bluuebunny/crossref_metadata_2025_split huggingface dataset:
Fine-mapping of Parkinson’s disease susceptibility loci identifies putative causal variants
Authors: Schilder Brian M , Raj Towfique 
Published: October 2021

AbstractRecent genome-wide association studies have identified 78 loci associated with Parkinson’s disease susceptibility but the underlying mechanisms remain largely unclear. To identify likely causal variants for disease risk, we fine-mapped these Parkinson’s-associated loci using four different fine-mapping methods. We then integrated multi-assay cell type–specific epigenomic profiles to pinpoint the likely mechanism of action of each variant, allowing us to identify Consensus single nucleotide polymorphism (SNPs) that disrupt LRRK2 and FCGR2A regulatory elements in microglia, an MBNL2 enhancer in oligodendrocytes, and a DYRK1A enhancer in neurons. This genome-wide functional fine-mapping investigation of Parkinson’s disease substantially advances our understanding of the causal mechanisms underlying this complex disease while avoiding focus on spurious, non-causal mechanisms. Together, these results provide a robust, comprehensive list of the likely causal variants, genes and cell-types underlying Parkinson’s disease risk as demonstrated by consistently greater enrichment of our fine-mapped SNPs relative to lead GWAS SNPs across independent functional impact annotations. In addition, our approach prioritized an average of 3/85 variants per locus as putatively causal, making downstream experimental studies both more tractable and more likely to yield disease-relevant, actionable results. Large-scale studies comparing individuals with Parkinson’s disease to age-matched controls have identified many regions of the genome associated with the disease. However, there is widespread correlation between different parts of the genome, making it difficult to tell which genetic variants cause Parkinson’s and which are simply co-inherited with causal variants. We therefore applied a suite of statistical models to identify the most likely causal genetic variants (i.e. fine-mapping). We then linked these genetic variants with epigenomic and gene expression signatures across a wide variety of tissues and cell types to identify how these variants cause disease. Therefore, this study provides a comprehensive and robust list of cellular and molecular mechanisms that may serve as targets in the development of more effective Parkinson’s therapeutics.
Research and application progress of transcritical CO2 refrigeration cycle system: a review
Authors: Yang Dazhang , Li Yang , Xie Jing , Wang Jinfeng 
Published: October 2021

AbstractCO2 refrigerant and its transcritical cycle system have become the research focus in the refrigeration field due to their advantages of environmentally friendly, safe and low environmental temperature adaptability. This paper summarizes the research progress on the modified methods for the defects of basic transcritical CO2 refrigeration cycle system in recent years. Meanwhile, the technical status of transcritical CO2 refrigeration technology in commercial supermarket refrigeration, heat pump system, automobile air conditioning and artificial ice rink is discussed in detail. Finally, the development of transcritical CO2 refrigeration cycle system is prospected and the key problems to be solved are put forward.
Laplace–Beltrami spectrum of ellipsoids that are close to spheres and analytic perturbation theory
Authors: Eswarathasan Suresh , Kolokolnikov Theodore 
Published: October 2021

Abstract
We study the spectrum of the Laplace–Beltrami operator on ellipsoids. For ellipsoids that are close to the sphere, we use analytic perturbation theory to estimate the eigenvalues up to two orders. We show that for biaxial ellipsoids sufficiently close to the sphere, the first $L^2$ eigenvalues have multiplicity at most two, and characterize those that are simple. For the triaxial ellipsoids sufficiently close to the sphere that are not biaxial, we show that at least the first 16 eigenvalues are all simple. We also give the results of various numerical experiments, including comparisons to our results from the analytic perturbation theory, and approximations for the eigenvalues of ellipsoids that degenerate into infinite cylinders or two-dimensional disks. We propose a conjecture on the exact number of nodal domains of near-sphere ellipsoids.
Frequent but fragmented: use of note templates to document outpatient visits at an academic health center
Authors: Rule Adam , Hribar Michelle R 
Published: October 2021

Abstract
Recent changes to billing policy have reduced documentation requirements for outpatient notes, providing an opportunity to rethink documentation workflows. While many providers use templates to write notes—whether to insert short phrases or draft entire notes—we know surprisingly little about how these templates are used in practice. In this retrospective cross-sectional study, we observed the templates that primary providers and other members of the care team used to write the provider progress note for 2.5 million outpatient visits across 52 specialties at an academic health center between 2018 and 2020. Templates were used to document 89% of visits, with a median of 2 used per visit. Only 17% of the 100 230 unique templates were ever used by more than one person and most providers had their own full-note templates. These findings suggest template use is frequent but fragmented, complicating template revision and maintenance. Reframing template use as a form of computer programming suggests ways to maintain the benefits of personalization while leveraging standardization to reduce documentation burden.
Procedural Cross-Fertilization in International Commercial and Investment Arbitration: A Functional Approach
Authors: Meshel Tamar 
Published: October 2021

Abstract
This article examines the potential for beneficial procedural cross-fertilization between internationalcommercial and investment arbitration from a functional perspective. The article argues that botharbitration regimes share a ‘private’ dispute resolution function of resolving specific disputes, butonly investment arbitral tribunals also exercise a ‘public’ law-making function of developing the lawapplicable to the resolution of disputes. The article considers two recent procedural developmentsin international arbitration rulesjoinder of third parties and publication of arbitral awardsin thelight of these private and public functions. It argues that joinder, as an efficiency-enhancingmeasure, can lead to beneficial cross-fertilization between commercial and investment arbitrationbecause it reinforces the ‘private’ dispute resolution function shared by both regimes. In contrast,the default publication of arbitral awards, to the extent that it is intended to be systematic and createinformal precedent, is appropriate in investment but not in commercial arbitration because onlyinvestment arbitral tribunals exercise a ‘public’ law-making function that justifies and stands tobenefit from this practice. In this regard, the article rejects three rationales for default publication ofinternational commercial arbitral awards: improving consistency/predictability, enhancingtransparency and developing transnational commercial law. The article concludes that crossfertilizationbetween investment and commercial arbitration can be valuable so long as it concernstheir shared private dispute resolution function. However, attempting to develop internationalcommercial arbitral practice in the shadow of the public law-making function of investment arbitraltribunals may result in counterproductive practices and undermine the proper functioning ofinternational commercial arbitration as a whole.
A new framework for understanding systematic errors in cluster lens modelling – I. Selection and treatment of cluster member galaxies
Authors: Raney Catie A , Keeton Charles R , Zimmerman Dhruv T 
Published: October 2021

ABSTRACT
With high-quality data from programs like the Hubble Frontier Fields, cluster lensing has reached the point that models are dominated by systematic rather than statistical uncertainties. We introduce a Bayesian framework to quantify systematic effects by determining how different lens modelling choices affect the results. Our framework includes a new two-sample test for quantifying the difference between posterior probability distributions that are sampled by methods like Monte Carlo Markov chains. We use the framework to examine choices related to the selection and treatment of cluster member galaxies in two of the Frontier Field clusters: Abell 2744 and MACS J0416.1–2403. When selecting member galaxies, choices about depth and area affect the models; we find that model results are robust for an I-band magnitude limit of mlim ≥ 22.5 mag and a radial cut of rlim ≥ 90 arcsec (from the centre of the field), although the radial limit likely depends on the spatial extent of lensed images. Mass is typically assigned to galaxies using luminosity/mass scaling relations. We find that the slopes of the scaling relations can have significant effects on lens model parameters but only modest effects on lensing magnifications. Interestingly, scatter in the scaling relations affects the two fields differently. This analysis illustrates how our framework can be used to analyse lens modelling choices and guide future cluster lensing programs.
Bringing faint active galactic nuclei (AGNs) to light: a view from large-scale cosmological simulations
Authors: Schirra Adrian P , Habouzit Mélanie , Klessen Ralf S , Fornasini Francesca , Nelson Dylan , Pillepich Annalisa , Anglés-Alcázar Daniel , Davé Romeel , Civano Francesca 
Published: October 2021

ABSTRACT
The sensitivity of X-ray facilities and our ability to detect fainter active galactic nuclei (AGNs) will increase with the upcoming Athena mission and the AXIS and Lynx concept missions, thus improving our understanding of supermassive black holes (BHs) in a luminosity regime that can be dominated by X-ray binaries. We analyse the population of faint AGNs ($L_{\rm x, 2{-}10 \, keV}\leqslant 10^{42}\, \rm erg\,s^{ -1}$) in the Illustris, TNG100, EAGLE, and SIMBA cosmological simulations, and find that the properties of their host galaxies vary from one simulation to another. In Illustris and EAGLE, faint AGNs are powered by low-mass BHs located in low-mass star-forming galaxies. In TNG100 and SIMBA, they are mostly associated with more massive BHs in quenched massive galaxies. We model the X-ray binary (XRB) populations of the simulated galaxies, and find that AGNs often dominate the galaxy AGN + XRB hard X-ray luminosity at z &gt; 2, while XRBs dominate in some simulations at z &lt; 2. Whether the AGN or XRB emission dominates in star-forming and quenched galaxies depends on the simulations. These differences in simulations can be used to discriminate between galaxy formation models with future high-resolution X-ray observations. We compare the luminosity of simulated faint AGN host galaxies to observations of stacked galaxies from Chandra. Our comparison indicates that the simulations post-processed with our X-ray modelling tend to overestimate the AGN + XRB X-ray luminosity; luminosity that can be strongly affected by AGN obscuration. Some simulations reveal clear AGN trends as a function of stellar mass (e.g. galaxy luminosity drop in massive galaxies), which are not apparent in the observations.
Ordinal regression increases statistical power to predict epilepsy surgical outcomes
Authors: Dickey Adam S. , Krafty Robert T. , Pedersen Nigel P. 
Published: October 2021

ABSTRACTObjectiveStudies of epilepsy surgery outcomes are often small and thus underpowered to reach statistically valid conclusions. We hypothesized that ordinal logistic regression would have greater statistical power than binary logistic regression when analyzing epilepsy surgery outcomes.MethodsWe reviewed 10 manuscripts included in a recent meta-analysis which found that mesial temporal sclerosis (MTS) predicted better surgical outcome after a stereotactic laser amygdalohippocampectomy (SLAH). We extracted data from 239 patients from eight studies which reported four discrete Engel surgical outcomes after SLAH, stratified by the presence or absence of MTS.ResultsThe rate of freedom from disabling seizures (Engel I) was 64.3% (110/171) for patients with MTS compared to 44.1% (30/68) without MTS. The statistical power to detect MTS as a predictor for better surgical outcome after a SLAH was 29% using ordinal regression, which was significantly more than the 13% power using binary logistic regression (paired t-test, p<0.001). Only 120 patients are needed to achieve 80% power to detect MTS as a predictor using ordinal regression, compared to 210 patients that are needed to achieve 80% power using binary logistic regression.ConclusionOrdinal regression should be considered when analyzing ordinal outcomes (such as Engel surgical outcome), especially for datasets with small sample sizes.
Detection of the 40-Hz Auditory Steady-state Response with Optically Pumped Magnetometers
Authors: An Kyung-min , Shim Jung Hyun , Kwon Hyukchan , Lee Young-Ho , Yu Kwon-Kyu , Kwon Moonyoung , Chun Woo Young , Hirosawa Tetsu , Hasegawa Chiaki , Iwasaki Sumie , Kikuchi Mitsuru , Kim Kiwoong 
Published: October 2021

AbstractMagnetoencephalography (MEG) is a functional neuroimaging technique that noninvasively detects the brain magnetic field from neuronal activations. Conventional MEG measures brain signals using superconducting quantum interference devices (SQUIDs). SQUID-MEG requires a cryogenic environment involving a bulky non-magnetic dewar and the consumption of liquid helium, which restricts the variability of the sensor array and the gap between the cortical sources and sensors. Recently, miniature optically pumped magnetometers (OPMs) have been developed and commercialized. OPMs do not require cryogenic cooling and can be placed within millimeters from the scalp. In the present study, we arranged six OPM sensors on the temporal area to detect auditory-related brain responses in a two-layer magnetically shielded room. We presented the auditory stimuli of 1-kHz pure-tone bursts with 200-ms duration and obtained the M50 and M100 components of auditory evoked fields. We delivered the periodic stimuli with a 40-Hz repetition rate and observed the gamma-band power changes and inter-trial phase coherence of auditory steady-state responses at 40 Hz. We found that the OPM sensors have a performance comparable to that of conventional SQUID-MEG sensors, and our results suggest the feasibility of using OPM sensors for functional neuroimaging and brain–computer interface applications.
Episodic timing: how spontaneous alpha clocks, retrospectively
Authors: Azizi Leila , Polti Ignacio , van Wassenhove Virginie 
Published: October 2021

AbstractWe seldom time life events intently yet recalling the duration of events is lifelike. Is episodic time the outcome of a rational after-thought or of physiological clocks keeping track of time without our conscious awareness of it? To answer this, we recorded human brain activity with magnetoencephalography (MEG) during quiet wakefulness. Unbeknownst to participants, we asked them after the MEG recording to guess its duration. In the absence of overt attention to time, the relative amount of time participants’ alpha brain rhythms (α ~10 Hz) were in bursting mode predicted participants’ retrospective duration estimate. This relation was absent when participants prospectively measured elapsed time during the MEG recording. We conclude that α bursts embody discrete states of awareness for episodic timing.One-Sentence SummaryIn the human brain, the relative number of alpha oscillatory bursts at ~10 Hz can tell time when the observer does not attend to it.
Macroscopic dynamics of gene regulatory networks revealed by individual entropy
Authors: Liu Cong , Hao Lijie , Lei Jinzhi 
Published: October 2021

AbstractComplex systems are usually high-dimensional with intricate interactions among internal components, and may display complicated dynamics under different conditions. While it is difficult to measure detail dynamics of each component, proper macroscopic description of a complex system is crucial for quantitative studies. In biological systems, each cell is a complex system containing a huge number of molecular components that are interconnected with each other through intricate molecular interaction networks. Here, we consider gene regulatory networks in a cell, and introduce individual entropy as a macroscopic variable to quantify the transcriptional dynamics in response to changes in random perturbations and/or network structures. The proposed individual entropy measures the information entropy of a system at each instant with respect to a basal reference state, and may provide temporal dynamics to characterize switches of system states. Individual entropy provides a method to quantify the stationary macroscopic dynamics of a gene set that is dependent on the gene regulation connections, and can be served as an indicator for the evolution of network structure variation. Moreover, the individual entropy with reference to a preceding state enable us to characterize different dynamic patterns generated from varying network structures. Our results show that the proposed individual entropy can be a valuable macroscopic variable of complex systems in characterizing the transition processes from order to disorder dynamics, and to identify the critical events during the transition process.
Functional alterations of two salience-related systems jointly and independently contribute to psychosis
Authors: Miyata Jun , Winton-Brown Toby , Sedlak Thomas , Aso Toshihiko , Cascella Nicola , Coughlin Jennifer , Crossley Nicolas A. , Duezel Emrah , Ezaki Takahiro , Fukunaga Masaki , Howell Carolyn , Isobe Masanori , Kamiya Kouhei , Kasai Kiyoto , Kochiyama Takanori , Koike Shinsuke , Kunimatsu Akira , Masuda Naoki , Mori Susumu , Mori Yasuo , Murai Toshiya , Nemoto Kiyotaka , Nucifora Frederick , Ohi Kazutaka , Okada Naohiro , Sakai Yuki , Sawamoto Nobukatsu , Takahashi Tsutomu , Urayama Shinichi , Watanabe Yoshiyuki , Watkins Crystal C. , Yamamori Hidenaga , Yasuda Yuka , Hashimoto Ryota , Takahashi Hidehiko , Sawa Akira , McGuire Philip 
Published: October 2021

AbstractBackground and hypothesisSalience is a critical mechanism for animal survival. Aberrant salience is essentially implicated in psychosis, involving the midbrain–striatum–hippocampus and the anterior cingulate cortex (ACC)–insula salience network (SN) systems. However, whether these two systems jointly or independently contribute to psychosis traits, staging, and state remains unknown.Study designEight scanners at seven institutions recruited 209 subjects with psychosis at the ultra-high-risk (UHR), first-episode (FEP), and chronic (ChrP) stages and 279 matched healthy controls (HC). Resting-state functional MRI data, which were intensively denoised and scanner effect-removed, revealed the two systems comprising five networks: midbrain-thalamic and striatal parts of the basal ganglia network (BGN-MbThal and BGN-Str), the medial temporal lobe network (MTLN), and the ACC and insular parts of the SN (SN-ACC and SN-Ins). Group differences, correlations with positive symptoms, and effects of medication/psychosis type of the networks were investigated in each psychosis stage.Study resultsConnectivity within the SN-ACC was reduced in UHR compared to HC (p<0.05, family-wise-error [FWE] corrected) and in the FEP and ChrP stages at liberal thresholds, with effect sizes of UHR>FEP>ChrP. FEP showed reduced connectivity within the BGN-MbThal, increased brain-state instability among the five networks, and positive correlations between positive symptoms and connectivity within and between the MTLN (all p<0.05, FWE). The correlation was stronger in unmedicated than in medicated, and in affective than in non-affective psychosis patients (p<0.05, FWE).ConclusionsThe results provide a novel concept that the two salience mechanisms work in an integrated and separate manner in psychosis.
Characterization of Heat Responsive microRNAs and Phased Small Interfering RNAs in Reproductive Development of Flax
Authors: Pokhrel Suresh , Meyers Blake C. 
Published: October 2021

AbstractPlants will face increased heat stress due to rising global temperatures. Heat stress affects plant reproductive development and decreases productivity; however, the underlying molecular mechanisms of these processes are poorly characterized. Plant small RNAs (sRNAs) have important regulatory roles in plant reproductive development following abiotic stress responses. We generated sRNA transcriptomes of three reproductive bud stages at three different time points to identify sRNA-mediated pathways responsive to heat stress in flax. With added sRNA transcriptomes of vegetative tissues, we comprehensively annotated miRNA and phasiRNA-encoding genes (PHAS) in flax. We identified 173 miRNA genes, of which 42 are novel. Our analysis revealed that 141 miRNA genes were differentially expressed between tissue types while 18 miRNA genes were differentially expressed in reproductive tissues following heat stress, including members of miR2118/482 and miR2275 families, known triggers of reproductive phasiRNAs. Furthermore, we identified 68 21-PHAS flax loci from protein coding and non-coding regions, four 24-PHAS loci triggered by miR2275, and 658 24-PHAS-like loci with unknown triggers, derived mostly from non-coding regions. The reproductive phasiRNAs are mostly downregulated in response to heat stress. Overall, we found that several previously unreported miRNAs and phasiRNAs are responsive to heat stress in flax reproductive tissues.
De Novo Whole Genome Assembly of the Roborovski Dwarf Hamster (Phodopus roborovskii) Genome, an Animal Model for Severe/Critical COVID-19
Authors: Andreotti Sandro , Altmüller Janine , Quedenau Claudia , Borodina Tatiana , Nouailles Geraldine , Alves Luiz Gustavo Teixeira , Landthaler Markus , Bieniara Maximilian , Trimpert Jakob , Wyler Emanuel 
Published: October 2021

AbstractThe Roborovski dwarf hamster Phodopus roborovskii belongs to the Phodopus genus, one of seven within Cricetinae subfamily. Like other rodents such as mice, rats or ferrets, hamsters can be important animal models for a range of diseases. Whereas the Syrian hamster from the genus Mesocricetus is now widely used as a model for mild to moderate COVID-19, Roborovski dwarf hamster show a severe to lethal course of disease upon infection with the novel human coronavirus SARS-CoV-2.