bluuebunny/crossref_metadata_2025 huggingface dataset:
Impact of the COVID‐19 pandemic on chronic disease management and patient reported outcomes in patients with pulmonary hypertension: The Pulmonary Hypertension Association Registry
Authors: Mayer Megan , Badesch David B. , Nielsen Kelly H. , Kawut Steven , Bull Todd , Ryan John J. , Sager Jeffrey , Mazimba Sula , Hemnes Anna , Klinger James , Runo James , McConnell John W. , De Marco Teresa , Chakinala Murali M. , Yung Delphine , Elwing Jean , Kaplan Adolfo , Argula Rahul , Pomponio Raymond , Peterson Ryan , Hountras Peter
Published: April 2023

To better understand the impact of the COVID‐19 pandemic on the care of patients with pulmonary hypertension, we conducted a retrospective cohort study evaluating health insurance status, healthcare access, disease severity, and patient reported outcomes in this population. Using the Pulmonary Hypertension Association Registry (PHAR), we defined and extracted a longitudinal cohort of pulmonary arterial hypertension (PAH) patients from the PHAR's inception in 2015 until March 2022. We used generalized estimating equations to model the impact of the COVID‐19 pandemic on patient outcomes, adjusting for demographic confounders. We assessed whether insurance status modified these effects via covariate interactions. PAH patients were more likely to be on publicly‐sponsored insurance during the COVID‐19 pandemic compared with prior, and did not experience statistically significant delays in access to medications, increased emergency room visits or nights in the hospital, or worsening of mental health metrics. Patients on publicly‐sponsored insurance had higher healthcare utilization and worse objective measures of disease severity compared with privately insured individuals irrespective of the COVID‐19 pandemic. The relatively small impact of the COVID‐19 pandemic on pulmonary hypertension‐related outcomes was unexpected but may be due to pre‐established access to high quality care at pulmonary hypertension comprehensive care centers. Irrespective of the COVID‐19 pandemic, patients who were on publicly‐sponsored insurance seemed to do worse, consistent with prior studies highlighting outcomes in this population. We speculate that previously established care relationships may lessen the impact of an acute event, such as a pandemic, on patients with chronic illness.
Percutaneous endovascular biopsy for the diagnosis of pulmonary artery masses: A preliminary study of single‐center
Authors: Hong Cheng , Lin Jie‐Long , Chen Hai‐Ming , Guo Wen‐Liang , Li Xiao‐Yan , Wu Xiao‐Feng
Published: April 2023

Percutaneous endovascular biopsy (PEB) including forceps biopsy and catheter aspiration has been used to make a pretreatment diagnosis for pulmonary artery (PA) masses. This retrospective study aims to describe the procedure of PEB and compare the diagnostic yield of forceps biopsy and catheter aspiration for a definite diagnosis in patients with PA masses. All consecutive 22 patients (53 ± 14 years), 11 males and 11 females, who underwent PEB for pathologic confirmation between November 2018 and November 2022 were enrolled. All 22 patients performed computed tomography pulmonary angiography or positron emission tomography‐computed tomography to confirm the filling defects suspicious for PA malignancy before intervention. And then, all patients underwent PEB successfully without acute or fatal complications, including both forceps biopsy and catheter aspiration in 15 cases, only forceps biopsy in 5 cases, and only catheter aspiration in 2 cases. Histopathological analysis provided a definite diagnosis in all PEBs with a clinical success of 91.0% (20/22). Among them, in 15 patients who underwent both forceps biopsy and aspiration biopsy, the technical success using forceps biopsy was 93.3% (14/15), and aspiration biopsy was 6.7% (1/15), and there was a significant difference in diagnostic accuracy when comparing two techniques. Twenty‐one out of 22 PA masses (95.5%) were malignant, of which, the most frequent malignant lesion observed was PA sarcoma (66.7%, 14/21). Benign lesion included one thrombus (4.5%, 1/22). In conclusion, PEB is an effective and safe diagnostic method for differentiating benign and malignant PA masses and could be peformed when PA masses appeared clinically malignant.
Facile formulation of graphene oxide modified commercial polyurea grease and its enhanced tribological capability under extremely high contact stress
Authors: Xia Yana , Wang Junyang , Wang Zaizhou , Zhang Chunxiang
Published: April 2023

Grease lubricants have been widely applied to the rubbing components to increase the operation stability and reliability. In this study, graphene oxide modified polyurea grease was prepared by formulating different amounts of exfoliated expandable graphite (EG) into commercial polyurea grease with combined mechanical agitation and grinding processes, tribological characteristics of graphene oxide modified polyurea grease were subsequently evaluated under extremely higher contacting stress. Among all the formulated polyurea grease specimens, polyurea grease with 2.0 wt.% graphene oxide displays better capabilities of minimizing friction and wear. In particular, the wear loss reduces considerably by 80% meanwhile the averaged friction coefficient decreases to 0.10, as referenced with existing polyurea grease. The improved tribological behavior is proposed to be associated with the in‐situ produced graphene oxide solids that enhances extremely lower shearing ability and promotes the fatigue resistance of grease, as well as its desired chemical compatibility with resulting iron sulfide tribofilm. Particularly, graphene oxide works as the dispersed precipitate within the dense iron sulfide/oxide layer induced from ZDDP that covers on the steel substrate.
Inhibiting Interfacial Diffusion in Heterojunction Perovskite Solar Cells by Replacing Low‐Dimensional Perovskite with Uniformly Anchored Quaternized Polystyrene
Authors: Tian Congcong , Sun Anxin , Liang Jianghu , Zhang Zhanfei , Zheng Yiting , Wu Xueyun , Liu Yuan , Tang Chen , Chen Chun‐Chao
Published: April 2023

Surface heterojunction has been regarded as an effective method to improve the device efficiency of perovskite solar cells. Nevertheless, the durability of different heterojunction under thermal stress is rarely investigated and compared. In this work, benzylammonium chloride and benzyltrimethylammonium chloride are utilized to construct 3D/2D and 3D/1D heterojunctions, respectively. A quaternized polystyrene is synthesized to construct a three‐dimensional perovskite/amorphous ionic polymer (3D/AIP) heterojunction. Due to the migration and volatility of organic cations, severe interfacial diffusion is found among 3D/2D and 3D/1D heterojunctions, in which the quaternary ammonium cations in the 1D structure are less volatile and mobile than the primary ammonium cations in the 2D structure. 3D/AIP heterojunction remains intact under thermal stress due to the strong ionic bond anchoring at the interface and the ultra‐high molecular weight of AIP. Furthermore, the dipole layer formed by AIP can further reduce the voltage loss caused by nonradiative recombination at the interface by 0.088 V. Therefore, the devices based on the 3D/AIP heterojunction achieve a champion power conversion efficiency of 24.27% and maintain 90% of its initial efficiency after either thermal aging for 400 h or wet aging for 3000 h, showing a great promise for polymer/perovskite heterojunction towards real applications.
CsPbBr3 Perovskite Nanoparticles causes Colitis‐Like Symptom via Promoting Intestinal Barrier Damage and Gut Microbiota Dysbiosis
Authors: Mei Linqiang , Guo Junsong , He Rendong , Ding Xuefeng , Yin Wenyan , Gu Zhanjun
Published: April 2023

Lead‐based perovskite nanoparticles (Pb‐PNPs) with superior optoelectronic properties are promising alternatives for the next generation of photovoltaics materials. This raises a great concern about their potential exposure toxicity in biological systems. However, little is known about their adverse effects on the gastrointestinal tract system so far. Here, the aim is to investigate the biodistribution, biotransformation, potential gastrointestinal tract toxicity, and effect on the gut microbiota after oral exposure to the CsPbBr3 perovskite nanoparticles (CPB PNPs). The advanced synchrotron radiation based microscopic X‐ray fluorescence scanning and X‐ray absorption near‐edge spectroscopy demonstrate that high doses of CPB (CPB‐H) PNPs can gradually transform into different lead‐based compounds, subsequently accumulating in the gastrointestinal tract, especially the colon. Meanwhile, the pathological changes of stomach, small intestine, and colon reveal that CPB‐H PNPs have higher gastrointestinal tract toxicity than Pb(Ac)2, consequently leading to colitis‐like symptoms. More importantly, 16S rRNA gene sequencing analysis discloses that CPB‐H PNPs cause more significant alterations in the richness and diversity of the gut microbiota related to inflammation, intestinal barrier, and immune function than Pb(Ac)2. The findings may contribute to shedding light on understanding the adverse effects on gastrointestinal tract and gut microbiota of Pb‐PNPs.
Enhancing both strength and permeability of pervious concrete by optimizing pore structure: An experimental study
Authors: Yu Fan , Guo Jianxiang , Li Zheng , Huang Yubin
Published: April 2023

The large porosity enables pervious concrete to obtain water permeability, but seriously decreases its strength. Hence, how to coordinate the contradiction between strength and permeability is a critical challenge for pervious concrete. This research was mainly aimed at mix design of pervious concrete for enhancing both strength and permeability by optimizing the pore structure. Six groups of pervious concrete with 15% target porosity were prepared by 10–15 mm coarse aggregate and different fine aggregate (natural sand, basalt aggregate, and steel slag). Moreover, a group of pervious concrete with 20% target porosity as control samples was prepared by 4.75–9.5 mm aggregate. The compressive strength and permeability coefficient of these samples were tested. Based on CT scanning and image analysis, the influence of pore structure optimization on permeability and compressive strength was analyzed. The results show that though the porosity is reduced by 5% after pore structure optimization, the porosity of large pores and medium pores changes little, the porosity of small pores decreased significantly, and finally the average pore size is still increased. This can explain why the experimental groups gain a similar/better permeability as the control group. The experimental groups of cement or steel slag have an increased compressive strength compared to the control group, which is due to the decrease of porosity and “small pores” content, as well as more abundant hydration products.
Can spatial and temporal differences in fish assemblage structure inform conservation of an endangered sucker in a large western reservoir?
Authors: Pennock Casey A. , Albrecht Brandon , Rogers Ronald J. , McKinstry Mark C.
Published: April 2023

Objective

Conversion of lotic to lentic habitat after river impoundment can lead to habitat loss and threats from introduced species to native aquatic organisms. Some native species can persist in reservoirs despite these alterations. Some of the largest reservoirs in North America were constructed in the Colorado River basin and are used by endangered Razorback Sucker Xyrauchen texanus. This species successfully spawns in several reservoirs and recruits to adulthood in Lake Mead, whereas recruitment in other reservoirs and altered river habitats is limited or nonexistent. Hypothesized mechanisms for the general lack of recruitment include flow and habitat alteration as well as competition and predation from nonnative fishes.

Methods

We analyzed 16 years of netting data from Lake Mead to assess spatial and temporal patterns in fish assemblage structure and the size structure of Razorback Sucker across four sites.

Result

There was a substantial shift in assemblage structure across all sites after the establishment of Gizzard Shad Dorosoma cepedianum in 2010–2011 and an apparent decline in Threadfin Shad D. petenense. Captures of juvenile Razorback Sucker (<450 mm total length in Lake Mead) were higher at sites where overall fish abundance was also higher, suggesting that all fishes might be responding to similar spatial and temporal environmental variation. We identified differences in Razorback Sucker size structure that varied over time and among sites, largely driven by the presence of juvenile Razorback Sucker at some sites in some years.

Conclusion

Razorback Sucker was among the top-10 most abundant species at all sites sampled, but assemblages were dominated by abundant nonnative fishes. Razorback Sucker continue to recruit in Lake Mead in the face of abundant and diverse nonnative fishes, but the adult population size remains relatively small (<1000). Further investigation of limiting factors will be necessary to understand which actions might be successful at improving recruitment conditions.
Improving the thermal stability of polysulfidic crosslinks by hexamethylene‐1, 6‐bis(thiosulfate) disodium salt as the curing agent of natural rubber
Authors: He Mingbin , Pan Qiwei , Chen Zhaohui , Zou Lijing
Published: April 2023

When vulcanized with sulfur, the natural rubber (NR) usually accompanies reversion, and the proportion of polysulfidic crosslinks decreases considerably, leading to significantly performance decay. In the rubber industry, hexamethylene‐1, 6‐bis(thiosulfate) disodium salt (HTS) is used as a multifunctional agent to improve not only the reversion and fatigue properties of NR, but also the adhesive properties between NR and steel cords. However, there is few research about the working mechanism of HTS. In this work, HTS is added to belt compounds in doses of 0 to 5 phr. The cure characteristics, crosslinking structures, physical‐mechanical properties, dynamic viscoelastic behavior, and T‐pull adhesion forces of the NR composites are investigated. The results show that the total crosslinking density and T‐pull adhesion forces of the composites both pass through a maximum and then decrease with the increasing dosage of HTS. Meanwhile, the formation of hybrid crosslinks during the prolonged cure time enhances the thermal stability and retention of the polysulfidic crosslinks of the NR composites. Surprisingly, the reduction in the proportion of polysulfidic crosslinks from optimum cure time (Tc90) to 60 min just reaches 15.9% with the addition of 5 phr HTS, whereas that value is 30.9% without adding HTS, which shows the excellent antireversion ability of the HTS in the belt compound. Our work reveals some new features of HTS, which can lead to a more profound understanding of HTS.
1 Stalled labour market recovery undermines social justice
Authors: Kühn Stefan , Ernst Ekkehard
Published: April 2023

This chapter presents the state of the world's labour markets, presenting three main findings. First, major decent work deficits persist around the world, including lack of access to employment, poverty, inequality and lack of social protection. Second, the global labour market recovery is projected to stall in 2023 amidst a worsening economic outlook. Third, the quality of jobs is equally likely to deteriorate. These profound challenges can undermine social justice.
Assessment of yeast physiology during industrial‐scale brewing practices using the redox‐sensitive dye resazurin
Authors: Dilmetz Brooke A. , Desire Christopher T. , Donnellan Leigh , Meneses Jon , Klingler‐Hoffmann Manuela , Young Clifford , Hoffmann Peter
Published: April 2023

Beer refermentation in bottles is an industrial process utilized by breweries where yeast and fermentable extract are added to green beer. The beer is refermented for a minimum of 2 weeks before distribution, with the physiological state of the yeast a critical factor for successful refermentation. Ideally, fresh yeast that is propagated from a dedicated propagation plant should be used for refermentation in bottles. Here, we explored the applicability of the fluorescent and redox‐sensitive dye, resazurin, to assess cellular metabolism in yeast and its ability to differentiate between growth stages. We applied this assay, with other markers of yeast physiology, to evaluate yeast quality during a full‐scale industrial propagation. Resazurin allowed the discrimination between the different growth phases in yeast and afforded a more in‐depth understanding of yeast metabolism during propagation. This assay can be used to optimize the yeast propagation process and cropping time to improve beer quality.
Autonomous Guidance Control for Ascent Flight
Authors: Song Zhengyu , Wang Cong , He Yong
Published: April 2023

The purpose of the guidance control is to release a payload into a prescribed target orbit (PTO) accurately. The parameters that determine an orbit are called orbital elements (OEs), which include the semi-major axis a, the eccentricity e, the argument of perigee $$\omega $$
ω
, the inclination angle i, and the longitude of ascending node (LAN) or the right ascension of ascending node (RAAN) $$\Omega $$
Ω
, where a and e can be converted to the perigee height $$h_p$$

h
p

and the apogee height $$h_a$$

h
a

. Thus, the guidance mission of a launcher is a typical optimal control problem with multi-terminal constraints, which requires complex iterative calculations. Considering various constraints in practical applications, such as the accuracy of inertial navigation systems and the performances of embedded computing devices (speed and storage capacity), guidance methods need to balance the mission requirements, hardware resources, and algorithm complexity. A variety of guidance methods has been developed with distinct era characteristics.
Ascent Predictive Guidance for Thrust Drop Fault of Launch Vehicles Using Improved GS-MPSP
Authors: Yan Xiaodong , Zhou Cong
Published: April 2023

Increasing complex space missions require launch vehicles to be with greater load-carrying capacity, better orbit injection accuracy and higher reliability. Such demands also cause the increased complexity of the vehicle, leading to a higher probability of fault, especially for the propulsion system. To remedy this issue, an advanced and robust ascent guidance capable of fault-tolerant is critical for the success of mission. Iterative guidance method [1] (IGM) and powered explicit guidance [2] (PEG) are two commonly used methods for the ascent phase of launch vehicles. These two guidance methods work well in the nominal condition and can adapt to many off-nominal conditions [3]. However, they lack of strong adaptive capacity, which cannot guarantee the reliability when the dynamic model or parameters change significantly. Alternatively, numerical approaches based on the optimal control theory may be the better choice. The existing algorithms can be divided into direct methods and indirect methods. Using the indirect methods, the guidance problem is transformed into Hamilton two-point boundary value problems [4] (TPBVP), but the solving process of this Hamilton two-point boundary value problem is complicated and highly sensitive to the initial guess. Using the direct method, the guidance problem is transformed into a nonlinear programming problem [5] (NLP). However, solving such problem is extremely computational intensive, which is difficult to meet the real-time requirement for online application.
The chaotic emergence of thermalization in highly excited string decays
Authors: Firrotta Maurizio
Published: April 2023

Abstract

We analyse the most general process of a generic highly excited string that decays into a less excited, yet generic, highly excited string emitting a tachyon. We provide a simple and compact analytic description of the decay process which discriminates between and within the structure of every single microstate of the initial and final highly excited string. Taking into account the random nature of the decay process we extract the energy spectrum of highly excited strings, microstate by microstate, finding a behavior which corresponds to the greybody emission spectrum. In addition, by exploiting the analytic control of the decay process, we identify the origin of thermal effects which are triggered by the chaotic nature of the highly excited string interactions modeled by the microstates structure.
Helical inflation correlators: partial Mellin-Barnes and bootstrap equations
Authors: Qin Zhehan , Xianyu Zhong-Zhi
Published: April 2023

Abstract

Massive spinning particles acquire helicity-dependent chemical potentials during the inflation from axion-type couplings. Such spinning fields can mediate sizable inflaton correlators which we call the helical inflation correlators. Helical inflaton correlators are approximately scale invariant, dS boost breaking, parity violating, and are promising observables of cosmological collider physics. In this work, we present complete and analytical results for 4-point helical inflation correlators with tree-level exchanges of massive spinning particles, including both the smooth background and the oscillatory signals. We compute the bulk Schwinger-Keldysh integrals in two independent ways, including the partial Mellin-Barnes representation and solving bootstrap equations. We also present new closed-form analytical results for 3-point functions with massive scalar or helical spinning exchanges. The analytical results allow us to concretely and efficiently explore the phenomenological consequences of helicity-dependent chemical potentials. In particular, we show that the chemical potential can exponentially enhance oscillatory signals of both local and nonlocal types, but only affects the background in a rather mild way. Our results extend the de Sitter bootstrap program to include nonperturbative breaking of de Sitter boosts. Our results also explicitly verify the recently proposed cutting rule for cosmological collider signals.
Line operators in Chern-Simons-Matter theories and Bosonization in Three Dimensions II: Perturbative analysis and all-loop resummation
Authors: Gabai Barak , Sever Amit , Zhong De-liang
Published: April 2023

Abstract

We study mesonic line operators in Chern-Simons theories with bosonic or fermionic matter in the fundamental representation. In this paper, we elaborate on the classification and properties of these operators using all loop resummation of large N perturbation theory. We show that these theories possess two conformal line operators in the fundamental representation. One is a stable renormalization group fixed point, while the other is unstable. They satisfy first-order chiral evolution equations, in which a smooth variation of the path is given by a factorized product of two mesonic line operators. The boundary operators on which the lines can end are classified by their conformal dimension and transverse spin, which we compute explicitly at finite ’t Hooft coupling. We match the operators in the bosonic and fermionic theories. Finally, we extend our findings to the mass deformed theories and discover that the duality still holds true.
Revelations of Folies through Geometric Transformations
Authors: Càndito Cristina , Meloni Alessandro
Published: April 2023

This article presents an activity carried out in a course on representation in a master’s degree in architecture, which aims to train students in the practice and theory of geometric transformation for the production of shapes, using a case study from contemporary architectural design: the folies of the Parc de la Villette.
Omics are Getting Us Closer to Understanding IgA Nephropathy
Authors: Mucha Krzysztof , Pac Michał , Pączek Leszek
Published: April 2023

During the last decade, thanks to omics technologies, new light has been shed on the pathogenesis of many diseases. Genomics, epigenomics, transcriptomics, and proteomics have helped to provide a better understanding of the origin and heterogeneity of several diseases. However, the risk factors for most autoimmune diseases remain unknown. The successes and pitfalls of omics have also been observed in nephrology, including immunoglobulin A nephropathy (IgAN), the most common form of glomerulonephritis and a principal cause of end-stage renal disease worldwide. Unfortunately, the immense progress in basic research has not yet been followed by the satisfactory development of a targeted treatment. Although, most omics studies describe changes in the immune system, there is still insufficient data to apply their results in the constantly evolving multi-hit pathogenesis model and thus do to provide a complete picture of the disease. Here, we describe recent findings regarding the pathophysiology of IgAN and link omics studies with immune system dysregulation. This review provides insights into specific IgAN markers, which may lead to the identification of potential targets for personalised treatment in the future.
Transgressive and parental dominant gene expression and cytosine methylation during seed development in Brassica napus hybrids
Authors: Orantes-Bonilla Mauricio , Wang Hao , Lee Huey Tyng , Golicz Agnieszka A. , Hu Dandan , Li Wenwen , Zou Jun , Snowdon Rod J.
Published: April 2023

Key message

Transcriptomic and epigenomic profiling of gene expression and small RNAs during seed and seedling development reveals expression and methylation dominance levels with implications on early stage heterosis in oilseed rape.

The enhanced performance of hybrids through heterosis remains a key aspect in plant breeding; however, the underlying mechanisms are still not fully elucidated. To investigate the potential role of transcriptomic and epigenomic patterns in early expression of hybrid vigor, we investigated gene expression, small RNA abundance and genome-wide methylation in hybrids from two distant Brassica napus ecotypes during seed and seedling developmental stages using next-generation sequencing. A total of 31117, 344, 36229 and 7399 differentially expressed genes, microRNAs, small interfering RNAs and differentially methylated regions were identified, respectively. Approximately 70% of the differentially expressed or methylated features displayed parental dominance levels where the hybrid followed the same patterns as the parents. Via gene ontology enrichment and microRNA-target association analyses during seed development, we found copies of reproductive, developmental and meiotic genes with transgressive and paternal dominance patterns. Interestingly, maternal dominance was more prominent in hypermethylated and downregulated features during seed formation, contrasting to the general maternal gamete demethylation reported during gametogenesis in angiosperms. Associations between methylation and gene expression allowed identification of putative epialleles with diverse pivotal biological functions during seed formation. Furthermore, most differentially methylated regions, differentially expressed siRNAs and transposable elements were in regions that flanked genes without differential expression. This suggests that differential expression and methylation of epigenomic features may help maintain expression of pivotal genes in a hybrid context. Differential expression and methylation patterns during seed formation in an F1 hybrid provide novel insights into genes and mechanisms with potential roles in early heterosis.
Symmetry Results for Compactly Supported Steady Solutions of the 2D Euler Equations
Authors: Ruiz David
Published: April 2023

In this paper we present symmetry results regarding compactly supported solutions of the 2D steady Euler equations. Assuming that $$\Omega = \{x \in {\mathbb {R}}^2:\ u(x) \ne 0\}$$

Ω
=
{
x
∈

R

2

:

u

(
x
)

≠
0
}

is an annular domain, we prove that the streamlines of the flow are circular. We are also able to remove the topological condition on $$\Omega $$
Ω
if we impose regularity and nondegeneracy assumptions on u at $$\partial \Omega $$

∂
Ω

. The proof uses the corresponding stream function solves an elliptic semilinear problem $$-\Delta \phi = f(\phi )$$

-
Δ
ϕ
=
f
(
ϕ
)

with $$\nabla \phi =0$$

∇
ϕ
=
0

at the boundary. One of the main difficulties in our study is that f is not Lipschitz continuous near the boundary values. However, $$f(\phi )$$

f
(
ϕ
)

vanishes at the boundary values and then we can apply a local symmetry result of F. Brock to conclude. In the case $$\partial _{\nu } u \ne 0$$

∂
ν

u
≠
0

at $$\partial \Omega $$

∂
Ω

this argument is not possible. In this case we are able to use the moving plane scheme to show symmetry, despite the possible lack of regularity of f. We think that such result is interesting in its own right and will be stated and proved also for higher dimensions. The proof requires the study of maximum principles, The Hopf lemma and The Serrin corner lemma for elliptic linear operators with singular coefficients.
Population plasma and urine pharmacokinetics and the probability of target attainment of fosfomycin in healthy male volunteers
Authors: Edwina Angela Elma , Koch Birgit C. P. , Muller Anouk E. , al Jalali Valentin , Matzneller Peter , Zeitlinger Markus , Sassen Sebastiaan D. T.
Published: April 2023

Purpose

A population pharmacokinetic model of fosfomycin was developed in healthy volunteers after intravenous administration, and different dosing regimens were evaluated in terms of the probability of target attainment for Escherichia coli using both plasma and urinary pharmacokinetic/pharmacodynamic targets.

Methods

Eight healthy men received fosfomycin as both intermittent 8 g q8h and continuous infusion 1 g/h with a loading dose of 8 g in a crossover study design. Dense sampling was conducted during both regimens. Population pharmacokinetic modelling was performed using NONMEM. Monte Carlo simulations were conducted to evaluate the Probability of Target Attainment (PTA) of different dosing regimens using bactericidal (AUC24h/MIC of 83 and 75%T>MIC) and bacteriostatic (AUC24h/MIC of 25) plasma targets and bacteriostatic (AUC24h/MIC of 3994) urine target.

Results

A total of 176 plasma and 86 urine samples were available for PK analysis. A two-compartment model with a urine compartment best described the data. Glomerular filtration rate (GFR) showed a significant correlation with renal clearance and was implemented in the final model. Simulation results show that the dose of 4 g q8h reached 100% of PTA using bactericidal and bacteriostatic targets for MIC up to 16 mg/L.

Conclusion

For the clinical breakpoint of 32 mg/L, the standard dosing regimen (4 g q8h) might not be sufficient to reach the bactericidal target. Higher dosing of 8 g q8h as an intermittent infusion or 0.75 g/h as a continuous infusion might be required. Continuous infusion resulted in better attainment of the %T>MIC target than intermittent infusion.
Metabarcoding inventory of an arctic tundra soil ecosystem reveals highly heterogeneous communities at a small scale
Authors: Jorna Jesse , Vandenbrink Bryan , Hogg Ian D. , Wall Diana H. , Adams Byron J.
Published: April 2023

Biodiversity surveys of Arctic soil ecosystems are limited. Here, we provide a sequence-based inventory of soil fauna from an Arctic tundra ecosystem near the Canadian High Arctic Research Station in Cambridge Bay, Nunavut. Invertebrate communities were extracted at a vegetated and non-vegetated site in three replicates and inventoried using 18S metabarcode sequencing. A total of 361 amplicon sequence variants (ASV) were identified and assigned to the closest matching taxonomic orders, most of which belonged to the Nematoda and Arthropoda. Vegetated soils showed no significantly higher ASV richness relative to non-vegetated soils although they contained a significantly higher diversity of arthropod taxa including insects, mites, and springtails. Most taxa were found only at a single location and even samples from the same site displayed distinct communities, suggesting that belowground species richness in Arctic tundra habitats is highly heterogeneous. Preserving soil biodiversity in a changing Arctic is essential for Inuit communities who rely on intact tundra ecosystems for their health and wellbeing.
Halved contrast medium dose in lower limb dual-energy computed tomography angiography—a randomized controlled trial
Authors: Kristiansen Cathrine Helgestad , Thomas Owen , Tran Thien Trung , Roy Sumit , Hykkerud Dan Levi , Sanderud Audun , Geitung Jonn Terje , Lauritzen Peter M.
Published: April 2023

Objectives

To compare vascular attenuation (VA) of an experimental half iodine-load dual-layer spectral detector CT (SDCT) lower limb computed tomography angiography (CTA) with control (standard iodine-load conventional 120-kilovolt peak (kVp) CTA).

Methods

Ethical approval and consent were obtained. In this parallel RCT, CTA examinations were randomized into experimental or control. Patients received 0.7 vs 1.4 mL/kg of iohexol 350 mgI/mL in the experimental- vs the control group. Two experimental virtual monoenergetic image (VMI) series at 40 and 50 kiloelectron volts (keV) were reconstructed. Primary outcome: VA. Secondary outcomes: image noise (noise), contrast- and signal-to-noise ratio (CNR and SNR), and subjective examination quality (SEQ).

Results

A total of 106 vs 109 were randomized and 103 vs 108 were analyzed in the experimental vs, control groups, respectively. VA was higher on experimental 40 keV VMI than on control (p < 0.0001), but lower on 50 keV VMI (p < 0.022). Noise was higher on experimental 40 keV VMI than on control (p = 0.00022), but lower on 50 keV VMI (p = 0.0033). CNR and SNR were higher than the control on experimental 40 keV VMI (both p < 0.0001) and 50 keV (p = 0.0058 and p = 0.0023, respectively). SEQ was better on both VMIs in the experimental group than in the control (both p < 0.0001).

Conclusions

Half iodine-load SDCT lower limb CTA at 40 keV achieved higher VA than the control. CNR, SNR, noise, and SEQ were higher at 40 keV, while 50 keV showed lower noise.

Clinical relevance statement

Spectral detector CT with low-energy virtual monoenergetic imaging performed halved iodine contrast medium (CM) lower limb CT-angiography with sustained objective and subjective quality. This facilitates CM reduction, improvement of low CM-dosage examinations, and examination of patients with more severe kidney impairment.

Trial registration

Retrospectively registered 5 August 2022 at clinicaltrials.gov NCT05488899.

Key Points

• Contrast medium dosage may be halved in lower limb dual-energy CT angiography with virtual monoenergetic images at 40 keV, which may reduce contrast medium consumption in the face of a global shortage.

• Experimental half-iodine-load dual-energy CT angiography at 40 keV showed higher vascular attenuation, contrast-to-noise ratio, signal-to-noise ratio, and subjective examination quality than standard iodine-load conventional.

• Half-iodine dual-energy CT angiography protocols may allow us to reduce the risk of PC-AKI, examine patients with more severe kidney impairment, and provide higher quality examinations or salvage poor examinations when impaired kidney function limits the CM dose.
Quo vadis Radiomics? Bibliometric analysis of 10-year Radiomics journey
Authors: Volpe Stefania , Mastroleo Federico , Krengli Marco , Jereczek-Fossa Barbara Alicja
Published: April 2023

Objectives

Radiomics is the high-throughput extraction of mineable and—possibly—reproducible quantitative imaging features from medical imaging. The aim of this work is to perform an unbiased bibliometric analysis on Radiomics 10 years after the first work became available, to highlight its status, pitfalls, and growing interest.

Methods

Scopus database was used to investigate all the available English manuscripts about Radiomics. R Bibliometrix package was used for data analysis: a cumulative analysis of document categories, authors affiliations, country scientific collaborations, institution collaboration networks, keyword analysis, comprehensive of co-occurrence network, thematic map analysis, and 2021 sub-analysis of trend topics was performed.

Results

A total of 5623 articles and 16,833 authors from 908 different sources have been identified. The first available document was published in March 2012, while the most recent included was released on the 31st of December 2021. China and USA were the most productive countries. Co-occurrence network analysis identified five words clusters based on top 50 authors’ keywords: Radiomics, computed tomography, radiogenomics, deep learning, tomography. Trend topics analysis for 2021 showed an increased interest in artificial intelligence (n = 286), nomogram (n = 166), hepatocellular carcinoma (n = 125), COVID-19 (n = 63), and X-ray computed (n = 60).

Conclusions

Our work demonstrates the importance of bibliometrics in aggregating information that otherwise would not be available in a granular analysis, detecting unknown patterns in Radiomics publications, while highlighting potential developments to ensure knowledge dissemination in the field and its future real-life applications in the clinical practice.

Clinical relevance statement

This work aims to shed light on the state of the art in radiomics, which offers numerous tangible and intangible benefits, and to encourage its integration in the contemporary clinical practice for more precise imaging analysis.

Key Points

• ML-based bibliometric analysis is fundamental to detect unknown pattern of data in Radiomics publications.

• A raising interest in the field, the most relevant collaborations, keywords co-occurrence network, and trending topics have been investigated.

• Some pitfalls still exist, including the scarce standardization and the relative lack of homogeneity across studies.
The estimated causal effect on the variance based on the front-door criterion in Gaussian linear structural equation models: an unbiased estimator with the exact variance
Authors: Kuroki Manabu , Tezuka Taiki
Published: April 2023

In this paper, we assume that cause–effect relationships between random variables can be represented by a Gaussian linear structural equation model and the corresponding directed acyclic graph. Then, we consider a situation where a set of random variables that satisfies the front-door criterion is observed to estimate a total effect. In this situation, when the ordinary least squares method is utilized to estimate the total effect, we formulate the unbiased estimator of the causal effect on the variance of the outcome variable. In addition, we provide the exact variance formula of the proposed unbiased estimator.
Effects of hyperventilation on oxygenation, apnea breaking points, diving response, and spleen contraction during serial static apneas
Authors: Pernett Frank , Bergenhed Pontus , Holmström Pontus , Mulder Eric , Schagatay Erika
Published: April 2023

Purpose

Hyperventilation is considered a major risk factor for hypoxic blackout during breath-hold diving, as it delays the apnea breaking point. However, little is known about how it affects oxygenation, the diving response, and spleen contraction during serial breath-holding.

Methods

18 volunteers with little or no experience in freediving performed two series of 5 apneas with cold facial immersion to maximal duration at 2-min intervals. In one series, apnea was preceded by normal breathing and in the other by 15 s of hyperventilation. End-tidal oxygen and end-tidal carbon dioxide were measured before and after every apnea, and peripheral oxygen saturation, heart rate, breathing movements, and skin blood flow were measured continuously. Spleen dimensions were measured every 15 s.

Results

Apnea duration was longer after hyperventilation (133 vs 111 s). Hyperventilation reduced pre-apnea end-tidal CO2 (17.4 vs 29.0 mmHg) and post-apnea end-tidal CO2 (38.5 vs 40.3 mmHg), and delayed onset of involuntary breathing movements (112 vs 89 s). End-tidal O2 after apnea was lower in the hyperventilation trial (83.4 vs 89.4 mmHg) and so was the peripheral oxygen saturation nadir after apnea (90.6 vs 93.6%). During hyperventilation, the nadir peripheral oxygen saturation was lower in the last apnea than in the first (94.0% vs 86.7%). There were no differences in diving response or spleen volume reduction between conditions or across series.

Conclusions

Serial apneas  revealed a previously undescribed aspect of hyperventilation; a progressively increased desaturation across the series, not observed after normal breathing and could heighten the risk of a blackout.
The HDAC inhibitor domatinostat induces type I interferon α in Merkel cell carcinoma by HES1 repression
Authors: Srinivas Nalini , Song Lina , Lei Kuan Cheok , Gravemeyer Jan , Furtmann Frauke , Gambichler Thilo , Becker Jürgen C. , Sriram Ashwin
Published: April 2023

Background

Class I selective histone deacetylase inhibitors (HDACi) have been previously demonstrated to not only increase major histocompatibility complex class I surface expression in Merkel cell carcinoma (MCC) cells by restoring the antigen processing and presentation machinery, but also exert anti-tumoral effect by inducing apoptosis. Both phenomena could be due to induction of type I interferons (IFN), as has been described for HDACi. However, the mechanism of IFN induction under HDACi is not fully understood because the expression of IFNs is regulated by both activating and inhibitory signaling pathways. Our own preliminary observations suggest that this may be caused by suppression of HES1.

Methods

The effect of the class I selective HDACi domatinostat and IFNα on cell viability and the apoptosis of MCPyV-positive (WaGa, MKL-1) and -negative (UM-MCC 34) MCC cell lines, as well as, primary fibroblasts were assessed by colorimetric methods or measuring mitochondrial membrane potential and intracellular caspase-3/7, respectively. Next, the impact of domatinostat on IFNA and HES1 mRNA expression was measured by RT-qPCR; intracellular IFNα production was detected by flow cytometry. To confirm that the expression of IFNα induced by HDACi was due to the suppression of HES1, it was silenced by RNA interference and then mRNA expression of IFNA and IFN-stimulated genes was assessed.

Results

Our studies show that the previously reported reduction in viability of MCC cell lines after inhibition of HDAC by domatinostat is accompanied by an increase in IFNα expression, both of mRNA and at the protein level. We confirmed that treatment of MCC cells with external IFNα inhibited their proliferation and induced apoptosis. Re-analysis of existing single-cell RNA sequencing data indicated that induction of IFNα by domatinostat occurs through repression of HES1, a transcriptional inhibitor of IFNA; this was confirmed by RT-qPCR. Finally, siRNA-mediated silencing of HES1 in the MCC cell line WaGa not only increased mRNA expression of IFNA and IFN-stimulated genes but also decreased cell viability.

Conclusion

Our results demonstrate that the direct anti-tumor effect of HDACi domatinostat on MCC cells is at least in part mediated via decreased HES1 expression allowing the induction of IFNα, which in turn causes apoptosis.
Practice variation and outcomes of minimally invasive minor liver resections in patients with colorectal liver metastases: a population-based study
Authors: de Graaff Michelle R. , Klaase Joost M. , de Kleine Ruben , Elfrink Arthur K. E. , Swijnenburg Rutger-Jan , M. Zonderhuis Babs , D. Mieog J. Sven , Derksen Wouter J. M. , Hagendoorn Jeroen , van den Boezem Peter B. , Rijken Arjen M. , Gobardhan Paul D. , Marsman Hendrik A. , Liem Mike S. L. , Leclercq Wouter K. G. , van Heek Tjarda N. T. , Pantijn Gijs A. , Bosscha Koop , Belt Eric J. T. , Vermaas Maarten , Torrenga Hans , Manusama Eric R. , van den Tol Petrousjka , Oosterling Steven J. , den Dulk Marcel , Grünhagen Dirk J. , Kok Niels F. M. ,   For Dutch Hepato Biliary Audit Group, Collaborators
Published: April 2023

Introduction

In 2017, the Southampton guideline stated that minimally invasive liver resections (MILR) should considered standard practice for minor liver resections. This study aimed to assess recent implementation rates of minor MILR, factors associated with performing MILR, hospital variation, and outcomes in patients with colorectal liver metastases (CRLM).

Methods

This population-based study included all patients who underwent minor liver resection for CRLM in the Netherlands between 2014 and 2021. Factors associated with MILR and nationwide hospital variation were assessed using multilevel multivariable logistic regression. Propensity-score matching (PSM) was applied to compare outcomes between minor MILR and minor open liver resections. Overall survival (OS) was assessed with Kaplan–Meier analysis on patients operated until 2018.

Results

Of 4,488 patients included, 1,695 (37.8%) underwent MILR. PSM resulted in 1,338 patients in each group. Implementation of MILR increased to 51.2% in 2021. Factors associated with not performing MILR included treatment with preoperative chemotherapy (aOR 0.61 CI:0.50–0.75, p < 0.001), treatment in a tertiary referral hospital (aOR 0.57 CI:0.50–0.67, p < 0.001), and larger diameter and number of CRLM. Significant hospital variation was observed in use of MILR (7.5% to 93.0%). After case-mix correction, six hospitals performed fewer, and six hospitals performed more MILRs than expected. In the PSM cohort, MILR was associated with a decrease in blood loss (aOR 0.99 CI:0.99–0.99, p < 0.01), cardiac complications (aOR 0.29, CI:0.10–0.70, p = 0.009), IC admissions (aOR 0.66, CI:0.50–0.89, p = 0.005), and shorter hospital stay (aOR CI:0.94–0.99, p < 0.01). Five-year OS rates for MILR and OLR were 53.7% versus 48.6%, p = 0.21.

Conclusion

Although uptake of MILR is increasing in the Netherlands, significant hospital variation remains. MILR benefits short-term outcomes, while overall survival is comparable to open liver surgery.

Graphical abstract
Robotic-assisted versus laparoscopic bowel anastomoses: randomized crossover in vivo experimental study
Authors: Haney Caelán Max , Kowalewski Karl-Friedrich , Schmidt Mona Wanda , Lang Franziska , Bintintan Vasile , Fan Carolyn , Wehrtmann Fabian , Studier-Fischer Alexander , Felinska Eleni Amelia , Müller-Stich Beat Peter , Nickel Felix
Published: April 2023

Background

Initial learning curves are potentially shorter in robotic-assisted surgery (RAS) than in conventional laparoscopic surgery (LS). There is little evidence to support this claim. Furthermore, there is limited evidence how skills from LS transfer to RAS.

Methods

A randomized controlled, assessor blinded crossover study to compare how RAS naïve surgeons (n = 40) performed linear-stapled side-to-side bowel anastomoses in an in vivo porcine model with LS and RAS. Technique was rated using the validated anastomosis objective structured assessment of skills (A-OSATS) score and the conventional OSATS score. Skill transfer from LS to RAS was measured by comparing the RAS performance of LS novices and LS experienced surgeons. Mental and physical workload was measured with the NASA-task load index (NASA-Tlx) and the Borg-scale.

Outcomes

In the overall cohort, there were no differences between RAS and LS for surgical performance (A-OSATS, time, OSATS). Surgeons that were naïve in both LS and RAS had significantly higher A-OSATS scores in RAS (Mean (Standard deviation (SD)): LS: 48.0 ± 12.1; RAS: 52.0 ± 7.5); p = 0.044) mainly deriving from better bowel positioning (LS: 8.7 ± 1.4; RAS: 9.3 ± 1.0; p = 0.045) and closure of enterotomy (LS: 12.8 ± 5.5; RAS: 15.6 ± 4.7; p = 0.010). There was no statistically significant difference in how LS novices and LS experienced surgeons performed in RAS [Mean (SD): novices: 48.9 ± 9.0; experienced surgeons: 55.9 ± 11.0; p = 0.540]. Mental and physical demand was significantly higher after LS.

Conclusion

The initial performance was improved for RAS versus LS for linear stapled bowel anastomosis, whereas workload was higher for LS. There was limited transfer of skills from LS to RAS.