bluuebunny/crossref_metadata_2025_split huggingface dataset:
Molecular, structural and biochemical characterization of a novel recombinant chlorophyllase from cyanobacterium Oscillatoria acuminata PCC 6304
Authors: Gu Sitian , Dai Xiaojun , Xu Zhengjun , Niu Qiwen , Jiang Jiang , Liu Yuanfa 
Published: January 2021

Abstract
Background

Chlorophyllase catalyzes the hydrolysis of chlorophyll and produces chlorophyllide and phytol. Cyanobacterial chlorophyllases are likely to be more highly heterologously expressed than plant chlorophyllases. A novel recombinant chlorophyllase from the cyanobacterium Oscillatoria acuminata PCC 6304 was successfully expressed in Escherichia coli BL21(DE3).

Results
The putative N-terminal 28-amino-acid signal peptide sequence of O. acuminata chlorophyllase (OaCLH) is essential for its activity, but may confer poor solubility on OaCLH. The C-terminal fusion of a 6 × His tag caused a partial loss of activity in recombinant OaCLH, but an N-terminal 6 × His tag did not destroy its activity. The optimal pH and temperature for recombinant OaCLH activity are 7.0 and 40 °C, respectively. Recombinant OaCLH has hydrolysis activities against chlorophyll a, chlorophyll b, bacteriochlorophyll a, and pheophytin a, but prefers chlorophyll b and chlorophyll a as substrates. The results of site-directed mutagenesis experiments indicated that the catalytic triad of OaCLH consists of Ser159, Asp226, and His258.

Conclusions
The high-level expression and broad substrate specificity of recombinant OaCLH make it suitable for genetically engineering and a promising biocatalyst for industrial production, with applications in vegetable oil refining and laundry detergents.
CDCA4 suppresses epithelial–mesenchymal transtion (EMT) and metastasis in Non-small cell lung cancer through modulating autophagy
Authors: Xu Chenxin , Cao Haixia , Sui Ying , Zhang Hui , Shi Chen , Wu Jianzhong , Ma Rong , Feng Jifeng 
Published: January 2021

Abstract
Background
Cell division cycle associated 4 (CDCA4) has been reported to be engaged into the progression of several cancers. The function of CDCA4 in Non-small cell lung cancer (NSCLC) was unknown. We aimed to explore the critical role of CDCA4 in NSCLC.

Methods
CDCA4 stably knocking down and overexpression cell lines were established and Western blotting assay was applied to measure relevant protein expression of Epithelial-Mesenchymal Transtion (EMT) and cell autophagy. Staining of acidic vacuoles, transmission electron microscopy and immunofluorescence staining were employed to detect autophagy. The ability of cells to migrate and invade were detected by Transwell migration and invasion assays. The interaction of CDCA4 with CARM1 was identified by immunoprecipitation and Western blotting analysis.

Results
In the present study, it was found that inhibition of CDCA4 induced EMT, migration and invasion of NSCLC cells while inhibiting autophagy of NSCLC cells. Meanwhile, overexpression of CDCA4 in NSCLC cells showed the opposite function. More importantly, the inhibition of autophagy could promote the EMT, migration and invasion of NSCLC cells, which should be impaired via the activation of autophagy. In addition, CDCA4-inhibited EMT, migration and invasion could be partially aggravated by autophagy activator, rapamycin, and reversed by autophagy inhibitor, 3-MA. Correspondingly, the application of rapamycin or 3-MA to CDCA4 knockdown cells showed the opposite effects. Further investigation suggested that CDCA4 could interact with coactivator associated arginine methyltransferase 1 (CARM1). Autophagy was induced while cell migration and invasion were inhibited in CARM1 knockdown cells. CDCA4 could suppress the protein expression CARM1 and knocking down of CARM1 could alter cell autophagy, migratory and invasive abilities regulated by CDCA4.

Conclusion
All data indicated that CDCA4 inhibited the EMT, migration and invasion of NSCLC via interacting with CARM1 to modulate autophagy.
Prognosis analysis of patients with pancreatic neuroendocrine tumors after surgical resection and the application of enucleation
Authors: Chen Junzhang , Yang Yongyu , Liu Yuanhua , Kan Heping 
Published: January 2021

Abstract
Objective
To investigate the prognostic factors of patients with pancreatic neuroendocrine tumor (pNETs) after surgical resection, and to analyze the value of enucleation for pNETs without distant metastasis that are well-differentiated (G1) and have a diameter ≤ 4 cm.

Methods
Data from pNET patients undergoing surgical resection between 2004 and 2017 were collected from the Surveillance, Epidemiology, and End Results (SEER) database. Kaplan–Meier analysis and log-rank testing were used for the survival comparisons. Adjusted HRs with 95% CIs were calculated using univariate and multivariate Cox regression models to estimate the prognostic factors. P < 0.05 was regarded as statistically significant.

Results
This study found that female, cases diagnosed after 2010, and pancreatic body/tail tumors were protective factors for good survival, while histological grade G3, a larger tumor size, distant metastasis, AJCC 8th stage III-IV and age over 60 were independent prognostic factors for a worse OS/CSS. For the pNETs that were well-differentiated (G1) and had a tumor diameter ≤ 4 cm, the type of surgery was an independent factor for the long-term prognosis of this group. Compared with pancreaticoduodenectomy and total pancreatectomy, patients who were accepted enucleation had better OS/CSS.

Conclusion
For pNETs patients undergoing surgical resection, sex, year of diagnosis, tumor location, pathological grade, tumor size, distant metastasis, race, and age were independent prognostic factors associated with the OS/CSS of patients. For pNETs patients with G1 and a tumor diameter less than 4 cm, if the tumor was located over 3 mm from the pancreatic duct, enucleation may be a wise choice.
Nodal histiocytic sarcoma with prominent eosinophilic infiltration: expression of eotaxin-2 on tumor cells
Authors: Ohe Rintaro , Kabasawa Takanobu , Utsunomiya Aya , Urano Yuka , Kitaoka Takumi , Suzuki Kazushi , Aung Naing Ye , Kawamura Ichiro , Tajima Katsushi , Ishiyama Tomoharu , Yamakawa Mitsunori 
Published: January 2021

Abstract
Background
Histiocytic sarcoma (HS) is a rare neoplasm showing morphological and immunophenotypic features of mature tissue histiocytes. We report a patient with nodal HS exhibiting prominent reactive eosinophilic infiltration.

Case presentation
A 68-year-old man presented with intermittent left lower abdominal pain and weight loss over 3 months. A computed tomography scan revealed multiple abdominal nodules. Open biopsy of the mesenteric tumors was performed for definitive diagnosis. Histologically, the tumor was comprised of a diffuse noncohesive proliferation of pleomorphic large cells, including multinucleated cells. Neoplastic cells were positive for histiocytic markers (CD68, CD163, and LIGHT) and PD-L1 but lacked markers of Langerhans cells, follicular dendritic cells, and epithelial cells. Frequent reactive inflammatory cells were intermingled in the background. Interestingly, prominent eosinophilic infiltration was also noted. Spindle neoplastic cells were prone to be present around areas with little to no eosinophilic infiltration and exhibiting fibrosis and lymphatic vessel proliferation. Conversely, polygonal neoplastic cells were prone to be present around areas with relatively large amounts of eosinophilic infiltration without fibrosis or lymphatic vessel proliferation. Immunohistochemically, the tumor cells and reactive eosinophils expressed eotaxin-2 and eotaxin-3, respectively.

Conclusion
We revealed that eotaxins induced the selective migration of eosinophils into tissues in this case. These eosinophils may affect the tumor remodeling and tumor biology characteristics of HS, such as fibrosis and lymphatic vessel proliferation.
Imaging biomarkers of contrast-enhanced computed tomography predict survival in oesophageal cancer after definitive concurrent chemoradiotherapy
Authors: Zeng Chengbing , Zhai Tiantian , Chen Jianzhou , Guo Longjia , Huang Baotian , Guo Hong , Liu Guozhi , Zhuang Tingting , Liu Weitong , Luo Ting , Wu Yanxuan , Peng Guobo , Li Derui , Chen Chuangzhen 
Published: January 2021

Abstract
Background
This study aimed to evaluate the predictive potential of contrast-enhanced computed tomography (CT)-based imaging biomarkers (IBMs) for the treatment outcomes of patients with oesophageal squamous cell carcinoma (OSCC) after definitive concurrent chemoradiotherapy (CCRT).

Methods
Altogether, 154 patients with OSCC who underwent definitive CCRT were included in this retrospective study. All patients were randomised to the training cohort (n = 99) or the validation cohort (n = 55). Pre-treatment contrast-enhanced CT scans were obtained for all patients and used for the extraction of IBMs. An IBM score, was constructed by using the least absolute shrinkage and selection operator with Cox regression analysis, which was equal to the log-partial hazard of the Cox model in the training cohort and tested in the validation cohort. IBM nomograms were built based on IBM scores for individualised survival estimation. Finally, a decision curve analysis was performed to estimate the clinical usefulness of the nomograms.

Results
Altogether, 96 IBMs were extracted from each contrast-enhanced CT scan. IBM scores were constructed from 11 CT-based IBMs for overall survival (OS) and 8 IBMs for progression-free survival (PFS), using the LASSO-Cox regression method in the training cohort. Multivariate analysis revealed that IBM score was an independent prognostic factor correlated with OS and PFS. In the training cohort, the C-indices of IBM scores were 0.734 (95% CI 0.664–0.804) and 0.658 (95% CI 0.587–0.729) for OS and PFS, respectively. In the validation cohort, C-indices were 0.672 (95% CI 0.578–0.766) and 0.666 (95% CI 0.574–0.758) for OS and PFS, respectively. Kaplan–Meier survival analysis showed a significant difference between risk subgroups in the training and validation cohorts. Decision curve analysis confirmed the clinical usefulness of the IBM score.

Conclusions
The IBM score based on pre-treatment contrast-enhanced CT could predict the OS and PFS for patients with OSCC after definitive CCRT. Further multicentre studies with larger sample sizes are warranted.
An ensemble learning approach for modeling the systems biology of drug-induced injury
Authors: Aguirre-Plans Joaquim , Piñero Janet , Souza Terezinha , Callegaro Giulia , Kunnen Steven J. , Sanz Ferran , Fernandez-Fuentes Narcis , Furlong Laura I. , Guney Emre , Oliva Baldo 
Published: January 2021

AbstractBackgroundDrug-induced liver injury (DILI) is an adverse reaction caused by the intake of drugs of common use that produces liver damage. The impact of DILI is estimated to affect around 20 in 100,000 inhabitants worldwide each year. Despite being one of the main causes of liver failure, the pathophysiology and mechanisms of DILI are poorly understood. In the present study, we developed an ensemble learning approach based on different features (CMap gene expression, chemical structures, drug targets) to predict drugs that might cause DILI and gain a better understanding of the mechanisms linked to the adverse reaction.ResultsWe searched for gene signatures in CMap gene expression data by using two approaches: phenotype-gene associations data from DisGeNET, and a non-parametric test comparing gene expression of DILI-Concern and No-DILI-Concern drugs (as per DILIrank definitions). The average accuracy of the classifiers in both approaches was 69%. We used chemical structures as features, obtaining an accuracy of 65%. The combination of both types of features produced an accuracy around 63%, but improved the independent hold-out test up to 67%. The use of drug-target associations as feature obtained the best accuracy (70%) in the independent hold-out test.ConclusionsWhen using CMap gene expression data, searching for a specific gene signature among the landmark genes improves the quality of the classifiers, but it is still limited by the intrinsic noise of the dataset. When using chemical structures as a feature, the structural diversity of the known DILI-causing drugs hampers the prediction, which is a similar problem as for the use of gene expression information. The combination of both features did not improve the quality of the classifiers but increased the robustness as shown on independent hold-out tests. The use of drug-target associations as feature improved the prediction, specially the specificity, and the results were comparable to previous research studies.
A comparison of different community models of antiretroviral therapy delivery with the standard of care among stable HIV+ patients: rationale and design of a non-inferiority cluster randomized trial, nested in the HPTN 071 (PopART) study
Authors:   on behalf of the HPTN 071 (PopART) Study Team, Limbada Mohammed , Bwalya Chiti , Macleod David , Floyd Sian , Schaap Ab , Situmbeko Vasty , Hayes Richard , Fidler Sarah , Ayles Helen 
Published: January 2021

Abstract
Background
Following the World Health Organization’s (WHO) 2015 guidelines recommending initiation of antiretroviral therapy (ART) irrespective of CD4 count for all people living with HIV (PLHIV), many countries in sub-Saharan Africa have adopted this strategy to reach epidemic control. As the number of PLHIV on ART rises, maintenance of viral suppression on ART for over 90% of PLHIV remains a challenge to government health systems in resource-limited high HIV burden settings. Non facility-based antiretroviral therapy (ART) delivery for stable HIV+ patients may increase sustainable ART coverage in resource-limited settings. Within the HPTN 071 (PopART) trial, two models, home-based delivery (HBD) or adherence clubs (AC), were offered to assess whether they achieved similar viral load suppression (VLS) to standard of care (SoC). In this paper, we describe the trial design and discuss the methodological issues and challenges.

Methods
A three-arm cluster randomized non-inferiority trial, nested in two urban HPTN 071 trial communities in Zambia, randomly allocated 104 zones to SoC (35), HBD (35), or AC (34). ART and adherence support were delivered 3-monthly at home (HBD), adherence clubs (AC), or clinic (SoC). Adult HIV+ patients defined as “stable” on ART were eligible for inclusion. The primary endpoint was the proportion of PLHIV with virological suppression (≤ 1000 copies HIV RNA/ml) at 12 months (± 3months) after study entry across all three arms. Viral load measurement was done at the routine government laboratories in accordance with national guidelines, annually. The study was powered to determine if either of the community-based interventions would yield a viral suppression rate drop compared to SoC of no more than 5% in its absolute value. Both community-based interventions were delivered by community HIV providers (CHiPs). An additional qualitative study using observations, interviews with PLHIV, and FGDs with community HIV providers was nested in this study to complement the quantitative data.

Discussion
This trial was designed to provide rigorous randomized evidence of safety and efficacy of non-facility-based delivery of ART for stable PLHIV in high-burden resource-limited settings. This trial will inform policy regarding best practices and what is needed to strengthen scale-up of differentiated models of ART delivery in resource-limited settings.

Trial registration
ClinicalTrials.gov NCT03025165. Registered on 19 January 2017
Bacteroides, butyric acid and t10,c12-CLA changes in colorectal adenomatous polyp patients
Authors: Chen Ciyan , Niu Min , Pan Junxi , Du Na , Liu Shumin , Li Huanqin , He Qiuyue , Mao Jian , Duan Yong , Du Yan 
Published: January 2021

Abstract
Background
Colorectal adenomatous polyps (CAPs) are considered precancerous lesions of colorectal cancer (CRC). The gut microbiota participates in the process of digestion and, in the process, produces metabolites, mainly short-chain fatty acids (SCFAs), secondary bile acids and conjugated linoleic acid (CLA). This study aimed to investigate the gut microbiota constituents and metabolites in the faeces of CAP patients to identify microbiota or metabolites that can be used as sensitive biological predictors and to provide a theoretical basis for the clinical treatment of CAPs.

Methods
16S rRNA sequence analysis was used to detect microbial changes in the faeces of CAP patients. qPCR analysis was used to evaluate the ability of the microbiota to produce metabolites, and the contents of metabolites in faeces were detected by ion chromatography and ultra-performance liquid chromatography-tandem mass spectrometry (UPLC-MS/MS).

Results
Based on the detection of the gut microbiota, patients with CAPs had increased abundances of Bacteroides and Citrobacter, and the abundances of Weissella and Lactobacillus were decreased. We also explored gene expression, and the abundance of butyrate-producing bacterial genes was significantly increased in the faeces of CAP patients, but those of secondary bile acid-producing and CLA-producing bacterial genes showed no differences in faecal samples. The acetic acid and butyric acid contents were increased in the faeces of the CAP group, and the healthy control group had higher t10,c12-CLA contents.

Conclusion
The gut microbiota analysis results, assessed in faeces, showed that Bacteroides and Citrobacter were positively correlated with CAPs, which indicated that changes in specific genera might be detrimental to intestinal health. In addition, t10,c12-CLA played an important role in protecting the intestine.
Ovarian borderline tumor presenting as ovarian torsion in a 17-year-old patient: a case report
Authors: Vicente Ana Patrícia , Gomes Andrea Sousa , Jokubkiene Ligita , Sladkevicius Povilas 
Published: January 2021

Abstract
Background
Ovarian torsion is a gynecological surgical emergency whose diagnosis remains a challenge. Torsion occurs most frequently in women of reproductive age. It is usually associated with the presence of benign masses in the ovary, as malignant tumors are less frequent and less prone to undergo torsion.

Case presentation
We report the case of a 17-year-old Caucasian patient who presented to the emergency department with lower abdominal pain. Ultrasonography evaluation revealed a unilateral ovarian lesion, 11.2 cm, with features suspicious for malignancy and torsion. The patient was referred for surgical torsion treatment and underwent unilateral salpingo-oophorectomy. The pathology report confirmed a serous borderline ovarian tumor with torsion.

Conclusions
Malignant ovarian torsion in pediatric age groups is rare. Ultrasound examination should be recognized as a powerful tool for diagnosis and management, especially when performed by an experienced ultrasonographer.
Community engagement in public health: a bibliometric mapping of global research
Authors: Yuan Ming , Lin Han , Wu Hengqin , Yu Mingchuan , Tu Juan , Lü Yong 
Published: January 2021

Abstract
Background
Community engagement (CE) has been regarded as a critical element of successful health programs to achieve “the health for all” goals. Numerous studies have shown that it plays a significant role in reducing inequalities, improving social justice, enhancing benefits, and sharing responsibility towards public health. Despite this, the extant literature of community engagement in public health (CEPH) has topic-focused boundaries and is scattered across disciplinary. Large-scale studies are needed to systematically identify current status, hotspots, knowledge structure, dynamic trends, and future developments in this field.

Methods
The bibliometric techniques were applied in the analysis of publications on CEPH in Web of Science Core Collection from Thomson Reuters. One thousand one hundred two papers out of 70.8 million publications over the period of 1980 to 2020 and their 15,116 references were retrieved as the sample set. First, basic characteristics of publications, including distributions of geography, journals and categories, productive authors and frequently cited articles, etc. were obtained. Then, four bibliometric methods, i.e. social network analysis, co-citation analysis, co-occurrence clustering, and burst detection, were further conducted to sketch the contours of the structure and evolution of CEPH.

Results
Between Jan 1, 1980, and Apr 25, 2020, CEPH has attracted a sharp increase in interest all over the world. Total 117 countries or regions have participated in the field of CEPH and the contributions are geographically and institutionally distinct. The United States is the key region performing such research, which accounts for more than half of the total number of publications. Developing countries, such as South Africa, India, Brazil and China also contributed a lot. The advancements of CEPH are marked by historically momentous public health events and evolved from macroscopic strategies to mesoscopic and microscopic actions. Based on keyword clustering and co-citation clustering, we propose a 4O (i.e. orientation, object, operation, and outcome) framework of CEPH to facilitate a better understanding of the current global achievements and an elaborate structuring of developments in the future.

Conclusion
This study draws an outline of the global review on the contemporary and cross-disciplinary research of CEPH which might present an opportunity to take stock and understand the march of knowledge as well as the logical venation underlying research activities which are fundamental to inform policy making.