bluuebunny/crossref_metadata_2025 huggingface dataset:
Experimental study on the unsteady evolution mechanism of centrifugal pump impeller wake under solid–liquid two-phase conditions: Impact of particle concentration
Authors: Pu Wei , Ji Leilei , Li Wei , Yang Qiaoyue , Liu Zhenbo , Yang Yang , Li Haoming , Huang Wei , Agarwal Ramesh
Published: November 2024

To study the spatiotemporal evolution process of particle wakes behind the impeller in the centrifugal pump, this paper utilized high-speed photography to capture the particle motion characteristics under different solid-phase particle concentrations (1%, 1.5%, and 2%). First, this paper studies the changes in hydraulic performance of the centrifugal pump under solid–liquid two-phase flow conditions. It then introduces the evolution process of the impeller particle wake, comparing the differences in particle wake evolution under varying solid-phase concentrations. Finally, the impact of the solid-phase concentration on the wear of the volute's partitions is investigated. This study found that as the solid-phase particle concentration increases, the hydraulic performance of the pump gradually declines. Under the design conditions, when the solid-phase concentration increases by 0.5%, the efficiency of the centrifugal pump decreases by 0.56% and 0.35%. There is mutual transport of particles between adjacent wakes, and the movement of particle wakes within the volute passage is not equidistant over time. As the solid-phase particle concentration increases, wake cutting occurs at the volute partitions, and there is a significant solid–liquid separation between the particle wakes. The spatial evolution of the particle wakes is significantly influenced by the solid-phase concentration. Wear at the volute partitions intensifies with increasing solid-phase concentration and is also affected by changes in the particle wakes. The research results provide a basis for further exploration of the solid–liquid two-phase flow dynamics within centrifugal pumps.
Study on fish damage mechanism of the large flow rate centrifugal pump in hydraulic engineering pump station
Authors: Zhu Lufeng , Zhang Fan , Xu Zhengxuan , Yuan Shouqi , Zulu Bernard , Hong Qiuhong
Published: November 2024

Large high-head centrifugal pumps have the characteristics of large flow rate, high head, and high specific speed, making them important engineering equipment in large-scale water transfer projects. However, these pumps inevitably cause the death of a large number of fish during operation, which has adverse effects on the ecological environment. Therefore, studying the damage of large high-head centrifugal pump stations on fish is of great significance. This article establishes a new mathematical model for blade strike and predicts the strike probability and mortality rate of fish passing through the inlet of the centrifugal pump impeller. The prediction results show that under various flow conditions, the strike mortality rate for 50 mm fish passing through the model pump exceeds 82.5%, indicating that the model pump will cause significant damage to the pumped fish. This article further investigates the damage to fish caused by unstable flow inside the impeller and diffuser in low-pressure, high-shear, and high-pressure gradient regions. The research results show that fish suffer less low-pressure damage and more high-pressure gradient damage while passing through the model pump.
The kinetics of SARS-CoV-2 infection based on a human challenge study
Authors: Iyaniwura Sarafa A. , Ribeiro Ruy M. , Zitzmann Carolin , Phan Tin , Ke Ruian , Perelson Alan S.
Published: November 2024

Studying the early events that occur after viral infection in humans is difficult unless one intentionally infects volunteers in a human challenge study. Here, we use data about severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) in such a study in combination with mathematical modeling to gain insights into the relationship between the amount of virus in the upper respiratory tract and the immune response it generates. We propose a set of dynamic models of increasing complexity to dissect the roles of target cell limitation, innate immunity, and adaptive immunity in determining the observed viral kinetics. We introduce an approach for modeling the effect of humoral immunity that describes a decline in infectious virus after immune activation. We fit our models to viral load and infectious titer data from all the untreated infected participants in the study simultaneously. We found that a power-law with a power
h
< 1 describes the relationship between infectious virus and viral load. Viral replication at the early stage of infection is rapid, with a doubling time of ~2 h for viral RNA and ~3 h for infectious virus. We estimate that adaptive immunity is initiated ~7 to 10 d postinfection and appears to contribute to a multiphasic viral decline experienced by some participants; the viral rebound experienced by other participants is consistent with a decline in the interferon response. Altogether, we quantified the kinetics of SARS-CoV-2 infection, shedding light on the early dynamics of the virus and the potential role of innate and adaptive immunity in promoting viral decline during infection.
A nucleobase-driven P450 peroxidase system enables regio- and stereo-specific formation of C─C and C─N bonds
Authors: Wei Guangzheng , Duan Borui , Zhou Tai-Ping , Tian Wenya , Sun Chenghai , Lin Zhi , Deng Zixin , Wang Binju , Zhang Zhengyu , Qu Xudong
Published: November 2024

P450 peroxidase activities are valued for their ability to catalyze complex chemical transformations using economical H2O2; however, they have been largely underexplored compared to their monooxygenase and peroxygenase activities. In this study, we identified an unconventional P450 enzyme, PtmB, which catalyzes the dimerization of purine nucleobases and tryptophan-containing diketopiperazines (TDKPs), yielding C3-nucleobase pyrroloindolines and nucleobase-TDKP dimers. Unlike typical TDKP P450 enzymes reliant on NAD(P)H cofactors and electron transfer systems, PtmB, and its analogs exhibit remarkable peroxidase activity in synthesizing adenine and other modified 6-aminopurine nucleobase-TDKP dimers. Structural analysis of the PtmB–substrate complex, mutation assays, and computational investigations reveal adenine’s dual role as both substrate and acid–base catalyst in activating H2O2to generate Compound I (Cpd I). This initiates a specific radical cascade reaction, facilitating the formation of precise C─C and C─N bonds. Biochemical assays and molecular dynamics simulations demonstrate that adenine’s 6-NH2hydrogen-bonding networks induce necessary conformational changes for H2O2activation, thereby driving peroxidase activity. This study unveils an unusual catalytic mechanism for the P450 peroxidase system and underscores the pivotal role of nucleobases in enzyme-mediated reactions, which offers different prospects for developing P450 peroxidases and nucleobase-based biocatalysts.
Harmonizing food systems emissions accounting for more effective climate action
Authors: Karl Kevin , Tubiello Francesco N , Crippa Monica , Poore Joseph , Hayek Matthew N , Benoit Philippe , Chen Minpeng , Corbeels Marc , Flammini Alessandro , Garland Sarah , Leip Adrian , McClelland Shelby C , Mencos Contreras Erik , Sandalow David , Quadrelli Roberta , Sapkota Tek B , Rosenzweig Cynthia
Published: November 2024

Food systems—encompassing activities in food production, land-use change, supply chains and waste management—contribute significantly to climate change. Recent estimates indicate that food systems produce over 30% of annual anthropogenic greenhouse gas (GHG) emissions (about 20% of CO2, 50% of CH4, and 75% of N2O), with the Intergovernmental Panel on Climate Change (IPCC) estimating a notably broad range of 23%–42% of global GHG emissions. This paper synthesizes current research on the contributions of food systems to climate change, highlights challenges in quantifying their impact and proposes a harmonized accounting framework for more effective climate action. We recommend that an expert committee aligned with the IPCC develop guidance for food systems emissions accounting in four key areas, including: (1) defining system boundaries and nomenclature; (2) developing protocols to allocate broader sectoral emissions to food systems; (3) prioritizing critical areas for research into activity data and emissions factors; and (4) developing a balanced framework for evaluating the impact of mitigation interventions in light of other food systems imperatives. The committee should be integrated into two key international policy processes—the United Nations Framework Convention on Climate Change and the United Nations Food Systems Summit—to support coordinated action towards global net-zero goals. Guidance from the committee could significantly improve the ability of governments, companies, and researchers to estimate, report, monitor and ultimately reduce the climate impacts of food systems.
Justice and Natural Law
Authors: Olsthoorn Johan
Published: November 2024

This chapter provides a major new interpretation of Hobbes’s natural law ethics. It does so by reconstructing Hobbes’s disentanglement of the domains of natural law and justice of actions. Hobbes stresses that sovereigns and pre-statist individuals alike can flout natural law duties without thereby committing any injustice or injury to humans. How come? Dismissing Abizadeh’s recent suggestion that deontic obligations of justice provide different kinds of reasons for action than prudential natural law duties, the chapter argues that Hobbes’s idiosyncratic conception of injury explains how humans, equal by nature, can have the right to sin vis-à-vis their fellows. Violations of natural law are neither unjust nor injurious as long as agents remain entitled to follow their own judgement about what (if anything) morality demands in practice. Rights of private judgement shield sinners from all warranted moral accusation. The chapter ends by discussing the difference between justice of actions vs. justice of manners.
Justice and Property
Authors: Olsthoorn Johan
Published: November 2024

This chapter explores changing conceptual relations between justice, law, and property rights. Hobbes unwaveringly maintained that private property rights: (1) presuppose the existence of a legal system; (2) and never exclude the sovereign. Over time, he developed three distinct arguments for the first thesis: the Security, Precision, and Creation Arguments. The last argument is deeply conventionalist: distributive civil laws create from scratch all exclusive rights in external things. Premised upon Leviathan’s novel account of distributive justice as a virtue of arbitrators, the Creation Argument at once explains why property rights, constituted by law, do not constrain the sovereign legislator. For that thesis, the early works had relied on the so-called Allotment Argument, modelling sovereignty on the despotic power of slaveholders and conceiving of citizens’ property rights as revocable allotments from their master’s stock. Leviathan’s reconceptualization of distributive justice helps explain the diminishing centrality of despotic sovereignty in Hobbes’s mature thought.
Justice and Civil Law
Authors: Olsthoorn Johan
Published: November 2024

Was Hobbes a legal positivist? Ongoing debates on this question are marred by the common tendency to conflate justice with natural law. This chapter provides new arguments for interpreting Hobbes’s legal theory along non-positivist lines. Existing anti-positivist readings must be rejected as untenable: civil laws that materially contradict natural law are legally valid. Against positivist readings, I contend that Hobbes rejected both hallmarks of legal positivism: the Sources Thesis and Separability Thesis. An ineliminable conceptual connection obtains between civil law and justice: no civil law can possibly be unjust or injurious to citizens. A key part of Hobbes’s vindicatory project, this connection holds true in virtue of Leviathan’s authorization thesis. Authorization precludes accusations of injustice—and citizens have individually authorized all the sovereign’s actions without exception, including immoral ones. Indeed, immoral laws and decrees are legally valid precisely because and insofar as they have been authorized by citizens.
Graph domain adaptation–based framework for gene expression enhancement and cell type identification in large-scale spatially resolved transcriptomics
Authors: Shen Rongbo , Cheng Meiling , Wang Wencang , Fan Qi , Yan Huan , Wen Jiayue , Yuan Zhiyuan , Yao Jianhua , Li Yixue , Yuan Jiao
Published: November 2024

Spatially resolved transcriptomics (SRT) technologies facilitate gene expression profiling with spatial resolution in a naïve state. Nevertheless, current SRT technologies exhibit limitations, manifesting as either low transcript detection sensitivity or restricted gene throughput. These constraints result in diminished precision and coverage in gene measurement. In response, we introduce SpaGDA, a sophisticated deep learning–based graph domain adaptation framework for both scenarios of gene expression imputation and cell type identification in spatially resolved transcriptomics data by impartially transferring knowledge from reference scRNA-seq data. Systematic benchmarking analyses across several SRT datasets generated from different technologies have demonstrated SpaGDA's superior effectiveness compared to state-of-the-art methods in both scenarios. Further applied to three SRT datasets of different biological contexts, SpaGDA not only better recovers the well-established knowledge sourced from public atlases and existing scientific literature but also yields a more informative spatial expression pattern of genes. Together, these results demonstrate that SpaGDA can be used to overcome the challenges of current SRT data and provide more accurate insights into biological processes or disease development. The SpaGDA is available in https://github.com/shenrb/SpaGDA.
Phylogenetic-informed graph deep learning to classify dynamic transmission clusters in infectious disease epidemics
Authors: Sun Chaoyue , Li Yanjun , Marini Simone , Riva Alberto , Wu Dapeng Oliver , Fang Ruogu , Salemi Marco , Rife Magalis Brittany
Published: November 2024

Motivation

In the midst of an outbreak, identification of groups of individuals that represent risk for transmission of the pathogen under investigation is critical to public health efforts. Dynamic transmission patterns within these clusters, whether it be the result of changes at the level of the virus (e.g. infectivity) or host (e.g. vaccination), are critical in strategizing public health interventions, particularly when resources are limited. Phylogenetic trees are widely used not only in the detection of transmission clusters, but the topological shape of the branches within can be useful sources of information regarding the dynamics of the represented population.

Results

We evaluated the limitation of existing tree shape metrics when dealing with dynamic transmission clusters and propose instead a phylogeny-based deep learning system –DeepDynaTree– for dynamic classification. Comprehensive experiments carried out on a variety of simulated epidemic growth models and HIV epidemic data indicate that this graph deep learning approach is effective, robust, and informative for cluster dynamic prediction. Our results confirm that DeepDynaTree is a promising tool for transmission cluster characterization that can be modified to address the existing limitations and deficiencies in knowledge regarding the dynamics of transmission trajectories for groups at risk of pathogen infection.

Availability and implementation

DeepDynaTree is available under an MIT Licence in https://github.com/salemilab/DeepDynaTree.
FEHAT: efficient, large scale and automated heartbeat detection in Medaka fish embryos
Authors: Ferreira Marcio Soares , Stricker Sebastian , Fitzgerald Tomas , Monahan Jack , Defranoux Fanny , Watson Philip , Welz Bettina , Hammouda Omar , Wittbrodt Joachim , Birney Ewan
Published: November 2024

High-resolution imaging of model organisms allows the quantification of important physiological measurements. In the case of fish with transparent embryos, these videos can visualize key physiological processes, such as heartbeat. High throughput systems can provide enough measurements for the robust investigation of developmental processes as well as the impact of system perturbations on physiological state. However, few analytical schemes have been designed to handle thousands of high-resolution videos without the need for some level of human intervention. We developed a software package, named FEHAT, to provide a fully automated solution for the analytics of large numbers of heart rate imaging datasets obtained from developing Medaka fish embryos in 96-well plate format imaged on an Acquifer machine. FEHAT uses image segmentation to define regions of the embryo showing changes in pixel intensity over time, followed by the classification of the most likely position of the heart and Fourier Transformations to estimate the heart rate. Here, we describe some important features of the FEHAT software, showcasing its performance across a large set of medaka fish embryos and compare its performance to established, less automated solutions. FEHAT provides reliable heart rate estimates across a range of temperature-based perturbations and can be applied to tens of thousands of embryos without the need for any human intervention.

Availability and implementation

Data used in this manuscript will be made available on request.
Exploration of the mutational landscape of cutaneous leiomyoma confirms FH as a driver gene and identifies targeting purine metabolism as a potential therapeutic strategy
Authors: van der Weyden Louise , Del Castillo Velasco-Herrera Martin , Cheema Saamin , Wong Kim , Boccacino Jacqueline M , Vermes Ian , Offord Victoria , Droop Alastair , Jones David R A , Anderson Elizabeth , Hardy Claire , de Saint Aubain Nicolas , Ferguson Peter M , Mogler Carolin , Rajan Neil , Frew Derek , Harms Paul W , Billings Steven D , Schatton Désirée , Segarra-Mondejar Marc , Arends Mark J , Ferreira Ingrid , Brenn Thomas , Frezza Christian , Adams David J
Published: November 2024

To comprehensively explore the mutational landscape of cutaneous leiomyoma (cLM) and identify candidate driver events, we performed a retrospective, multi-institutional, whole-exome sequencing and RNA sequencing study. We confirmed that a large proportion of patients with cLM have germline FH variants and additionally showed that somatic alteration of FH also drives cLM, with biallelic inactivation of FH being a frequent event. Treatment of Fh1-proficient and -deficient cell lines with the purine antagonist and chemotherapeutic agent, mercaptopurine, significantly decreased growth/colony formation; however, the addition of nucleosides was able to rescue only the Fh1-proficient cells, suggesting that purine metabolism is a targetable vulnerability for FH-deficient cLMs.
Artificial daylight photodynamic therapy using methyl aminolaevulinate in a real-world setting in Germany: results from the noninterventional study ArtLight
Authors: Philipp-Dormston Wolfgang G , Brückner Matthias , Hoffmann Matthias , Baé Melvin , Fränken Jörg , Großmann Bernd , Paasch Uwe , Quist Sven , Lang Berenice M , Chavda Rajeev , Szeimies Rolf-Markus
Published: November 2024

Background

Artificial daylight photodynamic therapy (ADL-PDT) is an alternative, all-year applicable, nearly painless treatment approach for actinic keratosis (AK) with comparable effectiveness to daylight or conventional PDT. At the time this study was initiated, methyl aminolaevulinate (MAL) was the only photosensitizer approved for ADL-PDT in Germany.

Objectives

To gain comprehensive insights into the practicability of MAL-ADL-PDT in patients with AK using different artificial daylight sources under real-world conditions.

Methods

This prospective, noninterventional, multicentre study (ArtLight, NCT05725213) enrolled patients with Olsen grade 1 or 2 AK on the face and scalp in Germany. Patients were treated with MAL-ADL-PDT (160 mg g–1 MAL cream). The primary outcome measure was the practicability of MAL-ADL-PDT assessed as rate of resolved AK lesions in the focus area (10 × 10-cm area within the treatment area). Secondary outcomes included treatment-associated pain (numeric rating scale, NRS), Actinic Keratosis Area and Severity Index (AKASI), total lesion count over time, skin preparation, safety, overall assessment of effectiveness, tolerability, adherence and patient satisfaction.

Results

In total, 224 patients [median age 75.0 (range 50–91) years, 85.3% male, 62.5% AK Olsen grade 2, 55.4% treatment-naïve] were included and treated with MAL-ADL-PDT. Three months after treatment, lesion counts were reduced in the focus area by 71% (P < 0.001) indicating practicability of the treatment. Nearly all patients (93.3%) experienced no or mild pain during PDT (NRS score 0–3). Median AKASI decreased from 6.2 at baseline to 3.4 at month 3 (95% confidence interval 2.4–3.0; P < 0.001). The majority of investigators (82.8%) and patients (80.0%) were satisfied with the treatment. No new safety signals were reported.

Conclusions

The clinical practicability of MAL-ADL-PDT was demonstrated under real-world conditions by effective lesion reduction and predominantly none-to-mild procedural pain. Thus, MAL-ADL-PDT is a convenient way for healthcare professionals to deliver PDT treatment to patients with AK located on the face and scalp.
Polyfluorene bearing quinoline and ferrocene as the pendant groups for bioelectronics
Authors: Zhang Chenjian , Qian Ning , Qin Tianhao , Chen Qian , Liu Jiaxuan , He Haidong , Chen Yu
Published: November 2024

Analog-type polymer memristors are preeminent candidates for neuromorphic computation and synaptic biomimicking. A novel polyfluorene bearing quinoline and ferrocene as the pendant groups (PQF) is synthesized. The PQF film sandwiched between the Al and ITO electrodes exhibits outstanding analog-type memristive performance at a small sweep voltage range of ±1 V, with 42 distinguishable conductance states. In comparison, poly{[9,9-di(2,4-diphenylquinoline)-fluorene]-alt-[9,9-bis(6-bromohexyl)-9H-fluorene]}, and poly {[9H-fluorene]-alt-[fluorene with triazole and ferrocene moieties in the sidechains]} only show 12 and 15 distinguishable conductance states, respectively. The former only involves intramolecular charge transfer from the polymer backbone to the quinolone moieties, while the latter mainly concerns redox effect from the ferrocene moieties. These results demonstrate that the combined action of intramolecular electron transfer and redox effect could dramatically increase the number of distinguishable conductive states of the resultant materials. Associated with the exceptional memristive performance, the PQF-based memristor can accurately recognize human emotions. After 150 training sessions, the accuracy of emotion recognition reaches up to 98.74%.
Comprehensive Review on Plant Cytochrome P450 Evolution: Copy Number, Diversity, and Motif Analysis From Chlorophyta to Dicotyledoneae
Authors: Fang Yuanpeng , Tai Zheng , Hu Keyi , Luo Lingfeng , Yang Sanwei , Liu Mengmeng , Xie Xin
Published: November 2024

Cytochrome P450 enzymes (CYPs) are widely distributed among various plant groups and constitute approximately 1% of the total number of protein-coding genes. Extensive studies suggest that CYPs are involved in nearly all molecular processes that occur in plants. Over the past two decades, the identification of CYP genes has expanded rapidly, with more than 40,000 CYP genes and 819 CYP families being discovered. Copy number variation is a significant evolutionary characteristic of gene families, yet a systematic characterization of the copy evolution patterns in plant CYP gene families has been lacking, resulting in confusion and challenges in understanding CYP functions. To address these concerns, this review provides comprehensive statistics and analyses of the copy number and diversity of almost all plant CYP gene families, focusing on CYP evolution from Chlorophyta to Dicotyledoneae. Additionally, we examined the subfamily characteristics of certain CYP families with restricted copy changes and identified several CYP subfamilies that play pivotal roles in this event. Furthermore, we analyzed the structural conservation of CYPs across different taxa and compiled a comprehensive database to support plant CYP studies. Our analysis revealed differences in the six core conserved motifs of plant CYP proteins among various clans and plant taxa, while demonstrating similar conservation patterns for the ERR (glutamic acid-arginine-arginine) triad motifs. These findings will significantly facilitate the understanding of plant CYP gene evolution and metabolic diversity and serve as a valuable reference for researchers studying CYP enzymes.
Genome-wide association for agro-morphological traits in a triploid banana population with large chromosome rearrangements
Authors: Rio Simon , Toniutti Lucile , Salmon Frédéric , Hervouet Catherine , Cardi Céline , Mournet Pierre , Guiougou Chantal , Marius Franck , Mina Claude , Delos Jean-Marie Eric , Lambert Frédéric , Madec Camille , Efile Jean-Claude , Cruaud Corinne , Aury Jean Marc , D’Hont Angélique , Hoarau Jean-Yves , Martin Guillaume
Published: November 2024

Banana breeding is hampered by the very low fertility of domesticated bananas and the lack of knowledge about the genetic determinism of agronomic traits. We analysed a breeding population of 2723 triploid hybrids resulting from crosses between diploid and tetraploid Musa acuminata parents, which was evaluated over three successive crop cycles for 24 traits relating to yield components and plant, bunch, and fruit architectures. A subset of 1129 individuals was genotyped by sequencing, revealing 205 612 single-nucleotide polymorphisms (SNPs). Most parents were heterozygous for one or several large reciprocal chromosomal translocations, which are known to impact recombination and chromosomal segregation. We applied two linear mixed models to detect associations between markers and traits: (i) a standard model with a kinship calculated using all SNPs and (ii) a model with chromosome-specific kinships that aims at recovering statistical power at alleles carried by long non-recombined haplotypic segments. For 23 of the 24 traits, we identified one to five significant quantitative trait loci (QTLs) for which the origin of favourable alleles could often be determined amongst the main ancestral contributors to banana cultivars. Several QTLs, located in the rearranged regions, were only detected using the second model. The resulting QTL landscape represents an important resource to support breeding programmes. The proposed strategy for recovering power at SNPs carried by long non-recombined rearranged haplotypic segments is an important methodological advance for future association studies in banana and other species affected by chromosomal rearrangements.
Diagnostic performance of a newly launched Canadian fast-track ultrasound clinic by rheumatologists for the diagnosis of giant cell arteritis
Authors: Mourot Jean-Charles , Yuen Sai Yan , Popescu Mihaela Luminita , Richard Nicolas
Published: November 2024

Background

Giant cell arteritis (GCA) can present diagnostic challenges and early diagnosis is crucial due to potential ischemic complications. Recent guidelines suggest that a suspected diagnosis should be confirmed with temporal artery biopsy or imaging, including ultrasound (US). In our Canadian setting, point-of-care temporal artery US was near unavailable, and biopsy remains the standard of care. We hypothesize that launching a fast-track US clinic by rheumatologists may spare the need for a temporal artery biopsy. Therefore, this study aimed to assess the diagnostic performance of US in this newly launched fast-track clinic.

Methods

In this single-center retrospective cross-sectional analysis, 99 visits were identified from the fast-track clinic between January 2020 and July 2022. Each subject had an US according to a standard protocol for suspicion of either new-onset or relapse of GCA. Ultrasonographers were rheumatologists who acquired training on vascular US techniques before launching the clinic. For each patient presenting with suspected new-onset GCA, the pretest probability was calculated using the Southend GCA probability score. The sensitivity, specificity, positive predictive value (PPV), and negative predictive value (NPV) were calculated using the rheumatologist clinical diagnosis as the gold standard for GCA diagnosis.

Results

A total of 22 subjects had a diagnostic of GCA and 77 had another diagnostic. Patients with and without GCA were, respectively, 81.8% versus 72.7% females, had a mean age of 76.6 ± 7.7 versus. 74.8 ± 9.8 years, and a mean CRP of 73.4 ± 57.8 versus 38.3 ± 59.9 mg/l. Temporal artery US demonstrated a sensitivity of 86.3% [95% confidence interval (CI), 65.1–97.1%], a specificity of 90.9% (95% CI, 82.2–6.3%), a PPV of 73.1% (95% CI, 56.8–84.9%), and a NPV of 95.9% (95% CI, 89.0–.5%). 14 patients had a suspicion of relapse and were all correctly identified by the US. Among those with suspicion of new-onset 27, 34 and 24 US were performed for high, intermediate, and low pretest probability of GCA, respectively. The high-risk subgroup demonstrated higher PPV while similar sensitivity/specificity was observed between all three subgroups.

Conclusion

Our results highlight the benefits of US as a key diagnostic tool for GCA, particularly when combined with clinical evaluations. An excellent discriminative ability for diagnosis of GCA was shown in this newly launched clinic suggesting that the role of TAB may need to be redefined. These findings will guide on broader implementation of US programs for GCA.
Toxicity and residual activity of insecticides to Grapholita molesta (Lepidoptera: Tortricidae) in apple orchards: implications for insecticide resistance management
Authors: Stupp Paloma , Lerin Sabrina , Gomes da Silva Filho José , Arioli Cristiano João , Bernardi Daniel
Published: November 2024

Organophosphate (OP) insecticides have been used to control Grapholita molesta (Busck, 1916) in Brazil since 1990. However, the evolution of pest insecticide resistance and toxicological reassessments has led to the replacement of OPs with other chemical groups. This study evaluated the toxicity of the insecticides abamectin + cyantraniliprole (1.1 + 3.7 g a.i./100 L−1), acetamiprid + etofenproxi (9.1 + 16.5 g a.i./100 L−1), emamectin benzoate (0.5 g a.i./100 L−1), Sophora flavescens (Fabales: Fabaceae) (22.8 g a.i./100 L−1), phosmet (87.5 g a.i./100 L−1), and indoxacarb (11.2 g a.i./100 L−1) to eggs, larvae, and adults of G. molesta. Additionally, the residual activity of these insecticides in apple orchards was assessed, and the diagnostic concentration for resistance monitoring was estimated using LC99 values (Lethal Concentration that causes 99% mortality in a susceptible population). In larval studies, all insecticides resulted in mortality rates of more than 90%. The insecticide acetamiprid + etofenproxi reduced larval hatching by 99%. This insecticide with phosmet and Sophora flavescens caused over 80% adult mortality and had a 14-day residual activity in apple orchards. The estimated LC99 (μg.ml−1) for resistance monitoring were 1.75 (indoxacarb), 6.45 (metaflumizone), 9.10 (acetamiprid + etofenproxi), 9.67 (Sophora flavescens), 36.13 (phosmet), and 45.61 (abamectin + cyantraniliprole). The insecticides evaluated have high toxicity for G. molesta, being new tools for integrated pest management and for insecticide resistance management in apple orchards.
Decreasing the Use of Cefdinir for Pediatric Urinary Tract Infections in a Rural Health Care System: A Quasi-experimental Study
Authors: Berglund Kelly , Whitfield Philip Logan , Gabor Rachel M , Boyce Thomas G
Published: November 2024

There are several antimicrobial options for treating urinary tract infections in children. Although cefdinir is commonly used, better options exist. We developed an intervention bundle to reduce the use of cefdinir in favor of cephalexin. The intervention bundle decreased cefdinir use by 19.1% (73% relative decrease) while the use of cephalexin increased by 19.8%.
Robotic resection of a giant thymolipoma in a pediatric patient
Authors: Hanke Rae , Emr Bryanna , Taylor Matthew , Fahy Aodhnait S
Published: November 2024

Thymolipomas are benign lesions in the anterior mediastinum that most commonly present in the first three decades of life. They often are asymptomatic and can be very large at time of diagnosis. After incidental detection of a thoracic mass on an abdominal ultrasound, an otherwise well 10 years old male was evaluated with further imaging, including a cardiac-gated magnetic resonance imaging (MRI) study. This demonstrated that the mass was intimate with but did not appear to invade the pericardium, likely originating from the thymus. Despite the large size, the patient underwent robotic resection of the mass and we include photographs illustrating the minimally invasive approach and highlighting critical structures. The patient tolerated the procedure well and recovered quickly. Final pathology was consistent with a giant thymolipoma. In summary, workup of giant thymolipomas is optimized with cardiac gated imaging. Despite their large size, these can be safely managed in a minimally invasive fashion in pediatric patients.
Untying the Knot: How Child Support and Alimony Affect Couples’ Dynamic Decisions and Welfare
Authors: Foerster Hanno
Published: November 2024

In many countries, divorce law mandates post-marital maintenance payments (child support and alimony) to insure the lower earner in married couples against financial losses upon divorce. This paper studies how maintenance payments affect couples’ intertemporal decisions and welfare. I develop a dynamic model of family labour supply, home production, savings, and divorce and estimate it using Danish register and survey data. The model captures the policy tradeoff between providing insurance to the lower earner and enabling couples to specialise efficiently, on the one hand, and maintaining labour supply incentives for divorcees, on the other hand. I use the estimated model to study various counterfactual policy scenarios. I find that alimony comes with more substantial labour supply disincentives compared to child support payments and is less efficient in providing consumption insurance. The welfare maximising policy, within the status quo policy space, involves increasing child support and reducing alimony payments. My results show that Pareto improvements beyond this welfare maximising policy are feasible, highlighting limitations of how child support and alimony policies are commonly implemented.
In- & Out-Cloning: plasmid toolboxes for scarless transcription unit and modular Golden Gate acceptor plasmid assembly
Authors: de Vries Stijn T , Köbel Tania S , Sanal Ahmet , Schindler Daniel
Published: November 2024

Golden Gate cloning has become one of the most important DNA assembly strategies. The construction of standardized and reusable part libraries, their assembly into transcription units, and the subsequent assembly of multigene constructs is highly reliable and sustainable. Researchers can quickly construct derivatives of their assemblies or entire pathways, and importantly, the standardization of Golden Gate assemblies is compatible with laboratory automation. Most Golden Gate strategies rely on 4-nt overhangs generated by commonly used Type IIS enzymes. However, reduction to 3-nt overhangs allows the use of codons as fusion sites and reduces potential scar sequences. This is particularly important when studying biological functions, as additional nucleotides may alter the structure or stability of the transcribed RNA. To address this issue we use SapI, a Type IIS enzyme generating three nucleotide overhangs, for transcription unit assembly, allowing for codon-based fusion in coding sequences. We created a corresponding plasmid toolbox for basic part generation and transcription unit assembly, a workflow we term as In-Cloning. In-Cloning is downstream compatible with the Modular Cloning standard developed by Sylvestre Marillonnet’s group for standardized assembly of multigene constructs. However, the multigene construct plasmids may not be compatible for use with the model organism of choice. Therefore, we have developed a workflow called Out-Cloning to rapidly generate Golden Gate acceptor plasmids. Out-Cloning uses standardized plasmid parts that are assembled into Golden Gate acceptor plasmids using flexible linkers. This allows the systematic construction of acceptor plasmids needed to transfer assembled DNA into the organism of interest.
Limitations of acetaminophen as a reference hepatotoxin for the evaluation of in vitro liver models
Authors: Livoti Lucia A , Sison-Young Rowena , Reddyhoff Dennis , Fisher Ciarán P , Gardner Iain , Diaz-Nieto Rafael , Goldring Christopher E , Copple Ian M
Published: November 2024

Acetaminophen is commonly used as a reference hepatotoxin to demonstrate that in vitro human liver platforms can emulate features of clinical drug-induced liver injury. However, the induction of substantial cell death in these models typically requires acetaminophen concentrations (∼10 mM) far higher than blood concentrations of the drug associated with clinical hepatotoxicity (∼1 mM). Using the cytochrome P450 inhibitor 1-aminobenzotriazole, we show that acetaminophen toxicity in cultured human, mouse, and rat hepatocytes is not dependent on N-acetyl-p-benzoquinonimine formation, unlike the in vivo setting. This finding highlights the limitation of using acetaminophen as a reference hepatotoxin for the evaluation of in vitro liver models. Hence, we make recommendations on the selection of reference hepatotoxins for this purpose.
Optimization of Timing for Risk-Reducing Salpingectomy and Oophorectomy
Authors: Pennington Kathryn P. , Pugh Stephanie L. , Huh Warner , Walker Joan L. , Jewell Elizabeth , Havrilesky Laura J. , Carter Jeanne , Muller Carolyn Y. , Drapkin Ronny , Lankes Heather A. , Castellano Tara , Zamorano Abigail S. , Blank Stephanie V. , Kachnic Lisa A.
Published: November 2024

Most cases of ovarian cancer are diagnosed at an advanced stage, and long-term survival rates are low. Because no effective ovarian cancer screening has yet been developed, the primary focus to reduce ovarian cancer mortality is surgical prevention. For individuals with a significantly increased risk of ovarian cancer, risk-reducing bilateral salpingo-oophorectomy is highly effective, but uptake at the recommended age is suboptimal, likely because of concerns about premature menopause. Evidence suggests that many “ovarian” cancers originate in the distal fallopian tube, thus making bilateral salpingectomy after completion of childbearing with delayed oophorectomy an attractive but still unproven risk-reduction option for those who decline or are not yet ready for risk-reducing bilateral salpingo-oophorectomy. Two clinical trials (SOROCk [A Non-randomized Prospective Clinical Trial Comparing the Non-inferiority of Salpingectomy to Salpingo-oophorectomy to Reduce the Risk of Ovarian Cancer Among BRCA1 Carriers], NCT04251052; and TUBA-WISP2 [Tubectomy With Delayed Oophorectomy as an Alternative to Risk-Reducing Salpingo-oophorectomy in High-Risk Women to Assess the Safety of Prevention]; NCT04294927) are ongoing to determine whether bilateral salpingectomy with delayed oophorectomy is as effective as risk-reducing bilateral salpingo-oophorectomy to prevent ovarian cancer. The SOROCk trial is a national, prospective nonrandomized trial powered to test the hypothesis that bilateral salpingectomy with delayed oophorectomy is noninferior to risk-reducing bilateral salpingo-oophorectomy to reduce the incidence of ovarian cancer among people with deleterious germline BRCA1 mutations. Gynecologists and gynecologic oncologists in both community-based and academic practices may perform risk-reducing surgeries and have their patients participate in the SOROCk trial. We review key aspects of the SOROCk clinical trial and discuss how surgeons can partner with SOROCk clinical trial sites and facilitate their patients' participation to help answer this important clinical question.

CLINICAL TRIAL REGISTRATION:

ClinicalTrials.gov, NCT04251052.
Trends in Short Interpregnancy Interval Births in the United States, 2016–2022
Authors: Admon Lindsay K. , MacCallum-Bridges Colleen , Daw Jamie R.
Published: November 2024

OBJECTIVE:

To measure contemporary trends in the prevalence of short interpregnancy interval (IPI) births in the United States.

METHODS:

We conducted a repeated cross-sectional analysis using 2016–2022 natality data from the National Vital Statistics System. We included all singleton live births to individuals with at least one prior live birth. We examined trends over time in short IPIs less than 18 months, as well as for specific durations within this time frame (less than 6 months, 6–11 months, and 12–17 months), using linear probability models that estimated changes in the prevalence of each IPI duration over time. We then estimated the prevalence of each short IPI duration by maternal race and ethnicity, socioeconomic characteristics (age, education, insurance payer at delivery), and geography (U.S. census region, state of residence).

RESULTS:

The study sample included 14,770,411 singleton live births to individuals with at least one prior live birth in 2016–2022. Roughly a third (29.8%) of births had an overall IPI of less than 18 months (5.0% less than 6 months, 11.0% 6–11 months, and 13.8% 12–17 months). For IPIs less than 6 months, a slight statistical decline in prevalence was identified over the study period in unadjusted and adjusted models (adjusted annual percentage point change −0.02, 95% CI, −0.03 to −0.02). Slight statistical increases in the prevalence of IPIs of 6–11 and 12–17 months were identified in unadjusted models but were no longer significant and reversed direction in adjusted models, respectively. Long-standing inequities in the distribution of the shortest IPIs (less than 6 months) were stable compared with prior work across the indicators examined in this study.

CONCLUSION:

Overall, it appears the prevalence of short IPIs has remained stable between 2016 and 2022.
Corneal Ectasia Following Cosmetic Keratopigmentation
Authors: Nouzovská Kateřina , Noveyri Behzad Barazandeh , Abu-Mustafa Sabat , Alió Jorge L.
Published: November 2024

Purpose:

The purpose of this study was to describe 5 cases (10 eyes) that, following purely cosmetic femtosecond laser-assisted keratopigmentation (KTP), showed evolution toward corneal ectasia during a variable postoperative period.

Methods:

In a case series, 5 patients after bilateral purely cosmetic KTP showed progressive changes in topographic, refractive, and even in visual performance values manifesting from 6 months to 4 years following the procedure. A femtosecond laser-assisted cosmetic intrastromal KTP technique was performed in all patients using micronized mineral pigments. Two patients underwent a retouch using superficial automated KTP to optimize cosmetic outcome.

Results:

All patients preoperatively demonstrated normal corneal topography with no intraocular pathology and unimpaired visual acuity. One of the cases developed corneal ectasia after magnetic resonance imaging, another confirmed intensive eye rubbing due to allergic conjunctivitis, and 1 patient underwent previous myopic laser in situ keratomileusis procedure. The rest did not show any preoperative clinical evidence potentially related to the development of the keratectasia. One case rather demonstrated modification of keratometry (K) values than a clear corneal ectasia. Three cases were treated with epi-off corneal cross-linking.

Conclusions:

Corneal ectasia is a potential complication after cosmetic KTP and should be included in the preoperative informed consent. A comprehensive preoperative screening is necessary to exclude suspicious cases, and patients should be instructed to avoid eye rubbing and other maneuvers that could affect the potential development of this complication.
The impact of recipient hypernatremia on pediatric liver transplantation outcomes
Authors: He Zhi Mei Sonia , Reyes Gabriel , Liu Tommy , McDonald Malcolm , Kamepalli Spoorthi , Goss John A. , Galvan Nhu Thao Nguyen , Rana Abbas
Published: November 2024

In pediatric liver transplants, dysnatremias have been found to have an impact on pre- and post-transplant outcomes. However, much of the current literature has focused on wait-list survival, secondary organ damage, and dysnatremia in donors rather than in recipients. To understand the effect of recipient immediate pre-transplant hypernatremia on post-transplant mortality, we conducted a multivariable retrospective review analyzing data from 8,011 pediatric patients undergoing liver transplantation provided by the United Network for Organ Sharing (UNOS). Multivariable analysis of hypernatremia showed an increased risk of mortality (odds ratio [OR]: 2.49, 95% confidence interval [CI]: 1.75, 3.54 for a serum sodium between 150-155 mEq/L) while hyponatremia did not show a significant increase in relative risk for mortality (HR: 1.11, 95% CI: 0.75, 1.63 for a serum sodium between 125-130 mEq/L). Kaplan-Meier (KM) curves stratified by sodium level showed statistically significant differences in outcomes with progressively increasing mortality associated with increasing serum sodium levels. In particular, there is a statistically significant increase in 90-day mortality with serum sodium levels above 150 mEq/L. Hyponatremia had a moderate impact on mortality but was not statistically significant. Our analysis of immediate pre-transplantation resolution of hypernatremia also showed improved survival outcomes with a decreased mortality compared to transplant patients with unresolved hypernatremia. In conclusion, immediate pre-transplant recipient hypernatremia has a substantial impact on pediatric post-liver transplantation survival. Corrected hypernatremia resulted in decreased mortality compared to uncorrected hypernatremia. Recipient hypernatremia is an important indicator of disease processes and a predictor of poor post-transplantation mortality outcomes.
Outcomes following the use of HBsAg-positive liver allografts in HBsAg-negative recipients
Authors: Myer Adam S. , Seccurro Drake A. , Sherman Kenneth E. , Sharma Yeshika
Published: November 2024

The use of positive HBsAg (HBsAg+) liver allografts has been increasing globally and is gaining wider acceptance within the United States. However, most of the data supporting the use of HBsAg+ organs has been in the setting of recipients with chronic hepatitis B. We aim to describe our institutional experience using HBsAg+ liver donors in HBsAg-negative recipients through case series. Between 2019 and 2021, 10 HBsAg-negative recipients received an HBsAg+ liver transplant. Kaplan-Meier survival analysis showed no difference in survival when compared to all other liver transplants performed at the institution during the same period (p = 0.5, HR = 1.6, CI = 0.4–6.5). Based on these findings, the use of HBsAg+ liver donors appears to be safe; however, continued follow-up is required to understand further risks associated with the use of HBsAg+ liver allografts.