bluuebunny/crossref_metadata_2025_split huggingface dataset:
Correlations of inclusion-based rock-physics model inputs from Bayesian analysis
Authors: Spikes Kyle T , Sen Mrinal K 
Published: September 2022

AbstractFor any given rock-physics model, knowledge of correlations among its inputs helps to define geologically and physically meaningful and informed models for a given problem. These informed models can, in turn, reduce the uncertainty in forward and inverse problems. We use a Bayesian framework to identify such correlations among inputs of two rock-physics models. That framework makes use of velocity and porosity measurements on both dry and brine-saturated carbonate samples. Two inclusion-based rock-physics models, the self-consistent approximation and the differential effective medium model, are analyzed along with these data to identify the underlying correlations. To do so, the posterior distribution must be evaluated, which is based on a prior model and the calculated likelihood function. Exhaustive sampling of the posterior is convenient in this case because relatively few input parameters to consider. Results are multi-variate histograms that indicate maximum a posteriori values of the inputs. Correlations among the inputs become evident when the Bayesian analysis is repeated many times with different prior models. These correlated values provide the inputs to optimized maximum a posteriori models. The correlations identified for the two rock-physics models under study should be used in relevant applications. Finally, all rock-physics models, along with an appropriate data set, should be examined in a similar Bayesian framework.
Prevalence and risk estimation of cancer-predisposing genes for upper urinary tract urothelial carcinoma in Japanese
Authors: Sekine Yuya , Iwasaki Yusuke , Hakozaki Nozomi , Endo Mikiko , Kamatani Yoichiro , Matsuda Koichi , Murakami Yoshinori , Sano Takeshi , Akamatsu Shusuke , Kobayashi Takashi , Nakagawa Hidewaki , Numakura Kazuyuki , Narita Shintaro , Habuchi Tomonori , Momozawa Yukihide 
Published: September 2022

Abstract
Upper urinary tract urothelial carcinoma is a rare cancer that has been associated with mismatch repair genes such as MLH1, MSH2, MSH6 and PMS2. In addition, patients with pathogenic variants of cancer-predisposing genes such as BRCA1 and BRCA2 have been reported. However, how cancer-predisposing genes affect the risk of upper urinary tract urothelial carcinoma in the Japanese population remains unclear. Thus, we performed a case–control sequencing study of 27 cancer-predisposing genes in 208 upper urinary tract urothelial carcinoma patients and 37 727 controls. Only MSH6 and MSH2 were observed with a value of P &lt; 0.05. However, there was no difference in the prevalence of pathogenic variants of BRCA1/2, which does not support the use of a poly adenosine diphosphate-ribose polymerase inhibitor in patients with upper urinary tract urothelial carcinoma. Only mismatch repair genes were associated with patients with upper urinary tract urothelial carcinoma, but the prevalence of pathogenic variants in mismatch repair genes was lower than that reported in previous studies from other populations.
Prescribing unproven cancer drugs: physician perspectives on expanded access and right to try
Authors: Manley Haley , Sisk Bryan A , Master Zubin , Scott Christopher Thomas 
Published: September 2022

Abstract

Background
For gravely ill patients who have no treatment options and who are ineligible for clinical trials, the US Food and Drug Administration (FDA) established the Expanded Access Program (EAP). Motivated by efforts to weaken FDA regulation and sold as providing greater access to experimental drugs, the federal Right to Try Act (RTT) was passed in 2017. It reduces FDA oversight by not requiring physicians to report safety data and foregoes approval of protocols by local institutional review boards.

Methods
This study explored the views of 17 neuro-oncologists from 15 different academic medical centers with varying experience with EAP and RTT using convenience sampling. We conducted semi-structured interviews and qualitative analysis to identify emerging themes.

Results
Most oncologists were confused between the two pathways, had little familiarity with RTT, and had little knowledge about experimental medicine available through either pathway. Oncologists reported a preference of enrolling patients in clinical trials over off-trial preapproval pathways with scant data. As a result, oncologists revealed concerns over properly evaluating risks for their patients.

Conclusion
Our findings suggest that neuro-oncologists need better resources and clearer mechanisms at their institutions to help navigate EAP and RTT in order to counsel patients interested in experimental medicine.
Predicting plant Rubisco kinetics from RbcL sequence data using machine learning
Authors: Iqbal Wasim A , Lisitsa Alexei , Kapralov Maxim V 
Published: September 2022

AbstractRibulose-1,5-bisphosphate carboxylase/oxygenase (Rubisco) is responsible for the conversion of atmospheric CO2 to organic carbon during photosynthesis, and often acts as a rate limiting step in the later process. Screening the natural diversity of Rubisco kinetics is the main strategy used to find better Rubisco enzymes for crop engineering efforts. Here, we demonstrate the use of Gaussian processes (GPs), a family of Bayesian models, coupled with protein encoding schemes, for predicting Rubisco kinetics from Rubisco large subunit (RbcL) sequence data. GPs trained on published experimentally obtained Rubisco kinetic datasets were applied to over 9000 sequences encoding RbcL to predict Rubisco kinetic parameters. Notably, our predicted kinetic values were in agreement with known trends, e.g. higher carboxylation turnover rates (Kcat) for Rubisco enzymes from C4 or crassulacean acid metabolism (CAM) species, compared with those found in C3 species. This is the first study demonstrating machine learning approaches as a tool for screening and predicting Rubisco kinetics, which could be applied to other enzymes.
Distribution, trends, and antifungal susceptibility ofCandidaspecies causing candidemia in Japan, 2010–2019: A retrospective observational study based on national surveillance data
Authors: Kajihara Toshiki , Yahara Koji , Nagi Minoru , Kitamura Norikazu , Hirabayashi Aki , Hosaka Yumiko , Abe Masahiro , Miyazaki Yoshitsugu , Sugai Motoyuki 
Published: September 2022

AbstractThe increasing incidence of candidemia and the emergence of drug-resistant Candida species are major concerns worldwide. Therefore, long-term surveillance studies are required. Here, we provide one of the largest longitudinal overviews of the trends in the prevalence of Candida species using national data of 57 001 candidemia isolates obtained from &gt; 2000 hospitals for the 2010–2019 period in the Japan Nosocomial Infections Surveillance database. The proportion of Candida species, except Candida krusei and Candida guilliermondii, was almost the same during the study period. The proportion of C. guilliermondii surpassed that of C. krusei in 2014. The incidence of candidemia due to C. albicans (P &lt; 0.0001), C. parapsilosis (P = 0.0002), and C. tropicalis (P &lt; 0.0001) have decreased significantly over this period. Azole susceptibility of C. tropicalis was low, with 17.8% of isolates resistant to fluconazole and 13.5% resistant to voriconazole. The micafungin susceptibility of C. glabrata was low, with 8.0% of isolates showing resistance. The resistance rate of C. krusei toward amphotericin B fluctuated considerably (between 3.2% and 35.7%) over this period. The incidence rate of candidemia caused by C. parapsilosis and C. guilliermondii in hospitals responsible for bone marrow transplantation was significantly higher than that in other hospitals. Overall, our study suggests that in Japan, the species distribution of Candida was almost the same in this period and similar to that reported in North America and Europe. A relatively high resistance to azoles and micafungin was observed in C. glabrata, C. tropicalis, and C. krusei isolates, which require continued surveillance.
Could kilomasers pinpoint supermassive stars?
Authors: Nowak Katarzyna , Krause Martin G H , Schaerer Daniel 
Published: September 2022

ABSTRACT
A strong nuclear kilomaser, W1, has been found in the nearby galaxy NGC 253, associated with a forming super star cluster. Kilomasers could arise from the accretion disc around supermassive stars (&gt;103 M⊙), hypothetical objects that have been proposed as polluters responsible for the chemical peculiarities in globular clusters. The supermassive stars would form via runaway collisions, simultaneously with the cluster. Their discs are perturbed by stellar flybys, inspiralling and colliding stars. This raises the question if an accretion disc would at all be able to survive in such a dynamic environment and mase water lines. We investigated what the predicted maser spectrum of such a disc would look like using 2D hydrodynamic simulations and compared this to the W1 kilomaser. We derived model maser spectra from the simulations by using a general maser model for appropriate disc temperatures. All our model discs survived. The model maser spectra for the most destructive case for the simulations of M⋆ = 1000 M⊙ are a reasonable match with the W1 kilomaser spectrum in terms of scaling, flux values and some of the signal trends. Details in the spectrum suggest that a star of a few 1000 M⊙ might fit even better, with 10 000 M⊙ clearly giving too large velocities. Our investigations thus support the hypothesis that kilomasers could pinpoint supermassive stars.
Turbulence in outer protoplanetary discs: MRI or VSI?
Authors: Cui Can , Bai Xue-Ning 
Published: September 2022

ABSTRACT
The outer protoplanetary discs (PPDs) can be subject to the magnetorotational instability (MRI) and the vertical shear instability (VSI). While both processes can drive turbulence in the disc, existing numerical simulations have studied them separately. In this paper, we conduct global 3D non-ideal magnetohydrodynamic (MHD) simulations for outer PPDs, with ambipolar diffusion and instantaneous cooling, and hence conductive to both instabilities. Given the range of ambipolar Elsässer numbers (Am) explored, it is found that the VSI turbulence dominates over the MRI when ambipolar diffusion is strong (Am = 0.1); the VSI and MRI can co-exist for Am = 1; and the VSI is overwhelmed by the MRI when ambipolar diffusion is weak (Am = 10). Angular momentum transport process is primarily driven by MHD winds, while viscous accretion due to MRI and/or VSI turbulence makes a moderate contribution in most cases. Spontaneous magnetic flux concentration and formation of annular substructures remain robust in strong ambipolar diffusion-dominated discs (Am ≤ 1) with the presence of the VSI. Ambipolar diffusion is the major contributor to the magnetic flux concentration phenomenon rather than advection.
Cytoprotective and genoprotective effects of taxifolin against oxidative damage in HTR-8/SVneo human trophoblast cells
Authors: Bruić Marija , Pirković Andrea , Vilotić Aleksandra , Jovanović-Krivokuća Milica , Spremo-Potparević Biljana 
Published: September 2022

Abstract
An increase of reactive oxygen species in the placenta and oxidative disbalance has been recognized as a significant factor contributing to pregnancy complications. Dietary intake of food rich in antioxidants during pregnancy could exert a protective role in the prevention of adverse outcomes such as preeclampsia, miscarriage, and others. Flavonoid taxifolin has shown numerous health-promoting effects in a large number of studies conducted on animals, as well as various human cell types in vitro. However, its effects on human placental cells—trophoblasts—have yet to be determined. Therefore, cytoprotective and genoprotective effects of taxifolin on trophoblast cell line HTR-8/SVneo under induced oxidative stress were explored in this study. Cytotoxicity of a range of taxifolin concentrations (1–150 µM) was evaluated using the MTT and crystal violet assays. A model of oxidative stress was achieved by exposing HTR-8/SVneo cells to H2O2. To determine cytoprotective and antigenotoxic effects, the cells were pre-incubated with three concentrations of taxifolin (10, 50, and 100 µM) and then exposed to H2O2. Taxifolin in concentrations of 1, 5, 10, 25, 50, and 100 µM showed no cytotoxic effects on HTR-8/SVneo cells, but 150 µM of taxifolin caused a significant decrease in adherent cell number, as detected by crystal violet assay. Pretreatment with the chosen concentrations of taxifolin showed a significant cytoprotective effect on H2O2-induced cytotoxicity, as determined by the MTT assay. Furthermore, taxifolin showed a significant reduction in H2O2-induced DNA damage, measured by comet assay. This study showed protective effects of taxifolin on human trophoblast cells exposed to oxidative damage. Further studies are needed to explore the underlying mechanisms.
Single and combined potential of polystyrene microparticles and fluoranthene in the induction of DNA damage in haemocytes of Mediterranean mussel (Mytilus galloprovincialis)
Authors: Kolarević Stoimir , Kračun-Kolarević Margareta , Marić Jovana Jovanović , Djordjević Jelena , Vuković-Gačić Branka , Joksimović Danijela , Martinović Rajko , Bajt Oliver , Ramšak Andreja 
Published: September 2022

Abstract
In this study, the possible ‘vector effect’ within the exposure of Mediterranean mussels (Mytilus galloprovincialis) to polystyrene microplastics with adsorbed fluoranthene was investigated by applying the multibiomarker approach. The major focus was placed on genotoxicological endpoints as to our knowledge there are no literature data on the genotoxicity of polystyrene microparticles alone or with adsorbed fluoranthene in the selected experimental organisms. DNA damage was assessed in haemocytes by comet assay and micronucleus test. For the assessment of neurotoxicity, acetylcholinesterase activity was measured in gills. Glutathione S-transferase was assessed in gills and hepatopancreas since these enzymes are induced for biotransformation and excretion of lipophilic compounds such as hydrocarbons. Finally, differences in physiological response within the exposure to polystyrene particles, fluoranthene, or particles with adsorbed fluoranthene were assessed by the variation of heart rate patterns studied by the noninvasive laser fibre-optic method. The uniform response of individual biomarkers within the exposure groups was not recorded. There was no clear pattern in variation of acetylcholinesterase or glutathione S-transferase activity which could be attributed to the treatment. Exposure to polystyrene increased DNA damage which was detected by the comet assay but was not confirmed by micronucleus formation. Data of genotoxicity assays indicated differential responses among the groups exposed to fluoranthene alone and fluoranthene adsorbed to polystyrene. Change in the heart rate patterns within the studied groups supports the concept of the Trojan horse effect within the exposure to polystyrene particles with adsorbed fluoranthene.
Advanced transcriptomic analysis reveals the role of efflux pumps and media composition in antibiotic responses ofPseudomonas aeruginosa
Authors: Rajput Akanksha , Tsunemoto Hannah , Sastry Anand V , Szubin Richard , Rychel Kevin , Chauhan Siddharth M , Pogliano Joe , Palsson Bernhard O 
Published: September 2022

AbstractPseudomonas aeruginosa is an opportunistic pathogen and major cause of hospital-acquired infections. The virulence of P. aeruginosa is largely determined by its transcriptional regulatory network (TRN). We used 411 transcription profiles of P. aeruginosa from diverse growth conditions to construct a quantitative TRN by identifying independently modulated sets of genes (called iModulons) and their condition-specific activity levels. The current study focused on the use of iModulons to analyze the biofilm production and antibiotic resistance of P. aeruginosa. Our analysis revealed: (i) 116 iModulons, 81 of which show strong association with known regulators; (ii) novel roles of regulators in modulating antibiotics efflux pumps; (iii) substrate-efflux pump associations; (iv) differential iModulon activity in response to beta-lactam antibiotics in bacteriological and physiological media; (v) differential activation of ‘Cell Division’ iModulon resulting from exposure to different beta-lactam antibiotics and (vi) a role of the PprB iModulon in the stress-induced transition from planktonic to biofilm lifestyle. In light of these results, the construction of an iModulon-based TRN provides a transcriptional regulatory basis for key aspects of P. aeruginosa infection, such as antibiotic stress responses and biofilm formation. Taken together, our results offer a novel mechanistic understanding of P. aeruginosa virulence.
Domain function and predicted structure of three heterodimeric endonuclease subunits of RNA editing catalytic complexes in Trypanosoma brucei
Authors: Carnes Jason , McDermott Suzanne M , Lewis Isaac , Tracy Maxwell , Stuart Kenneth 
Published: September 2022

Abstract
Each of the three similar RNA Editing Catalytic Complexes (RECCs) that perform gRNA-directed uridine insertion and deletion during Trypanosoma brucei mitochondrial (mt) mRNA editing has a distinct endonuclease activity that requires two related RNase III proteins, with only one competent for catalysis. We identified multiple loss-of-function mutations in the RNase III and other motifs of the non-catalytic KREPB6, KREPB7, and KREPB8 components by random mutagenesis and screening. These mutations had various effects on growth, editing, and both the abundances and RECC associations of these RNase III protein pairs in bloodstream form (BF) and procyclic form (PF) cells. Protein structure modelling predicted that the Zinc Finger (ZnF) of each paired RNase III protein contacts RNA positioned at the heterodimeric active site which is flanked by helices of a novel RNase III-Associated Motif (RAM). The results indicate that the protein domains of the non-catalytic subunits function together in RECC integrity, substrate binding, and editing site recognition during the multistep RNA editing process. Additionally, several mutants display distinct functional consequences in different life cycle stages. These results highlight the complementary roles of protein pairs and three RECCs within the complicated T. brucei mRNA editing machinery that matures mt mRNAs differentially between developmental stages.
Yeast transcriptional device libraries enable precise synthesis of value-added chemicals from methanol
Authors: Zhu Qiaoyun , Liu Qi , Yao Chaoying , Zhang Yuanxing , Cai Menghao 
Published: September 2022

Abstract
Natural methylotrophs are attractive methanol utilization hosts, but lack flexible expression tools. In this study, we developed yeast transcriptional device libraries for precise synthesis of value-added chemicals from methanol. We synthesized transcriptional devices by fusing bacterial DNA-binding proteins (DBPs) with yeast transactivation domains, and linking bacterial binding sequences (BSs) with the yeast core promoter. Three DBP–BS pairs showed good activity when working with transactivation domains and the core promoter of PAOX1 in the methylotrophic yeast, Pichia pastoris. Fine-tuning of the tandem BSs, spacers and differentiated input promoters further enabled a constitutive transcriptional device library (cTRDL) composed of 126 transcriptional devices with an expression strength of 16–520% and an inducible TRDL (iTRDL) composed of 162 methanol-inducible transcriptional devices with an expression strength of 30–500%, compared with PAOX1. Selected devices from iTRDL were adapted to the dihydromonacolin L biosynthetic pathway by orthogonal experimental design, reaching 5.5-fold the production from the PAOX1-driven pathway. The full factorial design of the selected devices from the cTRDL was adapted to the downstream pathway of dihydromonacolin L to monacolin J. Monacolin J production from methanol reached 3.0-fold the production from the PAOX1-driven pathway. Our engineered toolsets ensured multilevel pathway control of chemical synthesis in methylotrophic yeasts.
Splicing of branchpoint-distant exons is promoted by Cactin, Tls1 and the ubiquitin-fold-activated Sde2
Authors: Anil Anupa T , Choudhary Karan , Pandian Rakesh , Gupta Praver , Thakran Poonam , Singh Arashdeep , Sharma Monika , Mishra Shravan Kumar 
Published: September 2022

AbstractIntron diversity facilitates regulated gene expression and alternative splicing. Spliceosomes excise introns after recognizing their splicing signals: the 5′-splice site (5′ss), branchpoint (BP) and 3′-splice site (3′ss). The latter two signals are recognized by U2 small nuclear ribonucleoprotein (snRNP) and its accessory factors (U2AFs), but longer spacings between them result in weaker splicing. Here, we show that excision of introns with a BP-distant 3′ss (e.g. rap1 intron 2) requires the ubiquitin-fold-activated splicing regulator Sde2 in Schizosaccharomyces pombe. By monitoring splicing-specific ura4 reporters in a collection of S. pombe mutants, Cay1 and Tls1 were identified as additional regulators of this process. The role of Sde2, Cay1 and Tls1 was further confirmed by increasing BP–3′ss spacings in a canonical tho5 intron. We also examined BP-distant exons spliced independently of these factors and observed that RNA secondary structures possibly bridged the gap between the two signals. These proteins may guide the 3′ss towards the spliceosome's catalytic centre by folding the RNA between the BP and 3′ss. Orthologues of Sde2, Cay1 and Tls1, although missing in the intron-poor Saccharomyces cerevisiae, are present in intron-rich eukaryotes, including humans. This type of intron-specific pre-mRNA splicing appears to have evolved for regulated gene expression and alternative splicing of key heterochromatin factors.
Impact of Antibiotics on the Lung Microbiome and Lung Function in Children With Cystic Fibrosis 1 Year After Hospitalization for an Initial Pulmonary Exacerbation
Authors: Inam Zaina , Felton Erin , Burrell Aszia , Chaney Hollis , Sami Iman , Koumbourlis Anastassios C , Freishtat Robert J , Zemanick Edith T , Crandall Keith A , Hahn Andrea 
Published: September 2022

Abstract

Background
Cystic fibrosis (CF) is characterized by recurrent pulmonary exacerbations (PEx) and lung function decline. PEx are frequently treated with antibiotics. However, little is known about the effects of antibiotics on the airway microbiome of persons with CF over time. The purpose of this study was to evaluate changes in the microbiome and lung function in persons with CF over 1 year following an initial study pulmonary exacerbation (iPEx).

Methods
Twenty children aged ≤18 years with CF were enrolled in the study, which occurred prior to the routine administration of highly effective modulator therapy. Respiratory samples and spirometry were obtained at a minimum of quarterly visits and up to 1 year after an iPEx. Metagenomic sequencing was performed, and bacterial taxa were assigned using MetaPhlAn 2.0. Paired t test, analysis of variance, and generalized least squares regression were used to compare outcome variables.

Results
The mean age of study participants at the time of the iPEx was 10.6 years. There were 3 ± 1.6 PEx treated with antibiotics per person during the study period. Bacterial richness was similar at 1 year compared to iPEx (40.3 vs 39.3, P = .852), whereas the mean Shannon diversity index was significantly higher at 1 year (2.84 vs 1.62, P &lt; .001). The number of PEx treated with antibiotics was not associated with changes in microbial diversity but was associated with changes in lung function.

Conclusions
In our 1-year prospective study, we found that microbial diversity increased despite decreases in lung function associated with repeated PEx events requiring antibiotic therapy.