bluuebunny/crossref_metadata_2025_split huggingface dataset:
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

Abstract
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

Abstract
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

AbstractBackgroundExtracorporeal 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.MethodsCount 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.ResultsBoth 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.ConclusionAdditional 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

Abstract
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

Abstract
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

Abstract
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

Abstract
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

AbstractLactobacillus 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

Abstract
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

AbstractThere 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

AbstractFriction 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.