bluuebunny/crossref_metadata_2025 huggingface dataset:
Reference genome for the Mojave poppy bee (Perdita meconis), a specialist pollinator of conservation concern
Authors: Schweizer Rena M , Meidt Colleen G , Benavides Ligia R , Wilson Joseph S , Griswold Terry L , Sim Sheina B , Geib Scott M , Branstetter Michael G
Published: December 2023

The Mojave poppy bee, Perdita meconis Griswold (Hymenoptera: Anthophila: Andrenidae), is a species of conservation concern that is restricted to the eastern Mojave Desert of North America. It is a specialist pollinator of two poppy genera, Arctomecon and Argemone (Papaveraceae), and is being considered for listing under the US Endangered Species Act along with one of its pollinator hosts, the Las Vegas bearpoppy (Arctomecon californica). Here, we present a near chromosome-level genome of the Mojave poppy bee to provide a genomic resource that will aid conservation efforts and future research. We isolated DNA from a single, small (<7 mm), male specimen collected using non-ideal preservation methods and then performed whole-genome sequencing using PacBio HiFi technology. After quality and contaminant filtering, the final draft genome assembly is 327 Mb, with an N50 length of 17.5 Mb. Annotated repetitive elements compose 37.3% of the genome, although a large proportion (24.87%) of those are unclassified repeats. Additionally, we annotated 18,245 protein-coding genes and 19,433 transcripts. This genome represents one of only a few genomes from the large bee family Andrenidae and one of only a few genomes for pollinator specialists. We highlight both the potential of this genome as a resource for future research, and how high-quality genomes generated from small, non-ideal (in terms of preservation) specimens could facilitate biodiversity genomics.
Leading with the trailing edge: facilitating patient choice for insulin products
Authors: Feldman Robin
Published: December 2023

Insulin prices have risen sharply, despite a century since its introduction. Against this backdrop, companies have discontinued dozens of insulin products. Discontinuation could relate to safety or effectiveness, or to the overwhelming benefits of newer products. On the other hand, discontinuation could suggest strategic behavior hampering competition and supporting prices. To test these theories, this project examined every insulin discontinuation, analyzing the role discontinuations play in insulin affordability. No evidence emerged of any discontinuation for safety or effectiveness. Rather, dozens of viable products were removed from the market, followed by more expensive versions, often with little or no clinical improvement. Insulin pens with a phone app may provide advantages, for example. However, for older patients, who may find the technology confusing, or for patients with budget constraints, the value proposition falters. Moreover, discontinuation blocks biosimilars from market entry because they cannot demonstrate biosimilarity without the drug. The problem exists for all biosimilars. If there are willing buyers and willing sellers of clinically effective products that are off-patent, entry should be facilitated. This article suggests a requirement that companies deposit samples at the time of FDA approval, laying the groundwork for later entry of trailing-edge products with clinically viable outcomes.
On the effects of photoionization feedback on second-generation star formation in globular clusters of different masses
Authors: Yaghoobi A , Rosdahl J , Calura F , Ataiee S
Published: December 2023

We simulate the formation of second-generation (SG) stars in young clusters with masses of 105 and $10^6\, \mathrm{M}_{\odot }$ within $30\!-\!100\, \mathrm{Myr}$ after the formation of clusters. We assume the clusters move through a uniform interstellar medium with gas densities of 10−24 and $10^{-23}\, \mathrm{g\, cm}^{-3}$ and consider the stellar winds from asymptotic giant branch (AGB) stars, gas accretion on to the cluster, ram pressure, star formation, and photoionization feedback of our stellar systems including binary stars. We find that SG stars can be formed only within the $10^6\, \mathrm{M}_{\odot }$ cluster in the high-density simulation, where the cluster can accrete sufficient pristine gas from their surrounding medium, leading to efficient cooling required for the ignition of SG formation and sufficient dilution of the AGB ejecta. Hence, our results indicate that a denser environment is another requirement for the AGB scenario to explain the presence of multiple populations in globular clusters. On the other hand, the ionizing feedback becomes effective in heating the gas in our low-density simulations. As a result, the clusters cannot accumulate a considerable amount of pristine gas at their centre. The gas mass within the clusters in these simulations is similar to that in young massive clusters (YMCs). Hence, our studies can provide a possible reason for the lack of gas, star formation, and SG stars in YMCs. Our results indicate that the ionizing stellar feedback is not a severe problem for SG formation; rather, it can help the AGB scenario to account for some observables.
Preparing for low surface brightness science with the Vera C. Rubin Observatory: a comparison of observable and simulated intracluster light fractions
Authors: Brough Sarah , Ahad Syeda Lammim , Bahé Yannick M , Ellien Amaël , Gonzalez Anthony H , Jiménez-Teja Yolanda , Kimmig Lucas C , Martin Garreth , Martínez-Lombilla Cristina , Montes Mireia , Pillepich Annalisa , Ragusa Rossella , Remus Rhea-Silvia , Collins Chris A , Knapen Johan H , Mihos J Christopher
Published: December 2023

Intracluster light (ICL) provides an important record of the interactions galaxy clusters have undergone. However, we are limited in our understanding by our measurement methods. To address this, we measure the fraction of cluster light that is held in the Brightest Cluster Galaxy and ICL (BCG+ICL fraction) and the ICL alone (ICL fraction) using observational methods (surface brightness threshold-SB, non-parametric measure-NP, composite models-CM, and multi-galaxy fitting-MGF) and new approaches under development (wavelet decomposition-WD) applied to mock images of 61 galaxy clusters (14 <log10M200c/M⊙ < 14.5) from four cosmological hydrodynamical simulations. We compare the BCG+ICL and ICL fractions from observational measures with those using simulated measures (aperture and kinematic separations). The ICL fractions measured by kinematic separation are significantly larger than observed fractions. We find the measurements are related and provide equations to estimate kinematic ICL fractions from observed fractions. The different observational techniques give consistent BCG+ICL and ICL fractions but are biased to underestimating the BCG+ICL and ICL fractions when compared with aperture simulation measures. Comparing the different methods and algorithms, we find that the MGF algorithm is most consistent with the simulations, and CM and SB methods show the smallest projection effects for the BCG+ICL and ICL fractions, respectively. The Ahad (CM), MGF, and WD algorithms are best set up to process larger samples; however, the WD algorithm in its current form is susceptible to projection effects. We recommend that new algorithms using these methods are explored to analyse the massive samples that Rubin Observatory’s Legacy Survey of Space and Time will provide.
Constraining the X-ray radiation origin of 3C 273 in the low state by polarization
Authors: Liu Mingjun , Zhang Wenda , Yuan Weimin
Published: December 2023

3C 273 is one of the nearest high-luminosity quasars. Although classified as a blazar, 3C 273 also has some features in Seyferts, whose X-ray may originate from the corona. Since both jet and corona produce power-law spectra in X-ray, the spectrum cannot completely distinguish their contributions to 3C 273 in the low state. X-ray polarimetric observations provide the chance to constrain the X-ray radiation origin of 3C 273 in the low state. We perform general relativistic radiative transfer simulations with the code monk to compute the X-ray polarization in 2–10 keV from the jets, sphere coronae, and slab coronae for 3C 273. We find that the radiation from the jet in 2–10 keV has a larger polarization degree than that of the corona: the polarization degree in 2–10 keV from the corona is unpolarized, while these are 4.1 per cent–15.8 per cent for the jet with a vertical or radial magnetic field and ≤5.0 per cent for the jet with toroidal magnetic field. The X-ray polarization of the corona and jet is sensitive to optical depth and geometry, and the main driver for this dependence is the number of scatterings. These results show that X-ray polarization can effectively constrain the X-ray radiation origin of 3C 273 in the low state.
Stability and Ly α emission of Cold Stream in the Circumgalactic Medium: impact of magnetic fields and thermal conduction
Authors: Ledos Nicolas , Takasao Shinsuke , Nagamine Kentaro
Published: December 2023

Cold streams of gas with temperatures around 104 K play a crucial role in the gas accretion on to high-redshift galaxies. The current resolution of cosmological simulations is insufficient to fully capture the stability and Ly α emission characteristics of cold stream accretion, underscoring the imperative need for conducting idealized high-resolution simulations. We investigate the impact of magnetic fields at various angles and anisotropic thermal conduction (TC) on the dynamics of radiatively cooling streams through a comprehensive suite of two-dimensional high-resolution simulations. An initially small magnetic field ($\sim 10^{-3} \, \mu\rm G$), oriented non-parallel to the stream, can grow significantly, providing stability against Kelvin–Helmholtz instabilities and reducing the Ly α emission by a factor of <20 compared to the hydrodynamics case. With TC, the stream evolution can be categorized into three regimes: (1) the Diffusing Stream regime, where the stream diffuses into the surrounding hot circumgalactic medium; (2) the Intermediate regime, where TC diffuses the mixing layer, resulting in enhanced stabilization and reduced emissions; (3) the Condensing Stream regime, where the impact of magnetic field and TC on the stream’s emission and evolution becomes negligible. Extrapolating our findings to the cosmological context suggests that cold streams with a radius of $\le 1 \rm \, {\rm kpc}$ may fuel galaxies with cold metal-enriched magnetized gas ($B \sim 0.1\!-\!1 \, \mu \rm G$) for a longer time, leading to a broad range of Ly α luminosity signatures of $\sim 10^{37}\!-\!10^{41}\, \rm \, erg \, s^{-1}$.
Galaxy kinematics and mass estimates at z ∼ 1 from ionized gas and stars
Authors: Übler Hannah , Förster Schreiber Natascha M , van der Wel Arjen , Bezanson Rachel , Price Sedona H , D’Eugenio Francesco , Wisnioski Emily , Genzel Reinhard , Tacconi Linda J , Wuyts Stijn , Naab Thorsten , Lutz Dieter , Straatman Caroline M S , Shimizu Thomas Taro , Davies Ric , Liu Daizhong , Mendel Trevor
Published: December 2023

We compare ionized gas and stellar kinematics of 16 star-forming galaxies (log (M⋆/M⊙) = 9.7–11.2, SFR =6 − 86 M⊙ yr−1) at z ∼ 1 using near-infrared integral field spectroscopy (IFS) of Hα emission from the KMOS3D (the K-band Multi-Object Spectrograph 3D) survey and optical slit spectroscopy of stellar absorption and gas emission from the LEGA-C (Large Early Galaxy Astrophysics Census) survey. Hα is dynamically colder than stars, with higher disc rotation velocities (by ∼45 per cent) and lower disc velocity dispersions (by a factor ∼2). This is similar to trends observed in the local Universe. We find higher rotational support for Hα relative to [O ii], potentially explaining systematic offsets in kinematic scaling relations found in the literature. Regarding dynamical mass measurements, for six galaxies with cumulative mass profiles from Jeans Anisotropic Multi-Gaussian Expansion (JAM) models the Hα dynamical mass models agree remarkably well out to ∼10 kpc for all but one galaxy (average $\Delta M_{\rm dyn}(R_{e,\rm F814W})\lt 0.1$ dex). Simpler dynamical mass estimates based on integrated stellar velocity dispersion are less accurate (standard deviation 0.24 dex). Differences in dynamical mass estimates are larger, for example, for galaxies with stronger misalignments of the Hα kinematic major axis and the photometric position angle, highlighting the added value of IFS observations for dynamics studies. The good agreement between the JAM and the dynamical models based on Hα kinematics at z ∼ 1 corroborates the validity of dynamical mass measurements from Hα IFS observations, which can be more easily obtained for higher redshift galaxies.
‘Life’ of dust originating from the irregular satellites of Jupiter
Authors: Chen Zhenghan , Yang Kun , Liu Xiaodong
Published: December 2023

The irregular satellites of Jupiter produce dust particles through the impact of interplanetary micrometeoroids. In this paper, the dynamics of these particles is studied by both high-accuracy numerical simulation and analytical theory, in order to learn their transport, final fate, and spatial distribution. The perturbation forces that are considered in our dynamical model include the solar radiation pressure, solar gravity, Poynting–Robertson drag, Jovian oblateness, and the Galilean satellites’ gravity. The trajectories of different size particles are simulated until they hit Jupiter, the Galilean satellites, or escape from the Jovian system. The average dynamical lifetimes of dust with different grain sizes are calculated, and the final fate of dust particles is reported and analysed. The steady-state spatial number density of particles is estimated by integrating the trajectories of dust particles over their initial size distribution, and compared to the previous work. The impact sites of dust on Callisto’s surface are recorded and provide an important clue for the study of the hemisphere asymmetry of Callisto. Besides, the mass accretion rate, cross-sectional area influx, and mass influx density of dust on Callisto are calculated. A ring outside the orbit of Callisto dominated by dust between 2 and 25 µm from Jupiter’s irregular satellites is suggested, with the average normal geometric optical depth of the order of 10−8 and the configuration of the ring ansae similar to Jupiter’s gossamer rings.
Galaxies decomposition with spiral arms – I: 29 galaxies from S4G
Authors: Chugunov Ilia V , Marchuk Alexander A , Mosenkov Aleksandr V , Savchenko Sergey S , Shishkina Ekaterina V , Chazov Maxim I , Nazarova Aleksandra E , Skryabina Maria N , Smirnova Polina I , Smirnov Anton A
Published: December 2023

Spiral structure can occupy a significant part of the galaxy, but properly accounting for it in photometric decomposition is rarely done. This may lead to significant errors in the parameters determined. To estimate how exactly neglecting the presence of spiral arms affects the estimation of galaxy decomposition parameters, we perform fitting of 29 galaxies considering spiral arms as a separate component. In this study, we utilize 3.6 μm-band images from the S4G survey and use a new 2D photometric model where each spiral arm is modelled independently. In our model, the light distribution both along and across the arm and its overall shape can be varied significantly. We analyse the differences between models with and without spiral arms, and show that neglecting spiral arms in decomposition causes errors in estimating the parameters of the disc, the bulge, and the bar. We retrieve different parameters of the spiral arms themselves, including their pitch angles, widths, and spiral-to-total luminosity ratio, and examine various relations between them and other galaxy parameters. In particular, we find that the spiral-to-total ratio is higher for galaxies with more luminous discs and with higher bulge-to-total ratios. We report that the pitch angle of spiral arms decreases with increasing bulge or bar fraction. We measure the width of the spiral arms to be 53 per cent of the disc scale length, on average. We examine the contribution of the spiral arms to the azimuthally averaged brightness profile and find that spiral arms produce a ‘bump’ on this profile with a typical height of 0.3–0.7 mag.
HetFCM: functional co-module discovery by heterogeneous network co-clustering
Authors: Tan Haojiang , Guo Maozu , Chen Jian , Wang Jun , Yu Guoxian
Published: December 2023

Functional molecular module (i.e., gene–miRNA co-modules and gene–miRNA–lncRNA triple-layer modules) analysis can dissect complex regulations underlying etiology or phenotypes. However, current module detection methods lack an appropriate usage and effective model of multi-omics data and cross-layer regulations of heterogeneous molecules, causing the loss of critical genetic information and corrupting the detection performance. In this study, we propose a heterogeneous network co-clustering framework (HetFCM) to detect functional co-modules. HetFCM introduces an attributed heterogeneous network to jointly model interplays and multi-type attributes of different molecules, and applies multiple variational graph autoencoders on the network to generate cross-layer association matrices, then it performs adaptive weighted co-clustering on association matrices and attribute data to identify co-modules of heterogeneous molecules. Empirical study on Human and Maize datasets reveals that HetFCM can find out co-modules characterized with denser topology and more significant functions, which are associated with human breast cancer (subtypes) and maize phenotypes (i.e., lipid storage, drought tolerance and oil content). HetFCM is a useful tool to detect co-modules and can be applied to multi-layer functional modules, yielding novel insights for analyzing molecular mechanisms. We also developed a user-friendly module detection and analysis tool and shared it at http://www.sdu-idea.cn/FMDTool.
Behavioral and Pharmacokinetic Assessment of Nicotine e-Cigarette Inhalation in Female Rats
Authors: Roeder Nicole M , Mihalkovic Abrianna , Richardson Brittany J , Penman Samantha L , Novalen Maria , Hammond Nikki , Eiden Rina , Khokhar Jibran Y , Tyndale Rachel F , Thanos Panayotis K
Published: December 2023

Introduction

Nicotine and tobacco use remain high both globally and in the United States, contributing to large health care expenditures. With a rise in e-cigarette use, it is important to have clinically relevant models of inhaled nicotine exposure.

Aims and Methods

This study aims to extend prior preclinical nicotine inhalation animal data to females and provide both behavior and serum pharmacokinetics. We tested two inhalation doses of nicotine (24 mg/mL and 59 mg/ mL) and compared these to injected doses (0.4 mg/kg and 1 mg/kg). In addition, we assessed locomotor behavior after the same doses. Blood was collected at 10- and 120-minutes post-administration. We assessed nicotine and cotinine serum concentrations by LC–MS/MS.

Results

Showed that while nicotine serum concentrations for the respective high and low-dose administrations were similar between both routes of administration, the route had differential effects on locomotor behavior. Inhaled nicotine showed a dose-dependent decrease in locomotor activity while injected doses showed the opposite trend.

Conclusions

Our results indicate that the route of administration is an important factor when establishing preclinical models of nicotine exposures. Given that the overall use of e-cigarettes in vulnerable populations is on the rise, our study provides important behavioral and pharmacokinetic information to advance our currently limited understanding of the effects of nicotine vapor exposure.

Implications

This study highlights behavioral differences between different routes of administration of similar doses of nicotine. Using a low and high dose of nicotine, we found that nicotine serum concentrations were similar between the different routes of administration. Our results indicate that different routes of administration have opposing effects on locomotor activity. These findings provide important implications for future behavioral models.
First-Generation Cephalosporins for Treatment of Acute Hematogenous Osteomyelitis in Children: A Study of Efficacy and Adverse Effects
Authors: Hiskey Lisa , Saifuddin Hiba , Levy Emily R , Hentz Roland , Rajapakse Nipunie S , Dinnes Laura M , Ristagno Elizabeth H
Published: December 2023

Background

Acute hematogenous osteomyelitis (AHO) is a relatively infrequent but significant infection in pediatric patients. As Staphylococcus aureus is the most common cause of AHO, intravenous and oral first-generation cephalosporins are common therapies. Cephalexin is a commonly prescribed oral therapy for pediatric AHO, although it requires frequent dosing that may affect adherence. Cefadroxil is a comparable oral first-generation cephalosporin with a more desirable dosing schedule.

Methods

We reviewed pediatric patients admitted to Mayo Clinic between March 2002 and September 2020 for management of AHO who received treatment with a first-generation cephalosporin. We reviewed timing of oral therapy transition, therapy-associated adverse effects, and recurrence of disease after completion of therapy.

Results

There were 59 patients included in the study. There was similar occurrence of adverse effects in patients receiving cefadroxil and cephalexin, although use of cefadroxil coincided with more gastrointestinal adverse effects and leukopenia and use of cephalexin with more rash and neutropenia. One secondary treatment failure occurred in our study, in a patient receiving cephalexin for treatment of septic arthritis.

Conclusions

Cefadroxil may be a reasonable alternative oral therapy for methicillin-susceptible S aureus or culture-negative AHO in pediatric patients, particularly when a less frequent dosing schedule is desired. Future study with a larger sample size is warranted.
Creating a Low-Stimulus Clinic to improve immunization success rates for children with alternate environment needs: A quality improvement initiative
Authors: McDonald Megan , Gallaugher Shauna , Kammerer Elise , Ali Samina
Published: December 2023

Patients with specific sensory needs may face barriers to receiving their immunizations. Therefore, a Low-Stimulus Clinic was created in Alberta. Modifications to regular clinic space included lower visual and auditory input, access to longer appointment times and private clinic spaces, development of pre-appointment comfort plans, and offering of in-vehicle immunization. Between April 2021 and May 2022, 90% (641/712) of booked patients were successfully immunized. The top reasons for accessing the clinic included autism spectrum disorder (229/712, 32%), and needle fear/phobia (195/712, 27%). The Low-Stimulus Clinic had a high rate of successful vaccination for populations that may otherwise have been less likely to receive immunizations. Its workflows support the principles of choice, collaboration, and control in creating a positive immunization experience for patients and their families. Having such clinics widely available is a key step in reducing barriers to accessing vaccines for individuals with specific sensory needs.
A high-resolution gene expression map of the medial and lateral domains of the gynoecium of Arabidopsis
Authors: Luna-García Valentín , Bernal Gallardo Judith Jazmin , Rethoret-Pasty Martin , Pasha Asher , Provart Nicholas J , de Folter Stefan
Published: December 2023

Angiosperms are characterized by the formation of flowers, and in their inner floral whorl, one or various gynoecia are produced. These female reproductive structures are responsible for fruit and seed production, thus ensuring the reproductive competence of angiosperms. In Arabidopsis (Arabidopsis thaliana), the gynoecium is composed of two fused carpels with different tissues that need to develop and differentiate to form a mature gynoecium and thus the reproductive competence of Arabidopsis. For these reasons, they have become the object of study for floral and fruit development. However, due to the complexity of the gynoecium, specific spatio-temporal tissue expression patterns are still scarce. In this study, we used precise laser-assisted microdissection and high-throughput RNA sequencing to describe the transcriptional profiles of the medial and lateral domain tissues of the Arabidopsis gynoecium. We provide evidence that the method used is reliable and that, in addition to corroborating gene expression patterns of previously reported regulators of these tissues, we found genes whose expression dynamics point to being involved in cytokinin and auxin homeostasis and in cell cycle progression. Furthermore, based on differential gene expression analyses, we functionally characterized several genes and found that they are involved in gynoecium development. This resource is available via the Arabidopsis eFP browser and will serve the community in future studies on developmental and reproductive biology.
Deep learning approaches to the phylogenetic placement of extinct pollen morphotypes
Authors: Adaïmé Marc-Élie , Kong Shu , Punyasena Surangi W
Published: December 2023

The phylogenetic interpretation of pollen morphology is limited by our inability to recognize the evolutionary history embedded in pollen features. Deep learning offers tools for connecting morphology to phylogeny. Using neural networks, we developed an explicitly phylogenetic toolkit for analyzing the overall shape, internal structure, and texture of a pollen grain. Our analysis pipeline determines whether testing specimens are from known species based on uncertainty estimates. Features from specimens with uncertain taxonomy are passed to a multilayer perceptron network trained to transform these features into predicted phylogenetic distances from known taxa. We used these predicted distances to place specimens in a phylogeny using Bayesian inference. We trained and evaluated our models using optical superresolution micrographs of 30 extant Podocarpus species. We then used trained models to place nine fossil Podocarpidites specimens within the phylogeny. In doing so, we demonstrate that the phylogenetic history encoded in pollen morphology can be recognized by neural networks and that deep-learned features can be used in phylogenetic placement. Our approach makes extinction and speciation events that would otherwise be masked by the limited taxonomic resolution of the fossil pollen record visible to palynological analysis.
Intradiscal inflammatory stimulation induces spinal pain behavior and intervertebral disc degeneration in vivo
Authors: Lisiewski Lauren E. , Jacobsen Hayley E. , Viola Dan C. M. , Kenawy Hagar M. , Kiridly Daniel N. , Chahine Nadeen O.
Published: December 2023

Degeneration of the intervertebral disc (IVD) results in a range of symptomatic (i.e., painful) and asymptomatic experiences. Components of the degenerative environment, including structural disruption and inflammatory cytokine production, often correlate with pain severity. However, the role of inflammation in the activation of pain and degenerative changes has been complex to delineate. The most common IVD injury model is puncture; however, it initiates structural damage that is not representative of the natural degenerative cascade. In this study, we utilized in vivo injection of lipopolysaccharide (LPS), a pro‐inflammatory stimulus, into rat caudal IVDs using 33G needles to induce inflammatory activation without the physical tissue disruption caused by puncture using larger needles. LPS injection increased gene expression of pro‐inflammatory cytokines (Tnfa, Il1b) and macrophage markers (Inos, Arg1), supported by immunostaining of macrophages (CD68, CCR7, Arg1) and systemic changes in blood cytokine and chemokine levels. Disruption of the IVD structural integrity after LPS injection was also evident through changes in histological grading, disc height, and ECM biochemistry. Ultimately, intradiscal inflammatory stimulation led to local mechanical hyperalgesia, demonstrating that pain can be initiated by inflammatory stimulation of the IVD. Gene expression of nociceptive markers (Ngf, Bdnf, Cgrp) and immunostaining for neuron ingrowth (PGP9.5) and sensitization (CGRP) in the IVD were also shown, suggesting a mechanism for the pain exhibited. To our knowledge, this rat IVD injury model is the first to demonstrate local pain behavior resulting from inflammatory stimulation of caudal IVDs. Future studies will examine the mechanistic contributions of inflammation in mediating pain.
In Vitro Model of Prepacked Carbon Dioxide Absorber Use: Development and Testing
Authors: Jouwena Jennifer , Verbeke Delphine , De Wolf Andre M. , Neyrinck Arne , Hendrickx Jan F. A.
Published: December 2023

Background

Carbon dioxide absorbers allow the use of fresh gas flow below minute ventilation (

). Models are developed and tested in vitro to quantify their performance with variable carbon dioxide load (

), fresh gas flow,

, end-tidal carbon dioxide (ETco
2) fraction, and the type of workstation used.

Methods

First principles are used to derive a linear relationship between fresh gas flow and fractional canister usage or FCU0.5 (the reciprocal of the time for the inspiratory carbon dioxide fraction to reach 0.5%). This forms the basis for two basic models in which

was measured by spirometry or calculated. These models were extended by multiplying

with an empirical workstation factor. To validate the four models, two hypotheses were tested. To test whether the FCU0.5 intercept varied proportionally with

and was independent of

, FCU was measured for 10 canisters tested with a fixed 0.3 l/min fresh gas flow and a range of

while

was either constant or adjusted to maintain ETco
2 fraction. A t test was used to compare the two groups. To confirm whether a change in

accompanied by a change in

to maintain ETco
2 fraction would shift the linear fresh gas flow–FCU0.5 relationship in a parallel manner, 19 canisters were tested with different combinations of

and fresh gas flow. These measured FCU values were compared to those predicted by the four models using Varvel’s performance criteria.

Results

With 0.3 l/min fresh gas flow, FCU0.5 was proportional with

and independent of whether

was adjusted to maintain ETco
2 fraction or not (P = 0.962). The hypothesized parallel shift of the fresh gas flow–FCU0.5 relationship was confirmed. Both extended models are good candidate models.

Conclusions

The models predict prepacked canister performance in vitro over the range of

, fresh gas flow, and

likely to be encountered in routine clinical practice. In vivo validation is still needed.

Editor’s Perspective

What We Already Know about This Topic

What This Article Tells Us That Is New
Feasibility of Prone Positioning for Brain-injured Patients with Severe Acute Respiratory Distress Syndrome: A Systematic Review and Pilot Study (ProBrain)
Authors: Elmaleh Yoann , Yavchitz Amélie , Léguillier Teddy , Squara Pierre-Alexandre , Palpacuer Clément , Grégoire Charles
Published: December 2023

Background

Prone position is a key component to treat hypoxemia in patients with severe acute respiratory distress syndrome. However, most studies evaluating it exclude patients with brain injuries without any medical evidence.

Methods

This study includes a systematic review to determine whether brain-injured patients were excluded in studies evaluating prone position on acute respiratory distress syndrome; a prospective study including consecutive brain-injured patients needing prone position. The primary endpoint was the evaluation of cerebral blood flow using transcranial Doppler after prone positioning. Secondary outcomes were intracranial pressure, cerebral perfusion pressure, and tissue oxygen pressure.

Results

From 8,183 citations retrieved, 120 studies were included in the systematic review. Among them, 90 studies excluded brain-injured patients (75%) without any justification, 16 included brain-injured patients (4 randomized, 7 nonrandomized studies, 5 retrospective), and 14 did not retrieve brain-injured data. Eleven patients were included in the authors’ pilot study. No reduction of cerebral blood flow surrogates was observed during prone positioning, with diastolic speed values (mean ± SD) ranging from 37.7 ± 16.2 cm/s to 45.2 ± 19.3 cm/s for the right side (P = 0.897) and 39.6 ± 18.2 cm/s to 46.5 ± 21.3 cm/s for the left side (P = 0.569), and pulsatility index ranging from 1.14 ± 0.31 to 1.0 ± 0.32 for the right side (P = 0.145) and 1.14 ± 0.31 to 1.02 ± 0.2 for the left side (P = 0.564) before and during prone position.

Conclusions

Brain-injured patients are largely excluded from studies evaluating prone position in acute respiratory distress syndrome. However, cerebral blood flow seems not to be altered considering increasing of mean arterial pressure during the session. Systematic exclusion of brain-injured patients appears to be unfounded, and prone position, while at risk in brain-injured patients, should be evaluated on these patients to review recommendations, considering close monitoring of neurologic and hemodynamic parameters.

Editor’s Perspective

What We Already Know about This Topic

What This Article Tells Us That Is New
Effect of Automated Real-Time Feedback on Early-Sepsis Care: A Pragmatic Clinical Trial*
Authors: Leisman Daniel E. , Deng Hao , Lee Andy H. , Flynn Micah H. , Rutkey Hayley , Copenhaver Martin S. , Gay Elizabeth A. , Dutta Sayon , McEvoy Dustin S. , Dunham Lisette N. , Mort Elizabeth A. , Lucier David J. , Sonis Jonathan D. , Aaronson Emily L. , Hibbert Kathryn A. , Safavi Kyan C.
Published: December 2023

OBJECTIVES:

To determine if a real-time monitoring system with automated clinician alerts improves 3-hour sepsis bundle adherence.

DESIGN:

Prospective, pragmatic clinical trial. Allocation alternated every 7 days.

SETTING:

Quaternary hospital from December 1, 2020 to November 30, 2021.

PATIENTS:

Adult emergency department or inpatients meeting objective sepsis criteria triggered an electronic medical record (EMR)-embedded best practice advisory. Enrollment occurred when clinicians acknowledged the advisory indicating they felt sepsis was likely.

INTERVENTION:

Real-time automated EMR monitoring identified suspected sepsis patients with incomplete bundle measures within 1-hour of completion deadlines and generated reminder pages. Clinicians responsible for intervention group patients received reminder pages; no pages were sent for controls. The primary analysis cohort was the subset of enrolled patients at risk of bundle nonadherent care that had reminder pages generated.

MEASUREMENTS AND MAIN RESULTS:

The primary outcome was orders for all 3-hour bundle elements within guideline time limits. Secondary outcomes included guideline-adherent delivery of all 3-hour bundle elements, 28-day mortality, antibiotic discontinuation within 48-hours, and pathogen recovery from any culture within 7 days of time-zero. Among 3,269 enrolled patients, 1,377 had reminder pages generated and were included in the primary analysis. There were 670 (48.7%) at-risk patients randomized to paging alerts and 707 (51.3%) to control. Bundle-adherent orders were placed for 198 intervention patients (29.6%) versus 149 (21.1%) controls (difference: 8.5%; 95% CI, 3.9–13.1%; p = 0.0003). Bundle-adherent care was delivered for 152 (22.7%) intervention versus 121 (17.1%) control patients (difference: 5.6%; 95% CI, 1.4–9.8%; p = 0.0095). Mortality was similar between groups (8.4% vs 8.3%), as were early antibiotic discontinuation (35.1% vs 33.4%) and pan-culture negativity (69.0% vs 68.2%).

CONCLUSIONS:

Real-time monitoring and paging alerts significantly increased orders for and delivery of guideline-adherent care for suspected sepsis patients at risk of 3-hour bundle nonadherence. The trial was underpowered to determine whether adherence affected mortality. Despite enrolling patients with clinically suspected sepsis, early antibiotic discontinuation and pan-culture negativity were common, highlighting challenges in identifying appropriate patients for sepsis bundle application.
Metabolic plasticity of T cell fate decision
Authors: Pan Xiaoli , Wang Jiajia , Zhang Lianjun , Li Guideng , Huang Bo
Published: December 2023

The efficacy of adaptive immune responses in cancer treatment relies heavily on the state of the T cells. Upon antigen exposure, T cells undergo metabolic reprogramming, leading to the development of functional effectors or memory populations. However, within the tumor microenvironment (TME), metabolic stress impairs CD8+T cell anti-tumor immunity, resulting in exhausted differentiation. Recent studies suggested that targeting T cell metabolism could offer promising therapeutic opportunities to enhance T cell immunotherapy. In this review, we provide a comprehensive summary of the intrinsic and extrinsic factors necessary for metabolic reprogramming during the development of effector and memory T cells in response to acute and chronic inflammatory conditions. Furthermore, we delved into the different metabolic switches that occur during T cell exhaustion, exploring how prolonged metabolic stress within the TME triggers alterations in cellular metabolism and the epigenetic landscape that contribute to T cell exhaustion, ultimately leading to a persistently exhausted state. Understanding the intricate relationship between T cell metabolism and cancer immunotherapy can lead to the development of novel approaches to improve the efficacy of T cell-based treatments against cancer.
Defining an approach for therapeutic strategies in metabolic dysfunction–associated steatotic liver disease after liver transplantation
Authors: Siddiqui Mohammad Shadab , Muthiah Mark , Satapathy Sanjaya K. , Patidar Kavish R. , Bhat Mamatha , Brandman Danielle , Watt Kymberly D. , Rinella Mary
Published: December 2023

Occurrence of metabolic dysfunction–associated steatotic liver disease (MASLD) is common following liver transplantation (LT). MASLD can be classified as a recurrent disease when it occurs in patients receiving LT for metabolic dysfunction–associated steatohepatitis (MASH) or as de novo when it occurs in patients undergoing transplantation for non-metabolic dysfunction–associated steatohepatitis etiologies of liver disease. Fibrosis progression in patients with MASLD is accelerated, with progression to cirrhosis occurring more rapidly compared with the general (ie, non-LT) population. Moreover, the metabolic burden in LT recipients with MASLD is high and synergizes with liver disease to negatively affect the clinical course. Despite the oversized clinical burden of MASLD among LT recipients, there is currently a lack of regulatory approach and pathway for therapeutics development in this patient population. The present document, thus, provides guidance for therapeutics development that incorporates nuances of transplant care in patients with post-LT MASLD to facilitate drug development.
Accumulation of advanced glycation end products in skin and increased vascular ageing in the general population: the Malmö Offspring Study
Authors: Jujic Amra , Engström Gunnar , Nilsson Peter M. , Johansson Madeleine
Published: December 2023

Objectives:

Advanced glycation end product (AGE) is an established risk marker for diabetic vascular disease, and associated with the degree of diabetes complications, renal failure, and atherosclerosis in middle-aged and older individuals. The relationship between AGEs and aortic stiffness has not been thoroughly examined in the younger general population. We aimed to evaluate the association between AGEs and aortic stiffness in the general population of young and middle-aged adults.

Methods:

We analysed cross-sectionally 2518 participants from a Swedish population-based cohort, the Malmö Offspring Study (mean age 41.8 ± 14.5 years, 52.2%). Advanced glycation end-products (AGEs) were measured by a well validated, noninvasive method using skin autofluorescence with AGE-Reader. Aortic stiffness was assessed by carotid–femoral pulse wave velocity (PWV) and augmentation index (Aix) was calibrated to a standard heart rate of 75 bpm at the arteria radialis using SphygmoCor. Multivariable linear regression was performed stratified by age to analyse the association between skin AGE and aortic stiffness.

Results:

Increased levels of AGEs were significantly associated with higher direct measurements of aortic stiffness (vascular ageing) in younger individuals (PWV β 0.55 m/s, P < 0.001) after adjustment for traditional cardiometabolic risk factors, however, not in older individuals (PWV β 0.23 m/s, P = 0.10). Indirect vascular ageing was also significantly associated with higher levels of AGEs in both younger (Aix β 7.78, P < 0.001) and older individuals (Aix β 3.69, P < 0.001).

Conclusion:

Higher levels of skin autofluorescence-AGEs are positively associated with increased vascular ageing in younger adults from the general population, independent of cardiometabolic risk factors.
OCULAR ISCHEMIC SYNDROME IN THE SETTING OF NORMAL CAROTID DUPLEX ULTRASOUND
Authors: Ghoraba Hashem H. , Yu Michael , Yu Gina , Wang Sean , Or Chris , Karaca Irmak , Nguyen Quan Dong
Published: December 2023

Purpose:

The aim of this study was to describe two cases of ocular ischemic syndrome (OIS) that were initially ruled out because of a negative carotid duplex ultrasound but eventually confirmed by angiography studies.

Methods:

This is a case series.

Results:

Case 1: A 67-year-old woman presented with symptoms suggestive of OIS, but carotid duplex ultrasound was negative, and the patient was diagnosed with occlusive retinal vasculitis due to retinal nonperfusion and vascular leakage on fluorescein angiography. Immunosuppressive therapy was initiated, but her symptoms did not improve. Computerized tomography angiography was significant for severe osteal stenosis of the aortic arch vessels. Left common carotid angioplasty and stenting resulted in complete resolution of the symptoms and vascular leakage of the left eye. Case 2: A 41-year-old man with cryoglobulinemia-associated vasculitis complained of symptoms consistent with OIS, which was initially ruled out through a negative carotid duplex ultrasound. Fluorescein angiography revealed delayed arterial filling with poor retinal perfusion. Magnetic resonance angiography revealed ophthalmic artery stenosis, which was attributed to the underlying systemic vasculitis.

Conclusion:

Computerized tomography angiography or magnetic resonance angiography should be performed to rule out OIS if duplex ultrasound is negative in the setting of high clinical suspicion. Carotid ostial and ophthalmic artery stenoses are rare but possible causes of OIS.
ACUTE ATROPHIC EVOLUTION OF DRUSENOID PIGMENT EPITHELIUM DETACHMENT AFTER PHOTOBIOMODULATION
Authors: Battaglia Parodi Maurizio , Antropoli Alessio , Arrigo Alessandro , Cicinelli Maria Vittoria , Bianco Lorenzo , Saladino Andrea , Moretti Enea , Bandello Francesco , Mansour Ahmad
Published: December 2023

Purpose:

The aim of this study was to report the acute onset of macular atrophy soon after photobiomodulation (PBM) administration in a patient with intermediate age-related macular degeneration.

Methods:

Optical coherence tomography was performed in the study eye before and after PBM.

Results:

A patient with drusenoid pigment epithelium detachment (D-PED) underwent PBM. A few weeks after PBM, the D-PED collapsed, resulting in complete retinal pigment epithelium and outer retinal atrophy with visual acuity worsening.

Conclusion:

Thinning of the outer retinal layers over a D-PED and posterior hypertransmission may represent bad prognostic factors for PBM, accelerating the lesion's natural history toward atrophic evolution.
RELENTLESS PLACOID CHORIORETINITIS RESPONSIVE TO INTRAVITREAL TRIAMCINOLONE AND SYSTEMIC ADALIMUMAB
Authors: Porteny Jacqueline R. , Witkin Andre J.
Published: December 2023

Purpose:

The authors describe a case of relentless placoid chorioretinitis that was responsive to intravitreal triamcinolone and systemic adalimumab, but suboptimally responsive to oral prednisone.

Methods

: This is an interventional case report.

Results:

A 23-year-old woman presented with macular placoid chorioretinitis in the left eye and visual acuity of finger counting at 3 feet. Despite a 2-week course of 60 mg oral prednisone, the choroiditis expanded dramatically in the midperiphery. She was admitted to the hospital for high-dose IV corticosteroids, which stopped the progression of disease. After discharge, the patient was started on adalimumab and restarted oral prednisone; however, on resumption of oral prednisone 60 mg, the disease started to progress again over the next 2 weeks. An intravitreal injection of triamcinolone (intravitreal triamcinolone) 2 mg was given, which halted the progression of the disease for at least 9 weeks, at which time it was believed that the adalimumab started to also have an effect. The visual acuity 9 weeks after intravitreal triamcinolone had improved to 20/20. The patient was lost to follow-up after this point.

Conclusion:

This is a case of relentless placoid chorioretinitis that continued to progress despite high-dose oral corticosteroids, but which responded to intravitreal triamcinolone and systemic adalimumab. This indicates that intravitreal corticosteroids may represent an alternative treatment option to oral corticosteroids in the short-term management of macula-threatening noninfectious chorioretinitis, particularly in patients with a suboptimal response to oral corticosteroids.
IDENTIFICATION OF CHOROIDAL VASCULAR ABNORMALITIES IN PATIENTS WITH HEREDITARY HEMORRHAGIC TELANGIECTASIA
Authors: Luong Hanna N. , Houghton Odette M.
Published: December 2023

Purpose:

The aim of this study was to evaluate the frequency of ocular imaging in patients with hereditary hemorrhagic telangiectasia (HHT) at a large academic medical institution, characterize the choroidal vascular changes on indocyanine green angiography and optical coherence tomography, and explore the relationship of these ocular features with HHT genotypes and systemic manifestations.

Methods:

This is a retrospective review of patients with HHT who were seen in the Mayo Clinic ophthalmology department between 2011 and 2021.

Results:

Of the 71 patients with HHT identified, 7 patients (10%) had qualifying imaging defined as radial or raster spectral-domain optical coherence tomography scans and/or indocyanine green angiography. Four patients (57%) had enlarged choroidal vessels detected on optical coherence tomography and/or indocyanine green angiography. Three patients (43%) had retinal telangiectasias. Patients with choroidal changes (mean age 67 years) had the endoglin gene mutation, gastrointestinal arteriovenous malformations, and facial and mucocutaneous telangiectasias. By contrast, patients without choroidal changes (mean age 45 years) included the activin A receptor-like kinase 1 gene mutation.

Conclusion:

Only a small proportion of patients with HHT undergo ophthalmic imaging at the authors’ institution. The presence of choroidal abnormalities is associated with the endoglin gene mutation, older age, corroborating retinal vascular changes, and increased systemic manifestations.