bluuebunny/crossref_metadata_2025_split huggingface dataset:
Exploring LGBTQ+ pedagogy in Japanese university classrooms
Authors: Lawrence Luke , Nagashima Yuzuko 
Published: December 2020

AbstractAlthough ostensibly a free and open society, Japan is often seen to be lagging behind in terms of lesbian, gay, bisexual, transgender, queer, and other (LGBTQ+) rights and understanding of LGBTQ+ issues. This lack of understanding leads to a high degree of invisibility for LGBTQ+ members and a lack of inclusivity in educational curriculums. In this article, the authors document their explorations of introducing both explicit and implicit LGBTQ+ content into university English classes in Japan and their efforts to create a safe and inclusive classroom environment. After reporting on students’ reactions and feelings towards these activities, we recommend a varied approach to LGBTQ+ topics in the classroom that we hope will be of use to teachers not only in Japan, but around the world too.
A systematic review of general practice-based pharmacists’ services to optimize medicines management in older people with multimorbidity and polypharmacy
Authors: Hasan Ibrahim Ameerah S , Barry Heather E , Hughes Carmel M 
Published: December 2020

Abstract

Background
Few studies have evaluated roles of general practice-based pharmacists (PBPs), particularly in optimizing medicines management for older people with both multimorbidity and polypharmacy.

Objective
To explore the types and effectiveness of services provided by PBPs, either alone or in collaboration with other primary health care professionals, that sought to optimize medicines management for older people with multimorbidity and polypharmacy.

Methods
Eight electronic databases and three trial registries were searched for studies published in English until April 2020. Inclusion criteria were randomized controlled trials, non-randomized controlled trials and controlled before-and-after studies of services delivered by PBPs in primary care/general practice, for patients aged ≥65 years with both multimorbidity and polypharmacy that focused on a number of outcomes. The Cochrane risk of bias tool for randomized trials (RoB 1) and the Risk of Bias in Non-randomized Studies-of Interventions (ROBINS-I) assessment tool were used for quality assessment. A narrative synthesis was conducted due to study heterogeneity.

Results
Seven studies met inclusion criteria. All included studies employed PBP-led medication review accompanied by recommendations agreed and implemented by general practitioners. Other patient-level and practice-level interventions were described in one study. The limited available evidence suggested that PBPs, in collaboration with other practice team members, had mixed effects on outcomes focused on optimizing medicines management for older people. Most included studies were of poor quality and data to estimate the risk of bias were often missing.

Conclusion
Future high-quality studies are needed to test the effects of PBP interventions on a well-defined range of medicines management-related outcomes.
microeco: an R package for data mining in microbial community ecology
Authors: Liu Chi , Cui Yaoming , Li Xiangzhen , Yao Minjie 
Published: December 2020

ABSTRACT
A large amount of sequencing data is produced in microbial community ecology studies using the high-throughput sequencing technique, especially amplicon-sequencing-based community data. After conducting the initial bioinformatic analysis of amplicon sequencing data, performing the subsequent statistics and data mining based on the operational taxonomic unit and taxonomic assignment tables is still complicated and time-consuming. To address this problem, we present an integrated R package-‘microeco’ as an analysis pipeline for treating microbial community and environmental data. This package was developed based on the R6 class system and combines a series of commonly used and advanced approaches in microbial community ecology research. The package includes classes for data preprocessing, taxa abundance plotting, venn diagram, alpha diversity analysis, beta diversity analysis, differential abundance test and indicator taxon analysis, environmental data analysis, null model analysis, network analysis and functional analysis. Each class is designed to provide a set of approaches that can be easily accessible to users. Compared with other R packages in the microbial ecology field, the microeco package is fast, flexible and modularized to use and provides powerful and convenient tools for researchers. The microeco package can be installed from CRAN (The Comprehensive R Archive Network) or github (https://github.com/ChiLiubio/microeco).
Metabolic engineering of Saccharomyces cerevisiae for production of β-carotene from hydrophobic substrates
Authors: Fathi Zahra , Tramontin Larissa Ribeiro Ramos , Ebrahimipour Gholamhossein , Borodina Irina , Darvishi Farshad 
Published: December 2020

ABSTRACT
β-Carotene is a yellow–orange–red pigment used in food, cosmetics and pharmacy. There is no commercial yeast-based process for β-carotene manufacturing. In this work, we engineered the baker's yeast Saccharomyces cerevisiae by expression of lipases and carotenogenic genes to enable the production of β-carotene on hydrophobic substrates. First, the extracellular lipase (LIP2) and two cell-bound lipases (LIP7 and LIP8) from oleaginous yeast Yarrowia lipolytica were expressed either individually or in combination in S. cerevisiae. The engineered strains could grow on olive oil and triolein as the sole carbon source. The strain expressing all three lipases had ∼40% lipid content per dry weight. Next, we integrated the genes encoding β-carotene biosynthetic pathway, crtI, crtYB and crtE from Xanthophyllomyces dendrorhous. The resulting engineered strain bearing the lipases and carotenogenic genes reached a titer of 477.9 mg/L β-carotene in yeast peptone dextrose (YPD) medium supplemented with 1% (v/v) olive oil, which was 12-fold higher than an analogous strain without lipases. The highest β-carotene content of 46.5 mg/g DCW was obtained in yeast nitrogen base (YNB) medium supplemented with 1% (v/v) olive oil. The study demonstrates the potential of applying lipases and hydrophobic substrate supplementation for the production of carotenoids in S. cerevisiae.
A Blind Spot in the Use of the Weibull Function for Modeling Diameter Distributions
Authors: Goodwin Adrian Norman 
Published: December 2020

AbstractDiameter distribution models based on probability density functions are integral to many forest growth and yield systems, where they are used to estimate product volumes within diameter classes. The three-parameter Weibull function with a constrained nonnegative lower bound is commonly used because of its flexibility and ease of fitting. This study compared Weibull and reverse Weibull functions with and without a lower bound constraint and left-hand truncation, across three large unthinned plantation cohorts in which 81% of plots had negatively skewed diameter distributions. Near-optimal lower bounds for the unconstrained Weibull function were negative for negatively skewed data, and the left-truncated Weibull using these bounds was 14.2% more accurate than the constrained Weibull, based on the Kolmogorov-Smirnov statistic. The truncated reverse Weibull fit dominant tree distributions 23.7% more accurately than the constrained Weibull, based on a mean absolute difference statistic. This work indicates that a blind spot may have developed in plantation growth modeling systems deploying constrained Weibull functions, and that left-truncation of unconstrained functions could substantially improve model accuracy for negatively skewed distributions.
SNP-adjacent super enhancer network mediates enhanced osteogenic differentiation of MSCs in ankylosing spondylitis
Authors: Yu Wenhui , Chen Keng , Ye Guiwen , Wang Shan , Wang Peng , Li Jinteng , Zheng Guan , Liu Wenjie , Lin Jiajie , Su Zepeng , Che Yunshu , Ye Feng , Ma Mengjun , Xie Zhongyu , Shen Huiyong 
Published: December 2020

Abstract
Ankylosing spondylitis (AS) is a rheumatic disease with pathological osteogenesis that causes bony ankylosis and even deformity over time. Mesenchymal stem cells (MSCs) are multipotent stem cells that are the main source of osteoblasts. We previously demonstrated that enhanced osteogenic differentiation of MSCs from AS patients (ASMSCs) is related to pathological osteogenesis in AS. However, the more concrete mechanism needs further exploration. Super enhancers (SEs) are dense clusters of stitched enhancers that control cell identity determination and disease development. Single-nucleotide polymorphisms (SNPs) regulate the formation and interaction of SEs and denote genes accounting for AS susceptibility. Via integrative analysis of multiomic data, including histone 3 lysine 27 acetylation (H3K27ac), chromatin immunoprecipitation sequencing (ChIP-seq), SNPs and RNA sequencing (RNA-seq) data, we discovered a transcription network mediated by AS SNP-adjacent SEs (SASEs) in ASMSCs and identified key genes, such as Toll-like receptor 4 (TLR4), interleukin 18 receptor 1 (IL18R1), insulin-like growth factor binding protein 4 (IGFBP4), transportin 1 (TNPO1) and proprotein convertase subtilisin/kexin type 5 (PCSK5), which are pivotal in osteogenesis and AS pathogenesis. The SASE-regulated network modulates the enhanced osteogenic differentiation of ASMSCs by synergistically activating the PI3K-Akt, NF-kappaB and Hippo signaling pathways. Our results emphasize the crucial role of the SASE-regulated network in pathological osteogenesis in AS, and the preferential inhibition of ASMSC osteogenic differentiation by JQ1 indicates that SEs may be attractive targets in future treatment for new bone formation in AS.
Mycoplasma genitalium infections can comprise a mixture of both fluoroquinolone-susceptible and fluoroquinolone-resistant strains
Authors: Sweeney Emma L , Lowry Kym , Bletchly Cheryl , Nimmo Graeme R , Whiley David M 
Published: December 2020

Abstract

Background
Mycoplasma genitalium was recently added to the CDC’s antimicrobial resistance threats ‘watch list’, as it has rapidly become resistant to mainstay treatments. In Australia, treatment failure with fluoroquinolones remain commonplace, even when Sanger sequencing fails to identify evidence of resistance mutations.

Methods
Suspecting that Sanger sequencing may miss low-load mixed infections, we applied three additional PCR-based approaches (allele-specific primer-based PCR, probe-based PCR and amplicon deep sequencing) to detect mutations associated with fluoroquinolone susceptibility/resistance. We focused on resistance mutations at amino acid positions 83 and 87 of parC, as these were previously shown to be common in Australia.

Results
Our results showed evidence of mixtures of fluoroquinolone-susceptible and -resistant strains in up to 27/423 samples (6.4%). These included 1 sample that was indicated to be mixed by Sanger sequencing and all three additional PCR methods, 6 samples detected by two or more of the additional PCRs but not by Sanger sequencing and finally 20 samples that were detected by only one of the additional PCR methods. A key question was whether Sanger sequencing failed to detect fluoroquinolone resistance in any samples; overall, we observed that Sanger sequencing failed to detect fluoroquinolone resistance in up to 3.8% (16/423) of samples.

Conclusions
The presence of mixed susceptibility infections may have important implications for clinical patient management and stresses the need for appropriate detection of resistance and selection of antimicrobials to ensure appropriate treatment of M. genitalium infections.
Dynamics of creatinine estimated glomerular filtration rate using one or more antiretrovirals that inhibit creatinine tubular secretion
Authors: Perez Elias Maria Jesus , Alejos Belen , Gutierrez Maria Mar , Crespo Manuel , De Los Santos Gil Ignacio , Ribera Esteve , Galindo Maria Jose , Lozano Fernando , Payeras Cifre Antonio , Boix Vicente , Montero-Alonso Marta , Sanz José , De La Torre Lima Javier , Palacios Rosario , De La Fuente Moral Sara , Martinez Esteban ,   the Codar Study Group, Callau Pilar , Cajal Ramon y , Moreno Ana , Casado Jose Luis , Sanchez Javier Martinez , Ayerbe Cristina Gómez , Vizcarra Pilar , del Campo Santos , Negredo Eugenia , Campos Isabel , Puig Jordi , Ribera Esteban , Torrella Ariadna , Planas Bibiana , Knobel Hernando , Ferrando Ramon , Crespo Manuel , Ocampo Antonio , Sanz José , de los Santos Ignacio , Moreno Alfonso , Díaz Alberto , Carbonero Luz Martin , de la Torre Javier , De Lomas Jose María Garcia , Reina Mercedes Rivas , Santos Jesús , González Domenech Carmen María , Gutierrez Ma Mar , Montero Marta , Cuéllar Sandra , Tasias María , Castro Iván , Boix Vicente , Payeras Antonio , Ryan Pablo , Torralba Miguel , Aznar Esther , Esteban Herminia , de Miguel Marta , Gonzalez Patricia , Yllescas María 
Published: December 2020

AbstractBackgroundCobicistat, dolutegravir and rilpivirine are all modest inhibitors of proximal tubular creatinine secretion (IPTCrS) and hence a moderate and early non-progressive creatinine estimated glomerular filtration rate (Cr-eGFR) reduction has been observed in clinical trials. Data regarding the impact of combination of those drugs on Cr-eGFR, in the clinical practice, are scarcely known.MethodsChanges in Cr-eGFR after starting darunavir/cobicistat alone or in combination with dolutegravir and/or rilpivirine were studied in a nationwide retrospective cohort study of consecutive HIV-infected patients initiating darunavir/cobicistat. The relationship between Cr-eGFR changes over time and the use of darunavir/cobicistat alone or darunavir/cobicistat plus dolutegravir and/or rilpivirine adjusted by different HIV patient’s characteristics, socio-demographics, HIV severity and use of tenofovir concomitant medication other than antiretrovirals was explored through univariate and multivariate analyses.ResultsThe analysis included 725 patients. At 48 weeks, the combination of two or more IPTCrS (darunavir/cobicistat with rilpivirine and/or dolutegravir) was associated with higher decreases in Cr-eGFR [adjusted median difference (±SD) –3.5 ± 1.6 (95% CI –6.6 to –0.3), P = 0.047], and a decrease up to or higher than 15 mL/min/1.73 m2 was more frequent [adjusted OR 3.233 (95% CI 1.343–7.782), P = 0.009], with respect to darunavir/cobicistat alone. The Cr-eGFR changes between darunavir/cobicistat and darunavir/cobicistat with rilpivirine and/or dolutegravir showed more significant decreases in patients taking two or more IPTCrS at 12, 24 and 48 weeks. (ClinicalTrials.gov: NCT03042390).ConclusionsConcomitant use of darunavir/cobicistat plus IPTCrS dolutegravir, rilpivirine, or both produced an additive effect in the expected Cr-eGFR decrease.
Pragmatic options for dose optimization of ceftazidime/avibactam with aztreonam in complex patients
Authors: Falcone Marco , Menichetti Francesco , Cattaneo Dario , Tiseo Giusy , Baldelli Sara , Galfo Valentina , Leonildi Alessandro , Tagliaferri Enrico , Di Paolo Antonello , Pai Manjunath P 
Published: December 2020

Abstract

Background
Avibactam is a β-lactamase inhibitor that is combined with aztreonam against Enterobacterales co-expressing serine- and metallo-β-lactamases (MBL). Optimal dosing of aztreonam with avibactam is not well-defined in critically ill patients and contingent on ceftazidime/avibactam product labelling.

Objectives
To identify a pragmatic dosing strategy for aztreonam with avibactam to maximize the probability of target attainment (PTA).

Methods
We conducted a prospective observational pharmacokinetic study. Five blood samples were collected around the fourth dose of aztreonam or ceftazidime/avibactam and assayed for all three drugs. Population pharmacokinetic (PK) analysis coupled with Monte Carlo simulations were used to create a dosing nomogram for aztreonam and ceftazidime/avibactam based on drug-specific pharmacodynamic (PD) targets.

Results
A total of 41 participants (59% male) median age of 75 years (IQR 63–79 years) were enrolled. They were critically ill (46%) with multiple comorbidities and complications including burns (20%). Population PK analysis identified higher volume of distribution and lower clearance (CL) compared with typical value expectations for aztreonam and ceftazidime/avibactam. Estimated glomerular filtration (eGFR) rate using the CKD-EPI equation predicted CL for all three drugs. The need for high doses of aztreonam and ceftazidime/avibactam above those in the existing product labels are not predicted by this analysis with the exception of ceftazidime/avibactam for patients with eGFR of 6–15 mL/min, in whom suboptimal PTA of ≤71% is predicted.

Conclusions
Pragmatic and lower daily-dose options are predicted for aztreonam and ceftazidime/avibactam when the eGFR is &lt;90 mL/min. These options should be tested prospectively.
Maternal and direct genetic parameters for tail length, tail lesions, and growth traits in pigs
Authors: Aikins-Wilson Sheila , Bohlouli Mehdi , König Sven 
Published: December 2020

AbstractTail length and tail lesions are the major triggers for tail biting in pigs. Against this background, 2 datasets were analyzed to estimate genetic parameters for tail characteristics and growth traits. Dataset 1 considered measurements for trait tail length (T-LEN) and for the growth traits birth weight (BW), weaning weight (WW), postweaning weight (PWW), and average daily gain (ADG) from 9,348 piglets. Piglets were born in the period from 2015 to 2018 and kept on the university Gießen research station. Dataset 2 included 4,943 binary observations from 1,648 pigs from the birth years 2016 to 2019 for tail lesions (T-LES) as indicators for nail necrosis, tail abnormalities, or tail biting. T-LES were recorded at 30 ± 7 d after entry for rearing (T-Les-1), at 50 ± 7 d after entry for rearing (end of the rearing period, T-LES-2), and 130 ± 20 d after entry for rearing (end of fattening period, T-LES-3). Genetic statistical model evaluation for dataset 1 based on Akaike’s information criterion and likelihood ration tests suggested multiple-trait animal models considering covariances between direct and maternal genetic effects. The direct heritability for T-LEN was 0.42 (±0.03), indicating the potential for genetic selection on short tails. The maternal genetic heritability for T-LEN was 0.05 (±0.04), indicating the influence of uterine characteristics on morphological traits. The negative correlation between direct and maternal effects for T-LEN of –0.35 (±0.13), as well as the antagonistic relationships (i.e., positive direct genetic correlations in the range from 0.03 to 0.40) between T-LEN with the growth traits BW, WW, PWW, and ADG, complicate selection strategies and breeding goal definitions. The correlations between direct effects for T-LEN and maternal effects for breeding goal traits, and vice versa, were positive but associated with a quite large SE. The heritability for T-LES when considering the 3 repeated measurements was 0.23 (±0.04) from the linear (repeatability of 0.30) and 0.21 (±0.06; repeatability of 0.29) from the threshold model. The breeding value correlations between T-LES-3 with breeding values from the repeatability models were quite large (0.74 to 0.90), suggesting trait lesion recording at the end of the rearing period. To understand all genetic mechanisms in detail, ongoing studies are focusing on association analyses between T-LEN and T-LES, and the identification of tail biting from an actor’s perspective.
The presence of multiple copies of the vitellogenin gene in Fenneropenaeus merguiensis (De Man, 1888) (Decapoda: Dendrobranchiata: Penaeidae): Evidence for gene expansion and functional diversification in shrimps
Authors: Zhao Jichen , Wang Wei , Wang Chenggui , Shi Lili , Wang Gang , Sun Chengbo , Chan Siuming F 
Published: December 2020

Abstract
Vitellogenin (Vg) is the precursor of egg yolk that provides nutrients to embryos of oviparous animals. We identified three Vg genes (FmVg1, FmVg2, and FmVg3) from the banana shrimp Fennerpenaeus merguiensis (De Man, 1888) (Penaeidae). The cDNAs ranged from 7,758 to 7,764 bp, and the encoded protein consisted of 2,553–2,585 amino acid residues. The genome structures of FmVg1, FmVg2, and FmVg3 were highly conserved, containing 15 exons and 14 introns. FmVg1-FmVg2, FmVg1-FmVg3, and FmVg2-FmVg3 shared a moderate 52.25%, 60.77%, and 56.45%, respectively. Phylogenetic analysis further revealed that the FmVg1 class vitellogenins are more conserved among the shrimps. The expression patterns of FmVg1, FmVg2, and FmVg3 were similar in the hepatopancreas at different ovarian developmental stages, whereas the expression trends between FmVg1 and FmVg2/3 in the ovary were remarkably different. During ontogenic development, the expression of these Vg genes all reached the highest levels at the post-larval stage. The three Vg genes also exhibited dynamic expression changes at different molting stages, with the highest expression level detected at the intermolt stage. Our study provides evidence that at least three copies of the Vg gene are present in the banana shrimp. These Vg genes are potentially involved in ovary maturation and larval development, and the divergence in their sequences, structures, and expression dynamics reflects their functional diversification in F. merguiensis. The expression of these Vg genes is therefore tightly regulated spatially and temporally. This is the first report for the molecular characterization of multiple vitellogenin genes in shrimps. Our results indicate that the vitellogenin gene is multi-functional and shows a non-sex specific expression pattern.
Measuring Systemic Risk Using Multivariate Quantile-Located ES Models
Authors: Garcia-Jorcano Laura , Sanchis-Marco Lidia 
Published: December 2020

AbstractWe examine the tail systemic risk between the global financial system and financial institutions that belong to different industry groups. Our main contribution is the development of a systemic risk measure Delta Quantile-Located Conditional Autoregressive Expected Shortfall, ΔQLMV−CoCARES. This new measure captures the extreme downside risk in terms of the ES of the system should both the financial system and the institution simultaneously be in distress. The evidence suggests that cross significant volatility and ES effects exist between the system and financial institutions. Furthermore, our measure presents better forecasting performance than standard or novel systemic risk measures based on VaR such as CoVaR or ΔQLMV−CoCAViaR and it is effective at predicting financial crises. We also develop a new systemic stress indicator SSIES based on ΔQLMV−CoCARES systemic risk measure which presents higher forecasting ability than other standard stress indicators.