bluuebunny/crossref_metadata_2025 huggingface dataset:
Statistical investigation of the widths of supra-arcade downflows observed during a solar flare
Authors: Tan Guangyu , Hou Yijun , Tian Hui
Published: April 2023

Supra-arcade downflows (SADs) are dark voids descending towards the post-reconnection flare loops and exhibit obvious variation in properties like width. However, due to the lack of further statistical studies, the mechanism behind such variations hitherto remains elusive. Here, we statistically investigated widths of 81 SADs observed in one flare by the Solar Dynamics Observatory (SDO). For each of SADs, six moments were selected with equal time intervals to measure their widths at different stages of their evolution. It is found that most SADs show a roughly monotonous width decrease during their descents, while some SADs with small initial widths can have complex evolutions. 3D reconstruction results based on SDO and Solar Terrestrial Relations Observatory Ahead (STEREO-A) images and thermal properties analysis reveal that differences in magnetic and plasma environments may result in that SADs in the north are overall wider than those in the south. Additionally, correlation analysis between the width and other parameters of SADs was further conducted and revealed that (1) SADs with different initial widths show no significant differences in their temperature and density evolution characteristics; (2) SADs with small initial widths usually appear in lower heights, where more frequent collisions between SADs could lead to their intermittent acceleration, width increment, and curved trajectories. These results indicate that SADs with different initial widths are produced the same way, while different environments (magnetic field or plasma) could affect their subsequent width evolutions.
Impact of turbulence intensity and fragmentation velocity on dust particle size evolution and non-ideal magnetohydrodynamics effects
Authors: Kawasaki Yoshihiro , Machida Masahiro N
Published: April 2023

We investigate the influence of dust particle size evolution on non-ideal magnetohydrodynamic (MHD) effects during the collapsing phase of star-forming cores, taking both the turbulence intensity in the collapsing cloud core and the fragmentation velocity of dust particles as parameters. When the turbulence intensity is small, the dust particles do not grow significantly, and the non-ideal MHD effects work efficiently in high-density regions. The dust particles rapidly grow in a strongly turbulent environment, while the efficiency of non-ideal MHD effects in such an environment depends on the fragmentation velocity of the dust particles. When the fragmentation velocity is small, turbulence promotes coagulation growth and collisional fragmentation of dust particles, producing small dust particles. In this case, the adsorption of charged particles on the dust particle surfaces becomes efficient and the abundance of charged particles decreases, making non-ideal MHD effects effective at high densities. On the other hand, when the fragmentation velocity is high, dust particles are less likely to fragment, even if the turbulence is strong. In this case, the production of small dust particles becomes inefficient and non-ideal MHD effects become less effective. We also investigate the effect of the dust composition on the star and disc formation processes. We constrain the turbulence intensity of a collapsing core and the fragmentation velocity of dust for circumstellar disc formation due to the dissipation of the magnetic field.
Shock waves in (1 + 1-dimensional) curved space-time
Authors: Verma Anshuman , Mallick Ritam
Published: April 2023

Shock jump conditions are widely used to solve various astrophysical problems. From the hydrodynamic equation, we derive the jump condition and the Taub adiabat equation in curve space-time for both time-like and space-like shocks. We find that the change in entropy for the weak shocks for curved space-time is small, similar to that for flat space-time. We also find that for general relativistic space-like shocks, the Chapman–Jouguet point does not necessarily correspond to the sonic point for downstream matter, unlike the special relativistic case. To analyse the shock wave solution for the curved space-time, one needs the information of metric potentials describing the space-time, which is assumed to be a neutron star for the present work. Assuming a shock wave is generated at the star’s centre, and as it propagates outward, it combusts nuclear matter to quark matter. We find that the general relativistic treatment of shock conditions is necessary to study shocks in neutron stars so that the results are consistent. We also find that with such general relativistic treatment, the combustion process in neutron stars is always a detonation.
The shared evaporation history of three sub-Neptunes spanning the radius–period valley of a hyades star
Authors: Fernández Fernández Jorge , Wheatley Peter J , King George W
Published: April 2023

We model the evaporation histories of the three planets around K2-136, a K-dwarf in the Hyades open cluster with an age of 700 Myr. The star hosts three transiting planets, with radii of 1.0, 3.0, and 1.5 Earth radii, where the middle planet lies above the radius–period valley and the inner and outer planets are below. We use an XMM–Newton observation to measure the XUV radiation environment of the planets, finding that the X-ray activity of K2-136 is lower than predicted by models but typical of similar Hyades members. We estimate the internal structure of each planet, and model their evaporation histories using a range of structure and atmospheric escape formulations. While the precise X-ray irradiation history of the system may be uncertain, we exploit the fact that the three planets must have shared the same history. We find that the Earth-sized K2-136b is most likely rocky, with any primordial gaseous envelope being lost within a few Myr. The sub-Neptune, K2-136c, has an envelope contributing 1–1.7 per cent of its mass that is stable against evaporation thanks to the high mass of its rocky core, whilst the super-Earth, K2-136d, must have a mass at the upper end of the allowed range in order to retain any of its envelope. Our results are consistent with all three planets beginning as sub-Neptunes that have since been sculpted by atmospheric evaporation to their current states, stripping the envelope from planet b and removing most from planet d whilst preserving planet c above the radius-period valley.
AGNs in the CALIFA survey: X-ray detection of nuclear sources
Authors: Osorio-Clavijo N , Gonzalez-Martín O , Sánchez S F , Guainazzi M , Cruz-González I
Published: April 2023

A complete demographic of active galactic nuclei (AGNs) is essential to understand the evolution of the Universe. Optical surveys estimate the population of AGNs in the local Universe to be of ∼ 4 per cent. However, these results could be biased towards bright sources, not affected by the host galaxy attenuation. An alternative method for detecting these objects is through the X-ray emission. In this work, we aim to complement the AGN population of the optical CALIFA survey (941 sources), by using X-ray data from Chandra, which provides the best spatial resolution to date, essential to isolate the nuclear emission from the host galaxy. We study a total of 138 sources with available data. We find 34 new bona fide AGNs and 23 AGN candidates, which could increase the AGN population to 7–10  per cent among the CALIFA survey. X-rays are particularly useful for low-luminosity AGNs since they are excluded by the criterion of large equivalent width of the $\rm {H\alpha }$ emission line when applied to optical selections. Indeed, placing such a restrictive criteria might cause a loss of up to 70 per cent of AGN sources. X-ray detected sources are preferentially located in the right side of the [${\mathrm{O}}\, {\small {\rm III}}$ ]/Hβ versus [${\mathrm{N}}\, {\small {\rm II}}$ ]/Hα diagram, suggesting that this diagram might be the most reliable at classifying AGN sources. Our results support the idea that multiwavelength studies are the best way to obtain a complete AGN population.
Comparison of burst properties between FRB 20190520B and FRB 20121102A
Authors: Lyu Fen , Liang En-Wei
Published: April 2023

A comparative analysis of the individual bursts between FRB 20190520B and FRB 20121102A is presented by compiling a sample of bursts in multiple wavelengths. It is found that the peak frequency (νp) distribution of the bursts of FRB 20190520B illustrates four discrete peaks in ∼1–6 GHz and their spectral width distribution can be fitted with a lognormal function peaking at 0.35 GHz. The discrete νp distribution and the narrow-banded spectral feature are analogous to FRB 20121102A. The burst duration of FRB 20190520B in the rest frame averages to 10.72 ms, longer than that of FRB 20121102A by a factor 3. The specific energy $\left(E_{\rm\mu_{\rm c}}\right)$ at 1.25 GHz of FRB 20190520B observed with the Five-hundred-meter Aperture Spherical Radio Telescope narrowly ranges in [0.4, 1] × 1038 erg, different from the bimodal $E_{\rm \mu _{\rm c}}$ distribution of FRB 20121102A. Assuming a Gaussian spectral profile of the bursts, our Monte Carlo simulation analysis suggests that a power law (PL) or a cut-off power-law (CPL) energy function can comparably reproduce the $E_{\rm \mu _{\rm c}}$ distribution of FRB 20190520B. The derived energy function index of the PL model is 4.46 ± 0.17, much steeper than that of FRB 20121102A ($1.82^{+0.10}_{-0.30}$ ). For the CPL model, we obtain an index of 0.47 and a cut-off energy of 7.4 × 1037 erg. Regarding the predicted νp distribution in 1–2 GHz, the CPL model is more preferred than the PL model. These results indicate that FRB 20190520B and FRB 20121102A share similar spectral properties, but their energy functions are intrinsically different.
A variational encoder–decoder approach to precise spectroscopic age estimation for large Galactic surveys
Authors: Leung Henry W , Bovy Jo , Mackereth J Ted , Miglio Andrea
Published: April 2023

Constraints on the formation and evolution of the Milky Way Galaxy require multidimensional measurements of kinematics, abundances, and ages for a large population of stars. Ages for luminous giants, which can be seen to large distances, are an essential component of studies of the Milky Way, but they are traditionally very difficult to estimate precisely for a large data set and often require careful analysis on a star-by-star basis in asteroseismology. Because spectra are easier to obtain for large samples, being able to determine precise ages from spectra allows for large age samples to be constructed, but spectroscopic ages are often imprecise and contaminated by abundance correlations. Here we present an application of a variational encoder–decoder on cross-domain astronomical data to solve these issues. The model is trained on pairs of observations from APOGEE and Kepler of the same star in order to reduce the dimensionality of the APOGEE spectra in a latent space while removing abundance information. The low dimensional latent representation of these spectra can then be trained to predict age with just ∼1000 precise seismic ages. We demonstrate that this model produces more precise spectroscopic ages ($\sim 22~{{\ \rm per\ cent}}$ overall, $\sim 11~{{\ \rm per\ cent}}$ for red-clump stars) than previous data-driven spectroscopic ages while being less contaminated by abundance information (in particular, our ages do not depend on [α/M]). We create a public age catalogue for the APOGEE DR17 data set and use it to map the age distribution and the age-[Fe/H]-[α/M] distribution across the radial range of the Galactic disc.
2D k-th nearest neighbour statistics: a highly informative probe of galaxy clustering
Authors: Yuan Sihan , Zamora Alvaro , Abel Tom
Published: April 2023

Beyond standard summary statistics are necessary to summarize the rich information on non-linear scales in the era of precision galaxy clustering measurements. For the first time, we introduce the 2D k-th nearest neighbour (kNN) statistics as a summary statistic for discrete galaxy fields. This is a direct generalization of the standard 1D kNN by disentangling the projected galaxy distribution from the redshift-space distortion signature along the line-of-sight. We further introduce two different flavours of 2D kNNs that trace different aspects of the galaxy field: the standard flavour which tabulates the distances between galaxies and random query points, and a ‘DD’ flavour that tabulates the distances between galaxies and galaxies. We showcase the 2D kNNs’ strong constraining power both through theoretical arguments and by testing on realistic galaxy mocks. Theoretically, we show that 2D kNNs are computationally efficient and directly generate other statistics such as the popular two-point correlation function (2PCF), voids probability function, and counts-in-cell statistics. In a more practical test, we apply the 2D kNN statistics to simulated galaxy mocks that fold in a large range of observational realism and recover parameters of the underlying extended halo occupation distribution (HOD) model that includes velocity bias and galaxy assembly bias. We find unbiased and significantly tighter constraints on all aspects of the HOD model with the 2D kNNs, both compared to the standard 1D kNN, and the classical redshift-space 2PCF.
Allosteric regulation and crystallographic fragment screening of SARS-CoV-2 NSP15 endoribonuclease
Authors: Godoy Andre Schutzer , Nakamura Aline Minalli , Douangamath Alice , Song Yun , Noske Gabriela Dias , Gawriljuk Victor Oliveira , Fernandes Rafaela Sachetto , Pereira Humberto D Muniz , Oliveira Ketllyn Irene Zagato , Fearon Daren , Dias Alexandre , Krojer Tobias , Fairhead Michael , Powell Alisa , Dunnet Louise , Brandao-Neto Jose , Skyner Rachael , Chalk Rod , Bajusz Dávid , Bege Miklós , Borbás Anikó , Keserű György Miklós , von Delft Frank , Oliva Glaucius
Published: April 2023

Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) is the causative agent of coronavirus disease 2019 (COVID-19). The NSP15 endoribonuclease enzyme, known as NendoU, is highly conserved and plays a critical role in the ability of the virus to evade the immune system. NendoU is a promising target for the development of new antiviral drugs. However, the complexity of the enzyme's structure and kinetics, along with the broad range of recognition sequences and lack of structural complexes, hampers the development of inhibitors. Here, we performed enzymatic characterization of NendoU in its monomeric and hexameric form, showing that hexamers are allosteric enzymes with a positive cooperative index, and with no influence of manganese on enzymatic activity. Through combining cryo-electron microscopy at different pHs, X-ray crystallography and biochemical and structural analysis, we showed that NendoU can shift between open and closed forms, which probably correspond to active and inactive states, respectively. We also explored the possibility of NendoU assembling into larger supramolecular structures and proposed a mechanism for allosteric regulation. In addition, we conducted a large fragment screening campaign against NendoU and identified several new allosteric sites that could be targeted for the development of new inhibitors. Overall, our findings provide insights into the complex structure and function of NendoU and offer new opportunities for the development of inhibitors.
Roles of the leader-trailer helix and antitermination complex in biogenesis of the 30S ribosomal subunit
Authors: Warner Benjamin R , Bundschuh Ralf , Fredrick Kurt
Published: April 2023

Ribosome biogenesis occurs co-transcriptionally and entails rRNA folding, ribosomal protein binding, rRNA processing, and rRNA modification. In most bacteria, the 16S, 23S and 5S rRNAs are co-transcribed, often with one or more tRNAs. Transcription involves a modified RNA polymerase, called the antitermination complex, which forms in response to cis-acting elements (boxB, boxA and boxC) in the nascent pre-rRNA. Sequences flanking the rRNAs are complementary and form long helices known as leader-trailer helices. Here, we employed an orthogonal translation system to interrogate the functional roles of these RNA elements in 30S subunit biogenesis in Escherichia coli. Mutations that disrupt the leader-trailer helix caused complete loss of translation activity, indicating that this helix is absolutely essential for active subunit formation in the cell. Mutations of boxA also reduced translation activity, but by only 2- to 3-fold, suggesting a smaller role for the antitermination complex. Similarly modest drops in activity were seen upon deletion of either or both of two leader helices, termed here hA and hB. Interestingly, subunits formed in the absence of these leader features exhibited defects in translational fidelity. These data suggest that the antitermination complex and precursor RNA elements help to ensure quality control during ribosome biogenesis.
Prediction of cooperative homeodomain DNA binding sites from high-throughput-SELEX data
Authors: Cain Brittany , Webb Jordan , Yuan Zhenyu , Cheung David , Lim Hee-Woong , Kovall Rhett A , Weirauch Matthew T , Gebelein Brian
Published: April 2023

Homeodomain proteins constitute one of the largest families of metazoan transcription factors. Genetic studies have demonstrated that homeodomain proteins regulate many developmental processes. Yet, biochemical data reveal that most bind highly similar DNA sequences. Defining how homeodomain proteins achieve DNA binding specificity has therefore been a long-standing goal. Here, we developed a novel computational approach to predict cooperative dimeric binding of homeodomain proteins using High-Throughput (HT) SELEX data. Importantly, we found that 15 of 88 homeodomain factors form cooperative homodimer complexes on DNA sites with precise spacing requirements. Approximately one third of the paired-like homeodomain proteins cooperatively bind palindromic sequences spaced 3 bp apart, whereas other homeodomain proteins cooperatively bind sites with distinct orientation and spacing requirements. Combining structural models of a paired-like factor with our cooperativity predictions identified key amino acid differences that help differentiate between cooperative and non-cooperative factors. Finally, we confirmed predicted cooperative dimer sites in vivo using available genomic data for a subset of factors. These findings demonstrate how HT-SELEX data can be computationally mined to predict cooperativity. In addition, the binding site spacing requirements of select homeodomain proteins provide a mechanism by which seemingly similar AT-rich DNA sequences can preferentially recruit specific homeodomain factors.
The sodium glucose co-transporter 2 inhibitor dapagliflozin ameliorates the fluid-retaining effect of the endothelin A receptor antagonist zibotentan
Authors: Veenit Vandana , Heerspink Hiddo J L , Ahlström Christine , Greasley Peter J , Skritic Stanko , van Zuydam Natalie , Kohan Donald E , Hansen Pernille B L , Menzies Robert I
Published: April 2023

Background

Endothelin A receptor antagonists (ETARA) slow chronic kidney disease (CKD) progression but their use is limited due to fluid retention and associated clinical risks. Sodium–glucose co-transporter 2 inhibitors (SGLT2i) cause osmotic diuresis and improve clinical outcomes in CKD and heart failure. We hypothesized that co-administration of the SGLT2i dapagliflozin with the ETARA zibotentan would mitigate the fluid retention risk using hematocrit (Hct) and bodyweight as proxies for fluid retention.

Methods

Experiments were performed in 4% salt fed WKY rats. First, we determined the effect of zibotentan (30, 100 or 300 mg/kg/day) on Hct and bodyweight. Second, we assessed the effect of zibotentan (30 or 100 mg/kg/day) alone or in combination with dapagliflozin (3 mg/kg/day) on Hct and bodyweight.

Results

Hct at Day 7 was lower in zibotentan versus vehicle groups [zibotentan 30 mg/kg/day, 43% (standard error 1); 100 mg/kg/day, 42% (1); and 300 mg/kg/day, 42% (1); vs vehicle, 46% (1); P < .05], while bodyweight was numerically higher in all zibotentan groups compared with vehicle. Combining zibotentan with dapagliflozin for 7 days prevented the change in Hct [zibotentan 100 mg/kg/day and dapagliflozin, 45% (1); vs vehicle 46% (1); P = .44] and prevented the zibotentan-driven increase in bodyweight (zibotentan 100 mg/kg/day + dapagliflozin 3 mg/kg/day = –3.65 g baseline corrected bodyweight change; P = .15).

Conclusions

Combining ETARA with SGLT2i prevents ETARA-induced fluid retention, supporting clinical studies to assess the efficacy and safety of combining zibotentan and dapagliflozin in individuals with CKD.
Mitogen-induced defective mitosis transforms neural progenitor cells
Authors: Omairi Hiba K , Grisdale Cameron J , Meode Mathieu , Bohm Alexandra K , Black Sophie , Adam Nancy J , Chapman Cassidy P , Maroilley Tatiana , Kelly John J , Tarailo-Graovac Maja , Jones Steven J M , Blough Michael D , Cairncross John Gregory
Published: April 2023

Background

Chromosome instability (CIN) with recurrent copy number alterations is a feature of many solid tumors, including glioblastoma (GBM), yet the genes that regulate cell division are rarely mutated in cancers. Here, we show that the brain-abundant mitogen, platelet-derived growth factor-A (PDGFA) fails to induce the expression of kinetochore and spindle assembly checkpoint genes leading to defective mitosis in neural progenitor cells (NPCs).

Methods

Using a recently reported in vitro model of the initiation of high-grade gliomas from murine NPCs, we investigated the immediate effects of PDGFA exposure on the nuclear and mitotic phenotypes and patterns of gene and protein expression in NPCs, a putative GBM cell of origin.

Results

NPCs divided abnormally in defined media containing PDGFA with P53-dependent effects. In wild-type cells, defective mitosis was associated with P53 activation and cell death, but in some null cells, defective mitosis was tolerated. Surviving cells had unstable genomes and proliferated in the presence of PDGFA accumulating random and clonal chromosomal rearrangements. The outcome of this process was a population of tumorigenic NPCs with recurrent gains and losses of chromosomal regions that were syntenic to those recurrently gained and lost in human GBM. By stimulating proliferation without setting the stage for successful mitosis, PDGFA-transformed NPCs lacking P53 function.

Conclusions

Our work describes a mechanism of transformation of NPCs by a brain-associated mitogen, raising the possibility that the unique genomic architecture of GBM is an adaptation to defective mitosis that ensures the survival of affected cells.
The “Serial Generation”
Authors: Borio Gianmario
Published: April 2023

Often praised or rejected for its technicity, serialism should not be situated only within the field of compositional techniques or through its ideological background, but rather considered as an attitude toward composition that involved a great number of composers born in the 1920s. A comparative reading of philological studies and of the sources related to the compositional process sheds light on the operational horizon of the “serial generation” that goes beyond the stylistic peculiarities of each one of its members. In order to substantiate this hypothesis, this chapter shows that these composers elevated music analysis and theoretical thinking to permanent components of their creativity, which can be observed in both the editorial and analytical stakes of their working method. Finally, the chapter demonstrates that the new listening experience was an essential part of their aesthetic project.
An artificial intelligence-powered, patient-centric digital tool for self-management of chronic pain: a prospective, multicenter clinical trial
Authors: Barreveld Antje M , Rosén Klement Maria L , Cheung Sophia , Axelsson Ulrika , Basem Jade I , Reddy Anika S , Borrebaeck Carl A K , Mehta Neel
Published: April 2023

Objective

To investigate how a behavioral health, artificial intelligence (AI)-powered, digital self-management tool affects the daily functions in adults with chronic back and neck pain.

Design

Eligible subjects were enrolled in a 12-week prospective, multicenter, single-arm, open-label study and instructed to use the digital coach daily. Primary outcome was a change in Patient-Reported Outcomes Measurement Information Systems (PROMIS) scores for pain interference. Secondary outcomes were changes in PROMIS physical function, anxiety, depression, pain intensity scores and pain catastrophizing scale (PCS) scores.

Methods

Subjects logged daily activities, using PainDrainerTM, and data analyzed by the AI engine. Questionnaire and web-based data were collected at 6 and 12 weeks and compared to subjects’ baseline.

Results

Subjects completed the 6- (n = 41) and 12-week (n = 34) questionnaires. A statistically significant Minimal Important Difference (MID) for pain interference was demonstrated in 57.5% of the subjects. Similarly, MID for physical function was demonstrated in 72.5% of the subjects. A pre- to post-intervention improvement in depression score was also statistically significant, observed in 100% of subjects, as was the improvement in anxiety scores, evident in 81.3% of the subjects. PCS mean scores was also significantly decreased at 12 weeks.

Conclusion

Chronic pain self-management, using an AI-powered, digital coach anchored in behavioral health principles significantly improved subjects’ pain interference, physical function, depression, anxiety, and pain catastrophizing over the 12-week study period.
Problematic technology use and sleep quality in young adulthood: novel insights from a nationally representative twin study
Authors: Madrid-Valero Juan J , Matthews Timothy , Barclay Nicola L , Odgers Candice L , Moffitt Terrie E , Caspi Avshalom , Arseneault Louise , Gregory Alice M
Published: April 2023

Study Objectives

Digital technology use is associated with poor sleep quality in adolescence and young adulthood although research findings have been mixed. No studies have addressed the association between the two using a genetically informative twin design which could extend our understanding of the etiology of this relationship. This study aimed to test: (1) the association between adolescents’ perceived problematic use of digital technology and poor sleep quality, (2) whether the association between problematic use of technology and poor sleep quality remains after controlling for familial factors, and (3) genetic and environmental influences on the association between problematic use of technology and poor sleep quality.

Methods

Participants were 2232 study members (18-year-old twins) of the Environmental Risk (E-Risk) Longitudinal Twin Study. The sample was 48.9% male, 90% white, and 55.6% monozygotic. We conducted regression and twin difference analyses and fitted twin models.

Results

Twin differences for problematic use of technology were associated with differences for poor sleep quality in the whole sample (p < 0.001; B = 0.15) and also when we limited the analyses to identical twins only (p < 0.001; B = 0.21). We observed a substantial genetic correlation between problematic use of technology and sleep quality (rA = 0.31), whereas the environmental correlation was lower (rE = 0.16).

Conclusions

Adolescent reported problematic use of digital technology is associated with poor sleep quality—even after controlling for familial factors including genetic confounds. Our results suggest that the association between adolescents’ sleep and problematic digital technology use is not accounted for by shared genetic liability or familial factors but could reflect a causal association. This robust association needs to be examined in future research designed to test causal associations.
Pain Management Interventions for the Treatment of Chronic Low Back Pain
Authors: Mekhail Nagy , Eldabe Sam , Templeton Erin , Costandi Shrif , Rosenquist Richard
Published: April 2023

Objective:

Determine the relative effectiveness and safety profiles of percutaneous and minimally invasive interventions for chronic low back pain.

Methods:

A systematic search was performed for randomized controlled trials published in the past 20 years reporting on radiofrequency ablation of the basivertebral, disk annulus and facet nerve structures, steroid injection of the disk, facet joint, and medial branch, biological therapies, and multifidus muscle stimulation. Outcomes evaluated included Visual Analog Scale (VAS) pain scores, Oswestry Disability Index (ODI) scores, quality of life (SF-36 and EQ-5D) scores, and serious adverse event (SAE) rates. Basivertebral nerve (BVN) ablation was chosen as the subject of comparison to all other therapies using a random-effects meta-analysis.

Results:

Twenty-seven studies were included. BVN ablation was found to provide statistically significant improvements in VAS and ODI scores for 6-, 12- and 24-month follow-up (P≤0.05). Biological therapy and multifidus muscle stimulation were the only 2 treatments with both VAS and ODI outcomes not significantly different from BVN ablation at 6-, 12-, and 24-month follow-up. All outcomes found to be statistically significant represented inferior results to those of BVN ablation. Insufficient data precluded meaningful comparisons of SF-36 and EQ-5D scores. The SAE rates for all therapies and all reported time points were not significantly different from BVN ablation except for biological therapy and multifidus muscle stimulation at the 6-month follow-up.

Conclusions:

BVN ablation, biological therapy, and multifidus stimulation all provide significant, durable improvements in both pain and disability compared with other interventions, which provided only short-term pain relief. Studies on BVN ablation reported no SAEs, a significantly better result than for studies of biological therapy and multifidus stimulation.
Human leucocyte antigen-B27 testing in clinical practice: a global perspective
Authors: Ziade Nelly
Published: April 2023

Purpose of review

The association between human leucocyte antigen (HLA)-B27 and spondyloarthritis (SpA) was described half a century ago. New insights about pathophysiologic pathways and their role in bone formation were reported in recent years and will be discussed in this review.

Recent findings

There is a considerable variation in the association between HLA-B27 and SpA across the globe, with the strongest association reported in populations of Northern European and Asian descent and the lowest in the Middle East and Africa. Other genes are also involved in disease susceptibility, highlighting the importance of newly proposed weighted genetic scores to support the diagnosis. On the global level, the interaction between genetic background and gut dysbiosis seems critical for disease predisposition. As for the individual patient, the presence of HLA-B27 can have a significant influence on SpA diagnosis and disease phenotype. More importantly, new studies suggested a role for HLA-B27 in radiographic damage in the sacroiliac joints and the progression of bone formation in the spine.

Findings in recent years have enhanced our understanding of the role of HLA-B27 in the pathophysiology and in disease-related bone formation in SpA, which may pave the way for new therapeutic targets.
Minimizing Surgeon Radiation Exposure During Operative Treatment of Pediatric Supracondylar Humerus Fractures
Authors: Montgomery Blake K. , Cidambi Emily O. , Birch Craig M. , Wang Kemble , Miller Patricia E. , Kim Don-Soo , Shore Benjamin J.
Published: April 2023

Background:

Orthopaedic surgeons are exposed to high levels of radiation, which may lead to higher rates of cancer among orthopaedic surgeons. There are a series of techniques currently practiced to pin supracondylar humerus fractures including pinning the arm on the C-arm itself, using a plexiglass rectangle or a graphite floating arm board; however, the variation in radiation exposure to the surgeon is unknown. We aimed to determine how the position of the C-arm affects radiation exposure to the surgeon during the treatment of a pediatric supracondylar humerus fracture.

Material and Methods:

A simulated operating room was created to simulate a closed reduction and percutaneous pinning of a supracondylar humerus fracture. A phantom model was used to simulate the patient’s arm. We assessed performing the procedure with the arm on plexiglass, graphite, or on top of the C-arm image receptor. The C-arm was positioned either with the source down and image receptor up (standard position) or with the source up and image receptor down (inverted position). Radiation exposure was recorded from levels corresponding to the surgeon’s head, midline, and groin. The estimated effective dose equivalent was calculated to account for the varying radiation sensitivity of different organs.

Results:

We found the effective dose equivalent, or the overall body damage from radiation, was 5.4 to 7.8% higher than the surgeon when the C-arm was in the inverted position (source up, image receptor down). We did not find any differences in radiation exposure to the surgeon when the arm was supported on plexiglass versus graphite.

Conclusion:

The C-arm positioned in the standard fashion exposes the surgeon to less damaging radiation. Therefore, when the surgeon is standing, we recommend using the C-arm in the standard position.

Clinical Relevance:

Orthopaedic surgeons who stand should use the C-arm in the standard position to pin supracondylar humerus fractures to lower the risk of ionizing radiation exposure.
ADAR1 affects gastric cancer cell metastasis and reverses cisplatin resistance through AZIN1
Authors: Wang Honghong , Yang Lina , Liu Rui , He Haiyan , Zhang Miao , Xu Yuanyi
Published: April 2023

Adenosine deaminases acting on RNA1 (ADAR1) are involved in the occurrence and development of cancers. Although the role of ADAR1 in gastric cancer metastasis has been reported, the role of ADAR1 in the mechanism of cisplatin resistance in gastric cancer is not clear. In this study, human gastric cancer tissue specimens were used to construct cisplatin-resistant gastric cancer cells; the results indicated that the mechanism underlying the inhibition of gastric cancer metastasis and reversal of cisplatin-resistant gastric cancer by ADAR1 inhibits gastric cancer occurs through the antizyme inhibitor 1 (AZIN1) pathway. We assessed ADAR1 and AZIN1 expression in the tissues of patients with low to moderately differentiated gastric cancer. Gastric cancer cells (human gastric adenocarcinoma cell line [AGS] and HGC-27 cells) and gastric cancer cisplatin-resistant cells (AGSCDDP and HGC-27CDDP) were selected, and the protein expression of ADAR1 and AZIN1 was detected using immunocytochemistry and immunocytofluorescence. The effects of ADAR1 small interfering RNA (siRNA) on the invasion, migration and proliferation of cisplatin-resistant gastric cancer cells were investigated. Western blot assays were used to assess the protein expression levels of ADAR1, AZIN1 and epithelial–mesenchymal transition (EMT)-related markers. In-vivo experiments, a subcutaneous tumor formation model of nude mice was established, and the effects of ADAR1 on tumor growth and AZIN1 expression level were detected by hematoxylin and eosin, immunohistochemistry and western blot. The expression of ADAR1 and AZIN1 in human gastric cancer tissue was significantly higher than that in paracancerous tissues. The colocalization of ADAR1, AZIN1 and E-cadherin expression in immunofluorescence assays indicated a significant correlation between the three. In in-vitro experiments, ADAR1 knockout not only reduced the invasion and migration ability of AGS and HGC-27 cells but also reduced that of cisplatin-resistant gastric cancer cells. ADAR1 siRNA inhibited the proliferation and decreased the colony number of cisplatin-resistant gastric cancer cells. ADAR1 siRNA decreased the expression of AZIN1 and EMT-related marker proteins (vimentin, N-cadherin, β-catenin, MMP9, MMP2 and TWIST). The effect of ADAR1 siRNA combined with AZIN1 siRNA was more significant. In-vivo, the knockdown of ADAR1 significantly inhibited tumor growth and AZIN1 expression. ADAR1 and AZIN1 are antimetastatic targets of gastric cancer, and AZIN1 is a downstream regulatory target of ADAR1. ADAR1 knockout can inhibit the metastasis of gastric cancer cells and reverse the cisplatin resistance of gastric cancer cells by downregulating the expression of AZIN1, potentially resulting in increased treatment efficacy.
Enhancing the Anti-tumor Potency of a Novel Siglec-15 Antibody by Engineering its Fc-mediated Effector Functions
Authors: Ding Huandi , Yao Bing , Ci Lei , Feng Jing , Ouyang Pingkai , Chen Guoguang , Hui Xiwu , Zhou Demin
Published: April 2023

Siglec-15, an inhibitory immune checkpoint, is an emerging target in cancer immunotherapy. Blocking the function of Siglec-15 is an excellent strategy for cancer treatment and antibody blockade has been used to target Siglec-15. However, whether Fc-mediated effector functions contribute to the therapeutic effect of antibodies remains unclear. Herein, we generated a monoclonal antibody, 1-15D1, which had a high binding affinity with Siglec-15 and strongly activated T-cell immune response in vitro. Subsequently, the Fc-mediated effector functions of 1-15D1 were explored in a Siglec-15 humanized mouse model, and further improvement in antitumor efficacy was observed in the mouse IgG2a isotype group. Thus, we demonstrate that the antitumor effects of 1-15D1 were mediated via multiple factors. In addition to the T-cell immune response, 2 novel mechanisms were explored, including the internalization of the cell surface Siglec-15 and Fc-mediated effector functions. In conclusion, our studies not only provide a potential agent for the improvement of cancer immunotherapy but also suggest that a specific role of Fc-mediated immune regulation may improve the therapeutic potency of Siglec-15 monoclonal antibody.
Malondialdehyde levels in diabetic retinopathy patients: a systematic review and meta-analysis
Authors: Jiang Fanwen , Zhou Lin , Zhang Chun , Jiang Hui , Xu Zhuping
Published: April 2023

Background:

It remains unclear whether circulating malondialdehyde (MDA) levels change in people with diabetic retinopathy (DR). This systematic review compared circulating MDA levels in diabetic people with and without DR.

Methods:

The authors searched PubMed, Medline (Ovid), Embase (Ovid), and Web of Science for case-control studies conducted before May 2022 in English that compared circulating MDA levels in people with and without DR. The following MeSH search terms were used: (“malondialdehyde” or “thiobarbituric acid reactive substances (TBARS)” or “lipid peroxidation” or “oxidative stress”) and “diabetic retinopathy.” Newcastle–Ottawa Quality Assessment Scale was used to evaluate the quality of the included studies. Random-effects pairwise meta-analysis pooled the effect size with standardized mean difference (SMD) and 95% confidence intervals (CIs).

Results:

This meta-analysis included 29 case-control studies with 1680 people with DR and 1799 people with diabetes but not DR. Compared to people without DR, the circulating MDA levels were higher in those with DR (SMD, 0.897; 95% CI, 0.631 to 1.162; P < 0.001). The study did not identify credible subgroup effects or publication bias and the sensitivity analysis confirmed the robustness of the study.

Conclusions:

Circulating MDA levels are higher in people with DR compared to those without. Future comparative studies that use more specific methods are required to draw firm conclusions.

Registration:

PROSPERO; https://www.crd.york.ac.uk/PROSPERO/; No. CRD42022352640.
COL1A1–PDGFB Fusion Gene Detection Through Bulk RNA-Seq and Transcriptomic Features of Dermatofibrosarcoma Protuberans
Authors: Peng Rui , Zhang Guohong , Li Hang
Published: April 2023

BACKGROUND

Dermatofibrosarcoma protuberans (DFSP) is a cutaneous sarcoma with obscure origin and multidirectional differentiation. Application of RNA-Seq in the detection of COL1A1–PDGFB is still at early stages.

OBJECTIVE

We aim to test the efficacy of fusion gene detection using bulk RNA-Seq in DFSPs, explore altered molecular pathways and biological processes for evidences of tumor origin and cell identity shift.

MATERIALS AND METHODS

Dermatofibrosarcoma protuberans and normal dermis samples were acquired for RNA-Seq. Fusion gene detection was performed using STAR-Fusion. RNA-Seq 2G yielded differentially expressed genes. Altered pathways, key gene ontology terms, and similar cell/tissue types were identified with gene set enrichment analysis. xCell was used for cell types enrichment analysis.

RESULTS

28/30 CD34(+) cases were positive for COL1A1–PDGFB. 406 upregulated and 543 downregulated genes were determined. Among the top 10 upregulated genes, 6 had neural distribution, function, or disease correlation. The upregulated genes were related to synapse, trans-synaptic signaling, neural development, and extracellular matrix. Similarities between DFSP and nervous system components were highlighted, with fibroblast cellular abundancy increased during xCell analysis.

CONCLUSION

Bulk RNA-Seq provided with high detection rate of COL1A1-PDGFB. Dermatofibrosarcoma protuberans showed fibroblastic activity and neural features, which validated DFSP's fibroblast origin and tendency of neural differentiation.
The Lions Eye Bank of Western Australia: 35 Years of Eye Banking (1986–2021)
Authors: Kezic Jelena M. , Buckland Lisa , Wiffen Steven
Published: April 2023

Purpose:

The purpose of this study was to review the trends in preparation, storage, and usage of donor corneal tissue from 35 years of eye banking at the Lions Eye Bank of Western Australia (LEBWA).

Methods:

Donor and recipient records for the period July 1986 to July 2021 were evaluated with relation to donor demographics, cause of death, storage medium, corneal utilization, type of corneal graft, and indication for graft.

Results:

Six thousand two hundred nine eyes from 3328 donors were retrieved in the 35-year period reviewed. Sixty-six percent of eye donors were male, and 33% were female. The median age of donor was 61 years (2–98 years). The most frequent cause of donor death was a cardiac event, followed by intracerebral hemorrhage and malignancy. A total of 5219 corneal transplants were performed, with a corneal utilization rate of 84%. Storage of corneal tissue was primarily in Optisol-GS until 2010, when organ culture medium was introduced. Of 5219 recipients, 52% were male and 47% were female. The median recipient age was 63 years (1–98 years). Penetrating keratoplasty was the most common surgery performed over the 35-year period, followed by endothelial keratoplasty. The most common indications for grafts were ectasia/thinning, repeat corneal transplants, endothelial dystrophies, and postcataract surgery edema.

Conclusions:

We present trends in the acquisition and utilization of corneal tissue across 35 years at LEBWA. The most significant changes over this period include methods of corneal storage and advances in surgical techniques that has led to a greater usage of endothelial grafts.
Three-dimensional Medical Printing and Associated Legal Issues in Plastic Surgery: A Scoping Review
Authors: Knoedler Leonard , Knoedler Samuel , Kauke-Navarro Martin , Knoedler Christoph , Hoefer Simon , Baecher Helena , Gassner Ulrich M. , Machens Hans-Guenther , Prantl Lukas , Panayi Adriana C.
Published: April 2023

Three-dimensional printing (3DP) represents an emerging field of surgery. 3DP can facilitate the plastic surgeon’s workflow, including preoperative planning, intraoperative assistance, and postoperative follow-up. The broad clinical application spectrum stands in contrast to the paucity of research on the legal framework of 3DP. This imbalance poses a potential risk for medical malpractice lawsuits. To address this knowledge gap, we aimed to summarize the current body of legal literature on medical 3DP in the US legal system. By combining the promising clinical use of 3DP with its current legal regulations, plastic surgeons can enhance patient safety and outcomes.
Mincle-GSDMD-mediated release of IL-1β small extracellular vesicles from hepatic macrophages in ethanol-induced liver injury
Authors: Zhang Quanri , Liu Weiwei , Bulek Katarzyna , Wang Han , McMullen Megan R. , Wu Xiaoqin , Welch Nicole , Zhang Renliang , Dasarathy Jaividhya , Dasarathy Srinivasan , Nagy Laura E. , Li Xiaoxia
Published: April 2023

Background:

Macrophage-inducible C-type lectin (Mincle) is expressed on hepatic macrophages and senses ethanol (EtOH)-induced danger signals released from dying hepatocytes and promotes IL-1β production. However, it remains unclear what and how EtOH-induced Mincle ligands activate downstream signaling events to mediate IL-1β release and contribute to alcohol-associated liver disease (ALD). In this study, we investigated the association of circulating β-glucosylceramide (β-GluCer), an endogenous Mincle ligand, with severity of ALD and examined the mechanism by which β-GluCer engages Mincle on hepatic macrophages to release IL-1β in the absence of cell death and exacerbates ALD.

Method and Results:

Concentrations of β-GluCer were increased in serum of patients with severe AH and correlated with disease severity. Challenge of hepatic macrophages with lipopolysaccharide and β-GluCer induced formation of a Mincle and Gsdmd-dependent secretory complex containing chaperoned full-length gasdermin D (Hsp90-CDC37-NEDD4) with polyubiquitinated pro-IL-1β and components of the Caspase 8-NLRP3 inflammasome loaded as cargo in small extracellular vesicles (sEVs). Gao-binge EtOH exposure to wild-type, but not Mincle

−/−
and Gsdmd

−/−
, mice increased release of IL-1β-containing sEVs from liver explant cultures. Myeloid-specific deletion of Gsdmd similarly decreased the formation of sEVs by liver explant cultures and protected mice from EtOH-induced liver injury. sEVs collected from EtOH-fed wild-type, but not Gsdmd

−/−
, mice promoted injury of cultured hepatocytes and, when injected into wild-type mice, aggravated Gao-binge EtOH-induced liver injury.

Conclusion:

β-GluCer functions as a danger-associated molecular pattern activating Mincle-dependent gasdermin D-mediated formation and release of IL-1β-containing sEVs, which in turn exacerbate hepatocyte cell death and contribute to the pathogenesis of ALD.
Integrated hepatology and addiction care for inpatients with alcohol use disorder improves outcomes: a prospective study
Authors: Mahle Rachael , McLean Diaz Paige , Marshall Chantelle , Goodman Russell P. , Schaefer Esperance , Luther Jay
Published: April 2023

Background:

Growing literature highlights the need to integrate hepatology and addiction care to improve outcomes for patients with alcohol use disorder and alcohol-associated liver disease. However, prospective data for this approach are lacking.

Methods:

We prospectively examined the efficacy of an integrated hepatology and addiction medicine approach on alcohol use and hepatology outcomes in inpatients with alcohol use disorder.

Findings:

An integrated approach improved the uptake of medical alcohol therapy, hepatic fibrosis screening, and viral hepatitis vaccination compared with a historical control of patients who received addiction medicine care alone. There were no differences in the rates of early alcohol remission. The integration of hepatology and addiction care may improve outcomes in patients with alcohol use disorder.