bluuebunny/crossref_metadata_2025_split huggingface dataset:
Probing the origin of 4FGL J0822.8–4207: cosmic ray illumination from the SNR Puppis A and the Herbig–Haro object HH219
Authors: Araya M , Gutiérrez L , Kerby S 
Published: November 2021

ABSTRACT
4FGL J0822.8–4207 is a point source found in the 4FGL-DR2 catalogue by the gamma-ray observatory Fermi-LAT and has no known association. We carry out X-ray observations of 4FGL J0822.8–4207 to help understand its nature. We explore two scenarios for the origin of 4FGL J0822.8–4207 . In the first case, we study the possibility that cosmic rays from the supernova remnant (SNR) Puppis A, seen nearby in the sky, reach the dense gas at the location of the source and produce the gamma-rays through inelastic proton–proton collisions. We apply a standard model for particle diffusion in the interstellar medium and derive the required physical parameters. We find that this scenario for the gamma-rays is possible if the gas is located at a distance that is not higher than ∼40 pc from Puppis A, unless the SNR is older than 7 kyr or the diffusion coefficient is higher than typical Galactic values, and relatively low-energy cosmic rays are currently escaping from the SNR. In the second scenario, we consider the protostellar jet HH219 as the origin of the GeV source and find the very interesting possibility that particles could be accelerated up to energies of at least several TeV in HH219. This would make this system the first known of its kind to produce gamma-ray emission extending up to hundreds of GeV without any apparent cut-off and an excellent laboratory to study the process of particle acceleration.
Survival and mass growth of cold gas in a turbulent, multiphase medium
Authors: Gronke Max , Oh S Peng , Ji Suoqing , Norman Colin 
Published: November 2021

ABSTRACT
Astrophysical gases are commonly multiphase and highly turbulent. In this work, we investigate the survival and growth of cold gas in such a turbulent, multiphase medium using three-dimensional hydrodynamical simulations. Similar to previous work simulating coherent flow (winds), we find that cold gas survives if the cooling time of the mixed gas is shorter than the Kelvin–Helmholtz time of the cold gas clump (with some weak additional Mach number dependence). However, there are important differences. Near the survival threshold, the long-term evolution is highly stochastic, and subject to the existence of sufficiently large clumps. In a turbulent flow, the cold gas continuously fragments, enhancing its surface area. This leads to exponential mass growth, with a growth time given by the geometric mean of the cooling and the mixing time. The fragmentation process leads to a large number of small droplets which follow a scale-free dN/dm ∝ m−2 mass distribution, and dominate the area covering fraction. Thus, whilst survival depends on the presence of large ‘clouds’, these in turn produce a ‘fog’ of smaller droplets tightly coupled to the hot phase which are probed by absorption line spectroscopy. We show with the aid of Monte Carlo simulations that the simulated mass distribution emerges naturally due to the proportional mass growth and the coagulation of droplets. We discuss the implications of our results for convergence criteria of larger scale simulations and observations of the circumgalactic medium.
A temporal scale to track the spectral transitions in low-mass X-ray binaries
Authors: Sonbas E , Mohamed K , Dhuga K S , Göğüş E 
Published: November 2021

ABSTRACT
The results of a temporal analysis of observations for a sample of nine low-mass X-ray binaries (LMXBs) are presented. Of these sources, five host a neutron star (NS) primary (4U1608−52, Aql X-1, 4U1705−44, GX17+2-, and Cyg X-2), and four host a black hole (BH) (GX339-4, XTE J1859+226, H1743−322, and MAXI J1659−152). The NS group includes three Atolls and two Z-type sources. We utilized archival Proportional Counter Array (PCA)/RXTE data to construct high-resolution light-curves. A wavelet transform of the light curves is deployed to extract a minimal time-scale (MTS) associated with the spectral state of the sources. The MTS, together with the fractional root-mean-square (rms) and hardness ratios, is used to construct RMS–MTS and hardness–MTS diagrams that enable a direct comparison of the evolution of spectral transitions in the target sources. Observations with high fractional rms and high hardness cluster in a broad region occupied jointly by BH and NS sources. For low fractional rms observations, the Atolls exhibit large MTS whereas Z-type sources exhibit small MTS. This new feature raises the possibility of discriminating between these two types of sources. Moreover, in the hardness–MTS plane, BH sources are the sole occupiers of the low-hardness and small-MTS domain thus potentially signalling a unique property for distinguishing BH and NS hosts in LMXBs.
Lenses In VoicE (LIVE): searching for strong gravitational lenses in the VOICE@VST survey using convolutional neural networks
Authors: Gentile Fabrizio , Tortora Crescenzo , Covone Giovanni , Koopmans Léon V E , Spiniello Chiara , Fan Zuhui , Li Rui , Liu Dezi , Napolitano Nicola R , Vaccari Mattia , Fu Liping 
Published: November 2021

ABSTRACT
We present a sample of 16 likely strong gravitational lenses identified in the VST Optical Imaging of the CDFS and ES1 fields (VOICE survey) using convolutional neural networks (CNNs). We train two different CNNs on composite images produced by superimposing simulated gravitational arcs on real Luminous Red Galaxies observed in VOICE. Specifically, the first CNN is trained on single-band images and more easily identifies systems with large Einstein radii, while the second one, trained on composite RGB images, is more accurate in retrieving systems with smaller Einstein radii. We apply both networks to real data from the VOICE survey, taking advantage of the high limiting magnitude (26.1 in the r band) and low PSF FWHM (0.8 arcsec in the r band) of this deep survey. We analyse ∼21 200 images with magr &lt; 21.5, identifying 257 lens candidates. To retrieve a high-confidence sample and to assess the accuracy of our technique, nine of the authors perform a visual inspection. Roughly 75 per cent of the systems are classified as likely lenses by at least one of the authors. Finally, we assemble the LIVE sample (Lenses In VoicE) composed by the 16 systems passing the chosen grading threshold. Three of these candidates show likely lensing features when observed by the Hubble Space Telescope. This work represents a further confirmation of the ability of CNNs to inspect large samples of galaxies searching for gravitational lenses. These algorithms will be crucial to exploit the full scientific potential of forthcoming surveys with the Euclid satellite and the Vera Rubin Observatory.
PRGdb 4.0: an updated database dedicated to genes involved in plant disease resistance process
Authors: Calle García Joan , Guadagno Anna , Paytuvi-Gallart Andreu , Saera-Vila Alfonso , Amoroso Ciro Gianmaria , D’Esposito Daniela , Andolfo Giuseppe , Aiese Cigliano Riccardo , Sanseverino Walter , Ercolano Maria Raffaella 
Published: November 2021

Abstract
The Plant Resistance Genes database (PRGdb; http://prgdb.org/prgdb4/) has been greatly expanded, keeping pace with the increasing amount of available knowledge and data (sequenced proteomes, cloned genes, public analysis data, etc.). The easy-to-use style of the database website has been maintained, while an updated prediction tool, more data and a new section have been added. This new section will contain plant resistance transcriptomic experiments, providing additional easy-to-access experimental information. DRAGO3, the tool for automatic annotation and prediction of plant resistance genes behind PRGdb, has been improved in both accuracy and sensitivity, leading to more reliable predictions. PRGdb offers 199 reference resistance genes and 586.652 putative resistance genes from 182 sequenced proteomes. Compared to the previous release, PRGdb 4.0 has increased the number of reference resistance genes from 153 to 199, the number of putative resistance genes from 177K from 76 proteomes to 586K from 182 sequenced proteomes. A new section has been created that collects plant-pathogen transcriptomic data for five species of agricultural interest. Thereby, with these improvements and data expansions, PRGdb 4.0 aims to serve as a reference to the plant scientific community and breeders worldwide, helping to further study plant resistance mechanisms that contribute to fighting pathogens.
Heterozygous COL4A3/COL4A4 mutations: the hidden part of the iceberg?
Authors: Mastrangelo Antonio , Madeira Catarina , Castorina Pierangela , Giani Marisa , Montini Giovanni 
Published: November 2021

ABSTRACT

Background
Single mutations in COL4A3/COL4A4 genes have been described in patients with autosomal dominant Alport syndrome and thin basement membrane nephropathy, without a shared definition of these patients within the medical community. We aimed to better categorize this clinical entity by examining clinical manifestations, family history, pathological features and genetics.

Methods
We retrospectively analyzed patients with causative heterozygous COL4A3/COL4A4 mutations referred to us between 1990 and 2019. Index cases were defined as children who were the first to be diagnosed in their families.

Results
The study included 24 index cases and 29 affected relatives, belonging to 25 families with a heterozygous mutation in the COL4A3/COL4A4 genes. During the follow-up, nine patients developed proteinuria [median age 15.7 years (range 5.6–33)], six at clinical diagnosis and four with progression toward chronic kidney disease (CKD) (three required kidney replacement therapy at 25, 45 and 53 years and one had CKD Stage 2 at 46 years). Extrarenal involvement was observed in 24.5% of patients. Hematuria was transmitted in consecutive generations, while CKD was reported in nonconsecutive generations of 11 families [median age 53 years (range 16–80)]. Seventeen patients (32%) underwent kidney biopsy: findings were consistent with Alport syndrome in 12 cases and with thin basement membrane nephropathy in 5 cases.

Conclusions
Despite the benign course for these patients described in the literature, a significant percentage is at risk for disease progression. Consequently, we suggest that the assessment of these patients must take into account family history, genetic analysis and pathologic findings. After comparison with the literature, our data suggest that a different definition for Alport syndrome must be considered.
Healthcare utilization and economic burden in systemic sclerosis: a systematic review
Authors: Martin Calderon Leonardo , Chaudhary Mitali , Pope Janet E 
Published: November 2021

Abstract

Objective
Systemic sclerosis (SSc) is characterized by vasculopathy, fibrosis of skin and internal organs, and autoimmunity with complications including interstitial lung disease, pulmonary hypertension, and digital ulcers with substantial morbidity and disability. Patients with SSc may require considerable healthcare resources with economic impact. The purpose of this systematic review was to provide a narrative synthesis of the economic impact and healthcare resource utilization associated with SSc.

Methods
MEDLINE and EMBASE were searched from inception to 20 January 2021. Studies were included if they provided information regarding the total, direct and indirect cost of SSc. The cost of SSc subtypes and associated complications was determined. Risk of bias assessments through the Joanna Briggs Institute cross-sectional and case series checklists, and the Newcastle–Ottawa Cohort and Case–Control study scales were performed. A narrative synthesis of included studies was planned.

Results
The number of publications retrieved was 1778, of which 34 were included representing 20 cross-sectional, 11 cohort, and three case–control studies. Studies used various methods of calculating cost including prevalence-based cost-of-illness approach and health resource units cost analysis. Overall SSc total annual cost ranged from USD $14 959 to $23 268 in USA, CAD $10 673 to $18 453 in Canada, €4607 to €30 797 in Europe, and AUD $7060 to $11 607 in Oceania. Annual cost for SSc-associated interstitial lung disease and pulmonary hypertension was USD $31 285–55 446 and $44 454–63 320, respectively.

Conclusion
Cost-calculation methodology varied greatly between included studies. SSc represents a significant patient and health resource economic burden. SSc-associated complications increase economic burden and are variable depending on geographical location and access.
Lipopolysaccharide-Induced Cytokine Secretion from In Vitro Mouse Slow and Fast Limb Muscle
Authors: Mattingly Alex J. , Laitano Orlando , Garcia Christian K. , Robinson Gerard P. , Clanton Thomas L. 
Published: November 2021

ABSTRACT
Skeletal muscles play important roles in innate immunity. However, in vitro, their sensitivity to LPS is low. In other tissues, LPS sensing is facilitated by the presence of plasma, LPS binding protein (LBP), or soluble CD14 (sCD14). This study addressed whether these are critical for LPS sensitivity in skeletal muscle and whether LPS responsiveness is different between slow versus fast muscle. Soleus (SOL) or extensor digitorum longus (EDL) muscles from adult male C57bl/6 mice were mounted in 1 mL oxygenated baths containing: buffer only; buffer+1% mouse plasma; buffer+1 μg/mL LBP; or buffer+1% plasma from sCD14-/- mice. In each condition, muscles were exposed to LPS from 0 μg/mL to 1.0 μg/mL. Bath samples were collected at 0, 1, and 2 h, and analyzed using cytokine multiplex arrays. In both SOL and EDL the predominant responding cytokines/chemokines were KC(CXCL1), IL-6, and MCP-1(CCL2) and their average responses were amplified by ∼10-fold in the presence of 1% plasma. Overall, SOL and EDL exhibited similar secretory responses in the presence of 1% plasma, with a lower limit of sensitivity to LPS of 0.01 μg/mL. LBP supplementation did not augment secretion; however, 1% plasma from CD14-/- mice suppressed cytokine/chemokine secretion from EDL muscle. In conclusion, intact slow and fast mouse muscles have similar cytokine/chemokine responses to LPS but depend on the presence of low levels of plasma constituents. Though sCD14 plays some role in EDL muscle, neither sCD14 nor LBP can fully account for the strong effects of plasma on LPS sensitivity.
Prehospital predictors for return of spontaneous circulation in traumatic cardiac arrest
Authors: Benhamed Axel , Canon Valentine , Mercier Eric , Heidet Matthieu , Gossiome Amaury , Savary Dominique , El Khoury Carlos , Gueugniaud Pierre-Yves , Hubert Hervé , Tazarourte Karim 
Published: November 2021

BACKGROUND
Traumatic cardiac arrests (TCAs) are associated with high mortality and the majority of deaths occur at the prehospital scene. The aim of the present study was to assess, in a prehospital physician-led emergency medical system, the factors associated with sustained return of spontaneous circulation (ROSC) in TCA, including advanced life procedures. The secondary objectives were to assess factors associated with 30-day survival in TCA, evaluate neurological recovery in survivors, and describe the frequency of organ donation among patients experiencing a TCA.

METHODS
We conducted a retrospective study of all TCA patients included in the French nationwide cardiac arrest registry from July 2011 to November 2020. Multivariable logistic regression analysis was used to identify factors independently associated with ROSC.

RESULTS
A total of 120,045 out-of-hospital cardiac arrests were included in the registry, among which 4,922 TCA were eligible for analysis. Return of spontaneous circulation was sustained on-scene in 21.1% (n = 1,037) patients. Factors significantly associated with sustained ROSC were not-asystolic initial rhythms (pulseless electric activity (odds ratio [OR], 1.81; 95% confidence interval [CI], 1.40–2.35; p < 0.001), shockable rhythm (OR, 1.83; 95% CI, 1.12–2.98; p = 0.016), spontaneous activity (OR, 3.66; 95% CI, 2.70–4.96; p < 0.001), and gasping at the mobile medical team (MMT) arrival (OR, 1.40; 95% CI, 1.02–1.94; p = 0.042). The MMT interventions significantly associated with ROSC were as follows: intravenous fluid resuscitation (OR, 3.19; 95% CI, 2.69–3.78; p < 0.001), packed red cells transfusion (OR, 2.54; 95% CI, 1.84–3.51; p < 0.001), and external hemorrhage control (OR, 1.74; 95% CI, 1.31–2.30; p < 0.001). Among patients who survived (n = 67), neurological outcome at Day 30 was favorable (cerebral performance categories 1–2) in 72.2% cases (n = 39/54) and 1.4% (n = 67/4,855) of deceased patients donated one or more organ.

CONCLUSION
Sustained ROSC was frequently achieved in patients not in asystole at MMT arrival, and higher ROSC rates were achieved in patients benefiting from specific advanced life support interventions. Organ donation was somewhat possible in TCA patients undergoing on-scene resuscitation.

LEVEL OF EVIDENCE
Prognostic and epidemiologic, Level III.
American Association for the Surgery of Trauma/American College of Surgeons-Committee on Trauma Clinical Protocol for inpatient venous thromboembolism prophylaxis after trauma
Authors: Yorkgitis Brian K. , Berndtson Allison E. , Cross Alisa , Kennedy Ryan , Kochuba Matthew P. , Tignanelli Christopher , Tominaga Gail T. , Jacobs David G. , Marx William H. , Ashley Dennis W. , Ley Eric J. , Napolitano Lena , Costantini Todd W. 
Published: November 2021

ABSTRACT
Trauma patients are at increased risk of venous thromboembolism (VTE), which includes both deep vein thrombosis and pulmonary embolism. Pharmacologic VTE prophylaxis is a critical component of optimal trauma care that significantly decreases VTE risk. Optimal VTE prophylaxis protocols must manage the risk of VTE with the competing risk of hemorrhage in patients following significant trauma. Currently, there is variability in VTE prophylaxis protocols across trauma centers. In an attempt to optimize VTE prophylaxis for the injured patient, stakeholders from the American Association for the Surgery of Trauma and the American College of Surgeons-Committee on Trauma collaborated to develop a group of consensus recommendations as a resource for trauma centers. The primary goal of these recommendations is to help standardize VTE prophylaxis strategies for adult trauma patients (age ≥15 years) across all trauma centers. This clinical protocol has been developed to (1) provide standardized medication dosing for VTE prophylaxis in the injured patient; and (2) promote evidence-based, prompt VTE prophylaxis in common, high-risk traumatic injuries.

LEVEL OF EVIDENCE
Therapeutic/Care Management; Level V.
sc2MeNetDrug: A computational tool to uncover inter-cell signaling targets and identify relevant drugs based on single cell RNA-seq data
Authors: Feng Jiarui , Goedegebuure S. Peter , Zeng Amanda , Bi Ye , Wang Ting , Payne Philip , Ding Li , DeNardo David , Hawkins William , Fields Ryan C. , Li Fuhai 
Published: November 2021

AbstractSingle-cell RNA sequencing (scRNA-seq) is a powerful technology to investigate the transcriptional programs in stromal, immune, and disease cells, like tumor cells or neurons within the Alzheimer’s Disease (AD) brain or tumor microenvironment (ME) or niche. Cell-cell communications within ME play important roles in disease progression and immunotherapy response and are novel and critical therapeutic targets. Though many tools of scRNA-seq analysis have been developed to investigate the heterogeneity and sub-populations of cells, few were designed for uncovering cell-cell communications of ME and predicting the potentially effective drugs to inhibit the communications. Moreover, the data analysis processes of discovering signaling communication networks and effective drugs using scRNA-seq data are complex and involve a set of critical analysis processes and external supportive data resources, which are difficult for researchers who have no strong computational background and training in scRNA-seq data analysis. To address these challenges, in this study, we developed a novel open-source computational tool, sc2MeNetDrug (https://fuhaililab.github.io/sc2MeNetDrug/). It was specifically designed using scRNA-seq data to identify cell types within disease MEs, uncover the dysfunctional signaling pathways within individual cell types and interactions among different cell types, and predict effective drugs that can potentially disrupt cell-cell signaling communications. sc2MeNetDrug provided a user-friendly graphical user interface to encapsulate the data analysis modules, which can facilitate the scRNA-seq data-based discovery of novel inter-cell signaling communications and novel therapeutic regimens.
Tunable Transcription Factor Library for Robust Quantification of Gene Expression Dynamics in E. coli
Authors: Parisutham Vinuselvi , Chhabra Shivani , Ali Md Zulfikar , Brewster Robert C. 
Published: November 2021

ABSTRACTPredicting the quantitative regulatory function of a TF based on factors such as binding sequence, binding location and promoter type is not possible. The interconnected nature of gene networks and the difficulty in tuning individual TF concentrations makes the isolated study of TF function challenging. Here we present a library of E. coli strains designed to allow for precise control of the concentration of individual TFs enabling the study of the role of TF concentration on physiology and regulation. We demonstrate the usefulness of this resource by measuring the regulatory function of the zinc responsive TF, ZntR and the paralogous TF pair, GalR/GalS. For ZntR, we find that zinc alters ZntR regulatory function in a way that enables activation of the regulated gene to be robust with respect to ZntR concentration. For GalR and GalS, we are able to demonstrate that these parlogous TFs have fundamentally distinct regulatory roles beyond differences in binding affinity.
Dual roles of mTORC1-dependent activation of the ubiquitin-proteasome system in muscle proteostasis
Authors: Kaiser Marco S. , Milan Giulia , Lin Shuo , Oliveri Filippo , Chojnowska Kathrin , Tintignac Lionel A. , Mittal Nitish , Zimmerli Christian E. , Glass David J. , Zavolan Mihaela , Ham Daniel J. , Rüegg Markus A. 
Published: November 2021

AbstractMuscle size is controlled by the PI3K-PKB/Akt-mTORC1-FoxO pathway, which integrates signals from growth factors, energy and amino acids to activate protein synthesis and inhibit protein breakdown. While mTORC1 activity is necessary for PKB/Akt-induced muscle hypertrophy, its constant activation alone induces muscle atrophy. Here we show that this paradox is based on mTORC1 activity promoting protein breakdown through the ubiquitin-proteasome system (UPS) by simultaneously inducing ubiquitin E3 ligase expression via feedback inhibition of PKB/Akt and proteasome biogenesis via Nuclear Factor Erythroid 2-Like 1 (Nrf1). Muscle growth was restored by reactivation of PKB/Akt, but not by Nrf1 knockdown, implicating ubiquitination as the limiting step. However, both PKB/Akt activation and proteasome depletion by Nrf1 knockdown led to an immediate disruption of proteome integrity with rapid accumulation of damaged material. These data highlight the physiological importance of mTORC1-mediated PKB/Akt inhibition and point to juxtaposed roles of the UPS in atrophy and proteome integrity.