bluuebunny/crossref_metadata_2025 huggingface dataset:
Spectroscopic study of Herbig Ae/Be stars in the Galactic anti-centre region from LAMOST DR5
Authors: Nidhi S , Mathew Blesson , Shridharan B , Arun R , Anusha R , Kartha Sreeja S
Published: July 2023

We study a sample of 119 Herbig Ae/Be stars in the Galactic anti-centre direction using the spectroscopic data from large sky area multi-object fiber spectroscopic telescope survey program. Emission lines of hydrogen belonging to the Balmer and Paschen series, and metallic lines of species such as Fe ii, O i, Ca ii triplet are identified. A moderate correlation is observed between the emission strengths of  Hα and Fe ii 5169 Å, suggesting a possible common emission region for Fe ii lines and one of the components of  Hα. We explored a technique for the extinction correction of the HAeBe stars using diffuse interstellar bands present in the spectrum. We estimated the stellar parameters such as age and mass of these HAeBe stars, which are found to be in the range 0.1–10 Myr and 1.5–10 M ⊙, respectively. We found that the mass accretion rate of the HAeBe stars in the Galactic anti-centre direction follows the relation $\dot{M}_{\mathrm{ acc}}$ ∝ $M_{*}^{3.12^{+0.21}_{-0.34}}$, which is similar to the relation derived for HAeBe stars in other regions of the Galaxy. The mass accretion rate of HAeBe stars is found to have a functional form of $\dot{M}_{\mathrm{ acc}} \propto t^{-1.1\, \pm\, 0.2}$ with age, in agreement with previous studies.
On the Tremaine–Weinberg method: how much can we trust gas tracers to measure pattern speeds?
Authors: Borodina Olga , Williams Thomas G , Sormani Mattia C , Meidt Sharon , Schinnerer Eva
Published: July 2023

Pattern speeds are a fundamental parameter of the dynamical features (e.g. bars, spiral arms) of a galaxy, setting resonance locations. Pattern speeds are not directly observable, so the Tremaine–Weinberg (TW) method has become the most common method used to measure them in galaxies. However, it has not been tested properly whether this method can straightforwardly be applied to gas tracers, despite this being widely done in the literature. When applied to observations, the TW method may return invalid results, which are difficult to diagnose due to a lack of ground truth for comparison. Although some works applying the TW method to simulated galaxies exist, only stellar populations have been tested. Therefore, here we explore the applicability of the TW method for gas tracers, by applying it to hydrodynamical simulations of galaxies, where we know the true value of the bar pattern speed. We perform some simple tests to see if the TW method has a physically reasonable output. We add different kinds of uncertainties (e.g. in position angle or flux) to the data to mock observational errors based on the magnitude of uncertainty present in the observations. Secondly, we test the method on 3D simulations with chemical networks. We show that in general, applying TW to observations of gas will not recover the true pattern speed. These results have implications for many ‘pattern speeds’ reported in the literature, and based on these tests we also give some best practices for measuring pattern speeds using gas tracers going forwards.
Discovery of a radio jet in the Cloverleaf quasar at z = 2.56
Authors: Zhang Lei , Zhang Zhi-Yu , Nightingale James W , Zou Ze-Cheng , Cao Xiaoyue , Tsai Chao-Wei , Yang Chentao , Shi Yong , Wang Junzhi , Xu Dandan , Lin Ling-Rui , Zhou Jing , Li Ran
Published: July 2023

The fast growth of supermassive black holes and their feedback to the host galaxies play an important role in regulating the evolution of galaxies, especially in the early Universe. However, due to cosmological dimming and the limited angular resolution of most observations, it is difficult to resolve the feedback from the active galactic nuclei (AGNs) to their host galaxies. Gravitational lensing, for its magnification, provides a powerful tool to spatially differentiate emission originating from AGN and host galaxy at high-redshifts. Here, we report a discovery of a jet-like radio structure in a strongly lensed starburst quasar, H1413+117 or Cloverleaf at redshift z = 2.56, based on observational data at optical, submillimetre, and radio wavelengths. With both parametric and non-parametric lens models and with reconstructed images in the source plane, we find a well-separated, kpc-scaled, single-sided radio jet located at projected ${\sim }1.2\, \mathrm{kpc}$ to the north-west of the host galaxy in the source plane. This could indicate the co-existence of feedback from the AGN by both wind and jet in the Cloverleaf quasar.
The incidence of AGN in galaxies with different stellar population ages
Authors: Ni Q , Aird J , Merloni A , Birchall K L , Buchner J , Salvato M , Yang G
Published: July 2023

It has been argued that recycled gas from stellar mass loss in galaxies might serve as an important fuelling source for black holes (BHs) in their centres. Utilizing spectroscopic samples of galaxies from the Sloan Digital Sky Survey (SDSS) at z = 0–0.35 and the Large Early Galaxy Astrophysics Census (LEGA-C) survey at z = 0.6–1 that have X-ray coverage from XMM–Newton or Chandra, we test this stellar mass loss fuelling scenario by investigating how AGN activity and BH growth vary with the break strength at 4000 Å, $\rm D_{n}4000$ (which is closely related to the age of stellar populations), as younger galaxies are considered to have higher stellar mass loss rates. We found that when controlling for host-galaxy properties, the fraction of log LX/M⋆ >32 (which roughly corresponds to Eddington ratios ≳ 1 per cent) AGN and sample-averaged black hole accretion rate ($\rm \overline{BHAR}$) decrease with $\rm D_{n}4000$ among $\rm D_{n}4000$ ≲ 1.9 galaxies, suggesting a higher level of AGN activity among younger galaxies, which supports the stellar mass loss fuelling scenario. For the oldest and most massive galaxies at z = 0–0.35, this decreasing trend is not present anymore. We found that, among these most massive galaxies at low redshift, the fraction of low specific-accretion-rate (31 < log LX/M⋆ < 32) AGNs increases with $\rm D_{n}4000$, which may be associated with additional fuelling from hot halo gas and/or enhanced accretion capability.
Far beyond the Sun − II. Probing the stellar magnetism of the young Sun
ι
Horologii from the photosphere to its corona
Authors: Amazo-Gómez E M , Alvarado-Gómez J D , Poppenhäger K , Hussain G A J , Wood B E , Drake J J , do Nascimento J-D , Anthony F , Sanz-Forcada J , Stelzer B , Del Sordo F , Damasso M , Redfield S , Donati J F , König P C , Hébrard G , Miles-Páez P A
Published: July 2023

A comprehensive multiwavelength campaign has been carried out to probe stellar activity and variability in the young Sun-like star ι-Horologii. We present the results from long-term spectropolarimetric monitoring of the system by using the ultra-stable spectropolarimeter/velocimeter HARPS at the ESO 3.6-m telescope. Additionally, we included high-precision photometry from the NASA Transiting Exoplanet Survey Satellite (TESS) and observations in the far- and near-ultraviolet spectral regions using the STIS instrument on the NASA/ESA Hubble Space Telescope (HST). The high-quality data set allows a robust characterization of the star’s rotation period, as well as a probe of the variability using a range of spectroscopic and photometric activity proxies. By analysing the gradient of the power spectra (GPS) in the TESS light curves, we constrained the faculae-to-spot driver ratio ($\rm S_{fac}/S_{spot}$) to 0.510 ± 0.023, which indicates that the stellar surface is spot dominated during the time of the observations. We compared the photospheric activity properties derived from the GPS method with a magnetic field map of the star derived using Zeeman–Doppler imaging (ZDI) from simultaneous spectropolarimetric data for the first time. Different stellar activity proxies enable a more complete interpretation of the observed variability. For example, we observed enhanced emission in the HST transition line diagnostics C iv and C iii, suggesting a flaring event. From the analysis of TESS data acquired simultaneously with the HST data, we investigate the photometric variability at the precise moment that the emission increased and derive correlations between different observables, probing the star from its photosphere to its corona.
Gamma-ray emission from spectrally resolved cosmic rays in galaxies
Authors: Werhahn Maria , Girichidis Philipp , Pfrommer Christoph , Whittingham Joseph
Published: July 2023

Cosmic rays (CRs) are ubiquitous in the interstellar medium (ISM) of nearby galaxies, but many of their properties are not well-constrained. Gamma-ray observations provide a powerful tool in this respect, allowing us to constrain both the interaction of CR protons with the ISM and their transport properties. To help better understand the link between observational signatures and CR physics, we use a series of magneto-hydrodynamical arepo simulations of isolated galaxies performed using spectrally resolved CR transport in every computational cell, with subsequent gamma-ray emission calculated using the Crayon + (Cosmic RAY emissiON) code. In each of our simulated haloes, modelling the energy-dependent spatial diffusion of CRs leads to a more extended distribution of high-energy (~100 GeV) gamma rays compared to that predicted by a ‘grey’ steady-state model, which is especially visible in the corresponding emission maps and radial profiles. Despite this, the total gamma-ray spectra can often be well approximated by the steady-state model, although recovering the same spectral index typically requires a minor variation of the energy dependence of the diffusion coefficient. Our simulations reproduce the observed shapes of the gamma-ray spectra of nearby star-forming galaxies and also match recent observations of the far infrared–gamma-ray relation. We find, however, that the spectrally resolved model yields marginally smaller luminosities for lower star formation rates compared to grey simulations of CRs. Our work highlights the importance of modelling spectrally resolved CR transport for an accurate prediction of spatially resolved high-energy gamma-ray emission, as will be probed by the upcoming Cherenkov Telescope Array observatory.
Results of the first nationwide cohort study of outcomes in dialysis and kidney transplant patients before and after vaccination for COVID-19
Authors: Wijkström Julia , Caldinelli Aurora , Bruchfeld Annette , Nowak Alexandra , Artborg Angelica , Stendahl Maria , Segelmark Mårten , Lindholm Bengt , Bellocco Rino , Rydell Helena , Evans Marie
Published: July 2023

Background

Patients on kidney replacement therapy (KRT) have been identified as a vulnerable group during the coronavirus disease 2019 (COVID-19) pandemic. This study reports the outcomes of COVID-19 in KRT patients in Sweden, a country where patients on KRT were prioritized early in the vaccination campaign.

Methods

Patients on KRT between January 2019 and December 2021 in the Swedish Renal Registry were included. Data were linked to national healthcare registries. The primary outcome was monthly all-cause mortality over 3 years of follow-up. The secondary outcomes were monthly COVID-19-related deaths and hospitalizations. The results were compared with the general population using standardized mortality ratios. The difference in risk for COVID-19-related outcomes between dialysis and kidney transplant recipients (KTRs) was assessed in multivariable logistic regression models before and after vaccinations started.

Results

On 1 January 2020, there were 4097 patients on dialysis (median age 70 years) and 5905 KTRs (median age 58 years). Between March 2020 and February 2021, mean all-cause mortality rates increased by 10% (from 720 to 804 deaths) and 22% (from 158 to 206 deaths) in dialysis and KTRs, respectively, compared with the same period in 2019. After vaccinations started, all-cause mortality rates during the third wave (April 2021) returned to pre-COVID-19 mortality rates among dialysis patients, while mortality rates remained increased among transplant recipients. Dialysis patients had a higher risk for COVID-19 hospitalizations and death before vaccinations started {adjusted odds ratio [aOR] 2.1 [95% confidence interval (CI) 1.7–2.5]} but a lower risk after vaccination [aOR 0.5 (95% CI 0.4–0.7)] compared with KTRs.

Conclusions

The COVID-19 pandemic in Sweden resulted in increased mortality and hospitalization rates among KRT patients. After vaccinations started, a distinct reduction in hospitalization and mortality rates was observed among dialysis patients, but not in KTRs. Early and prioritized vaccinations of KRT patients in Sweden probably saved many lives.
Chronic kidney disease: the missing concept in the 2019 EULAR/ERA-EDTA recommendations for lupus nephritis
Authors: Rojas-Rivera Jorge E , Bakkaloglu Sevcan A , Bolignano Davide , Nistor Ionut , Sarafidis Pantelis A , Stoumpos Sokratis , Cozzolino Mario Gennaro , Ortiz Alberto
Published: July 2023

Chronic kidney disease (CKD) is diagnosed when glomerular filtration rate (GFR) falls below 60 ml/min/1.73 m2 or urinary albumin:creatinine ratio (UACR) reaches ≥30 mg/g, as these two thresholds indicate a higher risk of adverse health outcomes, including cardiovascular mortality. CKD is classified as mild, moderate or severe, based on GFR and UACR values, and the latter two classifications convey a high or very high cardiovascular risk, respectively. Additionally, CKD can be diagnosed based on abnormalities detected by histology or imaging. Lupus nephritis (LN) is a cause of CKD. Despite the high cardiovascular mortality of patients with LN, neither albuminuria nor CKD are discussed in the 2019 European League Against Rheumatism (EULAR)/European Renal Association–European Dialysis and Transplant Association recommendations for the management of LN or the more recent 2022 EULAR recommendations for cardiovascular risk management in rheumatic and musculoskeletal diseases. Indeed, the proteinuria target values discussed in the recommendations may be present in patients with severe CKD and a very high cardiovascular risk who may benefit from guidance detailed in the 2021 European Society of Cardiology guidelines on cardiovascular disease prevention in clinical practice. We propose that the recommendations should move from a conceptual framework of LN as an entity separate from CKD to a framework in which LN is considered a cause of CKD and evidence generated from large CKD trials applies unless demonstrated otherwise.
Interpretation of GFR slope in untreated and treated adult Fabry patients
Authors: Pisani Antonio , Pieruzzi Federico , Cirami Calogero Lino , Riccio Eleonora , Mignani Renzo
Published: July 2023

Nephropathy is one of the main features of Fabry disease (FD) that leads, in untreated patients with classical mutations, to end-stage renal disease (ESRD) from the third to the fifth decade of life. The availability of a specific treatment modified the natural history of FD; in particular, it was widely reported that enzyme replacement therapy (ERT) is able to slow the progression of the disease. Regarding Fabry nephropathy, several reports have documented an elevated estimated glomerular filtration rate (eGFR) slope in untreated patients as expression of a rapid disease progression towards ESRD. Otherwise, the prompt start of treatment may be beneficial in stabilizing renal function or slowing its decline. Therefore, based on data in the literature about the effects of ERT on eGFR decline and on the evidence supporting the role of eGFR slope as a surrogate endpoint for chronic kidney disease progression, we suggest, in this ‘Expert Opinion’, that a treatment should be defined effective when eGFR decline is <1 ml/min/1.73 m2/year and not effective when eGFR loss remains ≥3 ml/min/1.73 m2/year (≥2.5 ml/min/1.73 m2/year in females). Moreover, practical clinical recommendations and guidance for Fabry patients suggests that a change in treatment may be appropriate if individualized therapeutic goals are not achieved. Since a dose-dependent efficacy has been demonstrated for ERT, we suggest considering a switch to a higher dose of ERT in symptomatic adult Fabry patients (ages 18–60 years) with an eGFR of 45–90 ml/min/1.73 m2 and treated with a stable dose of ERT for at least 1 year, in which a linear negative slope of eGFR of 3 ml/min/1.73 m2/year for males (2.5 ml/min/1.73 m2/year for females) was observed.
Novel SOX10 indel mutations drive schwannomas through impaired transactivation of myelination gene programs
Authors: Williams Erik A , Ravindranathan Ajay , Gupta Rohit , Stevers Nicholas O , Suwala Abigail K , Hong Chibo , Kim Somang , Yuan Jimmy Bo , Wu Jasper , Barreto Jairo , Lucas Calixto-Hope G , Chan Emily , Pekmezci Melike , LeBoit Philip E , Mully Thaddeus , Perry Arie , Bollen Andrew , Van Ziffle Jessica , Devine W Patrick , Reddy Alyssa T , Gupta Nalin , Basnet Kristen M , Macaulay Robert J B , Malafronte Patrick , Lee Han , Yong William H , Williams Kevin Jon , Juratli Tareq A , Mata Douglas A , Huang Richard S P , Hiemenz Matthew C , Pavlick Dean C , Frampton Garrett M , Janovitz Tyler , Ross Jeffrey S , Chang Susan M , Berger Mitchel S , Jacques Line , Song Jun S , Costello Joseph F , Solomon David A
Published: July 2023

Background

Schwannomas are common peripheral nerve sheath tumors that can cause severe morbidity given their stereotypic intracranial and paraspinal locations. Similar to many solid tumors, schwannomas and other nerve sheath tumors are primarily thought to arise due to aberrant hyperactivation of the RAS growth factor signaling pathway. Here, we sought to further define the molecular pathogenesis of schwannomas.

Methods

We performed comprehensive genomic profiling on a cohort of 96 human schwannomas, as well as DNA methylation profiling on a subset. Functional studies including RNA sequencing, chromatin immunoprecipitation-DNA sequencing, electrophoretic mobility shift assay, and luciferase reporter assays were performed in a fetal glial cell model following transduction with wildtype and tumor-derived mutant isoforms of SOX10.

Results

We identified that nearly one-third of sporadic schwannomas lack alterations in known nerve sheath tumor genes and instead harbor novel recurrent in-frame insertion/deletion mutations in SOX10, which encodes a transcription factor responsible for controlling Schwann cell differentiation and myelination. SOX10 indel mutations were highly enriched in schwannomas arising from nonvestibular cranial nerves (eg facial, trigeminal, vagus) and were absent from vestibular nerve schwannomas driven by NF2 mutation. Functional studies revealed these SOX10 indel mutations have retained DNA binding capacity but impaired transactivation of glial differentiation and myelination gene programs.

Conclusions

We thus speculate that SOX10 indel mutations drive a unique subtype of schwannomas by impeding proper differentiation of immature Schwann cells.
COMPARING THE EFFICIENCY OF A REAL-TIME ARTIFICIAL INTELLIGENCE INSTRUCTOR TO HUMAN EXPERT INSTRUCTORS IN SIMULATED SURGICAL TECHNICAL SKILLS TRAINING– A RANDOMIZED CONTROLLED TRIAL
Authors: Yilmaz Recai , Bakhaidar Mohamad , Alsayegh Ahmad , Hamdan Nour Abou , Fazlollahi Ali M , Agu Chinyelum , Pachchigar Puja , Del Maestro Rolando
Published: July 2023

BTFC travel award recipient

Artificial intelligence systems provide risk-free training on realistically simulated patient cases and objective assessment of surgical technical skills. This randomized controlled study compared a real-time intelligent tutoring system in technical skills learning with human expert instructor-mediated training.

METHODS: Ninety-eight medical students performed six simulated brain tumor resections. Participants were randomly allocated into (1)no-real-time feedback, (2)real-time intelligent instruction, and (3)in- person human instruction. All students performed the first repetition without receiving feedback (baseline). Group-1 received visual feedback only after each procedure based on expert benchmarks. Group-2 was instructed by the intelligent system in real-time. After each task, the students were shown their error-video clips generated by this system alongside expert-level demonstrations on how to improve. Group-3 was instructed by human instructors during the tasks. After each task, instructors summarized the areas of improvement and demonstrated correction techniques. Participant performance was scored by the intelligent system and also by blinded experts using OSATS scores. The performance score was compared within groups and between groups to compare learning. RESULTS: Compared to baseline performance, Group-2 and Group-3 significantly improved in the performance score by the third and second repetition, respectively (p<0.01, p=0.01). The between-groups comparison demonstrated that Group-2 scored significantly higher than Group-3 in the fifth repetition (p<0.01). Group-2 achieved significantly higher OSATS scores than Group-1 in the sixth task. CONCLUSIONS: Artificial intelligence may facilitate trainee learning by providing equally or more efficient learning when compared to human instruction. These systems may aid in developing competency-based standardized curricula in surgical training.
AUTOLOGOUS PATIENT-DERIVED CAR-TS SHOW FUNCTIONAL DEFICITS AGAINST HUMAN GLIOBLASTOMA
Authors: Salim Sabra K , Shaikh Vaseem , Maich William T , Anand Alisha , Brakel Benjamin , Wei Jeffrey , Subapanditha Minomi K , Alizada Zahra , Suk Yujin , Singh Manoj , Dimitrov Vassil , Tabunshchyk Zoya , Chen Katie , Vora Parvez , Venugopal Chitra , Moffat Jason , Singh Sheila K
Published: July 2023

Glioblastoma (GBM) is the most common malignant brain tumor in adults, with a poor prognosis despite aggressive standard of care. Chimeric antigen receptor T-cell (CAR-T) therapy has shown promising results in liquid malignancies, but clinical trials in GBM targeting various tumor antigens have not shown durable clinical benefit. While this may be attributable to various tumor-intrinsic immune evasion strategies characteristic of GBM, little work has assessed whether the issue is due to the quality of the CAR-T treatment itself. Currently, CAR-Ts for GBMs and liquid malignancies are manufactured in an autologous setting in which T-cells are extracted from patients, engineered ex-vivo, and subsequently reinfused back. However, peripheral T-cells taken from untreated GBM patients have demonstrated qualitative and functional deficits, which may contribute to suboptimal treatment outcomes. Thus, we aimed to establish whether CAR-Ts generated from GBM patients would show reduced efficacy in comparison to healthy donors using our previously validated CD133 CAR-T. In this work, we show pre-treatment exhaustion and reduced survival advantage in autologous, patient-derived CD133-targeting CAR-T cell products using an orthotopic xenograft model of human GBM. To overcome the functional and logistical considerations of autologous therapy, we additionally aimed to generate an “off-the-shelf” allogeneic CD133 CAR-T. Using CRISPR gene editing technology, we generated TCR-knockout CAR-T cells with comparable pre- clinical efficacy to our autologous models. Ultimately, this work highlights the need to reassess autologous CAR-T therapy for GBM, and consider allogeneic approaches as biologically-informed therapeutic alternatives.
RE-IRRADIATION FOR RECURRENT HIGH-GRADE GLIOMA: AN ANALYSIS OF PROGNOSTIC FACTORS FOR SURVIVAL AND PREDICTORS OF RADIATION NECROSIS
Authors: Moore-Palhares Daniel , Chen Hanbo , Keith Julia , Wang Michael , Myrehaug Sten , Tseng Chia-Lin , Detsky Jay , Perry James , Lim-Fat Mary Jane , Heyn Chris , Maralani Pejman , Lipsman Nir , Das Sunit , Sahgal Arjun , Soliman Hany
Published: July 2023

Recurrent high-grade glioma (rHGG) is a heterogeneous population, and the ideal patient selection for reirradiation (re-RT) has yet to be established. This study aims to identify prognostic factors for rHGG patients treated with re-RT.

METHODS: We retrospectively reviewed consecutive adults with rHGG who underwent re-RT from 2009-2020 from our institutional database. The primary objective was overall survival (OS). The secondary outcomes included prognostic factors for early death (<6 months after re-RT) and predictors of radiation necrosis (RN). RESULTS: For the 79 patients identified, the median OS after re-RT was 9.9 months (95% CI 8.3-11.6). On multivariate analyses (MVA), re-resection at progression (HR=0.56, p=0.027), interval from primary treatment to first progression ≥16.3 months (HR=0.61, p=0.034), interval from primary treatment to re-RT ≥23.9 months (HR=0.35, p<0.001), and re-RT PTV volume <112 cc (HR=0.27, p<0.001) were prognostic for improved OS. Patients who had unmethylated-MGMT tumours (OR=12.4, p=0.034), ≥3 prior systemic treatment lines (OR=29.1, p=0.22), interval to re-RT <23.9 months (OR=9.0, p=0.039), and re-RT PTV volume ≥112 cc (OR=17.8, p=0.003) were more likely to survive <6 months. The cumulative incidence of RN was 11.4% (95% CI 4.3-18.5) at 12 months. Concurrent bevacizumab use (HR<0.001, p<0.001) and cumulative equivalent dose in 2 Gy fractions (cEQD2, a/b=2) <99 Gy2 (HR<0.001, p<0.001) were independent protective factors against RN. CONCLUSIONS: We observe favorable OS rates following re-RT and identified prognostic factors, including methylation status, that can assist in patient selection and clinical trial design. Concurrent use of bevacizumab and cEQD2 <99 Gy2 mitigates the risk of RN.
SHH PATHWAY ACTIVATION IN DEDIFFERENTIATION DURING TUMOR PROGRESSION IN MPNST
Authors: Yakubov R Y , Bunda S B , Zadeh G Z
Published: July 2023

Malignant peripheral nerve sheath tumours (MPNST) are highly aggressive sarcomas with little progress on outcomes and treatment strategies. Previous work conducted in our lab used unsupervised analyses of methylome and transcriptome profiles of 108 peripheral nerve sheath tumours to uncover two subgroups of MPNSTs that predict progression-free survival, MPNST-G1 (characterized by SHH pathway activation) and MPNST-G2 (characterized by WNT/ß-catenin/CCND1 pathway activation). Further, single nuclear RNA-sequencing revealed that MPNST-G1 and MPNST-G2 cells resemble neural crest-like and Schwann cell precursor-like cells, respectively. Purpose & Hypothesis: To examine the expression of transcription factors (TWIST1, SOX9, SNAI2, OTX2, PAX3, and PAX6) known to play canonical roles in the early neural crest cell specification in MPNST-G1 cells. We speculate that MPNST-G1 cells will display overexpression of these transcription factors compared to MPNST-G2 cells and that Sonidegib (SMO inhibitor) will revert dedifferentiation by decreasing activation of the SHH pathway.

METHODS: Dedifferentiation transcription factor expression and the effects of SMO activation and inhibition in MPNST-G1 and MPNST-G2 cells were analyzed using RT-PCR and western blotting. Alamar blue and Trypan blue assays were used to determine the effect of SMO inhibition on proliferation. RESULTS: Compared to MPNST-G2 cells, MPNST-G1 cells displayed elevated expression of dedifferentiation transcription factors, SMO inhibition was able to reverse these effects. Conversely SMO activation induced the expression of these factors and induced an increase in proliferation. CONCLUSIONS: The SHH pathway activation promotes the expression of important transcription factors in dedifferentiation. This finding provides insights into the transformation process of MPNST and novel therapeutic options for these lethal cancers.
UPAR AS A NOVEL IMMUNOTHERAPEUTIC TARGET IN RECURRENT GLIOBLASTOMA
Authors: Maich William , Shaikh Vaseem , Puri Anish , Anand Alisha , Rosotti Martin , Savage Neil , Chokshi Chirayu , Suk Yujin , Savage Neil , Gwynne Will , Seyfrid Mathieu , Venugopal Chitra , Henry Kevin , Singh Sheila
Published: July 2023

Glioblastoma (GBM) is the common malignant brain tumor in adults, accounting for approximately 15% of all CNS tumors, and 48.6% of malignant brain tumors, with a median survival of approximately 15 months, and minimal clinical progress having been made in the past two decades. GBM is characterized by extensive inter- and intra-tumoral heterogeneity as well as an extremely immunosuppressive tumor microenvironment. Following Standard-of-Care (SoC) surgical resection and chemoradiotherapy at primary diagnosis, few therapeutic avenues exist at recurrence, owing in part due to a lack of clinically relevant targets. Data from our multi-institutional target pipeline suggests that the extracellular urokinase plasminogen activator receptor (uPAR) is significantly upregulated at recurrence on putative GBM brain tumor initiating cells (BTICs), which are believed to drive de novo tumor formation, tumor recurrence, and therapeutic resistance. uPAR plays an important role in the plasminogen activation system, and in the context of cancer, has been implicated in numerous pro-tumorigenic processes such as invasion, proliferation, epithelial-to-mesenchymal transition, and therapy resistance. In vitro, knockout of uPAR expression in recurrent GBM cells significantly reduces proliferation and sphere formation capacity, two stem-like traits associated with BTICs. Additionally, uPAR knockout cells display increased sensitivity to standard-of-care chemoradiotherapy, implicating uPAR expression in therapy resistance, as seen in recurrent disease. From these initial studies, we believe uPAR to be a clinically relevant target in recurrent GBM, and further investigation into therapeutic strategies to target uPAR-positive GBMs should be investigated further.
LONGITUDINAL NEUROLOGICAL ASSESSMENTS IN BRAIN TUMOR PATIENTS: CORRELATION BETWEEN NANO DOMAINS AND PERFORMANCE STATUS
Authors: Machado M , Roberto K , Melhem J , Theriault A , Chan A , Granovskaya I , Perry J , Chen H , Lim-Fat M J
Published: July 2023

The Karnofsky Performance Status (KPS) and Eastern Cooperative Oncology Group (ECOG) performance status are clinician-reported outcomes critical in guiding management and prognostication in patients with primary brain tumors as they can reflect longitudinal functional changes. However, they are subjective. The Neurologic Assessment in Neuro-Oncology (NANO) scale is a metric with specific neurological domains that was subsequently developed to provide an objective standardized measure of the neurologic functional status of patients, but how longitudinal changes in NANO scale relate to KPS or ECOG scores is unknown.

METHODS: A linear mixed model analysis involving 111 patients with primary brain tumors was performed. RESULTS: Statistically significant associations were identified between changes in specific NANO domains and KPS or ECOG scores. After controlling for time course both in univariable and multivariable analyses, worsening scores in gait, language and behavior domains showed significant association with decreased KPS. Gait and behavior were demonstrated to be significantly associated with ECOG both in univariable and multivariable analyses. CONCLUSIONS: The neurologic status of patients with a primary brain tumor is closely related to their performance status. In particular, the patient’s cognitive status and mobility have the greatest impact on their functional status and therefore their prognosis. Interventions and supportive care targeting these domains of function may help improve the outcomes of patients with brain tumors.
SURVEY OF CANADIAN NEURO-ONCOLOGY CLINICIANS ABOUT THE TREATMENT OF ADULT MEDULLOBLASTOMA
Authors: Cacciotti Chantel , Roberto Katrina , Climans Seth , Lim-Fat Mary Jane
Published: July 2023

Given the rarity of adult medulloblastoma, the optimal chemotherapy strategy is unknown and its management is thought to vary from institution to institution. Guidelines often omit suggestions for specific chemotherapy regimens, reflecting the lack of high-quality evidence in this population. We sought to understand Canadian adult medulloblastoma practice patterns, hoping to inform future quality metrics and guidelines.

METHODS: In March 2022, a 30-question survey was sent out to 71 adult neuro-oncology clinicians on the Canadian Adolescent and Young Adult national rounds mailing list. Snowball sampling was permitted. RESULTS: The response rate was 35%. Radiation oncologists (11), neuro-oncologists (8), medical oncologists (4), and neurosurgeons (2) responded from 6/10 Canadian provinces. They each treated on average 1.6 medulloblastoma patients per year. Most (61%) said that molecular subgrouping was always done at their centre. Half indicated that cerebrospinal fluid testing was always done at diagnosis. The most common (64%) radiation regimen was 36 Gy (in 20 fractions) craniospinal irradiation + 18 Gy (in 10 fractions) boost. Concomitant chemotherapy was rarely given while adjuvant chemotherapy was frequently administered. The most common adjuvant chemotherapy was Cisplatin/Lomustine/Vincristine (57%), but other regimens included Cisplatin/ Lomustine/ Vincristine alternating with Cyclophosphamide/ Vincristine (21%), Cisplatin/ Cyclophosphamide/ Vincristine (14%), and carboplatin-based regimens (14%). Respondents noted challenges prescribing chemotherapy in this population: drug toxicities, limited resources, and clinical uncertainty. There was support for standard-of-care adult medulloblastoma guidelines in 92%. CONCLUSIONS: There is significant practice variation among Canadian neuro-oncology centres treating adult medulloblastoma. This variation can serve as an opportunity for quality improvement and clinical research.
NEURO-CRITICAL CARE UNIT OR POST-ANESTHESIA CARE UNIT RECOVERY? ANALYSIS OF 24-HOUR OUTCOMES FOLLOWING 1078 ADULT BRAIN TUMOR SURGERIES
Authors: Yang Angela , Almansouri Abdulrahman , Djedid Anissa , Emara Ashraf , Nadaf Javad , Petrecca Kevin
Published: July 2023

Post-craniotomy recovery in a neuro-critical care unit (NCCU) has been routine for most patients. There is no evidence to support this practice. To address this, we assessed the development of post-operative adverse events in brain tumor resection patients surveilled in the NCCU or the post-anesthesia care unit (PACU).

METHODS: All brain tumor craniotomies performed between 2016-2021 (KP) were reviewed. Inclusion criteria were: age >18; craniotomy for biopsy or resection of intracerebral or extracerebral tumors. Cohorts were divided into two groups based on recovery destination: NCCU or PACU. Past medical history, pre- and post-operative neuroradiological imaging, surgical resection features, and neuropathology results were reviewed for both groups. RESULTS: There were 681 patients in NCCU group and 397 in the PACU group. Mean ages were 55.6 (NCCU) and 59.7 (PACU) (p <0.001). The American Society of Anesthesiologists (ASA) class was not significantly different between groups (p=0.89). Median recovery time in the NCCU group was 19 hours, and 4 hours in the PACU group. The incidence of adverse events within 24 hours post- surgery was 0.04 in NCCU group and 0.03 in PACU group (p=0.46). Post-operative hospital stay was 9.5 days in the NCCU group and 8.5 days in PACU group (p <0.001). CONCLUSION: The incidence of adverse events within 24 hours post brain tumor surgery is not different between patients being surveilled for a long period in a NCCU, or a short period in a PACU.
Effect of vitamin D on inflammatory and clinical outcomes in patients with rheumatoid arthritis: a systematic review and dose–response meta-analysis of randomized controlled trials
Authors: Al-Saoodi Hagir , Kolahdooz Fariba , Andersen Jens Rikardt , Jalili Mahsa
Published: July 2023

Context

Rheumatoid arthritis is a chronic inflammatory disease that causes synovitis. Vitamin D deficiency is common in rheumatoid arthritis.

Objective

This systematic review and meta-analysis investigated whether vitamin D supplementation affects the inflammatory and clinical outcomes in patients with rheumatoid arthritis on the basis of randomized clinical trials.

Data Sources

A literature search was performed in the Cochrane Central Register of Controlled Trials (CENTRAL), PubMed, MEDLINE, Embase, and Google Scholar for articles published until May 2022.

Data Extraction

The studies were selected according to PRISMA guidelines, and the risk of bias was assessed for randomized controlled trials.

Data Analysis

A random effects model was used to conduct a meta-analysis, and heterogeneity was assessed using the I2 statistic. Of 464 records, 11 studies were included from 3049 patients. Conclusion: Vitamin D supplementation did not significantly reduce C-reactive protein (CRP), erythrocyte sedimentation rate (ESR), disease activity score in 28 joints (DAS28), or the health assessment questionnaire score; however, the response to supplementation was highly heterogeneous. The pooled analysis showed that vitamin D significantly reduced the pain–visual analogue scale (VAS) weighted mean difference (WMD = –1.30, 95% confidence interval [CI] [–2.34, −27], P = .01), DAS28–CRP (WMD = –.58, 95% CI [–.86, –.31], P < .0001), and DAS28–ESR (WMD = –.58, 95% CI [–.86, –.31], P = .0001). Subgroup analysis for vitamin D doses (>100 µg per day versus <100 µg per day) showed that the higher doses had a more significant effect on CRP than the lower doses (P < .05).

Conclusions

There was no significant difference between the effect of 2 vitamin D doses on ESR and DAS28. To minimize the high heterogeneity among studies in this meta-analysis, other confounding factors such as baseline vitamin D, age, dietary vitamin D, time of year, sun exposure, drug interaction, effect dosage, and power of study should be examined.
Food Insecurity Is Associated With Low Tenofovir Diphosphate in Dried Blood Spots in South African Persons With HIV
Authors: Hirsh Molly L , Edwards Jonathan A , Robichaux Chad , Brijkumar Jaysingh , Moosa Mahomed-Yunus S , Ofotokun Igho , Johnson Brent A , Pillay Selvan , Pillay Melendhran , Moodley Pravi , Sun Yan V , Liu Chang , Dudgeon Mathew R , Ordoñez Claudia , Kuritzkes Daniel R , Sunpath Henry , Morrow Mary , Anderson Peter L , Ellison Lucas , Bushman Lane R , Marconi Vincent C , Castillo-Mancilla Jose R
Published: July 2023

Background

Food insecurity has been linked to suboptimal antiretroviral therapy (ART) adherence in persons with HIV (PWH). This association has not been evaluated using tenofovir diphosphate (TFV-DP) in dried blood spots (DBSs), a biomarker of cumulative ART adherence and exposure.

Methods

Within a prospective South African cohort of treatment-naive PWH initiating ART, a subset of participants with measured TFV-DP in DBS values was assessed for food insecurity status. Bivariate and multivariate median-based regression analysis compared the association between food insecurity and TFV-DP concentrations in DBSs adjusting for age, sex, ethnicity, medication possession ratio (MPR), and estimated glomerular filtration rate.

Results

Drug concentrations were available for 285 study participants. Overall, 62 (22%) PWH reported worrying about food insecurity and 44 (15%) reported not having enough food to eat in the last month. The crude median concentrations of TFV-DP in DBSs differed significantly between those who expressed food insecurity worry versus those who did not (599 [interquartile range {IQR}, 417–783] fmol/punch vs 716 [IQR, 453–957] fmol/punch; P = .032). In adjusted median-based regression, those with food insecurity worry had concentrations of TFV-DP that were 155 (95% confidence interval, −275 to −35; P = .012) fmol/punch lower than those who did not report food insecurity worry. Age and MPR remained significantly associated with TFV-DP.

Conclusions

In this study, food insecurity worry is associated with lower TFV-DP concentrations in South African PWH. This highlights the role of food insecurity as a social determinant of HIV outcomes including ART failure and resistance.
From Sanitation Science to Geroscience: Public Health Must Transcend ‘Folkbiology’
Authors: Farrelly Colin
Published: July 2023

Folkbiology refers to people’s everyday understanding of the biological world. The early twentieth-century pioneers of public health C.-E.A Winslow (1877–1957), and his mentor H. Biggs (1859–1923), conceptualized public health as the ‘purchasable’ science of preventing disease and death from unfavorable economic and living conditions. Their ideas were foundational in shaping public health’s strategy of a ‘war against disease’ (Winslow, 1903), a strategy that was very successful in preventing the early-life mortality risks from infectious diseases, and was eventually extended to combating the chronic diseases of late life (like cancer). However, the initial framing of public health, through the lens of sanitation science, was predicated upon folkbiological premises that geroscience must abate in order to direct public health interventions toward the goal of improving the quality of life for older persons in the twenty-first century. Three folkbiological premises of sanitation science’s ‘war against disease’ are identified and critiqued: (i) the belief that health is the ‘normal’ condition of the human mechanism and disease ‘unnecessary’; (ii) the belief that the proximate causes of disease are the only modifiable risk factors public health interventions can alter; and (iii) the belief that the rate of biological aging is universal.
The transcription factor MYB156 controls the polar stiffening of guard cell walls in poplar
Authors: Zheng Lin , Chen Yajuan , Ding Liping , Zhou Ying , Xue Shanshan , Li Biying , Wei Jianhua , Wang Hongzhi
Published: July 2023

The mechanical properties of guard cells have major effects on stomatal functioning. Reinforced stiffness in the stomatal polar regions was recently proposed to play an important role in stomatal function, but the underlying molecular mechanisms remain elusive. Here, we used genetic and biochemical approaches in poplar (Populus spp.) to show that the transcription factor MYB156 controls pectic homogalacturonan–based polar stiffening through the downregulation of the gene encoding pectin methylesterase 6 (PME6). Loss of MYB156 increased the polar stiffness of stomata, thereby enhancing stomatal dynamics and response speed to various stimuli. In contrast, overexpression of MYB156 resulted in decreased polar stiffness and impaired stomatal dynamics, accompanied by smaller leaves. Polar stiffening functions in guard cell dynamics in response to changing environmental conditions by maintaining normal stomatal morphology during stomatal movement. Our study revealed the structure–function relationship of the cell wall of guard cells in stomatal dynamics, providing an important means for improving the stomatal performance and drought tolerance of plants.
Mitogen-activated protein kinase 2 specifically regulates photorespiration in rice
Authors: Xu Zheng , Guo Weidong , Mo Benqi , Pan Qing , Lu Jiatian , Wang Ziwei , Peng Xinxiang , Zhang Zhisheng
Published: July 2023

Photorespiration begins with the oxygenation reaction catalyzed by Rubisco and is the second highest metabolic flux in plants after photosynthesis. Although the core biochemical pathway of photorespiration has been well characterized, little is known about the underlying regulatory mechanisms. Some rate-limiting regulation of photorespiration has been suggested to occur at both the transcriptional and posttranslational levels, but experimental evidence is scarce. Here, we found that mitogen-activated protein kinase 2 (MAPK2) interacts with photorespiratory glycolate oxidase and hydroxypyruvate reductase, and the activities of these photorespiratory enzymes were regulated via phosphorylation modifications in rice (Oryza sativa L.). Gas exchange measurements revealed that the photorespiration rate decreased in rice mapk2 mutants under normal growth conditions, without disturbing photosynthesis. Due to decreased photorespiration, the levels of some key photorespiratory metabolites, such as 2-phosphoglycolate, glycine, and glycerate, significantly decreased in mapk2 mutants, but those of photosynthetic metabolites were not altered. Transcriptome assays also revealed that the expression levels of some flux-controlling genes in photorespiration were significantly downregulated in mapk2 mutants. Our findings provide molecular evidence for the association between MAPK2 and photorespiration and suggest that MAPK2 regulates the key enzymes of photorespiration at both the transcriptional and posttranslational phosphorylation levels in rice.
Enhancing cell adhesive and antibacterial activities of glass-fibre-reinforced polyetherketoneketone through Mg and Ag PIII
Authors: Tan Xin , Wang Zhongyi , Yang Xin , Yu Ping , Sun Manlin , Zhao Yuwei , Yu Haiyang
Published: July 2023

Glass-fibre-reinforced polyetherketoneketone (PEKK-GF) shows great potential for application as a dental implant restoration material; however, its surface bioinertness and poor antibacterial properties limit its integration with peri-implant soft tissue, which is critical in the long-term success of implant restoration. Herein, functional magnesium (Mg) and silver (Ag) ions were introduced into PEKK-GF by plasma immersion ion implantation (PIII). Surface characterization confirmed that the surface morphology of PEKK-GF was not visibly affected by PIII treatment. Further tests revealed that PIII changed the wettability and electrochemical environment of the PEKK-GF surface and enabled the release of Mg2+ and Ag+ modulated by Giavanni effect. In vitro experiments showed that Mg/Ag PIII-treated PEKK-GF promoted the proliferation and adhesion of human gingival fibroblasts and upregulated the expression of adhesion-related genes and proteins. In addition, the treated samples inhibited the metabolic viability and adhesion of Streptococcus mutans and Porphyromonas gingivalis on their surfaces, distorting bacterial morphology. Mg/Ag PIII surface treatment improved the soft tissue integration and antibacterial activities of PEKK-GF, which will further support and broaden its adoption in dentistry.
Efficacy and safety of tonic motor activation (TOMAC) for medication-refractory restless legs syndrome: a randomized clinical trial
Authors: Bogan Richard K , Roy Asim , Kram Jerrold , Ojile Joseph , Rosenberg Russell , Hudson J Douglas , Scheuller H Samuel , Winkelman John W , Charlesworth Jonathan D
Published: July 2023

Study Objectives

The purpose of this study was to evaluate the efficacy and safety/tolerability of bilateral high-frequency tonic motor activation (TOMAC) in patients with medication-refractory restless legs syndrome (RLS).

Methods

RESTFUL was a multicenter, randomized, double-blind, sham-controlled trial in adults with medication-refractory moderate-to-severe primary RLS. Participants were randomized 1:1 to active or sham TOMAC for a double-blind, 4-week stage 1 and all received active TOMAC during open-label, 4-week stage 2. The primary endpoint was the Clinical Global Impressions-Improvement (CGI-I) responder rate at the end of stage 1. Key secondary endpoints included change to International RLS Study Group (IRLS) total score from study entry to the end of stage 1.

Results

A total of 133 participants were enrolled. CGI-I responder rate at the end of stage 1 was significantly greater for the active versus sham group (45% vs. 16%; Difference = 28%; 95% CI 14% to 43%; p = .00011). At the end of stage 2, CGI-I responder rate further increased to 61% for the active group. IRLS change at the end of stage 1 improved for the active versus sham group (−7.2 vs. −3.8; difference = −3.4; 95% CI −1.4 to −5.4; p = .00093). There were no severe or serious device-related adverse events (AEs). The most common AEs were mild discomfort and mild administration site irritation which resolved rapidly and reduced in prevalence over time.

Conclusions

TOMAC was safe, well tolerated, and reduced symptoms of RLS in medication-refractory patients. TOMAC is a promising new treatment for this population.

Clinical Trial

Noninvasive Peripheral Nerve Stimulation for Medication-Refractory Primary RLS (The RESTFUL Study); clinicaltrials.gov/ct2/show/NCT04874155; Registered at ClinicalTrials.gov with the identifier number NCT04874155.