bluuebunny/crossref_metadata_2025_split huggingface dataset:
Characterization of the human TARDBP gene promoter
Authors: Baralle Marco , Romano Maurizio 
Published: May 2021

AbstractThe expression of TDP-43, the main component of neuronal intracellular inclusions across a broad spectrum of ALS and FTD disorders, is developmentally regulated and studies in vivo have shown that TDP-43 overexpression can be toxic, even before observation of pathological aggregates. Starting from these observations, the regulation of its expression at transcriptional level might represent a further key element for the pathogenesis of neurodegenerative diseases. Therefore, we have characterized the human TARDBP promoter, in order to study the transcriptional mechanisms of expression. Mapping of cis-acting elements by luciferase assays in different cell outlined that the activity of the promoter seems to be higher in SH-SY5Y, Neuro2A, and HeLa than in HEK293. In addition, we tested effects of two SNPs found in the promoter region of ALS patients and observed no significant effect on transcription levels in all tested cell lines. Lastly, while TDP-43 overexpression did not affect significantly the activity of its promoter (suggesting that TDP-43 does not influence its own transcription), the presence of the 5′UTR sequence and of intron-1 splicing seem to impact positively on TDP-43 expression without affecting transcript stability. In conclusion, we have identified the region spanning nucleotides 451–230 upstream from the transcription start site as the minimal region with a significant transcription activity. These results lay an important foundation for exploring the regulation of the TARDBP gene transcription by exogenous and endogenous stimuli and the implication of transcriptional mechanisms in the pathogenesis of TDP-43 proteinopathies.
Changes in retinal layers in type 1 diabetes mellitus without retinopathy measured by spectral domain and swept source OCTs
Authors: Orduna-Hospital Elvira , Sanchez-Cano Ana , Perdices Lorena , Acha Javier , Lopez-Alaminos Elena María , Pinilla Isabel 
Published: May 2021

AbstractTo evaluate changes in inner retinal layer (IRL) thicknesses in patients with type 1 diabetes mellitus (DM1) with no diabetic retinopathy (DR) using two different optical coherence tomography (OCT) devices. Ninety DM1 and 60 healthy eyes were evaluated using spectral domain (SD)-OCT and swept source (SS)-OCT to measure changes in the retinal nerve fiber layer (RNFL), ganglion cell layer (GCL), inner plexiform layer (IPL) and inner nuclear layer (INL) thicknesses in all Early Treatment of Diabetic Retinopathy Study (ETDRS) macular areas. Functional tests were performed in both groups, including ETDRS with 100, 2.5 and 1.25% contrast, and color vision. The mean ages were 42.93 ± 13.62 and 41.52 ± 13.05 years in the diabetic and control groups, respectively. Visual acuity (VA) with ETDRS 1.25% was lower in the DM1 patients. Both ETDRS 2.5% and color vision were lower in the DM1 group but did not reach statistical significance. Retinal thicknesses in the central area and in the vertical outer areas were higher in the DM1 group. Differences were found in the IRL with no changes in the outer ones. Long-term DM1 patients with no DR maintained visual function, with a decrease in VA with 1.25% ETDRS contrast. Macular thickness measurements were higher using Spectralis SD-OCT than DRI Triton SS-OCT, and DM1 patients had a decrease in IRL thickness, especially in the GCL at the parafoveal level, generating thinning of the RNFL in the peripheral areas. There were no differences in outer retinal layer (ORL) thickness.
Status and development for detection and control of ammonium bisulfate as a by-product of SCR denitrification
Authors: Jiao Kunling , Chen Xiangyang , Bie Xuan , Liu Daokuan , Qiu Mingjie , Ma Shuangchen 
Published: May 2021

AbstractWhen denitrification technology using NH3 or urea as the reducing agent is applied to remove NOx from the flue gas, ammonium bisulfate (ABS) by-product will also be generated in the flue gas. ABS has an impact on catalyst life span, denitrification efficiency etc., air preheater and its downstream thermal equipment also have a significant negative impact due to its plugging and corrosion. The requirement for NOx removal efficiency is improved by ultra-low emissions in China. However, wide-load denitrification makes the flue gas composition and temperature changing more complicated. Increasing ammonia injection can improve the NOx removal effect, but too much ammonia injection will lead to the formation of ABS and the increase of deposition risk, the contradiction between these two aspects is amplified by ultra-low emissions and wide-load denitrification in many plants. Coordinating NOx control and reducing the impact of ABS on equipment are issues that the industry needs to solve urgently. In recent years, extensive research on ABS had been carried out deeply, consequently, there has been a relatively in-deepth knowledge foundation for ABS formation, formation temperature, deposition temperature, dew point temperature, decomposition behavior, etc., but the existing researches are insufficient to support the problem of ABS under full load denitrification completely resolved. Therefore, some analysis and detection methods related to ABS are reviewed in this paper, and the impact of ABS on SCR, air preheater and other equipment and the existing research results on reducing the impact of ABS are summarized also. It is hoped that this review will provide a reference for the industry to solve the problems of ABS that hinder wide-load denitrification and affect ultra-low emissions.
A tyrosine kinase inhibitor-induced interferon response positively associates with clinical response in EGFR-mutant lung cancer
Authors: Gurule Natalia J. , McCoach Caroline E. , Hinz Trista K. , Merrick Daniel T. , Van Bokhoven Adriaan , Kim Jihye , Patil Tejas , Calhoun Jacob , Nemenoff Raphael A. , Tan Aik Choon , Doebele Robert C. , Heasley Lynn E. 
Published: May 2021

AbstractTyrosine kinase inhibitors (TKIs) targeting EGFR-mutant lung cancers promote a range of tumor regression responses to yield variable residual disease, a likely incubator for acquired resistance. Herein, rapid transcriptional responses induced by TKIs early in treatment that associate with the range of patient responses were explored. RNAseq was performed on EGFR mutant cell lines treated in vitro with osimertinib and on tumor biopsies of eight EGFR mutant lung cancer patients before and after 2 weeks of TKI treatment. Data were evaluated for gene expression programs altered upon TKI treatment. Chemokine and cytokine expression were measured by ELISA and quantitative RT-PCR. IκB Kinase (IKK) and JAK-STAT pathway dependence was tested with pharmacologic and molecular inhibitors. Tumor sections were stained for the T-cell marker CD3. Osimertinib stimulated dynamic, yet wide-ranging interferon (IFN) program regulation in EGFR mutant cell lines. IL6 and CXCL10 induction varied markedly among the EGFR mutant cell lines and was sensitive to IKK and JAK-STAT inhibitors. Analysis of matched patient biopsy pairs revealed marked, yet varied enrichment of IFN transcriptional programs, effector immune cell signatures and T-cell content in treated tumors that positively correlated with time to progression in the patients. EGFR-specific TKIs induce wide-ranging IFN response program activation originating within the cancer cell. The strong association of IFN program induction and duration of clinical response indicates that the TKI-induced IFN program instructs variable recruitment and participation of immune cells in the overall therapeutic response.
Genome-wide bioinformatic analyses predict key host and viral factors in SARS-CoV-2 pathogenesis
Authors: Ferrarini Mariana G. , Lal Avantika , Rebollo Rita , Gruber Andreas J. , Guarracino Andrea , Gonzalez Itziar Martinez , Floyd Taylor , de Oliveira Daniel Siqueira , Shanklin Justin , Beausoleil Ethan , Pusa Taneli , Pickett Brett E. , Aguiar-Pulido Vanessa 
Published: May 2021

AbstractThe novel betacoronavirus severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) caused a worldwide pandemic (COVID-19) after emerging in Wuhan, China. Here we analyzed public host and viral RNA sequencing data to better understand how SARS-CoV-2 interacts with human respiratory cells. We identified genes, isoforms and transposable element families that are specifically altered in SARS-CoV-2-infected respiratory cells. Well-known immunoregulatory genes includingCSF2, IL32, IL-6andSERPINA3were differentially expressed, while immunoregulatory transposable element families were upregulated. We predicted conserved interactions between the SARS-CoV-2 genome and human RNA-binding proteins such as the heterogeneous nuclear ribonucleoprotein A1 (hnRNPA1) and eukaryotic initiation factor 4 (eIF4b). We also identified a viral sequence variant with a statistically significant skew associated with age of infection, that may contribute to intracellular host–pathogen interactions. These findings can help identify host mechanisms that can be targeted by prophylactics and/or therapeutics to reduce the severity of COVID-19.
Effects of HIF-1α on renal fibrosis in cisplatin-induced chronic kidney disease
Authors: Zhao Hao , Han Yachun , Jiang Na , Li Chenrui , Yang Ming , Xiao Ying , Wei Ling , Xiong Xiaofen , Yang Jinfei , Tang Chengyuan , Xiao Li , Liu Fuyou , Liu Yu , Sun Lin 
Published: May 2021

Abstract
Cisplatin (Cis) can cause chronic kidney disease (CKD) and promote renal fibrosis, but the underlying mechanism is not fully understood. Hypoxia inducible factor-1α (HIF-1α) can promote renal fibrosis in some kidney diseases, but its role in Cis-induced CKD is still unknown. Notch-1 is a recognized molecule that promotes renal fibrosis under pathological circumstances, and evidence shows that HIF-1α and Notch-1 are closely related to each other. In the present study, mice with HIF-1α gene knockout in proximal tubular cells (PTCs) (PT-HIF-1α-KO) were generated and treated with Cis to induce CKD. A human proximal tubular cell line (HK-2) and primary mouse PTCs were used for in vitro studies. The results showed that HIF-1α was increased in the kidneys of Cis-treated wild-type mice, accompanied by elevated Notch-1, Notch-1 intracellular domain (N1ICD), Hes-1 and renal fibrosis. However, these alterations were partially reversed in PT-HIF-1α-KO mice. Similar results were observed in HK-2 cells and primary mouse PTCs. In addition, treating the cells with Cis induced a marked interaction of HIF-1α and N1ICD. Further inhibiting Notch-1 significantly reduced cellular fibrogenesis but did not affect HIF-1α expression. The data suggested that HIF-1α could promote renal fibrosis in Cis-induced CKD by activating Notch-1 both transcriptionally and post-transcriptionally and that HIF-1α may serve as a potential therapeutic target for Cis-induced CKD.
Development and Initial Validation of the Lifetime Exposure to Noise and Solvents Questionnaire in U.S. Service Members and Veterans
Authors: Griest-Hines Susan E. , Bramhall Naomi F. , Reavis Kelly M. , Theodoroff Sarah M. , Henry James A. 
Published: May 2021

Purpose
A need exists to investigate the short- and long-term impact of noise exposures during and following military service on auditory health. Currently available questionnaires are limited in their ability to meet this need because of (a) inability to evaluate noise exposures beyond a limited time frame, (b) lack of consensus on scoring, (c) inability to assess impulse exposures (e.g., firearm use), (d) lack of a single questionnaire that assesses both military and nonmilitary exposures, and (e) lack of validity and reliability data. To address these limitations, the Lifetime Exposure to Noise and Solvents Questionnaire (LENS-Q) was developed. The purpose of this report is to describe the development and initial validation of the LENS-Q as a measure of self-reported noise exposure.

Method
Six hundred ninety participants, consisting of current Service members and recently military-separated (within about 2.5 years) Veterans, completed the LENS-Q, additional study questionnaires, and comprehensive audiometric testing. Noise exposure scores were computed from LENS-Q responses using a simple scoring algorithm that distinguishes between different cumulative levels of exposure and allows for the inclusion of both continuous and impulse noise exposures.

Results
The LENS-Q demonstrates good construct validity as evidenced by measures of hearing loss, tinnitus, and subjective hearing difficulties all increasing with an increase in noise exposure scores. A logistic regression, adjusting for age and sex, revealed that participants in the highest exposure group were 2.4–3.9 times more likely to experience hearing loss, 2.7–2.8 times more likely to experience tinnitus, and 3.0–3.7 times more likely to report hearing difficulties compared with individuals in the lowest exposure group.

Conclusions
The LENS-Q captures noise exposure over an individual's lifetime and provides an alternative scoring metric capable of representing exposure to both continuous and impulse noise. Findings suggest that the LENS-Q is a valuable tool for capturing and measuring both military and nonmilitary noise exposure.

Supplemental Material

https://doi.org/10.23641/asha.14582937
Study of the thermal and nonthermal emission components in M 31: the Sardinia Radio Telescope view at 6.6 GHz
Authors: Fatigoni S. , Radiconi F. , Battistelli E. S. , Murgia M. , Carretti E. , Castangia P. , Concu R. , de Bernardis P. , Fritz J. , Genova-Santos R. , Govoni F. , Guidi F. , Lamagna L. , Masi S. , Melis A. , Paladini R. , Perez-Toledo F. M. , Piacentini F. , Poppi S. , Rebolo R. , Rubino-Martin J. A. , Surcis G. , Tarchi A. , Vacca V. 
Published: May 2021

Context.The Andromeda galaxy is the best-known large galaxy besides our own Milky Way. Several images and studies exist at all wavelengths from radio to hard X-ray. Nevertheless, only a few observations are available in the microwave range where its average radio emission reaches the minimum.Aims.In this paper, we want to study the radio morphology of the galaxy, decouple thermal from nonthermal emission, and extract the star formation rate. We also aim to derive a complete catalog of radio sources for the mapped patch of sky.Methods.We observed the Andromeda galaxy with the Sardinia Radio Telescope at 6.6 GHz with very high sensitivity and angular resolution, and an unprecedented sky coverage.Results.Using new 6.6 GHz data and Effelsberg radio telescope ancillary data, we confirm that, globally, the spectral index is ∼0.7−0.8, while in the star forming regions it decreases to ∼0.5. By disentangling (gas) thermal and nonthermal emission, we find that at 6.6 GHz, thermal emission follows the distribution of HII regions around the ring. Nonthermal emission within the ring appears smoother and more uniform than thermal emission because of diffusion of the cosmic ray electrons away from their birthplaces. This causes the magnetic fields to appear almost constant in intensity. Furthermore, we calculated a map of the star formation rate based on the map of thermal emission. Integrating within a radius ofRmax = 15 kpc, we obtained a total star formation rate of 0.19 ± 0.01 M⊙yr−1in agreement with previous results in the literature. Finally, we correlated our radio data with infrared images of the Andromeda galaxy. We find an unexpectedly high correlation between nonthermal and mid-infrared data in the central region, with a correlation parameterr = 0.93. Finally, by computing the logarithmic 24μm/21cmratioq24 μm, we find a decreasing trend with increasing galactocentric distance and an increasing dispersion. The logarithmic far-infrared-to-radio ratio is found to be 2.41 ± 0.04.
The imprint of X-ray photoevaporation of planet-forming discs on the orbital distribution of giant planets
Authors: Monsch Kristina , Picogna Giovanni , Ercolano Barbara , Preibisch Thomas 
Published: May 2021

Context. Numerical models have shown that disc dispersal via internal photoevaporation driven by the host star can successfully reproduce the observed pile-up of warm Jupiters near 1–2 au. However, since a range of different mechanisms have been proposed to cause the same feature, clear observational diagnostics of disc dispersal leaving an imprint in the observed distribution of giant planets could help in constraining the dominant mechanisms.
Aims. We aim to assess the impact of disc dispersal via X-ray-driven photoevaporation (XPE) on giant planet separations in order to provide theoretical constraints on the location and size of any possible features related to this process within the observed semi-major axis distribution of giant planets.
Methods. For this purpose, we perform a set of 1D planet population syntheses with varying initial conditions and correlate the gas giants’ final parking locations with the X-ray luminosities of their host stars in order to quantify observables of this process within the semi-major axis versus host star X-ray luminosity plane of these systems.
Results. We find that XPE does create an under-density of gas giants near the gravitational radius, with corresponding pile-ups inside and/or outside this location. However, the size and location of these features are strongly dependent on the choice of initial conditions in our model, such as the assumed formation location of the planets.
Conclusions. XPE can strongly affect the migration process of giant planets and leave potentially observable signatures within the observed orbital separations of giant planets. However, due to the simplistic approach employed in our model, which lacks a self-consistent treatment of planet formation within an evolving disc, a quantitative analysis of the final planet population orbits is not possible. Our results, however, should strongly motivate future studies to include realistic disc dispersal mechanisms in global planet population synthesis models with self-consistent planet formation modules.
G 112-43/44: A metal-poor binary star with a unique chemical composition and Helmi stream kinematics
Authors: Nissen P. E. , Silva-Cabrera J. S. , Schuster W. J. 
Published: May 2021

Context. Correlations between high-precision elemental abundance ratios and the kinematics of halo stars provide interesting information about the formation and early evolution of the Galaxy.
Aims. Element abundances of G 112-43/44, a metal-poor wide-orbit binary star with extreme kinematics, are revisited.
Methods. High-precision studies of the chemical compositions of 94 metal-poor dwarf stars in the solar neighbourhood are used to compare abundance ratios for G 112-43/44 with ratios for stars that have similar metallicities, taking into account the effect of deviations from local thermodynamic equilibrium on the derived abundances. Gaia EDR3 data are used to compare the kinematics.
Results. The X/Fe abundance ratios of the two components of G 112-43/44 agree within ±0.05 dex for nearly all elements, but there is a hint of a correlation between the difference in [X/H] and the elemental condensation temperature, which may be due to planet-star interactions. The Mg/Fe, Si/Fe, Ca/Fe, and Ti/Fe ratios of G 112-43/44 agree with the corresponding ratios for accreted (Gaia-Enceladus) stars, but Mn/Fe, Ni/Fe, Cu/Fe, and Zn/Fe are significantly enhanced, with Δ [Zn/Fe] reaching 0.25 dex. The kinematics show that G 112-43/44 belongs to the Helmi streams in the solar neighbourhood. In view of this, we discuss if the abundance peculiarities of G 112-43/44 can be explained by chemical enrichment from supernova events in the progenitor dwarf galaxy of the Helmi streams. Interestingly, yields calculated for a helium shell detonation Type Ia supernova model can explain the enhancement of Mn/Fe, Ni/Fe, Cu/Fe, and Zn/Fe in G 112-43/44 and three other α-poor stars in the Galactic halo with abundances from the literature, one of which has Helmi stream kinematics. However, the helium shell detonation model also predicts enhanced abundance ratios of Ca/Fe, Ti/Fe, and Cr/Fe, in disagreement with the observed ratios.
Catalytic Synthesis of PEGylated EGCG Conjugates that Disaggregate Alzheimer’s Tau
Authors: Eisenberg David S. , Harran Patrick G. , El Khoury Anton , Seidler Paul M. 
Published: May 2021

AbstractThe naturally occurring flavonoid (–)-epigallocatechin gallate (EGCG) is a potent disaggregant of tau fibrils. Guided by the recent cryo-electron microscopy (cryoEM) structure of EGCG bound to fibrils of tau derived from an Alzheimer’s brain donor, methods to site-specifically modify the EGCG D-ring with aminoPEGylated linkers are reported. The resultant molecules inhibit tau fibril seeding by Alzheimer’s brain extracts. Formulations of aminoPEGylated EGCG conjugated to the (quasi)-brain-penetrant nanoparticle Ferumoxytol inhibit seeding by AD-tau with linker length affecting activity. The protecting group-free catalytic cycloaddition of amino azides to mono-propargylated EGCG described here provides a blueprint for access to stable nanoparticulate forms of EGCG potentially useful as therapeutics to eliminate Alzheimer’s-related tau tangles.
Nickel-Catalyzed Homocoupling of Aryl Ethers with Magnesium Anthracene Reductant
Authors: Higashida Kosuke , Sawamura Masaya , Rawat Vishal Kumar 
Published: May 2021

AbstractNickel-catalyzed reductive homocoupling of aryl ethers has been achieved with Mg(anthracene)(thf)3 as a readily available low-cost reductant. DFT calculations provided a rationale for the specific efficiency of the diorganomagnesium-type two-electron reducing agent. The calculations show that the dianionic anthracene-9,10-diyl ligand reduces the two aryl ether substrates, resulting in the homocoupling reaction through supply of electrons to the Ni-Mg bimetallic system to form organomagnesium nickel(0)-ate complexes, which cause two sequential C–O bond cleavage reactions. The calculations also showed cooperative actions of Lewis acidic magnesium atoms and electron-rich nickel atoms in the C–O cleavage reactions.
Dual Ligand-Enabled Late-Stage Fujiwara–Moritani Reactions
Authors: van Gemmeren Manuel , Santiago Carlos , Chen Hao , Mondal Arup 
Published: May 2021

AbstractIn this study, we describe the use of dual ligand-based palladium catalysts for the late-stage olefination of arenes. Building upon a method previously developed for simple arenes, a variety of complex arene substrates were functionalized. Importantly, the method uses the arene as a limiting reactant and is therefore suitable for valuable starting materials that cannot be used in excess. The regioselectivity of the transformation is controlled by the steric and electronic properties of the substrate, providing access to regioisomers that would be challenging to prepare through other synthetic approaches.
The Pathophysiology of Hypercoagulability and Infertility
Authors: Malinowski Ann Kinga 
Published: May 2021

AbstractAlongside an interplay of a multitude of factors, attainment of a favorable pregnancy outcome is predicated on successful implantation, which in itself is a complex process anchored by balanced interchange with the hemostatic system. Among other etiologies, failure of implantation can result in infertility, and lead affected couples to consider assisted reproductive technology (ART) in an effort to fulfill their desire for procreation. Given the critical role of the hemostatic system in the process of implantation, documentation of a hypercoagulable state during controlled ovarian stimulation in the context of in vitro fertilization, as well as the potential association of its derangement in the setting of thrombophilia, with infertility, ART, ovarian hyperstimulation syndrome, and failure of implantation are explored. Additionally, current evidence addressing the relationship between ART and thromboembolism is examined, as is the role of therapy with heparin and aspirin to decrease thrombotic risk and improve ART-related pregnancy outcomes. Evidence-based recommendations from relevant professional societies are summarized.