the UL28 and UL33 homologs of oncogenic MDV for DNA packaging and replication in cultured cells, we generated MDV mutant clones deficient in UL28 or UL33 of full-length MDV genomes. Transfection of UL28- or UL33-deleted BAC DNA into chicken embryo fibroblast (CEF) did not result either in the production of visible virus plaques, or detectable single cell infection after passaging onto fresh CEF cells. However, typical MDV plaques were detectable in CEF transfected with the DNA of revertant mutants where the deleted genes were precisely reinserted. Moreover, the replication defect of the UL28-deficient mutant was completely restored when fragment encoding the fullUL28gene was co-transfected into CEF cells. Viruses recovered from the revertant construct, as well as by theUL28co-transfection, showed replication ability comparable with parental virus. Furthermore, the transmission electron microscopy study indicated that immature capsids were assembled without the UL28 expression, but with the loss of infectivity. Importantly, predicted three-dimensional structures of UL28 between MDV and HSV-1 suggests conserved function in virus replication. For the first time, these results revealed that both UL28 and UL33 are essential for MDV replication through regulating DNA cleavage and packaging.
A Branch-and-Bound Algorithm for Building Optimal Data Gathering Tree in Wireless Sensor Networks
Authors: Zhu Xiaojun , Tang Shaojie 
Published: February 2021

In this paper, we consider the maximum lifetime data gathering tree (MLDT) problem in sensor networks. A data gathering tree is a spanning tree rooted at a specified sink so that every node can send its messages to the sink along the tree. The lifetime of a tree is defined as the minimum lifetime among nodes where each node’s lifetime is determined by its initial energy and transmission load. The MLDT problem is NP-hard, and the state-of-the-art solution formulates a decision version of the problem as an integer linear program (ILP) and then solves it by conducting binary search over all possible lifetimes. In this paper, we first give an ILP for the optimization problem rather than its decision version, and then show that using ILP solvers to solve these programs could be highly inefficient. We then propose a branch-and-bound algorithm that incorporates two novel features. First, the bounding method takes into account integer flows, and contains a new set of constraints. Second, a special set of edges are deleted to reduce the number of subproblems generated by the branching process. Numerical simulations on randomly generated networks show that the proposed algorithm outperforms existing algorithms in terms of the number of solved problem instances in a fixed amount of time. Summary of Contribution: We study the maximum lifetime data gathering tree (MLDT) problem in the context of wireless sensor network. MLDT is a fundamental problem in both computer science and operations research. Since sensor nodes are often resource limited, the data gathering tree must be carefully constructed to prolong the network lifetime. In this paper, we first give an integer linear program for the optimization problem rather than its decision version, and then show that using ILP solvers to solve these programs could be highly inefficient. We then propose a branch and bound algorithm that incorporates two novel features.
Efficacy and safety of a porcine peritoneum-derived matrix in diabetic foot ulcer treatment: a pilot study
Authors: Al-Jalodi Omar , Sabo Matthew , Patel Keyur , Bullock Neal , Serena Laura , Breisinger Kristy , Serena Thomas E 
Published: February 2021

Objective: A third of people with diabetes will develop a foot ulcer during their lifetime. The absence of pain secondary to neuropathy often leads to a delay in diagnosis and treatment. Diabetic foot ulcer (DFU) complications, such as infection and amputation, increase mortality and strain the financial resources of health systems across the world. Cellular and/or tissue products (CTPs) have played an important role in the closure of DFUs. Investigators continue to search for new CTPs that facilitate healing. The aim of this study was to assess the efficacy and safety of a porcine peritoneum-derived matrix in DFU treatment. Method: Patients with longstanding DFUs participated in this institutional review board-approved, multicentre, prospective pilot study evaluating the time to healing over 12 weeks. In addition to weekly assessments for wound size, investigators analysed bacterial burden using the MolecuLight procedure (MLiX) and bacterial protease (BPA) testing. Participants received a weekly application of Meso Wound Matrix Scaffold (MWM), a lyophilised porcine peritoneum-derived matrix (DSM Biomedical Inc., Exton, PA, US) for up to eight weeks. Descriptive statistics were chosen for this analysis. Results: A total of 12 male patients and three female patients with an average age of 57 years were enrolled over a two-month period. The average wound duration was 30 weeks. Due to unrelated health issues, four participants were withdrawn. For the study endpoint of complete wound closure at 12 weeks, six (55%) of the remaining 11 patients achieved complete closure, and four (36%) patients healed during the 8-week treatment period. The average number of CTP applications was six. Patients who healed all had negative BPA by nine weeks and no fluorescence on MLiX, indicating low bacterial load. Conclusion: This small pilot study indicates that patients with longstanding DFUs may respond to a porcine peritoneal-derived CTP. In this study, the CTP appears to have inhibited bacterial growth in the wound; however, further research is needed.
Impact of seven years of mass drug administration and recrudescence of Schistosoma haematobium infections after one year of treatment gap in Zanzibar: Repeated cross-sectional studies
Authors: Trippler Lydia , Ame Shaali Makame , Hattendorf Jan , Juma Saleh , Abubakar Salum , Ali Said Mohammed , Kabole Fatma , Rollinson David , Knopp Stefanie 
Published: February 2021

Background
Considerable progress towards the elimination of urogenital schistosomiasis was made by the Zanzibar Elimination of Schistosomiasis Transmission project from 2012 till 2016, when biannual praziquantel mass drug administration (MDA) alone or with additional snail control or behaviour change interventions were implemented. Annual MDA was continued in 2017 and 2018, but not in 2019, imposing a 16-month treatment gap. We monitored the Schistosoma haematobium prevalence from 2012 till 2020 and assessed recrudescence patterns with focus on 2020.

Methodology
Repeated cross-sectional surveys were conducted from 2011/12 till 2020 in 90 communities and 90 schools in Zanzibar. Annually, around 4,500 adults and up to 20,000 schoolchildren were surveyed. The S. haematobium prevalence was detected by urine filtration and reagent strips. In 2020, risk factors for infection were investigated using generalized estimated equation models.

Principal findings
In adults, the apparent S. haematobium prevalence was 3.9% in 2011 and 0.4% in 2020. In schoolchildren, the prevalence decreased from 6.6% in 2012 to 1.2% in 2019 with vicissitudes over the years. Prominent recrudescence of infection from 2.8% in 2019 to 9.1% (+225%) in 2020 was observed in 29 schools with historically moderate prevalences (≥10%). Compared with 2019, reinfection in 2020 was particularly striking in boys aged 9–16 years. Being male was a risk factor for infection in 2020 (adults: odds ratio (OR): 6.24, 95% confidence interval (95% CI): 1.96–19.60; schoolchildren: OR: 2.06, 95% CI: 1.52–2.78). Living near to a natural freshwater body significantly increased the odds of infection in adults (OR: 2.90, CI: 1.12–7.54).

Conclusions/Significance
After 11 rounds of MDA over 7 years and a 16-month treatment gap, the urogenital schistosomiasis prevalence considerably rebounded in hotspot areas. Future elimination efforts in Zanzibar should focus on re-intensifying MDA plus additional interventions in hotspot areas. In low-prevalence areas, the strategy might be adapted from MDA to targeted surveillance-response.
Total plaque score helps to determine follow-up strategy for carotid artery stenosis progression in head and neck cancer patients after radiation therapy
Authors: Liu Chi-Hung , Chang Joseph Tung-Chieh , Lee Tsong-Hai , Chang Pi-Yueh , Chang Chien-Hung , Wu Hsiu-Chuan , Chang Ting-Yu , Huang Kuo-Lun , Lin Chien-Yu , Fan Kang-Hsing , Chu Chan-Lin , Chang Yeu-Jhy 
Published: February 2021

Background
To identify predictors of carotid artery stenosis (CAS) progression in head and neck cancer (HNC) patients after radiation therapy (RT).

Methods
We included 217 stroke-naïve HNC patients with mild carotid artery stenosis after RT in our hospital. These patients underwent annual carotid duplex ultrasound (CDU) studies to monitor CAS progression. CAS progression was defined as the presence of ≥50% stenosis of the internal/common carotid artery on follow-up CDU. We recorded total plaque score (TPS) and determined the cut-off TPS to predict CAS progression. We categorized patients into high (HP) and low plaque (LP) score groups based on their TPS at enrolment. We analyzed the cumulative events of CAS progression in the two groups.

Results
The TPS of the CDU study at enrolment was a significant predictor for CAS progression (adjusted odds ratio [aOR] = 1.69, p = 0.002). The cut-off TPS was 7 (area under the curve: 0.800), and a TPS ≥ 7 strongly predicted upcoming CAS progression (aOR = 41.106, p = 0.002). The HP group had a higher risk of CAS progression during follow-up (adjusted hazard ratio = 6.15; 95% confident interval: 2.29–16.53) in multivariable Cox analysis, and also a higher trend of upcoming ischemic stroke (HP vs. LP: 8.3% vs. 2.2%, p = 0.09).

Conclusions
HNC patients with a TPS ≥ 7 in any CDU study after RT are susceptible to CAS progression and should receive close monitoring within the following 2 years.