bluuebunny/crossref_metadata_2025_split huggingface dataset:
Inference about causation from examination of familial confounding (ICE FALCON): a model for assessing causation analogous to Mendelian randomization
Authors: Li Shuai , Bui Minh , Hopper John L 
Published: March 2020

Abstract

Background
We developed a method to make Inference about Causation from Examination of FAmiliaL CONfounding (ICE FALCON) using observational data for related individuals and considering changes in a pair of regression coefficients. ICE FALCON has some similarities to Mendelian randomization (MR) but uses in effect all the familial determinants of the exposure, not just those captured by measured genetic variants, and does not require genetic data nor make strong assumptions. ICE FALCON can assess tracking of a measure over time, an issue often difficult to assess using MR due to lack of a valid instrumental variable.

Methods
We describe ICE FALCON and present two empirical applications with simulations.

Results
We found evidence consistent with body mass index (BMI) having a causal effect on DNA methylation at the ABCG1 locus, the same conclusion as from MR analyses but providing about 2.5 times more information per subject. We found evidence that tracking of BMI is consistent with longitudinal causation, as well as familial confounding. The simulations supported the validity of ICE FALCON.

Conclusions
There are conceptual similarities between ICE FALCON and MR, but empirically they are giving similar conclusions with possibly more information per subject from ICE FALCON. ICE FALCON can be applied to circumstances in which MR cannot be applied, such as when there is no a priori genetic knowledge and/or data available to create a valid instrumental variable, or when the assumptions underlying MR analysis are suspect. ICE FALCON could provide insights into causality for a wide range of public health questions.
Evaluation of the effect of UGT1A1 polymorphisms on the pharmacokinetics of oral and long-acting injectable cabotegravir
Authors: Patel Parul , Xue Zhengyu , King Karen S , Parham Laura , Ford Susan , Lou Yu , Bakshi Kalpana K , Sutton Kenneth , Margolis David , Hughes Arlene R , Spreen William R 
Published: March 2020

Abstract

Background
Cabotegravir is an HIV integrase inhibitor in clinical development with both oral and long-acting (LA) injectable formulations. Cabotegravir is primarily metabolized by uridine 5′-diphospho-glucuronosyltransferase (UGT) 1A1, a known polymorphic enzyme with functional variants that can affect drug metabolism and exposure.

Objectives
To investigate the pharmacogenetic effects of the reduced-function alleles UGT1A1*6, UGT1A1*28 and/or UGT1A1*37 on steady-state pharmacokinetics (PK) and safety of oral cabotegravir (30 mg/day) and intramuscular cabotegravir LA (400 mg every 4 weeks or 600 mg every 8 weeks).

Methods
Plasma cabotegravir PK was assessed in 346 UGT-genotyped participants with and without UGT1A1 functional variants across six studies (four Phase I and two Phase II) of oral cabotegravir, including 215 HIV-infected participants who received oral cabotegravir followed by cabotegravir LA. Changes from baseline in total bilirubin and ALT were assessed in one study (LATTE; NCT01641809).

Results
Statistically significant (P &lt; 0.05) associations were observed between UGT1A1 genotype and plasma cabotegravir PK parameters, with 28%–50% increases following oral cabotegravir [plasma cabotegravir concentration at the end of the dosing interval (Ctau), 1.50-fold; AUCtau, 1.41-fold; and Cmax, 1.28-fold] and 16%–24% increases following cabotegravir LA administration (48 week Ctau, 1.24-fold; AUCtau, 1.16-fold; and Cmax, 1.18-fold) among those with low-versus-normal genetically predicted UGT1A1 activity. A statistically significant (P &lt; 10−5) association between predicted UGT1A1 activity and maximum change in total bilirubin was also observed (2.45-fold asymptomatic increase for low versus normal) without a corresponding change in ALT.

Conclusions
This modest increase in oral and parenteral cabotegravir exposure associated with a reduced function of UGT1A1 is not considered clinically relevant based on accumulated safety data; no dose adjustment is required.
Interface 2.0 in Rules on State-Owned Enterprises: A Comparative Institutional Approach
Authors: Ding Ru 
Published: March 2020

ABSTRACT
Interface mechanisms in international economic law refer to international, regional, or domestic legal instruments that resolve problems arising from differences in economic systems. The existing interface mechanism regarding disciplining state-owned enterprises (SOEs)’ activities remains unclear and has led to disputes and a divergence of views among major trading partners, most notably between the United States and China. The underlying cause is the lack of an analytical framework to understand SOEs from a comparative view that may foster consensus-building discussions. This article constructs a comparative institutional framework to understand SOEs in a variety of market economy settings, which inspires new approaches in analyzing SOE-related legal issues in international economic law. This article takes the ‘public body’ issue in the WTO and the new disciplines on SOEs as examples, demonstrating that a type of activity-based approach can be a new interface mechanism for international rules on SOEs.
Forecasting Equity Index Volatility by Measuring the Linkage among Component Stocks*
Authors: Qiu Yue , Xie Tian , Yu Jun , Zhou Qiankun 
Published: March 2020

Abstract
The linkage among the realized volatilities of component stocks is important when modeling and forecasting the relevant index volatility. In this article, the linkage is measured via an extended Common Correlated Effects (CCEs) approach under a panel heterogeneous autoregression model where unobserved common factors in errors are assumed. Consistency of the CCE estimator is obtained. The common factors are extracted using the principal component analysis. Empirical studies show that realized volatility models exploiting the linkage effects lead to significantly better out-of-sample forecast performance, for example, an up to 32% increase in the pseudo R2. We also conduct various forecasting exercises on the linkage variables that compare conventional regression methods with popular machine learning techniques.
Proportion of Patients in Phase I Oncology Trials Receiving Treatments That Are Ultimately Approved
Authors: Zhang Sean X , Fergusson Dean , Kimmelman Jonathan 
Published: March 2020

Abstract

Background
Phase I oncology trials are often regarded as a therapeutic option for patients. However, such claims have relied on surrogate measures of benefit, such as objective response.

Methods
Using a systematic search of publications, we assessed the therapeutic value of phase I cancer trial participation by determining the probability that patients will receive active doses of treatments that eventually receive FDA approval or a National Comprehensive Cancer Network (NCCN) guideline recommendation for their indication. ClinicalTrials.gov, PubMed, American Society of Clinical Oncology reports, NCCN guidelines, and Drugs@FDA were searched between May 1, 2018, and July 31, 2018. All statistical tests were 2-sided.

Results
A total of 1000 phase I oncology trials initiated between 2005 and 2010 and enrolling 32 582 patients were randomly sampled from 3229 eligible trials on ClinicalTrials.gov. A total of 386 (1.2%) patients received a treatment that was approved by the US Food and Drug Administration for their malignancy at a dose delivered in the trial; including NCCN guideline recommendations, the number and proportion are 1168 (3.6%). Meta-regression showed a statistically significantly greater proportion of patients receiving a drug that was ultimately FDA approved in biomarker trials (rate ratio = 4.49, 95% confidence interval [CI] = 1.53 to 13.23; P = .006) and single-indication trials (rate ratio = 3.32, 95% CI = 1.21 to 9.15; P  = .02); proportions were statistically significantly lower for combination vs monotherapy trials (rate ratio = 0.09, 95% CI = 0.01 to 0.68; P  = .02).

Conclusions
One in 83 patients in phase I cancer trials received a treatment that was approved for their indication at the doses received. Given published estimates of serious adverse event rates of 10%-19%, this represents low therapeutic value for phase I trial participation.
On The Etymology Of Biblical Hebrew : A Contribution to the ‘Sin Offering’ vs. ‘Purification Offering’ Debate
Authors: Lam Joseph 
Published: March 2020

Abstract
This article evaluates Jacob Milgrom's widely-cited argument that the Biblical Hebrew offering term , by virtue of its derivation from a *qattalt noun pattern with gemination of the second root consonant, is intrinsically connected in its semantics to the Piel of (‘to purify, purge’) — an argument often used to support a rendering of as ‘purification offering’ (instead of the traditional ‘sin offering’). This argument is untenable, not only because it is based on an outmoded approach to the Semitic noun system, but also because it fails to explain how came simultaneously to denote ‘sin’ in Biblical Hebrew. Instead, the most plausible account of the term sees the ‘sin’ meaning as primary, with the ‘offering’ usage derived via metonymy, i.e., ‘an offering that deals with ’. Also, given the explanations of the *qattal(a)t pattern in the comparative Semitic literature, (‘sin’) is best understood as an abstract substantive derived from, or viewed as a counterpart to, the *qattal noun (‘sinful’, ‘[habitual] sinner’), with perhaps a secondary association with malady — another common semantic connotation of Biblical Hebrew *qattalt.
A two-sided but significantly beamed jet in the supercritical accretion quasar IRAS F11119+3257
Authors: Yang Jun , Paragi Zsolt , An Tao , Baan Willem A , Mohan Prashanth , Liu Xiang 
Published: March 2020

ABSTRACT
Highly accreting quasars are quite luminous in the X-ray and optical regimes; while, they tend to become radio quiet and have optically thin radio spectra. Among the known quasars, IRAS F11119+3257 is a supercritical accretion source because it has a bolometric luminosity slightly above the Eddington limit and extremely powerful X-ray outflows. To probe its radio structure, we investigated its radio spectrum between 0.15 and 96.15 GHz and performed very-long-baseline interferometric (VLBI) observations with the European VLBI Network (EVN) at 1.66 and 4.93 GHz. The deep EVN image at 1.66 GHz shows a two-sided jet with a projected separation about 200 pc and a very high flux density ratio of about 290. Together with the best-fitting value of the integrated spectral index of −1.31 ± 0.02 in the optically thin part, we infer that the approaching jet has an intrinsic speed at least 0.57 times of the light speed. This is a new record among the known all kinds of super-Eddington accreting sources and unlikely accelerated by the radiation pressure in a certain models. We propose a scenario in which IRAS F11119+3257 is an unusual compact symmetric object with a small jet viewing angle and a radio spectrum peaking at 0.53 ± 0.06 GHz mainly due to the synchrotron self-absorption.
Performance limits of adaptive-optics/high-contrast imagers with pyramid wavefront sensors
Authors: Correia Carlos M , Fauvarque Olivier , Bond Charlotte Z , Chambouleyron Vincent , Sauvage Jean-François , Fusco Thierry 
Published: March 2020

ABSTRACTAdvanced adaptive-optics (AO) systems will likely utilize pyramid wavefront sensors (PWFSs) over the traditional Shack–Hartmann sensor in the quest for increased sensitivity, peak performance and ultimate contrast. Here, we explain and quantify the PWFS theoretical limits as a means to highlight its properties and applications. We explore forward models for the PWFS in the spatial-frequency domain: these prove useful because (i) they emanate directly from physical-optics (Fourier) diffraction theory; (ii) they provide a straightforward path to meaningful error breakdowns; (iii) they allow for reconstruction algorithms with $O (n\, \log(n))$ complexity for large-scale systems; and (iv) they tie in seamlessly with decoupled (distributed) optimal predictive dynamic control for performance and contrast optimization. All these aspects are dealt with here. We focus on recent analytical PWFS developments and demonstrate the performance using both analytic and end-to-end simulations. We anchor our estimates on observed on-sky contrast on existing systems, and then show very good agreement between analytical and Monte Carlo performance estimates on AO systems featuring the PWFS. For a potential upgrade of existing high-contrast imagers on 10-m-class telescopes with visible or near-infrared PWFSs, we show, under median conditions at Paranal, a contrast improvement (limited by chromatic and scintillation effects) of 2×–5× when just replacing the wavefront sensor at large separations close to the AO control radius where aliasing dominates, and of factors in excess of 10× by coupling distributed control with the PWFS over most of the AO control region, from small separations starting with an inner working angle of typically 1–2 λ/D to the AO correction edge (here 20 λ/D).
Modelling the stochasticity of high-redshift halo bias
Authors: Nasirudin Ainulnabilah , Iliev Ilian T , Ahn Kyungjin 
Published: March 2020

ABSTRACT
A very large dynamic range with simultaneous capture of both large and small scales in the simulations of cosmic structures is required for correct modelling of many cosmological phenomena, particularly at high redshift. This is not always available, or when it is, it makes such simulations very expensive. We present a novel subgrid method for modelling low-mass ($10^5\, {\rm M}_\odot \le M_{\rm halo}\le 10^9\, {\rm M}_\odot$) haloes, which are otherwise unresolved in large-volume cosmological simulations limited in numerical resolution. In addition to the deterministic halo bias that captures the average property, we model its stochasticity that is correlated in time. We find that the instantaneous binned distribution of the number of haloes is well approximated by a lognormal distribution, with overall amplitude modulated by this ‘temporal correlation bias’. The robustness of our new scheme is tested against various statistical measures, and we find that temporally correlated stochasticity generates mock halo data that is significantly more reliable than that from temporally uncorrelated stochasticity. Our method can be applied for simulating processes that depend on both the small- and large-scale structures, especially for those that are sensitive to the evolution history of structure formation such as the process of cosmic reionization. As a sample application, we generate a mock distribution of medium-mass (108 ≤ M/M⊙ ≤ 109) haloes inside a 500 Mpc $\, h^{-1}$, 3003 grid simulation box. This mock halo catalogue bears a reasonable statistical agreement with a halo catalogue from numerically resolved haloes in a smaller box, and therefore will allow a very self-consistent sets of cosmic reionization simulations in a box large enough to generate statistically reliable data.
New observations of DW Cnc: where is the 38 min signal?
Authors: Segura Montero O , Ramírez S H , Echevarría J 
Published: March 2020

ABSTRACT
We present extensive radial velocity observations of the intermediate polar DW Cnc during its 2018–2019 low state. We show that the 86 min signal associated with the orbital period is strong in our radial velocity analysis, power spectrum search, and in our Doppler tomography. However, we find that the velocity modulation associated with the 70 min beat period and the 38 min spin cycle is dramatically weaker than that previously observed. We put forward two interpretations for this change. The first is that a sudden drop into a low state detected in 2018–2019 caused an episode of low mass transfer from the companion, thus inhibiting the lighthouse effect produced by the rebound emission. The second is that this is a consequence of a rare outburst detected in 2007 by Crawford et al. (2008). We find this post-outburst hypothesis to be less likely. If the first scenario is correct, we predict that DW Cnc will recover its intermediate polar characteristics. A new ephemeris is presented by combining Patterson et al. (2004) radial velocities with ours.
The population of galaxies that contribute to the H i mass function
Authors: Dutta Saili , Khandai Nishikanta , Dey Biprateep 
Published: March 2020

ABSTRACT
We look at the contribution of different galaxy populations to the atomic hydrogen (H i) mass function (HIMF) and the H i density parameter, ΩH i, in the local Universe. Our analysis is based on a sample of 7857 H i selected galaxies selected from a volume common to the Sloan Digital Sky Survey (SDSS) and Arecibo Fast Legacy ALFA (40 per cent catalogue – α.40) surveys. We define different populations of galaxies in the colour (u − r)–magnitude (Mr) plane and compute the HIMF for each of them. Additionally we compute the HIMF for dark galaxies; these are undetected in SDSS and represent $\sim 2{{\ \rm per\ cent}}$ of the total sample. We find that the luminous red population dominates the total HIMF for $\log _{10}(M_{\rm{H\,{\small I}}}h^2_{70}/M_{\odot }) \ge 10.4$. The full red population – luminous and faint – represents about $\sim 17{{\ \rm per\ cent}}$ of the ΩH i budget, while that of the dark population is $\sim 3{{\ \rm per\ cent}}$. The HIMF about the knee, $\log _{10}(M_{\rm{H\,{\small I}}}h^2_{70}/M_{\odot }) \in [8,10.4]$, is dominated by the faint and luminous blue populations, the latter dominating at larger masses in this interval. Their total contribution to ΩH i is $\sim 55\!-\!70{{\ \rm per\ cent}}$, the variation depending on the definition of population. The dominant populations at the low-mass end, $\log _{10}(M_{\rm{H\,{\small I}}}h^2_{70}/M_{\odot }) \le 8.0$ are the faint blue and faint bluer populations, the latter’s dominance being sensitive to its definition. The full blue (blue–bluer luminous and faint) population represents $\sim 80{{\ \rm per\ cent}}$ of ΩH i. A bimodal HIMF suggested by our results is however not seen since the amplitude of the HIMF of the luminous red population is small compared to that of the luminous blue population.
Reaffirmation of cosmological oscillations in the scale factor from the Pantheon compilation of 1048 Type Ia supernovae
Authors: Ringermacher H I , Mead L R 
Published: March 2020

ABSTRACTWe observe damped temporal oscillations in the scale factor at a dominant frequency of ∼7 cycles/Hubble-time in the Pantheon compilation of 1048 Type Ia supernovae (SNe Ia). The residual oscillations observed in the Pantheon data closely match and reaffirm our initial observation of oscillations from earlier SNe data (primarily SNLS3 data of Conley 2011) at 2σ confidence. The nearly identical shapes in amplitude, frequency, phase, and damping constant makes it highly likely that the signal is real. Furthermore, two-thirds of the Pantheon SNe cover different portions of the sky compared with SNLS3 strengthening this conclusion. Our model describing the oscillation, presented in an earlier paper, is a simple scalar field harmonic oscillator coupled to the Lambda cold dark matter (ΛCDM) Friedmann equation, but carried into the present epoch. The scalar field energy density plays the role of the dark matter energy density in ΛCDM cosmology, fits well as an average, and closely matches the present dark matter density parameter, suggesting the oscillation plays a role in the dark matter sector. Temporal oscillations in the scale factor and its derivative, as described in this work, would also induce temporal oscillations of the Hubble parameter.
Tumor mutational burden predicts survival in patients with low-grade gliomas expressing mutated IDH1
Authors: Alghamri Mahmoud S , Thalla Rohit , Avvari Ruthvik P , Dabaja Ali , Taher Ayman , Zhao Lili , Ulintz Peter J , Castro Maria G , Lowenstein Pedro R 
Published: March 2020

Abstract

Background
Gliomas are the most common primary brain tumors. High-Grade Gliomas have a median survival (MS) of 18 months, while Low-Grade Gliomas (LGGs) have an MS of approximately 7.3 years. Seventy-six percent of patients with LGG express mutated isocitrate dehydrogenase (mIDH) enzyme. Survival of these patients ranges from 1 to 15 years, and tumor mutational burden ranges from 0.28 to 3.85 somatic mutations/megabase per tumor. We tested the hypothesis that the tumor mutational burden would predict the survival of patients with tumors bearing mIDH.

Methods
We analyzed the effect of tumor mutational burden on patients’ survival using clinical and genomic data of 1199 glioma patients from The Cancer Genome Atlas and validated our results using the Glioma Longitudinal AnalySiS consortium.

Results
High tumor mutational burden negatively correlates with the survival of patients with LGG harboring mIDH (P = .005). This effect was significant for both Oligodendroglioma (LGG-mIDH-O; MS = 2379 vs 4459 days in high vs low, respectively; P = .005) and Astrocytoma (LGG-mIDH-A; MS = 2286 vs 4412 days in high vs low respectively; P = .005). There was no differential representation of frequently mutated genes (eg, TP53, ATRX, CIC, and FUBP) in either group. Gene set enrichment analysis revealed an enrichment in Gene Ontologies related to cell cycle, DNA-damage response in high versus low tumor mutational burden. Finally, we identified 6 gene sets that predict survival for LGG-mIDH-A and LGG-mIDH-O.

Conclusions
we demonstrate that tumor mutational burden is a powerful, robust, and clinically relevant prognostic factor of MS in mIDH patients.
Unveiling the molecule–plasmon interactions in surface-enhanced infrared absorption spectroscopy
Authors: Yi Jun , You En-Ming , Ding Song-Yuan , Tian Zhong-Qun 
Published: March 2020

Abstract
Nanostructure-based surface-enhanced infrared absorption (SEIRA) spectroscopy has attracted tremendous interest as an ultrasensitive detection tool that supplies chemical-fingerprint information. The interactions between molecular vibrations and plasmons lead to not only the enhancement of spectral intensity, but also the distortion of spectral Lorentzian lineshapes into asymmetric Fano-type or more complicated lineshapes in the SEIRA spectra; this effect hampers the correct readout of vibrational frequencies and intensities for an accurate interpretation of the measured spectra and quantitative analysis. In this work, we investigate the Fano interference between molecular vibrations and plasmons based on exact electrodynamic simulations and theoretical models. We report that, even if the molecular vibrational energy is equal to the plasmon resonant energy, the molecule–nanostructure distance-dependent dipole–dipole interactions, the plasmon-mediated coherent intermolecular interactions and the decay rates of plasmons have a significant impact on the SEIRA lineshapes. This study paves the way for controllable Fano interference at the nanoscale and more studies on plasmon-dressed molecular electronic or vibrational excited states.