bluuebunny/crossref_metadata_2025 huggingface dataset:
Mediating Nostalgia: The Meaning of Ranchera Music at a Mexican Community Radio Station
Authors: Hayes Joy Elizabeth
Published: June 2020

This study investigates a battle over music and identity at Radio Zapotitlán, a community radio station in the state of Jalisco, Mexico. An analysis of over 20 interviews with station organizers, volunteers and listeners conducted in 2009 and 2010 indicates that while organizers and older listeners celebrated Ranchera music as the station’s predominant musical content, younger listeners fought to broadcast contemporary Banda music. An historical and theoretical analysis of Ranchera music explores its cultural role in mediating experiences of migration and nostalgia. This study finds that Radio Zapotitlán organizers promoted Ranchera music in order to engage the national and transnational nostalgia of Zapotitlán’s displaced migrants, and to meet the expectations of government regulators and transnational nongovernmental organizations (NGOs). It concludes that local, regional, national and transnational interests cannot be disentangled in musical articulations of identity at Radio Zapotitlán.
Rocking the boat while staying in it: connecting ends and means in radical community work
Authors: Ardle Oonagh Mc
Published: June 2020

At a time when the term ‘radical’ is predominantly associated with intolerance and violence, this article explicitly interrogates its meaning and application in community development praxis. Based on a qualitative inquiry, influenced by community development principles, community workers with rich experience at both micro- and macro-levels in Ireland were interviewed individually, then collectively to elicit their perspectives on the possibilities and challenges for radical community work in Ireland. While specifically located, its conclusions have relevance for community work and community development globally.

Findings show that being a professional and a radical are not incompatible. Some radical community workers recognize their dual role in service of the state and their obligation to work with others to change it. Acknowledging that marginalized communities do not have the access to power available to more privileged communities necessitates strategies to maximize influence. At the same time, there is an intimate connection between the methods used to transform society and the nature of the subsequent society. As workers accountable to communities, funders and the profession itself, the strategies engaged with and tactics adopted warrant careful consideration.

This article seeks to challenge the dichotomy of either conflict or consensus approaches as overly simplistic. Its suggests that some community workers can hold a radical agenda and conflictual ideology while pro-actively engaging with decision-makers who, although part of systems, which perpetuate inequality, can also be agents of change.
The Effectiveness of Individual and Environmental Infection Control Measures in Reducing the Transmission of Mycobacterium tuberculosis: A Systematic Review
Authors: Fox Greg J , Redwood Lisa , Chang Vicky , Ho Jennifer
Published: June 2020

Background

Transmission of Mycobacterium tuberculosis in healthcare settings is a preventable driver of the global tuberculosis epidemic. We aimed to assess the evidence for infection control interventions, including cough etiquette, engineering and personal respiratory protection measures, to prevent transmission of M. tuberculosis in healthcare settings.

Methods

Three independent systematic reviews were performed using 6 databases and clinical trials websites. Randomized trials, cohort studies, before-after studies, and case-control studies were included. Searches were performed for controlled studies evaluating respiratory hygiene, engineering, and personal respiratory protection measures. Outcome measures included the incidence of tuberculosis infection and disease. Studies involving transmission to either humans or animals were included.

Results

Evaluation of respiratory hygiene and cough etiquette interventions identified 4 human studies, with 22 855 participants, and 1 guinea pig study. Studies in humans evaluated the effects of multiple concurrent interventions. Patient use of surgical masks reduced infection by 14.8%, and tuberculosis disease was reduced by between 0.5% and 28.9%. Engineering and environmental interventions were evaluated in 10 studies of humans, including 31 776 human participants, and 2 guinea pig studies. Mechanical ventilation was associated with between 2.9% and 14% less infection. Nine studies of personal respiratory protection were included, including 33 913 participants. Infection was reduced by between 0% and 14.8% in studies where particulate respirators were used. The quality of included studies was assessed as low.

Conclusions

Respiratory hygiene, engineering, and environmental infection controls and personal respiratory protection interventions were associated with reduced transmission of M. tuberculosis and reduced tuberculosis disease in healthcare settings.
HOME2 Study: Household Versus Personalized Decolonization in Households of Children With Methicillin-Resistant Staphylococcus aureus Skin and Soft Tissue Infection—A Randomized Clinical Trial
Authors: Hogan Patrick G , Parrish Katelyn L , Mork Ryan L , Boyle Mary G , Muenks Carol E , Thompson Ryley M , Morelli John J , Sullivan Melanie L , Hunstad David A , Bubeck Wardenburg Juliane , Rzhetsky Andrey , Gehlert Sarah J , Burnham Carey-Ann D , Fritz Stephanie A
Published: June 2020

Background

A household approach to decolonization decreases skin and soft tissue infection (SSTI) incidence, though this is burdensome and costly. As prior SSTI increases risk for SSTI, we hypothesized that the effectiveness of decolonization measures to prevent SSTI when targeted to household members with prior year SSTI would be noninferior to decolonizing all household members.

Methods

Upon completion of our 12-month observational Household Observation of Methicillin-resistant Staphylococcus aureus in the Environment (HOME) study, 102 households were enrolled in HOME2, a 12-month, randomized noninferiority trial. Pediatric index patients with community-associated methicillin-resistant Staphylococcus aureus (MRSA) SSTI, their household contacts, and pets were enrolled. Households were randomized 1:1 to the personalized (decolonization performed only by household members who experienced SSTI during the HOME study) or household (decolonization performed by all household members) approaches. The 5-day regimen included hygiene education, twice-daily intranasal mupirocin, and daily bleach-water baths. At 5 follow-up visits in participants’ homes, swabs to detect S. aureus were collected from participants, environmental surfaces, and pets; incident SSTIs were ascertained.

Results

Noninferiority of the personalized approach was established for the primary outcome 3-month cumulative SSTI: 23 of 212 (10.8%) participants reported SSTI in household approach households, while 23 of 236 (9.7%) participants reported SSTI in personalized approach households (difference in proportions, −1.1% [95% confidence interval, −6.7% to 4.5%]). In multivariable analyses, prior year SSTI and baseline MRSA colonization were associated with cumulative SSTI.

Conclusions

The personalized approach was noninferior to the household approach in preventing SSTI. Future studies should interrogate longer durations of decolonization and/or decontamination of the household environment to reduce household MRSA burden.

Clinical Trials Registration

NCT01814371.
Delamanid Resistance: Update and Clinical Management
Authors: Nguyen Thi Van Anh , Anthony Richard M , Cao Thi Thu Huyen , Bañuls Anne-Laure , Nguyen Van Anh Thi , Vu Dinh Hoa , Nguyen Nhung Viet , Alffenaar Jan-Willem C
Published: June 2020

Delamanid, a-first-in-class bicyclic nitroimidazole, was recently approved for multidrug-resistant tuberculosis treatment. Pitted against the hope for improving treatment outcomes is the threat of the rapid resistance emergence. This review provides information on the mechanisms of action, resistance emergence, and drug susceptibility testing (DST) for delamanid. Delamanid resistance has already been reported in both in vitro experiments and clinical settings. Although mutations conferring delamanid resistance have been identified in fbiA, fbiB, fbiC, ddn, and fgd1 genes of Mycobacterium tuberculosis, knowledge about the molecular resistance mechanisms is limited, and there remains no standardized DST method. The rapid acquisition of delamanid resistance emphasizes the need for optimal use of new drugs, the need for drug resistance surveillance, and a comprehensive understanding of drug resistance mechanisms. Further studies are necessary to investigate genetic and phenotypic changes that determine clinically relevant delamanid resistance to help develop a rapid delamanid DST.
Two-Factor Decryption: A Better Way to Protect Data Security and Privacy
Authors: Cui Hui , Paulet Russell , Nepal Surya , Yi Xun , Mbimbi Butrus
Published: June 2020

Biometric information is unique to a human, so it would be desirable to use the biometric characteristic as the private key in a cryptographic system to protect data security and privacy. In this paper, we introduce a notion called two-factor decryption (TFD). Informally speaking, a TFD scheme is a variant of the public-key encryption (PKE) scheme. In a TFD scheme, messages are encrypted under public keys as that in a standard PKE scheme, but both private keys (i.e. the first factor) and biometric inputs (i.e. the second factor) are required to decrypt the ciphertexts and obtain the underlying plaintexts. We first describe a framework of TFD, and then define a formal security model for TFD. Thereafter, we present a generic construction on TFD based on the cryptographic primitives of linear sketch and functional encryption (FE) with certain properties and analyse its security. In addition, we give instantiations of TFD by applying concrete FE schemes into the generic construction and show their applications.
Transcatheter aortic valve implantation in patients with a left ventricular assist device: a word of caution
Authors: Ali Jason , Catarino Pedro , Abu-Omar Yasir
Published: June 2020

We describe a patient with a HeartMate 3 left ventricular assist device in whom we attempted transcatheter aortic valve implantation for severe aortic regurgitation. The valve migrated into the left ventricle and lodged on the left ventricular assist device inflow cannula. Caution should be exercised when considering the use of transcatheter aortic valve implantation in patients with an implanted left ventricular assist device, with pure aortic regurgitation.
A comparative environmental life cycle assessment of hatchery, cultivation, and preservation of the kelpSaccharina latissima
Authors: Thomas J -B E , Sodré Ribeiro M , Potting J , Cervin G , Nylund G M , Olsson J , Albers E , Undeland I , Pavia H , Gröndahl F
Published: June 2020

Seaweed cultivation and processing industries could contribute to sustainable blue growth and the European bioeconomy. This article contributes a case study evaluation of environmental sustainability of preserved brown seaweed Saccharina latissima by means of environmental life cycle assessment of a pilot facility in Sweden. The study accounts for nutrient bioremediation and carbon capture and includes two alternative hatchery processes, a 2-ha longline cultivation, and four alternative preservation methods (hang-drying outdoors, heated air-cabinet drying, ensiling, and freezing). The study found that as a result of carbon capture and nitrogen and phosphorus uptake (bioremediation) by seaweed, more CO2 and PO4 equivalents are (temporarily) absorbed than emitted by the supply chain. The extent of emissions is most affected by preservation methods undertaken. Impact profiles of the supply chain show that the greatest impact shares result from freezing and air-cabinet drying, both the two most energy-intensive processes, followed by the cultivation infrastructure, highlighting strategic optimization opportunities. Hatchery processes, harvesting, and the low-energy ensilage and hang-drying outdoors were found to have relatively small impact shares. These findings presage the environmentally friendliness of seaweed-based products by documenting their potential to mitigate eutrophication and climate change, even when taking a life cycle perspective.
A multiplex assay for characterization of antimicrobial resistance in Neisseria gonorrhoeae using multi-PCR coupled with mass spectrometry
Authors: Li Yamei , Xiu Leshan , Liu Jingwei , Zhang Chi , Wang Feng , Yin Yueping , Peng Junping
Published: June 2020

Background

Complicated mechanisms and variable determinants related to drug resistance pose a major challenge to obtain comprehensive antimicrobial resistance (AMR) profiles of Neisseria gonorrhoeae. Meanwhile, cephalosporin-resistant mosaic penA alleles have been reported worldwide. Therefore, it is urgent to monitor the expansion of cephalosporin-resistant mosaic penA alleles.

Objectives

To develop a comprehensive high-throughput method to efficiently screen AMR determinants.

Methods

We developed a method based on multiplex PCR with MALDI-TOF MS, which can simultaneously screen for 24 mutations associated with multiple antimicrobial agents in 19 gonococcal AMR loci (NG-AMR-MS). The performance of the NG-AMR-MS method was assessed by testing 454 N. gonorrhoeae isolates with known MICs of six antibiotics, eight non-gonococcal Neisseria strains, 214 clinical samples and three plasmids with a confirmed mosaic penA allele.

Results

The results show that NG-AMR-MS had a specificity of 100% with a sensitivity as low as 10 copies per reaction (except for PorB A121D/N/G, 100 copies per reaction). For clinical samples with gonococcal load >5 copies/μL, the method can accurately identify 20 AMR mutations. In addition, the method successfully detected specific cephalosporin-resistant strains with the A311V mutation in the penA allele.

Conclusions

Our high-throughput method can provide comprehensive AMR profiles within a multiplex format. Furthermore, the method can be directly applied to screening for AMR among clinical samples, serving as an effective tool for overall monitoring of N. gonorrhoeae AMR and also provides a powerful means to comprehensively improve the level of monitoring.
Dried yeast cell walls high in beta-glucan and mannan-oligosaccharides positively affect microbial composition and activity in the canine gastrointestinal tract in vitro
Authors: Van den Abbeele Pieter , Duysburgh Cindy , Rakebrandt Maike , Marzorati Massimo
Published: June 2020

The outer cell wall of yeast is characterized by high levels of β-glucans and mannan-oligosaccharides (MOS), which have been linked with beneficial effects on intestinal health and immune status in dogs. In this study, a standardized in vitro simulation of the canine gastrointestinal tract (Simulator of the Canine Intestinal Microbial Ecosystem; SCIME) was used to evaluate the effect of a Saccharomyces cerevisiae-based product, consisting of 27.5% β-glucans and 22.5% MOS, on the activity (as assessed by measurement of fermentative metabolites) and composition (as assessed by 16S-targeted Illumina sequencing) of canine intestinal microbiota. The S. cerevisiae-based product was tested at three different dosages, i.e., 0.5, 1.0, and 2.0 g/d. A dose-dependent fermentation pattern was observed along the entire length of the colon, as shown by the increased production of the health-related acetate, propionate, and butyrate for the three concentrations tested (0.5, 1.0, and 2.0 g/d). A consistent finding for all three tested concentrations was the increased propionate production (P < 0.05) in the simulated proximal and distal colon. These changes in terms of fermentative metabolites could be linked to specific microbial alterations at the family level, such as the specific stimulation of the propionate-producing families Porphyromonadaceae and Prevotellaceae upon in vitro exposure to the S. cerevisiae-based product. Other consistent changes in community composition upon repeated exposure included the decrease in the Enterobacteriaceae and the Fusobacteriaceae families, which both contain several potentially opportunistic pathogens. Altogether, the generated data support a possible health-promoting role of a product high in β-glucans and MOS when supplemented to the dogs’ diet.
Comprehensive analysis of the transient X-ray pulsar MAXI J1409−619
Authors: Dönmez Ç K , Serim M M , İnam S Ç , Şahiner Ş , Serim D , Baykal A
Published: June 2020

We probe the properties of the transient X-ray pulsar MAXI J1409−619 through RXTE and Swift follow-up observations of the outburst in 2010. We are able to phase-connect the pulse arrival times for the 25 d episode during the outburst. We suggest that either an orbital model (with Porb ≃ 14.7(4) d) or a noise process due to random torque fluctuations (with Sr ≈ 1.3 × 10−18 Hz2 s−2 Hz−1) is plausible to describe the residuals of the timing solution. The frequency derivatives indicate a positive torque–luminosity correlation, which implies temporary accretion disc formation during the outburst. We also discover several quasi-periodic oscillations in company with their harmonics whose centroid frequencies decrease as the source flux decays. The variation of the pulsed fraction and spectral power-law index of the source with X-ray flux is interpreted as the sign of transition from a critical to a sub-critical accretion regime at the critical luminosity within the range of 6 × 1037–1.2 × 1038 erg s−1. Using pulse-phase-resolved spectroscopy, we show that the phases with higher flux tend to have lower photon indices, indicating that the polar regions produce spectrally harder emission.
Chemical abundances in active galaxies
Authors: Flury Sophia R , Moran Edward C
Published: June 2020

The Sloan Digital Sky Survey (SDSS) has proved to be a powerful resource for understanding the physical properties and chemical composition of star-forming galaxies in the local Universe. The SDSS population of active galactic nuclei (AGNs) remains as of yet less explored in this capacity. To extend the rigorous study of H ii regions in the SDSS to AGNs, we adapt methods for computing direct-method chemical abundances for application to the narrow-line regions (NLR) of AGNs. By accounting for triply ionized oxygen, we are able to more completely estimate the total oxygen abundance. We find a strong correlation between electron temperature and oxygen abundance due to collisional cooling by metals. Furthermore, we find that nitrogen and oxygen abundances in AGNs are strongly correlated. From the metal–temperature relation and the coupling of nitrogen and oxygen abundances, we develop a new, empirically and physically motivated method for determining chemical abundances from the strong emission lines commonly employed in flux-ratio diagnostic diagrams (BPT diagrams). Our approach, which for AGNs reduces to a single equation based on the BPT line ratios, consistently recovers direct-method abundances over a 1.5 dex range in oxygen abundance with an rms uncertainty of 0.18 dex. We have determined metallicities for thousands of AGNs in the SDSS, and in the process have discovered an ionization-related discriminator for Seyfert and LINER galaxies.
Revealing the intermediate-mass black hole at the heart of the dwarf galaxy NGC 404 with sub-parsec resolution ALMA observations
Authors: Davis Timothy A , Nguyen Dieu D , Seth Anil C , Greene Jenny E , Nyland Kristina , Barth Aaron J , Bureau Martin , Cappellari Michele , den Brok Mark , Iguchi Satoru , Lelli Federico , Liu Lijie , Neumayer Nadine , North Eve V , Onishi Kyoko , Sarzi Marc , Smith Mark D , Williams Thomas G
Published: June 2020

We estimate the mass of the intermediate-mass black hole at the heart of the dwarf elliptical galaxy NGC 404 using Atacama Large Millimetre/submillimetre Array (ALMA) observations of the molecular interstellar medium at an unprecedented linear resolution of ≈0.5 pc, in combination with existing stellar kinematic information. These ALMA observations reveal a central disc/torus of molecular gas clearly rotating around the black hole. This disc is surrounded by a morphologically and kinematically complex flocculent distribution of molecular clouds, that we resolve in detail. Continuum emission is detected from the central parts of NGC 404, likely arising from the Rayleigh–Jeans tail of emission from dust around the nucleus, and potentially from dusty massive star-forming clumps at discrete locations in the disc. Several dynamical measurements of the black hole mass in this system have been made in the past, but they do not agree. We show here that both the observed molecular gas and stellar kinematics independently require a ≈5 × 105 M⊙ black hole once we include the contribution of the molecular gas to the potential. Our best estimate comes from the high-resolution molecular gas kinematics, suggesting the black hole mass of this system is 5.5$^{+4.1}_{-3.8}\times 10^5$ M⊙ (at the 99 per cent confidence level), in good agreement with our revised stellar kinematic measurement and broadly consistent with extrapolations from the black hole mass–velocity dispersion and black hole mass–bulge mass relations. This highlights the need to accurately determine the mass and distribution of each dynamically important component around intermediate-mass black holes when attempting to estimate their masses.
Bayesian approach to constraining the properties of ionized bubbles during reionization
Authors: Ghara Raghunath , Choudhury T Roy
Published: June 2020

A possible way to study the reionization of cosmic hydrogen is by observing the large ionized regions (bubbles) around bright individual sources, e.g. quasars, using the redshifted 21 cm signal. It has already been shown that matched filter-based methods are not only able to detect the weak 21 cm signal from these bubbles but also aid in constraining their properties. In this work, we extend the previous studies to develop a rigorous Bayesian framework to explore the possibility of constraining the parameters that characterize the bubbles. To check the accuracy with which we can recover the bubble parameters, we apply our method on mock observations appropriate for the upcoming SKA1-low. For a region of size ≳50 cMpc around a typical quasar at redshift 7, we find that ≈20 h of integration with SKA1-low will be able to constrain the size and location of the bubbles, as well as the difference in the neutral hydrogen fraction inside and outside the bubble, with $\lesssim 10$ per cent precision. The recovery of the parameters are more precise and the signal-to-noise ratio of the detected signal is higher when the bubble sizes are larger and their shapes are close to spherical. Our method can be useful in identifying regions in the observed field that contain large ionized regions and hence are interesting for following up with deeper integration times.
Cosmic variance of z > 7 galaxies: prediction from bluetides
Authors: Bhowmick Aklant K , Somerville Rachel S , Di Matteo Tiziana , Wilkins Stephen , Feng Yu , Tenneti Ananth
Published: June 2020

In the coming decade, a new generation of telescopes, including JWST and WFIRST, will probe the period of the formation of first galaxies and quasars, and open up the last frontier for structure formation. Recent simulations and observations have suggested that these galaxies are strongly clustered (with large-scale bias ≳6), and therefore have significant cosmic variance. In this work, we use bluetides, the largest volume cosmological simulation of galaxy formation, to directly estimate the cosmic variance for current and upcoming surveys. Given its resolution and volume, bluetides can probe the bias and cosmic variance of z > 7 galaxies between magnitude MUV ∼ −16 and MUV ∼ −22 over survey areas ∼0.1 arcmin2 to ∼10 deg2. Within this regime, the cosmic variance decreases with survey area/ volume as a power law with exponents between ∼−0.25 and ∼−0.45. For the planned 10 deg2 field of WFIRST, the cosmic variance is between $3{{\ \rm per\ cent}}$ and $10{{\ \rm per\ cent}}$. Upcoming JWST medium/ deep surveys with areas up to A ∼ 100 arcmin2 will have cosmic variance ranging from ${\sim}20\,\mathrm{ to}\,50{{\ \rm per\ cent}}$. Lensed surveys have the highest cosmic variance ${\gtrsim}40{{\ \rm per\ cent}}$; the cosmic variance of MUV ≲ −16 galaxies is ${\lesssim}100{{\ \rm per\ cent}}$ up to z ∼ 11. At higher redshifts such as z ∼ 12 (14), effective volumes of ≳ (8 Mpc h−1)3 (≳(12 Mpc h−1)3) are required to limit the cosmic variance to within $100{{\ \rm per\ cent}}$. Finally, we find that cosmic variance is larger than Poisson variance and forms the dominant component of the overall uncertainty in all current and upcoming surveys. We present our calculations in the form of simple fitting functions and an online cosmic variance calculator (CV_AT_COSMIC_DAWN) that we publicly release.
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

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

RNA 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

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

Objectives

Fibroblast-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.

Methods

Cultured 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.

Results

Apremilast 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.

Conclusion

Apremilast 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

Objective

CD4 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.

Methods

T 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.

Results

Deletion 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.

Conclusion

Our 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

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

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

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

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.