bluuebunny/crossref_metadata_2025_split huggingface dataset:
Dependence of gravitational wave transient rates on cosmic star formation and metallicity evolution history
Authors: Tang Petra N , Eldridge J J , Stanway Elizabeth R , Bray J C 
Published: January 2020

ABSTRACT
We compare the impacts of uncertainties in both binary population synthesis models and the cosmic star formation history on the predicted rates of gravitational wave (GW) compact binary merger events. These uncertainties cause the predicted rates of GW events to vary by up to an order of magnitude. Varying the volume-averaged star formation rate density history of the Universe causes the weakest change to our predictions, while varying the metallicity evolution has the strongest effect. Double neutron star merger rates are more sensitive to assumed neutron star kick velocity than the cosmic star formation history. Varying certain parameters affects merger rates in different ways depending on the mass of the merging compact objects; thus some of the degeneracy may be broken by looking at all the event rates rather than restricting ourselves to one class of mergers.
Lysine acetylation of the housekeeping sigma factor enhances the activity of the RNA polymerase holoenzyme
Authors: Kim Ji-Eun , Choi Joon-Sun , Kim Jong-Seo , Cho You-Hee , Roe Jung-Hye 
Published: January 2020

Abstract
Protein lysine acetylation, one of the most abundant post-translational modifications in eukaryotes, occurs in prokaryotes as well. Despite the evidence of lysine acetylation in bacterial RNA polymerases (RNAPs), its function remains unknown. We found that the housekeeping sigma factor (HrdB) was acetylated throughout the growth of an actinobacterium, Streptomyces venezuelae, and the acetylated HrdB was enriched in the RNAP holoenzyme complex. The lysine (K259) located between 1.2 and 2 regions of the sigma factor, was determined to be the acetylated residue of HrdB in vivo by LC–MS/MS analyses. Specifically, the label-free quantitative analysis revealed that the K259 residues of all the HrdB subunits were acetylated in the RNAP holoenzyme. Using mutations that mimic or block acetylation (K259Q and K259R), we found that K259 acetylation enhances the interaction of HrdB with the RNAP core enzyme as well as the binding activity of the RNAP holoenzyme to target promoters in vivo. Taken together, these findings provide a novel insight into an additional layer of modulation of bacterial RNAP activity.
A multi-modal coarse grained model of DNA flexibility mappable to the atomistic level
Authors: Walther Jürgen , Dans Pablo D , Balaceanu Alexandra , Hospital Adam , Bayarri Genís , Orozco Modesto 
Published: January 2020

Abstract
We present a new coarse grained method for the simulation of duplex DNA. The algorithm uses a generalized multi-harmonic model that can represent any multi-normal distribution of helical parameters, thus avoiding caveats of current mesoscopic models for DNA simulation and representing a breakthrough in the field. The method has been parameterized from accurate parmbsc1 atomistic molecular dynamics simulations of all unique tetranucleotide sequences of DNA embedded in long duplexes and takes advantage of the correlation between helical states and backbone configurations to derive atomistic representations of DNA. The algorithm, which is implemented in a simple web interface and in a standalone package reproduces with high computational efficiency the structural landscape of long segments of DNA untreatable by atomistic molecular dynamics simulations.
CRISPR-Cas12a based internal negative control for nonspecific products of exponential rolling circle amplification
Authors: Tian Bo , Minero Gabriel Antonio S , Fock Jeppe , Dufva Martin , Hansen Mikkel Fougt 
Published: January 2020

Abstract
False-positive results cause a major problem in nucleic acid amplification, and require external blank/negative controls for every test. However, external controls usually have a simpler and lower background compared to the test sample, resulting in underestimation of false-positive risks. Internal negative controls, performed simultaneously with amplification to monitor the background level in real-time, are therefore appealing in both research and clinic. Herein, we describe a nonspecific product-activated single-stranded DNA-cutting approach based on CRISPR (clustered regularly interspaced short palindromic repeats) Cas12a (Cpf1) nuclease. The proposed approach, termed Cas12a-based internal referential indicator (CIRI), can indicate the onset of nonspecific amplification in an exponential rolling circle amplification strategy here combined with an optomagnetic readout. The capability of CIRI as an internal negative control can potentially be extended to other amplification strategies and sensors, improving the performance of nucleic acid amplification-based methodologies.
Prediction of all-cause mortality in haemodialysis patients using a Bayesian network
Authors: Siga Marleine Mefeugue , Ducher Michel , Florens Nans , Roth Hubert , Mahloul Nadir , Fouque Denis , Fauvel Jean-Pierre 
Published: January 2020

Abstract

Background
All-cause mortality in haemodialysis (HD) is high, reaching 15.6% in the first year according to the European Renal Association.

Methods
A new clinical tool to predict all-cause mortality in HD patients is proposed. It uses a post hoc analysis of data from the prospective cohort study Photo-Graph V3. A total of 35 variables related to patient characteristics, laboratory values and treatments were used as predictors of all-cause mortality. The first step was to compare the results obtained using a logistic regression to those obtained by a Bayesian network. The second step aimed to increase the performance of the best prediction model using synthetic data. Finally, a compromise between performance and ergonomics was proposed by reducing the number of variables to be entered in the prediction tool.

Results
Among the 9010 HD patients included in the Photo-Graph V3 study, 4915 incident patients with known medical status at 2 years were analysed. All-cause mortality at 2 years was 34.1%. The Bayesian network provided the most reliable prediction. The final optimized models that used 14 variables had areas under the receiver operating characteristic curves of 0.78 ± 0.01, sensitivity of 72 ± 2%, specificity of 69 ± 2%, predictive positive value of 70 ± 1% and negative predictive value of 71 ± 2% for the prediction of all-cause mortality.

Conclusions
Using artificial intelligence methods, a new clinical tool to predict all-cause mortality in incident HD patients is proposed. The latter can be used for research purposes before its external validation at: https://www.hed.cc/? a=twoyearsallcausemortalityhemod&n=2-years%20All-cause%20Mortality%20Hemodialysis.neta.
KIF11 and KIF15 mitotic kinesins are potential therapeutic vulnerabilities for malignant peripheral nerve sheath tumors
Authors: Terribas Ernest , Fernández Marco , Mazuelas Helena , Fernández-Rodríguez Juana , Biayna Josep , Blanco Ignacio , Bernal Gabriela , Ramos-Oliver Irma , Thomas Craig , Guha Rajiv , Zhang Xiaohu , Gel Bernat , Romagosa Cleofé , Ferrer Marc , Lázaro Conxi , Serra Eduard 
Published: January 2020

AbstractBackgroundMalignant peripheral nerve sheath tumor (MPNST) constitutes the leading cause of neurofibromatosis type 1–related mortality. MPNSTs contain highly rearranged hyperploid genomes and exhibit a high division rate and aggressiveness. We have studied in vitro whether the mitotic kinesins KIF11, KIF15, and KIF23 have a functional role in maintaining MPNST cell survival and can represent potential therapeutic vulnerabilities.MethodsWe studied the expression of kinesin mRNAs and proteins in tumors and cell lines and used several in vitro functional assays to analyze the impact of kinesin genetic suppression (KIF15, KIF23) and drug inhibition (KIF11) in MPNST cells. We also performed in vitro combined treatments targeting KIF11 together with other described MPNST targets.ResultsThe studied kinesins were overexpressed in MPNST samples. KIF15 and KIF23 were required for the survival of MPNST cell lines, which were also more sensitive than benign control fibroblasts to the KIF11 inhibitors ispinesib and ARRY-520. Co-targeting KIF11 and BRD4 with ARRY-520 and JQ1 reduced MPNST cell viability, synergistically killing a much higher proportion of MPNST cells than control fibroblasts. In addition, genetic suppression of KIF15 conferred an increased sensitivity to KIF11 inhibitors alone or in combination with JQ1.ConclusionsThe mitotic spindle kinesins KIF11 and KIF15 and the cytokinetic kinesin KIF23 play a clear role in maintaining MPNST cell survival and may represent potential therapeutic vulnerabilities. Although further in vivo evidences are still mandatory, we propose a simultaneous suppression of KIF11, KIF15, and BRD4 as a potential therapy for MPNSTs.
MCT4 regulates de novo pyrimidine biosynthesis in GBM in a lactate-independent manner
Authors: Spina Raffaella , Voss Dillon M , Yang Xiaohua , Sohn Jason W , Vinkler Robert , Schraner Julianna , Sloan Anthony , Welford Scott M , Avril Norbert , Ames Heather M , Woodworth Graeme F , Bar Eli E 
Published: January 2020

Abstract

Background
Necrotic foci with surrounding hypoxic cellular pseudopalisades and microvascular hyperplasia are histological features found in glioblastoma (GBM). We have previously shown that monocarboxylate transporter 4 (MCT4) is highly expressed in necrotic/hypoxic regions in GBM and that increased levels of MCT4 are associated with worse clinical outcomes.

Methods
A combined transcriptomics and metabolomics analysis was performed to study the effects of MCT4 depletion in hypoxic GBM neurospheres. Stable and inducible MCT4-depletion systems were used to evaluate the effects of and underlining mechanisms associated with MCT4 depletion in vitro and in vivo, alone and in combination with radiation.

Results
This study establishes that conditional depletion of MCT4 profoundly impairs self-renewal and reduces the frequency and tumorigenicity of aggressive, therapy-resistant, glioblastoma stem cells. Mechanistically, we observed that MCT4 depletion induces anaplerotic glutaminolysis and abrogates de novo pyrimidine biosynthesis. The latter results in a dramatic increase in DNA damage and apoptotic cell death, phenotypes that were readily rescued by pyrimidine nucleosides supplementation. Consequently, we found that MCT4 depletion promoted a significant prolongation of survival of animals bearing established orthotopic xenografts, an effect that was extended by adjuvant treatment with focused radiation.

Conclusions
Our findings establish a novel role for MCT4 as a critical regulator of cellular deoxyribonucleotide levels and provide a new therapeutic direction related to MCT4 depletion in GBM.
Ultrafast growth of large single crystals of monolayer WS2 and WSe2
Authors: Zhang Zhengwei , Chen Peng , Yang Xiangdong , Liu Yuan , Ma Huifang , Li Jia , Zhao Bei , Luo Jun , Duan Xidong , Duan Xiangfeng 
Published: January 2020

Abstract
Monolayer transition metal dichalcogenides (TMDs) have attracted considerable attention as atomically thin semiconductors for the ultimate transistor scaling. For practical applications in integrated electronics, large monolayer single crystals are essential for ensuring consistent electronic properties and high device yield. The TMDs available today are generally obtained by mechanical exfoliation or chemical vapor deposition (CVD) growth, but are often of mixed layer thickness, limited single crystal domain size or have very slow growth rate. Scalable and rapid growth of large single crystals of monolayer TMDs requires maximization of lateral growth rate while completely suppressing the vertical growth, which represents a fundamental synthetic challenge and has motivated considerable efforts. Herein we report a modified CVD approach with controllable reverse flow for rapid growth of large domain single crystals of monolayer TMDs. With the use of reverse flow to precisely control the chemical vapor supply in the thermal CVD process, we can effectively prevent undesired nucleation before reaching optimum growth temperature and enable rapid nucleation and growth of monolayer TMD single crystals at a high temperature that is difficult to attain with use of a typical thermal CVD process. We show that monolayer single crystals of 450 μm lateral size can be prepared in 10 s, with the highest lateral growth rate up to 45 μm/s. Electronic characterization shows that the resulting monolayer WSe2 material exhibits excellent electronic properties with carrier mobility up to 90 cm2 V−1 s−1, comparable to that of the best exfoliated monolayers. Our study provides a robust pathway for rapid growth of high-quality TMD single crystals.
Antibiotic Prescribing in New York State Medicare Part B Beneficiaries Diagnosed With Cystitis Between 2016 and 2017
Authors: Yu Joyce Y , McKenna Valerie A , Dumyati Ghinwa K , Lubowski Teresa J , Carreno Joseph J 
Published: January 2020

AbstractBackgroundStatewide tracking and reporting is an outpatient antimicrobial stewardship tool that may be useful for many stakeholders. However, to date, these evaluations have been limited. This study aimed to track and report outpatient antibiotic prescribing in Medicare Part B enrollees diagnosed with cystitis in the outpatient setting.MethodsThis was a retrospective, cohort study of Medicare Part B enrollees in New York State. Inclusion criteria include outpatient visit in 2016 or 2017, cystitis diagnosis code, and oral antibiotic prescription ≤3 days after diagnosis of cystitis. Antibiotics were categorized as first-line, oral β-lactams, fluoroquinolones, or other per Infectious Diseases Society of America acute uncomplicated cystitis guidelines. Data were stratified by sex. Annual prescriptions proportions were compared using χ 2 test or Fisher’s exact test as appropriate.ResultsA total of 50 658 prescriptions were included. For females’ prescriptions, first line increased (41.5% vs 43.8%, P &lt; .0001), oral β-lactams increased (17.8% vs 20.5%, P &lt; .0001), fluoroquinolones decreased (34.1% vs 29.1%, P &lt; .0001), and other increased (6.5% vs 6.6%, P = .76) in 2017. For males’ prescriptions, first line increased (25.2% vs 26.7%, P = .11), oral β-lactams increased (23.1% vs 26.2%, P = .0003), fluoroquinolones decreased (44.0% vs 39.3%, P &lt; .0001), and other remained unchanged (7.8% vs 7.8%, P = .92) in 2017.ConclusionsGuideline concordant therapy prescribing for cystitis increased among Medicare Part B beneficiaries in New York State between 2016 and 2017. However, there was still a high prevalence of fluoroquinolone prescribing. These data highlight the need for additional outpatient antimicrobial stewardship efforts in New York State.
In Vitro Pharmacodynamic Analyses Help Guide the Treatment of Multidrug-Resistant Enterococcus faecium and Carbapenem-Resistant Enterobacter cloacae Bacteremia in a Liver Transplant Patient
Authors: Wenzler Eric , Santarossa Maressa , Meyer Kevin A , Harrington Amanda T , Reid Gail E , Clark Nina M , Albarillo Fritzie S , Bulman Zackery P 
Published: January 2020

AbstractBackgroundInfections due to multidrug-resistant pathogens are particularly deadly and difficult to treat in immunocompromised patients, where few data exist to guide optimal antimicrobial therapy. In the absence of adequate clinical data, in vitro pharmacokinetic (PK)/pharmacodynamic (PD) analyses can help to design treatment regimens that are bactericidal and may be clinically effective.MethodsWe report a case in which in vitro pharmacodynamic analyses were utilized to guide the treatment of complex, recurrent bacteremias due to vancomycin-, daptomycin-, and linezolid-resistant Enterococcus faecium and carbapenem-resistant Enterobacter cloacae complex in a liver transplant patient.ResultsWhole-genome sequencing revealed unique underlying resistance mechanisms and explained the rapid evolution of phenotypic resistance and complicated intrahost genomic dynamics observed in vivo. Performing this comprehensive genotypic and phenotypic testing and time-kill analyses, along with knowledge of institution and patient-specific factors, allowed us to use precision medicine to design a treatment regimen that maximized PK/PD.ConclusionsThis work provides a motivating example of clinicians and scientists uniting to optimize care in the era of escalating antimicrobial resistance.
Genetic Determinants of Trehalose Utilization Are Not Associated With Severe Clostridium difficile Infection Outcome
Authors: Saund Katie , Rao Krishna , Young Vincent B , Snitkin Evan S 
Published: January 2020

Abstract
In a case–control study of patients with Clostridium difficile infection, we found no statistically significant association between the presence of trehalose utilization variants in infecting C. difficile strains and development of severe infection outcome. These results do not support trehalose utilization conferring enhanced virulence in the context of human C. difficile infections.
Fishing for a Diagnosis, the Impact of Delayed Diagnosis on the Course of Mycobacterium marinum Infection: 21 Years of Experience at a Tertiary Care Hospital
Authors: Castillo Natalia E , Gurram Pooja , Sohail M Rizwan , Fida Madiha , Abu Saleh Omar 
Published: January 2020

AbstractBackgroundMycobacterium marinum is a common but underreported mycobacterial infection. We conducted a large retrospective study to determine risk factors and describe the therapeutic interventions and outcomes in patients with uncomplicated and complicated M. marinum infection.MethodsCulture-confirmed M. marinum infection cases were identified from the Mayo Clinic Clinical Mycology Laboratory from January 1998 to December 2018. Complicated M. marinum infection was defined as the presence of tenosynovitis, septic arthritis, or osteomyelitis. Differences in complicated vs uncomplicated M. marinum infections were analyzed using statistical comparisons.ResultsTwelve cases had a complicated M. marinum infection. Patients with a complicated infection were older (64.3 ± 11.1 vs 55.8 ± 14.5; P = .03), had longer duration of symptoms (5 vs 3 months; P = .011), and had more surgical debridements (1 vs 0; P &lt; .001). Length of treatment and number of drugs used were not statistically significant. Complicated M. marinum cases received more medications (2 vs 1; P = .263) and were treated longer (5.7 vs 3.5 months; P = .067). Antibiotic susceptibilities were performed in 59% of the patients. All isolates were susceptible to clarithromycin. From the tetracyclines, doxycycline had a better susceptibility pattern.ConclusionsM. marinum infection is an important cause of skin and soft tissue infection. Poor water exposure documentation, unusual clinical presentation, and empiric antibiotic treatment before definitive M. marinum diagnosis often contribute to a delayed diagnosis. Complicated M. marinum cases had longer duration of symptoms and more surgical debridements. No difference in the number of drugs used or clinical outcome was observed.
Eosinopenia and Binary Toxin Increase Mortality in Hospitalized Patients With Clostridioides difficile Infection
Authors: Carlson Travis J , Endres Bradley T , Le Pham Julie , Gonzales-Luna Anne J , Alnezary Faris S , Nebo Kimberly , Miranda Julie , Lancaster Chris , Bassères Eugénie , Begum Khurshida , Alam M Jahangir , Reveles Kelly R , Garey Kevin W 
Published: January 2020

Abstract

Background
Patients with Clostridioides difficile infection (CDI) with either eosinopenia or infected with a binary toxin strain have increased likelihood of mortality. However, the relationship between binary toxin and eosinopenia to synergistically increase mortality has not been studied in humans. We hypothesized that patients with CDI due to binary toxin strains and concomitant peripheral eosinopenia would have a higher likelihood of inpatient mortality.

Methods
This multicenter, retrospective cohort study included adult patients with CDI of known ribotypes stratified by eosinopenia, defined as an absence of eosinophils in the peripheral blood (Houston cohort). The primary outcome was inpatient mortality. Results were supported by a separate national cohort of veterans with CDI (Veterans’ cohort).

Results
In the Houston cohort, a total of 688 patients from 13 institutions in 6 cities were included. Of these, 132 (19%) had an eosinophil count of 0.0 cells/µL (0.0 cells*109/L) and 109 (16%) were infected with a binary toxin strain. After adjusting for covariates, the combination of eosinopenia and infection with a binary toxin strain was an independent predictor of inpatient mortality (odds ratio [OR], 7.8; 95% confidence interval [CI], 1.9–33.2; P = .005). In the separate Veterans’ cohort (n = 790), this combination was also a significant predictor of inpatient mortality (OR, 6.1; 95% CI, 1.5–23.9; P = .009).

Conclusions
In conclusion, the combination of eosinopenia and CDI due to a binary toxin strain was correlated with increased mortality in hospitalized patients from 2 independent cohorts. Prospective studies should further study this important subset of patients at the time of CDI diagnosis.
A Randomized Controlled Trial Assessing the Evolution of the Weight-Bearing Ankle Dorsiflexion Range of Motion Over 6 Sessions of Talus Mobilizations in Older Adults
Authors: Hernández-Guillén David , Blasco José-María 
Published: January 2020

Abstract

Background
Ankle range of motion declines with age, affecting mobility and postural control.

Objective
The objective of this study was to investigate the effects of a talus mobilization-based intervention among healthy community-dwelling older adults presenting with limited weight-bearing ankle dorsiflexion range of motion and determine how ankle mobility evolved over the treatment.

Design
This was a randomized clinical trial.

Setting
This study was conducted in an outpatient clinic.

Participants
Community-dwelling, older adults over 60 years of age who had limited ankle mobility participated in this study.

Interventions
The experimental intervention consisted of 6 sessions of manual therapy applied in the ankle joint. The control group received the same volume of sham treatment.

Measurements
The primary outcome was the weight-bearing ankle dorsiflexion range of motion as measured using the lunge test. Data were collected at 9 time points: baseline, after each session, and follow-up.

Results
A total of 36 participants were analyzed. A single session of mobilization increased ankle range of motion by 8 degrees (95% confidence interval = 6 to 11). At the end of the sixth session, this effect had increased slightly to 11 degrees (95% confidence interval = 9 to 13). Significant between-group differences were found throughout the intervention.

Limitations
Optimal dose and effects from follow-up evaluations for treatment volumes of fewer than 6 sessions remain unknown.

Conclusions
Six sessions of a talus mobilization-based intervention in healthy community-dwelling older adults found that the greatest mobility gain in terms of the weight-bearing ankle dorsiflexion range of motion is produced after the first session. Additional sessions produce smaller improvements with a slight upward trend. Importantly, the restoration of joint mobility is enhanced over time after the end of the intervention.