bluuebunny/crossref_metadata_2025_split huggingface dataset:
Identification of bacterial pathogens in cultured fish with a custom peptide database constructed by matrix-assisted laser desorption/ionization time-of-flight mass spectrometry (MALDI-TOF MS)
Authors: Piamsomboon Patharapol , Jaresitthikunchai Janthima , Hung Tran Quang , Roytrakul Sittiruk , Wongtavatchai Janenuj 
Published: February 2020

Abstract
Background
The majority of infectious diseases of cultured fish is caused by bacteria. Rapid identification of bacterial pathogens is necessary for immediate management. The present study developed a custom Main Spectra Profile (MSP) database and validate the method using matrix-assisted laser desorption/ionization time-of-flight mass spectrometry (MALDI-TOF MS) for rapid identification of fish bacterial pathogens. Streptococcus agalactiae, Streptococcus iniae, Aeromonas hydrophila, Aeromonas veronii, and Edwardsiella tarda obtained from diseased fish were used as representative bacterial pathogens in this study. Bacterial peptides were extracted to create a Main Spectra Profile (MSP), and the MSPs of each bacterial species was added into the MALDI Biotyper database. Fifteen additional isolates of each bacterial species were tested to validate the utilized technique.

Results
The MSPs of all field isolates were clearly distinguishable, and the MSPs of the same species were clustered together. The identification methodology was validated with 75 bacterial isolates. The reliability and specificity of the method were determined with MALDI Biotyper log score values and matching results with 16 s rDNA sequencing. The species identification using the public MALDI Biotyper library (Bruker MALDI Biotyper) showed unreliable results (log score < 2.000) with 42.67% matching result with the reference method. In contrast, accurate identification was obtained when using the custom-made database, giving log score > 2.115, and a 100% matching result.

Conclusion
This study demonstrates an effective identification of fish bacterial pathogens when a complete custom-made MSP database is applied. Further applications require a broad, well-established database to accommodate prudent identification of many fish bacterial pathogens by MALDI-TOF MS.
Heterologous caffeic acid biosynthesis in Escherichia coli is affected by choice of tyrosine ammonia lyase and redox partners for bacterial Cytochrome P450
Authors: Haslinger Kristina , Prather Kristala L. J. 
Published: February 2020

Abstract
Background
Caffeic acid is industrially recognized for its antioxidant activity and therefore its potential to be used as an anti-inflammatory, anticancer, antiviral, antidiabetic and antidepressive agent. It is traditionally isolated from lignified plant material under energy-intensive and harsh chemical extraction conditions. However, over the last decade bottom-up biosynthesis approaches in microbial cell factories have been established, that have the potential to allow for a more tailored and sustainable production. One of these approaches has been implemented in Escherichia coli and only requires a two-step conversion of supplemented l-tyrosine by the actions of a tyrosine ammonia lyase and a bacterial Cytochrome P450 monooxygenase. Although the feeding of intermediates demonstrated the great potential of this combination of heterologous enzymes compared to others, no de novo synthesis of caffeic acid from glucose has been achieved utilizing the bacterial Cytochrome P450 thus far.

Results
The herein described work aimed at improving the efficiency of this two-step conversion in order to establish de novo caffeic acid formation from glucose. We implemented alternative tyrosine ammonia lyases that were reported to display superior substrate binding affinity and selectivity, and increased the efficiency of the Cytochrome P450 by altering the electron-donating redox system. With this strategy we were able to achieve final titers of more than 300 µM or 47 mg/L caffeic acid over 96 h in an otherwise wild type E. coli MG1655(DE3) strain with glucose as the only carbon source. We observed that the choice and gene dose of the redox system strongly influenced the Cytochrome P450 catalysis. In addition, we were successful in applying a tethering strategy that rendered even a virtually unproductive Cytochrome P450/redox system combination productive.

Conclusions
The caffeic acid titer achieved in this study is about 10% higher than titers reported for other heterologous caffeic acid pathways in wildtype E. coli without l-tyrosine supplementation. The tethering strategy applied to the Cytochrome P450 appears to be particularly useful for non-natural Cytochrome P450/redox partner combinations and could be useful for other recombinant pathways utilizing bacterial Cytochromes P450.
Asymptomatic malaria infection among pregnant women attending antenatal care in malaria endemic areas of North-Shoa, Ethiopia: a cross-sectional study
Authors: Feleke Daniel Getacher , Adamu Aderaw , Gebreweld Angesom , Tesfaye Melkam , Demisiss Wondmagegn , Molla Genet 
Published: February 2020

Abstract
Background
The effort to reduce the burden of malaria should target transmission in the community by accurate identification of asymptomatic infections. In malaria-endemic areas, asymptomatic malaria infection is still associated with complications. Malaria during pregnancy is characterized by anaemia and placental malaria, leading to low birth weight and perinatal morbidity and mortality. This study aimed to provide reliable data on the burden of asymptomatic malaria among pregnant women in malaria endemic areas of North-Shoa, Ethiopia.

Methods
Cross-sectional study was carried out to assess the prevalence and predictors of asymptomatic malaria in pregnant women from November 2018 to January 2019. Multistage sampling technique was employed to include 263 study participants. Data were analysed using SPSS version 20.0 statistical software. In all comparisons, p-values ≤ 0.05 was considered as statistically significant.

Results
The prevalence of asymptomatic malaria infection was 5.7% (15/263) and 3.4% (9/263) by using microscopy and RDTs, respectively. Plasmodium falciparum was a dominant species 9 (3.4%) and Plasmodium vivax accounted for 6 (2.3%) of Plasmodium infections as detected by microscopy. Multivariate analysis showed that ITN usage and haemoglobin level had a statistically significant association with Plasmodium infection after adjusting other possible factors. Compared to those who were using ITN always, the odds of Plasmodium infection was 18.16 times higher (95% CI 1.84–179.07) in pregnant women who were not using ITN, and 5.19 times higher (95% CI 0.55–49.21) in pregnant women who were using ITN sometimes. Asymptomatic malaria infected pregnant women were 3.78 times (95% CI 0.98–14.58) more likely to be anaemic compared to non-infected pregnant women.

Conclusion
The present study showed asymptomatic malaria is prevalent in pregnant women and it has statistically significance association with the haemoglobin level of pregnant women. This indicates pregnant women have to be screened for asymptomatic malaria to avoid health consequences of malaria infection during pregnancy for the mother and fetus.
miR-124 and miR-203 synergistically inactivate EMT pathway via coregulation of ZEB2 in clear cell renal cell carcinoma (ccRCC)
Authors: Chen Jiajia , Zhong Yuqing , Li Liangzhi 
Published: February 2020

AbstractBackgroundClear cell renal cell carcinoma (ccRCC) is one of the most aggressive urological malignancies. MicroRNAs (miRNAs) are post-transcriptional gene regulators in tumor pathophysiology. As miRNAs exert cooperative repressive effects on target genes, studying the miRNA synergism is important to elucidate the regulation mechanism of miRNAs.MethodsWe first created a miRNA-mRNA association network based on sequence complementarity and co-expression patterns of miRNA-targets. The synergism between miRNAs was then defined based on their expressional coherence and the concordance between target genes. The miRNA and mRNA expression were detected in RCC cell lines (786-O) using quantitative RT-PCR. Potential miRNA-target interaction was identified by Dual-Luciferase Reporter assay. Cell proliferation and migration were assessed by CCK-8 and transwell assay.ResultsA synergistic miRNA–miRNA interaction network of 28 miRNAs (52 miRNA pairs) with high coexpression level were constructed, among which miR-124 and miR-203 were identified as most tightly connected. ZEB2 expression is inversely correlated with miR-124 and miR-203 and verified as direct miRNA target. Cotransfection of miR-124 and miR-203 into 786-O cell lines effectively attenuated ZEB2 level and normalized renal cancer cell proliferation and migration. The inhibitory effects were abolished by ZEB2 knockdown. Furthermore, pathway analysis suggested that miR-124 and miR-203 participated in activation of epithelial-to-mesenchymal transition (EMT) pathway via regulation of ZEB2.ConclusionsOur findings provided insights into the role of miRNA–miRNA collaboration as well as a novel therapeutic approach in ccRCC.
Development and validation of a novel immune-related prognostic model in hepatocellular carcinoma
Authors: Wang Zheng , Zhu Jie , Liu Yongjuan , Liu Changhong , Wang Wenqi , Chen Fengzhe , Ma Lixian 
Published: February 2020

Abstract
Background
Growing evidence has suggested that immune-related genes play crucial roles in the development and progression of hepatocellular carcinoma (HCC). Nevertheless, the utility of immune-related genes for evaluating the prognosis of HCC patients are still lacking. The study aimed to explore gene signatures and prognostic values of immune-related genes in HCC.

Methods
We comprehensively integrated gene expression data acquired from 374 HCC and 50 normal tissues in The Cancer Genome Atlas (TCGA). Differentially expressed genes (DEGs) analysis and univariate Cox regression analysis were performed to identify DEGs that related to overall survival. An immune prognostic model was constructed using the Lasso and multivariate Cox regression analyses. Furthermore, Cox regression analysis was applied to identify independent prognostic factors in HCC. The correlation analysis between immune-related signature and immune cells infiltration were also investigated. Finally, the signature was validated in an external independent dataset.

Results
A total of 329 differentially expressed immune‐related genes were detected. 64 immune‐related genes were identified to be markedly related to overall survival in HCC patients using univariate Cox regression analysis. Then we established a TF-mediated network for exploring the regulatory mechanisms of these genes. Lasso and multivariate Cox regression analyses were applied to construct the immune-based prognostic model, which consisted of nine immune‐related genes. Further analysis indicated that this immune-related prognostic model could be an independent prognostic indicator after adjusting to other clinical factors. The relationships between the risk score model and immune cell infiltration suggested that the nine-gene signature could reflect the status of tumor immune microenvironment. The prognostic value of this nine-gene prognostic model was further successfully validated in an independent database.

Conclusions
Together, our study screened potential prognostic immune-related genes and established a novel immune-based prognostic model of HCC, which not only provides new potential prognostic biomarkers and therapeutic targets, but also deepens our understanding of tumor immune microenvironment status and lays a theoretical foundation for immunotherapy.
JCPyV NCCR analysis in PML patients with different risk factors: exploring common rearrangements as essential changes for neuropathogenesis
Authors: Ciardi Maria Rosa , Zingaropoli Maria Antonella , Iannetta Marco , Prezioso Carla , Perri Valentina , Pasculli Patrizia , Lichtner Miriam , d’Ettorre Gabriella , Altieri Marta , Conte Antonella , Pietropaolo Valeria , Mastroianni Claudio Maria , Vullo Vincenzo 
Published: February 2020

Abstract
Background
During severe immunosuppression or treatment with specific biological drugs, human polyomavirus JC (JCPyV) may establish a lytic infection in oligodendrocytes, leading to progressive multifocal leukoencephalopathy (PML). Beyond AIDS, which represents the most common predisposing condition, several biological drugs have been associated to the development of PML, such as natalizumab, fingolimod and dimethyl fumarate, which have been showed to increase the risk of PML in the multiple sclerosis (MS) population. JCPyV non-coding control region (NCCR) can be found in two different forms: a virulent neurotropic pathogenic form and a latent non-pathogenic form. The neurotropic forms contain a rearranged NCCR and are typically found in the cerebrospinal fluid, brain or blood of PML patients.

Case presentation
We sequenced and critically examined JCPyV NCCR from isolates detected in the cerebrospinal fluid of four newly diagnosed progressive multifocal leukoencephalopathy patients: two HIV-positive and two HIV-negative multiple sclerosis patients. More complex NCCR rearrangements were observed in the two HIV-positive patients compared to the HIV-negative multiple sclerosis patients with PML.

Conclusions
The comparison of HIV-positive and HIV-negative MS patients with PML, allowed us to evidence the presence of a common pattern of JCPyV NCCR rearrangement, characterized by the deletion of the D-block, which could be one of the initial rearrangements of JCPyV NCCR needed for the development of PML.
Correction to: Timing of pubertal stages and breast cancer risk: the Breakthrough Generations Study
Authors: Bodicoat Danielle H. , Schoemaker Minouk J. , Jones Michael E. , McFadden Emily , Griffin James , Ashworth Alan , Swerdlow Anthony J. 
Published: February 2020

As a consequence of responding to colleagues who asked about the publication of the original article [1], the authors have determined that the data published in Table 4 of the paper are incorrect.
A randomized controlled trial protocol comparing the feeds of fresh versus frozen mother’s own milk for preterm infants in the NICU
Authors: Sun Huiqing , Cao Yun , Han Shuping , Cheng Rui , Liu Ling , Liu Jiangqin , Xia Shiwen , Zhang Jiajie , Li Zhankui , Cheng Xiuyong , Yang Chuanzhong , Pan Xinnian , Li Long , Ding Xin , Wang Rensheng , Wu Mingyuan , Li Xiaoying , Shi Liping , Xu Falin , Yu Fengqin , Pan Jiahua , Zhang Xiaolan , Li Li , Yang Jie , Li Mingxia , Yan Changhong , Zhou Qi , Lu Jiao , Wei Mou , Wang Laishuan , Yang Ling , Ye Xiang Y. , Unger Sharon , Kakulas Foteini , Lee Shoo K. 
Published: February 2020

AbstractBackgroundNecrotizing enterocolitis (NEC) is the leading cause of death among preterm infants born at < 30 weeks’ gestation. The incidence of NEC is reduced when infants are fed human milk. However, in many neonatal intensive care units (NICUs), it is standard practice to freeze and/or pasteurize human milk, which deactivates bioactive components that may offer additional protective benefits. Indeed, our pilot study showed that one feed of fresh mother’s own milk per day was safe, feasible, and can reduce morbidity in preterm infants. To further evaluate the benefits of fresh human milk in the NICU, a randomized controlled trial is needed.MethodsOur prospective multicenter, double-blinded, randomized, controlled trial will include infants born at < 30 weeks’ gestation and admitted to one of 29 tertiary NICUs in China. Infants in the intervention (fresh human milk) group (n = 1549) will receive at least two feeds of fresh human milk (i.e., within 4 h of expression) per day from the time of enrollment until 32 weeks’ corrected age or discharge to home. Infants in the control group (n = 1549) will receive previously frozen human milk following the current standard protocols. Following informed consent, enrolled infants will be randomly allocated to the control or fresh human milk groups. The primary outcome is the composite outcome mortality or NEC ≥ stage 2 at 32 weeks’ corrected age, and the secondary outcomes are mortality, NEC ≥ stage 2, NEC needing surgery, late-onset sepsis, retinopathy of prematurity (ROP), bronchopulmonary dysplasia (BPD), weight gain, change in weight, increase in length, increase in head circumference, time to full enteral feeds, and finally, the number and type of critical incident reports, including feeding errors.DiscussionOur double-blinded, randomized, controlled trial aims to examine whether fresh human milk can improve infant outcomes. The results of this study will impact both Chinese and international medical practice and feeding policy for preterm infants. In addition, data from our study will inform changes in health policy in NICUs across China, such that mothers are encouraged to enter the NICU and express fresh milk for their infants.Trial registrationChinese Clinical Trial Registry; #ChiCTR1900020577; registered January 1, 2019;http://www.chictr.org.cn/showprojen.aspx?proj=34276
Evaluation of the effects of pycnogenol (French maritime pine bark extract) supplementation on inflammatory biomarkers and nutritional and clinical status in traumatic brain injury patients in an intensive care unit: A randomized clinical trial protocol
Authors: Malekahmadi Mahsa , Moradi Moghaddam Omid , Islam Sheikh Mohammed Shariful , Tanha Kiarash , Nematy Mohsen , Pahlavani Naseh , Firouzi Safieh , Zali Mohammad Reza , Norouzy Abdolreza 
Published: February 2020

Abstract
Background
Traumatic brain injury (TBI) is one of the major health and socioeconomic problems in the world. Immune-enhancing enteral formula has been proven to significantly reduce infection rate in TBI patients. One of the ingredients that can be used in immunonutrition formulas to reduce inflammation and oxidative stress is pycnogenol.

Objective
The objective of this work is to survey the effect of pycnogenol on the clinical, nutritional, and inflammatory status of TBI patients.

Methods
This is a double-blind, randomized controlled trial. Block randomization will be used. An intervention group will receive pycnogenol supplementation of 150 mg for 10 days and a control group will receive a placebo for the same duration. Inflammatory status (IL-6, IL- 1β, C-reactive protein) and oxidative stress status (malondialdehyde, total antioxidant capacity), at the baseline, at the 5th day, and at the end of the study (10th day) will be measured. Clinical and nutritional status will be assessed three times during the intervention. The Sequential Organ Failure Assessment (SOFA) questionnaire for assessment of organ failure will be filled out every other day. The mortality rate will be calculated within 28 days of the start of the intervention. Weight, body mass index, and body composition will be measured. All analyses will be conducted by an initially assigned study arm in an intention-to-treat analysis.

Discussion
We expect that supplementation of 150 mg pycnogenol for 10 days will improve clinical and nutritional status and reduce the inflammation and oxidative stress of the TBI patients.

Trial registration
This trial is registered at clinicaltrials.gov (ref: NCT03777683) at 12/13/2018.
Improving the accuracy and efficacy of diagnosing polycystic ovary syndrome by integrating metabolomics with clinical characteristics: study protocol for a randomized controlled trial
Authors: Ni Cheng-Ming , Huang Wen-Long , Jiang Yan-Min , Xu Juan , Duan Ru , Zhu Yun-Long , Zhu Xu-Ping , Fan Xue-Mei , Luo Guo-An , Wang Yi-Ming , Li Yan-Yu , He Qing , Xu Lan 
Published: February 2020

Abstract
Background
Polycystic ovary syndrome (PCOS) is a complex endocrine syndrome with poorly understood mechanisms. To provide patients with PCOS with individualized therapy, it is critical to precisely diagnose the phenotypes of the disease. However, the criteria for diagnosing the different phenotypes are mostly based on symptoms, physical examination and laboratory results. This study aims to compare the accuracy and efficacy of diagnosing PCOS by integrating metabolomic markers with common clinical characteristics.

Methods
This is a prospective, multicenter, analyst-blinded, randomized controlled trial. Participants will be grouped into (1) people without PCOS (healthy control group), (2) patients diagnosed with PCOS based on clinical indices (experimental group 1), and (3) patients diagnosed with PCOS based on metabolomic indices (experimental group 2). A total of 276 participants, including 60 healthy people and 216 patients with PCOS, will be recruited. The 216 patients with PCOS will be randomly assigned to the two experimental groups in a 1:1 ratio, and each group will receive a different 6-month treatment. The primary outcome for the experimental groups will be the effect of PCOS treatment.

Discussion
The results of this trial should help to determine whether using metabolomic indices is more accurate and effective than using clinical characteristics in diagnosing the phenotypes of PCOS. The results could provide a solid foundation for the accurate diagnosis of different PCOS subgroups and for future research on individualized PCOS therapy.

Trial registration
Chinese Clinical Trial Registry, ID: ChiCTR-INR-1800016346. Registered 26 May 2018.
Electroacupuncture for postoperative pain after nasal endoscopic surgery: study protocol for a pilot randomized controlled trial
Authors: Li Shanshan , Zhang Qing , Yin Xuan , Yue Hongyu , Zhang Wei , Lao Lixing , Zhang Zhangjin , Wu Huangan , Xu Shifen 
Published: February 2020

Abstract
Background
Postoperative pain is common after nasal endoscopic surgery. It interferes with the quality of sleep and delays postoperative recovery. Acupuncture is an effective tool for pain management. However, electroacupuncture specifically for the relief of postoperative pain after nasal endoscopic surgery has not yet been studied in a randomized controlled trial.

Methods/design
This randomized sham-controlled patient- and assessor-blind pilot trial has been designed to evaluate the efficacy and safety of electroacupuncture in managing postoperative pain following nasal endoscopic surgery to treat sinusitis due to nasal polyps. Altogether, 30 participants will be randomly allocated to an electroacupuncture or non-invasive sham control in a 1:1 ratio. Treatment will occur within 2 h before the operation, immediately after the operation upon arrival in the recovery ward, and once daily for 3 days. The primary outcome is the pain numerical rating scale, which will be analyzed using the area under the curve. The secondary outcome measures include heart rate and blood pressure after the operation, sleep quality during the hospital stay (actigraph), quality of recovery, and the 36-item short form health survey. This trial will use an intention-to-treat analysis.

Discussion
This pilot randomized controlled trial will explore the feasibility of the further clinical application of electroacupuncture for the management of postoperative pain. It will inform the design of a further full-scale trial.

Trial registration
Chinese Clinical Trial Registry, ChiCTR1900024183. Registered on 29 June 2019.