bluuebunny/crossref_metadata_2025_split huggingface dataset:
MetaLAFFA: a flexible, end-to-end, distributed computing-compatible metagenomic functional annotation pipeline
Authors: Eng Alexander , Verster Adrian J. , Borenstein Elhanan 
Published: October 2020

Abstract
Background
Microbial communities have become an important subject of research across multiple disciplines in recent years. These communities are often examined via shotgun metagenomic sequencing, a technology which can offer unique insights into the genomic content of a microbial community. Functional annotation of shotgun metagenomic data has become an increasingly popular method for identifying the aggregate functional capacities encoded by the community’s constituent microbes. Currently available metagenomic functional annotation pipelines, however, suffer from several shortcomings, including limited pipeline customization options, lack of standard raw sequence data pre-processing, and insufficient capabilities for integration with distributed computing systems.

Results
Here we introduce MetaLAFFA, a functional annotation pipeline designed to take unfiltered shotgun metagenomic data as input and generate functional profiles. MetaLAFFA is implemented as a Snakemake pipeline, which enables convenient integration with distributed computing clusters, allowing users to take full advantage of available computing resources. Default pipeline settings allow new users to run MetaLAFFA according to common practices while a Python module-based configuration system provides advanced users with a flexible interface for pipeline customization. MetaLAFFA also generates summary statistics for each step in the pipeline so that users can better understand pre-processing and annotation quality.

Conclusions
MetaLAFFA is a new end-to-end metagenomic functional annotation pipeline with distributed computing compatibility and flexible customization options. MetaLAFFA source code is available at https://github.com/borenstein-lab/MetaLAFFA and can be installed via Conda as described in the accompanying documentation.
De novo transcriptome assembly from the gonads of a scleractinian coral, Euphyllia ancora: molecular mechanisms underlying scleractinian gametogenesis
Authors: Chiu Yi-Ling , Shikina Shinya , Yoshioka Yuki , Shinzato Chuya , Chang Ching-Fong 
Published: October 2020

Abstract
Background
Sexual reproduction of scleractinians has captured the attention of researchers and the general public for decades. Although extensive ecological data has been acquired, underlying molecular and cellular mechanisms remain largely unknown. In this study, to better understand mechanisms underlying gametogenesis, we isolated ovaries and testes at different developmental phases from a gonochoric coral, Euphyllia ancora, and adopted a transcriptomic approach to reveal sex- and phase-specific gene expression profiles. In particular, we explored genes associated with oocyte development and maturation, spermiogenesis, sperm motility / capacitation, and fertilization.

Results
1.6 billion raw reads were obtained from 24 gonadal samples. De novo assembly of trimmed reads, and elimination of contigs derived from symbiotic dinoflagellates (Symbiodiniaceae) and other organisms yielded a reference E. ancora gonadal transcriptome of 35,802 contigs. Analysis of 4 developmental phases identified 2023 genes that were differentially expressed during oogenesis and 678 during spermatogenesis. In premature/mature ovaries, 631 genes were specifically upregulated, with 538 in mature testes. Upregulated genes included those involved in gametogenesis, gamete maturation, sperm motility / capacitation, and fertilization in other metazoans, including humans. Meanwhile, a large number of genes without homology to sequences in the SWISS-PROT database were also observed among upregulated genes in premature / mature ovaries and mature testes.

Conclusions
Our findings show that scleractinian gametogenesis shares many molecular characteristics with that of other metazoans, but it also possesses unique characteristics developed during cnidarian and/or scleractinian evolution. To the best of our knowledge, this study is the first to create a gonadal transcriptome assembly from any scleractinian. This study and associated datasets provide a foundation for future studies regarding gametogenesis and differences between male and female colonies from molecular and cellular perspectives. Furthermore, our transcriptome assembly will be a useful reference for future development of sex-specific and/or stage-specific germ cell markers that can be used in coral aquaculture and ecological studies.
Influence of inoculated gut bacteria on the development of Bactrocera dorsalis and on its susceptibility to the entomopathogenic fungus, Metarhizium anisopliae
Authors: Gichuhi Joseph , Khamis Fathiya , Van den Berg Johnnie , Mohamed Samira , Ekesi Sunday , Herren Jeremy K. 
Published: October 2020

AbstractBackgroundSymbiotic interactions between insects and bacteria have been associated with a vast variety of physiological, ecological and evolutionary consequences for the host. A wide range of bacterial communities have been found in association with the oriental fruit fly,Bactrocera dorsalis(Hendel) (Diptera: Tephritidae), an important pest of cultivated fruit in most regions of the world. We evaluated the diversity of gut bacteria inB. dorsalisspecimens from several populations in Kenya and investigated the roles of individual bacterial isolates in the development of axenic (germ-free)B. dorsalisfly lines and their responses to the entomopathogenic fungus,Metarhizium anisopliae.ResultsWe sequenced 16S rRNA to evaluate microbiomes and coupled this with bacterial culturing. Bacterial isolates were mono-associated with axenicB. dorsalisembryos. The shortest embryonic development period was recorded in flies with an intact gut microbiome while the longest period was recorded in axenic fly lines. Similarly, larval development was shortest in flies with an intact gut microbiome, in addition to flies inoculated withProvidencia alcalifaciens.AdultB. dorsalisflies emerging from embryos that had been mono-associated with a strain ofLactococcus lactishad decreased survival when challenged with a standard dosage ofM. anisopliaeICIPE69 conidia. However, there were no differences in survival between the germ-free lines and flies with an intact microbiome.ConclusionsThese findings will contribute to the selection of probiotics used in artificial diets forB. dorsalisrearing and the development of improved integrated pest management strategies based on entomopathogenic fungi.
Development of a clinical diagnostic tool to differentiate multiple myeloma from bone metastasis in patients with destructive bone lesions (MM-BM DDx)
Authors: Phinyo Phichayut , Maihom Titinat , Phanphaisarn Areerak , Kerdsinchai Pakorn , Rattarittamrong Ekarat , Patumanond Jayanton , Pruksakorn Dumnoensun 
Published: October 2020

Abstract
Background
Most patients with destructive bone lesions undergo a comprehensive diagnostic procedure to ensure that proper treatment decisions are pursued. For patients with multiple myeloma, this can lead to delays in diagnosis and treatment initiation. This study was conducted to develop a diagnostic rule that could serve as a tool for early identification of multiple myeloma and promote timely referral of patients to haematologists.

Methods
The clinical prediction rule was developed using a retrospective case-series of patients with multiple myeloma (MM) and those with bone metastasis (BM) at Chiang Mai University Hospital from 2012 to 2015. Multivariable fractional polynomial logistic regression was used to derive a diagnostic model to differentiate between MM and BM patients (MM-BM DDx).

Results
A total of 586 patients (136 MM patients and 450 BM patients) were included. Serum creatinine, serum globulin, and serum alkaline phosphatase were identified as significant indicators for the differentiation of MM and BM patients. The MM-BM DDx model showed excellent discriminative ability [AuROC of 0.90 (95%CI 0.86 to 0.93)] and good calibration.

Conclusions
This MM-BM DDx model could potentially allow for early myeloma diagnosis and improvement of overall prognosis. A prospective validation study is needed to confirm the accuracy of the MM-BM DDx model prior to its application in clinical practice.
The role of circulating microRNAs for the diagnosis of hepatitis B virus-associated hepatocellular carcinoma with low alpha-fetoprotein level: a systematic review and meta-analysis
Authors: Peng Cheng , Li Zhuonan , Xie Zishan , Wang Zhanpeng , Ye Yanshuo , Li Bo , Li Wei 
Published: October 2020

Abstract
Background
Alpha-fetoprotein (AFP) has been widely used for many years as a serum marker for hepatocellular carcinoma (HCC). However, AFP has been recognized as having poor sensitivity. More and more studies have concluded that circulating microRNAs (miRNAs) might be a promising biomarker that could complement AFP. However, the diagnostic ability of circulating miRNAs has varied among the studies. Therefore, we performed the present meta-analysis to appraise the diagnostic performance of circulating miRNAs as a biomarker for hepatitis B virus-associated HCC (HBV-HCC) patients with low AFP levels.

Methods
We performed a systematic review and meta-analysis of the published literature to assess the diagnostic accuracy of circulating miRNAs in differentiating HBV-HCC patients with low AFP levels from non-HCC controls.

Results
Circulating miRNAs showed promising potential in the diagnosis of HBV-HCC patients with low AFP levels. In the low-AFP HBV-HCC patients, the area under the curve (AUC) was 0.88 (95% confidence interval [CI]: 0.84–0.90). The pooled sensitivity and specificity were 0.84 (95% CI: 0.78–0.88) and 0.76 (95% CI: 0.69–0.83), respectively.

Conclusions
The detection of circulating miRNAs provides a valuable method for the diagnosis of HBV-HCC in patients with low AFP levels.
Distinct clinicopathological differences between early gastric cardiac and non-cardiac carcinomas: a single-center retrospective study of 329 radical resection cases
Authors: Wang Yaohui , Li Xiuqing , Gao Lili , Wang Chenxi , Zhang Yifen , Huang Qin 
Published: October 2020

Abstract
Background
Early gastric carcinoma is heterogeneous and can be divided into early gastric cardiac carcinoma (EGCC) and early gastric non-cardiac carcinoma (EGNCC) groups. At present, differences in clinicopathology remains obscure between EGCC and EGNCC fundus–corpus and antrum–angularis–pylorus subgroups, especially between EGCC with and without oesophageal invasion.

Methods
In this study, we studied 329 consecutive early gastric carcinoma radical gastrectomies with 70 EGCCs and 259 EGNCCs.

Results
Compared to the EGNCC antrum–angularis–pylorus (n = 181), but not fundus–corpus (n = 78), sub-group, EGCC showed significantly older age, lower prevalence of the grossly depressed pattern, better tumor differentiation, higher percentage of tubular/papillary adenocarcinoma, but lower frequency of mixed poorly cohesive carcinoma with tubular/papillary adenocarcinoma, and absence of lymph node metastasis (LNM) in tumors with invasion up to superficial submucosa (SM1). In contrast, pure poorly cohesive carcinoma was less frequently seen in EGCCs than in EGNCCs, but mixed poorly cohesive carcinoma with tubular/papillary adenocarcinomas was significantly more common in the EGNCC antrum–angularis–pylorus sub-group than in any other group. No significant differences were found between EGCC and EGNCC sub-groups in gender, tumor size, H. pylori infection rate, and lymphovascular/perineural invasion. EGCC with oesophageal invasion (n = 22), compared to EGCC without (n = 48), showed no significant differences in the H. pylori infection rate and oesophageal columnar, intestinal, or pancreatic metaplasia, except for a higher percentage of the former in size > 2 cm and tubular differentiation.

Conclusions
There exist distinct clinicopathologic differences between EGCC and EGNCC sub-groups; EGCC was indeed of gastric origin. Further investigations with larger samples are needed to validate these findings.
Health care costs of injury in the older population: a prospective multicentre cohort study in the Netherlands
Authors: van der Vlegel Marjolein , Haagsma Juanita A. , Geraerds A. J. L. M. , de Munter Leonie , de Jongh Mariska A. C. , Polinder Suzanne 
Published: October 2020

Abstract
Background
With the ageing population, the number of older trauma patients has increased. The aim of this study was to assess non-surgical health care costs of older trauma patients and to identify which characteristics of older trauma patients were associated with high health care costs.

Methods
Trauma patients aged ≥65 years who were admitted to a hospital in Noord-Brabant, the Netherlands, were included in the Brabant Injury Outcome Surveillance (BIOS) study. Non-surgical in-hospital and up to 24- months post-hospital health care use were obtained from hospital registration data and collected with the iMTA Medical Consumption Questionnaire which patients completed 1 week and 1, 3, 6, 12 and 24 months after injury. Log-linked gamma generalized linear models were used to identify cost-driving factors.

Results
A total of 1910 patients were included in the study. Mean total health care costs per patient were €12,190 ranging from €8390 for 65–69 year-olds to €15,550 for those older than 90 years. Main cost drivers were the post-hospital costs due to home care and stay at an institution. Falls (72%) and traffic injury (15%) contributed most to the total health care costs, although costs of cause of trauma varied with age and sex. In-hospital costs were especially high in patients with high injury severity, frailty and comorbidities. Age, female sex, injury severity, frailty, having comorbidities and having a hip fracture were independently associated with higher post-hospital health care costs.

Conclusions
In-hospital health care costs were chiefly associated with high injury severity. Several patient and injury characteristics including age, high injury severity, frailty and comorbidity were associated with post-hospital health care costs. Both fall-related injuries and traffic-related injuries are important areas for prevention of injury in the older population.
The use of intravenous immunoglobulin gamma for the treatment of severe coronavirus disease 2019: a randomized placebo-controlled double-blind clinical trial
Authors: Gharebaghi Naser , Nejadrahim Rahim , Mousavi Seyed Jalil , Sadat-Ebrahimi Seyyed-Reza , Hajizadeh Reza 
Published: October 2020

AbstractBackgroundCoronavirus disease 2019 (COVID-19) has infected people in many countries worldwide. Discovering an effective treatment for this disease, particularly in severe cases, has become the subject of intense scientific investigation. Therefore, the objective of this study was to evaluate the efficacy of intravenous immunoglobulin (IVIg) in patients with severe COVID-19 infection.MethodsThis study was conducted as a randomized placebo-controlled double-blind clinical trial. Fifty-nine patients with severe COVID-19 infection who did not respond to initial treatments were randomly assigned into two groups. One group received IVIg (human)—four vials daily for 3 days (in addition to initial treatment), while the other group received a placebo. Patients’ demographic, clinical, and select laboratory test results, as well as the occurrence of in-hospital mortality, were recorded.ResultsAmong total study subjects, 30 patients received IVIg and 29 patients received a placebo. Demographics, clinical characteristics, and laboratory tests were not statistically different (P > 0.05) between the two groups. The in-hospital mortality rate was significantly lower in the IVIg group compared to the control group (6 [20.0%] vs. 14 [48.3%], respectively;P = 0.025). Multivariate regression analysis demonstrated that administration of IVIg did indeed have a significant impact on mortality rate (aOR = 0.003 [95% CI: 0.001–0.815];P = 0.042).ConclusionsOur study demonstrated that the administration of IVIg in patients with severe COVID-19 infection who did not respond to initial treatment could improve their clinical outcome and significantly reduce mortality rate. Further multicenter studies with larger sample sizes are nonetheless required to confirm the appropriateness of this medication as a standard treatment.Trial registrationA study protocol was registered at the Iranian Registry of Clinical Trials (www.IRCT.ir), numberIRCT20200501047259N1. It was registered retrospectively on May 17th, 2020.
Influence of family resources on secondhand smoking in pregnant women: a cross-sectional study in the border and minority urban areas of Northwest China
Authors: Chen Jiangyun , Li Xinhui , Fang Pengqian 
Published: October 2020

Abstract
Background
Pregnant women’s exposure to secondhand smoke is a very serious health issue in China. The purpose of our research is to identify factors that predict the probability of exposure to secondhand smoke among pregnant women from the perspective of a family-based open system.

Methods
From September 2014 to August 2015, Urumqi City, Shihezi City, and Shawan County-level City were sampled according to population characteristics. A revised structured questionnaire based on family resources was adapted for use in this study. Questionnaires were collected via convenience sampling at the hospitals with the largest number of local antenatal clients. A total of 1249 pregnant women of age 18–51 years were investigated. Descriptive statistics were calculated to characterize the participants and study variables. Binary logistic regression was performed to assess the impact of family resources corresponding variables on the likelihood that participants would be exposed to SHS. Both unadjusted and adjusted odds ratios (OR/AOR) [with 95% confidence intervals (CI)] were reported.

Results
The secondhand smoke exposure rate found in this study was 54.6%. Having good knowledge of the dangers of secondhand smoke had no effect on reducing the prevalence of exposure (P > 0.05). Even pregnant women whose husbands who did not use tobacco or never smoked nearby had a risk of exposure to secondhand smoke [adjusted odds ratio (AOR) 1.568, 95% CI 1.205–2.041] when the data were adjusted for age, gravidity, gestational weeks, knowledge of the dangers of secondhand smoke, location, and work status. Home smoking bans were confirmed to be an important protective factor (AOR 1.710, 95% CI 1.549–1.918); however, only one-third (33.5%) of participants reported having a smoking ban at home. Religion (mainly Islam), as a special external family resource, was a protective factor that reduced secondhand smoke exposure in pregnant women (AOR 0.399, 95% CI 0.312–0.510).

Conclusions
The effect of family resources on tobacco control should be considered in the development of effective and enduring strategies for indoor smoking bans and smoking cessation.
microRNA-451a promoter methylation regulated by DNMT3B expedites bladder cancer development via the EPHA2/PI3K/AKT axis
Authors: Liu Beibei , Sun Wei , Gao Wuyue , Li Liqiang , Cao Zhenxue , Yang Xiaohuai , Liu Jianmin , Guo Yuanyuan 
Published: October 2020

Abstract
Background
The downregulation of microRNA (miR)-451a has been reported in bladder cancer (BCa) tissues. Herein, we elucidated the role of miR-451a in BCa with the involvement of DNA methyltransferase 3B (DNMT3B).

Methods
We first screened the differentially expressed miRNAs from the serum of 12 BCa patients and 10 healthy controls in the BCa database GSE113486. Subsequently, we detected miR-451a expression and CpG island methylation of the promoter in BCa cells T24 and 5637 with DNMT3B knockdown. The downstream mRNAs of miR-451a were predicted by bioinformatics and KEGG enrichment analysis. Afterwards, the expression patterns of DNMT3B, miR-451a and erythropoietin-producing hepatocellular receptor tyrosine kinase class A2 (EPHA2) were altered in BCa cells to test the ability of cell proliferation, apoptosis, migration as well as invasion. Finally, the effect of miR-451a and DNMT3B was evaluated in vivo.

Results
miR-451a was significantly reduced in serum of BCa patients and cell lines. Moreover, the expression of DNMT3B in BCa cells was significantly increased, thus promoting methylation of the miR-451a promoter, resulting in miR-451a inhibition. Additionally, we found that miR-451a targeted and negatively regulated EPHA2, while EPHA2 could activate the PI3K/AKT signaling, driving BCa cell growth and metastasis.

Conclusions
Our study proposed and demonstrated that miR-451a downregulation mediated by DNMT3B is critical for proliferation, migration, and invasion of BCa, which may be beneficial for developing more effective therapies against BCa.
A modified Delphi to define drug dosing errors in pediatric critical care
Authors: Roumeliotis Nadia , Pullenayegum Eleanor , Rochon Paula , Taddio Anna , Parshuram Chris 
Published: October 2020

Abstract
Background
There is no globally accepted definition for dosing error in adult or pediatric practice. The definition of pediatric dosing error varies greatly in the literature. The objective of this study was to develop a framework, informed by a set of principles, for a clinician-based definition of drug dosing errors in critically ill children, and to identify the range that practitioners agree is a dosing error for different drug classes and clinical scenarios.

Methods
We conducted a nationwide three staged modified Delphi from May to December 2019. Expert clinicians included Canadian pediatric intensive care unit (PICU) physicians, pharmacists and nurses, with a least 5 years’ experience. Outcomes were underlying principles of drug dosing, and error thresholds, as defined by proportion above and below reference range, for common PICU medications and clinical scenarios.

Results
Forty-four participants met eligibility, and response rates were 95, 86 and 84% for all three rounds respectively. Consensus was achieved for 13 of 15 principles, and 23 of 30 error thresholds. An over-dosed drug that is intercepted, an under-dose of a possibly life-saving medication, dosing 50% above or below target range and not adjusting for a drug interaction were agreed principles of dosing error. Altough there remained much uncertainty in defining dosing error, expert clinicians agreed that, for most medication categories and clinical scenarios, dosing over or below 10% of reference range was considered an error threshold.

Conclusion
Dosing principles and threshold are complex in pediatric critical care, and expert clinicians were uncertain about whether many scenarios were considered in error. For most intermittent medications, dosing over 10% below or above reference range was considered a dosing error, although this was largely influenced by clinical context and drug properties. This consensus driven error threshold will help guide routine clinical dosing practice, standardized reporting and drug quality improvement in pediatric critical care.