bluuebunny/crossref_metadata_2025 huggingface dataset:
Diallyl disulfide, the bioactive component of Allium species, ameliorates pulmonary fibrosis by mediating the crosstalk of farnesoid X receptor and yes‐associated protein 1 signaling pathway
Authors: Dou Jia‐yi , Cui Zhen‐yu , Xuan Mei‐yan , Gao Chong , Li Zhao‐Xu , Lian Li‐hua , Cui Hao‐zhen , Nan Ji‐xing , Wu Yan‐ling
Published: June 2024

Environmental pollution, virus infection, allergens, and other factors may cause respiratory disease, which could be improved by dietary therapy. Allium species are common daily food seasoning and have high nutritional and medical value. Diallyl disulfide (DADS) is the major volatile oil compound of Allium species. The present study aims to explore the preventive effect and potential mechanism of DADS on pulmonary fibrosis. C57BL/6J mice were intratracheally injected with bleomycin (BLM) to establish pulmonary fibrosis and then administrated with DADS. Primary lung fibroblasts or A549 were stimulated with BLM, followed by DADS, farnesoid X receptor (FXR) agonist (GW4064), yes‐associated protein 1 (YAP1) inhibitor (verteporfin), or silencing of FXR and YAP1. In BLM‐stimulated mice, DADS significantly ameliorated histopathological changes and interleukin‐1β levels in bronchoalveolar lavage fluid. DADS decreased fibrosis markers, HIF‐1α, inflammatory cytokines, and epithelial‐mesenchymal transition in pulmonary mice and activated fibroblasts. DADS significantly enhanced FXR expression and inhibited YAP1 activation, which functions as GW4064 and verteporfin. A deficiency of FXR or YAP1 could result in the increase of these two protein expressions, respectively. DADS ameliorated extracellular matrix deposition, hypoxia, epithelial‐mesenchymal transition, and inflammation in FXR or YAP1 knockdown A549. Taken together, targeting the crosstalk of FXR and YAP1 might be the potential mechanism for DADS against pulmonary fibrosis. DADS can serve as a potential candidate or dietary nutraceutical supplement for the treatment of pulmonary fibrosis.
A high throughput approach for measuring soil slaking index
Authors: Phillips Claire L. , Casanova Joaquin J. , Emmett Bryan D.
Published: June 2024

Soil wet aggregate stability is widely measured for soil health ratings, and two mobile applications have been recently developed that provide simple and fast measurements of wet aggregate stability on three pea‐sized soil aggregates. However, techniques are needed to scale the test to make it practical for studies with large sample numbers. Here, we describe an approach to measure 10‐min slaking index on 20–36 aggregates simultaneously using a multi‐well plate and automated image analysis. We used this approach to measure 160 soil samples (2120 aggregates) from a long‐term tillage and cover crop trial in a corn (Zea mays L.)‐based agroecosystem in central Iowa. We evaluated the statistical power of slaking index, needed replication, sensitivity to cultural practices, and sensitivity to sample collection date to inform future sampling efforts. We found that small numbers of highly unstable aggregates lead to skewed distributions for slaking index. We concluded that at least 20 aggregates per sample were useful to provide confidence in measurement precision, although the experiment had high statistical power with only 10–12 replicates per sample. Slaking index was not sensitive to the initial size of dry aggregates (3‐ to 10‐mm diameter); therefore, pre‐sieving soils was not necessary. Consistent with prior studies, the field trial showed greater aggregate stability under no‐till than chisel plow practice and changing stability over a growing season. This multi‐well method will help researchers measure a useful soil health indicator with greater precision, and more efficiently sample spatial and temporal variation.
Synthesis of β‐Truxinate via [2+2] Cycloaddition of Methyl 4‐Nitrocinnamate: Kinetic Study of its Isomerization with DBU.
Authors: Bahena‐Martínez José Daniel , Flores Roberto , Domínguez‐Mendoza Blanca Eda , Hernández‐Vázquez Luis Gabriel , Juaristi Eusebio , Escalante Jaime
Published: June 2024

This work concerns the isomerization of the product obtained by dimerization of methyl 4‐nitrocinnamate. Subsequent isomerization was performed using 1,8‐diazabicyclo[5.4.0]undec‐7‐ene (DBU) as a base to obtain the corresponding ζ‐ and δ‐truxinate derivatives. The process was monitored by 1H NMR spectroscopy in different deuterated solvents with a wide range of dielectric constants, acetonitrile‐d3, acetone‐d6, tetrahydrofuran‐d8, and benzene‐d6. Each solvent was found to have a distinct influence on the reaction's rate constant k, with acetone‐d6 yielding the highest ratio of ζ‐truxinate derivative. Kinetic analysis of the reaction provided valuable information about the mechanism involved in the isomerization process.
Selective Electrochemical CO2 Reduction tuned by N Configuration on graphitic Shells of Nickel Particles
Authors: Xue Menghan , Li Fazhan , Li Zhen , Sun Yuxia , Guo Yiping , Li Yuehui
Published: June 2024

Despite of high conductivity and reducing ability, transition metal nanoparticles tend to aggregate and unavoidably impact the selectivity during the proton‐coupled reduction process of CO2RR. New strategy to regulate and utilize the electronic property of transition‐metal particles allows for effective tuning of eCO2RR activity. Through simple creation of N‐doped carbon shells surrounding Ni nanoparticles and controlling the amount and arrangement of the N atoms, successful and long‐lasting electrochemical reduction of CO2 was accomplished. The inherent HER activity was almost completely suppressed. It exhibited FECO above 90 % in a 500 mV potential window, with the optimal up to 96.5 % at −0.78 V vs RHE. In flow cell electrolysis, a current density of 289.4 mA/cm2 was achieved with Faradic efficiency of 96.4 % towards CO. The results of control experiments using different catalysts imply that electron transfer between Ni core and shells was significantly influenced by the property of N atoms. High content of graphitic nitrogen is crucial for the catalytic performance.
Unraveling the Oxidation Kinetics Through Electronic Structure Regulation of MnCo2O4.5@Ni3S2 p–n Junction for Urea‐Assisted Electrocatalytic Activity
Authors: Adhikari Sangeeta , Steinmann Stephan N. , Arunachalam Maheswari , Kang Soon Hyung , Kim Do‐Heyoung
Published: June 2024

A promising strategy to boost electrocatalytic performance is via assembly of hetero‐nanostructured electrocatalysts that delivers the essential specific surface area and also active sites by lowering the reaction barrier. However, the challenges associated with the intricate designs and mechanisms remain underexplored. Therefore, the present study constructs a p–n junction in a free‐standing MnCo2O4.5@Ni3S2 on Ni‐Foam. The space‐charge region's electrical characteristics is dramatically altered by the formed p–n junction, which enhances the electron transfer process for urea‐assisted electrocatalytic water splitting (UOR). The optimal MnCo2O4.5@Ni3S2 electrocatalyst results in greater oxygen evolution reactivity (OER) than pure systems, delivering an overpotential of only 240 mV. Remarkably, upon employing as UOR electrode the required potential decreases to 30 mV. The impressive performance of the designed catalyst is attributed to the enhanced electrical conductivity, greater number of electrochemical active sites, and improved redox activity due to the junction interface formed between p‐MnCo2O4.5 and n‐Ni3S2. There are strong indications that the in situ formed extreme‐surface NiOOH, starting from Ni3S2, boosts the electrocatalytic activity, i.e., the electrochemical  surface reconstruction generates the active species. In conclusion, this work presents a high‐performance p–n junction design for broad use, together with a viable and affordable UOR electrocatalyst.
Versatile Patterning of Liquid Metal via Multiphase 3D Printing
Authors: Patil Dhanush , Liu Siying , Ravichandran Dharneedar , Thummalapalli Sri Vaishnavi , Zhu Yuxiang , Tang Tengteng , Golan Yuval , Miquelard‐Garnier Guillaume , Asadi Amir , Li Xiangjia , Chen Xiangfan , Song Kenan
Published: June 2024

This paper presents a scalable and straightforward technique for the immediate patterning of liquid metal/polymer composites via multiphase 3D printing. Capitalizing on the polymer's capacity to confine liquid metal (LM) into diverse patterns. The interplay between distinctive fluidic properties of liquid metal and its self‐passivating oxide layer within an oxidative environment ensures a resilient interface with the polymer matrix. This study introduces an inventive approach for achieving versatile patterns in eutectic gallium indium (EGaIn), a gallium alloy. The efficacy of pattern formation hinges on nozzle's design and internal geometry, which govern multiphase interaction. The interplay between EGaIn and polymer within the nozzle channels, regulated by variables such as traverse speed and material flow pressure, leads to periodic patterns. These patterns, when encapsulated within a dielectric polymer polyvinyl alcohol (PVA), exhibit an augmented inherent capacitance in capacitor assemblies. This discovery not only unveils the potential for cost‐effective and highly sensitive capacitive pressure sensors but also underscores prospective applications of these novel patterns in precise motion detection, including heart rate monitoring, and comprehensive analysis of gait profiles. The amalgamation of advanced materials and intricate patterning techniques presents a transformative prospect in the domains of wearable sensing and comprehensive human motion analysis.
Amino‐Induced CO2 Spillover to Boost the Electrochemical Reduction Activity of CdS for CO Production
Authors: Li Ruina , Xie Fei , Kuang Panyong , Liu Tao , Yu Jiaguo
Published: June 2024

A considerable challenge in CO2 reduction reaction (CO2RR) to produce high‐value‐added chemicals comes from the adsorption and activation of CO2 to form intermediates. Herein, an amino‐induced spillover strategy aimed at significantly enhancing the CO2 adsorption and activation capabilities of CdS supported on N‐doped mesoporous hollow carbon sphere (NH2−CdS/NMHCS) for highly efficient CO2RR is presented. The prepared NH2−CdS/NMHCS exhibits a high CO Faradaic efficiency (FECO) exceeding 90% from −0.8 to −1.1 V versus reversible hydrogen electrode (RHE) with the highest FECO of 95% at −0.9 V versus RHE in H cell. Additional experimental and theoretical investigations demonstrate that the alkaline −NH2 group functions as a potent trapping site, effectively adsorbing the acidic CO2, and subsequently triggering CO2 spillover to CdS. The amino modification‐induced CO2 spillover, combined with electron redistribution between CdS and NMHCS, not only readily achieves the spontaneous activation of CO2 to *COOH but also greatly reduces the energy required for the conversion of *COOH to *CO intermediate, thus endowing NH2−CdS/NMHCS with significantly improved reaction kinetics and reduced overpotential for CO2‐to‐CO conversion. It is believed that this research can provide valuable insights into the development of electrocatalysts with superior CO2 adsorption and activation capabilities for CO2RR application.
Injectable Oxygen‐Carrying Microsphere Hydrogel for Dynamic Regulation of Redox Microenvironment of Wounds
Authors: Fu Ya‐Jun , Wang Rao‐Kaijuan , Ma Cheng‐Ye , Wang Li‐Ya , Long Si‐Yu , Li Kai , Zhao Xing , Yang Wei
Published: June 2024

The delayed healing of infected wounds can be attributed to the increased production of reactive oxygen species (ROS) and consequent damages to vascellum and tissue, resulting in a hypoxic wound environment that further exacerbates inflammation. Current clinical treatments including hyperbaric oxygen therapy and antibiotic treatment fail to provide sustained oxygenation and drug‐free resistance to infection. To propose a dynamic oxygen regulation strategy, this study develops a composite hydrogel with ROS‐scavenging system and oxygen‐releasing microspheres in the wound dressing. The hydrogel itself reduces cellular damage by removing ROS derived from immune cells. Simultaneously, the sustained release of oxygen from microspheres improves cell survival and migration in hypoxic environments, promoting angiogenesis and collagen regeneration. The combination of ROS scavenging and oxygenation enables the wound dressing to achieve drug‐free anti‐infection through activating immune modulation, inhibiting the secretion of pro‐inflammatory cytokines interleukin‐6, and promoting tissue regeneration in both acute and infected wounds of rat skins. Thus, the composite hydrogel dressing proposed in this work shows great potential for dynamic redox regulation of infected wounds and accelerates wound healing without drugs.
Designing 3D SnS@Cu‐Ni Nanoporous Column Array Electrode for High‐Capacity and High‐Rate Lithium‐Ion Batteries
Authors: Wang Haoyu , Liu Huanyan , Pan Tao , Zhang Shichao , Liu Wenbo
Published: June 2024

Sn‐based materials with high capacity showcase great potential for next‐generation lithium‐ion batteries (LIBs). Yet, the large volume change and limited ion/electron transfer efficiency of Sn‐based materials upon operation significantly compromises the battery performance. In this study, a unique 3D copper‐nickel nanoporous column array current collector is rationally developed via a facile template‐free galvanostatic electrodeposition method, followed by electrodepositing SnS active material onto it (denoted as 3D SnS@CNCA). Excitingly, the morphology of the 3D SnS@CNCA electrode perfectly inherited the nanoporous column array structure of the 3D current collector, which not only endows the electrode with a large specific surface area to provide more active sites and sufficient ion/electron transport pathways, but also effectively alleviates the volume expansion of SnS upon repeated charge–discharge cycles. Therefore, the binder‐free 3D SnS@CNCA electrode showcases a significantly enhanced Li storage performance, showing a high initial reversible capacity of 1019.7 mAh g−1 with noteworthy cycling stability (a capacity retention rate of 89.4% after 200 cycles). Moreover, the designed electrode also manifests high rate performance with a high capacity of 570.6 mAh g−1 at 4 A g−1. This work provides a novel design idea for the preparation of high‐performance electrodes beyond LIBs.
Defect Regulation Strategy of Porous Persistent Phosphors for Multiple and Dynamic Information Encryption
Authors: Shen Ruichen , He Tianpei , Yao Sailing , Zhang Yun , Peng Tianhuan , Tan Weihong , Chen Na , Yuan Quan
Published: June 2024

Optical encryption technologies based on persistent luminescence material have currently drawn increasing attention due to the distinctive and long‐lived optical properties, which enable multi‐dimensional and dynamic optical information encryption to improve the security level. However, the controlled synthesis of persistent phosphors remains largely unexplored and it is still a great challenge to regulate the structure for optical properties optimization, which inevitably sets significant limitations on the practical application of persistent luminescent materials. Herein, a controlled synthesis method is proposed based on defect structure regulation and a series of porous persistent phosphors is obtained with different luminous intensities, lifetime, and wavelengths. By simply using diverse templates during the sol–gel process, the oxygen vacancy defects structures are successfully regulated to improve the optical properties. Additionally, the obtained series of porous Al2O3 are utilized for multi‐color and dynamic optical information encryption to increase the security level. Overall, the proposed defect regulation strategy in this work is expected to provide a general and facile method for optimizing the optical properties of persistent luminescent materials, paving new ways for broadening their applications in multi‐dimensional and dynamic information encryption.
Evolution of Electromagnetic Fields and Forced Flow in a Metal Melt under the Impact of Hot‐Top Pulsed Magneto‐Oscillation
Authors: Zhou Yulan , Chen Gang , Zhang Yunhu , Wang Junjie , Xu Yanyi , Song Changjiang , Zheng Hongxing , Zhai Qijie
Published: June 2024

Hot‐top pulsed magneto‐oscillation (HPMO) is developed as a novel approach to achieve grain refinement and solute homogenization in heavy steel ingots. Through a combination of numerical simulations and melt flow measurements, this study investigates the evolution of electromagnetic fields and forced flow within alloy melts under the influence of HPMO, with a focus on varying electromagnetic parameters such as electric current intensity, frequency, and pulse length. The results of the simulations reveal the formation of double‐circulating flows in opposite directions within the melt. Experimental measurements of the flow field distribution closely align with the simulation outcomes. Furthermore, it is observed that the induced magnetic field inside the melt changes direction once, and the electromagnetic force changes direction three times within a single pulse length period under the influence of HPMO. Notably, the radial electromagnetic force, directed toward the interior of the melt, surpasses the normal electromagnetic force away from the melt. This phenomenon leads to a stable flow of the melt, contributing to grain refinement. The findings presented in this study offer valuable insights into the use of HPMO as a promising technique for improving the quality of heavy steel ingots.
Flexural mechanism and design method for precast concrete splice slabs with welded junction plates
Authors: Chen Ying , Shi Hai‐Rong , Zhu Hong , Wang Chun‐Lin , Zeng Bin
Published: June 2024

The joints of precast splice slabs significantly impact their flexural bearing capacity. This paper introduces a novel type of precast splice slab, termed the precast concrete splice slab with welded junction plates. A flexural loading test was conducted on 10 specimens (including eight precast splice slabs, one precast slab, and one cast‐in‐place slab). The main conclusions of the test are as follows. Severe damage barely occurred at the joint and at the interface between the precast unit and the cast‐in‐place concrete. The specimen produced flexural type vertical cracks in the tension zone and transverse cracks in the compression zone. When some longitudinal rebars in the precast unit of the specimens were bent into an arc, the cracking and yield loads were lower than those of the ordinary precast or cast‐in‐place slabs. The incorporation of lap‐splice rebar in the cast‐in‐place concrete improved only the yield load of the specimens, while the welding of additional rebar in the precast unit significantly enhanced both the cracking and yield loads. A design method for determining the flexural bearing capacity of the precast concrete splice slab with welded junction plates was established. Meanwhile, the force transfer mechanism of the junction plates needs to be further investigated to establish a more economical design method for the junction plates.
Saw‐cut method verification for determining the most important factors influencing its applicability
Authors: Kralovanec Jakub , Moravcik Martin , Zahuranec Michal , Sifta Radim , Somer Jakub
Published: June 2024

The current situation with prestressed structures raises questions about the ways how to determine residual prestressing which is the crucial factor for the evaluation of the prestressed structure. Therefore, this study aims to enhance existing knowledge of the so‐called Saw‐cut method which is considered a non‐destructive indirect technique. The presented study focuses on the determination of various factors which could influence the applicability and accuracy of this method such as both compressive and tensile normal stress release, the type of measuring instrument (linear foil strain gauge or newly developed FBG sensor), and the length of the normal stress release recording (up to almost 9 h). The obtained results suggest that tensile normal stress release could be more problematic for the evaluation than compressive normal stress release. Moreover, the application of FBG sensors seems to be more precise but also more complicated regarding the installation, recording and costs. Finally, the time span of the measurement can influence the residual normal stress release. For practical reasons, 60 min after the performance of the final sawing should be sufficient. Finally, when used at locations with adequate compressive normal stress, the Saw‐cut method seems to be a promising tool for prestressing evaluation.
High‐throughput classification of S. cerevisiae tetrads using deep learning
Authors: Szücs Balint , Selvan Raghavendra , Lisby Michael
Published: June 2024

Meiotic crossovers play a vital role in proper chromosome segregation and evolution of most sexually reproducing organisms. Meiotic recombination can be visually observed in Saccharomyces cerevisiae tetrads using linked spore‐autonomous fluorescent markers placed at defined intervals within the genome, which allows for analysis of meiotic segregation without the need for tetrad dissection. To automate the analysis, we developed a deep learning‐based image recognition and classification pipeline for high‐throughput tetrad detection and meiotic crossover classification. As a proof of concept, we analyzed a large image data set from wild‐type and selected gene knock‐out mutants to quantify crossover frequency, interference, chromosome missegregation, and gene conversion events. The deep learning‐based method has the potential to accelerate the discovery of new genes involved in meiotic recombination in S. cerevisiae such as the underlying factors controlling crossover frequency and interference.
New Well-Posed boundary conditions for semi-classical Euclidean gravity
Authors: Liu Xiaoyi , Santos Jorge E. , Wiseman Toby
Published: June 2024

Abstract

We consider four-dimensional Euclidean gravity in a finite cavity. Dirichlet conditions do not yield a well-posed elliptic system, and Anderson has suggested boundary conditions that do. Here we point out that there exists a one-parameter family of boundary conditions, parameterized by a constant p, where a suitably Weyl rescaled boundary metric is fixed, and all give a well-posed elliptic system. Anderson and Dirichlet boundary conditions can be seen as the limits p → 0 and ∞ of these. Focussing on static Euclidean solutions, we derive a thermodynamic first law. Restricting to a spherical spatial boundary, the infillings are flat space or the Schwarzschild solution, and have similar thermodynamics to the Dirichlet case. We consider smooth Euclidean fluctuations about the flat space saddle; for p > 1/6 the spectrum of the Lichnerowicz operator is stable — its eigenvalues have positive real part. Thus we may regard large p as a regularization of the ill-posed Dirichlet boundary conditions. However for p < 1/6 there are unstable modes, even in the spherically symmetric and static sector. We then turn to Lorentzian signature. For p < 1/6 we may understand this spherical Euclidean instability as being paired with a Lorentzian instability associated with the dynamics of the boundary itself. However, a mystery emerges when we consider perturbations that break spherical symmetry. Here we find a plethora of dynamically unstable modes even for p > 1/6, contrasting starkly with the Euclidean stability we found. Thus we seemingly obtain a system with stable thermodynamics, but unstable dynamics, calling into question the standard assumption of smoothness that we have implemented when discussing the Euclidean theory.
C. elegans foraging as a model for understanding the neuronal basis of decision-making
Authors: Haley Jessica A. , Chalasani Sreekanth H.
Published: June 2024

Animals have evolved to seek, select, and exploit food sources in their environment. Collectively termed foraging, these ubiquitous behaviors are necessary for animal survival. As a foundation for understanding foraging, behavioral ecologists established early theoretical and mathematical frameworks which have been subsequently refined and supported by field and laboratory studies of foraging animals. These simple models sought to explain how animals decide which strategies to employ when locating food, what food items to consume, and when to explore the environment for new food sources. These foraging decisions involve integration of prior experience with multimodal sensory information about the animal’s current environment and internal state. We suggest that the nematode Caenorhabditis elegans is well-suited for a high-resolution analysis of complex goal-oriented behaviors such as foraging. We focus our discussion on behavioral studies highlighting C. elegans foraging on bacteria and summarize what is known about the underlying neuronal and molecular pathways. Broadly, we suggest that this simple model system can provide a mechanistic understanding of decision-making and present additional avenues for advancing our understanding of complex behavioral processes.
Stress-constrained optimization of multiscale structures with parameterized microarchitectures using machine learning
Authors: Black Nolan , Najafi Ahmad
Published: June 2024

A multiscale topology optimization framework for stress-constrained design is presented. Spatially varying microstructures are distributed in the macroscale where their material properties are estimated using a neural network surrogate model for homogenized constitutive relations. Meanwhile, the local stress state of each microstructure is evaluated with another neural network trained to emulate second-order homogenization. This combination of two surrogate models — one for effective properties, one for local stress evaluation — is shown to accurately and efficiently predict relevant stress values in structures with spatially varying microstructures. An augmented lagrangian approach to stress-constrained optimization is then implemented to minimize the volume of multiscale structures subjected to stress constraints in each microstructure. Several examples show that the approach can produce designs with varied microarchitectures that respect local stress constraints. As expected, the distributed microstructures cannot surpass density-based topology optimization designs in canonical volume minimization problems. Despite this, the stress-constrained design of hierarchical structures remains an important component in the development of multiphysics and multifunctional design. This work presents an effective approach to multiscale optimization where a machine learning approach to local analysis has increased the information exchange between micro- and macroscales.
Arbitrariness of bibliometric parameters: a case study on leading scientists in the German Society for Experimental and Clinical Pharmacology and Toxicology (DGPT)
Authors: Fox Louisa Christin , Seifert Roland
Published: June 2024

Bibliometric rankings of researchers are increasingly important for academic hiring and for making grant application decisions in the biomedical sciences. As a case study, we performed a comprehensive bibliometric analysis of German pharmacology and toxicology. The 42 members of the German Society for Experimental and Clinical Pharmacology and Toxicology (DGPT) represented in the German ‘best scientist’ ranking in biology and biochemistry on www.research.com for the year 2022 were analyzed according to various aspects. The scientist ranking on Research.com is based on the Hirsch Index (h-Index). In the comparatively small field of pharmacology, which accounts for only 4.2% of the scientists in the ranking on Research.com, there are only two women. This shows that female pharmacologists are highly underrepresented in elite pharmacology. To achieve a high h-Index, a pharmacologist must publish more papers than a biochemist or biologist. Furthermore, German elite pharmacology was compared in the three sub-societies of the DGPT. There are no significant differences between elite pharmacologists and toxicologists in terms of productivity. Two large German pharmacology schools (Günter Schultz and Franz Hofmann) are similar in all bibliometric parameters except for number of total publications. Age-specific factors were also defined for the analysis: ‘academic age’ and the quotient of the h-Index by ‘academic age’. Any given bibliometric parameter (or combination of parameters) yielded different ranking results. This became even more evident when additionally considering the highly popular and widely used Laborjournal ranking of top pharmacology and toxicology researchers with only very few DGPT members listed. We unmasked 7 types of publication patterns of pharmacologists, an age-dependent publication peak at around 55 years and different trajectories for high- and low-volume publishing pharmacologists. In the future, less emphasis should be paid to bibliometric parameters in academic hiring and grant decisions than to the authentic societal and scientific impact of the research. Bibliometric parameters are very arbitrary within a very large segment of pharmacologists. Studies according to the paradigm of this account should be made for other countries, other learned societies, and other scientific fields. The different cultures among related scientific fields must be considered in bibliometric analyses as exemplified here for pharmacology versus biochemistry. Conversely, the bibliometric similarities between pharmacology and toxicology show that both fields belong together and have a very similar culture.
Connective tissue disease-associated lung disease in children
Authors: Schapiro Andrew H. , Morin Cara E. , Wikenheiser-Brokamp Kathryn A. , Tanimoto Aki A.
Published: June 2024

Connective tissue diseases are a heterogeneous group of autoimmune diseases that can affect a variety of organ systems. Lung parenchymal involvement is an important contributor to morbidity and mortality in children with connective tissue disease. Connective tissue disease-associated lung disease in children often manifests as one of several radiologic-pathologic patterns of disease, with certain patterns having a propensity to occur in association with certain connective tissue diseases. In this article, key clinical, histopathologic, and computed tomography (CT) features of typical patterns of connective tissue disease-associated lung disease in children are reviewed, with an emphasis on radiologic-pathologic correlation, to improve recognition of these patterns of lung disease at CT and to empower the pediatric radiologist to more fully contribute to the care of pediatric patients with these conditions.

Graphical abstract
Impact of cemiplimab treatment duration on clinical outcomes in advanced cutaneous squamous cell carcinoma
Authors: Mallardo Domenico , Sparano Francesca , Vitale Maria Grazia , Trojaniello Claudia , Fordellone Mario , Cioli Eleonora , Esposito Assunta , Festino Lucia , Mallardo Mario , Vanella Vito , Facchini Bianca Arianna , De Filippi Rosaria , Meinardi Paolo , Ottaviano Margaret , Caracò Corrado , Simeone Ester , Ascierto Paolo Antonio
Published: June 2024

Treatment duration with checkpoint inhibitors must be optimized to prevent unjustified toxicity, but evidence for the management of cutaneous squamous cell carcinoma is lacking. A retrospective study was performed to evaluate the survival of patients with cutaneous squamous cell carcinoma (CSCC) who discontinued cemiplimab due to different causes and without progression. Among 95 patients with CSCC who received cemiplimab, 22 (23%) patients discontinued immunotherapy due to causes other than progression, such as comorbidities, toxicity, complete response or lack of compliance (group that discontinued before censoring [DBC]), then 73 patients had standard treatment scheduled (STS). The overall survival was 25.2 months (95% CI: 8.9–29.4) in STS group and 28.3 months (95% CI: 12.7–28.3) in the DBC group; deaths for all causes were 11/22 (50%) in the DBC group and 34/73 (46.6%) in the STS group (p = 0.32). 10/22 (45.4%) subjects died due to CSCC in the DBC after discontinuation and 34/73 (46.6%) in the STS group, and the difference between groups was not significant (p = 0.230). Duration of treatment was significantly lower in subjects with stable disease versus those with complete or partial response (16.9, 30.6 and 34.9 months, respectively; p = 0.004). Among the 22 STS patients, 12 received cemiplimab for less than 12 months (10 [83%] died) and 10 for at least 12 months (1 [10%] died). Our observation, finding no outcome difference between DBC and STS groups, suggests that ICI treatment after one year might expose patients to further treatment related events without efficacy advantages.

Graphical abstract
Efficacy and safety of immune checkpoint inhibitors in solid tumor patients combined with chronic coronary syndromes or its risk factor: a nationwide multicenter cohort study
Authors: Liu Chao , Ruan Yuli , Huang Rui , Fang Lin , Wu Tong , Lv Ying , Cui Luying , Liao Yuanyu , Wang Bojun , Chen Zhuo , Su Dan , Ma Yue , Han Shuling , Guan Xin , Cui Jie , Yao Yang , Wang Yao , Wang Mengmeng , Liu Ruiqi , Zhang Yanqiao
Published: June 2024

Background

Although, immune checkpoint inhibitors (ICIs) have been widely applied in the therapy of malignant tumors, the efficacy and safety of ICIs in patients with tumors and pre-existing CAD, especially chronic coronary syndromes (CCS) or their risk factors (CRF), is not well identified.

Methods

This was a nationwide multicenter observational study that enrolled participants who diagnosed with solid tumors and received ICIs therapy. The main efficacy indicators were progression-free survival (PFS) and overall survival (OS), followed by objective response rate (ORR) and disease control rate (DCR). Safety was assessed by describing treatment-related adverse events (TRAEs) during ICIs therapy evaluated by the Common Terminology Criteria for Adverse Events 5.0 (CTCAE 5.0).

Results

In the current research, we retrospectively analyzed the data of 551 patients diagnosed with solid tumors and received ICIs therapy, and these patients were divided into CCS/CRF group and non-CCS/CRF group. Patients with CCS/CRF had more favorable PFS and OS than patients without CCS/CRF (P < 0.001) and the pre-existing CCS/CRF was a protective factor for survival. The ORR (51.8% vs. 39.1%) and DCR (95.8% vs. 89.2%) were higher in CCS/CRF group than in non-CCS/CRF group (P = 0.003, P = 0.006). In this study, there was no significant difference in treatment-related adverse events (TRAEs), including immune-related adverse events (irAEs), between the two groups.

Conclusions

We concluded that ICIs appear to have better efficacy in malignant solid tumor patients with pre-existing CCS/CRF and are not accompanied by more serious irAEs.
The biodistribution of triamcinolone acetonide injections in severe keloids: an exploratory three-dimensional fluorescent cryomicrotome study
Authors: Yin Qi , Bekkers Vazula Z. , Roelofs Maud C. M. , Dobbe Johannes G. G. , de Vos Judith , Bloemen Paul R. , Aalders Maurice C. G. , Gibbs Susan , Lapid Oren , Niessen Frank B. , van Doorn Martijn B. A. , Wolkerstorfer Albert
Published: June 2024

Intralesional corticosteroid injections are a first-line treatment for keloids; yet clinical treatment results are highly variable and often suboptimal. Variation in triamcinolone acetonide (TAC) biodistribution may be an important reason for the variable effects of TAC treatment in keloids. In this exploratory study we investigated the biodistribution of TAC in keloids and normal skin using different drug delivery techniques. Fluorescent-labeled TAC suspension was administered into keloids and normal skin with a hypodermic needle and an electronic pneumatic jet injector. TAC biodistribution was represented by the fluorescent TAC volume and 3D biodistribution shape of TAC, using a 3D-Fluorescence-Imaging Cryomicrotome System. Twenty-one keloid and nine normal skin samples were analyzed. With needle injections, the mean fluorescent TAC volumes were 990 µl ± 479 in keloids and 872 µl ± 227 in normal skin. With the jet injector, the mean fluorescent TAC volumes were 401 µl ± 252 in keloids and 249 µl ± 67 in normal skin. 3D biodistribution shapes of TAC were highly variable in keloids and normal skin. In conclusion, TAC biodistribution in keloids is highly variable for both needle and jet injection. This may partly explain the variable treatment effects of intralesional TAC in keloids. Future research is needed to confirm this preliminary finding and to optimize drug delivery in keloids.
Combination of autologous FCS and MPG versus each technique alone in the treatment of stable vitiligo
Authors: ElGhareeb Mohamed Ibrahim , Kandeel Abdullah Hassan , Attia Sara Ali
Published: June 2024

Follicular cell suspension (FCS) transplantation is a novel surgical method for treating resistant stable vitiligo, whereas mini punch grafting is an established effective method for treating stable vitiligo. The combination of FCS and mini punch grafting is a better strategy for the treatment of resistant stable vitiligo. The aim of the study was to evaluate the efficacy of follicular cell suspension, mini punch grafting, and a combination of both techniques in the treatment of stable vitiligo. This prospective comparative study was conducted on 48 patients with stable vitiligo. They were divided into three equal groups, including group A (treated with follicular cell suspension), group B (treated with mini punch grafting), and group C (treated with the combination of both techniques). All patients were followed-up for six months for the assessment of their therapeutic response regarding clinical outcomes. By comparing the data of the three studied groups, we found that the difference in the degree of re-pigmentation after one and three months of treatment was not significant. However, the progress of re-pigmentation was significantly different after six months of treatment among the three studied groups (P = 0.027). Specifically, re-pigmentation was significantly better in group C than in groups A and B (P = 0.037 and 0.017, respectively), but it was not significantly different between groups A and B.
Estimation of the tissue and serum levels of IL-35 in Mycosis fungoides: a case-control study
Authors: Elmasry Maha Fathy , Obaid Yasmine Ahmed , El-Samanoudy Solwan Ibrahim , Nour Zeinab Ahmed , Doss Sally Sameh
Published: June 2024

Mycosis fungoides (MF) is the most common primary cutaneous T-cell lymphoma (CTCL) with its etiology not yet fully understood. Interleukin (IL)-35 is an inhibitory cytokine that belongs to the IL-12 family. Elevated IL-35 in the plasma and the tumor microenvironment increases tumorigenesis and indicates poor prognosis in different types of malignancies. The objective of this study is to estimate the expression levels of IL-35 in tissue and serum of MF patients versus healthy controls. This case-control study included 35 patients with patch, plaque, and tumor MF as well as 30 healthy controls. Patients were fully assessed, and serum samples and lesional skin biopsies were taken prior to starting treatment. The IL-35 levels were measured in both serum and tissue biopsies by ELISA technique. Both tissue and serum IL-35 levels were significantly higher in MF patients than in controls (P < 0.001) and tissue IL-35 was significantly higher than serum IL-35 in MF patients (P < 0.001). Tissue IL-35 was significantly higher in female patients and patients with recurrent MF compared to male patients and those without recurrent disease (P < 0.001). Since both tissue and serum IL-35 levels are increased in MF, IL-35 is suggested to have a possible role in MF pathogenesis. IL-35 can be a useful diagnostic marker for MF. Tissue IL-35 can also be an indicator of disease recurrence.
Combined low-dose isotretinoin and long-pulsed nd: YAG laser in the treatment of post-acne erythema
Authors: Albalat Waleed , Ehab Rana , AbouHadeed Mohamed Hussein , Abd Allah Tarek N. , Essam Reham
Published: June 2024

Post-acne erythema (PAE) is a bothering skin condition that emerges from inflammatory acne and persists after its resolution. It is characterized by telangiectasia and erythematous macules. the role of 1064-nm Nd: YAG when combined with low-dose isotretinoin in the acne erythema treatment. forty-eight PAE patients were involved in the study. They were divided into two groups; group (A) patients administering a low dose of oral isotretinoin (10 mg/day) and underwent a total of six two-week interval sessions of 1064 ND-YAG laser treatment, group (B) patients administering a low dose of oral isotretinoin (10 mg/day) only. All adverse effects experienced during the course of therapy were documented, and photos were taken before the start of the treatment and following the end of the treatment duration. Following the completion of the therapeutic intervention, a significant improvement in clinical condition was observed in both groups, with more improvement in group (A) compared to group (B) as evidenced by a notable improvement in the score on the Clinician Erythema Assessment Scale (CEAS) and also a significant decrease in the mean value of optical density of the erythema. combined 1064-nm Nd: YAG with low-dose isotretinoin may be an efficient and secure line in the PAE treatment. Also, the combined therapy had superior results when compared to low-dose isotretinoin alone.
Naturalistic comparison of clomethiazole and Diazepam treatment in alcohol withdrawal: effects on oxidative stress, inflammatory cytokines and hepatic biomarkers
Authors: Strischewski David , Kalmar Amira , Guest Paul C. , Dobrowolny Henrik , Meyer-Lotz Gabriela , Schiffner Conrad J. , Jordan Wolfgang , Müller Ulf J. , Borucki Katrin , Böttcher Michael , Relja Borna , Steiner Johann
Published: June 2024

Ethanol is metabolized by alcohol dehydrogenase to acetaldehyde and induces cytochrome P450 2E1 (CYP2E1), which generates reactive oxygen species that cause inflammatory liver damage. Clomethiazole, a drug approved for alcohol withdrawal treatment (AWT) in some European countries, inhibits CYP2E1. We hypothesized that clomethiazole would lead to a faster reduction in oxidative stress, inflammatory cytokines, and liver enzymes compared to diazepam treatment. We analysed respective biomarkers in 50 patients undergoing AWT and 25 healthy individuals but found no statistical difference between the two medication groups over 3–5 days. Hence, our hypothesis was not confirmed during this observation period.
A 29-mRNA host-response classifier identifies bacterial infections following liver transplantation – a pilot study
Authors: Halder Amelie , Liesenfeld Oliver , Whitfield Natalie , Uhle Florian , Schenz Judith , Mehrabi Arianeb , Schmitt Felix C. F. , Weigand Markus A. , Decker Sebastian O.
Published: June 2024

Purpose

Infections are common complications in patients following liver transplantation (LTX). The early diagnosis and prognosis of these infections is an unmet medical need even when using routine biomarkers such as C-reactive protein (CRP) and procalcitonin (PCT). Therefore, new approaches are necessary.

Methods

In a prospective, observational pilot study, we monitored 30 consecutive patients daily between days 0 and 13 following LTX using the 29-mRNA host classifier IMX-BVN-3b that determine the likelihood of bacterial infections and viral infections. True infection status was determined using clinical adjudication. Results were compared to the accuracy of CRP and PCT for patients with and without bacterial infection due to clinical adjudication.

Results

Clinical adjudication confirmed bacterial infections in 10 and fungal infections in 2 patients. 20 patients stayed non-infected until day 13 post-LTX. IMX-BVN-3b bacterial scores were increased directly following LTX and decreased until day four in all patients. Bacterial IMX-BVN-3b scores detected bacterial infections in 9 out of 10 patients. PCT concentrations did not differ between patients with or without bacterial, whereas CRP was elevated in all patients with significantly higher levels in patients with bacterial infections.

Conclusion

The 29-mRNA host classifier IMX-BVN-3b identified bacterial infections in post-LTX patients and did so earlier than routine biomarkers. While our pilot study holds promise future studies will determine whether these classifiers may help to identify post-LTX infections earlier and improve patient management.

Clinical trial notation

German Clinical Trials Register: DRKS00023236, Registered 07 October 2020, https://drks.de/search/en/trial/DRKS00023236
High-dose chemotherapy and autologous hematopoietic stem cell transplantation for progressive systemic sclerosis: a retrospective study of outcome and prognostic factors
Authors: Pyka Vanessa , Vangala Deepak B. , Mika Thomas , Kreuter Alexander , Susok Laura , Baraliakos Xenofon , Treiber Hannes , Schroers Roland , Nilius-Eliliwi Verena
Published: June 2024

Purpose

Systemic sclerosis (SSc) is a rare autoimmune disease associated with high morbidity and mortality. SSc treatment is still challenging, and evidence is scarce. In the last decades high-dose chemotherapy and autologous stem cell transplantation (HD-ASCT) has proven to be effective. However, treatment related morbidity and mortality (TRM) are high. We conducted a retrospective, single-center analysis of SSc patients following HD-ASCT focusing on TRM and risk factors.

Methods

32 patients who underwent HD-ASCT at our hospital between June 2000 and September 2020 were included. Clinical characteristics were evaluated based on chart review before and after HD-ASCT. Analyses focused on overall survival (OS), TRM, and response to HD-ASCT.

Results

Median OS was 81 months (range 0–243). Within one year, 20 of 32 (76.9%) patients responded to HD-ASCT. Overall, 6 patients (18.8%) died in the context of HD-ASCT. Patients with subjective response to HD-ASCT (p = 0.024) and those with shorter time to platelet engraftment (p = 0.047) had significantly longer OS. Impaired renal function, age at HD-ASCT ≥ 55, disease duration < 12 months, high Hematopoietic cell transplantation-specific comorbidity index (HCT-CI) and Charlton Comorbidity Index (CCI) scores were associated with higher TRM. Patients receiving conditioning chemotherapy with thiotepa needed longer time for neutrophil (p = 0.035) and platelet engraftment (p = 0.021).

Conclusion

This study confirms the efficacy of HD-ASCT for patients with SSc in a single center real-world setting. High TRM is still a challenge. However, TRM could be reduced by exclusion of high-risk patients and attention to prognostic parameters and scores as suggested in this study.