bluuebunny/crossref_metadata_2025 huggingface dataset:
Imaging of Brain Structural and Functional Effects in People With Human Immunodeficiency Virus
Authors: O’Connor Erin E , Sullivan Edith V , Chang Linda , Hammoud Dima A , Wilson Tony W , Ragin Ann B , Meade Christina S , Coughlin Jennifer , Ances Beau M
Published: March 2023

Before the introduction of antiretroviral therapy, human immunodeficiency virus (HIV) infection was often accompanied by central nervous system (CNS) opportunistic infections and HIV encephalopathy marked by profound structural and functional alterations detectable with neuroimaging. Treatment with antiretroviral therapy nearly eliminated CNS opportunistic infections, while neuropsychiatric impairment and peripheral nerve and organ damage have persisted among virally suppressed people with HIV (PWH), suggesting ongoing brain injury. Neuroimaging research must use methods sensitive for detecting subtle HIV-associated brain structural and functional abnormalities, while allowing for adjustments for potential confounders, such as age, sex, substance use, hepatitis C coinfection, cardiovascular risk, and others. Here, we review existing and emerging neuroimaging tools that demonstrated promise in detecting markers of HIV-associated brain pathology and explore strategies to study the impact of potential confounding factors on these brain measures. We emphasize neuroimaging approaches that may be used in parallel to gather complementary information, allowing efficient detection and interpretation of altered brain structure and function associated with suboptimal clinical outcomes among virally suppressed PWH. We examine the advantages of each imaging modality and systematic approaches in study design and analysis. We also consider advantages of combining experimental and statistical control techniques to improve sensitivity and specificity of biotype identification and explore the costs and benefits of aggregating data from multiple studies to achieve larger sample sizes, enabling use of emerging methods for combining and analyzing large, multifaceted data sets. Many of the topics addressed in this article were discussed at the National Institute of Mental Health meeting “Biotypes of CNS Complications in People Living with HIV,” held in October 2021, and are part of ongoing research initiatives to define the role of neuroimaging in emerging alternative approaches to identifying biotypes of CNS complications in PWH. An outcome of these considerations may be the development of a common neuroimaging protocol available for researchers to use in future studies examining neurological changes in the brains of PWH.
Biotypes of Central Nervous System Complications in People Living With Human Immunodeficiency Virus (HIV): National Institute of Mental Health Perspectives on Advancing the Future of HIV Healthcare
Authors: Rao Vasudev R , Brouwers Pim , Joseph Jeymohan , Lawhorn Collene , Scott Sheldon Lori A J , Rausch Dianne M
Published: March 2023

Despite effective suppressive antiretroviral therapy, central nervous system (CNS) complications related to human immunodeficiency virus (HIV) remain a significant problem for people with HIV (PWH). Numerous studies have contributed data to define the mechanisms underlying HIV-associated CNS pathophysiology, but causality remains elusive, with no effective therapies to prevent, reduce, or reverse HIV-associated CNS complications. Multiple physiological, clinical, cognitive, behavioral, social, and environmental factors contribute to the observed heterogeneity of adverse CNS outcomes among PWH. The National Institute of Mental Health in collaboration with investigators engaged in research related to HIV associated CNS complications organized a series of meetings to review the state of the science and facilitate the development of biologically based measures to identify the phenotypic heterogeneity of CNS outcomes linked to pathophysiology (biotypes). In this article, we summarize the proceedings of these meetings and explore the precision medicine framework to identify critical factors linked to the etiopathogenesis of CNS outcomes in PWH.
Re-evaluation of cefepime or piperacillin/tazobactam to decrease use of carbapenems in ESBL-producing Enterobacterales urinary tract infections (REDUCE-UTI)
Authors: Branton Alexander C , Vu Catherine H , Venugopalan Veena , Santevecchi Barbara A , Cherabuddi Kartikeya , Ramphal Reuben , Manohar Tanvi , Desear Kathryn E
Published: March 2023

Objectives

To re-examine the use of non-carbapenems (NCBPs), specifically piperacillin/tazobactam and cefepime, for ESBL-producing Enterobacterales (ESBL-E) urinary tract infections (UTIs).

Patients

Retrospective cohort study of adults hospitalized between January 2016 and June 2020 with pyuria on urinalysis, a urine culture positive for ESBL-E treated with a study antibiotic (meropenem, ertapenem, cefepime or piperacillin/tazobactam) and did not meet criteria for study exclusion.

Methods

To compare carbapenems (CBPs) with cefepime or piperacillin/tazobactam for the treatment of ESBL-E UTI. The primary outcome was clinical cure, defined as complete resolution of signs and symptoms of infection. Secondary outcomes included in-hospital mortality, recurrence within 30 days and resistance emergence within 30 days.

Results

One-hundred and thirty-three patients were included, based on definitive therapy received; 69 (51.9%) received CBP and 64 (48.1%) received NCBP therapy. Of the total patient population, 17 (12.8%) were admitted to the ICU, 84 (63.1%) had a complicated UTI and 64 (48.1%) had pyelonephritis. There was no difference in clinical cure between the CBP and NCBP groups (95.7% versus 96.9%, P = 0.999). Additionally, no differences in secondary outcomes were observed.

Conclusions

When compared with CBPs, cefepime and piperacillin/tazobactam resulted in similar clinical cure, in-hospital mortality, recurrence and resistance emergence in the treatment of ESBL-E UTI.
Rapid molecular detection of CMY-2, and CTX-M group 1 and 9 variants via recombinase polymerase amplification
Authors: Ertl Nicole G , Irwin Adam D , Macdonald Joanne , Bauer Michelle J , Wang Claire Y T , Harris Patrick N A , Heney Claire , Zowawi Hosam M , Whiley David M
Published: March 2023

Background

Due to their prevalence worldwide, the β-lactamases CTX-M and plasmid-mediated CMY-2 are important antimicrobial resistance enzymes in a clinical setting. While culture- and PCR-based detection methods exist for these targets, they are time consuming and require specialist equipment and trained personnel to carry out.

Methods

In this study, three rapid diagnostic single-plex and a prototype triplex assay were developed, using recombinase polymerase amplification with lateral flow detection (RPA-LF), and tested for their sensitivity and specificity using two isolate DNA panels (n = 90 and n = 120 isolates). In addition, the RPA-LF assays were also tested with a small number of faecal extract samples (n = 18).

Results

The RPA-LF assays were able to detect blaCXT-M-group-1, blaCTX-M-group-9 and blaCMY-2-type variants with high sensitivity (82.1%–100%) and specificity (100%) within a short turnaround time (15–20 min for amplification and detection).

Conclusions

RPA-LF assays developed in this study have the potential to be used at or close to the point of care, as well as in low-resource settings, producing rapid results to support healthcare professionals in their treatment decisions.
Revealing the microbial diversity and physicochemical characteristics of Brazilian untreated green table olives
Authors: Simões Luara Aparecida , Fernandes Natalia de Andrade Teixeira , de Souza Angélica Cristina , Torres Luciana Marques , da Silva Luiz Fernando de Oliveira , Schwan Rosane Freitas , Dias Disney Ribeiro
Published: March 2023

Aim

This work evaluated the microbial diversity and physicochemical characteristics of fresh and fermented fruits from Brazilian untreated green table olives of the Ascolano and Grappolo cultivars.

Methods and results

Twenty species of mesophilic bacteria, seven lactic acid bacteria, and fourteen yeast were identified. Some species prevailed over others, such as the bacteria Levilactobacillus brevis, Lacticaseibacillus paracasei subsp. paracasei, Pantoea agglomerans, Staphylococcus warneri, Bacillus simplex, B. thuringiensis, and the yeasts Candida parapsilosis, Ca. orthopsilosis, and Cryptococcus flavescen. In the olive fruit and olive brine, the sugars: sucrose, glucose, mannitol, and fructose, and the acids: acetic, citric, lactic, malic, and succinic were identified. Thirty-seven volatile compounds belonging to different chemical classes of acids, alcohols, aldehydes, esters, hydrocarbons, phenols, ketones, and ether were identified in the fruits and brine olives.

Conclusion

The polyphasic methodology using matrix assisted laser desorption/ionization–time of flight and 16S rRNA sequencing was efficiently performed to identify microorganisms; chemical analysis helped to understand the fermentation process of olives.
Two species-specific TaqMan-based quantitative polymerase chain reaction assays for the detection in soil ofPaenibacillus polymyxainocula
Authors: Manfredini A , Malusà E , Trzcinski P , Ptaszek M , Sas-Paszt L , Mocali S , Pinzari F , Canfora L
Published: March 2023

Aims

The increasingly widespread use of beneficial microbial inocula in agriculture gives rise to two primary needs: i) the assessment of the environmental risk, i.e. their impact on local soil microbiome and soil properties; ii) being able to track them and monitor their persistence and fate to both optimize their formulation and application method. In previous years, PCR-based methods have detected bacterial or fungal bioinoculant at the species or strain level. However, the selective detection, quantification, and monitoring of target microbial species in a complex ecosystem such as soil require that the tests possess high specificity and sensitivity.

Methods and results

The work proposes a quantitative real-time PCR detection method using TaqMan chemistry, showing high specificity and sensitivity for the Paenibacillus polymyxa K16 strain. The primer and probe sets were designed using the polymyxin gene cluster targeting pmxC and pmxE sequences. Validation tests showed that these assays allowed a discriminant and specific detection of P. polymyxa K16 in soil.

Conclusion

The TaqMan-assay developed could thus ensure the necessary level of discrimination required by commercial and regulatory purposes to detect and monitor the bioinoculant in soil.
Application and comparison of lyophilisation protocols to enhance stable long-term storage of filovirus pseudotypes for use in antibody neutralisation tests
Authors: Neto Martin Mayora , Wright Edward , Temperton Nigel , Soema Peter , ten Have Rimko , Ploemen Ivo , Scott Simon
Published: March 2023

Aims

Filoviruses encompass highly pathogenic viruses placing significant public health burden on countries affected. Efforts for improved diagnostics and surveillance are needed. The requirement for high-containment can be circumvented by using pseudotype viruses (PV), which can be handled safely, in tropism, drug screening, vaccine evaluation, and serosurveillance studies. We assessed the stability and functionality after long-term storage of lyophilised filovirus pseudotypes for use in neutralisation assays.

Methods and results

We generated a panel of filovirus lentiviral pseudotypes followed by lyophilisation and storage in different conditions. Next, we reconstituted and tested PVs in infection experiments and pseudotype neutralisation assays where possible. Lyophilised Ebola and Marburg PVs retained production titres for at least two years when stored at +4˚C or less. Lyophilised Ebola PVs performed similarly to non-lyophilised PVs in neutralisation assays after reconstitution. When stored at high temperatures (+37˚C), lyophilised PVs did not retain titres after 1-month storage, however, when lyophilised using pilot-scale facilities EBOV PVs retained titres and performed as standard in neutralisation assays after on 1-month storage at 37˚C.

Conclusions

Filovirus PVs are amenable to lyophilisation and can be stored for at least 2 years in a household fridge to be used in antibody assays. Lyophilisation performed in the right conditions would allow transportation at room temperature, even in warmer climates.
Dietary potential probiotics and enzymes complex modulates the performance and rumen microbiota in weaned goats
Authors: Lu Jiawei , Chen Zili , Chen Peiyong , Li Zihao , Wan Yongjie , Song Yanlei , Wang Feng , Zhang Yanli
Published: March 2023

Aims

This trial was performed to investigate the effects of combined feeding of Candida utilis CICC 31170, Bacillus coagulans R11, and Lactobacillus acidophilus NCFM and a multi-enzyme complex on the growth performance, immune parameters, feed digestibility, and rumen microbiota of weaned goats.

Methods and Results

Thirty weaned goats were randomly divided into CON, PRB, and COB groups and fed different diets. End weight and ADG increased significantly in the PRB and COB groups (P < 0.05), and ADFI increased significantly in COB (P < 0.05). On day 80, there was a significant increase in IL-10 content in PRB and COB compared to the CON (P < 0.05). Highly significant increases in rumen papilla width, epithelial cell thickness, stratum spinosum+basale thickness, and stratum corneum thickness were found in PRB and COB (P < 0.05). COB group significantly increased the gene expression of HMGCL and MCT1 in rumen epithelium (P < 0.001). The COB group had the tendency to increase the feed digestibility of dry matter and crude fat compared with the CON group (P < 0.10). The abundance of Prevotellaceae_unclassified was significantly higher in PRB (P < 0.05), and the abundance of Fibrobacteres was significantly higher in COB in comparison to those in CON (P < 0.05).

Conclusions

The results indicate that the dietary potential probiotics and enzymes complex could modulate the growth performance, immunity, feed digestibility, and rumen microbiota in weaned goats.
Comparative impact of exogenous phenylalanine on oenological isolates ofKluyveromyces marxianusandSaccharomyces cerevisiae
Authors: Degenaar N , Divol B
Published: March 2023

Aims

Kluyveromyces marxianus’ high production of 2-phenylethyl acetate (2-PEA) via L-phenylalanine (Phe) catabolism makes it relevant for industries relying on the production of aroma compounds through fermentation processes. This study assessed the physiological impact of exogenous supplementation of Phe on cell viability, fermentation performance, and, by extension, on lipid and amino acid metabolism in a wine isolate of this yeast.

Methods and results

The data showed that Phe exerted cytotoxic effects on K. marxianus IWBT Y885, which were minimal on Saccharomyces cerevisiae and impacted amino acid metabolism and aroma production. We demonstrated that K. marxianus strains fermented sugars more effectively in the absence of Phe. While lipid supplementation did not mitigate any deleterious effects of Phe, it supported viability maintenance and fermentation performance in the absence of Phe. Phe supplementation succeeded in augmenting the production of 2-PE and 2-PEA.

Conclusions

The enhanced production of 2-PEA in K. marxianus suggests that this transesterification may be, at least in part, a compensatory detoxification mechanism for this yeast.
Biochemical and molecular regulatory mechanism of thepgpHgene on biofilm formation inListeria monocytogenes
Authors: Zhang Xinyi , Zheng Liping , Lu Zhaoxin , Zhou Libang , Meng Fanqiang , Shi Changzheng , Bie Xiaomei
Published: March 2023

Aims

PgpH gene has an important regulatory role on bacterial physiological activity, but studies on its regulation mechanism on biofilm formation of Listeria monocytogenes are lacking. Our aim was to investigate the effect of pgpH gene deletion on biofilm formation in L. monocytogenes.

Methods and results

The ΔpgpH deletion strain of L. monocytogenes LMB 33  426 was constructed by homologous recombination. Deletion of the pgpH gene resulted in a significant reduction in biofilm formation. The swimming ability of the ΔpgpH strain on semisolid plates was unchanged compared to the wild-type strain (WT), and the auto-aggregation capacity of L. monocytogenes was decreased. RNA-seq showed that ΔpgpH resulted in the differential expression of 2357 genes compared to WT. pgpH inactivation resulted in the significant downregulation of the cell wall formation-related genes dltC, dltD, walK, and walR and the flagellar assembly related genes fliG and motB.

Conclusions

This study shows that the deletion of pgpH gene regulates biofilm formation and auto-aggregation ability of L. monocytogenes by affecting the expression of flagellar assembly and cell wall related genes. pgpH has a global regulatory effect on biofilm formation in L. monocytogenes.
Faecal shedding models for SARS-CoV-2 RNA among hospitalised patients and implications for wastewater-based epidemiology
Authors: Hoffmann Till , Alsing Justin
Published: March 2023

The concentration of SARS-CoV-2 RNA in faeces is not well characterised, posing challenges for quantitative wastewater-based epidemiology (WBE). We developed hierarchical models for faecal RNA shedding and fitted them to data from six studies. A mean concentration of 1.9 × 106 mL-1 (2.3 × 105–2.0 × 108 95% credible interval) was found among unvaccinated inpatients, not considering differences in shedding between viral variants. Limits of quantification could account for negative samples based on Bayesian model comparison. Inpatients represented the tail of the shedding profile with a half-life of 34 hours (28–43 95% credible interval), suggesting that WBE can be a leading indicator for clinical presentation. Shedding among inpatients could not explain the high RNA concentrations found in wastewater, consistent with more abundant shedding during the early infection course.
Measurement invariance of the Arizona Sexual Experience Scale by sexual orientation: comparing the sexual functioning of gay and heterosexual individuals
Authors: Sierra Juan Carlos , Mangas Pablo , Guillén-Riquelme Alejandro , Muñoz-García Laura Elvira
Published: March 2023

Background

The assessment of sexual functioning requires accurate and reliable measures as well as short and easy to apply. The Arizona Sexual Experience Scale (ASEX), which provides a quick, easy, and nonintrusive assessment of sexual functioning in men and women, is a clear example of a commonly used scale that satisfies these qualities.

Aim

The study sought to examine measurement invariance and differential item functioning (DIF) by sexual orientation of the Spanish version of the ASEX.

Methods

A confirmatory factor analysis was performed on a sample of 1600 adults (800 gay and 800 heterosexual individuals), testing measurement invariance of the ASEX by sexual orientation in men and women separately, and calculating its reliability and DIF.

Outcomes

The measure provided by the Spanish version of the ASEX is reliable and valid for assessing the sexual functioning of gay men and lesbians, but comparisons by sexual orientation are not recommended for men.

Results

The results of the confirmatory factor analysis confirmed the unidimensional structure of the ASEX already found in the Spanish validation with heterosexual people. Measurement invariance showed that, in the men’s sample, the factor structure of the ASEX only reached the weak level of invariance, whereas in the women’s sample, strict invariance by sexual orientation was reached. The internal consistency reliability was adequate, with better coefficients in women than in men. No significant DIF was observed in either men or women.

Clinical Implications

Clinicians should further their training in sexual and gender diversity as approaches such as affirmative LGBT psychotherapy gain popularity, and they must have access to assessment instruments that are psychometrically robust enough to be used with this population.

Strengths and Limitations

This research has some limitations. Because the distribution was administered solely through social media platforms, those without access to social media were unable to participate. Beyond these restrictions, however, the findings are thought to be significant from a research and clinical perspective since measurement invariance is a step that is often excluded when using an instrument validated in a mostly heterosexual sample.

Conclusion

Validating assessment tools in gay men and lesbians is essential because sexual functioning is a crucial concept in sexual health. The findings of this study suggest that the Spanish version of the ASEX offers valid and reliable measures of sexual functioning for both heterosexual and gay people, though there would be bias in comparing men of both orientations.
Antibacterial and antioxidant activities of Streptomyces sp. strain FR7 isolated from forest soil
Authors: Weslati Imen , Simões Luara , Teixeira Ana , Parpot Pier , Raies Aly , Oliveira Rui
Published: March 2023

Actinomycetes produce secondary metabolites with many bioactivities such as antimicrobial, which can be useful as alternatives against resistant bacterial strains. Therefore, the screening of new habitats is likely to provide new strains with high potential. In this work, the antimicrobial capacity was used to select Streptomyces sp. strains isolated from Raf Raf forest (Tunisia). From the strain displaying higher activity, FR7, an ethyl acetate extract was prepared under optimized culturing conditions (10 days at 30°C in ISP2 medium with initial pH 8), showing significant antimicrobial activity against Micrococcus luteus and Staphylococcus aureus (MIC = 5 μg ml−1), and Listeria monocytogenes and Pseudomonas aeruginosa (MIC = 20 μg ml−1). The extract displayed strong DPPH radical scavenging activity (IC50 = 1.3 μg ml−1) and protection of yeast cells from H2O2-induced oxidative stress determined by flow cytometry with dichlorofluorescein diacetate. The crude extract showed the presence of polyketides, with methylsalicylic acid as moiety, a large and diverse group of secondary metabolites with a wide range of bioactivities, including antioxidant and antibacterial. Based on 16S RNA gene sequences, strain FR7 was identified as belonging to genus Streptomyces with high resemblance to S. iakyrus. Streptomyces sp. FR7 has great potential as a source of antibacterial and antioxidant metabolites.
Determining Stress in Metallic Conducting Layers of Microelectronics Devices Using High Resolution Electron Backscatter Diffraction and Finite Element Analysis
Authors: Ruggles Timothy , Grutzik Scott , Stephens Kelly , Michael Joseph
Published: March 2023

Delayed failure due to stress voiding is a concern with some aging microelectronics, as these voids can grow large enough to cause an open circuit. Local measurements of stress in the metallic layers are crucial to understanding and predicting this failure, but such measurements are complicated by the fact that exposing the aluminum conducting lines will relieve most of their stress. In this study, we instead mechanically thin the device substrate and measure distortions on the thinned surface using high resolution electron backscatter diffraction (HREBSD). These measurements are then related to the stresses in the metallic layers through elastic simulations. This study found that in legacy components that had no obvious voids, the stresses were comparable to the theoretical stresses at the time of manufacture (≈300 MPa). Distortion fields in the substrate were also determined around known voids, which may be directly compared to stress voiding models. The technique presented here for stress determination, HREBSD coupled with finite element analysis to infer subsurface stresses, is a valuable tool for assessing failure in layered microelectronics devices.
The properties of RR Lyrae variable stars in the isolated Local Group dwarf galaxy WLM
Authors: Sarajedini Ata
Published: March 2023

We present an analysis of 50 F475W (≈B filter) and F814W (≈I filter) archival images taken with the Hubble Space Telescope (HST)/Advanced Camera for Surveys of one field in the isolated Local Group dwarf galaxy Wolf–Lundmark–Melotte (WLM). From point spread function fitting photometry of these images, we construct a colour–magnitude diagram and identify and characterize 90 RR Lyrae variables (76 ab-type and 14 c-type) determining their mean magnitudes, colours, periods, and amplitudes in the HST passbands. We have also uncovered 79 Cepheid-type variables, but because of the short time window of our observations (1.85 d), we are not confident in their period determinations. The mean period of the ab-type RR Lyraes is found to be 〈Pab〉 = 0.609 ± 0.058 (ran) corresponding to a mean metallicity of 〈[Fe/H]〉 = −1.74 ± 0.02 (ran) on the Carretta et al. scale. We also present a re-analysis of the Hodge et al. colour–magnitude diagram of the WLM globular cluster and conclude that it is much more metal-poor than Hodge et al. quote. Based on a comparison of the WLM RR Lyraes with those in the other seven ‘isolated’ dwarf galaxies of the Local Group (i.e. Leo A, LGS 3, Cetus, IC 1613, Aquarius, Tucana, and Phoenix), we conclude that there was one unique epoch of early star formation common to all of these isolated dwarfs.
TESS shines light on the origin of the ambiguous nuclear transient ASASSN-18el
Authors: Hinkle Jason T , Kochanek Christopher S , Shappee Benjamin J , Vallely Patrick J , Auchettl Katie , Fausnaugh Michael , Holoien Thomas W-S , Treiber Helena P , Payne Anna V , Gaudi B Scott , Stassun Keivan G , Thompson Todd A , Tonry J L , Villanueva Steven
Published: March 2023

We analyse high-cadence data from the Transiting Exoplanet Survey Satellite (TESS) of the ambiguous nuclear transient (ANT) ASASSN-18el. The optical changing-look phenomenon in ASASSN-18el has been argued to be due to either a drastic change in the accretion rate of the existing active galactic nucleus (AGN) or the result of a tidal disruption event (TDE). Throughout the TESS observations, short-time-scale stochastic variability is seen, consistent with an AGN. We are able to fit the TESS light curve with a damped-random-walk (DRW) model and recover a rest-frame variability amplitude of $\hat{\sigma } = 0.93 \pm 0.02$ mJy and a rest-frame time-scale of $\tau _{DRW} = 20^{+15}_{-6}$ d. We find that the estimated τDRW for ASASSN-18el is broadly consistent with an apparent relationship between the DRW time-scale and central supermassive black hole mass. The large-amplitude stochastic variability of ASASSN-18el, particularly during late stages of the flare, suggests that the origin of this ANT is likely due to extreme AGN activity rather than a TDE.
A closer look at dark photon explanations of the excess radio background
Authors: Acharya Sandeep Kumar , Chluba Jens
Published: March 2023

The observed excess radio background has remained a puzzle for over a decade. A recent new physics solution involves dark matter that decays into dark photons in the presence of a thermal dark photon background. The produced non-thermal dark photon spectrum then converts into standard photons around the reionization era, yielding an approximate power-law radio excess with brightness temperature T(ν) ≃ ν−2.5 over a wide range of frequencies, ν. This simple power-law model comes intriguingly close to the current data, even if several ingredients are required to make it work. In this paper, we investigate some of the details of this model, showcasing the importance of individual effects. In particular, significant deviation from a power law is present at $\nu \lesssim 100\, {\rm MHz}$ and $\nu \gtrsim 1\, {\rm GHz}$. These effects result in improving the fit to data compared to a power-law spectrum, and may become testable in future observations. We also highlight independent signatures that can be tested with future cosmic microwave background spectral distortion experiments such as PIXIE. However, there are challenges for the model from the observed radio background anisotropies, as discussed here. We furthermore highlight a possible runaway process due to the finite width of the dark matter decay profile, which suggests that additional work might be required to obtain a viable model.
Computational fluid dynamics with the coupled discrete unified gas kinetic scheme (CDUGKS)
Authors: Zamora Alvaro , Slaughter Elliott , Abel Tom
Published: March 2023

In this paper, we introduce our open source implementation of the Coupled Discrete Unified Gas Kinetic Scheme (CDUGKS), a phase space scheme capable of handling a wide range of flow regimes. We demonstrate its performance on several well known test problems from the astrophysical fluid dynamics literature such as the 1D Sod shock tube and Einfeldt rarefaction, 2D Kelvin-Helmholtz instability, 1D thermoacoustic wave, a triangular Gresho vortex, a sine wave velocity perturbation. For these problems, we show that the code can simulate flows ranging from the inviscid/Eulerian regime to the free-streaming regime, capturing shocks and emergent diffusive processes in the appropriate regimes. We also use a variety of Prandtl numbers to demonstrate the scheme’s ability to simulate different thermal conductivities at fixed viscosity. The scheme is second-order accurate in space and time and, unlike many solvers, uses a time-step that is independent of the mean free path of the gas. Our code (mp-cdugks) is public under a CC0 1.0 Universal license and is available on GitHub.
NGC 4388: a test case for relativistic disc reflection and Fe K fluorescence features
Authors: Yaqoob Tahir , Tzanavaris P , LaMassa S
Published: March 2023

We present a new analysis of the Suzaku X-ray spectrum of the Compton-thin Seyfert 2 galaxy NGC 4388. The spectrum above ∼2 keV can be described by a remarkably simple and rather mundane model, consisting of a uniform, neutral spherical distribution of matter, with a radial column density of $2.58\pm 0.02 \times 10^{23} \ \rm cm^{-2}$, and an Fe abundance of $1.102^{+0.024}_{-0.021}$ relative to solar. The model does not require any phenomenological adjustments to self-consistently account for the low-energy extinction, the Fe Kα and Fe Kβ fluorescent emission lines, the Fe K edge, and the Compton-scattered continuum from the obscuring material. The spherical geometry is not a unique description, however, and the self-consistent, solar abundance MYTORUS model, applied with toroidal and non-toroidal geometries, gives equally good descriptions of the data. In all cases, the key features of the spectrum are so tightly locked together that for a wide range of parameters, a relativistic disc-reflection component contributes no more than $\sim 2{{\ \rm per\ cent}}$ to the net spectrum in the 2–20 keV band. We show that the commonly invoked explanations for weak X-ray reflection features, namely a truncated and/or very highly ionized disc, do not work for NGC 4388. If relativistically broadened Fe Kα lines and reflection are ubiquitous in Seyfert 1 galaxies, they should also be ubiquitous in Compton-thin Seyfert 2 galaxies. The case of NGC 4388 shows the need for similar studies of more Compton-thin AGN to ascertain whether this is true.
Study with WhoSGlAd of the acoustic depth of the helium glitch across the seismic HR diagram and its impact on the inferred helium abundance
Authors: Farnir M , Valentino A , Dupret M-A , Broomhall A-M
Published: March 2023

The acoustic glitches’ signature present in solar-like stars holds invaluable information. Indeed, it is caused by a sharp variation in the sound speed, therefore carrying localized information. One such glitch is the helium glitch caused by the hydrogen and first and second partial helium ionization region, allowing us to constrain the surface helium abundance. However, the function adjusted to the glitch signature depends non-linearly on the acoustic depth at which it occurs, He. Retrieving the faint glitch signature and estimating τHe are difficult but crucial tasks to accurately measure the glitch parameters and, ultimately, accurately infer the helium abundance. In this paper, we aim at providing a way to estimate τHe using precise seismic indicators, independent of stellar modelling. Consequently, we aim at improving the WhoSGlAd (Whole Spectrum and Glitches Adjustment) method by automatically providing a model-independent measure of the glitch’s parameters. We compute the evolution of THe, a dimensionless form of the acoustic depth, along a grid of models and adjust an empirical linear relation between THe and the mean large separation and frequency ratio as defined in WhoSGlAd. We further optimize over the value of this estimate to ensure the stability and accuracy of the approach. The proposed approach provides an excellent estimate of the acoustic depth and allows us to swiftly retrieve the glitch signature of observed spectra. We demonstrate that the we can accurately model the helium abundance of four Kepler targets by comparing model (both versions of WhoSGlAd) and literature values.
The connection between starspots and superflares: a case study of two stars
Authors: Araújo Alexandre , Valio Adriana
Published: March 2023

How do the characteristics of starspots influence the triggering of stellar flares? Here, we investigate the activity of two K-type stars, similar in every way from mass to rotation periods and planetary systems. Both stars exhibit about a hundred spots; however, Kepler-411 produced 65 superflares, while Kepler-210 presented none. The spots of both stars were characterized using the planetary transit mapping technique, which yields the intensity, temperature, and radius of starspots. The average radius was (17 ± 7) × 103  and (58 ± 23) × 103 km, while the intensity ratio with respect to the photosphere was (0.35 ± 0.24) and (0.64 ± 0.15) Ic, and the temperature was (3800 ± 700) and (4180 ± 240) K for spots of Kepler-411 and Kepler-210, respectively. Therefore, spots on the star with no superflares, Kepler-210, are mostly larger, less dark, and warmer than those on the flaring star, Kepler-411. This may be an indication of magnetic fields with smaller magnitude and complexity of the spots on Kepler-210 when compared to those on Kepler-411. Thus, starspot area appears not to be the main culprit of superflares triggering. Perhaps the magnetic complexity of active regions is more important.
Restoration of mitochondrial function through activation of hypomodified tRNAs with pathogenic mutations associated with mitochondrial diseases
Authors: Tomoda Ena , Nagao Asuteka , Shirai Yuki , Asano Kana , Suzuki Takeo , Battersby Brendan J , Suzuki Tsutomu
Published: March 2023

Mutations in mitochondrial (mt-)tRNAs frequently cause mitochondrial dysfunction. Mitochondrial myopathy, encephalopathy, lactic acidosis, and stroke-like episodes (MELAS), and myoclonus epilepsy associated with ragged red fibers (MERRF) are major clinical subgroups of mitochondrial diseases caused by pathogenic point mutations in tRNA genes encoded in mtDNA. We previously reported a severe reduction in the frequency of 5-taurinomethyluridine (τm5U) and its 2-thiouridine derivative (τm5s2U) in the anticodons of mutant mt-tRNAs isolated from the cells of patients with MELAS and MERRF, respectively. The hypomodified tRNAs fail to decode cognate codons efficiently, resulting in defective translation of respiratory chain proteins in mitochondria. To restore the mitochondrial activity of MELAS patient cells, we overexpressed MTO1, a τm5U-modifying enzyme, in patient-derived myoblasts. We used a newly developed primer extension method and showed that MTO1 overexpression almost completely restored the τm5U modification of the MELAS mutant mt-tRNALeu(UUR). An increase in mitochondrial protein synthesis and oxygen consumption rate suggested that the mitochondrial function of MELAS patient cells can be activated by restoring the τm5U of the mutant tRNA. In addition, we confirmed that MTO1 expression restored the τm5s2U of the mutant mt-tRNALys in MERRF patient cells. These findings pave the way for epitranscriptomic therapies for mitochondrial diseases.
7-Deazaguanines in DNA: functional and structural elucidation of a DNA modification system
Authors: Gedara Samanthi Herath , Wood Evan , Gustafson Andrew , Liang Cui , Hung Shr-Hau , Savage Joshua , Phan Phuc , Luthra Amit , de Crécy-Lagard Valérie , Dedon Peter , Swairjo Manal A , Iwata-Reuyl Dirk
Published: March 2023

The modified nucleosides 2′-deoxy-7-cyano- and 2′-deoxy-7-amido-7-deazaguanosine (dPreQ0 and dADG, respectively) recently discovered in DNA are the products of the bacterial queuosine tRNA modification pathway and the dpd gene cluster, the latter of which encodes proteins that comprise the elaborate Dpd restriction–modification system present in diverse bacteria. Recent genetic studies implicated the dpdA, dpdB and dpdC genes as encoding proteins necessary for DNA modification, with dpdD–dpdK contributing to the restriction phenotype. Here we report the in vitro reconstitution of the Dpd modification machinery from Salmonella enterica serovar Montevideo, the elucidation of the roles of each protein and the X-ray crystal structure of DpdA supported by small-angle X-ray scattering analysis of DpdA and DpdB, the former bound to DNA. While the homology of DpdA with the tRNA-dependent tRNA-guanine transglycosylase enzymes (TGT) in the queuosine pathway suggested a similar transglycosylase activity responsible for the exchange of a guanine base in the DNA for 7-cyano-7-deazaguanine (preQ0), we demonstrate an unexpected ATPase activity in DpdB necessary for insertion of preQ0 into DNA, and identify several catalytically essential active site residues in DpdA involved in the transglycosylation reaction. Further, we identify a modification site for DpdA activity and demonstrate that DpdC functions independently of DpdA/B in converting preQ0-modified DNA to ADG-modified DNA.
Recovery From Nicotine Addiction: A Diffusion Model Decomposition of Value-Based Decision-Making in Current Smokers and Ex-smokers
Authors: Copeland Amber , Stafford Tom , Field Matt
Published: March 2023

Introduction

A considerable number of people successfully give up tobacco smoking. In nicotine-dependent individuals, tobacco choice is determined by greater expected drug value; however, less is known about the underlying mechanisms through which people quit smoking.

Aims and Methods

This study aimed to explore whether computational parameters of value-based decision-making (VBDM) characterize recovery from nicotine addiction. Using a preregistered, between-subject design, current daily smokers (n = 51) and ex-smokers who used to smoke daily (n = 51) were recruited from the local community. Participants completed a two-alternative forced choice task in which they chose between either two tobacco-related images (in one block) or tobacco-unrelated images (in a different block). During each trial, participants pressed a computer key to select the image they rated most positively during a previous task block. To estimate evidence accumulation (EA) processes and response thresholds during the different blocks, a drift-diffusion model was fitted to the reaction time and error data.

Results

Ex-smokers had significantly higher response thresholds when making tobacco-related decisions (p = .01, d = 0.45) compared to current smokers, although there were no significant group differences during tobacco-unrelated decisions. Furthermore, there were no significant group differences in EA rates when making tobacco or tobacco-unrelated decisions.

Conclusions

Greater cautiousness when making value-based decisions about tobacco-related cues characterized recovery from nicotine addiction.

Implications

The number of people dependent on nicotine has decreased steadily during the past decade; however, the mechanisms that underlie recovery are currently less well understood. The present study applied advances in the measurement of value-based choice. The aim was to explore whether the internal processes that underpin VBDM discriminate current daily tobacco smokers from ex-tobacco smokers who used to smoke daily. Findings revealed that recovery from nicotine addiction was characterized by higher response thresholds when making value-based decisions about tobacco-related cues; this may serve as a novel target for treatment interventions that focus on helping people to stop smoking.
Effects of very low-carbohydrate ketogenic diets on lipid profiles in normal-weight (body mass index < 25 kg/m2) adults: a meta-analysis
Authors: Joo Minjin , Moon Sumin , Lee Young Seo , Kim Myeong Gyu
Published: March 2023

Context

Very low-carbohydrate diets or ketogenic diets (KDs) have garnered attention for weight loss in patients with overweight or obesity as well as for normal-weight adults, yet the adverse effects of KDs, such as dyslipidemia in normal-weight adults, have not been studied extensively.

Objective

This meta-analysis aimed to identify the effects of KDs on the lipid profile in normal-weight (body mass index [BMI] < 25 kg/m2) adults from randomized controlled trials.

Data Sources

PubMed and Embase databases were searched on November 21, 2021, using search terms representing KDs and lipid profiles. Two researchers independently screened articles according to PICOS inclusion criteria.

Data Extraction

General study information, dietary data, and lipid profiles were extracted from eligible studies. Risk of bias was assessed using the Cochrane risk of bias 2 tool.

Data Analysis

Fixed- or random-effects meta-analysis was performed to estimate the effects of KDs on total cholesterol (TC), high-density lipoprotein-cholesterol (HDL-C), low-density lipoprotein-cholesterol (LDL-C), triglycerides, apolipoprotein A (apoA), and apolipoprotein B (apoB), considering heterogeneity across studies. The certainty of evidence was assessed using the GRADE (Grading of Recommendations, Assessment, Development and Evaluation) approach.

Results

Three studies were selected for meta-analysis. A KD significantly increased TC by 1.47 mmol/L (95%CI, 0.72–2.22 mmol/L), LDL-C by 1.08 mmol/L (95%CI, 0.37–1.79 mmol/L), and apoB by 0.35 g/L (95%CI, 0.06–0.65 g/L). In addition, a KD significantly increased HDL-C by 0.35 mmol/L (95%CI, 0.27–0.42 mmol/L) and apoA by 0.34 g/L (95%CI, 0.28–0.41 g/L) compared with control diets. Triglyceride levels were not significantly different between KDs and control diets (P = 0.63).

Conclusion

This study suggests unfavorable effects of KDs on TC and LDL-C in normal-weight adults. Although an increase in HDL-C can compensate for unfavorable changes in lipids, normal-weight individuals should consider the risk of hypercholesterolemia when consuming a KD. Results for triglycerides were inconsistent.
Performance of the 2016 ACR-EULAR Myositis Response Criteria in adult dermatomyositis/polymyositis therapeutic trials and consensus profiles
Authors: Saygin Didem , Kim Hanna , Douglas Christian , Erman Brian , Wilkerson Jesse , McGrath John A , Oddis Chester V , Lundberg Ingrid E , Amato Anthony A , García-De La Torre Ignacio , Chinoy Hector , Fiorentino David , Chung Lorinda , Song Yeong-Wook , Miller Frederick W , Ruperto Nicolino , Vencovsky Jiri , Aggarwal Rohit , Rider Lisa G ,   for the International Myositis Assessment and Clinical Studies Group (IMACS), Kim Susan , Pinal-Fernandez Iago , Ascherman Dana , Schiffenbauer Adam
Published: March 2023

Objective

The ACR-EULAR Myositis Response Criteria (MRC) were developed as a composite measure using absolute percentage change in six core set measures (CSMs). We aimed to further validate the MRC by assessing the contribution of each CSM, frequency of strength vs extramuscular activity improvement, representation of patient-reported outcome measures (PROM), and frequency of CSM worsening.

Methods

Data from adult dermatomyositis/polymyositis patients in the rituximab (n = 147), etanercept (n = 14), and abatacept (n = 19) trials, and consensus patient profiles (n = 232) were evaluated. The Total Improvement Score (TIS), number of improving vs worsening CSMs, frequency of improvement with and without muscle-related CSMs, and contribution of PROM were evaluated by MRC category. Regression analysis was performed to assess contribution of each CSM to the MRC.

Results

Of 412 adults with dermatomyositis/polymyositis, there were 37%, 24%, 25%, and 14% with no, minimal, moderate, and major MRC improvement, respectively. The number of improving CSMs and absolute percentage change in all CSMs increased by improvement category. In minimal-moderate improvement, only physician-reported disease activity contributed significantly more than expected by MRC. Of patients with at least minimal improvement, 95% had improvement in muscle-related measures and a majority (84%) had improvement in PROM. Patients with minimal improvement had worsening in a median of 1 CSM, and most patients with moderate-major improvement had no worsening CSMs. Physician assessment of change generally agreed with MRC improvement categories.

Conclusion

The ACR-EULAR MRC performs consistently across multiple studies, further supporting its use as an efficacy end point in future myositis therapeutic trials.
Quantitative interstitial lung disease scores in idiopathic inflammatory myopathies: longitudinal changes and clinical implications
Authors: Yeo Jina , Yoon Soon Ho , Kim Ju Yeon , Lee Jeong Seok , Lee Eun Young , Goo Jin Mo , Pourzand Lila , Goldin Jonathan G , Kim Grace-Hyun J , Ha You-Jung
Published: March 2023

Objectives

To investigate computer-aided quantitative scores from high-resolution CT (HRCT) images and determine their longitudinal changes and clinical significance in patients with idiopathic inflammatory myopathies (IIMs)-related interstitial lung disease (IIMs-ILD).

Methods

The clinical data and HRCT images of 80 patients with IIMs who underwent serial HRCT scans at least twice were retrospectively analysed. Quantitative ILD (QILD) scores (%) were calculated as the sum of the extent of lung fibrosis, ground-glass opacity, and honeycombing. The individual time-estimated ΔQILD between two consecutive scans was derived using a linear approximation of yearly changes.

Results

The baseline median QILD (interquartile range) scores in the whole lung were 28.1% (19.1–43.8). The QILD was significantly correlated with forced vital capacity (r = −0.349, P = 0.002) and diffusing capacity for carbon monoxide (r = −0.381, P = 0.001). For ΔQILD between the first two scans, according to the visual ILD subtype, QILD aggravation was more frequent in patients with usual interstitial pneumonia (UIP) than non-UIP (80.0% vs 44.4%, P = 0.013). Multivariable logistic regression analyses identified UIP was significantly related to radiographic ILD progression (ΔQILD >2%, P = 0.015). Patients with higher baseline QILD scores (>28.1%) had a higher risk of lung transplantation or death (P = 0.015). In the analysis of three serial HRCT scans (n = 41), dynamic ΔQILD with four distinct patterns (improving, worsening, convex and concave) was observed.

Conclusion

QILD changes in IIMs-ILD were dynamic, and baseline UIP patterns seemed to be related to a longitudinal progression in QILD. These may be potential imaging biomarkers for lung function, changes in ILD severity and prognosis in IIMs-ILD.