bluuebunny/crossref_metadata_2025_split huggingface dataset:
Radical surgical excision of extensive perianal melanomas on standing horses: Twenty cases
Authors: Robert Mickaël P. , Buyck Camille , Tricaud Cyril , Cousty Matthieu , Pujol Raymond 
Published: November 2024

AbstractObjectiveTo report a radical surgical technique for perianal melanomas involving the anal margin in standing horses.Study designObservational retrospective study.Sample populationTwenty client‐owned horses presented for surgical excision of extensive (≥4 cm) perianal melanomas.MethodsDemographic data, surgical technique, intraoperative, immediate‐ and late‐postoperative complications were reviewed.ResultsAll horses (median age 15, Q1–Q3 12 to 17.3 years) were operated under standing sedation and epidural anesthesia. Median hospitalization period was 6.5 days (Q1–Q3 5 to 8.3 days). The anal margin was fully resected in 14 cases. A deep perirectal dissection was performed in 16 cases. Eight cases required additional local anesthetics. One case bled profusely during and after the procedure. One case became recumbent during the procedure, showed intense postoperative pain, and was eventually euthanized 6 weeks later because of ataxia. During hospitalization, one horse displayed colic signs and 10 others required manual evacuation of the rectum because of decreased fecal output. Complications after hospital discharge included mild colic signs (n = 4), partial wound dehiscence (n = 1) and hypergranulation of the wound (n = 2). All other cases healed without complications in 6 to 12 weeks. Median follow‐up period was 11.8 months (Q1–Q3 6.3 to 27.2 months). Six horses developed new melanomas with only one in the perianal region.ConclusionThis technique of surgical excision of extensive perianal melanomas was efficiently performed on standing horses with minimal local recurrence. This procedure led to high client satisfaction. Early postoperative pain was commonly encountered. Owners should be warned of the potentially large surgical wound that will be created.Clinical significanceThis technique allowed for removal of large perianal melanomas with limited recurrence during the long term follow up and may improve the quality of life of affected horses.
Model Parameter Extraction From Contact Geometry and Compliance in Tire–Soil Interaction
Authors: Sime Muluneh 
Published: November 2024

Abstract
A method for extracting traction model parameters from tire–soil interaction measurements and analysis to account for coupled tire–soil deformation is presented. The observable physical properties or conditions, measurable or explainable by principles of engineering mechanics, as factors affecting tire–soil contact surface geometry are identified. Tractive force and soil shear strength are dependent on the contact geometry. The rationale and methods to identify the confluence of parameters and their use to estimate an aggregate model parameter are discussed. The aggregate model parameter captures factors influencing the shape and scale of net tractive force and slip generated by driven tire, including in-situ soil water content and porosity, tire compliance, slip, and sinkage. One of the key aspirations of this paper is to show a method to estimate the soil strength parameter as a function of soil water content explicitly and incorporate in vehicle–ground interaction models.
Sound Mitigation by Metamaterials With Low-Transmission Flat Band
Authors: Zhang Ruojun , Zhang Lei , Hu Gengkai , Zhou Xiaoming 
Published: November 2024

Abstract
Space-coiling acoustic metamaterials dominated by the Fano resonance are being widely exploited for simultaneous control of sound isolation and air ventilation, and they usually achieve complete sound mitigation at multiple isolated frequencies. Here, we theoretically discover and experimentally demonstrate the low-transmission flat-band phenomenon in channeling-type acoustic metamaterials. The metamaterial is constructed with coupled coiling and straight channels, both working in acoustic resonant states. An analytic coupled-mode model is established to capture the coupling interaction between resonant states supported by two channels. A critical coupling condition is derived from the model, which can lead to sextremely low sound transmission in a finite band rather than at isolated frequencies, as validated by both numerical simulations and experiments. We then demonstrate the generality of the flat-band behavior of low transmission by a systematic survey of the coupling of different order resonant modes. Finally, the flat-band effect is also found to exist in the extended model with the side-loaded coiling channel as verified experimentally.
Generative AI-Enabled Conceptualization: Charting ChatGPT’s Impacts on Sustainable Service Design Thinking With Network-Based Cognitive Maps
Authors: Jiang Chenhan , Huang Rui , Shen Tao 
Published: November 2024

Abstract
The rise of generative artificial intelligence (GAI) applications, epitomized by ChatGPT, has reshaped design processes by enhancing idea generation and conceptual depth for designers. However, the facilitating effects on novice designers' thinking remain uncertain, particularly in the context of sustainable service concept generation. This study examines these impacts of ChatGPT on design thinking process and outcomes through controlled experiments with 36 novice designers with ChatGPT, Tiangong AI, and no tools under a sustainable service design task. Through the protocol analysis, this study visualizes the design thinking by network-based cognitive maps, then evaluates design outcomes and systematically analyzes characteristics of design thinking development under different tool interventions. Findings indicate that ChatGPT enhances design concept novelty and systematicity but has limited impact on originality and sustainability. Furthermore, ChatGPT plays an active role in fostering thinking divergence and fluency, especially in providing relevant guides for developed ideas and accelerating the evaluation and creation process. The network-based cognitive maps reveal distinct shifts and styles influenced by ChatGPT, providing references for novice designers using such tools to enhance inspiration and design fluency, and also effectively employ diverse tools during specific concept generation stage. The study also provides insights for enhancing the relevance of educational curricula and enabling bottom-up sustainable service innovations.
Kinematic Analysis and Trajectory Planning of Multi-Segment Continuum Manipulator
Authors: Bai Zhengfeng , Niu Yuxin , Kong Qingfeng 
Published: November 2024

Abstract
The flexible or continuum manipulators present excellent dexterity in confined space, which is beneficial to wide application prospects in many fields. In this paper, we establish the kinematic model and propose a trajectory planning algorithm for multi-segment continuum manipulators. The multi-level mapping from the actuator variables to the manipulator tip is described. A novel modal kinematic method is proposed to overcome the singularity problem generated by the piecewise constant curvature kinematics modeling method. Then, the improved particle swarm optimization algorithm is proposed to solve the problem of redundant inverse kinematics and realize the trajectory tracking of the manipulator tip. In addition, the configuration parameters are restricted by the constraint functions, so that the precise shape of the multi-segment manipulator can be controlled. Finally, a series of numerical simulations are conducted to implement the investigation. Simulation results demonstrate that the proposed modal kinematic method and the trajectory planning algorithm are effective for multi-segment continuum manipulator.
The Impact of Inflow Unsteadiness on Loss Prediction
Authors: Przytarski Pawel J. , Lengani Davide , Sandberg Richard 
Published: November 2024

Abstract
Stagnation pressure loss coefficient is still the most commonly used loss metric for performance evaluation and is routinely used to validate simulations. This is because it is easy to measure and readily available from the experiments. However, it was previously shown (TURBO-24-1006) that the stagnation pressure loss coefficient can become unreliable when high levels of inflow unsteadiness are present. As the current design trends are moving toward more compact machines and higher work coefficients, the levels of unsteadiness are likely to increase. It is therefore desirable to assess how higher inflow unsteadiness levels affect the performance of new blade designs and what loss metrics should be used to reliably estimate it. Motivated by the need to understand how performance prediction changes under highly unsteady inflow conditions, we perform a series of high-fidelity scale-resolving simulations. We use this data to construct energy budgets for a variety of mid-span compressor cases with varying Reynolds numbers and inflow turbulence intensities. This allows us to systematically assess the impact of inflow conditions on loss prediction when using stagnation pressure based loss metrics. Stagnation pressure loss coefficient was found to be least reliable for the high inflow turbulence intensities and at high Reynolds numbers.
Advanced Design of a Transition Duct for Supersonic Inlet Turbines in Rotating Detonation Engines
Authors: Mushtaq Noraiz , Pini Matteo , Gaetani Paolo 
Published: November 2024

Abstract
A supersonic inlet turbine can extract substantial energy from the highly fluctuating and transonic flow delivered by a rotating detonation combustor (RDC). However, a transition duct is necessary to achieve the supersonic inlet conditions required by the turbine. In this work, the supersonic transition duct is designed with the method of characteristics (MOC). A generalized implementation of the MOC is proposed for the generation of annular ducts with asymmetric and rotated hub and shroud walls. The model is extended to deal with ideal and non-ideal flows, namely flows characterized by non-ideal thermodynamic effects, and its accuracy has been verified through comparison with results obtained with computational fluid dynamics (CFD) simulations. In addition, boundary layer flow equations are combined with the MOC to predict viscous losses on the endwalls and to adjust duct geometry by accounting for the boundary layer thickness. Furthermore, it is essential to predict the effects of the large unsteadiness generated by the detonation combustor for an efficient operation of the turbine. The maximum incidence angle at the turbine inlet is predicted with a one-dimensional annular duct model. Supersonic duct flow behavior to unsteady inlet conditions is characterized through two-dimensional inviscid axisymmetric unsteady CFD simulations. The accuracy of the reduced order models is finally verified with a three-dimensional unsteady viscous simulation assuming inlet flow conditions representative of RDC operation.
Olorofim demonstrates
in vitro
activity against
Coccidioides
species, including isolates against which fluconazole has reduced activity
Authors: Wiederhold Nathan P. , Patterson Hoja P. , Ferrer Dora , Garcia Victor , Thompson George R. , Patterson Thomas F. 
Published: November 2024

ABSTRACT

We evaluated the
in vitro
activity of olorofim against
Coccidioides
species. Olorofim demonstrated potent
in vitro
activity against all isolates tested with a minimum inhibitory concentration (MIC) range ≤0.008–0.06 µg/mL and geometric mean MIC of 0.010 µg/mL. This activity was also maintained against isolates with elevated fluconazole MICs (≥16 µg/mL), including strains with MICs ≥32 µg/mL (olorofim MIC range ≤0.008–0.06 µg/mL and geometric mean MICs of ≤0.009 and ≤0.013 µg/mL, respectively).
Chicken ANP32A-independent replication of highly pathogenic avian influenza viruses potentially leads to mammalian adaptation-related amino acid substitutions in viral PB2 and PA proteins
Authors: Fujimoto Yoshikazu , Ozaki Kinuyo , Ono Etsuro 
Published: November 2024

ABSTRACT

Acidic nuclear phosphoprotein 32 family member A (ANP32A) is an important host factor that supports the efficient replication of avian influenza viruses (AIVs). To develop an antiviral strategy against Gs/Gd-lineage H5 highly pathogenic avian influenza (HPAI) viruses in chickens, we established chicken ANP32-knockout (chANP32A-KO) DF-1 cells and evaluated their antiviral efficacy through
in vitro
validation. The replication of all HPAI viruses tested in chANP32A-KO cells was significantly lower compared to that of wild-type DF-1 cells. However, when HPAI strains A/mountain hawk-eagle/Kumamoto/1/2007 (H5N1; MHE) and A/chicken/Aichi/2/2011 (H5N1; H5Aichi) were passed in chANP32A-KO cells, mutant viruses were generated, which exhibited comparable replication levels in both chANP32A-KO and wild-type DF-1 cells. Sequence analysis revealed that mammalian-adaptive amino acid mutations PB2_D256G and PA_T97I were present in the MHE mutant virus, and the PB2_E627K mutation was identified in the H5Aichi mutant virus. These mutations have also been reported to enhance the polymerase activity of AIVs in mammalian cells; however, the minigenome assay in the present study showed that the polymerase activity of mutant viruses in chANP32A-KO cells was not restored to levels comparable to those in wild-type DF-1 cells. These findings suggest that ANP32A-independent viral replication may induce amino acid substitutions associated with mammalian adaptation in AIVs. They also imply that the high efficiency of viral replication mediated by these amino acid mutations may not result from enhanced polymerase activity but rather involve other undefined mechanisms.

IMPORTANCE
During the host-switching of avian influenza viruses (AIVs) to mammalian hosts, introducing adaptive mutations into viral proteins is essential to ensure optimal functionality through virus-host protein interactions in mammalian cells. However, the mechanisms leading to adaptive mutations in viral proteins remain unclear. Among several host proteins that promote viral growth, acidic nuclear phosphoprotein 32 family member A (ANP32A) is known to be an important factor for efficient viral replication. Here, we generated mutant highly pathogenic avian influenza viruses capable of ANP32A-independent replication in a chicken-derived cell line. We demonstrated that several amino acid mutations found in the mutant viruses correspond to those associated with the mammalian adaptation of AIVs. These results suggest that ANP32A-independent viral replication is one of the mechanisms for introducing amino acid mutations that are reportedly involved in the mammalian adaptation of AIVs.
Augmented epigenetic repression of hepatitis B virus covalently closed circular DNA by interferon-α and small-interfering RNA synergy
Authors: Hu Kongying , Zai Wenjing , Xu Mingzhu , Wang Haiyu , Song Xinluo , Huang Chao , Liu Jiangxia , Chen Juan , Deng Qiang , Yuan Zhenghong , Chen Jieliang 
Published: November 2024

ABSTRACT

The persistence of hepatitis B virus (HBV) covalently closed circular DNA (cccDNA) is a key obstacle for HBV cure. This study aims to comprehensively assess the effect of interferon (IFN) and small-interfering RNA (siRNA) combination on the cccDNA minichromosome. Utilizing both cell and mouse cccDNA models, we compared the inhibitory effects of IFNα, siRNA, and their combination on cccDNA activity and assessed its epigenetic state. IFNα2 treatment alone reduced HBV RNAs, HBeAg, and HBsAg levels by approximately 50%, accompanied by a low-level reconstitution of SMC5/6—a chromatin modulator that restricts cccDNA transcription. HBx-targeting siRNA (siHBx) achieved significant suppression of viral antigens and reconstitution of SMC5/6, but this effect could be reversed by the deacetylase inhibitor Belinostat. The combination of IFN with siHBx resulted in over 95% suppression of virological markers, reduction in epigenetic activation modifications (H3Ac and H4Ac) on cccDNA, and further reduced cccDNA accessibility, with the effect not reversible by Belinostat. In an extracellular humanized IFNAR C57BL/6 mouse model harboring recombinant cccDNA, the effect of combination of clinically used pegylated IFNα2 and GalNac-siHBx was further clarified, indicating a higher and more durable suppression of cccDNA activity compared to either therapy alone. In conclusion, the combination of IFNα and siRNA achieves a more potent and durable epigenetic inhibition of cccDNA activity in cell and mouse models, compared to monotherapy. These findings deepen the understanding of cccDNA modulation and strengthen the scientific basis for the potential of combination therapy.

IMPORTANCE
Since there are currently no approved drugs targeting and silencing covalently closed circular DNA (cccDNA), achieving a “functional cure” remains difficult. This study aims to comprehensively compare the effects of IFNα, small-interfering RNA targeting hepatitis B virus (HBV), and their combination on the activity, accessibility, and epigenetic modifications of cccDNA minichromosomes in cell models. A more durable and stable inhibition of HBV RNAs and antigens expression by IFNα and HBx-targeting siRNA (siHBx) synergy was observed, associated with augmented epigenetic repression of the cccDNA minichromosome. Besides, in an extracellular humanized IFNAR mouse model harboring recombinant cccDNA with an intact response to human IFNα, the synergistic effect of clinically used pegylated IFNα2 and in-house-developed GalNac-siHBx was further clarified.
Identification of NECTIN1 as a novel restriction factor for flavivirus infection
Authors: Qi Shuhui , Sun Chao , Wang Jing , Wo Lijing , Li Yongfeng , Wang Chaonan , Zhang Ying , Bian Haiqiao , Guo Yongqi , Gao Ming , Wang Menghang , Tang Yandong , Zhu Yuanmao , Xue Fei , Pang Quanhai , Jiang Zhigang , Yin Xin 
Published: November 2024

ABSTRACT

Nectin cell adhesion molecule 1 (NECTIN1) is a cell adhesion molecule that belongs to the immunoglobulin superfamily. It has been considered the most ubiquitous receptor for herpesviruses. However, in the context of flavivirus infection, its role was previously unknown. In this study, we described an arrayed siRNA screen mainly targeting Ig-like proteins that showed NECTIN1-restricted bovine viral diarrhea virus (BVDV) infection. We demonstrated that the depletion of NECTIN1 could significantly enhance the infection of both biotypes and multiple genotypes of BVDV, including BVDV-1a, -1b, -1c, -1p, -1m, -1v, and -2a. Notably, the IgV of NECTIN1 has emerged as the key domain restricting BVDV infection. Moreover, NECTIN1 inhibited BVDV attachment without exerting a significant influence on BVDV translation or transcription. Furthermore, we demonstrated that both NECTIN1 and CD46 could bind to BVDV E2, while the binding affinity of NECTIN1 for BVDV E2 was greater than that for CD46. We further identified that the BVDV E2 domain DD was a key domain of BVDV interacting with NECTIN1. In addition, we showed that NECTIN1 inhibited infections by classical swine fever virus (CSFV), Japanese encephalitis virus (JEV), and Zika virus (ZIKV), which belong to the
Flaviviridae
family, but had limited effects on bluetongue virus (BTV), vesicular stomatitis virus (VSV), Akabane virus (AKAV), and Sindbis virus (SINV). Overall, our study has important implications for understanding the entry of BVDV and revealed a novel role for NECTIN1 as a restriction factor that inhibits flavivirus infection.

IMPORTANCE

NECTIN1, also known as CD111 or PVRL1, has been recognized as the primary receptor for several alpha herpesviruses, including herpes simplex virus (HSV), pseudorabies virus (PRV), and bovine herpesvirus 1 (BHV-1). However, our study revealed a novel role for NECTIN1 in the virus life cycle by influencing BVDV infection. Contrary to its role as a receptor for alpha herpesviruses, NECTIN1 acts as a restriction factor for BVDV by inhibiting viral attachment via competition with CD46 for binding to the domain DD of BVDV E2. We further revealed that the replication of members of the
Flaviviridae
family was inhibited by NECTIN1, while the replication of other RNA viruses did not significantly differ. Our results demonstrate that NECTIN1 is a novel factor restricting
Flaviviridae
family virus replication and highlight the complexity of virus-host interactions and the multifaceted nature of host factors involved in viral infection.
New insights on an old friend: AroA linked to iron-dependent outer membrane stability
Authors: Chin Priscilla , Anderson Christopher J. 
Published: November 2024

ABSTRACT

Salmonella
is a common causative agent of infectious intestinal and systemic disease and has been extensively studied for several decades. Yet, much of
Salmonella
pathogenicity remains a mystery due in part to the highly complex virulence and adaptation strategies at the pathogen’s disposal. One of the more influential tools within the field, an attenuated
aroA-
deficient
Salmonella
strain, has been used for many years to probe the host immune response that would otherwise be impossible with a fully virulent strain. Now, new work by Rooke et al. (J. L. Rooke, E. C. A. Goodall, K. Pullela, R. Da Costa, et al., mBio 15:e03319-23, 2024,
https://doi.org/10.1128/mbio.03319-23
) utilizes in-depth transposon-directed insertion-site sequencing to elucidate the contribution of genes to
Salmonella
fitness within isogenic wild-type and
aroA
-deficient strains. Specifically, Rooke et al. demonstrate that the deletion of the
aroA
gene leads to iron-dependent membrane instability, raising several exciting new ideas surrounding
Salmonella
biology and therapeutic strategies.