bluuebunny/crossref_metadata_2025 huggingface dataset:
The neurodivergent college learner: faculty perceptions of supporting individuals with ADHD in higher education
Authors: Nash-Luckenbach Denise M. , Friedman Zahava L.
Published: August 2024

Purpose

The purpose of this study is to understand how faculty members perceive learning needs of the attention-deficit hyperactive disorder (ADHD) student, as they acclimated to and performed within the higher education settings.

Design/methodology/approach

A phenomenological design was used to explore the faculty perceptions of ADHD college students. A sample of ten faculty members, employed in two-year, four-year, and graduate-level programs, participated in virtual semi-structured interviews. A six step thematic analysis of the codes was performed revealing three themes.

Findings

Results from the study yielded three themes: problem-based learning, time management and accommodations versus privilege. These themes highlight the complexity of the learning process, the limitations with time management, and the need for meaningful, rather than stereotypical, accommodations in these settings.

Practical implications

The number of students diagnosed with ADHD attending postsecondary education continues to rise, necessitating a critical lens on increasing neurodiversity-affirming practices in these settings. Despite noted strengths, students with this diagnosis struggle academically, resulting in academic challenges. To maximize each individual’s learning potential, systems of higher education need to carefully consider how to best design a positive learning environment with universally effective learning accommodations.

Originality/value

While faculty described accommodations and strategies provided to students, they also repeatedly shared concerning challenges and barriers to learning, as demonstrated by their students in various scenarios and situations. Results suggest areas of potential improvement, alongside the complexity of serving the need of the next generation of neurodivergent learners, in a world where equity and inclusion required additional time and thoughtful effort. Of greatest concern, perhaps, was the systems already in place, including offices of accommodations and services, that tended to use a “one-size-fits-all” approach, oversimplifying, rather than serving, student need.
Do executive facial trustworthiness have impact on IPO underpricing in the Indonesia stock exchange?
Authors: Hendrawan I. Putu Sukma , Utama Cynthia Afriani
Published: August 2024

Purpose

This study aims to investigate the impact of facial-based perceived trustworthiness on stock valuation, particularly, in the initial public offering (IPO). IPO settings provide the opportunity to investigate whether information asymmetry resulting from company newness in the market would influence the incorporation of soft information in the form of executive facial trustworthiness in stock valuation.

Design/methodology/approach

We use a recent machine learning algorithm to detect facial landmarks and then calculate a composite facial trustworthiness measure using several facial features that have previously been observed in neuroscience and psychological studies to be the most determining factor of perceived trustworthiness. We then regress the facial trustworthiness of IPO firm executives to IPO underpricing.

Findings

Utilizing machine learning algorithms, we find that the facial trustworthiness of the company executive negatively impacts the extent of IPO underpricing. This result implies that investors incorporate the facial trustworthiness of company executives into stock valuation. The IPO underpricing also shows that the cost of equity is higher when perceived trustworthiness is low. With regard to the higher information asymmetry in IPO transactions, such a negative impact implies the role of facial trustworthiness in alleviating information asymmetry.

Originality/value

This study provides evidence of the impact of top management personal characteristics on firms’ financial transactions in the Indonesian context. From the perspective of investors and other fund providers, this study shows evidence that heuristics still play an important role in financial decision-making. This is also an indication of investor reliance on soft information. Our research method also provides a new opportunity for the use of machine-learning algorithms in processing non-conventional types of data in finance research, which is still relatively rare in emerging markets like Indonesia. To the best of our knowledge, our study is the first to use personalized measures of trust generated through machine-learning algorithms in IPO settings in Indonesia.
Effect of scanning strategy and laser peening on microstructure and fatigue properties of laser-directed energy deposition-built 15-5 PH stainless steel
Authors: Pandey Susheel , Srivastava Rajeev , Paul Christ Prakash , Rai Arun Kumar , Narain Rakesh
Published: August 2024

Purpose

The aim of this paper is to study the effect of laser shock peening (LSP) on mechanical behaviour of the laser-directed energy deposition (LDED)-based printed 15-5 PH stainless steel with U and V notches. The study specifically concentrates on the evaluation of effect of scan strategy, machining and LSP processing on microstructural, texture evolution and fatigue behaviour of LDED-printed 15-5 PH steel.

Design/methodology/approach

For LSP treatment, 15-5 PH steel was printed using LDED process with bidirectional scanning strategy (XX [θ = 0°) and XY [θ = 90°]) at optimised laser power of 600 W with a scanning speed of 300 mm/min and a powder feed rate of 3 g/min. Furthermore, LSP treatment was conducted on the V- and U-notched fatigue specimens extracted from LDED-built samples at laser energy of 3.5 J with a pulse width of 10 ns using laser spot diameter of 3 mm. Post to the LSP treatment, the surface roughness, fatigue life assessment and microstructural evolution analysis is performed. For this, different advanced characterisation techniques are used, such as scanning electron microscopy attached with electron backscatter diffraction for microstructure and texture, X-ray diffraction for residual stress (RS) and structure information, Vicker’s hardness tester for microhardness and universal testing machine for low-cycle fatigue.

Findings

It is observed that both scanning strategies during the LDED printing of 15-5 PH steel and laser peening have played significant role in fatigue life. Specimens with the XY printing strategy shows higher fatigue life as compared to XX with both U- and V-notched conditions. Furthermore, machining and LSP treatment led to a significant improvement of fatigue life for both scanning strategies with U and V notches. The extent of increase in fatigue life for both XX and XY scanning strategy with V notch is found to be higher than U notch after LSP treatment, though without LSP samples with U notch have a higher fatigue life. As fabricated sample is found to have the lowest fatigue life as compared to machines and laser peened with both scan strategies.

Originality/value

This study presents an innovative method to improve the fatigue life of 15-5 PH stainless steel by changing the microstructure, texture and RS with the adoption of a suitable scanning strategy, machining and LSP treatment as post-processing. The combination of preferred microstructure and compressive RS in LDED-printed 15-5 PH stainless steel achieved with a synergy between microstructure and RS, which is responsible to improve the fatigue life. This can be adopted for the futuristic application of LDED-printed 15-5 PH stainless steel for different applications in aerospace and other industries.

Graphical abstract
Green building development in the US capitals: a focused comparative analysis with Baton Rouge
Authors: Awolesi Oluwafemi , Reams Margaret
Published: August 2024

Purpose

For over 25 years, the United States Green Building Council (USGBC) has significantly influenced the US sustainable construction through its leadership in energy and environmental design (LEED) certification program. This study aims to delve into how Baton Rouge, Louisiana, fares in green building adoption relative to other US capital cities and regions.

Design/methodology/approach

The study leverages statistical and geospatial analyses of data sourced from the USGBC, among other databases. It scrutinizes Baton Rouge’s LEED criteria performance using the mean percent weighted criteria to pinpoint the LEED criteria most readily achieved. Moreover, unique metrics, such as the certified green building per capita (CGBC), were formulated to facilitate a comparative analysis of green building adoption across various regions.

Findings

Baton Rouge’s CGBC stands at 0.31% (C+), markedly trailing behind the frontrunner, Santa Fe, New Mexico, leading at 3.89% (A+) and in LEED building per capita too. Despite the notable concentration of certified green buildings (CGBs) within Baton Rouge, the city’s green building development appears to be in its infancy. Innovation and design was identified as the most attainable LEED benchmark in Baton Rouge. Additionally, socioeconomic factors, including education and income per capita, were associated with a mild to moderate positive correlation (0.25 = r = 0.36) with the adoption of green building practices across the capitals, while sociocultural infrastructure exhibited a strong positive correlation (r = 0.99).

Practical implications

This study is beneficial to policymakers, urban planners and developers for sustainable urban development and a reference point for subsequent postoccupancy evaluations of CGBs in Baton Rouge and beyond.

Originality/value

This study pioneers the comprehensive analysis of green building adoption rates and probable influencing factors in capital cities in the contiguous US using distinct metrics.
Underexplored food safety hazards of beekeeping products: Key knowledge gaps and suggestions for future research
Authors: Végh Rita , Csóka Mariann , Sörös Csilla , Sipos László
Published: August 2024

These days, a growing consumer demand and scientific interest can be observed for nutraceuticals of natural origin, including apiculture products. Due to the growing emphasis on environmental protection, extensive research has been conducted on the pesticide and heavy metal contamination of bee products; however, less attention is devoted on other food safety aspects. In our review, scientific information on the less‐researched food safety hazards of honey, bee bread, royal jelly, propolis, and beeswax are summarized. Bee products originating from certain plants may inherently contain phytotoxins, like pyrrolizidine alkaloids, tropane alkaloids, matrine alkaloids, grayanotoxins, gelsemium alkaloids, or tutin. Several case studies evidence that bee products can induce allergic responses to sensitive individuals, varying from mild to severe symptoms, including the potentially lethal anaphylaxis. Exposure to high temperature or long storage may lead to the formation of the potentially toxic 5‐hydroxymethylfurfural. Persistent organic pollutants, radionuclides, and microplastics can potentially be transferred to bee products from contaminated environmental sources. And lastly, inappropriate beekeeping practices can lead to the contamination of beekeeping products with harmful microorganisms and mycotoxins. Our review demonstrates the necessity of applying good beekeeping practices in order to protect honeybees and consumers of their products. An important aim of our work is to identify key knowledge gaps regarding the food safety of apiculture products.
Using bioactive compounds to mitigate the formation of typical chemical contaminants generated during the thermal processing of different food matrices
Authors: Guo Zilong , Feng Xiao , He Guangyun , Yang Huanqi , Zhong Tian , Xiao Ying , Yu Xi
Published: August 2024

With rising consumer awareness of health and wellness, the demand for enhanced food safety is rapidly increasing. The generation of chemical contaminants during the thermal processing of food materials, including polycyclic aromatic hydrocarbons, heterocyclic aromatic amines, and acrylamide happens every day in every kitchen all around the world. Unlike extraneous chemical contaminants (e.g., pesticides, herbicides, and chemical fertilizers), these endogenic chemical contaminants occur during the cooking process and cannot be removed before consumption. Therefore, much effort has been invested in searching for ways to reduce such thermally induced chemical contaminants. Recently, the addition of bioactive compounds has been found to be effective and promising. However, no systematic review of this practical science has been made yet. This review aims to summarize the latest applications of bioactive compounds for the control of chemical contaminants during food thermal processing. The underlying generation mechanisms and the toxic effects of these chemical contaminants are discussed in depth to reveal how and why they are suppressed by the addition of certain bioactive ingredients. Examples of specific bioactive compounds, such as phenolic compounds and organic acids, as well as their application scenarios, are outlined. In the end, outlooks and expectations for future development are provided based on a comprehensive summary and reflection of references.
Comprehensive research on the properties of advanced glycation end products in food and biological samples and their harmful role in inducing metabolic diseases
Authors: Gu Min Ji , Lee Yu Ra , Kim Donghwan , Kim Yoonsook , Ha Sang Keun
Published: August 2024

Advanced glycation end products (AGEs) are formed by the Maillard reaction, a nonenzymatic process that occurs widely in cooking, food processing, and within the human body. Primarily, AGEs are formed by the glycation of reducing sugars with amino groups, and this process is heat‐dependent. With changes in lifestyle, there has been an increase in the diversity of dietary habits, including those patterns associated with Western diets, which include the consumption of processed foods that are rich in AGEs. Excessive intake and exposure to AGEs are known to cause abnormalities in body function such as obesity, diabetes, and fatty liver, and the beneficial effects of AGEs in food processing in improving food flavor and quality. To obtain meaningful data regarding AGEs in a variety of food and human samples, it is necessary to more precisely characterize and analyze the AGEs extracted from samples to obtain accurate results. This review explores the recent analytical research and characterization of AGEs in foods, including casein, β‐lactoglobulin, soy protein, and meat protein, and in human samples, such as glycated‐albumin, hemoglobin, and plasma. Additionally, it explores the metabolic fate of AGEs in the body and the mechanisms of disease associated with metabolic abnormalities that may be caused by the consumption of foods containing AGEs. This review aims to provide an overview of the perspectives of relevant recent and future research on metabolic abnormalities caused by foods containing AGEs or by AGEs produced in the body.
Decoding coffee cardiometabolic potential: Chemical composition, nutritional, and health relationships
Authors: Karagöz Mustafa Fevzi , Koçyiğit Emine , Koçak Tevfik , Özturan Şirin Ayçıl , Icer Mehmet Arif , Ağagündüz Duygu , Coreta‐Gomes Filipe
Published: August 2024

Coffee is one of the most consumed beverages worldwide, recognized for its unique taste and aroma and for its social and health impacts. Coffee contains a plethora of nutritional and bioactive components, whose content can vary depending on their origin, processing, and extraction methods. Gathered evidence in literature shows that the regular coffee consumption containing functional compounds (e.g., polysaccharides, phenolic compounds, and melanoidins) can have potential beneficial effects on cardiometabolic risk factors such as abdominal adiposity, hyperglycemia, and lipogenesis. On the other hand, coffee compounds, such as caffeine, diterpenes, and advanced glycation end products, may be considered a risk for cardiometabolic health. The present comprehensive review provides up‐to‐date knowledge on the structure–function relationships between different chemical compounds present in coffee, one of the most prevalent beverages present in human diet, and cardiometabolic health.
A comprehensive review of the characterization, host interactions, and stabilization advancements on probiotics: Addressing the challenges in functional food diversification
Authors: Fentie Eskindir Getachew , Lim Kyeongmo , Jeong Minsoo , Shin Jae‐Ho
Published: August 2024

The demand for functional food is rising in tandem with the prevalence of chronic diseases. Probiotics play a crucial role in functional food development, yet their ability to confer health benefits to the host remains a topic of debate according to Food and Agriculture Organization/World Health Organization requirements. The application of culturomics, innovative isolation techniques, within the realm of probiotics is increasingly deemed essential for fully harnessing the latent potential of microbial reservoirs. Nevertheless, its application remains confined predominantly to human fecal sources. Following the integration of probiogenomics, significant advancements have been made in the safety assessment of probiotics. However, the adoption of novel probiotic microorganisms has yet to match the requisite pace. Progress in research concerning host–probiotic interactions by employing omics technologies, particularly in animal models, is notable. Nonetheless, the comprehensive elucidation of mechanisms of action and human trial studies are lagging behind. Additionally, the viability of probiotics, spanning from their production as functional foods to their transit to the human colon, has markedly improved through encapsulation techniques. Nevertheless, opportunities for exploration persist regarding alternative coating materials and diverse encapsulation methodologies. Furthermore, there is a discernible transition in the domain of probiotic‐based functional foods, shifting away from a primarily dairy‐centric focus toward inclusion in a broader array of food categories. This comprehensive review addresses critical issues ranging from isolation sources and novel techniques to the final functional food developments. while doing so, it explores probiogenomics applications for probiotic characterization, investigations into host–probiotic interactions, and strategies for probiotic stabilization under harsh environmental conditions.
Expression, purification, and function of baculovirus infected insect cells‐derived hookworm AIP‐1 and AIP‐2 proteins
Authors: Lee Chae Eun , Chung Hyun Joo , Lee Da Won , Lim Jong Seok , Lee Jeong Hwan , Ko Kisung , Hong Soon Auck , Hong Min Eui , Kim Joo Young , Lee Hye Jun , Kim Jin Wook , Myung Soon Chul
Published: August 2024

Anti‐inflammatory protein (AIP)‐1 and AIP‐2, identified as parasite excretory/secretory (ES) proteins, play a crucial role in promoting the survival of the parasite and evading the host immunological response. Both proteins inhibit inflammatory reactions, induce apoptosis in effector cells, and influence the phenotype of the immune response. Numerous parasite‐derived proteins have shown promise as therapeutic targets for inflammatory and allergic diseases. Despite this, the precise biological roles, and molecular characteristics of many such proteins remain unclear.

In this study, AIP‐1 and AIP‐2 were produced in the baculovirus‐insect cell expression system (BEVS). The multiplicity of infection (MOI) and the duration of infection conditions for AIP‐1 and AIP‐2 protein expression were successfully optimized to induce the highest expression levels of AIP‐1 and AIP‐2 proteins in insect cells. The insect cell‐derived AIP‐1 and AIP‐2 exhibited inhibitory functions against human matrix metalloproteinases (MMPs). This study demonstrates that insect cell‐derived AIP‐1 and AIP‐2 have the potential as therapeutic proteins for MMP‐TIMP (Metalloprotease‐Tissue inhibitor of metalloprotease) axis related disease.
An ultrasensitive electrochemical method for rapid detection of mercury based on nanoporous gold capped with a novel Zr‐MOF‐SH/reduced graphene oxide aerogel composites
Authors: Wu Xi , Geng Chenggang , Cheng Weiwei , Wang Zhenjiong , Zhang Yan , Wu Di , Tang Xiaozhi
Published: August 2024

In this work, an ultrasensitive electrochemical sensor based on Zr‐MOF‐SH/rGA/NPG was developed for the first time for the rapid determination of mercury ions. First, nanoporous gold (NPG) film was covered on the glassy carbon electrode (GCE) to offer a desirable substrate. Then, Zr‐MOF‐SH/rGA composites were dropped on the NPG film to form a modified electrode. Mercapto functionalized MOFs (Zr‐MOF‐SH) showed strong adsorption capability toward mercury ions, and the unique structure of reduced graphene oxide aerogel (rGA) provided various sites for coupling with Zr‐MOF‐SH as well as improved the electrochemical activity. As a consequence of the synergistic effect of Zr‐MOF‐SH, rGA, and NPG, the optimized Zr‐MOF‐SH/rGA/NPG/GCE sensor showed excellent detection performance toward mercury ions with a linear range from 0 to 200 nM and a low limit of detection of 1.4 nM. Meanwhile, the fabricated electrochemical sensor exhibited outstanding stability, reproducibility, and anti‐interference ability. To verify the practical applicability, the Zr‐MOF‐SH/rGA/NPG/GCE was applied for the determination of mercury ions in real rice samples with desirable recovery rates ranging from 98.8% to 108.3%.
The combined effect of triglyceride–glucose index and high‐sensitivity C‐reactive protein on cardiovascular outcomes in patients with chronic coronary syndrome: A multicenter cohort study
Authors: Li Qinxue , Song Ying , Zhang Zheng , Xu Jingjing , Liu Zhenyu , Tang Xiaofang , Wang Xiaozeng , Chen Yan , Zhang Yongzhen , Zhu Pei , Guo Xiaogang , Jiang Lin , Wang Zhifang , Liu Ru , Wang Qingsheng , Yao Yi , Feng Yingqing , Han Yaling , Yuan Jinqing
Published: August 2024

Background

The triglyceride–glucose (TyG) index and high‐sensitivity C‐reactive protein (hsCRP) are the commonly used biomarkers for insulin resistance and systemic inflammation, respectively. We aimed to investigate the combined association of TyG and hsCRP with the major adverse cardiovascular events (MACE) in patients with chronic coronary syndrome (CCS).

Methods

A total of 9421 patients with CCS were included in this study. The primary endpoint was defined as a composite of MACE covering all‐cause death, nonfatal myocardial infarction, and revascularization.

Results

During the 2‐year follow‐up period, 660 (7.0%) cases of MACE were recorded. Participants were divided equally into three groups according to TyG levels. Compared with the TyG T1 group, the risk of MACE was significantly higher in the TyG T3 group. It is noteworthy that among patients in the highest tertile of TyG, hsCRP >3 mg/L was significantly associated with an increased risk of MACE, whereas the results were not significant in the medium to low TyG groups. When patients were divided into six groups according to hsCRP and TyG, the Cox regression analysis showed that patients in the TyG T3 and hsCRP >3 mg/L group had a significantly higher risk of MACE than those in the TyG T1 and hsCRP ≤3 mg/L group. However, no significant interaction was found between TyG and hsCRP on the risk of MACE.

Conclusion

Our study suggests that the concurrent assessment of TyG and hsCRP may be valuable in identifying high‐risk populations and guiding management strategies among CCS patients.

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Switch or perish? Prey–predator interactions in a Mediterranean area
Authors: Lazzeri L. , Pacini G. , Belardi I. , Fini G. , De Lillo C. , Ferretti F.
Published: August 2024

Predator–prey relationships can influence community processes, and a rich prey spectrum is important to favour carnivore conservation, as well as to buffer single prey towards intensive predation. Antipredator behavioural responses can occur and can be dynamic in time and space, which may generate counter‐responses in predators. However, data are scarce on their role in modulating carnivore diet and behaviour. Data are especially needed for European landscapes that are largely anthropized and have been recently recolonized by large carnivores. In a protected area in central Italy recently recolonized by the wolf and hosting a rich community of wild ungulates, we studied the interactions between this predator and three ungulate species. At the initial stage of wolf recovery, the fallow deer and the wild boar were the main prey, while the roe deer was a minor food item. Through camera‐trapping and predator food habits, we assessed temporal changes in wolf–prey relationships throughout 5 years (2017–2022). Wolf detection rates were spatially associated with those of fallow deer and wild boar, but shrub cover was positively related to predator and negatively to prey, suggesting possible prey avoidance of sites with lower visibility and greater predation risk. Throughout the years, the fallow deer increased its diurnal activity, with a decreasing temporal overlap with the predator. The wolf showed crepuscular/nocturnal activity, with an increased synchronization with the wild boar, which replaced the fallow deer as first prey. No support for major spatiotemporal responses was reported for wild boar and roe deer. With the ongoing recovery of carnivores across Europe, conservation priorities may emphasize the need to maintain an efficient ecological role of predators. Our results support the role of antipredator responses in modulating predator behaviour and diet and emphasize the importance of a diverse spectrum of wild prey to ensure the conservation of the ecological role of carnivores.
Inferring dolphin population status: using unoccupied aerial systems to quantify age‐structure
Authors: Vivier F. , Andrés C. , Gonzalvo J. , Fertitta K. , van Aswegen M. , Foroughirad V. , Mann J. , McEntee M. , Wells R. S. , Bejder L.
Published: August 2024

Assessing trends in population abundance and demographics is crucial for managing long‐lived and slow‐reproducing species. Obtaining demographic data, and age‐structure information, is challenging, notably for cetaceans. To address this, we combined Unoccupied Aerial System (UAS; drone) photogrammetry data with long‐term (>20 years) photo identification data to assess the age‐structure of the critically endangered sub‐population of common bottlenose dolphins (Tursiops truncatus) of the Gulf of Ambracia, Greece. We compared our findings with two extensively studied non‐endangered bottlenose dolphin populations (T. aduncus in Shark Bay, Australia, and T. truncatus in Sarasota Bay, USA). Using a log‐linear model, we estimated the total body lengths (TL) of 160 known‐aged dolphins between 2021 and 2023 from blowhole‐to‐dorsal‐fin distance (BHDF) measurements collected during surfacing. Subsequently, we tested four growth models to establish an age‐length growth curve. We assessed the sub‐population's age‐structure using three methods: (1) UAS‐derived TL estimates, (2) age‐length growth curve and (3) long‐term monitoring data (i.e. actual age‐structure). UAS‐measured TL (247.6 ± 32.2 cm) and UAS‐estimated TL (246.0 ± 34.7 cm) of the Greek sub‐population showed no differences. The Richards Growth model suggested an asymptotic length of 258.5 cm. In Greece, resulting age‐structure estimates across the three methods revealed no significant differences (P > 0.1). The Gulf of Ambracia and Shark Bay populations shared similar age‐structures, while Sarasota had higher proportions of 2–10 year‐olds and lower proportions of 10+ year‐olds. All populations had a comparable proportion of 0–2 year‐olds (~14%), indicating a similar reproductive rate. Our findings suggest stability in the Greek sub‐population; however, additional monitoring of reproductive parameters is essential before concluding its status. We demonstrated the effectiveness of UAS‐photogrammetry in rapidly quantifying population age‐structure, including scenarios with limited or no demographic data. This technique shows promise for enhancing precision, timeliness, cost‐effectiveness and efficiency in population monitoring and informing timely conservation management decisions.
Interleukin‐1 receptor‐associated kinase 4 (IRAK4) is a critical regulator of inflammatory signalling through toll‐like receptors 4 and 7/8 in murine and human lungs
Authors: Sayers Ian , Thakker Dhruma , Billington Charlotte , Kreideweiss Stefan , Grundl Marc A. , Bouyssou Thierry , Thamm Sven , Kreuz Sebastian , Hall Ian P.
Published: August 2024

Background and Purpose

Toll‐like receptors 4 (TLR4) and TLR7/TLR8 play an important role in mediating the inflammatory effects of bacterial and viral pathogens. Interleukin‐1 receptor‐associated kinase 4 (IRAK4) is an important regulator of signalling by toll‐like receptor (TLR) and hence is a potential therapeutic target in diseases characterized by increased lung inflammatory signalling.

Experimental Approach

We used an established murine model of acute lung inflammation, and studied human lung tissue ex vivo, to investigate the effects of inhibiting IRAK4 on lung inflammatory pathways.

Key Results

We show that TLR4 stimulation produces an inflammatory response characterized by neutrophil influx and tumour necrosis factor‐α (TNF‐α) production in murine lungs and that these responses are markedly reduced in IRAK4 kinase‐dead mice. In addition, we characterize a novel selective IRAK4 inhibitor, BI1543673, and show that this compound can reduce lipopolysaccharide (LPS)‐induced airway inflammation in wild‐type mice. Additionally, BI1543673 reduced inflammatory responses to both TLR4 and TLR7/8 stimulation in human lung tissue studied ex vivo.

Conclusion and Implications

These data demonstrate a key role for IRAK4 signalling in lung inflammation and suggest that IRAK4 inhibition has potential utility to treat lung diseases characterized by inflammatory responses driven through TLR4 and TLR7/8.
Promotion Effect of Catalpol on Angiogenesis and Potential Mechanisms: A Research Based on Network Pharmacology
Authors: Ni Jin‐rong , Zhang Qun‐hu , Deng Jie‐lin , Wang Hai‐hu , Duan Yong‐chi , Zhang Cheng‐ji , Jiang Lue‐tao
Published: August 2024

Catalpol, a natural iridoid glycoside, has potential therapeutic benefits, including anti‐inflammatory and neuroprotective effects. Investigating catalpol's role in angiogenesis is critical for understanding its potential therapeutic applications, particularly in diseases where modulating angiogenesis is beneficial. This study investigates catalpol's influence on angiogenesis and its mechanisms, combining network pharmacology and in vitro experiments. The target genes corresponding to the catalpol were analyzed by SwissTargetPrediction. Then angiogenesis‐related targets were acquired from databases like GeneCards. Subsequently, the Database for Annotation, Visualization and Integrated Discovery was employed for Gene Ontology and pathway analysis, while Cytoscape visualized protein interactions. The effect of catalpol on viability and angiogenesis of HUVECs was further examined using Cell Counting Kit‐8 and angiogenesis assays. RT‐qPCR and western blot were applied to check the expression of angiogenesis‐related proteins. Totally, 312 target genes of catalpol and 823 angiogenesis‐related targets were obtained with 56 common targets leading to PPI network analysis, highlighting hub genes (AKT1, EGFR, STAT3, MAPK3, and CASP3). These hub genes were mainly enriched in lipid and atherosclerosis pathway and EGFR‐related pathway. The in vitro experimental results showed that catalpol achieved a concentration‐dependent increase in HUVECs viability. Catalpol also promoted the migration and angiogenesis of HUVECs and up‐regulated the expression of EGFR. EGFR knockdown inhibited the effect of catalpol on HUVECs. Catalpol promotes angiogenesis in HUVECs by upregulating EGFR and angiogenesis‐related proteins, indicating its potential therapeutic application in vascular‐related diseases.
Cost‐Effectiveness of Digital Health Interventions for Asthma or COPD: Systematic Review
Authors: Ferreira Marta Alexandra Martins , dos Santos Adalberto Fernandes , Sousa‐Pinto Bernardo , Taborda‐Barata Luís
Published: August 2024

Objective

Digital interventions such as remote monitoring of symptoms and physiological measurements have the potential to reduce the economic burden of asthma and chronic obstructive pulmonary disease (COPD) but their cost‐effectiveness remains unclear. This systematic review of randomised controlled trials (RCT) aims to assess whether digital health interventions can be cost‐effective in these patients.

Design

Systematic review of RCTs. Study quality was assessed using RoB2 tool.

Data Sources

Systematic search in three databases: PubMed, Scopus and Web of Science.

Eligibility Criteria

Studies were eligible if they were RCTs with health economic evaluations assessing participants with asthma and/or COPD and comparing a digital health intervention to standard of care.

Results

We included 35 RCTs, of which 21 were related to COPD, 13 to asthma and one to both diseases. Overall, studies assessed four categories of digital health interventions: (i) Electronic patient diaries (n = 4), (ii) real‐time monitoring (n = 19), (iii) teleconsultations (n = 6) and (iv) others (n = 6). Eleven studies performed a full economic evaluation analysis, while 24 studies performed a partial economic analysis. Most studies involving real‐time monitoring or teleconsultations presented economic results in favour of digital health interventions (indicating them to be cost‐effective or less expensive than the standard of care). Mixed results were obtained for electronic patient diaries. In the studies that conducted a full economic analysis, the incremental cost‐effectiveness ratio (ICER) ranged from 3530,93€/QALY and 286,369,28€/QALY. In the studies that conducted a partial economic analysis, the cost differences between the intervention group and the control group ranged from 0,12€ and 85,217,86€. Half studies with low risk of bias concluded that the intervention was economically favourable.

Conclusion

Although costs varied based on intervention type, follow‐up period and country, most studies report digital health interventions to be affordable or associated with decreased costs.

Trial Registration

PROSPERO: CRD42023439195
Brain border‐derived CXCL2+ neutrophils drive NET formation and impair vascular reperfusion following ischemic stroke
Authors: Huang Tingting , Guo Yunlu , Xie Wanqing , Yin Jiemin , Zhang Yueman , Chen Weijie , Huang Dan , Li Peiying
Published: August 2024

Background

The brain border compartments harbor a diverse population of immune cells and serve as invasion sites for leukocyte influx into the brain following CNS injury. However, how brain‐border myeloid cells affect stroke pathology remains poorly characterized.

Methods and Results

Here, we showed that ischemic stroke‐induced expansion of CXCL2+ neutrophils, which exhibit highly proinflammatory features. We tracked CXCL2+ neutrophils in vivo by utilizing a photoconvertible Kik‐GR mouse (fluorescent proteins Kikume Green Red, Kik‐GR) and found that brain‐infiltrating CXCL2+ neutrophils following ischemic stroke were mainly derived from the brain border rather than the periphery. We demonstrated that CXCL2 neutralization inhibited the formation and releasing of neutrophil extracellular traps (NETs) from in vitro cultured primary neutrophils. Furthermore, CXCL2‐neutralizing antibody treatment reduced brain infarcts and improved vascular reperfusion at day 3 postischemic stroke.

Conclusions

Collectively, brain border‐derived CXCL2+ neutrophil expansion may impair vascular reperfusion by releasing NETs following ischemic stroke.
The repeat FIT (RFIT) study: Does repeating faecal immunochemical tests provide reassurance and improve colorectal cancer detection?
Authors: Farkas Nicholas G. , Palyvos Lampros , O'Brien James W. , Yu Kai Shing , Pigott Carolyn , Whyte Martin , Jourdan Iain , Rockall Timothy , Fraser Callum G. , Benton Sally C.
Published: August 2024

Aim

Faecal immunochemical tests (FIT) are highly sensitive for colorectal cancer (CRC) detection. Little evidence exists regarding repeat FIT. The repeat FIT (RFIT) study aimed to determine whether second and third FIT provide reassurance and improve CRC or significant bowel disease (SBD) identification.

Methods

This was a prospective observational study. Patients recruited from urgent referrals returned three FIT and underwent colonoscopy. Chi‐square tests compared categorical data. Diagnostic accuracy variables (sensitivity/specificity/positive predictive value [PPV]/negative predictive value [NPV]) were calculated for one, two and three FIT (95% CI). Three negative FIT (<10 μg Hb/g of faeces [μg/g]) groups (one, two, three) were compared with positive groups (one or more FIT ≥10 μg/g). CRC and SBD detection rates were compared by strategy.

Results

A total of 460 patients (mean age: 66.8 years, 233 males and 227 females, 23 CRC, 80 SBD) were included in the study. For one, two and three negative FIT, CRC sensitivity remained static (95.7%); specificity (44.6%, 40.7% and 38.4%) and NPV decreased (99.5%, 99.4% and 99.4%). For SBD, sensitivity increased (78.8%, 83.8% and 86.3%), specificity decreased (47.4%, 43.7% and 41.6%) and NPV increased (91.4%, 92.7% and 93.5%). In one, two and three positive FIT groups, CRC detection was 8.3%,16.1% and 20.9%. CRC mean FIT was 150 μg/g, <6 μg/g for benign pathology.

Conclusions

One or more negative FIT increases the sensitivity for CRC/SBD. Repeating FIT provides greater differentiation of patients with and without CRC/SBD compared to single FIT but is associated with decreased specificity and PPV. Multiple negative FIT may offer reassurance; however, application of repeating FIT may be restricted given the associated increase in investigations.
Mesothelin CAR‐engineered NK cells derived from human embryonic stem cells suppress the progression of human ovarian cancer in animals
Authors: Liu Yanhong , Zhang Min , Shen Xiaoyan , Xia Chengxiang , Hu Fangxiao , Huang Dehao , Weng Qitong , Zhang Qi , Liu Lijuan , Zhu Yanping , Wang Lei , Hao Jie , Zhang Mengyun , Wang Tongjie , Wang Jinyong
Published: August 2024

CAR‐NK cell therapy does not require HLA matching and has minimal side effects. However, traditional methods of engineering CARs into human tissue‐derived NK cells exhibit heterogeneity, low transduction efficiency, and high manufacturing costs. Here, we provide a reliable approach for generating large‐scale and cryopreserved mesothelin (MSLN) CAR‐NK cells from human embryonic stem cells (hESCs) as an alternative cell source. We first constructed MSLN CAR‐expressing hESCs to reduce CAR engineering costs and subsequently differentiated these stem cells into MSLN CAR‐NK cells via an efficient organoid induction system. The MSLN CAR‐NK cells exhibit the typical expression patterns of activating receptors, inhibitory receptors, and effector molecules of NK cells. In the presence of tumour cells, the MSLN CAR‐NK cells show increased secretion of IFN‐γ and TNF‐α, as well as elevated CD107a expression level compared with induced NK cells. We cryopreserved the MSLN CAR‐NK cells in liquid nitrogen using a clinical‐grade freezing medium (CS10) for more than 6 months to mimic an off‐the‐shelf CAR‐NK cell product. The thawed MSLN CAR‐NK cells immediately recovered after 48–72‐h culture and effectively eliminated ovarian tumour cells, including human primary ovarian tumour cells from patients. The thawed MSLN CAR‐NK cells efficiently suppressed ovarian tumour development in vivo and prolonged the survival of tumour‐bearing mice. Our study provides insights into the clinical translation of hESC‐derived MSLN CAR‐NK cells as a promising off‐the‐shelf cell product.
Epstein–Barr Virus‐Associated Smooth Muscle Tumor After Kidney Transplantation: A French Multicenter Retrospective Study
Authors: Tardieu Laurène , Anglicheau Dany , Sberro‐Soussan Rebecca , Lemoine Mathilde , Golbin Léonard , Fourdinier Ophélie , Bruneau Julie , Charbit Marina , Meatchi Tchao , Serre Jean‐Emmanuel , Le Quintrec Moglie , Karras Alexandre , Thervet Eric , Lazareth Hélène
Published: August 2024

Background

Epstein–Barr virus (EBV) is a herpesvirus linked to nine different human tumors and lymphoproliferative disorders. Immunosuppression promotes EBV‐driven malignancies. The most frequent EBV‐induced malignancies are lymphomas and nasopharyngeal carcinoma. By promoting smooth muscle proliferation, EBV can induce EBV‐associated smooth muscle tumors (EBV‐SMT). EBV‐SMT is a rare oncological entity for which no current guideline for diagnosis or management exists. Data on posttransplant EBV‐SMT (PT‐SMT) are scarce in kidney transplant recipients.

Methods

We conducted a national multicentric retrospective study and collected cases among transplantation centers in France. Kidney transplant recipients experiencing histologically proven PT‐SMT were included. We collected data on demographic characteristics of patient, history of kidney transplantation, history of PT‐SMT, evolution of graft function, and patient survival.

Results

Eight patients were included. The median age at PT‐SMT diagnosis was 31 years (range 6.5–40). PT‐SMT occurred after a median delay of 37.8 months after transplantation (range 6–175). PT‐SMT management consisted in immunosuppressive regimen minimization in all patients. Introduction of mTOR inhibitors was performed in two patients. Four patients (50%) needed chemotherapy. Surgical resection was performed in four patients. At last follow‐up after PT‐SMT diagnosis (median 33 months (range 17–132)), five patients were considered in complete remission, and two patients had died. Two patients experienced graft rejection; two resumed dialysis (25%). All patients with available data presented with impaired graft function at last follow‐up.

Conclusion

PT‐SMT is a subacute and progressive disease during kidney transplantation. Even if the risk of developing PT‐SMT is low in kidney transplant recipients (0.07% in our cohort), PT‐SMT is associated with significant graft loss, possibly due to reduced immunosuppression. Developing guidelines could help transplantation teams better manage these patients.
The Impact of Donor‐Recipient Human Leukocyte Antigen Matching on Bronchiolitis Obliterans‐Free Survival Among Lung Transplant Recipients With Connective Tissue Diseases
Authors: Courtwright Andrew M. , Diamond Joshua M. , Sandorfi Nora , Goldberg Hilary J.
Published: August 2024

Background

The development of connective tissue disease‐associated lung diseases (CTD‐LD) occurs in association with specific human leukocyte antigens (HLA). For CTD‐LD patients who require lung transplant, it is unknown whether utilization of donor organs expressing these same HLA impacts posttransplant outcomes.

Methods

Using the Scientific Registry of Transplant Recipients, we assessed whether CTD‐LD lung transplant recipients in the United States have worse bronchiolitis obliterans (BOS)‐free survival based on the degree of donor HLA matching. This included overall degree of donor‐recipient HLA matching, donor‐recipient matching at DR loci, and recipient matching with specific donor HLA antigens associated with the development of pulmonary disease in their condition.

Results

Among 1413 patients with CTD‐ILD, highly HLA‐matched donor‐recipients did not have worse adjusted survival (hazard ratio [HR] = 0.93, 95% confidence interval [CI] = 0.58–1.51, p = 0.77). Recipients who were fully matched at HLA DR did not have worse survival (HR = 0.82, 95% CI = 0.56–1.19, p = 0.29). Finally, among individual CTD‐LD, including rheumatoid arthritis, systemic sclerosis, the idiopathic inflammatory myopathies, and systemic lupus erythematous, transplant with a donor expressing HLA antigens associated with lung manifestations in these conditions was not associated with worse BOS‐free survival.

Conclusions

Among transplant recipients with CTD‐LD, HLA donor‐recipient matching, including at the DR loci, does not result in worse BOS‐free survival. Based on these findings, there is no reason to treat these as unacceptable antigens when considering donor offers for CTD‐LD candidates.
Soundscapes and airborne laser scanning identify vegetation density and its interaction with elevation as main driver of bird diversity and community composition
Authors: Seibold Sebastian , Richter Tobias , Geres Lisa , Seidl Rupert , Martin Ralph , Mitesser Oliver , Senf Cornelius , Griem Lukas , Müller Jörg
Published: August 2024

Aim

Mountain ecosystems are hotspots of biodiversity due to their high variation in climate and habitats. Yet, above average rates of climate change and enhanced forest disturbance regimes alter local climatic conditions and vegetation structure, which should impact biodiversity. We here investigated the impact of vegetation and elevation as well as their interactions on bird communities to improve our ability to predict climate change effects on bird communities.

Location

European Alps, Germany.

Methods

We studied patterns and drivers of bird communities at 213 plots along gradients in vegetation density and elevation using autonomous sound recorders. Bird species were identified from soundscapes by Convolutional Neural Networks (BirdNET) and taxonomists.

Results

Bird diversity and community metrics were moderately to strongly correlated for data based on either identification by BirdNET or taxonomists (Pearson's r = .47–.94), and ecological findings were overall similar for both datasets. Vegetation density 1–2 m and >2 m above ground strongly affected bird diversity and community composition and mediated effects of elevation. Community composition changed with elevation more strongly in habitats with low than high vegetation density >2 m. Species numbers decreased with elevation in habitats with low vegetation density 1–2 m and >2 m above ground, but increased in habitats with high vegetation density. Overall, functional and phylogenetic diversity increased with elevation indicating lower habitat filtering, but patterns were also mediated by vegetation density.

Main Conclusions

Our results indicate that bird communities in the German Alps are determined by strong interactive effects of elevation and vegetation, underlining the importance to consider variation in vegetation in studies of biodiversity patterns along elevational gradients and under climate change. Combining remote sensing data and biodiversity monitoring based on autonomous sampling and AI‐based species identification opens new avenues for bird monitoring and research in remote areas.