bluuebunny/crossref_metadata_2025 huggingface dataset:
BNP/NT-proBNP in pulmonary arterial hypertension: time for point-of-care testing?
Authors: Lewis Robert A. , Durrington Charlotte , Condliffe Robin , Kiely David G.
Published: May 2020

Despite the advent of new therapies and improved outcomes in patients with pulmonary arterial hypertension (PAH), it remains a life-shortening disease and the time to diagnosis remains unchanged. Strategies to improve outcomes are therefore currently focused on earlier diagnosis and a treatment approach aimed at moving patients with PAH into a category of low-risk of 1-year mortality. B-type natriuretic peptide (BNP; or brain natriuretic peptide) and N-terminal prohormone of BNP (NT-proBNP) are released from cardiac myocytes in response to mechanical load and wall stress. Elevated levels of BNP and NT-proBNP are incorporated into several PAH risk stratification tools and screening algorithms to aid diagnosis of systemic sclerosis. We have undertaken a systematic review of the literature with respect to the use of BNP and NT-proBNP in PAH and the use of these biomarkers in the diagnosis and risk stratification of PAH, their relation to pulmonary haemodynamics and the potential for point-of-care testing to improve diagnosis and prognosis.
Prognostic factors in chronic hypersensitivity pneumonitis
Authors: Creamer Andrew W. , Barratt Shaney L.
Published: May 2020

Hypersensitivity pneumonitis (HP) is an immunologically mediated lung disease resulting from exposure to inhaled environmental antigens. Prognosis is variable, with a subset of patients developing progressive fibrosis leading to respiratory failure and death. Therefore, there is an urgent need to identify factors which predict prognosis and survival in patients with HP. We undertook a narrative review of existing evidence to identify prognostic factors in patients with chronic HP. Patient demographics, smoking history, extent of antigen exposure and comorbidities all have reported associations with disease outcome, and physiological, radiological and laboratory markers have been shown to predict overall survival. While no single marker has been demonstrated to accurately and reliably predict prognosis, older age, more severe impairment of pulmonary function at baseline and established fibrosis on either biopsy or high-resolution computed tomography are consistently associated with worse survival. The vast majority of existing studies are retrospective, and this review identifies a need for prospective longitudinal studies with serial assessment of respiratory health to ascertain factors associated with nonfatal deterioration. Future developments, including the development of HP-specific composite scores may help further improve our ability to predict outcomes for individual patients.
Does distance matter in foreign direct investment sub-national location choice? Evidence from China
Authors: Bi Yibo , Ren Zhiyi , Bao Kun
Published: May 2020

Multinational enterprises (MNEs) make investment decisions according to the distance factors at a sub-national level. This paper made estimates using the gravity model with provincial foreign direct investment (FDI) data from 2000 to 2012 and employed three concepts of distance. Our empirical results indicate that geographic distance and cultural distance have significant negative effects on FDI flow, whereas economic distance has a significant positive effect. It suggests that FDI prefers to locate in regions that are geographically and culturally close but economically distant from the home country, which further implies that FDI in China is dominated by vertical FDI. Our findings suggest that Chinese provincial governments should place emphasis on attracting FDI from culturally close countries and provide institutional support to encourage and promote horizontal FDI.
CIPR: a web-based R/shiny app and R package to annotate cell clusters in single cell RNA sequencing experiments
Authors: Ekiz H. Atakan , Conley Christopher J. , Stephens W. Zac , O’Connell Ryan M.
Published: May 2020

Background

Single cell RNA sequencing (scRNAseq) has provided invaluable insights into cellular heterogeneity and functional states in health and disease. During the analysis of scRNAseq data, annotating the biological identity of cell clusters is an important step before downstream analyses and it remains technically challenging. The current solutions for annotating single cell clusters generally lack a graphical user interface, can be computationally intensive or have a limited scope. On the other hand, manually annotating single cell clusters by examining the expression of marker genes can be subjective and labor-intensive. To improve the quality and efficiency of annotating cell clusters in scRNAseq data, we present a web-based R/Shiny app and R package, Cluster Identity PRedictor (CIPR), which provides a graphical user interface to quickly score gene expression profiles of unknown cell clusters against mouse or human references, or a custom dataset provided by the user. CIPR can be easily integrated into the current pipelines to facilitate scRNAseq data analysis.

Results

CIPR employs multiple approaches for calculating the identity score at the cluster level and can accept inputs generated by popular scRNAseq analysis software. CIPR provides 2 mouse and 5 human reference datasets, and its pipeline allows inter-species comparisons and the ability to upload a custom reference dataset for specialized studies. The option to filter out lowly variable genes and to exclude irrelevant reference cell subsets from the analysis can improve the discriminatory power of CIPR suggesting that it can be tailored to different experimental contexts. Benchmarking CIPR against existing functionally similar software revealed that our algorithm is less computationally demanding, it performs significantly faster and provides accurate predictions for multiple cell clusters in a scRNAseq experiment involving tumor-infiltrating immune cells.

Conclusions

CIPR facilitates scRNAseq data analysis by annotating unknown cell clusters in an objective and efficient manner. Platform independence owing to Shiny framework and the requirement for a minimal programming experience allows this software to be used by researchers from different backgrounds. CIPR can accurately predict the identity of a variety of cell clusters and can be used in various experimental contexts across a broad spectrum of research areas.
An integrated software for virus community sequencing data analysis
Authors: Wang Mingjie , Li Jianfeng , Zhang Xiaonan , Han Yue , Yu Demin , Zhang Donghua , Yuan Zhenghong , Yang Zhitao , Huang Jinyan , Zhang Xinxin
Published: May 2020

Background

A virus community is the spectrum of viral strains populating an infected host, which plays a key role in pathogenesis and therapy response in viral infectious diseases. However automatic and dedicated pipeline for interpreting virus community sequencing data has not been developed yet.

Results

We developed Quasispecies Analysis Package (QAP), an integrated software platform to address the problems associated with making biological interpretations from massive viral population sequencing data. QAP provides quantitative insight into virus ecology by first introducing the definition “virus OTU” and supports a wide range of viral community analyses and results visualizations. Various forms of QAP were developed in consideration of broader users, including a command line, a graphical user interface and a web server. Utilities of QAP were thoroughly evaluated with high-throughput sequencing data from hepatitis B virus, hepatitis C virus, influenza virus and human immunodeficiency virus, and the results showed highly accurate viral quasispecies characteristics related to biological phenotypes.

Conclusions

QAP provides a complete solution for virus community high throughput sequencing data analysis, and it would facilitate the easy analysis of virus quasispecies in clinical applications.
Metabolic and transcriptomic analysis of two Cucurbita moschata germplasms throughout fruit development
Authors: Abbas Hafiz Muhammad Khalid , Huang He-Xun , Wang An-Jun , Wu Ting-Quan , Xue Shu-Dan , Ahmad Aqeel , Xie Da-Sen , Li Jun-Xing , Zhong Yu-Juan
Published: May 2020

Background

Pumpkins (Cucurbita moschata; Cucurbitaceae) are valued for their fruits and seeds and are rich in nutrients. Carotenoids and sugar contents, as main feature of pumpkin pulp, are used to determine the fruit quality.

Results

Two pumpkin germplasms, CMO-X and CMO-E, were analyzed regarding the essential quality traits such as dry weight, soluble solids, organic acids, carotenoids and sugar contents. For the comparison of fruit development in these two germplasms, fruit transcriptome was analyzed at 5 different developmental stages from 0 d to 40 d in a time course manner. Putative pathways for carotenoids biosynthesis and sucrose metabolism were developed in C. moschata fruit and homologs were identified for each key gene involved in the pathways. Gene expression data was found consistent with the accumulation of metabolites across developmental stages and also between two germplasms. PSY, PDS, ZEP, CRTISO and SUS, SPS, HK, FK were found highly correlated with the accumulation of carotenoids and sucrose metabolites, respectively, at different growth stages of C. moschata as shown by whole transcriptomic analysis. The results of qRT-PCR analysis further confirmed the association of these genes.

Conclusion

Developmental regulation of the genes associated with the metabolite accumulation can be considered as an important factor for the determination of C. moschata fruit quality. This research will facilitate the investigation of metabolic profiles in other cultivars.
Upregulation of pERK and c-JUN by γ-tocotrienol and not α-tocopherol are essential to the differential effect on apoptosis in prostate cancer cells
Authors: Moore Christine , Palau Victoria E. , Mahboob Rashid , Lightner Janet , Stone William , Krishnan Koyamangalath
Published: May 2020

Background

α-tocopherol (AT) and γ-tocotrienol (GT3) are vitamin E isoforms considered to have potential chemopreventive properties. AT has been widely studied in vitro and in clinical trials with mixed results. The latest clinical study (SELECT trial) tested AT in prostate cancer patients, determined that AT provided no benefit, and could promote cancer. Conversely, GT3 has shown antineoplastic properties in several in vitro studies, with no clinical studies published to date. GT3 causes apoptosis via upregulation of the JNK pathway; however, inhibition results in a partial block of cell death. We compared side by side the mechanistic differences in these cells in response to AT and GT3.

Methods

The effects of GT3 and AT were studied on androgen sensitive LNCaP and androgen independent PC-3 prostate cancer cells. Their cytotoxic effects were analyzed via MTT and confirmed by metabolic assays measuring ATP. Cellular pathways were studied by immunoblot. Quantitative analysis and the determination of relationships between cell signaling events were analyzed for both agents tested. Non-cancerous prostate RWPE-1 cells were also included as a control.

Results

The RAF/RAS/ERK pathway was significantly activated by GT3 in LNCaP and PC-3 cells but not by AT. This activation is essential for the apoptotic affect by GT3 as demonstrated the complete inhibition of apoptosis by MEK1 inhibitor U0126. Phospho-c-JUN was upregulated by GT3 but not AT. No changes were observed on AKT for either agent, and no release of cytochrome c into the cytoplasm was detected. Caspases 9 and 3 were efficiently activated by GT3 on both cell lines irrespective of androgen sensitivity, but not in cells dosed with AT. Cell viability of non-cancerous RWPE-1 cells was affected neither by GT3 nor AT.

Conclusions

c-JUN is a recognized master regulator of apoptosis as shown previously in prostate cancer. However, the mechanism of action of GT3 in these cells also include a significant activation of ERK which is essential for the apoptotic effect of GT3. The activation of both, ERK and c-JUN, is required for apoptosis and may suggest a relevant step in ensuring circumvention of mechanisms of resistance related to the constitutive activation of MEK1.
Poor outcome of octogenarians admitted to ICU due to periprosthetic joint infections: a retrospective cohort study
Authors: Yilmaz Emre , Poell Alexandra , Baecker Hinnerk , Frieler Sven , Waydhas Christian , Schildhauer Thomas A. , Hamsen Uwe
Published: May 2020

Background

Even though surgical techniques and implants have evolved, periprosthetic joint infection (PJI) remains a serious complication leading to poor postoperative outcome and a high mortality. The literature is lacking in studies reporting the mortality of very elderly patients with periprosthetic joint infections, especially in cases when an intensive care unit (ICU) treatment was necessary. We therefore present the first study analyzing patients with an age 80 and higher suffering from a periprosthetic joint infection who had to be admitted to the ICU.

Methods

All patients aged 80 and higher who suffered from a PJI (acute and chronic) after THR or TKR and who have been admitted to the ICU have been included in this retrospective, observational, single-center study.

Results

A total of 57 patients met the inclusion criteria. The cohort consisted of 24 males and 33 females with a mean age of 84.49 (± 4.0) years. The mean SAPS II score was 27.05 (± 15.7), the mean CCI was 3.35 (± 2.28) and the most patient had an ASA score of 3 or higher. The PJI was located at the hip in 71.9% or at the knee in 24.6%. Two patients (3.5%) suffered from a PJI at both locations. Sixteen patients did not survive the ICU stay. Non-survivors showed significantly higher CCI (4.94 vs. 2.73; p = 0.02), higher SAPS II score (34.06 vs. 24.32; p = 0.03), significant more patients who underwent an invasive ventilation (132.7 vs. 28.1; p = 0.006) and significantly more patients who needed RRT (4.9% vs. 50%; p < 0.001). In multivariate analysis, RRT (odds ratio (OR) 15.4, CI 1.69–140.85; p = 0.015), invasive ventilation (OR 9.6, CI 1.28–71.9; p = 0.028) and CCI (OR 1.5, CI 1.004–2.12; p = 0.048) were independent risk factors for mortality.

Conclusion

Very elderly patients with PJI who needs to be admitted to the ICU are at risk to suffer from a poor outcome. Several risk factors including a chronic infection, high SAPS II Score, high CCI, invasive ventilation and RRT might be associated with a poor outcome.
Influence of hemoadsorption during cardiopulmonary bypass on blood vesicle count and function
Authors: Wisgrill Lukas , Lamm Christian , Hell Lena , Thaler Johannes , Berger Angelika , Weiss Rene , Weber Viktoria , Rinoesl Harald , Hiesmayr Michael J. , Spittler Andreas , Bernardi Martin H.
Published: May 2020

Background

Extracorporeal circulation during major cardiac surgery triggers a systemic inflammatory response affecting the clinical course and outcome. Recently, extracellular vesicle (EV) research has shed light onto a novel cellular communication network during inflammation. Hemoadsorption (HA) systems have shown divergent results in modulating the systemic inflammatory response during cardiopulmonary bypass (CPB) surgery. To date, the effect of HA on circulating microvesicles (MVs) in patients undergoing CPB surgery is unknown.

Methods

Count and function of MVs, as part of the extracellular vesicle fraction, were assessed in a subcohort of a single-center, blinded, controlled study investigating the effect of the CytoSorb device during CPB. A total of 18 patients undergoing elective CPB surgery with (n = 9) and without (n = 9) HA device were included in the study. MV phenotyping and counting was conducted via flow cytometry and procoagulatory potential was measured by tissue factor-dependent MV assays.

Results

Both study groups exhibited comparable counts and post-operative kinetics in MV subsets. Tissue factor-dependent procoagulatory potential was not detectable in plasma at any timepoint. Post-operative course and laboratory parameters showed no correlation with MV counts in patients undergoing CPB surgery.

Conclusion

Additional artificial surfaces to the CPB-circuit introduced by the use of the HA device showed no effect on circulating MV count and function in these patients. Larger studies are needed to assess and clarify the effect of HA on circulating vesicle counts and function.

Trial registrationClinicalTrials.Gov Identifier: NCT01879176; registration date: June 17, 2013;https://clinicaltrials.gov/ct2/show/NCT01879176
Visualization of spatial gene expression in plants by modified RNAscope fluorescent in situ hybridization
Authors: Solanki Shyam , Ameen Gazala , Zhao Jin , Flaten Jordan , Borowicz Pawel , Brueggeman Robert S.
Published: May 2020

Background

In situ analysis of biomarkers such as DNA, RNA and proteins are important for research and diagnostic purposes. At the RNA level, plant gene expression studies rely on qPCR, RNAseq and probe-based in situ hybridization (ISH). However, for ISH experiments poor stability of RNA and RNA based probes commonly results in poor detection or poor reproducibility. Recently, the development and availability of the RNAscope RNA-ISH method addressed these problems by novel signal amplification and background suppression. This method is capable of simultaneous detection of multiple target RNAs down to the single molecule level in individual cells, allowing researchers to study spatio-temporal patterning of gene expression. However, this method has not been optimized thus poorly utilized for plant specific gene expression studies which would allow for fluorescent multiplex detection. Here we provide a step-by-step method for sample collection and pretreatment optimization to perform the RNAscope assay in the leaf tissues of model monocot plant barley. We have shown the spatial distribution pattern of HvGAPDH and the low expressed disease resistance gene Rpg1 in leaf tissue sections of barley and discuss precautions that should be followed during image analysis.

Results

We have shown the ubiquitous HvGAPH and predominantly stomatal guard cell associated subsidiary cell expressed Rpg1 expression pattern in barley leaf sections and described the improve RNAscope methodology suitable for plant tissues using confocal laser microscope. By addressing the problems in the sample collection and incorporating additional sample backing steps we have significantly reduced the section detachment and experiment failure problems. Further, by reducing the time of protease treatment, we minimized the sample disintegration due to over digestion of barley tissues.

Conclusions

RNAscope multiplex fluorescent RNA-ISH detection is well described and adapted for animal tissue samples, however due to morphological and structural differences in the plant tissues the standard protocol is deficient and required optimization. Utilizing barley specific HvGAPDH and Rpg1 RNA probes we report an optimized method which can be used for RNAscope detection to determine the spatial expression and semi-quantification of target RNAs. This optimized method will be immensely useful in other plant species such as the widely utilized Arabidopsis.
Detecting transcriptomic structural variants in heterogeneous contexts via the Multiple Compatible Arrangements Problem
Authors: Qiu Yutong , Ma Cong , Xie Han , Kingsford Carl
Published: May 2020

Background

Transcriptomic structural variants (TSVs)—large-scale transcriptome sequence change due to structural variation - are common in cancer. TSV detection from high-throughput sequencing data is a computationally challenging problem. Among all the confounding factors, sample heterogeneity, where each sample contains multiple distinct alleles, poses a critical obstacle to accurate TSV prediction.

Results

To improve TSV detection in heterogeneous RNA-seq samples, we introduce the Multiple Compatible Arrangements Problem (MCAP), which seeks k genome arrangements that maximize the number of reads that are concordant with at least one arrangement. This models a heterogeneous or diploid sample. We prove that MCAP is NP-complete and provide a $$\frac{1}{4}$$14-approximation algorithm for $$k=1$$k=1 and a $$\frac{3}{4}$$34-approximation algorithm for the diploid case ($$k=2$$k=2) assuming an oracle for $$k=1$$k=1. Combining these, we obtain a $$\frac{3}{16}$$316-approximation algorithm for MCAP when $$k=2$$k=2 (without an oracle). We also present an integer linear programming formulation for general k. We characterize the conflict structures in the graph that require $$k>1$$k>1 alleles to satisfy read concordancy and show that such structures are prevalent.

Conclusions

We show that the solution to MCAP accurately addresses sample heterogeneity during TSV detection. Our algorithms have improved performance on TCGA cancer samples and cancer cell line samples compared to a TSV calling tool, SQUID. The software is available at https://github.com/Kingsford-Group/diploidsquid.
Trauma complications and in-hospital mortality: failure-to-rescue
Authors: Abe Toshikazu , Komori Akira , Shiraishi Atsushi , Sugiyama Takehiro , Iriyama Hiroki , Kainoh Takako , Saitoh Daizoh
Published: May 2020

Background

Reducing medical errors and minimizing complications have become the focus of quality improvement in medicine. Failure-to-rescue (FTR) is defined as death after a surgical complication, which is an institution-level surgical safety and quality metric that is an important variable affecting mortality rates in hospitals. This study aims to examine whether complication and FTR are different across low- and high-mortality hospitals for trauma care.

Methods

This was a retrospective cohort study performed at trauma care hospitals registered at Japan Trauma Data Bank (JTDB) from 2004 to 2017. Trauma patients aged ≥ 15 years with injury severity score (ISS) of ≥ 3 and those who survived for > 48 h after hospital admission were included. The hospitals in JTDB were categorized into three groups by standardized mortality rate. We compared trauma complications, FTR, and in-hospital mortality by a standardized mortality rate (divided by the institute-level quartile).

Results

Among 184,214 patients that were enrolled, the rate of any complication was 12.7%. The overall mortality rate was 3.7%, and the mortality rate among trauma patients without complications was only 2.8% (non-precedented deaths). However, the mortality rate among trauma patients with any complications was 10.2% (FTR). Hospitals were categorized into high- (40 facilities with 44,773 patients), average- (72 facilities with 102,368 patients), and low- (39 facilities with 37,073 patients) mortality hospitals, using the hospital ranking of a standardized mortality rate. High-mortality hospitals showed lower ISS than low-mortality hospitals [10 (IQR, 9–18) vs. 11 (IQR, 9–20), P < 0.01]. Patients in high-mortality hospitals showed more complications (14.2% vs. 11.2%, P < 0.01), in-hospital mortality (5.1% vs. 2.5%, P < 0.01), FTR (13.6% vs. 7.4%, P < 0.01), and non-precedented deaths (3.6% vs. 1.9%, P < 0.01) than those in low-mortality hospitals.

Conclusions

Unlike reports of elective surgery, complication rates and FTR are associated with in-hospital mortality rates at the center level in trauma care.
Differential blood miRNA expression in brain amyloid imaging-defined Alzheimer’s disease and controls
Authors:   and the Australian Imaging Biomarkers and Lifestyle Flagship Study of Ageing, Wu Helen Zong Ying , Thalamuthu Anbupalam , Cheng Lesley , Fowler Christopher , Masters Colin L. , Sachdev Perminder , Mather Karen A.
Published: May 2020

Background

Peripheral blood microRNAs (miRNA) have been identified as potential biomarkers for Alzheimer’s disease (AD). Study results have generally been inconsistent and limited by sample heterogeneity. The aim of this study is to establish candidate blood miRNA biomarkers for AD by comparing differences in miRNA expression between participants with brain amyloid imaging-defined AD and normal cognition.

Methods

Blood RNA was extracted from a subset of participants from the Australian Imaging Biomarkers Lifestyle Study of Ageing cohort (AIBL) with brain amyloid imaging results. MiRNA profiling was performed using small RNA sequencing on 71 participants, comprising 40 AD with high brain amyloid burden on imaging (amyloid positive) and 31 cognitively normal controls with low brain amyloid burden (amyloid negative). Cross-sectional comparisons were made between groups to examine differential miRNA expression levels using Fisher’s exact tests. Replication of results was undertaken using a publicly available dataset of blood miRNA data of AD and controls. In silico analysis of downstream messenger RNA targets of candidate miRNAs was performed to elucidate potential biological function.

Results

After quality control, 816 miRNAs were available for analysis. There were 71 significantly differentially expressed miRNAs between the AD and control groups (p < 0.05). Two of these miRNAs, miR-146b-5p and miR-15b-5p, were also significant in the replication cohort. Pathways analysis showed these miRNAs to be involved in innate immune system and regulation of the cell cycle, respectively, both of which have relevance to AD pathogenesis.

Conclusion

Blood miR-146b-5p and miR15b-5p showed consistent differential expression in AD compared to controls. Further replication and translational studies in strictly phenotyped cohorts are needed to establish their role as biomarkers for AD to have clinical utility.
Isolation of novel Lactobacillus with lipolytic activity from the vinasse and their preliminary potential using as probiotics
Authors: Guan Chengran , Tao Zhiqiang , Wang Li , Zhao Ruifeng , Chen Xuan , Huang Xinyuan , Su Jianbo , Lu Zhen , Chen Xia , Gu Ruixia
Published: May 2020

Lactobacillus casei f1, L. paracasei f2 and L. paracasei f3 with lipolytic activity were isolated and identified from vinasses according to the morphological–physiological properties detection and 16S rDNA analysis. These three strains showed obvious lipase activities to olive oil and L. casei f1 performed highest enzyme activity of 17.8 U/mL. L. casei f1, L. paracasei f2 and L. paracasei f3 could lipolyze the blending oils, peanut oil and sesame oil with diverse degrading rates. The degrading rates to the preferred oils, L. casei f1 to blending oils, L. paracasei f2 to peanut oil and L. paracasei f3 to sesame oil, were 21.2%, 27.3% and 39.6%, respectively. The corresponding oil degrading rates increased as the cell growth and the highest degrading rates were obtained at the stationary phase with the viable count more than 7.5 LogCFU/mL. By GC–MS analysis, L. casei f1, L. paracasei f2 and L. paracasei f3 performed diverse lipolytic capacities to the 12 kinds of fat acids and all of them preferred to hydrolyze the linoleic acid with the degrading rate of 49.11%, 31.83% and 64.44%, respectively. These three strains showed considerable probiotic properties, displaying higher than 106 CFU/mL desirable viable count though the simulated gastrointestinal tract, as well as inhibiting six indicator bacteria. These results suggested that the three isolated strains could be considered as novel probiotic candidates and applied in the food industry.
Construction of habitat-specific training sets to achieve species-level assignment in 16S rRNA gene datasets
Authors: F. Escapa Isabel , Huang Yanmei , Chen Tsute , Lin Maoxuan , Kokaras Alexis , Dewhirst Floyd E. , Lemon Katherine P.
Published: May 2020

Background

The low cost of 16S rRNA gene sequencing facilitates population-scale molecular epidemiological studies. Existing computational algorithms can resolve 16S rRNA gene sequences into high-resolution amplicon sequence variants (ASVs), which represent consistent labels comparable across studies. Assigning these ASVs to species-level taxonomy strengthens the ecological and/or clinical relevance of 16S rRNA gene-based microbiota studies and further facilitates data comparison across studies.

Results

To achieve this, we developed a broadly applicable method for constructing high-resolution training sets based on the phylogenic relationships among microbes found in a habitat of interest. When used with the naïve Bayesian Ribosomal Database Project (RDP) Classifier, this training set achieved species/supraspecies-level taxonomic assignment of 16S rRNA gene-derived ASVs. The key steps for generating such a training set are (1) constructing an accurate and comprehensive phylogenetic-based, habitat-specific database; (2) compiling multiple 16S rRNA gene sequences to represent the natural sequence variability of each taxon in the database; (3) trimming the training set to match the sequenced regions, if necessary; and (4) placing species sharing closely related sequences into a training-set-specific supraspecies taxonomic level to preserve subgenus-level resolution. As proof of principle, we developed a V1–V3 region training set for the bacterial microbiota of the human aerodigestive tract using the full-length 16S rRNA gene reference sequences compiled in our expanded Human Oral Microbiome Database (eHOMD). We also overcame technical limitations to successfully use Illumina sequences for the 16S rRNA gene V1–V3 region, the most informative segment for classifying bacteria native to the human aerodigestive tract. Finally, we generated a full-length eHOMD 16S rRNA gene training set, which we used in conjunction with an independent PacBio single molecule, real-time (SMRT)-sequenced sinonasal dataset to validate the representation of species in our training set. This also established the effectiveness of a full-length training set for assigning taxonomy of long-read 16S rRNA gene datasets.

Conclusion

Here, we present a systematic approach for constructing a phylogeny-based, high-resolution, habitat-specific training set that permits species/supraspecies-level taxonomic assignment to short- and long-read 16S rRNA gene-derived ASVs. This advancement enhances the ecological and/or clinical relevance of 16S rRNA gene-based microbiota studies.
A step towards gender equity to strengthen the pharmaceutical workforce during COVID-19
Authors: Bukhari Nadia , Manzoor Mehr , Rasheed Huma , Nayyer Bismah , Malik Madeeha , Babar Zaheer-Ud-Din
Published: May 2020

There is plenty of evidence to support that women leaders are needed in the health and pharmaceutical sectors, although most of the leadership positions in global health are predominantly occupied by men. This is a major challenge to global health policy. Gender diversity and inclusion within the pharmaceutical workforce is integral to optimal patient care. Women continue to be underrepresented in senior and leadership positions within pharmacy, despite outnumbering the men in the global pharmacy workforce. This commentary highlights the need towards gender equity and discusses the several key initiatives that are building momentum and making substantial progress towards this agenda in the pharmaceutical workforce.
Effects of tool offset, pin offset, and alloys position on maximum temperature in dissimilar FSW of AA6061 and AA5086
Authors: Ghiasvand Amir , Kazemi Mahdi , Mahdipour Jalilian Maziar , Ahmadi Rashid Hossein
Published: May 2020

Friction stir welding (FSW) is a solid-state welding technique, which two workpieces join by pressure and large plastic deformation near their melting points. The tool offset, pin offset, and position of dissimilar alloys can highly affect the maximum temperature and heat distribution in FSW process. In current research, the effects of three mentioned variables on the maximum temperature of FSW of AA6061 and AA5086 alloys have been investigated. In this manner, Response Surface Methodology (RSM) as an auxiliary method has been used. The results show that pin offset is the most effective parameter affecting maximum achieved temperature. In all pin and tool offsettings, placing the harder alloy (AA6061) at advancing side results in more maximum temperature increment compared to the case which the harder alloy is at the retreating side.
Branch-type intraductal papillary neoplasm of the bile duct treated with laparoscopic anatomical resection: a case report
Authors: Matono Rumi , Ninomiya Mizuki , Morita Kazutoyo , Tomino Takahiro , Oshiro Yumi , Yokota Tomoyuki , Nishizaki Takashi
Published: May 2020

Background

Intraductal papillary neoplasm of the bile duct (IPNB) is characterized by an intraluminal, growing papillary tumor covered by neoplastic biliary epithelial cells with a fine fibrovascular core. IPNB was introduced as a precancerous and early neoplastic lesion in the 2010 World Health Organization classification of tumors of the digestive system. IPNB eventually invades the bile duct wall and progresses to invasive cholangiocarcinoma. IPNB resembles intraductal papillary mucinous neoplasm of the pancreas (IPMN), particularly the main pancreatic duct type.

IPNB cases, possibly corresponding to branch-type IPMN, have been recently reported, and these cases involved the peribiliary glands significantly and showed gross cystic dilatation. Small branch-type intrahepatic IPNB often mimics simple liver cysts, making the diagnosis of IPNB difficult. Some literature recommended surgical resection for treatment. Laparoscopic resection is a good treatment option for small tumor. We herein present the case of branch-type IPNB that was treated with laparoscopic anatomical liver resection 5 years after being detected.

Case presentation

A 64-year-old woman was undergoing follow-up for primary aldosteronism. In 2012, follow-up computed tomography (CT) incidentally revealed a 7-mm cystic lesion in segment 8 of the liver. From 2012 to 2017, the cystic lesion kept increasing in size, reaching 17 mm. In 2017, CT also revealed a 13-mm mural nodule in the cyst wall. Therefore, the patient was referred to our department for possible malignancy.

We suspected a branch-type IPNB; however, the mass was small and diagnosis could not be made without performing biopsy. Accordingly, surgical resection was performed for diagnosis and treatment. Because branch-type IPNB might show horizontal spread through the intrahepatic bile duct, we believed that anatomical resection of the liver was appropriate considering the malignant potential of the lesion. Therefore, laparoscopic anatomical resection of segment 8 of the liver was performed. The resected tumor measured 17 mm and was histologically diagnosed as a high-grade IPNB.

Conclusion

Branch-type IPNBs are rare but can potentially lead to malignant tumors. Surgical resection is the treatment of choice, with laparoscopic anatomical resection being a good treatment option for this small tumor.
The TDR MOOC training in implementation research: evaluation of feasibility and lessons learned in Rwanda
Authors: Hooley Cole , Baumann Ana A. , Mutabazi Vincent , Brown Angela , Reeds Dominic , Cade W. Todd , Fuentes Lisa de las , Proctor Enola K. , Karengera Stephen , Schecthman Kenneth , Goss Charles , Launois Pascal , Davila-Roman Victor G. , Mutimura Eugene
Published: May 2020

Background

Hypertension (HTN) affects nearly 1 billion people globally and is a major cause of morbidity and mortality. In low- and middle-income countries (LMICs), HTN represents an unmet health care gap that can be addressed by strengthening national health care systems. The National Heart, Lung, and Blood Institute recently funded the T4 Translation Research Capacity Building Initiative in Low Income Countries (TREIN) program to build capacity in dissemination and implementation (D&I) research in HTN in LMICs. The Special Programme for Research and Training in Tropical Diseases (TDR) at the World Health Organization (WHO) recently developed a massive open online course (MOOC) to train in D&I. Herein, we report on the use of the TDR WHO MOOC in D&I for the TREIN program in Rwanda, assessing feasibility of the MOOC and D&I competencies after MOOC training.

Methods

Participants in one-group MOOC training completed pre- and post-training questionnaires to assess dissemination and implementation (D&I) competency outcomes and feasibility. D&I competencies were measured by use of a scale developed for a US-based training program, with the change in competency scores assessed by paired t test. Feasibility was measured by completion of homework and final project assignment and analyzed using descriptive statistics.

Results

Of the 92 trainees enrolled, 35 (38%) completed all MOOC components. D&I competency scores showed strong evidence of improvements from pre- to post-test. The full-scale average score improved by an average of 1.09 points, representing an effect size of 1.25 (CI 0.48-2.00); all four subscales also showed strong evidence of improvements. Trainees reported challenges to MOOC course completion that included technological issues (i.e., limited internet access) and competing demands (i.e., work, family).

Conclusions

In the context of LMIC training, the MOOC course was feasible and course completion showed improvement in D&I competency scores. While the program was designed with a focus on training for tropical diseases, there is potential for scalability to a wider audience of health care researchers, workers, administrators, and policymakers in LMIC interested in D&I research in non-communicable diseases.
Classes of tree-based networks
Authors: Fischer Mareike , Galla Michelle , Herbst Lina , Long Yangjing , Wicke Kristina
Published: May 2020

Recently, so-called tree-based phylogenetic networks have attracted considerable attention. These networks can be constructed from a phylogenetic tree, called the base tree, by adding additional edges. The primary aim of this study is to provide sufficient criteria for tree-basedness by reducing phylogenetic networks to related graph structures. Even though it is generally known that determining whether a network is tree-based is an NP-complete problem, one of these criteria, namely edge-basedness, can be verified in linear time. Surprisingly, the class of edge-based networks is closely related to a well-known family of graphs, namely, the class of generalized series-parallel graphs, and we explore this relationship in full detail. Additionally, we introduce further classes of tree-based networks and analyze their relationships.
Multi-vortex laser enabling spatial and temporal encoding
Authors: Qiao Zhen , Wan Zhenyu , Xie Guoqiang , Wang Jian , Qian Liejia , Fan Dianyuan
Published: May 2020

Optical vortex is a promising candidate for capacity scaling in next-generation optical communications. The generation of multi-vortex beams is of great importance for vortex-based optical communications. Traditional approaches for generating multi-vortex beams are passive, unscalable and cumbersome. Here, we propose and demonstrate a multi-vortex laser, an active approach for creating multi-vortex beams directly at the source. By printing a specially-designed concentric-rings pattern on the cavity mirror, multi-vortex beams are generated directly from the laser. Spatially, the generated multi-vortex beams are decomposable and coaxial. Temporally, the multi-vortex beams can be simultaneously self-mode-locked, and each vortex component carries pulses with GHz-level repetition rate. Utilizing these distinct spatial-temporal characteristics, we demonstrate that the multi-vortex laser can be spatially and temporally encoded for data transmission, showing the potential of the developed multi-vortex laser in optical communications. The demonstrations may open up new perspectives for diverse applications enabled by the multi-vortex laser.
Multicenter Validation Study to Implement Plasma Epidermal Growth Factor Receptor T790M Testing in Clinical Laboratories
Authors: Leighl Natasha B. , Kamel-Reid Suzanne , Cheema Parneet K. , Laskin Janessa , Karsan Aly , Zhang Tong , Stockley Tracy , Barnes Tristan A. , Tudor Roxana A. , Liu Geoffrey , Owen Scott , Rothenstein Jeffrey , Burkes Ronald L. , Iqbal Mussawar , Spatz Alan , van Kempen Léon C. , Izevbaye Iyare , Laurence David , Le Lisa W. , Tsao Ming-Sound
Published: May 2020

PURPOSE

Plasma detection of EGFR T790M mutations is an emerging alternative to tumor rebiopsy in acquired epidermal growth factor receptor (EGFR) tyrosine kinase inhibitor resistance. Validation of analytical sensitivity and clinical utility is required before routine diagnostic use in clinical laboratories.

PATIENTS AND METHODS

Sixty-three patients with advanced EGFR-mutant lung cancer at 7 Canadian centers, who were being screened for the ASTRIS trial (ClinicalTrials.gov identifier: NCT02474355 ), participated in this companion study. Plasma T790M mutation was detected using droplet digital polymerase chain reaction, Cobas (Roche Diagnostics, Indianapolis, IN), or next-generation sequencing in 4 laboratories. T790M concordance was assessed between plasma and tumor samples.

RESULTS

Assessment of T790M in tumor biopsy tissue was successful in 81% of patients; 49% had confirmed T790M results (tumor or plasma) for ASTRIS. Plasma testing in this companion study yielded T790M results in 97% of patients; 62% had T790M-positive results, 36% had negative results, and 2% had indeterminate results. Of 38 patients with negative or indeterminate biopsy results, 55% had positive plasma T790M results, increasing the proportion with T790M-positive results to 73%. Sensitivity of plasma T790M testing was 75%. Overall concordance between tissue and plasma was 64%, and concordance among laboratories was 90.3%. Response to osimertinib and duration of therapy were similar irrespective of testing method (overall response rate, 62.5% for tissue, 66.7% for plasma, and 70.6% for both).

CONCLUSION

This multicenter validation study demonstrates that plasma EGFR T790M testing can identify significantly more patients than biopsy alone who may benefit from targeted therapy.
LncRNA NEAT1 mediates sepsis progression by regulating Irak2 via sponging miR-370-3p
Authors: Xiao Ting , Sun Chuihua , Xiao Ying , Li Yunbao
Published: May 2020

Background: Sepsis is a life-threatening condition and often associated with multiple organ failure. Nuclear-enriched abundant transcript 1 (NEAT1), a member of long non-coding RNAs (lncRNAs), was reported to be involved in the regulation of sepsis progression. However, its precise regulatory mechanism needs to be further explored.

Methods: CCK-8 assay was utilized to check cell viability. The qRT-PCR was employed to detect the expression levels of NEAT1, miR-370-3p and iIrak2. Flow cytometry assay and ELISA were used to check cell apoptosis and the concentrations of inflammatory cytokines, respectively. The starBase was used to predict binding sites between miR-370-3p and NEAT1 or Irak2 and the dual-luciferase reporter assay was performed to verify the interaction. The protein level of Irak2 in samples was measured by western blot.

Results: The high concentration of lipopolysaccharide (LPS) led to the high death ratio of RAW 264.7 and HL-1 cells. Besides, NEAT1 and Irak2 were upregulated in sepsis tissues and LPS-induced RAW 264.7 and HL-1 cells, opposite to the expression of miR-370-3p. In addition, knockdown of NEAT1 promoted viability, suppressed apoptosis and reduced the expression of inflammatory cytokines in LPS-induced RAW 264.7 and HL-1 cells. Moreover, we found that miR-370-3p interacted with NEAT1 and targeted the 3'UTR of Irak2. Further research indicated that downregulation of miR-370-3p or upregulation of IraK2 rescued NEAT1 silencing-mediated inhibitory effect on sepsis progression.

Conclusion: Knockdown of NEAT1 hampered sepsis progression by downregulating Irak2 via interacting with miR-370-3p in LPS-induced RAW 264.7 and HL-1 cells.
Characterization of MORN2 stability and regulatory function in LC3-associated phagocytosis in macrophages
Authors: Morita Maya , Kajiye Mayu , Sakurai Chiye , Kubo Shuichi , Takahashi Miki , Kinoshita Daiki , Hori Naohiro , Hatsuzawa Kiyotaka
Published: May 2020

Microtubule-associated protein A1/B1-light chain 3 (LC3)-associated phagocytosis (LAP) is a type of non-canonical autophagy that regulates phagosome maturation in macrophages. However, the role and regulatory mechanism of LAP remain largely unknown. Recently, membrane occupation and recognition nexus repeat-containing-2 (MORN2) was identified as a key component of LAP for the efficient formation of LC3-recruiting phagosomes. To characterize MORN2 and elucidate its function in LAP, we established a MORN2-overexpressing macrophage line. At steady state, MORN2 was partially cleaved by the ubiquitin-proteasome system. MORN2 overexpression promoted not only LC3-II production but also LAP phagosome (LAPosome) acidification during Escherichia coli uptake. Furthermore, the formation of LAPosomes containing the yeast cell wall component zymosan was enhanced in MORN2-overexpressing cells and depended on reactive oxygen species (ROS). Finally, MORN2-mediated LAP was regulated by plasma membrane-localized soluble N-ethylmaleimide-sensitive factor attachment protein receptors (SNAREs) such as SNAP-23 and syntaxin 11. Taken together, these findings demonstrate that MORN2, whose expression is downregulated via proteasomal digestion, is a limiting factor for LAP, and that the membrane trafficking by SNARE proteins is involved in MORN2-mediated LAP.
Lizard colour plasticity tracks background seasonal changes
Authors: Pellitteri-Rosa Daniele , Gazzola Andrea , Todisco Simone , Mastropasqua Fabio , Liuzzi Cristiano
Published: May 2020

Environmental heterogeneity on spatial and temporal scale fosters organism's capacity to plastically alter coloration. Predation risk might favour the evolution of phenotypic plasticity in colour patterns, as individuals, which change colour throughout the year, could be able to improve their fitness. Here we explored the change in dorsal pigmentation of the Italian wall lizard (Podarcis siculus campestris) along three time points (March, July, October) during the period of activity in a Mediterranean natural area in southern Italy. Following a preliminary investigation conducted in 2018, during 2019 we captured 135 lizards and took a picture of ventral scale to check for possible recaptures over the sessions. Lizard dorsal pictures were collected on the field, with the support of a reference chart, to quantitatively estimate chromatic variables (Hue, Saturation and Value). At the same time, pictures of environmental background were collected. Our findings suggest that lizards are capable of altering dorsal coloration during seasonal change. They vary from green, at the onset of spring, to brownish in the middle of summer, and greyish colour in October. This modification closely followed environmental background colour variation and enhanced lizard crypsis during each season.
Synergy between Acute Intermittent Hypoxia and Task-Specific Training
Authors: Welch Joseph F. , Sutor Tommy W. , Vose Alicia K. , Perim Raphael R. , Fox Emily J. , Mitchell Gordon S.
Published: May 2020

Acute intermittent hypoxia (AIH) and task-specific training (TST) synergistically improve motor function after spinal cord injury; however, mechanisms underlying this synergistic relation are unknown. We propose a hypothetical working model of neural network and cellular elements to explain AIH-TST synergy. Our goal is to forecast experiments necessary to advance our understanding and optimize the neurotherapeutic potential of AIH-TST.