bluuebunny/crossref_metadata_2025_split huggingface dataset:
Ultracontinuous Single Haplotype Genome Assemblies for the Domestic Cat (Felis catus) and Asian Leopard Cat (Prionailurus bengalensis)
Authors: Bredemeyer Kevin R , Harris Andrew J , Li Gang , Zhao Le , Foley Nicole M , Roelke-Parker Melody , O’Brien Stephen J , Lyons Leslie A , Warren Wesley C , Murphy William J 
Published: December 2020

AbstractIn addition to including one of the most popular companion animals, species from the cat family Felidae serve as a powerful system for genetic analysis of inherited and infectious disease, as well as for the study of phenotypic evolution and speciation. Previous diploid-based genome assemblies for the domestic cat have served as the primary reference for genomic studies within the cat family. However, these versions suffered from poor resolution of complex and highly repetitive regions, with substantial amounts of unplaced sequence that is polymorphic or copy number variable. We sequenced the genome of a female F1 Bengal hybrid cat, the offspring of a domestic cat (Felis catus) x Asian leopard cat (Prionailurus bengalensis) cross, with PacBio long sequence reads and used Illumina sequence reads from the parents to phase &gt;99.9% of the reads into the 2 species’ haplotypes. De novo assembly of the phased reads produced highly continuous haploid genome assemblies for the domestic cat and Asian leopard cat, with contig N50 statistics exceeding 83 Mb for both genomes. Whole-genome alignments reveal the Felis and Prionailurus genomes are colinear, and the cytogenetic differences between the homologous F1 and E4 chromosomes represent a case of centromere repositioning in the absence of a chromosomal inversion. Both assemblies offer significant improvements over the previous domestic cat reference genome, with a 100% increase in contiguity and the capture of the vast majority of chromosome arms in 1 or 2 large contigs. We further demonstrated that comparably accurate F1 haplotype phasing can be achieved with members of the same species when one or both parents of the trio are not available. These novel genome resources will empower studies of feline precision medicine, adaptation, and speciation.
Canadian Federal Court of Appeal Rules it can interpret contracts: rejects Goldilocks approach to jurisdiction  Salt Canada Inc v Baker, 2020 FCA 127, 28 July 2020
Authors: Crowne Emir 
Published: December 2020

Abstract
The Canadian Federal Court of Appeal ruled that it can interpret contracts without resorting to the ‘Goldilocks approach to jurisdiction, taste-testing each case for the appropriate amount of federal flavour and asserting jurisdiction only in cases where the federal content is, in the personal opinion of a judge, “just right”.’
The halo model as a versatile tool to predict intrinsic alignments
Authors: Fortuna Maria Cristina , Hoekstra Henk , Joachimi Benjamin , Johnston Harry , Chisari Nora Elisa , Georgiou Christos , Mahony Constance 
Published: December 2020

ABSTRACTIntrinsic alignments (IAs) of galaxies are an important contaminant for cosmic shear studies, but the modelling is complicated by the dependence of the signal on the source galaxy sample. In this paper, we use the halo model formalism to capture this diversity and examine its implications for Stage-III and Stage-IV cosmic shear surveys. We account for the different IA signatures at large and small scales, as well as for the different contributions from central/satellite and red/blue galaxies, and we use realistic mocks to account for the characteristics of the galaxy populations as a function of redshift. We inform our model using the most recent observational findings: we include a luminosity dependence at both large and small scales and a radial dependence of the signal within the halo. We predict the impact of the total IA signal on the lensing angular power spectra, including the current uncertainties from the IA best-fits to illustrate the range of possible impact on the lensing signal: the lack of constraints for fainter galaxies is the main source of uncertainty for our predictions of the IA signal. We investigate how well effective models with limited degrees of freedom can account for the complexity of the IA signal. Although these lead to negligible biases for Stage-III surveys, we find that, for Stage-IV surveys, it is essential to at least include an additional parameter to capture the redshift dependence.
Gene-specific mutagenesis enables rapid continuous evolution of enzymesin vivo
Authors: Park Hyojin , Kim Seokhee 
Published: December 2020

AbstractVarious in vivo mutagenesis methods have been developed to facilitate fast and efficient continuous evolution of proteins in cells. However, they either modify the DNA region that does not match the target gene, or suffer from low mutation rates. Here, we report a mutator, eMutaT7 (enhanced MutaT7), with very fast in vivo mutation rate and high gene-specificity in Escherichia coli. eMutaT7, a cytidine deaminase fused to an orthogonal RNA polymerase, can introduce up to ∼4 mutations per 1 kb per day, rivalling the rate in typical in vitro mutagenesis for directed evolution of proteins, and promotes rapid continuous evolution of model proteins for antibiotic resistance and allosteric activation. eMutaT7 provides a very simple and tunable method for continuous directed evolution of proteins, and suggests that the fusion of new DNA-modifying enzymes to the orthogonal RNA polymerase is a promising strategy to explore the expanded sequence space without compromising gene specificity.
Programmable gene regulation for metabolic engineering using decoy transcription factor binding sites
Authors: Wang Tiebin , Tague Nathan , Whelan Stephen A , Dunlop Mary J 
Published: December 2020

Abstract
Transcription factor decoy binding sites are short DNA sequences that can titrate a transcription factor away from its natural binding site, therefore regulating gene expression. In this study, we harness synthetic transcription factor decoy systems to regulate gene expression for metabolic pathways in Escherichia coli. We show that transcription factor decoys can effectively regulate expression of native and heterologous genes. Tunability of the decoy can be engineered via changes in copy number or modifications to the DNA decoy site sequence. Using arginine biosynthesis as a showcase, we observed a 16-fold increase in arginine production when we introduced the decoy system to steer metabolic flux towards increased arginine biosynthesis, with negligible growth differences compared to the wild type strain. The decoy-based production strain retains high genetic integrity; in contrast to a gene knock-out approach where mutations were common, we detected no mutations in the production system using the decoy-based strain. We further show that transcription factor decoys are amenable to multiplexed library screening by demonstrating enhanced tolerance to pinene with a combinatorial decoy library. Our study shows that transcription factor decoy binding sites are a powerful and compact tool for metabolic engineering.
Immersive 3-Dimensional Virtual Reality Modeling for Case-Specific Presurgical Discussions in Cerebrovascular Neurosurgery
Authors: Sugiyama Taku , Clapp Tod , Nelson Jordan , Eitel Chad , Motegi Hiroaki , Nakayama Naoki , Sasaki Tsukasa , Tokairin Kikutaro , Ito Masaki , Kazumata Ken , Houkin Kiyohiro 
Published: December 2020

Abstract

BACKGROUND
Adequate surgical planning includes a precise understanding of patient-specific anatomy and is a necessity for neurosurgeons. Although the use of virtual reality (VR) technology is emerging in surgical planning and education, few studies have examined the effectiveness of immersive VR during surgical planning using a modern head-mounted display.

OBJECTIVE
To investigate if and how immersive VR aids presurgical discussions of cerebrovascular surgery.

METHODS
A multiuser immersive VR system, BananaVisionTM, was developed and used during presurgical discussions in a prospective patient cohort undergoing cerebrovascular surgery. A questionnaire/interview was administered to multiple surgeons after the surgeries to evaluate the effectiveness of the VR system compared to conventional imaging modalities. An objective assessment of the surgeon's knowledge of patient-specific anatomy was also conducted by rating surgeons’ hand-drawn presurgical illustrations.

RESULTS
The VR session effectively enhanced surgeons’ understanding of patient-specific anatomy in the majority of cases (83.3%). An objective assessment of surgeons’ presurgical illustrations was consistent with this result. The VR session also effectively improved the decision-making process regarding minor surgical techniques in 61.1% of cases and even aided surgeons in making critical surgical decisions about cases involving complex and challenging anatomy. The utility of the VR system was rated significantly higher by trainees than by experts.

CONCLUSION
Although rated as more useful by trainees than by experts, immersive 3D VR modeling increased surgeons’ understanding of patient-specific anatomy and improved surgical strategy in certain cases involving challenging anatomy.
Preliminary evidence on abatacept safety and efficacy in refractory juvenile localized scleroderma
Authors: Li Suzanne C , Torok Kathryn S , Ishaq Sarah S , Buckley Mary , Edelheit Barbara , Ede Kaleo C , Liu Christopher , Rabinovich C Egla 
Published: December 2020

AbstractObjectiveTo evaluate the safety and efficacy of abatacept treatment for refractory juvenile localized scleroderma (jLS) in a retrospective study.MethodsA multicentre cohort study was performed to evaluate jLS subjects treated with abatacept with follow-up for 12 months to maximum of 24 months. Assessments at 6-month intervals included skin activity measures and physician global assessment of activity (PGA-A). Descriptive statistical analysis was performed.ResultsEighteen subjects were studied with median age of 13.4 years, the majority had linear scleroderma subtype, and musculoskeletal involvement. All had previously failed MTX and/or mycophenolate mofetil treatment and glucocorticoids. Abatacept was added to the subject’s maintenance DMARD treatment; 13 also received glucocorticoids at start of abatacept. No serious adverse events occurred. Skin activity and PGA-A scores declined in nearly all by 6 months and continued to improve from 6 to 12 months. At 12 months, 15 (83%) subjects were considered responders, two (11%) treatment failures, and one dropped out for adverse event. Response was sustained for 11 (61%) subjects to 18 months and eight (44%) to 24 months. Overall, four (22%) subjects were treatment failures and three (16.7%) discontinued abatacept for adverse event. Active musculoskeletal problems improved in most affected subjects. Ten subjects were able to discontinue initial glucocorticoid and six concomitant DMARD treatment.ConclusionAbatacept was found to be safe and effective for jLS subjects refractory to standard of care treatment. Subjects experienced improvement in both skin and musculoskeletal activity. Prospective studies should be performed to more fully evaluate abatacept’s efficacy.
Beta-cell function is disrupted in patients with systemic lupus erythematosus
Authors: García-Dorta Alicia , Quevedo-Abeledo Juan Carlos , Rua-Figueroa Íñigo , de Vera-González Antonia M , González-Delgado Alejandra , Medina-Vega Lilian , González-Rivero Agustín F , Francisco-Hernández Felix , González-Gay Miguel A , Ferraz-Amaro Iván 
Published: December 2020

Abstract

Objectives
To investigate how markers of beta-cell secretion (proinsulin-processing metabolites) are expressed in SLE patients and their potential relation to features associated with the disease such as activity or damage.

Methods
One hundred and forty-four SLE patients and 69 nondiabetic sex- and age-matched controls were assessed. Beta-cell secretion molecules, as measured by insulin, split and intact proinsulins, and C-peptide levels were analysed in both groups. Multiple regression analysis was performed to compare proinsulin propeptides between groups and to explore the interrelations with SLE features. Analyses were adjusted for glucocorticoid intake and for insulin resistance classic risk factors.

Results
Fully multivariable analysis demonstrated that regardless of glucocorticoid use, SLE patients exhibited higher levels of split proinsulin. Likewise, the split proinsulin-to-insulin ratio was upregulated in patients with SLE undergoing glucocorticoid therapy [beta coeficient 0.19 (95% Confidence Interval 0.07, 0.30), P = 0.002] or not [beta coef. 0.09 (95% CI: 0.01, 0.17), P = 0.025]. Similar results were found for the intact proinsulin-to-insulin ratio, although differences were only statistically significant for patients taking glucocorticoids [beta coef. 0.08 (95% CI: 0.03, 0.12), P = 0.001]. SLE damage score was associated with higher serum levels of intact [beta coef. 0.51 (95% CI 0.17, 0.86) pmol/l, P = 0.004] and split proinsulins [beta coef. 1.65 (95% CI 0.24, 3.06) pmol/l, P = 0.022] after multivariable analysis, including disease duration and prednisone use.

Conclusion
Among patients with SLE, proinsulin-processing metabolites, a marker of beta-cell disruption, are upregulated compared with matched controls. This disproportionate hyperproinsulinemia can be explained by the damage produced by the disease and occurs independently of prednisone use.
CD34+CD133+CD309+ circulating angiogenic cell level is reduced but positively related to hydroxychloroquine use in SLE patients—a case–control study and meta-regression analysis
Authors: Huang Jinghui , Kow Nien Yee , Lee Hui Yin , Fairhurst Anna-Marie , Mak Anselm 
Published: December 2020

AbstractObjectivesTo identify and quantify the level of CD34+CD133+CD309+ circulating angiogenic cells (CAC) and explore factors associated with the level of CAC in patients with SLE.MethodsThe peripheral blood mononuclear cells of consecutive SLE patients and demographically matched healthy controls (HC) were extracted and identified, enumerated and compared for CAC levels by multi-colour flow cytometry based on the EULAR Scleroderma Trials and Research (EUSTAR) recommendation. Meta-analyses were performed by combining the current and previous case–control studies, aiming to increase the statistical power to discern the difference in CAC level between SLE patients and HC. Mixed-model meta-regression was conducted to explore potential demographic and clinical factors that were associated with CAC level.ResultsA lower level of CAC was found in 29 SLE patients compared with 24 HC [mean (s.d.) 10.76 (13.9) vs 24.58 (25.4) cells/ml, P = 0.015]. Random-effects meta-analyses of the current and six previously published case–control studies involving 401 SLE patients and 228 HC revealed a lower CAC level compared with HC (standardized mean difference = –2.439, P = 0.001). Meta-regression analysis demonstrated that HCQ use was associated with a more discrepant CAC level between both groups (P = 0.01115).ConclusionSLE patients had a significantly lower CD34+CD133+CD309+ CAC level than HC, and HCQ use was associated with a more discrepant CAC level between SLE patients and HC. This study triggers further observational, interventional and mechanistic studies to address the beneficial impact of HCQ on the functionality of CAC in SLE patients.
Society of behavioral medicine statement on COVID-19 and rural health
Authors: Behrman Pamela , Fitzgibbon Marian L , Dulin Akilah , Wang Monica L , Baskin Monica 
Published: December 2020

Abstract
This position statement provides researchers, practitioners, and policymakers an overview of pre-existing and COVID-related rural health inequities in the United States (U.S.) and how they have been exacerbated by the COVID-19 pandemic. “Health deserts,” defined as “large areas with inadequate or nonexistent medical and trauma facilities,” are common in rural regions of the U.S. While telehealth could address some of these health-related inequities, significant gaps in broadband Internet availability are also common in these more remote areas. The Society of Behavioral Medicine urges Congress to authorize increased funding to rural healthcare facilities and staffing, along with the development of enhanced broadband Internet infrastructure. In addition, incentivizing rural healthcare systems to deliver value-based care could enhance their capacity to implement population health and behavioral health strategies. To stem the spread of COVID-19 in higher-risk rural-based industries (e.g., food processing plants), SBM urges Congress to require the Occupational Safety and Health Administration (OSHA) to routinely inspect for and enforce COVID-19 mitigation procedures, such as provision of effective Personal Protective Equipment (PPE) to all front-line workers and consistent implementation of standardized testing and social distancing advisories. The context of rural communities underscores the importance of tailored approaches to mitigate rural health inequities and promote the well-being of rural residents.
Parvularcula mediterranea sp. nov., isolated from marine plastic debris from Zakynthos Island, Greece
Authors: Al-Omari Jafar , Szabó István , Szerdahelyi Gábor Soma , Radó Júlia , Kaszab Edit , Griffitts Jeffrey , Táncsics András , Szoboszlay Sándor 
Published: December 2020

A Gram-negative, dark orange-pigmented, aerobic, non-spore-forming, coccoid-shaped bacterium designated as ZS-1/3T was isolated from a floating plastic litter (polypropylene straw) sample, collected from shallow seawater near the public beach of Laganas on Zakynthos island, Greece. Phylogenetic analysis based on 16S rRNA gene sequences indicated that the isolate is affiliated with the genus

Parvularcula

in the family

Parvularculaceae

. Its closest relatives are

Parvularcula lutaonensis

(98.09  %) and

Parvularcula oceanus

(95.89  %). The pH and temperature ranges for growth are pH 5–10 and 20–38 °C (optima, pH 7.0 and 28 °C). The predominant fatty acids are C18 : 1
ω7c (56.84  %), C16 : 0 (27.51  %), C18 : 0 (2.25  %) and C12 : 0 (1.42  %). The predominant respiratory quinone detected in strain ZS-1/3T is quinone-10 (Q10); the majority of detected polar lipids are glycolipid. The DNA G+C content is 62.5  mol%. Physiological and chemotaxonomic data further confirmed the distinctiveness of strain ZS-1/3T from other members of the genus

Parvularcula

. Thus, strain ZS-1/3T is considered to represent a novel species of the genus, for which the name Parvularcula mediterranea. sp. nov. is proposed. The type strain is ZS-1/3T (=NCAIM B 02654T=CCM 9032T).
Reduction of protein disulfide isomerase results in open conformations and stimulates dynamic exchange between structural ensembles
Authors: Chinnaraj Mathivanan , Flaumenhaft Robert , Pozzi Nicola 
Published: December 2020

AbstractProtein disulfide isomerase (PDI) is a ubiquitous redox-regulated enzyme that interacts with hundreds of client proteins intracellularly and extracellularly. It comprises two redox-sensitive domains, each hosting the conserved catalytic motif CxxC, two redox-insensitive protein-binding domains, and three linkers. Snapshots of oxidized and reduced PDI have been obtained by X-ray crystallography. Yet, how PDI’s structure dynamically changes in response to the redox microenvironment and ligand binding remain unknown. Here, we used multiparameter confocal single-molecule Förster resonance energy transfer (smFRET) and multiple FRET pairs to track the movements of the two catalytic domains with high temporal resolution. Our studies document that, at equilibrium, PDI visits three structurally distinct conformational ensembles, two “open” (O1 and O2) and one “closed” (C). We show that the redox environment dictates the time spent in each ensemble and the rate at which they exchange. While oxidized PDI samples O1, O2 and C more evenly and in a slower fashion, reduced PDI predominantly populates O1 and O2, and exchanges between them more rapidly, on the sub-millisecond timescale. These findings were not expected based on crystallographic data. Using mutational analyses, we further demonstrate that the two active sites are structurally nonequivalent and that ligands targeting the active sites of reduced PDI shift the equilibrium towards closed conformations of the enzyme. This work introduces a new structural framework that challenges current views of PDI dynamics, helps rationalize the multifaced role of PDI in biology and may assist drug development.
Combinatorial Screen of Dynamic Mechanical Stimuli for Predictive Control of MSC Mechano-Responsiveness
Authors: Liu Haijiao , Usprech Jenna F. , Parameshwar Prabu Karthick , Sun Yu , Simmons Craig A. 
Published: December 2020

AbstractMechanobiological-based control of mesenchymal stromal cells (MSCs) to aid in the engineering and regeneration of load-bearing tissues requires systematic investigations of specific dynamic mechanical stimulation protocols. Using deformable membrane microdevice arrays paired with combinatorial experimental design and modeling, we systematically probed the individual and integrative effects of mechanical stimulation parameters (strain magnitude (STRAIN), rate at which strain is changed (RATE) and duty period (DUTY)) on myofibrogenesis and matrix production of MSCs in 3D hydrogels. These functions were found to be dominantly influenced by a novel and higher-order interactive effect between STRAIN and DUTY. Empirical models based on our combinatorial cue-response data predicted an optimal loading regime in which STRAIN and DUTY were increased synchronously over time, which was validated to most effectively promote MSC matrix production. These findings inform the design of loading regimes for MSC-based engineered tissues and validate a broadly applicable approach to probe multifactorial regulating effects of microenvironmental and mechanobiological cues.
BIOME-Preserve: A Novel Storage and Transport Medium for Preserving Anaerobic Microbiota Samples for Culture Recovery
Authors: Hyde Embriette R. , Lozano Hiram , Cox Steven 
Published: December 2020

AbstractCulture-based study design is critical to advance research into the relationship between human health and the microbiome. Traditional sample collection protocols are focused on preserving nucleic acids and metabolites and are largely inappropriate for preserving sensitive anaerobic bacteria alive for later culture recovery. Here we introduce a novel microbiome preservation kit (BIOME-Preserve) that facilitates recovery of anaerobic organisms from human stool held at room temperature. Using a combination of culture recovery and shallow whole-genome shotgun sequencing, we characterized the culturable anaerobes from fresh human stool and from human stool held in BIOME-Preserve for up to 120 hours. We recovered several species of interest to microbiome researchers, includingBifidobacterium spp., Bacteroides spp., Blautia spp., Eubacterium halii, Akkermansia muciniphila, andFaecalibacterium prausnitzii. Together, our results suggest BIOME-Preserve is practical for the collection, transport, and culture of anaerobic bacteria from human samples and can help provide the foundation for culture collections that can be used in further research and in the development of microbiome-based therapeutics.ImportanceSequencing-based protocols for studying the human microbiome have unearthed a wealth of information about the relationship between the microbiome and human health. But these microbes cannot be leveraged as therapeutic targets without culture-based studies to phenotype species of interest and to establish culture collections for use in animal models. Contrary to popular opinion, most gastrointestinal bacteria can be cultured, yet most sample collection strategies are optimized for the preservation of nucleic acids and/or metabolites only and do not take into account considerations for preserving oxygen-sensitive anaerobes and facultative anaerobes, which comprise the majority of the human gut microbiome. A human microbiome sample transport and preservation medium such as the one described here can play an important role in enabling researchers to better understand the link between the microbiome and human health and how to leverage that link through novel microbiome-based therapeutics.