bluuebunny/crossref_metadata_2025_split huggingface dataset:
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

Abstract

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

ABSTRACT
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

ABSTRACT
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

ABSTRACT
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

Abstract
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

AbstractMicroRNAs (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

Abstract

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

Abstract

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

Abstract
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.
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.
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.