bluuebunny/crossref_metadata_2025_split huggingface dataset:
The possible disappearance of a massive star in the low-metallicity galaxy PHL 293B
Authors: Allan Andrew P , Groh Jose H , Mehner Andrea , Smith Nathan , Boian Ioana , Farrell Eoin J , Andrews Jennifer E 
Published: June 2020

ABSTRACT
We investigate a suspected very massive star in one of the most metal-poor dwarf galaxies, PHL 293B. Excitingly, we find the sudden disappearance of the stellar signatures from our 2019 spectra, in particular the broad H lines with P Cygni profiles that have been associated with a massive luminous blue variable (LBV) star. Such features are absent from our spectra obtained in 2019 with the Echelle Spectrograph for Rocky Exoplanet- and Stable Spectroscopic Observation and X-shooter instruments of the European Southern Observatory’s Very Large Telescope. We compute radiative transfer models using cmfgen, which fit the observed spectrum of the LBV and are consistent with ground-based and archival Hubble Space Telescope photometry. Our models show that during 2001–2011, the LBV had a luminosity L* = 2.5–3.5 × 106 L⊙, a mass-loss rate $\dot{M} = 0.005{-}0.020 ~{\rm M}_{\odot }$ yr−1, a wind velocity of 1000 km s−1, and effective and stellar temperatures of Teff = 6000–6800 and T* = 9500–15 000 K. These stellar properties indicate an eruptive state. We consider two main hypotheses for the absence of the broad emission components from the spectra obtained since 2011. One possibility is that we are seeing the end of an LBV eruption of a surviving star, with a mild drop in luminosity, a shift to hotter effective temperatures, and some dust obscuration. Alternatively, the LBV could have collapsed to a massive black hole without the production of a bright supernova.
RNAProbe: a web server for normalization and analysis of RNA structure probing data
Authors: Wirecki Tomasz K , Merdas Katarzyna , Bernat Agata , Boniecki Michał J , Bujnicki Janusz M , Stefaniak Filip 
Published: June 2020

AbstractRNA molecules play key roles in all living cells. Knowledge of the structural characteristics of RNA molecules allows for a better understanding of the mechanisms of their action. RNA chemical probing allows us to study the susceptibility of nucleotides to chemical modification, and the information obtained can be used to guide secondary structure prediction. These experimental results can be analyzed using various computational tools, which, however, requires additional, tedious steps (e.g., further normalization of the reactivities and visualization of the results), for which there are no fully automated methods. Here, we introduce RNAProbe, a web server that facilitates normalization, analysis, and visualization of the low-pass SHAPE, DMS and CMCT probing results with the modification sites detected by capillary electrophoresis. RNAProbe automatically analyzes chemical probing output data and turns tedious manual work into a one-minute assignment. RNAProbe performs normalization based on a well-established protocol, utilizes recognized secondary structure prediction methods, and generates high-quality images with structure representations and reactivity heatmaps. It summarizes the results in the form of a spreadsheet, which can be used for comparative analyses between experiments. Results of predictions with normalized reactivities are also collected in text files, providing interoperability with bioinformatics workflows. RNAProbe is available at https://rnaprobe.genesilico.pl.
Detection of base analogs incorporated during DNA replication by nanopore sequencing
Authors: Georgieva Daniela , Liu Qian , Wang Kai , Egli Dieter 
Published: June 2020

Abstract
DNA synthesis is a fundamental requirement for cell proliferation and DNA repair, but no single method can identify the location, direction and speed of replication forks with high resolution. Mammalian cells have the ability to incorporate thymidine analogs along with the natural A, T, G and C bases during DNA synthesis, which allows for labeling of replicating or repaired DNA. Here, we demonstrate the use of the Oxford Nanopore Technologies MinION to detect 11 different thymidine analogs including CldU, BrdU, IdU as well as EdU alone or coupled to Biotin and other bulky adducts in synthetic DNA templates. We also show that the large adduct Biotin can be distinguished from the smaller analog IdU, which opens the possibility of using analog combinations to identify the location and direction of DNA synthesis. Furthermore, we detect IdU label on single DNA molecules in the genome of mouse pluripotent stem cells and using CRISPR/Cas9-mediated enrichment, determine replication rates using newly synthesized DNA strands in human mitochondrial DNA. We conclude that this novel method, termed Replipore sequencing, has the potential for on target examination of DNA replication in a wide range of biological contexts.
Apremilast interferes with the TGFβ1-induced transition of human skin fibroblasts into profibrotic myofibroblasts:in vitrostudy
Authors: Cutolo Maurizio , Soldano Stefano , Montagna Paola , Martinelli Giulia , Tardito Samuele , Corallo Claudio , Giordano Nicola , Tavilla Pierpaolo , Cozzani Emanuele , Parodi Aurora , Sulli Alberto , Pizzorni Carmen , Patane Massimo , Smith Vanessa , Paolino Sabrina 
Published: June 2020

AbstractObjectivesFibroblast-to-myofibroblast transition and extracellular matrix overproduction represent progressive events in chronic inflammatory and fibrotic diseases, in which TGFβ1 is one of the key mediators. Phosphodiesterase 4 (PDE4) acts as a proinflammatory enzyme through the degradation of cyclic adenosine monophosphate and it is overexpressed in skin fibroblasts. The study investigated how apremilast (a PDE4 inhibitor) interferes with the intracellular signalling pathways responsible for the TGFβ1-induced fibroblast-to-myofibroblast transition and profibrotic extracellular matrix protein synthesis.MethodsCultured human skin fibroblasts were stimulated with TGFβ1 (10 ng/ml) alone or combined with apremilast (1 and 10 μM) for 4, 16 and 24 h. Other aliquots of the same cells were previously stimulated with TGFβ1 and then treated with apremilast (1 and 10 μM) for 4, 16 and 24 h, always under stimulation with TGFβ1. Gene and protein expression of αSMA, type I collagen (COL1) and fibronectin were evaluated, together with the activation of small mothers against decapentaplegic 2 and 3 (Smad2/3) and extracellular signal-regulated kinase (Erk1/2) proteins.ResultsApremilast reduced the TGFβ1-induced increase in αSMA, COL1 and fibronectin gene expression at 4 and 16 h, and protein synthesis at 24 h of treatment in cultured fibroblasts, even for cells already differentiated into myofibroblasts by way of a previous stimulation with TGFβ1. Apremilast inhibited the TGFβ1-induced Smad2/3 and Erk1/2 phosphorylation at 15 and 30 min.ConclusionApremilast seems to inhibit in vitro the fibroblast-to-myofibroblast transition and the profibrotic activity induced by TGFβ1 in cultured human skin fibroblasts by downregulating Smad2/3 and Erk1/2 intracellular signalling pathways.
Splicing factor SRSF1 limits IFN-γ production via RhoH and ameliorates experimental nephritis
Authors: Katsuyama Takayuki , Li Hao , Krishfield Suzanne M , Kyttaris Vasileios C , Moulton Vaishali R 
Published: June 2020

AbstractObjectiveCD4 T helper 1 (Th1) cells producing IFN-γ contribute to inflammatory responses in the pathogenesis of SLE and lupus nephritis. Moreover, elevated serum type II IFN levels precede the appearance of type I IFNs and autoantibodies in patient years before clinical diagnosis. However, the molecules and mechanisms that control this inflammatory response in SLE remain unclear. Serine/arginine-rich splicing factor 1 (SRSF1) is decreased in T cells from SLE patients, and restrains T cell hyperactivity and systemic autoimmunity. Our objective here was to evaluate the role of SRSF1 in IFN-γ production, Th1 differentiation and experimental nephritis.MethodsT cell-conditional Srsf1-knockout mice were used to study nephrotoxic serum-induced nephritis and evaluate IFN-γ production and Th1 differentiation by flow cytometry. RNA sequencing was used to assess transcriptomics profiles. RhoH was silenced by siRNA transfections in human T cells by electroporation. RhoH and SRSF1 protein levels were assessed by immunoblots.ResultsDeletion of Srsf1 in T cells led to increased Th1 differentiation and exacerbated nephrotoxic serum nephritis. The expression levels of RhoH are decreased in Srsf1-deficient T cells, and silencing RhoH in human T cells leads to increased production of IFN-γ. Furthermore, RhoH expression was decreased and directly correlated with SRSF1 in T cells from SLE patients.ConclusionOur study uncovers a previously unrecognized role of SRSF1 in restraining IFN-γ production and Th1 differentiation through the control of RhoH. Reduced expression of SRSF1 may contribute to pathogenesis of autoimmune-related nephritis through these molecular mechanisms.
Exposure Effects Beyond the Epithelial Barrier: Transepithelial Induction of Oxidative Stress by Diesel Exhaust Particulates in Lung Fibroblasts in an Organotypic Human Airway Model
Authors: Faber Samantha C , McNabb Nicole A , Ariel Pablo , Aungst Emily R , McCullough Shaun D 
Published: June 2020

Abstract
In vitro bronchial epithelial monoculture models have been pivotal in defining the adverse effects of inhaled toxicant exposures; however, they are only representative of one cellular compartment and may not accurately reflect the effects of exposures on other cell types. Lung fibroblasts exist immediately beneath the bronchial epithelial barrier and play a central role in lung structure and function, as well as disease development and progression. We tested the hypothesis that in vitro exposure of a human bronchial epithelial cell barrier to the model oxidant diesel exhaust particulates caused transepithelial oxidative stress in the underlying lung fibroblasts using a human bronchial epithelial cell and lung fibroblast coculture model. We observed that diesel exhaust particulates caused transepithelial oxidative stress in underlying lung fibroblasts as indicated by intracellular accumulation of the reactive oxygen species hydrogen peroxide, oxidation of the cellular antioxidant glutathione, activation of NRF2, and induction of oxidative stress-responsive genes. Further, targeted antioxidant treatment of lung fibroblasts partially mitigated the oxidative stress response gene expression in adjacent human bronchial epithelial cells during diesel exhaust particulate exposure. This indicates that exposure-induced oxidative stress in the airway extends beyond the bronchial epithelial barrier and that lung fibroblasts are both a target and a mediator of the adverse effects of inhaled chemical exposures despite being separated from the inhaled material by an epithelial barrier. These findings illustrate the value of coculture models and suggest that transepithelial exposure effects should be considered in inhalation toxicology research and testing.
Mistakes Made and Lessons Learned: A Mid-Career Pediatric Orthopaedic Surgeon’s Journey to Sustain Energy and Avoid Burnout
Authors: Flynn John M. 
Published: June 2020

Introduction:
Twenty-three years into this journey as a pediatric orthopaedic surgeon, my path is littered with mistakes made. The collision of a “family-first” philosophy with the demands of my busy academic surgical practice—not pretty. As a canary in a toxic coal mine, I have failed to fix the mine, so I have focused on being the very strongest and resilient canary possible.

Methods:
This is a retrospective study of mistakes made and lessons learned. The mistakes include submitting to the tyranny of perfectionism; failure to resist the tendency to measure ourselves against others; saying “yes” to every request; thinking my job is Monday to Friday, and career is nights/weekends; being given a big new job, but using same old time/energy management strategy; sloppy time management; failure to manage energy; considering sleep “a waste of time;” failure to manage attention; dragging the challenges from my day through the door each night; thinking that the skills that make me good at work are same that will make me good at home; aiming for work-life “balance;” and sometimes losing sight of our mission.

Results:
It is too soon to tell whether the lessons I have learned from all my mistakes are essential to preventing burnout. Although I am certain my results to date are significant, I cannot prove statistically significance. I am working to develop Appropriate Use Criteria for time and energy, and Best Practice Guidelines for prioritizing where to focus attention in life.

Discussion:
We need to manage our energy, time, and priorities with great care, and learn from the experts who are trying to teach corporate executives and professional athletes how to function in a high-pressure environment.

Conclusions:
Pediatric orthopaedics is one of the most wonderful professional callings. We can and should be happy and resilient canaries. The owners of the coal mine should hear us singing sweet songs about the children we care for even as they make the air increasingly toxic.
Insight into the Pro-inflammatory and Profibrotic Role of Macrophage in Heart Failure With Preserved Ejection Fraction
Authors: Shen Jin-lian , Xie Xiao-jie 
Published: June 2020

Abstract:
The prevalence of heart failure (HF) with preserved ejection fraction (HFpEF) is higher than that of HF with reduced/midrange ejection fraction (HFrEF/HFmrEF). However, no evidence-based guidelines for managing HFpEF have been generated. The current body of knowledge indicates that fibrosis and inflammation are important components of the cardiac remodeling process in HFpEF. In addition, macrophages potentially play an important role in pro-inflammatory and profibrotic processes in HFpEF patients, whereas HFpEF comorbidities could be a driving force for systemic microvascular inflammation and endothelial dysfunction. Under such circumstances, macrophages reportedly contribute to inflammation and fibrosis through 3 phases namely, inflammation, repair, and resolution. Signal transduction pathway-targeted therapies using animal experiments have generated important discoveries and breakthroughs for understanding the underlying mechanisms of HFpEF. However, only a handful of studies have reported promising results using human trials. Further investigations are therefore needed to elucidate the exact mechanisms underlying HFpEF and immune-pathogenesis of cardiac fibrosis.
Prospective Study of Saline versus Silicone Gel Implants for Subpectoral Breast Augmentation
Authors: Swanson Eric 
Published: June 2020

Background:
Silicone gel implants are regarded as esthetically superior to saline implants, offering a more natural consistency. They are also considered less susceptible to rippling. However, objective measurements and patient-reported outcome studies are lacking. Similarly, minimal data are available quantitating animation deformity.

Methods:
A 3-year prospective study was undertaken among 223 women undergoing primary subpectoral breast augmentation using either saline (n = 145) or silicone gel (n = 78) implants. Photographs obtained included frontal views with the patient flexing the pectoral muscles. Images were matched, and vertical differences in nipple position were measured. Breast implants were evaluated using high-resolution ultrasound to detect any ripples or folds at least 3 months after surgery. Outcome surveys were administered. Statistical analysis included the χ2 test, point-biserial correlations, and a power analysis.

Results:
Respondents reported visible rippling in 18% of women and palpable rippling in 32% of patients, with no significant difference between women treated with saline and silicone gel implants. Ripples were detected on ultrasound scans in 24% of women with saline implants and in 27% of women with silicone gel implants (difference not significant). Ripples were more common in women with lower body mass indices. Fifty percent of patients demonstrated nipple displacement <1 cm on animation. Nipple displacement occurred either up or down with equal frequency and a mean overall nipple displacement of zero.

Conclusions:
Saline and silicone breast implants produce similar degrees of rippling, as determined on outcome surveys and ultrasound examination. Animation deformities tend to be minor and well-tolerated.
Pain After Cochlear Implantation Without Signs of Inflammation: A Systematic Review
Authors: Sethi Mantegh , Hammond-Kenny Amy , Vijendren Ananth , Borsetto Daniele , Barker Eleanor J. , Tysome James R. , Donnelly Neil , Axon Patrick , Bance Manohar 
Published: June 2020

Objectives:
This review summarizes current evidence on causes and management strategies for delayed pain post-cochlear implantation (CI) surgery, without clinical evidence of inflammation or infection.

Methods:
The systematic review was undertaken in line with Preferred Reporting Items for Systematic review and Meta-Analysis Protocols 2015 guidelines. A literature search was undertaken, with inclusion of patients who underwent CI and presented with delayed pain (>3 months post-operatively) around their device site without an identifiable cause. Analysis was undertaken using MATLAB (MathWorks, Natick, MA) and the R-software package (www.r-project.org).

Results:
4 articles (48 patients), all retrospective case series, met inclusion criteria. The mean onset of pain post-CI was 60 months and mean follow-up was 15.8 months, there was no difference in the prevalence of pain between device brands (p=0.13). The majority (90%) did not have any hearing deterioration, and investigations did not reveal a cause for the pain in any of the patients. In terms of management, medical therapies, including oral therapy (analgesia, non-steroidal anti-inflammatories, antibiotics) and local treatments (topical, injections) resolved pain in 41% and 63%, respectively. Surgical intervention (explantation, magnet replacement, tympanic neurectomy), where undertaken, resolved pain in 100%. A minority had an identifiable infective microorganism cultured from intra-operative soft tissue or biofilm samples.

Conclusions:
Evidence for the causes and management of delayed pain post-CI without clinical evidence of inflammation is scarce. A stepwise approach is deemed best, with decisions being made on an individual basis, evaluating each patient's specific circumstances and priorities. Further evaluation of explanted devices would allow for better understanding of the causes and treatment of this group of patients.
Within-Family Transmission of Alcohol Use Disorder in Parent-Offspring, Sibling, and Cousin Pairs
Authors: Kendler Kenneth S. , Ohlsson Henrik , Sundquist Jan , Sundquist Kristina 
Published: June 2020

Abstract
To determine whether alcohol use disorder (AUD) is transmitted within families as predicted by contagion, we examined parent-offspring, siblings, and cousin pairs ascertained from Swedish registries with a primary case with AUD. Our outcome variable was AUD registration in at-risk secondary cases. In offspring, risks for AUD registration in the 3 years after a parental index registration residing in the same household, neighborhood, or municipality increased by 1.6%, −0.5%, and 0.3%, respectively. For siblings of sibling index cases, parallel results were 3.2%, 1.2%, and 0.3%. For cousins of cousin index cases, no excess risk was seen for those residing in the same neighborhood or municipality. In siblings, AUD transmission was stronger in same versus opposite sex pairs and from older to younger versus younger to older siblings. These results support the hypothesis that AUD is transmitted among close family relationships and over limited geographical distances by a temporally dynamic contagion model.
The Diagnosis of a Case of Household Cleaner Fatality
Authors: Das Siddhartha , Rahman Nisreen Abdul , Hanuman Srinivas Bheemanathi , Nandagopal Suresh 
Published: June 2020

Abstract
Household cleaners are an unavoidable entity in our routine domestic life. They are available either in company-labeled bottles or locally made unlabeled bottles especially in the developing countries. In this report, we are discussing a case of fatal ingestion of household cleaner, which was stored in an unlabeled bottle. The deceased developed features of gastrointestinal irritation, such as vomiting and pain in throat and abdomen. He also had features of aspiration such as cough and chest crepitation. Finally, he developed metabolic acidosis, gastric perforation, respiratory failure, and died within a day. The autopsy features such as teeth discoloration, corrosion of mouth and lips, and histopathological findings helped us in concluding that the ingredients contained some corrosive mineral acid. This case highlights the importance of histopathological examination of viscera in alleged cases of household cleaner poisoning where toxicological analysis of viscera gives negative results.
Sterol metabolism modulates susceptibility to HIV-1 Infection
Authors: Saulle Irma , Ibba Salomè Valentina , Vittori Cecilia , Fenizia Claudio , Mercurio Vincenzo , Vichi Francesca , Caputo Sergio Lo , Trabattoni Daria , Clerici Mario , Biasin Mara 
Published: June 2020

Background:
25-hydroxylase (CH25H) is an interferon-stimulated gene (ISG), which catalyzes the synthesis of 25-hydroxycholesterol (25HC). 25HC intervenes in metabolic and infectious processes and controls cholesterol homeostasis and influences viral entry into host cells. We verified whether natural resistance to HIV-1 infection in HIV-1-exposed seronegative (HESN) individuals is at least partially mediated by particularities in sterol biosynthesis.

Methods:
Peripheral blood mononuclear cells (PBMCs) and monocyte-derived macrophages (MDMs) isolated from 15 sexually exposed HESN and 15 healthy controls were in vitro HIV-1-infected and analyzed for: percentage of IFNα-producing plasmacytoid dendritic cells (pDCs); cholesterol signaling and inflammatory response RNA expression; resistance to HIV-1 infection. MDMs from five healthy controls were in vitro HIV-1-infected in the absence/presence of exogenously added 25HC.

Results:
IFNα-producing pDCs were augmented in HESN compared with healthy controls both in unstimulated and in in vitro HIV-1-infected PBMCs (P < 0.001). An increased expression of CH25H and of a number of genes involved in cholesterol metabolism (ABCA1, ABCG1, CYP7B1, LXRα, OSBP, PPARγ, SCARB1) was observed as well; this, was associated with a reduced susceptibility to in-vitro HIV-1-infection of PBMCs and MDMs (P < 0.01). Notably, addition of 25HC to MDMs resulted in increased cholesterol efflux and augmented resistance to in-vitro HIV-1-infection.

Conclusion:
Results herein show that in HESN sterol metabolism might be particularly efficient. This could be related to the activation of the IFNα pathway and results into a reduced susceptibility to in-vitro HIV-1 infection. These results suggest a possible basis for therapeutic interventions to modulate HIV-1 infection.