bluuebunny/crossref_metadata_2025 huggingface dataset:
Expression and prognostic value of DNA sensors in hepatocellular carcinoma
Authors: Chen Danchun , Ren He , Zhao Na , Hao Jianlei
Published: May 2023

DNA sensor proteins play an important role in transducing DNA signals to induce immune responses that initiate inflammation or clear pathogens. It has been previously shown that several DNA sensors are involved in regulating tumor biology and/or cancer immunology. However, a systemic analysis of DNA sensor expression and its correlation with prognosis has not been conducted. Here, we analyzed messenger RNA expression and protein abundance in liver cancer databases and found that the genes of 5 DNA sensors (POLR3A, PRKDC, DHX9, cGAS, and MRE11) were consistently upregulated in tumor tissue. Moreover, the expression of these DNA sensor genes correlated with patient survival. Using a gene alterations analysis, we discovered that patients with genetically altered DNA sensors had significantly lower survival compared with an unaltered group. Furthermore, receiver-operating characteristic curves confirmed that the signatures of the 5 DNA sensors were independent prognostic factors in hepatocellular carcinoma. Tumor-infiltrating immune cell analysis revealed that expression of all 5 DNA sensors correlated with the amount of B cells, CD8 T cells, CD4 T cells, Tregs, DCs, Mϕs, and neutrophils. Surprisingly, 4 of the DNA sensors (POLR3A, PRKDC, DHX9, and MRE11) were inversely correlated with the amount of γδ T cells. Gene set enrichment analysis showed that all 5 DNA sensor genes were enriched for oxidative phosphorylation and xenobiotic metabolism. These results suggest that expression of these DNA sensors is associated with a unique immune profile and metabolic regulation in hepatocellular carcinoma.
Clinical development of new drugs for adults and children with cancer, 2010-2020
Authors: Arfè Andrea , Narang Claire , DuBois Steven G , Reaman Gregory , Bourgeois Florence T
Published: May 2023

Background

Many new molecular entities enter clinical development to evaluate potential therapeutic benefits for oncology patients. We characterized adult and pediatric development of the set of new molecular entities that started clinical testing in 2010-2015 worldwide.

Methods

We extracted data from AdisInsight, an extensive database of global pharmaceutical development, and the FDA.gov website. We followed the cohort of new molecular entities initiating first-in-human phase I clinical trials in 2010-2015 to the end of 2020. For each new molecular entity, we determined whether it was granted US Food and Drug Administration (FDA) approval, studied in a trial open to pediatric enrollment, or stalled during development. We characterized the cumulative incidence of these endpoints using statistical methods for censored data.

Results

The 572 new molecular entities starting first-in-human studies in 2010-2015 were studied in 6142 trials by the end of 2020. Most new molecular entities were small molecules (n = 316, 55.2%), antibodies (n = 148, 25.9%), or antibody-drug conjugates (n = 44, 7.7%). After a mean follow-up of 8.0 years, 173 new molecular entities did not advance beyond first-in-human trials, and 39 were approved by the FDA. New molecular entities had a 10.4% estimated probability (95% confidence interval = 6.6% to 14.1%) of being approved by the FDA within 10 years of first-in-human trials. After a median of 4.6 years since start of first-in-human trials, 67 (11.7%) new molecular entities were tested in trials open to pediatric patients, and 5 (0.9%) were approved for pediatric indications.

Conclusions

More efficient clinical development strategies are needed to evaluate new cancer therapies, especially for children, and incorporate approaches to ensure knowledge gain from investigational products that stall in development.
Autoregressive optimal transport models
Authors: Zhu Changbo , Müller Hans-Georg
Published: May 2023

Series of univariate distributions indexed by equally spaced time points are ubiquitous in applications and their analysis constitutes one of the challenges of the emerging field of distributional data analysis. To quantify such distributional time series, we propose a class of intrinsic autoregressive models that operate in the space of optimal transport maps. The autoregressive transport models that we introduce here are based on regressing optimal transport maps on each other, where predictors can be transport maps from an overall barycenter to a current distribution or transport maps between past consecutive distributions of the distributional time series. Autoregressive transport models and their associated distributional regression models specify the link between predictor and response transport maps by moving along geodesics in Wasserstein space. These models emerge as natural extensions of the classical autoregressive models in Euclidean space. Unique stationary solutions of autoregressive transport models are shown to exist under a geometric moment contraction condition of Wu & Shao [(2004) Limit theorems for iterated random functions. Journal of Applied Probability 41, 425–436)], using properties of iterated random functions. We also discuss an extension to a varying coefficient model for first-order autoregressive transport models. In addition to simulations, the proposed models are illustrated with distributional time series of house prices across U.S. counties and annual summer temperature distributions.
arepo white dwarf merger simulations resulting in edge-lit detonation and run-away hypervelocity companion
Authors: Burmester Uri Pierre , Ferrario Lilia , Pakmor Rüdiger , Seitenzahl Ivo R , Ruiter Ashley J , Hole Matthew
Published: May 2023

We present a series of high-resolution simulations generated with the moving-mesh code arepo to model the merger of a 1.1-M⊙ carbon-oxygen primary white dwarf (WD) with an outer helium layer and a 0.35-M⊙ secondary helium WD. Our simulations lead to detonations that are consistent with the edge-lit scenario, where a helium detonation is ignited at the base of the helium layer of the primary WD, which triggers an off-centre carbon detonation. This produces an asymmetric ejecta pattern and differences in line-of-sight observables (e.g. mean atomic weight). The ejecta that are flung into space are dominated by 56Ni, 4He, 28Si, and 32S. Our simulations result in a surviving degenerate companion of mass 0.22–0.25 M⊙ moving at >1700 $\mathrm{km}\, \mathrm{s}^{-1}$, consistent with the observational findings of hypervelocity WDs. The secondary’s surface layers are enriched by heavy metals, with 56Ni making up approximately 0.8 per cent of the remaining mass. We also analyse the sensitivity of the outcome on simulation parameters, including the ‘inspiral time’, which defines a period of accelerated angular momentum loss. We find that the choice of ‘inspiral time’ qualitatively influences the simulation result, including the survival of the secondary. We argue that the shorter inspiral cases result in qualitatively and quantitatively similar outcomes. We also investigate the sensitivity of our results on the primary’s chemical profile by comparing simulations using isothermal, constant composition models with the same mass and central composition and characterized by either a bare carbon-oxygen core (no helium) or a carbon-oxygen core enveloped by a thick helium layer.
Probing sub-galactic mass structure with the power spectrum of surface-brightness anomalies in high-resolution observations of galaxy–galaxy strong gravitational lenses. II. Observational constraints on the subgalactic matter power spectrum
Authors: Bayer D , Chatterjee S , Koopmans L V E , Vegetti S , McKean J P , Treu T , Fassnacht C D , Glazebrook K
Published: May 2023

Stringent observational constraints on the subgalactic matter power spectrum would allow one to distinguish between the concordance ΛCDM and the various alternative dark-matter models that predict significantly different properties of mass structure in galactic haloes. Galaxy–galaxy strong gravitational lensing provides a unique opportunity to probe the subgalactic mass structure in lens galaxies beyond the Local Group. Here, we demonstrate the first application of a novel methodology to observationally constrain the subgalactic matter power spectrum in the inner regions of massive elliptical lens galaxies on 1–10 kpc scales from the power spectrum of surface-brightness anomalies in highly magnified galaxy-scale Einstein rings and gravitational arcs. The pilot application of our approach to Hubble Space Telescope (HST/WFC3/F390W) observations of the SLACS lens system SDSS J0252+0039 allows us to place the following observational constraints (at the 99 per cent confidence level) on the dimensionless convergence power spectrum $\Delta ^{2}_{\delta \kappa }$ and the standard deviation in the aperture mass σAM: $\Delta ^{2}_{\delta \kappa }\lt 1$ (σAM < 0.8 × 108 M⊙) on 0.5-kpc scale, $\Delta ^{2}_{\delta \kappa }\lt 0.1$ (σAM < 1 × 108 M⊙) on 1-kpc scale and $\Delta ^{2}_{\delta \kappa }\lt 0.01$ (σAM < 3 × 108 M⊙) on 3-kpc scale. These first upper-limit constraints still considerably exceed the estimated effect of CDM subhaloes. However, future analysis of a larger sample of galaxy–galaxy strong lens systems can substantially narrow down these limits and possibly rule out dark-matter models that predict a significantly higher level of density fluctuations on the critical subgalactic scales.
Probing sub-galactic mass structure with the power spectrum of surface-brightness anomalies in high-resolution observations of galaxy-galaxy strong gravitational lenses – I. Power-spectrum measurement and feasibility study
Authors: Bayer D , Koopmans L V E , McKean J P , Vegetti S , Treu T , Fassnacht C D , Glazebrook K
Published: May 2023

While the direct detection of the dark-matter particle remains very challenging, the nature of dark matter could be possibly constrained by comparing the observed abundance and properties of small-scale sub-galactic mass structures with predictions from the phenomenological dark-matter models, such as cold, warm, or hot dark matter. Galaxy-galaxy strong gravitational lensing provides a unique opportunity to search for tiny surface-brightness anomalies in the extended lensed images (i.e. Einstein rings or gravitational arcs), induced by possible small-scale mass structures in the foreground lens galaxy. In this paper, the first in a series, we introduce and test a methodology to measure the power spectrum of such surface-brightness anomalies from high-resolution Hubble Space Telescope (HST) imaging. In particular, we focus on the observational aspects of this statistical approach, such as the most suitable observational strategy and sample selection, the choice of modelling techniques, and the noise correction. We test the feasibility of the power-spectrum measurement by applying it to a sample of galaxy-galaxy strong gravitational lens systems from the Sloan Lens ACS Survey, with the most extended, bright, high-signal-to-noise-ratio lensed images, observed in the rest-frame ultraviolet. In the companion paper, we present the methodology to relate the measured power spectrum to the statistical properties of the underlying small-scale mass structures in the lens galaxy and infer the first observational constraints on the sub-galactic matter power spectrum in a massive elliptical (lens) galaxy.
Three-dimensional dust stirring by a giant planet embedded in a protoplanetary disc
Authors: Binkert Fabian , Szulágyi Judit , Birnstiel Til
Published: May 2023

The motion of solid particles embedded in gaseous protoplanetary discs is influenced by turbulent fluctuations. Consequently, the dynamics of moderately to weakly coupled solids can be distinctly different from the dynamics of the gas. Additionally, gravitational perturbations from an embedded planet can further impact the dynamics of solids. In this work, we investigate the combined effects of turbulent fluctuations and planetary dust stirring in a protoplanetary disc on three-dimensional dust morphology and on synthetic ALMA continuum observations. We carry out 3D radiative two-fluid (gas + 1-mm-dust) hydrodynamic simulations in which we explicitly model the gravitational perturbation of a Jupiter-mass planet. We derived a new momentum-conserving turbulent diffusion model that introduces a turbulent pressure to the pressureless dust fluid to capture the turbulent transport of dust. The model implicitly captures the effects of orbital oscillations and reproduces the theoretically predicted vertical settling-diffusion equilibrium. We find a Jupiter-mass planet to produce distinct and large-scale three-dimensional flow structures in the mm-sized dust, which vary strongly in space. We quantify these effects by locally measuring an effective vertical diffusivity (equivalent alpha) and find azimuthally averaged values in a range δeff ∼ 5 × 10−3–2 × 10−2 and local peaks at values of up to δeff ∼ 3 × 10−1. In synthetic ALMA continuum observations of inclined discs, we find effects of turbulent diffusion to be observable, especially at disc edges, and effects of planetary dust stirring in edge-on observations.
Timing analysis of Swift J0243.6+6124 with NICER and Fermi/GBM during the decay phase of the 2017–2018 outburst
Authors: Serim M M , Dönmez Ç K , Serim D , Ducci L , Baykal A , Santangelo A
Published: May 2023

We present a timing and noise analysis of the Be/X-ray binary system Swift J0243.6+6124 during its 2017–2018 super-Eddington outburst using NICER/XTI observations. We apply a synthetic pulse timing analysis to enrich the Fermi/GBM spin frequency history of the source with the new measurements from NICER/XTI. We show that the pulse profiles switch from double-peaked to single-peaked when the X-ray luminosity drops below ∼7 × 1036 erg s−1. We suggest that this transitional luminosity is associated with the transition from a pencil beam pattern to a hybrid beam pattern when the Coulomb interactions become ineffective to decelerate the accretion flow, which implies a dipolar magnetic field strength of ∼5 × 1012 G. We also obtained the power density spectra (PDS) of the spin frequency derivative fluctuations. The red noise component of the PDS is found to be steeper (ω−3.36) than the other transient accreting sources. We find significantly high noise strength estimates above the super-Eddington luminosity levels, which may arise from the torque fluctuations due to interactions with the quadrupole fields at such levels.
Primordial non-Gaussianity with angular correlation function: integral constraint and validation for DES
Authors: Riquelme Walter , Avila Santiago , García-Bellido Juan , Porredon Anna , Ferrero Ismael , Chan Kwan Chuen , Rosenfeld Rogerio , Camacho Hugo , Adame Adrian G , Carnero Rosell Aurelio , Crocce Martin , De Vicente Juan , Eifler Tim , Elvin-Poole Jack , Fang Xiao , Krause Elisabeth , Rodriguez Monroy Martin , Ross Ashley J , Sanchez Eusebio , Sevilla Ignacio
Published: May 2023

Local primordial non-Gaussianity (PNG) is a promising observable of the underlying physics of inflation, characterized by $f_{\rm NL}^{\rm loc}$. We present the methodology to measure $f_{\rm NL}^{\rm loc}$ from the Dark Energy Survey (DES) data using the two-point angular correlation function (ACF) with scale-dependent bias. One of the focuses of the work is the integral constraint (IC). This condition appears when estimating the mean number density of galaxies from the data and is key in obtaining unbiased $f_{\rm NL}^{\rm loc}$ constraints. The methods are analysed for two types of simulations: ∼246 goliat-png N-body small area simulations with fNL equal to −100 and 100, and 1952 Gaussian ice-cola mocks with fNL = 0 that follow the DES angular and redshift distribution. We use the ensemble of goliat-png mocks to show the importance of the IC when measuring PNG, where we recover the fiducial values of fNL within the 1σ when including the IC. In contrast, we found a bias of ΔfNL ∼ 100 when not including it. For a DES-like scenario, we forecast a bias of ΔfNL ∼ 23, equivalent to 1.8σ, when not using the IC for a fiducial value of fNL = 100. We use the ice-cola mocks to validate our analysis in a realistic DES-like set-up finding it robust to different analysis choices: best-fitting estimator, the effect of IC, BAO damping, covariance, and scale choices. We forecast a measurement of fNL within σ(fNL) = 31 when using the DES-Y3 BAO sample, with the ACF in the 1 deg < θ < 20 deg range.
The need for a risk-assessment tool among patients with chronic liver diseases interested in intermittent fasting: Ramadan model
Authors: Emara Mohamed H , Abdelaty Abdelaty I , Elbatae Hassan E , Abdelrazik Osama Mostafa , Elgammal Nahla E
Published: May 2023

Liver diseases, especially the chronic type, are a global concern. There is a growing interest in the intermittent fasting model due to its presumed health benefits. Ramadan fasting, although religious fasting, is one of the best examples of intermittent fasting, with some differences, and is observed by more than 1 billion Muslims around the world. This month follows the Arabic Hijri calendar, which is 12 days shorter than the Gregorian calendar; hence, this entire month of fasting may occur in any season of the year. There is evidence that many patients with chronic liver disease are prone to adverse events upon observing this month of continuous intermittent fasting, particularly during the hot summer with prolonged hours of fasting, if they are not adequately addressed and prevented from fasting. There is a need to sound the alarm to develop a risk-assessment tool to omit vulnerable patients with chronic liver disease—who are exempted on religious grounds from observing this pattern of fasting.
The Effects of Polarized Evaluations on Political Participation: Does Hating the Other Side Motivate Voters?
Authors: Ahn Chloe , Mutz Diana C
Published: May 2023

This study examines whether rising polarization in Americans’ partisan judgments has positive implications for political participation. Drawing on cross-sectional and panel survey data, we find evidence that polarized judgments are related to pre-election intent to vote, as well as to post-election self-reported voter turnout. Polarized evaluations also predict greater reporting of participation in campaign activities beyond voting. Polarization in candidate evaluations consistently has more of an impact than affective polarization. However, our results suggest that polarization in evaluations of both parties and candidates includes an expressive component that does not necessarily translate into political action. Roughly one-quarter to one-third of the actual change in turnout can potentially be attributed to polarization in evaluations of Republican and Democratic presidential candidates.
Data structures for photoadsorption within the ExoMol project
Authors: Tennyson Jonathan , Pezzella Marco , Zhang Jingxin , Yurchenko Sergei N
Published: May 2023

The ExoMol data base currently provides comprehensive line lists for modelling the spectroscopic properties of molecules in hot atmospheres. Extending the spectral range of the data provided to ultraviolet (UV) wavelengths brings into play three processes not currently accounted for in the ExoMol data structure, namely photodissociation, which is an important chemical process in its own right, the opacity contribution due to continuum absorption, and predissociation which can lead to significant and observable line-broadening effects. Data structures are proposed which will allow these processes to be correctly captured and the (strong) temperature-dependent effects predicted for UV molecular photoabsorption in general and photodissociation in particular to be represented.
Health-related quality of life in patients with ANCA vasculitides compared to rheumatoid arthritis: a cross-sectional comparative study
Authors: Panagiotopoulos Alexandros , Thomas Konstantinos , Argyriou Evangelia , Chalkia Aglaia , Kapsala Noemin , Koutsianas Christos , Mavrea Evgenia , Petras Dimitrios , Boumpas Dimitrios T , Vassilopoulos Dimitrios
Published: May 2023

Objectives

There are limited data regarding health-related quality of life (HRQoL) in patients with ANCA-associated vasculitides (AAVs). We aimed to evaluate the HRQoL in patients with AAVs and compare it to another chronic inflammatory disease like RA and to healthy controls (HC).

Methods

This was a multicentre, cross-sectional study of patients with AAVs and RA recruited from three tertiary rheumatology clinics. HRQoL was assessed with the Short Form 36 Health Survey, which included the physical and mental component summary scores (PCS and MCS). Data from 1007 HC served as historical controls.

Results

Sixty-six patients with AAVs and 71 with RA were included. Both AAV and RA patients had significantly lower PCS and MCS scores compared with HC (P < 0.05). HRQoL in AAV patients was worse in patients with microscopic polyangiitis compared with granulomatosis with polyangiitis (physical components) and those with high (VDI ≥ 3) vs low (VDI < 3) damage scores while it did not differ between those with active (BVASv3 ≥ 1) vs. inactive (BVASv3 < 1) disease. In contrast, in RA patients, HRQoL correlated both with disease activity (assessed by the DAS28-ESR) and functional impairment/damage (assessed by the HAQ). Although overall patients with RA had similar HRQoL compared with those with AAVs, those with active RA had worse HRQoL compared with those with active AAV.

Conclusions

In patients with AAVs, HRQoL correlated more with organ damage and less with disease activity whereas in RA patients, it correlated with both. These data emphasize the need for AAV therapies aiming at preventing organ damage and thus improving HRQoL.
Evaluation of selenium source on nursery pig growth performance, serum and tissue selenium concentrations, and serum antioxidant status
Authors: Rao Zhong-Xing , Tokach Mike D , Woodworth Jason C , DeRouchey Joel M , Goodband Robert D , Gebhardt Jordan T
Published: May 2023

A total of 3,888 pigs (337 × 1050, PIC, Hendersonville, TN; initially 6.0 ± 0.23 kg) were used in a 35-d study. At the time of placement, pens of pigs were weighed and allotted to one of three dietary treatments in a randomized complete block design with a blocking structure including sow farm origin, date of entry into the facility, and average pen body weight. A total of 144 pens were used with 72 double-sided 5-hole stainless steel fence line feeders, with one feeder serving as the experimental unit. For each feeder, 1 pen contained 27 gilts, and 1 pen contained 27 barrows. There were 24 replicates per dietary treatment. Diets were fed in three phases, and all contained 0.3 mg/kg added Se. A common phase 1 diet contained added Se from sodium selenite and was fed in pelleted form to all pigs from day 7 to approximately day 0. Three Se sources sodium selenite, Se yeast, and hydroxy-selenomethionine (OH-SeMet) were used to formulate three experimental diets in meal form for phase 2 (days 0 to 14) and phase 3 (days 14 to 35). During the pre-treatment period (days 7 to 0), there was a tendency (P = 0.097) of a difference in average daily feed intake between treatments, although no significant pairwise differences were observed (P > 0.05). There were no other differences in growth performance between treatments from days 7 to 0. Clinical disease attributed to Streptococcus suis was observed within the trial between days 0 and 14, and water-soluble antimicrobial therapy was administered to all treatment groups for 7 d. From days 0 to 35, pigs fed OH-SeMet tended to have decreased average daily gain (P < 0.10) and increased (P < 0.05) serum and tissue selenium concentration compared to other treatments. There was marginally significant evidence of a source × day interaction (P = 0.027) for total antioxidant capacity where the numerical increase over time was less for the OH-SeMet than sodium selenite or selenium yeast treatments. There was no difference (P > 0.05) in antioxidant status as measured by serum glutathione peroxidase or thiobarbituric acid reactive substances assay between treatments. In summary, compared to sodium selenite and selenium yeast, OH-SeMet may have a greater bioavailability as indicated by increased serum and tissue selenium concentration; however, antioxidant status was similar between treatments and OH-SeMet tended to reduce growth performance compared with pigs fed sodium selenite.
Comparative transcriptomics provides insights into the pathogenic immune response of brown leaf spots in weeping forsythia
Authors: Yuan Wang-Jun , He Zhi-Yin , Zhang Su-Ping , Zheng Yan-Ping , Zhang Xiao-Qian , He She-Qi , He Yan-Xia , Li Yong
Published: May 2023

Weeping forsythia is an important ornamental, ecological and medicinal plant. Brown leaf spots limit the large-scale production of weeping forsythia as a medicinal crop. Alternaria alternata is a pathogen causing brown leaf spots in weeping forsythia; however, its pathogenesis and the immune response mechanisms of weeping forsythia remain unclear. In this study, we identified two mechanisms based on morphological anatomy, physiological indexes and gene expression analyses. Our results showed that A. alternata induced leaf stomata to open, invaded the mesophyll, dissolved the cell wall, destroyed the cell membrane and decreased the number of chloroplasts by up-regulating the expression of auxin-activated signaling pathway genes. Alternaria alternata also down-regulated iron-ion homeostasis and binding-related genes, which caused an increase in the levels of iron ions and reactive oxygen species in leaves. These processes eventually led to programmed cell death, destroying palisade and spongy tissues and causing the formation of iron rust spots. Alternaria alternata also caused defense and hypersensitive responses in weeping forsythia through signaling pathways mediated by flg22-like and elf18-like polypeptides, ethylene, H2O2 and bacterial secretion systems. Our study provides a theoretical basis for the control of brown leaf spots in weeping forsythia.
Effects of combined drought and pathogen stress on growth, resistance and gene expression in young Norway spruce trees
Authors: Krokene P , Børja I , Carneros E , Eldhuset T D , Nagy N E , Volařík D , Gebauer R
Published: May 2023

Drought-induced mortality is a major direct effect of climate change on tree health, but drought can also affect trees indirectly by altering their susceptibility to pathogens. Here, we report how a combination of mild or severe drought and pathogen infection affected the growth, pathogen resistance and gene expression in potted 5-year-old Norway spruce trees [Picea abies (L.) Karst.]. After 5 weeks of drought, trees were inoculated with the fungal pathogen Endoconidiophora polonica. Combined drought–pathogen stress over the next 8 weeks led to significant reductions in the growth of drought-treated trees relative to well-watered trees and more so in trees subjected to severe drought. Belowground, growth of the smallest fine roots was most affected. Aboveground, shoot diameter change was most sensitive to the combined stress, followed by shoot length growth and twig biomass. Both drought-related and some resistance-related genes were upregulated in bark samples collected after 5 weeks of drought (but before pathogen infection), and gene expression levels scaled with the intensity of drought stress. Trees subjected to severe drought were much more susceptible to pathogen infection than well-watered trees or trees subjected to mild drought. Overall, our results show that mild drought stress may increase the tree resistance to pathogen infection by upregulating resistance-related genes. Severe drought stress, on the other hand, decreased tree resistance. Because drought episodes are expected to become more frequent with climate change, combined effects of drought and pathogen stress should be studied in more detail to understand how these stressors interactively influence tree susceptibility to pests and pathogens.
Corneal Collagen Cross-Linking for Late Onset Progressive Keratoconus in Iridocorneal Endothelial Syndrome
Authors: Phylactou Maria , Din Nizar , Aiello Francesco , Angunawela Romesh
Published: May 2023

Purpose:

The aim of this study was to report the first case of successful use of corneal collagen cross-linking (CXL) to halt the progression of keratoconus in a patient with concurrent iridocorneal endothelial (ICE) syndrome.

Methods:

A 30-year-old White man was referred to our subspecialty corneal clinic for further investigation of right corectopia. The patient was asymptomatic and was otherwise fit. Slit-lamp examination revealed a right oval-shaped pupil decentered superiorly, a transillumination defect at the 5-o'clock position, minimal gutta-like changes in the corneal endothelium, and few inferior peripheral anterior synechiae. Dilated fundoscopy was normal in both eyes, with healthy optic discs, maculae, and peripheral retinae. Specular microscopy and slit-lamp findings suggested ICE syndrome. Subsequent investigation with corneal tomography showed progressive signs of inferior corneal ectasia with steepening, and thinning in the right eye, consistent with keratoconus. The left eye was unremarkable.

Results:

Epithelium-off accelerated corneal CXL was performed in the affected eye. Early post-CXL follow-up (1 week) was unremarkable, and further follow-ups were arranged at 3, 6, 12, and 24 months, respectively. In subsequent reviews, the patient's vision and corneal tomography findings were stable.

Conclusions:

We describe the first case of corneal CXL for progressive keratoconus with ICE syndrome. co-existing keratoconus and ICE syndrome can occur, and corneal cross-linking was used successfully in this case to halt keratoconus progression. However, further studies will need to establish the impact of epithelium-off corneal cross-linking, especially in more severely affected eyes.
Negative Pressure Application via a Multi-Pressure Dial to Lower IOP in Patients with Suspected Glaucoma or Open Angle Glaucoma
Authors: Samuelson Thomas W. , Ferguson Tanner J. , Brubaker Jacob W. , Bacharach Jason , Gallardo Mark J. , Chaglasian Michael , Comer George , Yoo Paul
Published: May 2023

Précis:

The multi-pressure dial applies localized periocular negative pressure to safely and effectively lower IOP and represents the first non-invasive, non-pharmacologic device for IOP reduction.

Objective:

To evaluate the safety and effectiveness of the Multi-Pressure Dial (MPD) system, a device that applies periocular negative pressure to lower intraocular pressure (IOP).

Setting:

6 investigational sites, United States.

Design:

Prospective, assessor-masked, randomized controlled trial.

Methods:

Subjects with suspected glaucoma, ocular hypertension (OHTN), and open angle glaucoma (OAG) with baseline IOP ≥13 mmHg and ≤32 mmHg were enrolled. One eye of each subject was randomized to receive negative pressure application; the fellow eye served as a control. The study eye negative pressure setting was programmed for 60% of the baseline IOP. The primary effectiveness endpoint was the proportion of study eyes versus control eyes achieving an IOP reduction ≥20% at Day 90. Secondary endpoints included the proportion of eyes achieving an IOP reduction ≥25% at Day 90 as well as the proportion of eyes achieving an IOP reduction ≥20% at Days 30 and 60.

Results:

116 eyes of 58 subjects completed the study. At the Day 90 visit, 89.7% (n=52) of study eyes versus 3.4% (n=2) of control eyes achieved an IOP reduction ≥20% (P<0.001). At Day 90, 77.6% (n=45) of study eyes achieved a ≥25% IOP reduction compared to 1.7% (n=1) of control eyes (P<0.001). The most commonly reported adverse events were lid (17.2% study eye, 7.8% control eye) and periorbital edema (14.1% study eye, 10.9% control eye).

Conclusions:

This trial demonstrates that the MPD safely and effectively lowers IOP in a group of patients that included glaucoma suspects, OHTN, and patients with OAG.
Ahmed and Baerveldt Glaucoma Drainage Devices in Childhood Glaucoma: A Meta-Analysis
Authors: Elhusseiny Abdelrahman M. , Hassan Amr K. , Azhari Jamal O. , Elkheniny Fatmah D. , Chauhan Muhammad Z. , Chang Ta C. , VanderVeen Deborah K. , Oke Isdin , Mansour Munthir , Pakravan Mohammad , Shaarawy Tarek , Sallam Ahmed B.
Published: May 2023

Précis:

The effectiveness of Ahmed glaucoma valve (AGV) and Baerveldt glaucoma implant (BGI) was comparable in the management of childhood glaucoma over the long term despite initial better success rate with BGI. There were higher tube block and retraction rates in the BGI group and higher tube exposure rates in the AGV group.

Purpose:

To evaluate the outcomes and safety of AGV and BGI in childhood glaucoma.

Materials and Methods:

We performed a systematic literature review of publications from 1990 to 2022 in PubMed, EMBASE, ClinicalTrials.gov, Ovid MEDLINE, Cochrane CENTRAL, and google scholar for studies evaluating AGV and BGI in childhood glaucoma. Primary outcome measures were intraocular pressure (IOP) reduction and glaucoma medication reduction. The secondary outcome measures were the success rates and incidence of postoperative complications. We conducted a meta-analysis using a random effects model.

Results:

Thirty-two studies met the inclusion criteria. A total of 1480 eyes were included. The mean IOP reduction was 15.08 mm Hg (P < 0.00001) for AGV and 14.62 (P < 0.00001) for the BGI group. The mean difference between pre and postoperative glaucoma medications was 1 (P < 0.00001) fewer medications in the AGV group and 0.95 (P < 0.0001) fewer medications in the BGI group. There was a lower success rate in the AGV versus BGI groups at 2 years [63% vs 83%, respectively (P < 0.0001) and 3 years (43% vs 79%, respectively (P < 0.0001)]; however, the success was higher for AGV at 5 years (63% vs 56% in the BGI group, P < 0.001). The incidence of postoperative complications was comparable in the AGV and BGI groups, with rates of 28% and 27%, respectively.

Conclusions:

The IOP and glaucoma medication reduction, success rates, and incidence of postoperative complications were comparable in Ahmed and Baerveldt groups. Most literature comes from retrospective low-quality studies on refractory childhood glaucoma. Further larger cohort studies are needed.
Prognostic value of pretreatment skeletal muscle index in pancreatic carcinoma patients: A meta-analysis
Authors: Yang Li , Liao Xianghui , Xie Zhong , Li Haiwen
Published: May 2023

Background:

The association between pretreatment skeletal muscle index (SMI) and long-term survival of pancreatic carcinoma patients remains unclear up to now.

Methods:

The PubMed, Web of Science and EMBASE databases were searched up to March 1, 2022 for relevant studies. The primary and secondary outcomes were overall survival and progression-free survival, respectively. The hazard ratios (HRs) and 95% confidence intervals (CIs) were combined to assess the relationship between pretreatment SMI and prognosis of pancreatic carcinoma patients. All statistical analysis was conducted by STATA 15.0 software.

Results:

Twenty retrospective studies involving 3765 patients were included. The pooled results demonstrated that lower pretreatment SMI was significantly related to poorer overall survival (HR = 1.42, 95% CI: 1.25–1.62,P< .001) and progression-free survival (HR = 1.41, 95% CI: 1.08–1.84,P= .012). Besides subgroup analysis based on the treatment (non-surgery vs surgery) and tumor stage (advanced vs early stage) showed similar results.

Conclusion:

Pretreatment SMI could serve as a promising and reliable prognostic factor for pancreatic carcinoma patients and lower pretreatment SMI predicted worse prognosis.
Giant Cell Tumors With HMGA2::NCOR2 Fusion
Authors: Perret Raul , Malaka Zaki , Velasco Valérie , Llamas-Gutierrez Francisco , Ropars Mickael , Linck Pierre-Antoine , Hostein Isabelle , Azmani Rihab , Valo Isabelle , Galmiche Louise , Moreau Anne , de Pinieux Gonzague , Michot Audrey , Bochaton Dorian , Coindre Jean-Michel , Le Loarer François
Published: May 2023

Giant cell tumors (GCTs) with high mobility group AT-Hook 2 (HMGA2)::nuclear receptor corepressor 2 (NCOR2) fusion are rare mesenchymal tumors of controversial nosology, which have been anecdotally reported to respond to CSFR1 inhibitors. Here, we performed a comprehensive study of 6 GCTs with HMGA2::NCOR2 fusion and explored their relationship with other giant cell-rich neoplasms. Tumors occurred in 4 females and 2 males ranging in age from 17 to 32 years old (median 24). Three lesions originated in subcutaneous soft tissue and 3 in bone. Tumor size ranged from 20 to 33 mm (median 27 mm). The lesions had a nodular/multinodular architecture and were composed of sheets of mononuclear “histiocytoid” cells with uniform nuclei intermingled with multinucleated giant cells. Mitotic activity was low and nuclear atypia and metaplastic bone were absent. Variable findings included necrosis, cystic degeneration, lymphocytic infiltrate (sometimes forming nodules), and xanthogranulomatous inflammation. On immunohistochemistry, all cases focally expressed pan-keratin and were negative with SATB2 and H3.3G34W. Whole RNA-sequencing was performed in all cases of GCT with HMGA2::NCOR2 fusion and a subset of giant cell-rich tumors (tenosynovial-GCT, n = 19 and “wild-type” GCT of soft tissue, n = 9). Hierarchical clustering of RNA-sequencing data showed that GCT with HMGA2::NCOR2 fusion formed a single cluster, independent of the other 2 entities. Methylome profiling showed similar results, but the distinction from “wild-type” GCT of soft tissue was less flagrant. Gene expression analysis showed similar levels of expression of the CSF1/CSFR1 axis between GCT with HMGA2::NCOR2 fusion and tenosynovial-GCT, supporting their potential sensitivity to CSFR1 inhibitors. Clinical follow-up was available for 5 patients (range: 10 to 64 mo; median 32 mo). Three patients (60%) experienced local recurrences, whereas none had distant metastases or died of disease. Overall, our study confirms and expands previous knowledge on GCT with HMGA2::NCOR2 fusion and supports its inclusion as an independent entity.
A comparative analysis of the second and third wave of the Covid-19 pandemic: an experience from a tertiary care hospital in Western India
Authors: Swami Anjali , Mohanty Ankita , Jamwal Ashima , Turbadkar Dilip , Baveja Sujata , Shastri Jayanthi , Chitalia Vidushi
Published: May 2023

Introduction. As the world was still recovering from the 2020 pandemic, the devastating impact of Covid-19 driven by the Delta variant shook the world in 2021. As the second wave was declining, there was an unusual surge in Covid-19 positive cases by the end of 2021 which led to global concern about the change in virus characteristics.

Hypothesis/gap statement. Whole genome sequencing is critical for understanding a rapidly progressing pandemic.

Aim. To provide an insight into the major differences encountered in the changing characteristics between the second and third waves of the pandemic at a tertiary care hospital in India.

Methods. A retrospective observational cohort analysis was conducted on Covid-positive patients during the second wave of the Covid-19 pandemic (from March 2021 to April 2021) and the third wave of the Covid-19 pandemic (from December 2021 to January 2022).

Results. Out of 303 Covid-19 positive cases, 52 samples were tested by whole genome sequencing during the second wave and 108 during the third wave. A decline of 18.5 % was observed in the case fatality rate from the second wave to the third wave. There was a 5 % decline in the number of patients admitted with ARDS and a 16.3 % decline in the number of patients with co-morbidities.

In total, 51.9 percent of cases were due to the Delta variant during the second wave and 95 percent due to the Omicron variant during the third wave. We found that 36.5 % of Covid-positive patients during the second wave had been vaccinated compared to 40 % in the third wave.

Conclusion. Whole genome sequencing of clinical samples from a wide range of individuals during a viral epidemic will enable us to develop a more rapid public health response to new variants and identify the required vaccine modifications more quickly.
Feature selection for preserving biological trajectories in single-cell data
Authors: Ranek Jolene S. , Stallaert Wayne , Milner Justin , Stanley Natalie , Purvis Jeremy E.
Published: May 2023

Single-cell technologies can readily measure the expression of thousands of molecular features from individual cells undergoing dynamic biological processes, such as cellular differentiation, immune response, and disease progression. While examining cells along a computationally ordered pseudotime offers the potential to study how subtle changes in gene or protein expression impact cell fate decision-making, identifying characteristic features that drive continuous biological processes remains difficult to detect from unenriched and noisy single-cell data. Given that all profiled sources of feature variation contribute to the cell-to-cell distances that define an inferred cellular trajectory, including confounding sources of biological variation (e.g. cell cycle or metabolic state) or noisy and irrelevant features (e.g. measurements with low signal-to-noise ratio) can mask the underlying trajectory of study and hinder inference. Here, we present DELVE (dynamic selection of locally covarying features), an unsupervised feature selection method for identifying a representative subset of dynamically-expressed molecular features that recapitulates cellular trajectories. In contrast to previous work, DELVE uses a bottom-up approach to mitigate the effect of unwanted sources of variation confounding inference, and instead models cell states from dynamic feature modules that constitute core regulatory complexes. Using simulations, single-cell RNA sequencing data, and iterative immunofluorescence imaging data in the context of the cell cycle and cellular differentiation, we demonstrate that DELVE selects features that more accurately characterize cell populations and improve the recovery of cell type transitions. This feature selection framework provides an alternative approach for improving trajectory inference and uncovering co-variation amongst features along a biological trajectory. DELVE is implemented as an open-source python package and is publicly available at:https://github.com/jranek/delve.
5,6,7,8-Tetrahydro-[1,2,4]triazolo[5,1-b]quinazolin-9(4H)-one
Authors: Ettahiri Walid , Dalbouha Amal , Baouid Abdesselam , Alsubari Abdulsalam , Mague Joel T. , Taleb Mustapha , Ramli Youssef
Published: May 2023

The triazole ring in the title molecule, C9H10N4O, is not quite coplanar with the six-membered ring to which it is fused, the dihedral angle between the two least-squares planes being 2.52 (6)°. In the crystal, a layered structure is formed by N—H...N and C—H...O hydrogen bonds plus slipped π-stacking interactions, with the fused cyclohexene rings projecting to either side.
Identifying latent classes to successful AEC innovation through a survey of Finnish construction companies
Authors: Hänninen Kai , Juntunen Jouni , Haapasalo Harri
Published: May 2023

Purpose

The purpose of this study is to describe latent classes explaining the innovation logic in the Finnish construction companies. Innovativeness is a driver of competitive performance and vital to the long-term success of any organisation and company.

Design/methodology/approach

Using finite mixture structural equation modelling (FMSEM), the authors have classified innovation logic into latent classes. The method analyses and recognises classes for companies that have similar logic in innovation activities based on the collected data.

Findings

Through FMSEM analysis, the authors have identified three latent classes that explain the innovation logic in the Finnish construction companies – LC1: the internal innovators; LC2: the non-innovation-oriented introverts; and LC3: the innovation-oriented extroverts. These three latent classes clearly capture the perceptions within the industry as well as the different characteristics and variables.

Research limitations/implications

The presented latent classes explain innovation logic but is limited to analysing Finnish companies. Also, the research is quantitative by nature and does not increase the understanding in the same manner as qualitative research might capture on more specific aspects.

Practical implications

This paper presents starting points for construction industry companies to intensify innovation activities. It may also indicate more fundamental changes for the structure of construction industry organisations, especially by enabling innovation friendly culture.

Originality/value

This study describes innovation logic in Finnish construction companies through three models (LC1–LC3) by using quantitative data analysed with the FMSEM method. The fundamental innovation challenges in the Finnish construction companies are clarified via the identified latent classes.
Student perceptions and interests in sustainability: differences among student groups and impact on student sustainability program participation
Authors: Lee Megan , Byers Tyra , Powell Alyssa
Published: May 2023

Purpose

This study aims to examine factors that impact participation of diverse university students in an academic sustainability certificate and Office of Sustainability internships at the University of Georgia, recognizing the need for diverse voices and perspectives in addressing sustainability challenges and the current lack of diverse representation in the field.

Design/methodology/approach

A convenience sample of 77 student organizations and 35 departments, schools and colleges associated with the university was identified. The questionnaire was created using the Qualtrics online survey platform and distributed via email to potential participants. A total of 234 completed responses were collected. Descriptive statistics were calculated to determine the demographic composition of the sample. One-way ANOVAs were performed to examine the relationship between respondent demographics and perceptions of sustainability and participation in campus sustainability programs. Post hoc tests were conducted using Fisher’s least significant difference procedure.

Findings

Significant relationships were observed between perceptions of sustainability and race and current gender. A significant relationship was observed between race and participation in campus sustainability programs. Overall, students from diverse backgrounds believe that sustainability efforts contribute to racial justice and equity. Additionally, students from diverse backgrounds do want to participate in campus sustainability programs; however, there may be barriers preventing their participation.

Originality/value

This study examines how students from diverse backgrounds perceive sustainability efforts, as well as their interest in participating in campus sustainability programs. The results of this study can be used to inform recruitment and program development strategies for sustainability programs at higher education institutions. At the time of publication, no study could be located that examines the current study outcomes.