bluuebunny/crossref_metadata_2025 huggingface dataset:
Effect of isotope on state-to-state dynamics for reactive collision reactions

O(3P)+H2+→OH++H

and

O(3P)+H2+→OH+H+

in ground state 12A″ and first excited 12A′ potential energy surfaces*
Authors: Zhao Juan , Xu Ting , Zhang Lu-Lu , Wang Li-Fei
Published: December 2019

We carry out quantum scattering dynamics and quasi-classical trajectory (QCT) calculations for the

O
+

H
2
+

reactive collision in the ground (12A″) and first excited (12A′) potential energy surface. We calculate the reaction probabilities of

O
+

H
2
+

(
v
=
0
,
j
=
0
)
→

OH

+

+
H

and

O
+

H
2
+

(
v
=
0
,
j
=
0
)
→
OH
+

H
+

reaction for total angular momentum J = 0. The results calculated by QCT are consistent with those from quantum mechanical wave packet. Using the QCT method, we generate in the center-of-mass frame the product state-resolved integral cross-sections (ICSs); two commonly used generalized polarization-dependent differential cross-sections (PDDCSs), (2π/σ)(dσ
00/dω
t), (2π/σ)(dσ
20/dω
t); and three angular distributions of the product rotational vectors, P(θ
r), P(ϕ
r), and P(θ
r, ϕ
r). We discuss the influence on the scalar and vector properties of the potential energy surface, the collision energy, and the isotope mass. Since there are deep potential wells in these two potential energy surfaces, their kinetic characteristics are similar to each other and the isotopic effect is not obvious. However, the well depths and configurations of the two potential energy surfaces are different, so the effects of isotopic substitution on the integral cross-section and the rotational polarization of product are different.
Unified approach to various quantum Rabi models with arbitrary parameters*
Authors: Dong Xiao-Fei , Xie You-Fei , Chen Qing-Hu
Published: December 2019

A general approach is proposed to the quantum Rabi model and its several variants within the extended coherent states. The solutions to all these models including the anisotropy and the nonlinear Stark coupling are then obtained in an unified way. The essential characteristics such as the possible first-order phase transition can be detected analytically. This approach can be easily applied to the recent experiments with various tunable parameters without much additional effort, so it should be very helpful to the analysis of the experimental data.
Microstructural evolution, recovery and recrystallization kinetics of isothermally annealed ultra low carbon steel
Authors: Dutta Siuli , Panda Ashis K , Mitra Amitava , Chatterjee Subrata , Roy Rajat K
Published: December 2019

The recovery and recrystallization kinetics of 80% cold rolled ultra low carbon steel are investigated during isothermally annealing for temperature ranges 350–640 °C as a function of different annealing time. The recovery is assessed by magnetic coercivity (Hc), while the recrystallization is determined by mechanical hardness. At low temperature (350 to 520 °C) annealing, recovery dominates for long time (∼12 000 s), while the annealing at 550 °C/ 900s and 580 °C/ 300s causes the recrystallized nuclei formation . The recovery kinetics is introduced by differential rate equation, explaining the reduction in coercivity with the recovery progress and the variation of an activation energy from 41–113 kJ mol−1. The recrystallization kinetics is found faster at high annealing temperature 640 °C than 550 and 580 °C based on hardness measurement, justifying by apparent activation energy within 114–190 kJ mol−1. Furthermore, the recovery and recrystallization rate increase with different annealing time, consistent to the change of microstructures and grain boundary characteristics evaluated by the orientation imaging microscopy (OIM) of electron backscattered diffraction (EBSD).
Inpatient hip fractures: understanding and addressing the risk of this common injury
Authors: Singh Inderpal , Hooton Kate , Edwards Chris , Lewis Beverley , Anwar Anser , Johansen Antony
Published: December 2019

Introduction

The impact and outcome of hip fractures are well described for people living in the community, but inpatient hip fracture (IHF) have not been extensively studied. In this study, we examine the patient characteristics, common falls risk factors and clinical outcomes of this condition.

Methods

Between January 2016 and December 2017, we analysed all inpatient falls that resulted in hip fracture within Aneurin Bevan University Health Board (ABUHB) in Wales.

Results

The overall falls rate was 8.7/1000 occupied bed days (OBD). Over the 2 years, 118 patients sustained an IHF, giving a rate of 0.12/1000 OBD. The mean age was 81.8 ± 9.5 (range 49–97) years and 60% were women. Most patients (n = 112) were admitted from their own home. Mean Charlson Comorbidity Index and the number of medications on admission were 5.5 ± 1.9 and 8.5 ± 3.7, respectively.

Fifty-three patients (45%) sustained the IHF following their first inpatient fall. Twenty-four IHF (20%) occurred within 72 h. Mean length of stay was 84.9 ± 55.8 days. Only 43% were discharged back to their original place of residence following an IHF; 27% were discharged to a care home (26 new care home discharges), and 30% died as an inpatient. One-year mortality was 54% (n = 64/118). The most common comorbidity was dementia (63%).

Conclusion

Mortality and need for care home placement are both much higher after IHF than following community hip fracture. Most people who suffer a hip fracture in hospital have already demonstrated their need for falls risk management by having fallen previously during the same admission.
The Galaxy Plot: A New Visualization Tool for Bivariate Meta-Analysis Studies
Authors: Hong Chuan , Duan Rui , Zeng Lingzhen , Hubbard Rebecca A , Lumley Thomas , Riley Richard D , Chu Haitao , Kimmel Stephen E , Chen Yong
Published: December 2019

Funnel plots have been widely used to detect small-study effects in the results of univariate meta-analyses. However, there is no existing visualization tool that is the counterpart of the funnel plot in the multivariate setting. We propose a new visualization method, the galaxy plot, which can simultaneously present the effect sizes of bivariate outcomes and their standard errors in a 2-dimensional space. We illustrate the use of the galaxy plot with 2 case studies, including a meta-analysis of hypertension trials with studies from 1979–1991 (Hypertension. 2005;45(5):907–913) and a meta-analysis of structured telephone support or noninvasive telemonitoring with studies from 1966–2015 (Heart. 2017;103(4):255–257). The galaxy plot is an intuitive visualization tool that can aid in interpreting results of multivariate meta-analysis. It preserves all of the information presented by separate funnel plots for each outcome while elucidating more complex features that may only be revealed by examining the joint distribution of the bivariate outcomes.
Accuracy of the Montreal Cognitive Assessment in Detecting Mild Cognitive Impairment and Dementia in the Rural African Population
Authors: Masika Golden M , Yu Doris S F , Li Polly W C
Published: December 2019

Objective

The incidence of dementia in the sub-Saharan Africa is rising. However, screening tools for cognitive decline that fits their linguistic and cultural context are lacking. The aim of this study was to determine the accuracy of the Kiswahili version of Montreal Cognitive Assessment (K-MoCA) to detect mild cognitive impairment or dementia among older adults in the rural Tanzania.

Methods

We recruited 259 community-dwelling older adults in Chamwino district, Tanzania. The concurrent validity and discriminatory power of K-MoCA were examined by comparing its score with IDEA cognitive screening and psychiatrist’s diagnosis using DSM-V, respectively. All the questionnaires were administered in face-to-face interview.

Results

K-MoCA demonstrated acceptable reliability (Cronbach’s alpha = 0.780). Concurrent validity was evident by its significant correlation with the IDEA screening test (Pearson’s r = 0.651, p < 0.001). Using the psychiatrist’s rating as the reference, the optimal cut-off score for MCI and dementia was 19 and 15, respectively, which yielded the sensitivity of 70% and specificity of 60% for MCI, and sensitivity of 72% and specificity of 60% for dementia. Further analysis indicated that education and age influence performance on K-MoCA.

Conclusion

Overall, the K-MoCA is a reliable and valid tool for measuring cognitive decline. However, its limited discriminatory power for MCI and dementia may be compromised by the cultural irrelevance of some items.
Architecture and System Design for Marine Cloud Computing Assets
Authors: Periola A A , Alonge A A , Ogudo K A
Published: December 2019

The Ocean provides benefits of free cooling for cloud computing platforms. However, the use of the ocean for hosting cloud platforms needs to consider three challenges. The first challenge is identifying suitable underwater locations for siting underwater data centres. The second is designing a low-cost method for acquiring underwater data centres. The third is designing a mechanism ensuring that the use of the ocean for hosting data centres is scalable. This paper proposes the intelligent marine compute locator (IMCL) to identify suitable locations for siting underwater data centres. The proposed IMCL determines the specific heat capacity of different ocean locations at multiple epochs. In addition, the conversion of end-of-life vessels into artificial reefs that host open-source disaggregated hardware computing payload is proposed to reduce acquisition costs. The use of disaggregated architecture enables multiple cloud service providers to use limited ocean locations. The formulated metrics are the power usage effectiveness (PUE) and ocean space utilization (OSU). Simulations show that the use of disaggregated design architecture instead of non-disaggregated architecture (existing mechanism) enhances the PUE and OSU by 4.4 and 16.4% on average, respectively.
Combined effects of dosage compensation and incomplete dominance on gene expression in triploid cyprinids
Authors: Ren Li , Yan Xiaojing , Cao Liu , Li Jiaming , Zhang Xueyin , Gao Xin , Liu Jia , Cui Jialin , Liu Shaojun
Published: December 2019

Hybridization and polyploidy are pervasive evolutionary features of flowering plants and frequent among some animal groups, such as fish. These processes always lead to novel genotypes and various phenotypes, including growth heterosis. However, its genetic basis in lower vertebrate is still poorly understood. Here, we conducted transcriptome-level analyses of the allopolyploid complex of Carassius auratus red var. (R) (♀) × Cyprinus carpio L. (C) (♂), including the allodiploid and allotetraploid with symmetric subgenomes, and the two allotriploids with asymmetric subgenomes. The gradual changes of gene silencing and novel gene expression suggested the weakening of the constraint of polymorphic expression in genotypic changes. Then, analyses of the direction and magnitude of homoeolog expression exhibited various asymmetric expression patterns, which supported that R incomplete dominance and dosage compensation were co-regulated in the two triploids. Under these effects, various magnitudes of R-homoeolog expression bias were observed in growth-regulated genes, suggesting that they might contribute to growth heterosis in the two triploids. The determination of R incomplete dominance and dosage compensation, which might be led by asymmetric subgenomes and multiple sets of homologous chromosomes, explained why various expression patterns were shaped and their potential contribution to growth heterosis in the two triploids.
Differences in Early Season Emergence and Reproductive Activity Between Spathius agrili (Hymenoptera: Braconidae) and Spathius galinae, Larval Parasitoids of the Invasive Emerald Ash Borer (Coleoptera: Buprestidae)
Authors: Ragozzino Max , Meyer Ryan , Duan Jian , Slager Ben , Salom Scott
Published: December 2019

Both Spathius agrili Yang and Spathius galinae Belokobylskij and Strazanac are host-specific parasitic wasps introduced for biological control of emerald ash borer in North America. Spathius agrili is native to northeastern China and S. galinae comes from a more northern, colder climate in the Russian Far East. Their origin may lead to differing abilities to adapt to climate and their host in North America. We conducted both field and laboratory experiments to determine the timing of early season emergence and synchronization of each parasitoid species to their host in the United States, and if manipulating prerelease conditions could affect emergence time. A cold acclimatization treatment prior to parasitoid emergence was assessed and compared with untreated control group reared with standard rearing protocols. Stands of naturally emerald ash borer-infested ash were sampled at two locations in Virginia throughout the experiment to determine when the parasitoid-susceptible life stage (third to fourth instar) occurred. Untreated S. galinae emerged approximately 2 wk earlier than any other cohort, whereas cold acclimatized S. galinae emerged later than any other cohort. Emergence time of S. agrili was unaffected by cold acclimatization. Cold acclimatization treatment did not affect the parasitism rate of either species, nor did it have multigenerational effects. Emergence time of the subsequent generation of S. agrili was delayed by cold acclimatization treatment, whereas S. galinae experienced no multigenerational effects. At Virginia field sites, susceptible EAB larvae were present during the emergence time of all four groups of parasitoids. Untreated S. galinae had the least overlap with any susceptible EAB larvae.
Fracture risks among patients with atrial fibrillation receiving different oral anticoagulants: a real-world nationwide cohort study
Authors: Huang Huei-Kai , Liu Peter Pin-Sung , Hsu Jin-Yi , Lin Shu-Man , Peng Carol Chiung-Hui , Wang Jen-Hung , Loh Ching-Hui
Published: December 2019

Aims

To evaluate the fracture risk among patients with atrial fibrillation (AF) treated with non-vitamin K antagonist oral anticoagulants (NOACs) or warfarin.

Methods and results

We conducted a real-world nationwide retrospective cohort study using Taiwan’s National Health Insurance Research Database. All adult patients in Taiwan newly diagnosed with AF between 2012 and 2016 who received NOACs or warfarin were enrolled and followed up until 2017. Patients treated with NOACs were sub-grouped according to the NOAC used (dabigatran, rivaroxaban, and apixaban). Propensity score matching was performed for each head-to-head comparison. Cox regression analysis, with a shared frailty model, was used to calculate the adjusted hazard ratios (aHRs) for hip, vertebral, and humerus/forearm/wrist fractures. After matching, 19 414 patients were included (9707 in each NOAC and warfarin groups). The median follow-up time was 2.4 years. Compared with warfarin, NOACs were associated with a reduced fracture risk [aHR = 0.84, 95% confidence interval (CI) = 0.77–0.93; P < 0.001]. Sub-analyses revealed that each NOAC, namely dabigatran (aHR = 0.88, 95% CI = 0.78–0.99; P = 0.027), rivaroxaban (aHR = 0.81, 95% CI = 0.72–0.90; P < 0.001), and apixaban (aHR = 0.67, 95% CI = 0.52–0.87; P = 0.003), had a reduced fracture risk. Analyses including all eligible patients, without propensity score matching, generated similar results.

Conclusion

Compared with warfarin, NOAC was associated with a reduced fracture risk among AF patients. Therefore, if oral anticoagulants are indicated, NOACs rather than warfarin should be considered to lower the risk of fractures. However, further studies are needed to investigate the underlying mechanisms and elucidate causality.
Prevalence of three lifestyle factors among Australian adults from 2004 to 2018: an age–period–cohort analysis
Authors: Peng Yang , Wang Zhiqiang
Published: December 2019

Background

It has been reported that current smoking, overweight/obesity and physical inactivity are significant modifiable risk factors of all-cause mortality, cardiovascular disease and cancer. However, the effects of age, period and cohort on the prevalence of the three lifestyle factors among Australian adults are still unclear.

Methods

Our study analysed data from 2004 to 2005, 2007 to 2008, 2011 to 2012, 2014 to 2015 and 2017 to 2018 National Health Survey. We employed the age–period–cohort models to analyze the individual effects of age, period and cohort on the prevalence of current smoking, overweight/obesity and physical inactivity among Australian adults.

Results

A total of 76 489 adults were included. Age, period and cohort all showed significant independent effects on prevalence of current smoking, overweight/obesity and physical inactivity (P < 0.01) except the cohort effect on physical inactivity in females (P = 0.31). The prevalence of current smoking decreased with age and period, and it first increased with birth cohort and then declined. For overweight/obesity prevalence, it increased with age until early-60s and then dropped. We found a positive period effect on overweight/obesity; however, the prevalence of overweight/obesity experienced several shifts with birth cohort. Physical activity prevalence raised with age, and it has several fluctuations for curves of period and cohort.

Conclusion

Age effects showed a distinct pattern for the prevalence of the three lifestyle factors. The prevalence of overweight/obesity continued to rise during the study period. The raised physical inactivity prevalence in recent study cycles is also concerning. Recent birth cohorts may be at increased risk of overweight/obesity and physical inactivity.
Termite Diversity in Ecuador: A Comparison of Two Primary Forest National Parks
Authors: Dahlsjö Cecilia A L , Valladares Romero Cynthia S , Espinosa Iñiguez Carlos-Iván
Published: December 2019

Termites are one of the key ecosystem engineers in tropical forests where they play a major role in decomposition rates, both above and belowground. The interest in termite ecology and biogeography has increased in the last few decades; however, the lack of comparable data has limited the wider impact of termite research. For Ecuador, termite studies are relatively rare and comparable data that are collected using standardized sampling methods are missing. In this study, we aim to 1) provide comparable data of termite species and feeding-group diversity from two primary forests in Ecuador and 2) explore the differences in termite species and feeding-group diversity between the two forest sites. Sampling took place in the national parks of Yasuní and Podocarpus where three belt transects (100 × 2 m) following Jones and Eggleton (2000) were conducted in each forest. We found that termite species richness was higher in Yasuní (56 species) than in Podocarpus (24 species) and that 57% of the sampled termite genera had never previously been recorded in Ecuador. The inter-site species dissimilarity was almost complete (Bray Curtis (±SD), 0.91 ± 0.01), which may have been linked to the difference in tree density and species richness in the two forests. Termite feeding-groups diversity was significantly higher in Yasuní than in Podocarpus with the exception of soil-feeding termites which may have been due to competition between humus- and soil-feeding species.
Oral Oncology Parity Laws, Medication Use, and Out-of-Pocket Spending for Patients With Blood Cancers
Authors: Dusetzina Stacie B , Huskamp Haiden A , Jazowski Shelley A , Winn Aaron N , Wood William A , Olszewski Adam , Basch Ethan , Keating Nancy L
Published: December 2019

Background

In this study, we sought to estimate the association between oral oncology parity law adoption and anticancer medication use for patients with chronic myeloid leukemia or multiple myeloma.

Methods

This was an observational study of administrative claims from 2008 to 2017. Among individuals initiating tyrosine kinase inhibitors (TKIs) for chronic myeloid leukemia or immunomodulatory drugs for multiple myeloma, we compared out-of-pocket spending, adherence, and discontinuation before and after parity among individuals in fully insured plans (subject to parity) vs self-funded plans (exempt from parity) using propensity-score weighted difference-in-differences regression models.

Results

Among patients initiating TKIs (N = 2082) or immunomodulatory drugs (N = 3326) there were no statistically significant differences in adherence or discontinuation associated with parity. The proportion of patients with initial out-of-pocket payments of $0 increased in fully insured plans after parity from 5.7% to 46.1% for TKIs and from 10.9% to 48.8% for immunomodulatory drugs. Relative to changes in self-funded plans, those in fully insured plans were 4.27 (95% CI = 2.20 to 8.27) times as likely to pay nothing for TKIs and 1.96 (95% CI = 1.40 to 2.73) times as likely to pay nothing for immunomodulatory drugs after parity. Similarly, the proportion paying more than $100 decreased from 30.3% to 24.7% for TKIs and 30.6% to 27.5% for immunomodulatory drugs in fully insured plans after parity. Relative to changes in self-funded plans, those in fully insured plans were 0.74 (95% CI = 0.54 to 1.01) times as likely to pay more than $100 for TKIs and 0.85 (95% CI = 0.68 to 1.06) times as likely to pay more than $100 for immunomodulatory drugs after parity.

Conclusions

Among patients initiating TKIs or immunomodulatory drugs, parity was not associated with better adherence or less discontinuation of therapy but yielded decreased patient out-of-pocket payments for some patients.
Interaction of an accelerating layer with a cloud: formation of tails and cumulative jets
Authors: Kotova G Yu , Krasnobaev K V
Published: December 2019

We consider the penetration of spherical dense cloud into a planar layer of gas that is in gravitational equilibrium in a constant field of gravity with acceleration W. We take into account the compressibility of the medium in contrast to the classical problem of a drop falling on the surface of an incompressible fluid. Our goal is to study the formation of cumulative jets in relation to the conditions on the borders of H ii regions. We determine those features of motion that would distinguish jet streams from inhomogeneities of a different origin. Our simulation has shown that cumulative jets may arise in the presence of an acceleration layer W. The gas in jet moves in the direction opposite to the initial velocity Vc. At the same time, there are both a cumulative jet and tails, teardrop-shaped condensations, caused, respectively, by gas inflow in the wake behind the cloud and the classical Rayleigh–Taylor instability. We assume the model, according to which the H ii RCW 82 region formed in an initially homogeneous cloud. In framework of this model, we estimated the characteristic time of a cumulative jet formation ts ≈ 0.15 Myr. This is less than the present age of the H ii RCW 82 region, which is about 0.4 Myr. From the obtained estimates, it follows that the conditions at the periphery of the H ii RCW 82 region are favourable for the manifestation of cumulative effects on scales of ∼1.4 × 1017 cm, which are significantly smaller than the layer thickness.
The surprisingly small impact of magnetic fields on the inner accretion flow of Sagittarius A* fueled by stellar winds
Authors: Ressler S M , Quataert E , Stone J M
Published: December 2019

We study the flow structure in 3D magnetohydrodynamic (MHD) simulations of accretion on to Sagittarius A* via the magnetized winds of the orbiting Wolf–Rayet stars. These simulations cover over 3 orders of magnitude in radius to reach ≈300 gravitational radii, with only one poorly constrained parameter (the magnetic field in the stellar winds). Even for winds with relatively weak magnetic fields (e.g. plasma β ∼ 106), flux freezing/compression in the inflowing gas amplifies the field to β ∼ few well before it reaches the event horizon. Overall, the dynamics, accretion rate, and spherically averaged flow profiles (e.g. density, velocity) in our MHD simulations are remarkably similar to analogous hydrodynamic simulations. We attribute this to the broad distribution of angular momentum provided by the stellar winds, which sources accretion even absent much angular momentum transport. We find that the magneto-rotational instability is not important because of (i) strong magnetic fields that are amplified by flux freezing/compression, and (ii) the rapid inflow/outflow times of the gas and inefficient radiative cooling preclude circularization. The primary effect of magnetic fields is that they drive a polar outflow that is absent in hydrodynamics. The dynamical state of the accretion flow found in our simulations is unlike the rotationally supported tori used as initial conditions in horizon scale simulations, which could have implications for models being used to interpret Event Horizon Telescope and GRAVITY observations of Sgr A*.
UV bright red-sequence galaxies: how do UV upturn systems evolve in redshift and stellar mass?
Authors: Dantas M L L , Coelho P R T , de Souza R S , Gonçalves T S
Published: December 2019

The so-called ultraviolet (UV) upturn of elliptical galaxies is a phenomenon characterized by the up-rise of their fluxes in bluer wavelengths, typically in the 1200–2500 Å range. This work aims at estimating the rate of occurrence of the UV upturn over the entire red-sequence population of galaxies that show significant UV emission. This assessment is made considering it as function of three parameters: redshift, stellar mass, and – what may seem counter-intuitive at first – emission-line classification. We built a multiwavelength spectrophotometric catalogue from the Galaxy Mass Assembly survey, together with aperture-matched data from Galaxy Evolution Explorer Medium-Depth Imaging Survey (MIS) and Sloan Digital Sky Survey, covering the redshift range between 0.06 and 0.40. From this sample, we analyse the UV emission among UV bright galaxies, by selecting those that occupy the red-sequence locus in the (NUV− r) × (FUV−NUV) chart; then, we stratify the sample by their emission-line classes. To that end, we make use of emission-line diagnostic diagrams, focusing the analysis in retired/passive lineless galaxies. Then, a Bayesian logistic model was built to simultaneously deal with the effects of all galaxy properties (including emission-line classification or lack thereof). The main results show that retired/passive systems host an up-rise in the fraction of UV upturn for redshifts between 0.06 and 0.25, followed by an in-fall up to 0.35. Additionally, we show that the fraction of UV upturn hosts rises with increasing stellar mass.
Haplotyping by CRISPR-mediated DNA circularization (CRISPR-hapC) broadens allele-specific gene editing
Authors: Yu Jiaying , Xiang Xi , Huang Jinrong , Liang Xue , Pan Xiaoguang , Dong Zhanying , Petersen Trine Skov , Qu Kunli , Yang Ling , Zhao Xiaoying , Li Siyuan , Zheng Tianyu , Xu Zhe , Liu Chengxun , Han Peng , Xu Fengping , Yang Huanming , Liu Xin , Zhang Xiuqing , Bolund Lars , Luo Yonglun , Lin Lin
Published: December 2019

Allele-specific protospacer adjacent motif (asPAM)-positioning SNPs and CRISPRs are valuable resources for gene therapy of dominant disorders. However, one technical hurdle is to identify the haplotype comprising the disease-causing allele and the distal asPAM SNPs. Here, we describe a novel CRISPR-based method (CRISPR-hapC) for haplotyping. Based on the generation (with a pair of CRISPRs) of extrachromosomal circular DNA in cells, the CRISPR-hapC can map haplotypes from a few hundred bases to over 200 Mb. To streamline and demonstrate the applicability of the CRISPR-hapC and asPAM CRISPR for allele-specific gene editing, we reanalyzed the 1000 human pan-genome and generated a high frequency asPAM SNP and CRISPR database (www.crispratlas.com/knockout) for four CRISPR systems (SaCas9, SpCas9, xCas9 and Cas12a). Using the huntingtin (HTT) CAG expansion and transthyretin (TTR) exon 2 mutation as examples, we showed that the asPAM CRISPRs can specifically discriminate active and dead PAMs for all 23 loci tested. Combination of the CRISPR-hapC and asPAM CRISPRs further demonstrated the capability for achieving highly accurate and haplotype-specific deletion of the HTT CAG expansion allele and TTR exon 2 mutation in human cells. Taken together, our study provides a new approach and an important resource for genome research and allele-specific (haplotype-specific) gene therapy.
PAREameters: a tool for computational inference of plant miRNA–mRNA targeting rules using small RNA and degradome sequencing data
Authors: Thody Joshua , Moulton Vincent , Mohorianu Irina
Published: December 2019

MicroRNAs (miRNAs) are short, non-coding RNAs that modulate the translation-rate of messenger RNAs (mRNAs) by directing the RNA-induced silencing complex to sequence-specific targets. In plants, this typically results in cleavage and subsequent degradation of the mRNA. Degradome sequencing is a high-throughput technique developed to capture cleaved mRNA fragments and thus can be used to support miRNA target prediction. The current criteria used for miRNA target prediction were inferred on a limited number of experimentally validated A. thaliana interactions and were adapted to fit these specific interactions; thus, these fixed criteria may not be optimal across all datasets (organisms, tissues or treatments). We present a new tool, PAREameters, for inferring targeting criteria from small RNA and degradome sequencing datasets. We evaluate its performance using a more extensive set of experimentally validated interactions in multiple A. thaliana datasets. We also perform comprehensive analyses to highlight and quantify the differences between subsets of miRNA–mRNA interactions in model and non-model organisms. Our results show increased sensitivity in A. thaliana when using the PAREameters inferred criteria and that using data-driven criteria enables the identification of additional interactions that further our understanding of the RNA silencing pathway in both model and non-model organisms.
Klotho is a novel therapeutic target in peritoneal fibrosis via Wnt signaling inhibition
Authors: Kadoya Hiroyuki , Satoh Minoru , Nishi Yuko , Kondo Megumi , Wada Yoshihisa , Sogawa Yuji , Kidokoro Kengo , Nagasu Hajime , Sasaki Tamaki , Kashihara Naoki
Published: December 2019

Background

Long-term exposure to bioincompatible peritoneal dialysate causes the loss of mesothelial cells and accumulation of matrix proteins, leading to an increase in the thickness of the submesothelial layer, thereby limiting the long-term effectiveness of peritoneal dialysis (PD). However, the detailed molecular mechanisms underlying the process of peritoneal fibrosis have not been clearly elucidated. Wnt/β-catenin signaling pathway activation has been suggested to play a pivotal role in the development of organ fibrosis. Moreover, Klotho protein can regulate Wnt/β-catenin signaling. We examined the role of Klotho protein in reducing peritoneal fibrosis by inhibiting Wnt/β-catenin signaling.

Methods

The β-catenin-activated transgenic (BAT) driving expression of nuclear β-galactosidase reporter transgenic (BAT-LacZ) mice, the alpha-Klotho gene under control of human elongation factor 1 alpha promoter [Klotho transgenic (KLTG) and C57BL/6 background] and C57BL/6 mice [wild-type (WT)] were used. The mice received daily intraperitoneal (i.p.) injections of 4.25% glucose with lactate (PD solution) or saline as a control for 4 weeks. Other mice received daily i.p. injections of the same volume of saline (normal control).

Results

After exposure to PD, Wnt signal activation was observed on the peritoneal mesothelial cells in WT-PD mice. The peritoneal fibrosis was also accelerated in WT-PD mice. The protein expression of β-catenin and Wnt-inducible genes were also remarkably increased in WT-PD mice. On the other hand, KLTG-PD mice attenuated activation of Wnt/β-catenin signaling after exposure to PD and ameliorated the progression of peritoneal fibrosis.

Conclusions

Overexpression of Klotho protein protects the peritoneal membrane through attenuation of the Wnt/β-catenin signaling pathway. The availability of recombinant Klotho protein would provide a novel potential therapeutic target in peritoneal fibrosis.
Neuroprotection in the Acute Stage Enables Functional Recovery Following Repair of Chronic Cervical Root Transection After a 3-Week Delay
Authors: Chang Kai-Ting , Lin Yi-Lo , Lin Chi-Te , Hong Chen-Jei , Cheng Yung-Hsin , Tsai May-Jywan , Huang Wen-Cheng , Shih Yang-Hsin , Lee Yi-Yen , Cheng Henrich , Huang Ming-Chao
Published: December 2019

BACKGROUND

Preganglionic cervical root transection (PCRT) is the most severe type of brachial plexus injury. In some cases, surgical procedures must be postponed for ≥3 wk until electromyographic confirmation. However, research works have previously shown that treating PCRT after a 3-wk delay fails to result in functional recovery.

OBJECTIVE

To assess whether the immunosuppressive drug sirolimus, by promoting neuroprotection in the acute phase of PCRT, could enable functional recovery in cases of delayed repair.

METHODS

First, rats received a left 6th to 8th cervical root transection, after which half were administered sirolimus for 1 wk. Markers of microglia, astrocytes, neurons, and autophagy were assessed at days 7 and 21. Second, animals with the same injury received nerve grafts, along with acidic fibroblast growth factor and fibrin glue, 3 wk postinjury. Sirolimus was administered to half of them for the first week. Mechanical sensation, grasping power, spinal cord morphology, functional neuron survival, nerve fiber regeneration, and somatosensory-evoked potentials (SSEPs) were assessed 1 and 23 wk postinjury.

RESULTS

Sirolimus was shown to attenuate microglial and astrocytic proliferation and enhance neuronal autophagy and survival; only rats treated with sirolimus underwent significant sensory and motor function recovery. In addition, rats who achieved functional recovery were shown to have abundant nerve fibers and neurons in the dorsal root entry zone, dorsal root ganglion, and ventral horn, as well as to have SSEPs reappearance.

CONCLUSION

Sirolimus-induced neuroprotection in the acute stage of PCRT enables functional recovery, even if surgical repair is performed after a 3-wk delay.
Anisotropic response measurements of ZnWO4 scintillators to neutrons for developing a direction-sensitive dark matter detector
Authors: Pedersen Juan W , Sekiya Hiroyuki , Ichimura Koichi
Published: December 2019

The scintillation yields of ZnWO$_4$ crystals change depending on the incident direction of particles. This property can be used as a direction-sensitive dark matter detector, so we investigated the ZnWO$_4$ light yields ratio of neutron-induced nuclear recoils to gamma-ray-induced electron recoils (quenching factor). Two surfaces almost perpendicular to the crystal axis of ZnWO$_4$ were irradiated with a quasi-monochromatic neutron beam of 0.885 MeV, and the quenching factors of both surfaces for the oxygen-nucleus recoil in the ZnWO$_4$ crystal were measured. The obtained quenching factors of the two surfaces were $0.235 \pm 0.026$ and $0.199 \pm 0.020$, respectively, confirming 15.3% anisotropy.
Intrathecal Morphine in the Presence of a Syrinx in Pediatric Spinal Deformity Surgery
Authors: Ina Jason , Poe-Kochert Connie , Hardesty Christina K. , Son-Hing Jochen P. , Tripi Paul , Thompson George H.
Published: December 2019

Background:

Intrathecal morphine (IM) is a popular adjunct for pain relief during pediatric spinal deformity surgery. There is no literature regarding its usefulness and safety in the presence of a spinal cord syrinx for patients undergoing spinal instrumentation. Anesthesiologists have previously been reluctant to use IM in the presence of any syrinx.

Methods:

We retrospectively reviewed all patients with a preoperatively diagnosed spinal cord syrinx undergoing spinal deformity surgery who received IM and did not receive IM (non-IM). We recorded location of the syrinx, surgical time, length of stay, unexpected pediatric intensive care unit (PICU) admission, IM related complications (neurological, respiratory depression, or pruritus, nausea/vomiting), and reason for no IM administration. Patients with a syrinx and myelodysplasia (8), tethered spinal cord (4), paraplegia (1), holocord (1), neuroblastoma (1), and spinal cord glioma (1) were not given IM. Other reasons included a failed attempt (1), expectedly short surgical time (1), and anesthesiologist declined (2).

Results:

There were 42 patients who met the inclusion criteria. Twenty-two patients received IM, while 20 patients did not. Patients receiving IM had 4 cervical, 5 cervicothoracic, 12 thoracic syrinxes, and 1 holocord syrinx. The non-IM group had 8 cervicothoracic, 6 thoracic, 4 holocord syrinxes, and 2 had unclassified locations. There were no neurological complications in the IM group, and 1 patient experienced respiratory depression following a shorter than expected surgery and was observed overnight in the PICU. One patient in the non-IM group with a holocord syrinx had temporary lower extremity weakness postoperatively that completely resolved and 4 patients were unexpectedly admitted to the PICU. Pruritus and nausea/vomiting was mild and similar in both groups.

Conclusions:

Our study demonstrates that with careful preoperative evaluation, most patients with a spinal cord syrinx can safely be given IM. Certain patients, such as those with a spinal holocord syrinx may have anatomic reasons to avoid IM, but those who are deemed appropriate for IM can receive it safely.

Level of Evidence:

Level III—therapeutic study; retrospective comparative study.
Neuromuscular Electrostimulation Device Reduces Preoperative Edema and Accelerates Readiness for Theater in Patients Requiring Open Reduction Internal Fixation for Acute Ankle Fracture
Authors: Mahmood Ihsan , Chandler Henry , Kottam Lucksy , Eardley William , Rangan Amar , Baker Paul
Published: December 2019

Significant edema manifests as soft tissue swelling that can delay surgery in patients with ankle fractures. Interventions that expedite swelling reduction may yield clinical and economic benefits. This case-control pilot study aimed to assess the ability to recruit ankle fracture patients to a prospective study using a neuromuscular electrostimulation (NMES) device. Device effectiveness, safety, and patient acceptability were also assessed. Prospective evaluation of 20 patients admitted for ankle fracture fixation with the application of NMES device to the skin just below the knee (intervention arm). Participants were matched for baseline demographics and injury descriptors to a historical operative cohort (control arm). The time until the swelling had settled to a level permitting surgery (“readiness for surgery”) was recorded alongside patient tolerability and device acceptance. The mean time until swelling reduced to a level permitting surgery was 1.66 days (NMES) versus 3.66 days (control) (P=0.001). Overall 60% of participants were ready for theater after 2 days of treatment with the NMES device compared with 27% in the control group (P<0.01). Independent health economic modeling of this scenario suggests that the savings associated with this accelerated readiness for theater is £569 per patient. The NMES device is safe and well tolerated by patients with ankle fractures. It is easy to apply, can be worn continuously, and does not restrict patients to their bed space. This study suggests that it is effective in reducing ankle edema and accelerating readiness for theater and may therefore allow earlier surgery and reduced length of stay in this patient group.

Level of Evidence: Diagnostic Level 3. See Instructions for Authors for a complete description of levels of evidence.
Arthroscopic Tibiotalocalcaneal Arthrodesis
Authors: Vilá-Rico Jesús , Vacas-Sánchez Elena , Abarquero-Diezhandino Ana , Mellado-Romero María
Published: December 2019

Introduction:

Arthrodesis is still the gold standard for severe ankle and hindfoot osteoarthritis. The arthroscopic tibiotalocalcaneal arthrodesis technique has been described and developed in the past decade. Tibiotalocalcaneal arthrodesis (TTCA) is the election procedure for combined severe ankle and subtalar osteoarthritis after failure of conservative treatment. The arthroscopic technique is more respectful to the surrounding soft tissues and the vascular supply; hence, it provides a theoretical benefit in terms of consolidation, and it is suitable for cases in which the open surgery is not desirable. We perform the surgery with the patient in prone decubitus position, and we use conventional arthroscopic instruments. We use the posterior portals described by van Dijk to access both tibiotalar and posterior subtalar joints and perform the cartilage denudation. We aim to have a healthy, well-vascularized subchondral bone and obtain a good coaptation of the articular surfaces. The retrograde tibiotalocalcaneal nail is the implant of choice for the TTCA. We consider that the lower surgical aggression of the arthroscopic procedure compared with the open technique should allow a satisfactory union rate without bone grafting. The global consolidation rate reported is 67% to 100%. The global complication rate reported is 7% to 33%. Most are related to osteosynthesis material and superficial wound infections. Arthroscopic TTCA offers excellent results in selected patients. A protocolized surgical technique using posterior endoscopic portals is mandatory.

Level of Evidence: Diagnostic Level V. See Instructions for Authors for a complete description of levels of evidence.
Preoperative Optimization of Chronic Pain Patients Undergoing Surgery
Authors: Gulur Padma , Nelli Amanda
Published: December 2019

Surgery presents unique challenges in pain management for patients with chronic pain. A perioperative optimization program, starting at decision to surgery, is likely to yield the best results for this population. Perioperative optimization focuses on psychological, medical, and physical optimization. Psychological optimization includes cognitive behavior therapy, relaxation, and music therapy. Medical optimization focuses on the multimodal approaches of pharmacological adjustment and physical optimization focuses on prehabilitation and nutrition optimization. The ideal care model incorporates these optimization strategies into clinical practice to prepare the patient appropriately for the best possible outcomes. Although preoperative optimization is key for sustained outcomes, intraoperative and inpatient protocols are equally important, as is postdischarge subacute support by pain specialists, as needed, for up to 90 days after surgery.
Observational Study of Clinician Attentional Reserves (OSCAR): Acuity-Based Rounds Help Preserve Clinicians’ Attention
Authors: Miles Merrick , Mueller Dorothee , Gay-Betton Daniel , Baum Miller Sarah H. , Massa Scott , Shi Yaping , Shotwell Matthew S. , Lane-Fall Meghan , Schlesinger Joseph J.
Published: December 2019

Objectives:

Team rounding in the ICU can tax clinicians’ finite attentional resources. We hypothesized that a novel approach to rounding, where patients are seen in a decreasing order of acuity, would decrease attentional attrition.

Design:

Prospective interventional internal-control cohort study in which stop signal task testing was used as a proxy for attentional reserves. Stop signal task is a measure of cognitive control and response inhibition in addition to performance monitoring, all reflective of executive control abilities, and our surrogate for attentional reserves.

Setting:

The ICUs of Vanderbilt University Medical Center (site 1) and the University of Pennsylvania (site 2) from November 2014 to August 2017.

Subjects:

Thirty-three clinicians at site 1, and 24 clinicians at site 2.

Interventions:

Acuity-based rounding, in which clinicians round from highest to lowest acuity as determined by Sequential Organ Failure Assessment score or an equivalent acuity score.

Measurements and Main Results:

The stop signal task results of ICU staff at two sites were compared for conventional (in room order) versus novel (in decreasing order of acuity) rounding order. At site 1, the difference in stop signal reaction time change between two rounding types was –39.0 ms (95% CI, –50.6 to –27.4 ms; p < 0.001), and at site 2, the performance stop signal reaction time was –15.6 ms (95% CI, –29.1 to –2.1 ms; p = 0.023). These sub-second changes, while small, are significant in the neuroscience domain.

Conclusions:

Rounding in decreasing order of patient acuity mitigated attrition in attentional reserves when compared with the traditional rounding method.
Delay in Antibiotic Administration Is Associated With Mortality Among Septic Shock Patients With Staphylococcus aureus Bacteremia*
Authors: Corl Keith A. , Zeba Fatima , Caffrey Aisling R. , Hermenau Matthew , Lopes Vrishali , Phillips Gary , Merchant Roland C. , Levy Mitchell M. , LaPlante Kerry L.
Published: December 2019

Objectives:

The relationship between the timing of antibiotics and mortality among septic shock patients has not been examined among patients specifically with Staphylococcus aureus bacteremia.

Design:

Retrospective analysis of a Veterans Affairs S. aureus bacteremia database.

Setting:

One-hundred twenty-two hospitals in the Veterans Affairs Health System.

Patients:

Patients with septic shock and S. aureus bacteremia admitted directly from the emergency department to the ICU from January 1, 2003, to October 1, 2015, were evaluated.

Interventions:

Time to appropriate antibiotic administration and 30-day mortality.

Measurements and Main Results:

A total of 506 patients with S. aureus bacteremia and septic shock were included in the analysis. Thirty-day mortality was 78.1% for the entire cohort and was similar for those participants with methicillin-resistant S. aureus and methicillin-sensitive S. aureus bacteremia. Our multivariate analysis revealed that, as compared with those who received appropriate antibiotics within 1 hour after emergency department presentation, each additional hour that passed before appropriate antibiotics were administered produced an odds ratio of 1.11 (95% CI, 1.02–1.21) of mortality within 30 days. This odds increase equates to an average adjusted mortality increase of 1.3% (95% CI, 0.4–2.2%) for every hour that passes before antibiotics are administered.

Conclusions:

The results of this study further support the importance of prompt appropriate antibiotic administration for patients with septic shock. Physicians should consider acting quickly to administer antibiotics with S. aureus coverage to any patient suspected of having septic shock.
The correlation between IL-4 polymorphisms and colorectal cancer risk in a population in Northwest China
Authors: Wen Xiulin , Xin Xia , Li Jieqiong , Qiao Lina , Liu Fang , Guo Yuan , Qu Zhan , Wang Rui , Li Xiaomei
Published: December 2019

Our aim was to investigate whether polymorphisms in the interleukin-4 (IL-4) gene are associated with the risk of colorectal cancer (CRC) in a Chinese Han population. Six single-nucleotide polymorphisms (SNPs) in the IL-4 were genotyped by Agena MassARRAY in 248 CRC patients and 463 healthy controls. The association of IL-4 polymorphisms with CRC risk was assessed by genetic models, linkage disequilibrium, and haplotype analyses. The results suggested that the CC genotype of rs2243250 confers a lower risk of CRC in the recessive model [odds ratio (OR) =  0.42, 95% confidence interval (CI): 0.19–0.92, P = 0.020]. Similarly, rs2227284 GG was associated with a reduced risk of CRC in the codominant (OR = 0.18, 95% CI: 0.04–0.82, P = 0.027) and recessive (OR = 0.19, 95% CI: 0.04–0.83, P = 0.008) models adjusted for age. Our findings suggested that rs2243250 and rs2227284 in IL-4 are associated significantly with reduced CRC risk, which may facilitate the identification of CRC patients in Chinese populations.