bluuebunny/crossref_metadata_2025 huggingface dataset:
Identification of a novel DNA repair inhibitor using an in silico driven approach shows effective combinatorial activity with genotoxic agents against multidrug‐resistant Escherichia coli
Authors: Bernacchia Lorenzo , Paris Antoine , Gupta Arya , Charman Robert J. , McGreig Jake , Wass Mark N. , Kad Neil M.
Published: March 2024

Increasing antimicrobial drug resistance represents a global existential threat. Infection is a particular problem in immunocompromised individuals, such as patients undergoing cancer chemotherapy, due to the targeting of rapidly dividing cells by antineoplastic agents. We recently developed a strategy that targets bacterial nucleotide excision DNA repair (NER) to identify compounds that act as antimicrobial sensitizers specific for patients undergoing cancer chemotherapy. Building on this, we performed a virtual drug screening of a ~120,000 compound library against the key NER protein UvrA. From this, numerous target compounds were identified and of those a candidate compound, Bemcentinib (R428), showed a strong affinity toward UvrA. This NER protein possesses four ATPase sites in its dimeric state, and we found that Bemcentinib could inhibit UvrA's ATPase activity by ~90% and also impair its ability to bind DNA. As a result, Bemcentinib strongly diminishes NER's ability to repair DNA in vitro. To provide a measure of in vivo activity we discovered that the growth of Escherichia coli MG1655 was significantly inhibited when Bemcentinib was combined with the DNA damaging agent 4‐NQO, which is analogous to UV. Using the clinically relevant DNA‐damaging antineoplastic cisplatin in combination with Bemcentinib against the urological sepsis‐causing E. coli strain EC958 caused complete growth inhibition. This study offers a novel approach for the potential development of new compounds for use as adjuvants in antineoplastic therapy.
MA‐PEP: A novel anticancer peptide prediction framework with multimodal feature fusion based on attention mechanism
Authors: Liang Xiao , Zhao Haochen , Wang Jianxin
Published: March 2024

AntiCancer Peptides (ACPs) have emerged as promising therapeutic agents for cancer treatment. The time‐consuming and costly nature of wet‐lab discriminatory methods has spurred the development of various machine learning and deep learning‐based ACP classification methods. Nonetheless, current methods encountered challenges in efficiently integrating features from various peptide modalities, thereby limiting a more comprehensive understanding of ACPs and further restricting the improvement of prediction model performance. In this study, we introduce a novel ACP prediction method, MA‐PEP, which leverages multiple attention mechanisms for feature enhancement and fusion to improve ACP prediction. By integrating the enhanced molecular‐level chemical features and sequence information of peptides, MA‐PEP demonstrates superior prediction performance across several benchmark datasets, highlighting its efficacy in ACP prediction. Moreover, the visual analysis and case studies further demonstrate MA‐PEP's reliable feature extraction capability and its promise in the realm of ACP exploration. The code and datasets for MA‐PEP are available at https://github.com/liangxiaodata/MA-PEP.
Role of UDP‐N‐acetylmuramic acid in the regulation of MurA activity revealed by molecular dynamics simulations
Authors: de Oliveira Maycon Vinicius Damasceno , da Costa Kauê S. , Silva José Rogério A. , Lameira Jerônimo , Lima Anderson H.
Published: March 2024

The peptidoglycan biosynthesis pathway plays a vital role in bacterial cells, and facilitates peptidoglycan layer formation, a fundamental structural component of the bacterial cell wall. The enzymes in this pathway are candidates for antibiotic development, as most do not have mammalian homologues. The UDP‐N‐acetylglucosamine (UNAG) enolpyruvyl transferase enzyme (MurA) in the peptidoglycan pathway cytoplasmic step is responsible for the phosphoenolpyruvate (PEP)–UNAG catalytic reaction, forming UNAG enolpyruvate and inorganic phosphate. Reportedly, UDP‐N‐acetylmuramic acid (UNAM) binds tightly to MurA forming a dormant UNAM–PEP–MurA complex and acting as a MurA feedback inhibitor. MurA inhibitors are complex, owing to competitive binding interactions with PEP, UNAM, and UNAG at the MurA active site. We used computational methods to explore UNAM and UNAG binding. UNAM showed stronger hydrogen‐bond interactions with the Arg120 and Arg91 residues, which help to stabilize the closed conformation of MurA, than UNAG. Binding free energy calculations using end‐point computational methods showed that UNAM has a higher binding affinity than UNAG, when PEP is attached to Cys115. The unbinding process, simulated using τ–random acceleration molecular dynamics, showed that UNAM has a longer relative residence time than UNAG, which is related to several complex dissociation pathways, each with multiple intermediate metastable states. This prevents the loop from opening and exposing the Arg120 residue to accommodate UNAG and potential new ligands. Moreover, we demonstrate the importance of Cys115‐linked PEP in closed‐state loop stabilization. We provide a basis for evaluating novel UNAM analogues as potential MurA inhibitors.

Public significance

MurA is a critical enzyme involved in bacterial cell wall biosynthesis and is involved in antibiotic resistance development. UNAM can remain in the target protein's active site for an extended time compared to its natural substrate, UNAG. The prolonged interaction of this highly stable complex known as the ‘dormant complex’ comprises UNAM–PEP–MurA and offers insights into antibiotic development, providing potential options against drug‐resistant bacteria and advancing our understanding of microbial biology.
Design of a symmetry‐broken tetrahedral protein cage by a method of internal steric occlusion
Authors: Gladkov Nika , Scott Elena A. , Meador Kyle , Lee Eric J. , Laganowsky Arthur D. , Yeates Todd O. , Castells‐Graells Roger
Published: March 2024

Methods in protein design have made it possible to create large and complex, self‐assembling protein cages with diverse applications. These have largely been based on highly symmetric forms exemplified by the Platonic solids. Prospective applications of protein cages would be expanded by strategies for breaking the designed symmetry, for example, so that only one or a few (instead of many) copies of an exterior domain or motif might be displayed on their surfaces. Here we demonstrate a straightforward design approach for creating symmetry‐broken protein cages able to display singular copies of outward‐facing domains. We modify the subunit of an otherwise symmetric protein cage through fusion to a small inward‐facing domain, only one copy of which can be accommodated in the cage interior. Using biochemical methods and native mass spectrometry, we show that co‐expression of the original subunit and the modified subunit, which is further fused to an outward‐facing anti‐GFP DARPin domain, leads to self‐assembly of a protein cage presenting just one copy of the DARPin protein on its exterior. This strategy of designed occlusion provides a facile route for creating new types of protein cages with unique properties.
Viral envelope proteins fused to multiple distinct fluorescent reporters to probe receptor binding
Authors: Tomris Ilhan , van der Woude Roosmarijn , de Paiva Froes Rocha Rebeca , Torrents de la Peña Alba , Ward Andrew B. , de Vries Robert P.
Published: March 2024

Enveloped viruses carry one or multiple proteins with receptor‐binding functionalities. Functional receptors can be glycans, proteinaceous, or both; therefore, recombinant protein approaches are instrumental in attaining new insights regarding viral envelope protein receptor‐binding properties. Visualizing and measuring receptor binding typically entails antibody detection or direct labeling, whereas direct fluorescent fusions are attractive tools in molecular biology. Here, we report a suite of distinct fluorescent fusions, both N‐ and C‐terminal, for influenza A virus hemagglutinins and SARS‐CoV‐2 spike RBD. The proteins contained three or six fluorescent protein barrels and were applied directly to cells to assess receptor binding properties.
Output feedback H∞$$ {H}_{\infty } $$ control of linear systems with infinite distributed input delays
Authors: Zhou Qianghui , Liu Lu , Feng Gang
Published: March 2024

This article investigates the output feedback control problem of linear systems with infinite distributed input delays. An observer‐based output feedback (OBOF) controller is proposed via the predictor feedback approach, and a sufficient condition for the existence of the OBOF controller is given in terms of a set of linear matrix inequalities. It is shown that the resulting closed‐loop system is globally exponentially stable with a prescribed performance. The obtained results include some results on the same problem for linear systems with bounded distributed input delays as special cases. Two numerical examples are finally presented to illustrate the effectiveness of the proposed controller.
How optimal distinctiveness shapes platform complementors' adoption of boundary resources
Authors: Kang Hye Young , Grodal Stine
Published: March 2024

Research Summary

What drives platform complementors to adopt boundary resources? We address this question by drawing on optimal distinctiveness. We suggest that competitors' adoption of a platform boundary resource on the one hand increases the legitimacy of the resource, but on the other hand decreases a focal complementor's ability to differentiate by adopting it. We therefore hypothesize an inverted U‐shaped relationship between prior and future adoption of a platform boundary resource. In a dataset of health and fitness apps on the Apple iOS platform and through three online experiments, we find support for this relationship and for the existence of two important complementor‐specific contingencies that moderate this relationship. This paper expands our understanding of how optimal distinctiveness drives the dynamics of platform‐mediated markets.

Managerial Summary

In platform markets, complementors face a dilemma: which of the available platform boundary resources should they adopt? We show that a focal complementor's decision to adopt a boundary resource is the result of a strategic trade‐off between the desire to be both legitimate and to be differentiated from competitors. The result is that initially many complementors adopt the boundary resource and it becomes viewed as increasingly attractive by other platform complementors. However, over time as many complementors have adopted the boundary resource, the remaining complementors begin to shy away from adopting it because they worry that doing so might hurt their ability to be differentiated on the platform. These results are shaped by the complementors' performance and how dedicated they are to the platform.
The Future of ChatGPT in Medicinal Chemistry: Harnessing AI for Accelerated Drug Discovery
Authors: Pradhan Tathagata , Gupta Ojasvi , Chawla Gita
Published: March 2024

Artificial Intelligence (AI) has emerged as a transformative tool in various fields, including medicinal chemistry and drug discovery. The integration of artificial intelligence (AI) and machine learning (ML) technologies in medicinal chemistry has revolutionized drug discovery processes. Among AI models, ChatGPT (Generative Pre‐trained Transformer) has shown remarkable capabilities in natural language understanding and generation. This review article delves into the potential applications and prospects of ChatGPT in the domain of medicinal chemistry, focusing on its contributions to drug discovery, compound design, virtual screening, target identification, and optimization of pharmacokinetic properties. ChatGPT′s ability to generate contextually relevant text makes it a valuable tool for data mining and analysis of vast chemical and biological information repositories. In this review article, the authors have discussed the challenges and ethical considerations associated with the implementation of ChatGPT 3.5 in medicinal chemistry research. Authors also extend their acknowledgment to ChatGPT (version 3.5) for its contribution in furnishing responses to the prompt, thereby shedding light on the applications of ChatGPT in the field of medicinal chemistry. The authors have analyzed the responses of ChatGPT.
The Stabilizing Effect of Chitosan‐Modified Biochar (β‐CD/C‐BC) on Agricultural Soil Contaminated by the Cd‐Pyr Complex
Authors: Lin Ying , Li Haibo , Li Xinjing , Wu Yingying
Published: March 2024

The composite pollution of heavy metals (HMs) and polycyclic aromatic hydrocarbons (PAHs) in agricultural soil is increasingly severe. HMs can undergo surface adsorption, complexation, or chemical reactions to transform from bioavailable species to residual species, achieving chemical morphological stability. However, these processes have no effect on PAHs. Biochar (BC), due to its inherent characteristics, can significantly enhance the stability of PAHs and is recommended as a potential co‐stabilizing material for both heavy metals and PAHs. In this study, rice husk biochar modified with β‐cyclodextrin and chitosan (β‐CD/C‐BC) was utilized to stabilize agricultural soil contaminated by Cd and Pyrene (Pyr). One‐way tests were conducted on the dosage and curing time of biochar after a complete cycle of treatment. The results demonstrated that the optimal effect was achieved when the dosage of β‐CD/C‐BC was 7.5 % or the curing time was 21 days. The removal efficiencies for Cd and Pyr were found to be 84.62 %, 64.22 % or 85.90 %, 65.78 %, respectively. Additionally, BCR testing revealed that β‐CD/C‐BC could convert HMs in soil into a residual state (from 32 % to 82 %) with the highest stabilization rate, thereby reducing their migration ability and ecological risk.
Influence of shear strengthening of reinforced normal concrete beams incorporating sustainable materials
Authors: Hamoda Ahmed , Emara Mohamed , Abadel Aref A. , Sennah K.
Published: March 2024

This research studies shear strengthening performance for Normal Concrete (NC) beams employing Engineered Cementitious Composite (ECC) reinforced with Galvanized Welded Wire Mesh (GWWM) in conjunction with/without a prestressing system. Six full‐scale Reinforced Concrete (RC) beams were experimented under static monotonic loading at critical shear span zone up to collapse. The investigated factors were: the type and technique of strengthening, materials used for strengthening, and size and configuration of shear reinforcement. Two techniques were introduced: ECC layer reinforced with GWWM and pretensioned steel bars recovered by ECC with one GWWM. GWWM with and without pretensioned steel bars were delivered as shear reinforcement for strengthening. Vertical and inclined steel bars were the two configurations selected for the prestressing technique for suppressing shear stress. The study was discussed through the experimented beams' crack load and pattern, collapse mode, elastic stiffness, absorbed energy, initial cracking load, and ultimate load, along with the corresponding defection. Experimental results showed that both exploited techniques could govern crack patterns, enhance the failure mode, and upgrade ultimate loading capacity up to 52%. Finite element models were built up, simulating those strengthened with an ECC covering layer augmented with GWWM extracting a model with an error of about 3%.
Modified plastic damage model for steel fiber reinforced concrete
Authors: Tran Tung T. , Pham Thong M. , Tran Duong T. , Ha Ngoc San , Hao Hong
Published: March 2024

Steel fiber reinforced concrete (SFRC) structures have been widely adopted and attracted great research attention due to their excellent performance in resisting tension and flexure bending. However, the existing analytical and numerical analyses of SFRC structures rely mainly on the experimental data of material tests, thereby being suitable for a case‐by‐case basis. This is due to the lack of a general and reliable constitutive material model for SFRC, which analytically considers the fiber‐dependent parameters such as fiber geometry, fiber stiffness, and interface properties of fibers and concrete matrix. This study presents an approach to modify the concrete plastic damage model to represent the SFRC material constitutive relations for simulating the structural behavior of SFRC. In this approach, the general procedure to integrate the bridging effect of fibers through the pull‐out mechanism into the constitutive relation of SFRC was proposed. The comparison between the numerical and experimental results was conducted to verify the reliability of the proposed model. The results demonstrated the proposed model could well represent the material performance of SFRC and the numerical simulations could capture reasonably the effect of the volume fraction, geometry, and properties of fibers on the structural response of SFRC.
Dynamic compressive behaviors of polyethylene terephthalate fiber reinforced recycled aggregate concrete
Authors: Yan Zhi‐Wei , Bai Yu‐Lei , Chen Wensu
Published: March 2024

Polyethylene terephthalate (PET) fibers are green, environmentally friendly materials. They mainly come from recycled plastic bottles and other products. The addition of PET fibers to recycled aggregate concrete (RAC) has the potential to reduce concrete damage and increase specimen toughness. In this study, the influences of recycled coarse aggregate (RCA) replacement ratio and fiber volume ratio on the impact response of PET fiber reinforced RAC at various strain rates were experimentally investigated. It was found that the compressive strength, critical strain, and toughness grew with the increasing strain rate, followed by the aggravation of the concrete damage. Owing to the strain rate effect, the failure mode of concrete specimen at a high strain rate was different from that under a quasi‐static loading. This led to the reduction of differences in the dynamic compressive strength between the natural and recycled aggregate concrete at a high strain rate. Although the replacement of natural coarse aggregates with RCAs resulted in the decrease in the dynamic compressive strength, it increased the critical strain of the specimen. To reduce the brittleness of concrete materials, flexible fibers, PET fibers were added into the concrete matrix. It was found that the addition of PET fibers increased the critical strain and significantly reduced concrete damage. The empirical equations were proposed to describe the rate‐dependent dynamic compressive strength, critical strain, and toughness based on experimental data.
Effect of fiber type, size, and utilization rate on mechanical and thermal properties of lightweight concrete facade panels
Authors: Beytekin Hatice Elif , Kaya Yahya , Mardani Ali , Sezer Filiz Şenkal
Published: March 2024

It was understood that various studies were carried out on the strength, permeability, durability, increasing the thermal performance of lightweight concrete facade panels, and sustainable and energy‐efficient concepts. It was observed that fiber was added to the mixture to improve the properties in question. However, it was determined that contradictory results were obtained due to the large number of active parameters and whether the fiber was distributed homogeneously in the matrix. In this study, the effects of fiber type, length and usage rate on the strength, energy absorption capacity, elasticity modulus, water absorption, and thermal performance of lightweight concrete mixtures were investigated. For this purpose, three different types of fibers of different lengths: polypropylene (3, 6, and 12 mm), glass (13 and 25 mm) and polyamide (6 and 12 mm) were used at 0%, 0.25%, 0.50%, and 0.75% of the total volume. It was determined that the mixture containing 0.25% polypropylene fiber with a length of 3 mm exhibited the best performance in terms of both mechanical and thermal properties. In terms of these features, it was understood that the mixtures with 12 mm polypropylene with a usage rate of 0.75% and 6 mm polyamide fibers with a usage rate of 0.50% had the weakest performance.
International business entry modes and consumer ethnocentrism: A multi country perspective
Authors: Bose Tarun Kanti , Chew Tze Cheng , Purohit Sonal , Moser Roger
Published: March 2024

This study aims to assess the impact of changes in international business modes on consumer ethnocentrism. The study utilizes a quantitative research approach and is theoretically grounded in the resource‐based view. Data was collected from Bangladesh, China, India, and Malaysia using the consumer ethnocentrism tendencies scale (CETSCALE), and analyzed using quantitative methods. The results indicate that changes in international entry modes have an impact on the degree of consumer ethnocentrism. Across all countries studied, the highest level of consumer ethnocentrism was found for imported products, and this degree and intensity decreased when the entry modes changed from importing to joint venturing and FDI. This study contributes to the literature on both international business and consumer behavior by integrating the two fields, resulting in a robust theoretical contribution. The findings also suggest that the appropriate IB mode can act as a resource.
Seroprevalence and renal carriage of pathogenic Leptospira in livestock in Cotonou, Benin
Authors: Her Rebecca , Crespin Laurent , Etougbétché Jonas , Groud Karine , Gnolonfoun Mathias , Chapron Audrey , Evenamia Camille , Houéménou Gualbert , Lurier Thibaut , Cappelle Julien , Dobigny Gauthier , Ayral Florence
Published: March 2024

Background

Leptospirosis is a zoonotic disease. It is particularly prevalent in tropical countries and has major consequences for human and animal health. In Benin, the disease's epidemiology remains poorly understood, especially in livestock, for which data are lacking.

Objectives

To characterise Leptospira seroprevalence and locally circulating serogroups in livestock from Cotonou and to estimate the prevalence of Leptospira renal carriage in cattle.

Methods

We conducted a cross‐sectional study in February 2020 during which livestock were sampled at an abattoir and in an impoverished city district. We analysed blood samples from 279 livestock animals (i.e. cattle, sheep, goats and pigs) using the microscopic agglutination test. Additionally, samples of renal tissue from 100 cattle underwent 16s rRNA (rrs) real‐time PCR analysis.

Results

For the 131 cattle, 85 sheep, and 50 goats tested, seroprevalence was 18% (95% confidence interval [CI] [12%, 26%]), 9% (95% CI [4%, 17%] and 2% (95% CI [0%, 9%]), respectively, and most of the seropositive animals were associated with 1:100 titres. All 13 pigs were seronegative. Leptospira DNA was found in the renal tissue of 10% (95% CI [5%, 18%]) of the cattle tested (n = 100). Leptospira borgpetersenii was the main species present (n = 7), but Leptospira interrogans (n = 2) and Leptospira kirschneri (n = 1) were also detected. Various serogroups (Canicola, Grippotyphosa, Sejroe, Icterohaemorrhagiae, Pomona, Pyrogenes, Australis and Autumnalis) were detected using microscopic agglutination test without a clear predominance of any of them.

Conclusions

These results suggest that abattoir workers and people living in close contact with livestock in poor urban areas are exposed to the risk of Leptospira infection.
Ernst Denert Software Engineering Award 2022
Authors: Bodden Eric , Felderer Michael , Hasselbring Wilhelm , Herber Paula , Koziolek Heiko , Lilienthal Carola , Matthes Florian , Prechelt Lutz , Rumpe Bernhard , Schaefer Ina
Published: March 2024

The Ernst Denert Award is already existing since 1992, which does not only honor the award winners but also the software engineering field in total. Software engineering is a vivid and intensively extending field that regularly spawns new subfields such as automotive software engineering, research software engineering, or quantum software engineering, covering specific needs but also generalizing solutions, methods, and techniques when they become applicable. This is the introductory chapter of the book on the Ernst Denert Software Engineering Award 2022. It provides an overview of the five nominated PhD theses.
The origin of Calabi-Yau crystals in BPS states counting
Authors: Bao Jiakang , Seong Rak-Kyeong , Yamazaki Masahito
Published: March 2024

Abstract

We study the counting problem of BPS D-branes wrapping holomorphic cycles of a general toric Calabi-Yau manifold. We evaluate the Jeffrey-Kirwan residues for the flavoured Witten index for the supersymmetric quiver quantum mechanics on the worldvolume of the D-branes, and find that BPS degeneracies are described by a statistical mechanical model of crystal melting. For Calabi-Yau threefolds, we reproduce the crystal melting models long known in the literature. For Calabi-Yau fourfolds, however, we find that the crystal does not contain the full information for the BPS degeneracy and we need to explicitly evaluate non-trivial weights assigned to the crystal configurations. Our discussions treat Calabi-Yau threefolds and fourfolds on equal footing, and include discussions on elliptic and rational generalizations of the BPS states counting, connections to the mathematical definition of generalized Donaldson-Thomas invariants, examples of wall crossings, and of trialities in quiver gauge theories.
Deep learning bulk spacetime from boundary optical conductivity
Authors: Ahn Byoungjoon , Jeong Hyun-Sik , Kim Keun-Young , Yun Kwan
Published: March 2024

Abstract

We employ a deep learning method to deduce the bulk spacetime from boundary optical conductivity. We apply the neural ordinary differential equation technique, tailored for continuous functions such as the metric, to the typical class of holographic condensed matter models featuring broken translations: linear-axion models. We successfully extract the bulk metric from the boundary holographic optical conductivity. Furthermore, as an example for real material, we use experimental optical conductivity of UPd2Al3, a representative of heavy fermion metals in strongly correlated electron systems, and construct the corresponding bulk metric. To our knowledge, our work is the first illustration of deep learning bulk spacetime from boundary holographic or experimental conductivity data.
Polarized fragmenting jet functions in inclusive and exclusive jet production
Authors: Kang Zhong-Bo , Xing Hongxi , Zhao Fanyi , Zhou Yiyu
Published: March 2024

Abstract

In this work, we present a complete theoretical framework for analyzing the distribution of polarized hadrons within jets, with and without measuring the transverse momentum relative to the standard jet axis. Using soft-collinear effective theory (SCET), we derive the factorization and provide the theoretical calculation of both semi-inclusive and exclusive fragmenting jet functions (FJFs) under longitudinal and transverse polarization. With the polarized FJFs, one gains access to a variety of new observables that can be used for extracting both collinear and transverse momentum dependent parton distribution functions (PDFs) and fragmentation functions (FFs). As examples, we provide numerical results for the spin asymmetry $$ {A}_{TU,T}^{\cos \left({\phi}_S-{\hat{\phi}}_{S_h}\right)} $$

A

TU
,
T

cos

ϕ
S

−

ϕ
̂

S
h

from polarized semi-inclusive hadron-in-jet production in polarized pp collisions at RHIC kinematics, where a transversely polarized quark would lead to the transverse spin of the final-state hadron inside the jet and is thus sensitive to the transversity fragmentation functions. Similarly, another spin asymmetry, $$ {A}_{TU,L}^{\cos \left({\phi}_q-{\phi}_S\right)} $$

A

TU
,
L

cos

ϕ
q

−

ϕ
S

from polarized exclusive hadron-in-jet production in polarized ep collisions at EIC kinematics would allow us to access the helicity fragmentation functions. These observables demonstrate promising potential in investigating transverse momentum dependent PDFs and FFs and are worthwhile for further measurements.
Amplitude basis for conformal correlators
Authors: Lee Hayden , Wang Xinkang
Published: March 2024

Abstract

We present a classification of conformally-invariant three-point tensor structures in d dimensions that parallels the classification of three-particle scattering amplitudes in d + 1 dimensions. Using a set of canonically-normalized weight-shifting operators, we construct a basis of three-point structures involving conserved currents or stress tensors and non-conserved spinning operators, directly from their amplitude counterparts. As an application, we also examine the conformal block expansion of the four-point functions of external currents and stress tensors in this amplitude basis. Our results can be useful for conformal bootstrap applications involving spinning correlators as well as Witten diagram computations in anti-de Sitter space.
Ideal Structure of Nica-Toeplitz Algebras
Authors: Bilich Boris
Published: March 2024

We study the gauge-invariant ideal structure of the Nica-Toeplitz algebra $$\mathcal {N}\mathcal {T}(X)$$

N
T
(
X
)

of a product system (A, X) over $$\mathbb {N}^n$$

N

n

. We obtain a clear description of X-invariant ideals in A, that is, restrictions of gauge-invariant ideals in $$\mathcal {N\hspace{-1.111pt}T}(X)$$

N

T

(
X
)

to A. The main result is a classification of gauge-invariant ideals in $$\mathcal {N\hspace{-1.111pt}T}(X)$$

N

T

(
X
)

for a proper product system in terms of families of ideals in A. We also apply our results to higher-rank graphs.
Traumatic rhabdomyolysis: rare but morbid, potentially lethal, and inconsistently monitored
Authors: Giles Thomas , King Kate , Meakes Simone , Weaver Natasha , Balogh Zsolt J.
Published: March 2024

Purpose

Although traumatic rhabdomyolysis (TR) is shown to be associated with acute kidney injury (AKI), there are no large prospective epidemiological studies, interventional trials, official guidelines outlining the appropriate investigation, monitoring, and treatment on this poorly understood condition. We aimed to establish the contemporary epidemiology and describe current practices for TR to power future higher quality studies. We hypothesised that investigation and monitoring occur in an ad hoc fashion.

Material and methods

We conducted a 1-year retrospective cohort study of all patients > 16 years of age, with an ISS > 12 and, admitted to a level 1 trauma centre. Demographics, initial vital signs, admission laboratory values, and daily creatinine kinase (CK) values were collected. The primary outcome was TR (defined by CK > 5000 IU), secondary outcomes included AKI (KDIGO criteria), mortality, multiple organ failure, length of stay, and need for renal replacement therapy (RRT).

Results

586 patients met inclusion criteria and 15 patients (2.56%) developed TR. CK testing occurred in 78 (13.1%) patients with 29 (37.7%) of these having values followed until downtrending. AKI occurred in 63 (10.8%) patients within the entire study population. Among those with TR, nine (60%) patients developed AKI. Patients with TR had higher ISS (median 29 vs 18) and mortality (26.7% vs 8.9%).

Discussion

Whilst TR appears rare without liberal screening, it is strongly associated with AKI. Given the poor outcomes, standardised monitoring, and liberal testing of CK could be justified in trauma patients with higher injury severity. This epidemiological data can help to define study populations and power future multicentre prospective studies on this infrequent yet morbid condition.
Fighting pathogenic yeasts with plant defensins and anti-fungal proteins from fungi
Authors: Manzanares Paloma , Giner-Llorca Moisés , Marcos Jose F. , Garrigues Sandra
Published: March 2024

Fungal infections represent a significant health risk worldwide. Opportunistic infections caused by yeasts, particularly by Candida spp. and their virulent emerging isolates, have become a major threat to humans, with an increase in fatal cases of infections attributed to the lack of effective anti-yeast therapies and the emergence of fungal resistance to the currently applied drugs. In this regard, the need for novel anti-fungal agents with modes of action different from those currently available is undeniable. Anti-microbial peptides (AMPs) are promising candidates for the development of novel anti-fungal biomolecules to be applied in clinic. A class of AMPs that is of particular interest is the small cysteine-rich proteins (CRPs). Among CRPs, plant defensins and anti-fungal proteins (AFPs) of fungal origin constitute two of the largest and most promising groups of CRPs showing anti-fungal properties, including activity against multi-resistant pathogenic yeasts. In this review, we update and compare the sequence, structure, and properties of plant defensins and AFPs with anti-yeast activity, along with their in vitro and in vivo potency. We focus on the current knowledge about their mechanism of action that may lead the way to new anti-fungals, as well as on the developments for their effective biotechnological production.

Key points

• Plant defensins and fungal AFPs are alternative anti-yeast agents

• Their multi-faceted mode of action makes occurrence of resistance rather improbable

• Safe and cost-effective biofactories remain crucial for clinical application
Macrophage mannose receptor CD206 targeting of fluoride-18 labeled mannosylated dextran: A validation study in mice
Authors: Andriana Putri , Fair-Mäkelä Ruth , Liljenbäck Heidi , Kärnä Salli , Iqbal Imran , Makrypidi Konstantina , Rajander Johan , Pirmettis Ioannis , Li Xiang-Guo , Jalkanen Sirpa , Saraste Antti , Salmi Marko , Roivainen Anne
Published: March 2024

Purpose

Aluminum fluoride-18-labeled 1,4,7-triazacyclononane-1,4,7-triacetic acid-conjugated mannosylated dextran derivative (Al[18F]F-NOTA-D10CM) is a new tracer for PET imaging. We report here on in vitro and in vivo validation of the tracer’s ability to target the macrophage mannose receptor CD206.

Methods

First, the uptake of intravenously (i.v.) administered Al[18F]F-NOTA-D10CM was compared between wild-type (WT) and CD206−/− knockout (KO) mice. C57BL/6N mice were injected with complete Freund’s adjuvant (CFA) in the left hind leg and the uptake of Al[18F]F-NOTA-D10CM after i.v. or intradermal (i.d.) injection was studied at 5 and 14 days after CFA induction of inflammation. Healthy C57BL/6N mice were studied as controls. Mice underwent PET/CT on consecutive days with [18F]FDG, i.v. Al[18F]F-NOTA-D10CM, and i.d. Al[18F]F-NOTA-D10CM. After the last imaging, Al[18F]F-NOTA-D10CM was i.v. injected for an ex vivo biodistribution study and autoradiography of inflamed tissues. Blood plasma samples were analyzed using high-performance liquid chromatography. To evaluate the specificity of Al[18F]F-NOTA-D10CM binding, an in vitro competitive displacement study was performed on inflamed tissue sections using autoradiography. CD206 expression was assessed by immunohistochemical staining.

Results

Compared with WT mice, the uptake of Al[18F]F-NOTA-D10CM was significantly lower in several CD206−/− KO mice tissues, including liver (SUV 8.21 ± 2.51 vs. 1.06 ± 0.16, P < 0.001) and bone marrow (SUV 1.63 ± 0.37 vs. 0.22 ± 0.05, P < 0.0001). The uptake of i.v. injected Al[18F]F-NOTA-D10CM was significantly higher in inflamed ankle joint (SUV 0.48 ± 0.13 vs. 0.18 ± 0.05, P < 0.0001) and inflamed foot pad skin (SUV 0.41 ± 0.10 vs. 0.04 ± 0.01, P < 0.0001) than in the corresponding tissues in healthy mice. The i.d.-injected Al[18F]F-NOTA-D10CM revealed differences between CFA-induced lymph node activation and lymph nodes in healthy mice. Ex vivo γ-counting, autoradiography, and immunohistochemistry supported the results, and a decrease of ~ 80% in the binding of Al[18F]F-NOTA-D10CM in the displacement study with excess NOTA-D10CM confirmed that tracer binding was specific. At 60 min after i.v. injection, an average 96.70% of plasma radioactivity was derived from intact Al[18F]F-NOTA-D10CM, indicating good in vivo stability. The uptake of Al[18F]F-NOTA-D10CM into inflamed tissues was positively associated with the area percentage of CD206-positive staining.

Conclusion

The uptake of mannosylated dextran derivative Al[18F]F-NOTA-D10CM correlated with CD206 expression and the tracer appears promising for inflammation imaging.

Graphical abstract
Vacuum-assisted mini-percutaneous nephrolithotomy is associated with lower rates of infectious complications compared to vacuum-cleaner procedure in patients at high risk for infections: a single-center experience
Authors: Marmiroli Andrea , Nizzardo Marco , Zanetti Stefano Paolo , Lucignani Gianpaolo , Turetti Matteo , Silvani Carlo , Gadda Franco , Longo Fabrizio , De Lorenzis Elisa , Albo Giancarlo , Salonia Andrea , Montanari Emanuele , Boeri Luca
Published: March 2024

Purpose

To evaluate the impact of vacuum-assisted mini-percutaneous nephrolithotomy (vamPCNL) vs. vacuum-cleaner mPCNL (vcmPCNL) on the rate of postoperative infectious complications in a cohort of patients with high risk factors for infections.

Methods

We retrospectively analysed data from 145 patients who underwent mPCNL between 01/2016 and 12/2022. Patient’s demographics, stones characteristics and operative data were collected. vamPCNL and vcmPCNL were performed based on the surgeon’s preference. High-risk patients were defied as having ≥ 2 predisposing factors for infections such as a history of previous urinary tract infections, positive urine culture before surgery, stone diameter ≥ 3 cm, diabetes mellitus and hydronephrosis. Complications were graded according to modified Clavien classification. Descriptive statistics and logistic regression models were used to identify factors associated with postoperative infectious complications.

Results

vamPCNL and vcmPCNL were performed in 94 (64.8%) and 51 (35.2%) cases, respectively. After surgery, infectious complications occurred in 43 (29.7%) participants. Patients who developed infectious complications had larger stone volume (p = 0.02) and higher rate of multiple stones (p = 0.01) than those who did not. Infectious complications occurred more frequently after vcmPCNL than vamPCNL (55.9% vs. 44.1%. p = 0.01) in high-risk patients. Longer operative time (p < 0.01) and length of stay (p < 0.01) were observed in cases with infectious complications. At multivariable logistic regression analysis, longer operative time (OR 1.1, p = 0.02) and vcmPCNL (OR 3.1, p = 0.03) procedures were independently associated with the risk of infectious complications post mPCNL, after accounting for stone volume.

Conclusion

One out of three high-risk patients showed infectious complications after mPCNL. vamPCL and shorter operative time were independent protective factors for infections after surgery.
An interior penalty coupling strategy for isogeometric non-conformal Kirchhoff–Love shell patches
Authors: Guarino Giuliano , Antolin Pablo , Milazzo Alberto , Buffa Annalisa
Published: March 2024

This work focuses on the coupling of trimmed shell patches using Isogeometric Analysis, based on higher continuity splines that seamlessly meet the $$C^1$$

C
1

requirement of Kirchhoff–Love-based discretizations. Weak enforcement of coupling conditions is achieved through the symmetric interior penalty method, where the fluxes are computed using their correct variationally consistent expression that was only recently proposed and is unprecedentedly adopted herein in the context of coupling conditions. The constitutive relationship accounts for generically laminated materials, although the proposed tests are conducted under the assumption of uniform thickness and lamination sequence. Numerical experiments assess the method for an isotropic and a laminated plate, as well as an isotropic hyperbolic paraboloid shell from the new shell obstacle course. The boundary conditions and domain force are chosen to reproduce manufactured analytical solutions, which are taken as reference to compute rigorous convergence curves in the $$L^2$$

L
2

, $$H^1$$

H
1

, and $$H^2$$

H
2

norms, that closely approach optimal ones predicted by theory. Additionally, we conduct a final test on a complex structure comprising five intersecting laminated cylindrical shells, whose geometry is directly imported from a STEP file. The results exhibit excellent agreement with those obtained through commercial software, showcasing the method’s potential for real-world industrial applications.
Mid- and long-term results of open repair for chronic type B aortic dissection in endovascular era
Authors: Takazawa Akitoshi , Asakura Toshihisa , Kinoshita Osamu , Nakajima Hiroyuki , Yoshitake Akihiro
Published: March 2024

Medical management is the standard treatment of chronic type B aortic dissection (CTBAD). However, the roles of open surgical repair (OSR) and thoracic endovascular repair (TEVAR) in patients with CTBAD remain controversial. Thus, this study aimed to assess and compare the mid- and long-term clinical outcomes of OSR via left thoracotomy with that of TEVAR for CTBAD. The data of 85 consecutive patients who underwent surgery for CTBAD from April 2007 to May 2021 were retrospectively reviewed. The patients were divided into two groups: Group G, which included patients who underwent OSR, and Group E, which included patients who underwent TEVAR. Groups G and E comprised 33 and 52 patients, respectively. Preoperative and postoperative computed tomography (CT) studies were retrospectively analyzed for the maximum diameter. The mean duration of the follow-up period was 5.8 years. Operative mortality did not occur. There was no difference in complications, such as stroke (G: 2 vs. E: 0, p = 0.30), paraplegia (G: 1 vs. E: 1, p = 0.66), and respiratory failure (G: 2, vs. E: 0, p = 0.30). The difference in preoperative factors was observed, including the intervals between onset and operation (G; 4.9 years vs. E; 1.9 years, p < 0.01), maximum diameter in preoperative CT (G; 59.0 mm vs. E; 50.5 mm, p < 0.001), and maximum false lumen diameter (G; 35.5 mm vs. E; 29.0 mm, p < 0.01). There was no significant difference in the mid- and long-term survival rates (p = 0.49), aorta-related deaths (p = 0.33), and thoracic re-intervention rates (p = 0.34). Postoperative adverse events occurred in Group E: four cases of retrospective type A aortic dissection, two cases of aorto-bronchial fistula, and one case of aorto-esophagus fistula. Aorta-related death and re-intervention rates crossed over in both groups after seven years postoperatively. Although endovascular repair of CTBAD is less invasive, the rate of freedom from re-intervention was unsatisfactory. Some fatal complications were observed in the endovascular group, and the mid- and long-term outcomes were reversed compared with those in the OSR group. Although OSR is an invasive procedure, it could be performed safely without perioperative complications. OSR has more feasible mid- and long-term outcomes.
Metabolic changes contribute to maladaptive right ventricular hypertrophy in pulmonary hypertension beyond pressure overload: an integrative imaging and omics investigation
Authors: García-Lunar Inés , Jorge Inmaculada , Sáiz Jorge , Solanes Núria , Dantas Ana Paula , Rodríguez-Arias Juan José , Ascaso María , Galán-Arriola Carlos , Jiménez Francisco Rafael , Sandoval Elena , Nuche Jorge , Moran-Garrido Maria , Camafeita Emilio , Rigol Montserrat , Sánchez-Gonzalez Javier , Fuster Valentín , Vázquez Jesús , Barbas Coral , Ibáñez Borja , Pereda Daniel , García-Álvarez Ana
Published: March 2024

Right ventricular (RV) failure remains the strongest determinant of survival in pulmonary hypertension (PH). We aimed to identify relevant mechanisms, beyond pressure overload, associated with maladaptive RV hypertrophy in PH. To separate the effect of pressure overload from other potential mechanisms, we developed in pigs two experimental models of PH (M1, by pulmonary vein banding and M2, by aorto-pulmonary shunting) and compared them with a model of pure pressure overload (M3, pulmonary artery banding) and a sham-operated group. Animals were assessed at 1 and 8 months by right heart catheterization, cardiac magnetic resonance and blood sampling, and myocardial tissue was analyzed. Plasma unbiased proteomic and metabolomic data were compared among groups and integrated by an interaction network analysis. A total of 33 pigs completed follow-up (M1, n = 8; M2, n = 6; M3, n = 10; and M0, n = 9). M1 and M2 animals developed PH and reduced RV systolic function, whereas animals in M3 showed increased RV systolic pressure but maintained normal function. Significant plasma arginine and histidine deficiency and complement system activation were observed in both PH models (M1&M2), with additional alterations to taurine and purine pathways in M2. Changes in lipid metabolism were very remarkable, particularly the elevation of free fatty acids in M2. In the integrative analysis, arginine–histidine–purines deficiency, complement activation, and fatty acid accumulation were significantly associated with maladaptive RV hypertrophy. Our study integrating imaging and omics in large-animal experimental models demonstrates that, beyond pressure overload, metabolic alterations play a relevant role in RV dysfunction in PH.
Matching proposed clinical and MRI criteria of aggressive multiple sclerosis to serum and cerebrospinal fluid markers of neuroaxonal and glial injury
Authors: Schaller-Paule Martin A. , Maiworm Michelle , Schäfer Jan Hendrik , Friedauer Lucie , Hattingen Elke , Wenger Katharina Johanna , Weber Frank , Jakob Jasmin , Steffen Falk , Bittner Stefan , Yalachkov Yavor , Foerch Christian
Published: March 2024

Background

Definitions of aggressive MS employ clinical and MR imaging criteria to identify highly active, rapidly progressing disease courses. However, the degree of overlap between clinical and radiological parameters and biochemical markers of CNS injury is not fully understood. Aim of this cross-sectional study was to match clinical and MR imaging hallmarks of aggressive MS to serum/CSF markers of neuroaxonal and astroglial injury (neurofilament light chain (sNfL, cNfL), and glial fibrillary acidic protein (sGFAP, cGFAP)).

Methods

We recruited 77 patients with relapsing–remitting MS (RRMS) and 22 patients with clinically isolated syndrome. NfL and GFAP levels in serum and CSF were assessed using a single-molecule-array HD-1-analyzer. A general linear model with each biomarker as a dependent variable was computed. Clinical and imaging criteria of aggressive MS, as recently proposed by the ECTRIMS Consensus Group, were modeled as independent variables. Other demographic, clinical or laboratory parameters, were modeled as covariates. Analyses were repeated in a homogenous subgroup, consisting only of newly diagnosed, treatment-naïve RRMS patients presenting with an acute relapse.

Results

After adjusting for covariates and multiplicity of testing, sNfL and cNfL concentrations were strongly associated with the presence of ≥2 gadolinium-enhancing lesions (psNfL = 0.00008; pcNfL = 0.004) as well as the presence of infratentorial lesions on MRI (psNfL = 0.0003; pcNfL < 0.004). No other clinical and imaging criteria of aggressive MS correlated significantly with NfL or GFAP in serum and CSF. In the more homogeneous subgroup, sNfL still was associated with the presence of ≥2 gadolinium-enhancing lesions (psNfL = 0.001), presence of more than 20 T2-lesions (psNfL = 0.049) as well as the presence of infratentorial lesions on MRI (psNfL = 0.034), while cNfL was associated with the presence of ≥2 gadolinium-enhancing lesions (psNfL = 0.011) and presence of more than 20 T2-lesions (psNfL = 0.029).

Conclusions

Among proposed risk factors for an aggressive disease course, MRI findings but not clinical characteristics correlated with sNfL and cNfL as a marker of neuroaxonal injury and should be given appropriate weight considering MS prognosis and therapy. No significant correlation was detected for GFAP alone.