bluuebunny/crossref_metadata_2025 huggingface dataset:
Structural prediction of GluN3 NMDA receptors
Authors: Liu Yunsheng , Shao Da , Lou Shulei , Kou Zengwei
Published: August 2024

N-methyl-D-aspartate (NMDA) receptors are heterotetrametric ion channels composed of two obligatory GluN1 subunits and two alternative GluN2 or GluN3 subunits, forming GluN1-N2, GluN1-N3, and GluN1-N2-N3 type of NMDA receptors. Extensive research has focused on the functional and structural properties of conventional GluN1–GluN2 NMDA receptors due to their early discovery and high expression levels. However, the knowledge of unconventional GluN1-N3 NMDA receptors remains limited. In this study, we modeled the GluN1-N3A, GluN1-N3B, and GluN1-N3A-N3B NMDA receptors using deep-learned protein-language predication algorithms AlphaFold and RoseTTAFold All-Atom. We then compared these structures with GluN1-N2 and GluN1-N3A receptor cryo-EM structures and found that GluN1-N3 receptors have distinct properties in subunit arrangement, domain swap, and domain interaction. Furthermore, we predicted the agonist- or antagonist-bound structures, highlighting the key molecular–residue interactions. Our findings shed new light on the structural and functional diversity of NMDA receptors and provide a new direction for drug development. This study uses advanced AI algorithms to model GluN1-N3 NMDA receptors, revealing unique structural properties and interactions compared to conventional GluN1-N2 receptors. By highlighting key molecular–residue interactions and predicting ligand-bound structures, our research enhances the understanding of NMDA receptor diversity and offers new insights for targeted drug development.
Extracellular purines in lung endothelial permeability and pulmonary diseases
Authors: Gerasimovskaya Evgenia , Patil Rahul S. , Davies Adrian , Maloney McKenzie E. , Simon Liselle , Mohamed Basmah , Cherian-Shaw Mary , Verin Alexander D.
Published: August 2024

The purinergic signaling system is an evolutionarily conserved and critical regulatory circuit that maintains homeostatic balance across various organ systems and cell types by providing compensatory responses to diverse pathologies. Despite cardiovascular diseases taking a leading position in human morbidity and mortality worldwide, pulmonary diseases represent significant health concerns as well. The endothelium of both pulmonary and systemic circulation (bronchial vessels) plays a pivotal role in maintaining lung tissue homeostasis by providing an active barrier and modulating adhesion and infiltration of inflammatory cells. However, investigations into purinergic regulation of lung endothelium have remained limited, despite widespread recognition of the role of extracellular nucleotides and adenosine in hypoxic, inflammatory, and immune responses within the pulmonary microenvironment. In this review, we provide an overview of the basic aspects of purinergic signaling in vascular endothelium and highlight recent studies focusing on pulmonary microvascular endothelial cells and endothelial cells from the pulmonary artery vasa vasorum. Through this compilation of research findings, we aim to shed light on the emerging insights into the purinergic modulation of pulmonary endothelial function and its implications for lung health and disease.
Lentil adaptation to drought stress: response, tolerance, and breeding approaches
Authors: Noor Md. Mahmud Al , Tahjib-Ul-Arif Md. , Alim S. M. Abdul , Islam Md. Mohimenul , Hasan Md. Toufiq , Babar Md. Ali , Hossain Mohammad Anwar , Jewel Zilhas Ahmed , Murata Yoshiyuki , Mostofa Mohammad Golam
Published: August 2024

Lentil (Lens culinaris Medik.) is a cool season legume crop that plays vital roles in food and nutritional security, mostly in the least developed countries. Lentil is often cultivated in dry and semi-dry regions, where the primary abiotic factor is drought, which negatively impacts lentil growth and development, resulting in a reduction of yield. To withstand drought-induced multiple negative effects, lentil plants evolved a variety of adaptation strategies that can be classified within three broad categories of drought tolerance mechanisms (i.e., escape, avoidance, and tolerance). Lentil adapts to drought by the modulation of various traits in the root system, leaf architecture, canopy structure, branching, anatomical features, and flowering process. Furthermore, the activation of certain defensive biochemical pathways as well as the regulation of gene functions contributes to lentil drought tolerance. Plant breeders typically employ conventional and mutational breeding approaches to develop lentil varieties that can withstand drought effects; however, little progress has been made in developing drought-tolerant lentil varieties using genomics-assisted technologies. This review highlights the current understanding of morpho-physiological, biochemical, and molecular mechanisms of lentil adaptation to drought stress. We also discuss the potential application of omics-assisted breeding approaches to develop lentil varieties with superior drought tolerance traits.
Enhancing drought resistance in Pinus tabuliformis seedlings through root symbiotic fungi inoculation
Authors: Xu Lingjie , He Jiadong , Meng Yu , Zheng Yanyan , Lu Bin , Zhang Jiawen , Zhou Yong
Published: August 2024

Background

Drought constitutes a major abiotic stress factor adversely affecting plant growth and productivity. Plant-microbe symbiotic associations have evolved regulatory mechanisms to adapt to environmental stress conditions. However, the interactive effects of different fungi on host growth and stress tolerance under drought conditions remain unclear.

Objective

This study explored the effects of varying polyethylene glycol (PEG-6000) concentrations (0%, 15%, 25%, and 35%) on the growth and physiological responses of two ectomycorrhizal fungi (Suillus granulatus (Sg) and Pisolithus tinctorius (Pt)) and two dark septate endophytes (Pleotrichocladium opacum (Po) and Pseudopyrenochaeta sp. (Ps)) isolated from the root system of Pinus tabuliformis. Specifically, the study aimed to evaluate six inoculation treatments, including no inoculation (CK), single inoculations with Sg, Pt, Po, Ps, and a mixed inoculation (Sg: Pt : Po: Ps = 1:1:1:1), on the growth and physiological characteristics of P. tabuliformis seedlings under different water regimes: well-watered at 70% ± 5%, light drought at 50% ± 5%, and severe drought at 30% ± 5% of the maximum field water holding capacity.

Results

All four fungi exhibited the capacity to cope with drought stress by enhancing antioxidant activities and regulating osmotic balance. Upon successful root colonization, they increased plant height, shoot biomass, root biomass, total biomass, and mycorrhizal growth response in P. tabuliformis seedlings. Under drought stress conditions, fungal inoculation improved seedling drought resistance by increasing superoxide dismutase and catalase activities, free proline and soluble protein contents, and promoting nitrogen and phosphorus uptake. Notably, mixed inoculation treatments significantly enhanced antioxidant capacity, osmotic adjustment, and nutrient acquisition abilities, leading to superior growth promotion effects under drought stress compared to single inoculation treatments.

Conclusion

All four fungi tolerated PEG-induced drought stress, with increased antioxidant enzyme activities and osmotic adjustment substances and they promoted the growth and enhanced drought resistance of P. tabuliformis seedlings.
Plant competition cues activate a singlet oxygen signaling pathway in Arabidopsis thaliana
Authors: Berardi Nicole , Amirsadeghi Sasan , Swanton Clarence J.
Published: August 2024

Oxidative stress responses of Arabidopsis to reflected low red to far-red signals (R:FR ≈ 0.3) generated by neighboring weeds or an artificial source of FR light were compared with a weed-free control (R:FR ≈1.6). In the low R:FR treatments, induction of the shade avoidance responses (SAR) coincided with increased leaf production of singlet oxygen (1O2). This 1O2 increase was not due to protochlorophyllide accumulation and did not cause cell death. Chemical treatments, however, with 5-aminolevulinic acid (the precursor of tetrapyrrole biosynthesis) and glutathione (a quinone A reductant) enhanced cell death and growth inhibition. RNA sequencing revealed that transcriptome responses to the reflected low R:FR light treatments minimally resembled previously known Arabidopsis1O2 generating systems that rapidly generate 1O2 following a dark to light transfer. The upregulation of only a few early 1O2 responsive genes (6 out of 1931) in the reflected low R:FR treatments suggested specificity of the 1O2 signaling. Moreover, increased expression of two enzyme genes, the SULFOTRANSFERASE ST2A (ST2a) and the early 1O2-responsive IAA-LEUCINE RESISTANCE (ILR)-LIKE6 (ILL6), which negatively regulate jasmonate level, suggested that repression of bioactive JAs may promote the shade avoidance (versus defense) and 1O2 acclimation (versus cell death) responses to neighboring weeds.
From developmental theory to effective training: long-term and transfer effects of promoting the quantity–to–number word linkage in first-graders at risk for mathematical difficulties
Authors: Ennemoser Marco , Sinner Daniel , Nguyen Linda , Krajewski Kristin
Published: August 2024

Introduction

The model of quantity–to–number word linkage (QNL model) identifies relevant milestones in the process of early numerical acquisition and describes a developmental sequence that can guide the fostering of foundational mathematical abilities in at-risk children. While there is substantial evidence for the predictive value of the quantity-number competencies (QNC) described by the model, evidence supporting the preventive potential of interventions targeting these QNC is so far largely restricted to short-term effects. Findings regarding their long-term preventive impact, especially in terms of transfer to mathematical school achievement, are still limited. This quasi-experimental study aimed to address this gap by evaluating the long-term transfer effects of an intervention program that is strictly derived from the QNL model of mathematical development [QNL training; in German “Mengen, zählen, Zahlen” (MZZ)].

Methods

We assessed the quantity-number competencies of 575 first-graders and identified 119 of them as being at risk for mathematical learning difficulties, who were then assigned to three experimental conditions. Sixty one children received 12 sessions of the QNL training, while 30 underwent training in inductive reasoning. Another 28 children served as a control group, receiving no specific intervention.

Results and Discussion

Multi-level analyses confirmed both significant short-and long-term effects in the specifically trained quantity–number competencies as well as transfer effects on subsequent mathematical school achievement. In accordance with previous findings, transfer effects of the QNL training on mathematical school achievement were not yet evident immediately after the intervention but turned out to be significant after a delay of 6 months and remained stable even 15 months after training. Effect sizes ranged from d = 0.32 to d = 1.12. These findings both underscore the preventive potential of interventions that are strictly driven by developmental theory and, conversely, support the theoretical assumptions of the QNL model.
The relationship between physical exercise and sense of social fairness among college students: the chain-mediated role of perceived social support and life satisfaction
Authors: Sui Xiaodong , Zhao Bin , Na Di , Liu Jianwu , Zhang Qi
Published: August 2024

Background

The development of a stable society is closely linked to a prevalent sense of social fairness. Participating in physical activities, which are inherently social, plays a crucial role in fostering mental stability within social contexts.

Objective

This study aims to examine how physical exercise influences the sense of social fairness among college students, focusing on the potential mediating effects of perceived social support and life satisfaction.

Methods

The study surveyed 496 Chinese college students using several scales: the Physical Activity Rating Scale-3 (PARS-3), Perceived Social Support Scale (PSSS), Satisfaction with Life Scale (SWLS), and Social Justice Scale (SJS).

Results

(1) A positive correlation was found between physical exercise and sense of social fairness (r = 0.151, p < 0.01). A significant direct effect of physical exercise on sense of social fairness was also observed (β = 0.151, t = 3.971, p < 0.01). (2) Physical exercise was a positive predictor of perceived social support (β = 0.113, t = 4.062, p < 0.01), which in turn positively influenced both life satisfaction (β = 0.333, t = 18.047, p < 0.01) and sense of social fairness (β = 0.485, t = 6.931, p < 0.01). Additionally, life satisfaction had a positive effect on sense of social fairness (β = 0.431, t = 3.247, p < 0.01). (3) Both perceived social support and life satisfaction significantly mediated the relationship between physical exercise and sense of social fairness through two pathways: physical exercise → perceived social support → sense of social fairness (mediating effect: 0.055); and physical exercise → perceived social support → life satisfaction → sense of social fairness (mediating effect: 0.016).

Conclusion

(1) Physical exercise enhances both perceived social support and the sense of social fairness among college students, suggesting that it not only directly contributes to an enhanced sense of social fairness but also fosters supportive social relationships. (2) The influence of physical exercise on the sense of social fairness operates both directly and indirectly through the mediating roles of perceived social support and, sequentially, life satisfaction.
Associations between sugar-sweetened beverages consumption, duration of physical exercise, and depressive symptoms among Tibetan university students at high altitude
Authors: Yang Yang , Liu Jia , Dai Duo
Published: August 2024

Background

Depressive symptoms have become a public health issue of common concern in countries all over the world, and have many negative impacts on university students’ study and life. Depressive symptoms are influenced by many factors, including sugar-sweetened beverages (SSBs) consumption and duration of physical activity. However, no study has been conducted on the association between sugar-sweetened beverage consumption, duration of physical exercise, and depressive symptoms among Tibetan university students at high altitudes.

Methods

In this study, a self-assessment survey of SSBs consumption, duration of physical exercise, and depressive symptoms was conducted on 6,259 (2,745 boys, 43.86%) Tibetan university students aged 19–22 years in Lhasa and Ganzi areas, China, using stratified whole population sampling. The associations were also analyzed using one-way analysis of variance, binary logistic regression analysis, and ordered logistic regression analysis in the generalised linear model.

Results

The proportions of mild depression symptoms, moderate depression symptoms, and major depressive symptoms among Tibetan boys university students in high-altitude areas of China were 18.0, 22.9, and 1.5%, respectively; the proportions of girls students were 20.1, 21.9, and 1.5%, respectively, 1.5%, and the differences in the detection rates of depressive symptoms between sex were statistically significant (χ2 value = 14.253, p < 0.01). Ordered logistic regression analyses showed that using duration of physical exercise >60 min/d and SSBs ≤1 times/week as the reference group, the duration of physical exercise <30 min/d and SSBs ≥5 times/week groups had the highest risk of developing depressive symptoms was the highest risk (OR = 6.98, 95% CI: 5.05–9.65; p < 0.001).

Conclusion

This study confirmed that there was a positive association between SSBs consumption and depressive symptoms and a negative association between the duration of physical exercise and depressive symptoms among Tibetan university students at high altitudes in China. In the future, SSBs consumption should be effectively controlled and the duration of physical exercise should be increased to reduce the occurrence of depressive symptoms and promote the physical and mental health of Tibetan university students in high-altitude areas.
Mitigating the risk of inflammatory type primary graft dysfunction by applying an integrated approach to assess, modify and match risk factors in lung transplantation
Authors: Braithwaite Sue A. , Berg Elize M. , de Heer Linda M. , Jennekens Jitte , Neyrinck Arne , van Hooijdonk Elise , Luijk Bart , Buhre Wolfgang F. F. A. , van der Kaaij Niels P.
Published: August 2024

Long-term outcome following lung transplantation remains one of the poorest of all solid organ transplants with a 1- and 5-year survival of 85% and 59% respectively for adult lung transplant recipients and with 50% of patients developing chronic lung allograft dysfunction (CLAD) in the first 5 years following transplant. Reducing the risk of inflammatory type primary graft dysfunction (PGD) is vital for improving both short-term survival following lung transplantation and long-term outcome due to the association of early inflammatory-mediated damage to the allograft and the risk of CLAD. PGD has a multifactorial aetiology and high-grade inflammatory-type PGD is the result of cumulative insults that may be incurred in one or more of the three variables of the transplantation continuum: the donor lungs, the recipient and intraoperative process. We set out a conceptual framework which uses a fully integrated approach to this transplant continuum to attempt to identify and, where possible, modify specific donor, recipient and intraoperative PGD risk with the goal of reducing inflammatory-type PGD risk for an individual recipient. We also consider the concept and risk-benefit of matching lung allografts and recipients on the basis of donor and recipient PGD-risk compatibility. The use of ex vivo lung perfusion (EVLP) and the extended preservation of lung allografts on EVLP will be explored as safe, non-injurious EVLP may enable extensive inflammatory testing of specific donor lungs and has the potential to provide a platform for targeted therapeutic interventions on lung allografts.
Antiviral activity of SAFER®, a commercial acidifying desiccant powder, against African swine fever virus
Authors: Trinh Thi Bich Ngoc , Lazenec Elodie , Lai Thi Ngoc Ha , Matard-Mann Maria , Phat Luong Tan , Morvan Anne , Delahaye Anne-Cecile , Collén Pi Nyvall , Nguyen Thi Lan , Le Van Phan
Published: August 2024

African swine fever (ASF) is one of the deadliest swine diseases, causing significant economic losses, threatening food security, and limiting pig production in affected countries. In the absence of an effective ASF vaccine, prevention and control of ASF depend mainly on effective biosecurity measures. In this study, the efficacy of SAFER®, a powdered disinfectant containing clay, an acid complex, and the active ingredient thyme essential oil, was tested against the ASF virus. The results showed that ASFV isolate (VNUA/HY/ASF1/Vietnam/2019) was inactivated by 3.5 and 5 Log10HAD50/ml after 20 and 120 min of treatment with SAFER®, respectively. When body fluids contaminated with ASFV, such as blood, saliva, urine, and feces, were treated with SAFER® for 20 min, the ASFV titer was reduced by 1.6, 2.2, 2.0, and 2.2 Log10HAD50/ml, respectively.
Predictive Modelling of Diabetes Risk in Population Groups Defined by Socioeconomic and Lifestyle Factors in Canada: A Cross-Sectional Study
Authors: Lu Katherine , Kornas Kathy , Rosella Laura C.
Published: August 2024

Objectives

This study modelled diabetes risk for population groups in Canada defined by socioeconomic and lifestyle characteristics and investigated inequities in diabetes risk using a validated population risk prediction algorithm.

Methods

We defined population groups, informed by determinants of health frameworks. We applied the Diabetes Population Risk Tool (DPoRT) to 2017/2018 Canadian Community Health Survey data to predict 10-year diabetes risk and cases across population groups. We modelled a preventive intervention scenario to estimate reductions in diabetes for population groups and impacts on the inequity in diabetes risk across income and education.

Results

The population group with at least one lifestyle and at least one socioeconomic/structural risk factor had the highest estimated 10-year diabetes risk and number of new cases. When an intervention with a 5% relative risk reduction was modelled for this population group, diabetes risk decreased by 0.5% (females) and 0.7% (males) and the inequity in diabetes risk across income and education levels was reduced.

Conclusion

Preventative interventions that address socioeconomic and structural risk factors have potential to reduce inequities in diabetes risk and overall diabetes burden.
Post-Kidney Transplant Cancer: A Real-World Retrospective Analysis From a Single Italian Center
Authors: Re Sartò Giulia Vanessa , Alfieri Carlo , Cosmai Laura , Brigati Emilietta , Campise Mariarosaria , Regalia Anna , Verdesca Simona , Molinari Paolo , Pisacreta Anna Maria , Pirovano Marta , Nardelli Luca , Gallieni Maurizio , Castellano Giuseppe
Published: August 2024

We describe the epidemiology of cancer after kidney transplantation (KTx), investigating its risk factors and impact on therapeutic management and survival in KTx recipients (KTRs). The association between modification of immunosuppressive (IS) therapy after cancer and survival outcomes was analyzed. We collected data from 930 KTRs followed for 7 [1–19] years. The majority of KTRs received KTx from a deceased donor (84%). In total, 74% of patients received induction therapy with basiliximab and 26% with ATG. Maintenance therapy included steroids, calcineurin inhibitors, and mycophenolate. Patients with at least one cancer (CA+) amounted to 19%. NMSC was the most common tumor (55%). CA+ were older and had a higher BMI. Vasculitis and ADPKD were more prevalent in CA+. ATG was independently associated with CA+ and was related to earlier cancer development in survival and competing risk analyses (p = 0.01 and <0.0001; basiliximab 89 ± 4 vs. ATG 40 ± 4 months). After cancer diagnosis, a significant prognostic impact was derived from the shift to mTOR inhibitors compared to a definitive IS drug suspension (p = 0.004). Our data confirm the relevance of cancer as a complication in KTRs with ATG as an independent risk factor. An individualized choice of IS to be proposed at the time of KTx is crucial in the prevention of neoplastic risk. Finally, switching to mTORi could represent an important strategy to improve patient survival.
Refining the Definition and Typologies of Entrepreneurship in Africa: A Systematic Review
Authors: Chakuzira Wellington , Okoche John Michael Maxel , Mkansi Marcia
Published: August 2024

This paper aims to describe a highly pervasive and under-reported context-specific phenomenon of entrepreneurship, specifically in light of the rise in different types of entrepreneurial activities in Africa. Explicably, this paper accepts that entrepreneurship typologies are different across the globe. Utilising the Preferred Reporting Items for Systematic Reviews and Meta-Analysis (PRISMA), a total of 1230 articles were discovered from Scopus, Web of Science, and ProQuest databases. Subsequently, a screening for suitability was conducted, resulting in the exclusion of 1200 articles based on criteria such as publication year, jurisdiction, and abstract review. Ultimately, 30 journal articles were imported into Zotero Reference Manager and Atlas for further examination. This study found that a state of entrepreneurship mishap exists in Africa. The utilisation of a uniform approach in supporting entrepreneurs is identified as another challenge. Lastly, this study introduces nine novel entrepreneur typologies: Lifepreneurs, Part-timers, Hobbypreneurs, Entremployees, Empreneurs, Techpreneurs, Carte-blanche, Profeneurs, and Smartpreneurs. These typologies serve as a conceptual framework for categorising various entrepreneurial initiatives based on a true reflection of the African entrepreneurial ecosystem, attributes, and key success factors. Theoretically, our paper fills a gap in the academic literature regarding the study of entrepreneurship in developing countries and its classifications. Practically, this paper could offer African policymakers a blueprint for supporting startups at a local level. Significantly, this work stands out for providing a classification system that captures the authentic nature of entrepreneurial undertakings within African economies.
Yield Prediction Models for Rice Varieties Using UAV Multispectral Imagery in the Amazon Lowlands of Peru
Authors: Goigochea-Pinchi Diego , Justino-Pinedo Maikol , Vega-Herrera Sergio S. , Sanchez-Ojanasta Martín , Lobato-Galvez Roiser H. , Santillan-Gonzales Manuel D. , Ganoza-Roncal Jorge J. , Ore-Aquino Zoila L. , Agurto-Piñarreta Alex I.
Published: August 2024

Rice is cataloged as one of the most widely cultivated crops globally, providing food for a large proportion of the global population. Integrating Geographic Information Systems (GISs), such as unmanned aerial vehicles (UAVs), into agricultural practices offers numerous benefits. UAVs, equipped with imaging sensors and geolocation technology, enable precise crop monitoring and management, enhancing yield and efficiency. However, Peru lacks sufficient experience with the application of these technologies, making them somewhat unfamiliar in the context of modern agriculture. In this study, we conducted experiments involving four distinct rice varieties (n = 24) at various stages of growth to predict yield using vegetation indices (VIs). A total of nine VIs (NDVI, GNDVI, ReCL, CIgreen, MCARI, SAVI, CVI, LCI, and EVI) were assessed across four dates: 88, 103, 116, and 130 days after sowing (DAS). Pearson correlation analysis, principal component analysis (PCA), and multiple linear regression were used to build prediction models. The results showed a general prediction model (including all the varieties) with the best performance at 130 days after sowing (DAS) using NDVI, EVI, and SAVI, with a coefficient of determination (adjusted-R2 = 0.43). The prediction models by variety showed the best performance for Esperanza at 88 DAS (adjusted-R2 = 0.94) using EVI as the vegetation index. The other varieties showed their best performance using different indices at different times: Capirona (LCI and CIgreen, 130 DAS, adjusted-R2 = 0.62); Conquista Certificada (MCARI, 116 DAS, R2 = 0.52); and Conquista Registrada (CVI and LCI, 116 DAS, adjusted-R2 = 0.79). These results provide critical information for optimizing rice crop management and support the use of unmanned aerial vehicles (UAVs) to inform timely decision making and mitigate yield losses in Peruvian agriculture.
State Evaluation of Electrical Equipment in Substations Based on Data Mining
Authors: Dang Ding , Liu Yi , Lee Seon-Keun
Published: August 2024

This paper explores the combination of a data mining-based state evaluation method for electrical equipment in substations, analyzing the effectiveness and accuracy. First, a Gaussian mixture model is applied to fit all raw data of electrical equipment. The Expectation Maximization algorithm summarizes the data distribution characteristics and identifies outliers. The a priori algorithm is then employed for data mining to derive frequent itemsets and association rules between equipment quality and measurement data. For new equipment samples, conditional probabilities of each feature are independently calculated and combined to classify and evaluate equipment quality. The results suggest that equipment reliability in smart substations can be inferred from historical and real-time operational data using improved association rule algorithms and Naive Bayes classifiers. Finally, the proposed method was applied to analyze statistical data from a 110 kV substation of a power supply company. The states prediction accuracy exceeded 95% when compared with actual equipment quality. The effectiveness evaluation metrics demonstrated that this method outperforms single-category algorithms in terms of accuracy and discrimination ability.
Assessment of Perceived Indoor Air Quality in the Classrooms of Slovenian Primary Schools and Its Association with Indoor Air Quality Factors, for the Design of Public Health Interventions
Authors: Galičič An , Rožanec Jan , Kukec Andreja , Medved Sašo , Eržen Ivan
Published: August 2024

From a public health perspective, it is necessary to improve indoor air quality (IAQ) in schools. This study aims to assess the state of perceived IAQ in Slovenian school classrooms and its association with the selected IAQ factors to improve the understanding of perceived IAQ for designing public health interventions aimed to improve IAQ in schools. A national cross-sectional study was performed in all 454 Slovenian primary schools in the school year 2019/2020. The questionnaires were filled out by the 3rd-grade teachers with the support of the caretakers. Teachers rated the IAQ in the classroom as the worst in winter. We found that the teachers’ perceived IAQ in the classroom is statistically significantly associated with the micro location of the school and some of the IAQ factors. Poor IAQ is associated with reduced manual airing of classrooms due to the thermal comfort of the occupants. Interventions should be aimed at improving occupants’ adaptive behaviors to increase the frequency of natural ventilation in classrooms.
An Intrinsically Explainable Method to Decode P300 Waveforms from EEG Signal Plots Based on Convolutional Neural Networks
Authors: Ail Brian Ezequiel , Ramele Rodrigo , Gambini Juliana , Santos Juan Miguel
Published: August 2024

This work proposes an intrinsically explainable, straightforward method to decode P300 waveforms from electroencephalography (EEG) signals, overcoming the black box nature of deep learning techniques. The proposed method allows convolutional neural networks to decode information from images, an area where they have achieved astonishing performance. By plotting the EEG signal as an image, it can be both visually interpreted by physicians and technicians and detected by the network, offering a straightforward way of explaining the decision. The identification of this pattern is used to implement a P300-based speller device, which can serve as an alternative communication channel for persons affected by amyotrophic lateral sclerosis (ALS). This method is validated by identifying this signal by performing a brain–computer interface simulation on a public dataset from ALS patients. Letter identification rates from the speller on the dataset show that this method can identify the P300 signature on the set of 8 patients. The proposed approach achieves similar performance to other state-of-the-art proposals while providing clinically relevant explainability (XAI).
Two Different Immune Profiles Are Identified in Sentinel Lymph Nodes of Early-Stage Breast Cancer
Authors: Ribeiro Joana Martins , Mendes João , Gante Inês , Figueiredo-Dias Margarida , Almeida Vânia , Gomes Ana , Regateiro Fernando Jesus , Regateiro Frederico Soares , Caramelo Francisco , Silva Henriqueta Coimbra
Published: August 2024

In the management of early-stage breast cancer (BC), lymph nodes (LNs) are typically characterised using the One-Step Nucleic Acid Amplification (OSNA) assay, a standard procedure for assessing subclinical metastasis in sentinel LNs (SLNs). The pivotal role of LNs in coordinating the immune response against BC is often overlooked. Our aim was to improve prognostic information provided by the OSNA assay and explore immune-related gene signatures in SLNs. The expression of an immune gene panel was analysed in SLNs from 32 patients with Luminal A early-stage BC (cT1-T2 N0). Using an unsupervised approach based on these expression values, this study identified two clusters, regardless of the SLN invasion: one evidencing an adaptive anti-tumoral immune response, characterised by an increase in naive B cells, follicular T helper cells, and activated NK cells; and another with a more undifferentiated response, with an increase in the activated-to-resting dendritic cells (DCs) ratio. Through a protein—protein interaction (PPI) network, we identified seven immunoregulatory hub genes: CD80, CD40, TNF, FCGR3A, CD163, FCGR3B, and CCR2. This study shows that, in Luminal A early-stage BC, SLNs gene expression studies enable the identification of distinct immune profiles that may influence prognosis stratification and highlight key genes that could serve as potential targets for immunotherapy.
Trends and Age–Period–Cohort Effect on the Incidence of Early-Onset Colorectal Cancer (20–44 Years) from 1990 to 2021 in the United States
Authors: Aldhaleei Wafa A. , Wallace Michael B. , Bhagavathula Akshaya Srikanth
Published: August 2024

The incidence of early-onset colorectal cancer (EO-CRC) in individuals under 50 years old is rapidly increasing in the United States. This study aims to evaluate EO-CRC incidence rates using data from the Global Burden of Disease Study (GBD) 2021, providing insights into trends from 1990 to 2021. We employed an age–period–cohort (APC) model analysis to estimate the effects of age, time period, and birth cohort on EO-CRC incidence. Our findings indicate that the number of EO-CRC cases rose from 6256 (95% UI: 6059–6456) in 1990 to 9311 (95% UI: 8859–9744) in 2021, a 49% increase from 1990 to 2021. The age-standardized incidence rate per 100,000 population increased by 34% during this period. The net drift in females (0.22%, 95% CI: 0.20–0.24) was slightly higher than in males (0.21%, 95% CI: 0.19–0.23) (p = 0.45). The APC analysis revealed that being over 25 years old, the period from 2005–2021, and being born after 1983 negatively impacted EO-CRC incidence rates, with a sharp rise after 2000 and a reduction among females from 2017 to 2021. Our study highlights the need for targeted prevention strategies and further research to understand these trends.
Development of Ex Vivo Analysis for Examining Cell Composition, Immunological Landscape, Tumor and Immune Related Markers in Non-Small-Cell Lung Cancer
Authors: Ufimtseva Elena G. , Gileva Margarita S. , Kostenko Ruslan V. , Kozlov Vadim V. , Gulyaeva Lyudmila F.
Published: August 2024

NSCLC is a very aggressive solid tumor, with a poor prognosis due to post-surgical recurrence. Analysis of the specific tumor and immune signatures of NSCLC samples is a critical step in prognostic evaluation and management decisions for patients after surgery. Routine histological assays have some limitations. Therefore, new diagnostic tools with the capability to quickly recognize NSCLC subtypes and correctly identify various markers are needed. We developed a technique for ex vivo isolation of cancer and immune cells from surgical tumor and lung tissue samples of patients with NSCLC (adenocarcinomas and squamous cell carcinomas) and their examination on ex vivo cell preparations and, parallelly, on histological sections after Romanovsky–Giemsa and immunofluorescent/immunochemical staining for cancer-specific and immune-related markers. As a result, PD-L1 expression was detected for some patients only by ex vivo analysis. Immune cell profiling in the tumor microenvironment revealed significant differences in the immunological landscapes between the patients’ tumors, with smokers’ macrophages with simultaneous expression of pro- and anti-inflammatory cytokines, neutrophils, and eosinophils being the dominant populations. The proposed ex vivo analysis may be used as an additional diagnostic tool for quick examination of cancer and immune cells in whole tumor samples and to avoid false negatives in histological assays.
Evolving and Improving the Sustainability of Molecular Tumor Boards: The Value and Challenges
Authors: Bartels Marius , Chibaudel Benoist , Dienstmann Rodrigo , Lehtiö Janne , Piccolo Alberta , Michielin Olivier , O’Kane Grainne , Pruneri Giancarlo
Published: August 2024

The increasing volume of information for cancer care, and the evolution of molecularly guided therapies, have increased the need for molecular tumor boards (MTBs), which can integrate such data into personalized treatment plans to improve patient outcomes. However, recommendations for improving the sustainability of MTBs are lacking. A diverse committee of MTB experts was assembled (February–March 2023), with extensive experience in sustainability in healthcare ecosystems. The aim was to identify MTB-related hurdles throughout the patient journey and develop a general framework for MTBs to operate on larger scales locally, nationally, and internationally. The committee identified ten key pillars for sustainable and scalable MTBs, including technical solutions for data integration and visualization, interoperability, learning loops, clinical trial access, legal considerations, criteria for patient testing, decision standardization, making MTBs official bodies for treatment decisions, local leaders, and international networks. The need for scalable frameworks at academic and community levels was recognized, along with integrating MTBs into national health systems to enhance sustainability and ensure optimal treatment decisions. Irrespective of the health ecosystem, the sustainability and scalability of MTBs are essential. Our framework provides guidelines to address this and to help MTBs evolve towards integrated, essential components of the oncology healthcare system.
Implication of Capillary Morphogenesis Gene 2 (CMG2) in the Disease Progression and Peritoneal Metastasis of Pancreatic Cancer
Authors: Fang Ziqian , Bunston Carly , Xu Yali , Ruge Fiona , Sui Laijian , Liu Ming , Al-Sarireh Bilal , Griffiths Paul , Murphy Kate , Pugh Matthew R. , Hao Chunyi , Jiang Wen G. , Ye Lin
Published: August 2024

Capillary morphogenesis gene 2 (CMG2) mediates cell–matrix interactions to facilitate cell adhesion and migration. CMG2 has been implicated in the disease progression of breast cancer, prostate cancer and gastric cancer. The present study aims to determine the role of CMG2 in the disease progression and peritoneal metastasis of pancreatic cancer. Pancreatic tumour samples were collected from Peking University Cancer Hospital. CMG2 expression was determined using quantitative PCR. After the creation of knockdown and overexpression of CMG2 in pancreatic cancer cells, the effect of CMG2 on several cell functions and adhesion to the peritoneum was examined. Potential pathways regulated by CMG2 were found via proteomics analysis and drug tests. CMG2 was upregulated in pancreatic cancer tissues and associated with a poor prognosis. CMG2 was increased in metastatic lesions and those primary tumours with distant metastases. CMG2 promotes cell–cell, cell–matrix and cell–hyaluronic acid adhesion, which may be mediated by epidermal growth factor receptor (EGFR) and focal adhesion kinase (FAK) pathway activation.
Visual Evidence for the Recruitment of Four Enzymes with RNase Activity to the Bacillus subtilis Replication Forks
Authors: Hinrichs Rebecca , Graumann Peter L.
Published: August 2024

Removal of RNA/DNA hybrids for the maturation of Okazaki fragments on the lagging strand, or due to misincorporation of ribonucleotides by DNA polymerases, is essential for all types of cells. In prokaryotic cells such as Escherichia coli, DNA polymerase 1 and RNase HI are supposed to remove RNA from Okazaki fragments, but many bacteria lack HI-type RNases, such as Bacillus subtilis. Previous work has demonstrated in vitro that four proteins are able to remove RNA from RNA/DNA hybrids, but their actual contribution to DNA replication is unclear. We have studied the dynamics of DNA polymerase A (similar to Pol 1), 5′->3′ exonuclease ExoR, and the two endoribonucleases RNase HII and HIII in B. subtilis using single-molecule tracking. We found that all four enzymes show a localization pattern similar to that of replicative DNA helicase. By scoring the distance of tracks to replication forks, we found that all four enzymes are enriched at DNA replication centers. After inducing UV damage, RNase HIII was even more strongly recruited to the replication forks, and PolA showed a more static behavior, indicative of longer binding events, whereas RNase HII and ExoR showed no response. Inhibition of replication by 6(p hydroxyphenylazo)-uracil (HPUra) demonstrated that both RNase HII and RNase HIII are directly involved in the replication. We found that the absence of ExoR increases the likelihood of RNase HIII at the forks, indicating that substrate availability rather than direct protein interactions may be a major driver for the recruitment of RNases to the lagging strands. Thus, B. subtilis replication forks appear to be an intermediate between E. coli type and eukaryotic replication forks and employ a multitude of RNases, rather than any dedicated enzyme for RNA/DNA hybrid removal.
Efficacy of Vitamin B12 and Adenosine Triphosphate in Enhancing Skin Radiance: Unveiled with a Drug–Target Interaction Deep Learning-Based Model
Authors: Chun Hyeyeon , Lee Hyejin , Kim Jongwook , Yeo Hyerin , Hyung Kyongeun , Song Dayoung , Kim Moonju , Jun Seung-Hyun , Kang Nae-Gyu
Published: August 2024

Skin radiance is crucial for enhancing facial attractiveness and is negatively affected by factors like hyperpigmentation and aging-related changes. Current treatments often lack comprehensive solutions for improving skin radiance. This study aimed to develop a cosmetic formula that enhances skin radiance by reducing hyperpigmentation and improving skin regeneration by targeting specific receptors—the endothelin receptor type B (EDNRB) for hyperpigmentation and the adiponectin receptor 1 (ADIPOR1) for sagging and wrinkles. To achieve this, we used artificial intelligence technologies to screen and select ingredients with an affinity for EDNRB and ADIPOR1. Vitamin B12 (VitB12) was identified as a molecule that targets EDNRB, which is involved in melanogenesis. Adenosine triphosphate (ATP) targets ADIPOR1, which is associated with skin regeneration. VitB12 successfully inhibited intracellular calcium elevation and melanogenesis induced by endothelin-1. In contrast, ATP increased the mRNA expression of collagen and elastin and promoted wound healing. Moreover, the VitB12 and ATP complex significantly increased the expression of hyaluronan synthases, which are crucial for skin hydration. Furthermore, in human participants, the application of the VitB12 and ATP complex to one-half of the face significantly improved skin radiance, elasticity, and texture. Our findings provide valuable insights for the development of skincare formulations.
A Review of High-Speed Turning of AISI 4340 Steel with Minimum Quantity Lubrication (MQL)
Authors: Abdul Rahman Haniff , Jouini Nabil , Ghani Jaharah A. , Rasani Mohammad Rasidi Mohammad
Published: August 2024

AISI 4340 is a medium-carbon low-alloy steel that has gained distinctive attention due to its advanced properties including high strength, high toughness, and heat resistance. This has led to its commercial usage in a wide variety of industries such as construction, automotive, and aerospace. AISI 4340 is usually machined in a hardened state through a hard-turning process, which results in high heat generation, accelerated tool wear, low productivity, and poor surface quality. The application of high-speed machining helps improve the material removal rate and surface finish quality, yet the elevated temperature at the cutting zone still poses problems to the tool’s lifespan. Apart from using advanced cutting tool materials, which is costly, researchers have also explored various cooling methods to tackle the heat problem. This paper presents a review of a sustainable cooling method known as minimum quantity lubrication (MQL) for its application in the high-speed turning of AISI 4340 steel. This study is centered on high-speed turning and the application of MQL systems in machining AISI 4340 steel. It has been observed that the hard part turning of materials with a hardness exceeding 45 HRC offers advantages such as improved accuracy and tighter tolerances compared to traditional grinding methods. However, this process leads to increased temperatures, and MQL proves to be a viable alternative to dry conditions. Challenges in optimizing MQL performance include fluid penetration and lubrication effectiveness.
Influence of Scanning Paths on the Weld Pool Behavior, Microstructure, and Mechanical Property of AA2060 Al-Li Alloy Joints by Laser Beam Oscillation Welding
Authors: Song Yanbo , Liang Ying , Liu Hongbing , Lin Luchan , Gao Yanfeng , Zhang Hua , Yang Jin
Published: August 2024

In this paper, the laser beam oscillation welding (LBOW) was utilized to weld a 2 mm thick AA2060 aluminum-lithium (Al-Li) alloy plate. The weld pool behaviors under three scanning paths (pure laser, O-shaped, and ∞-shaped) were investigated. It was observed that the O-shaped scanning path resulted in the most stable welding process. In addition, the weld macroscopic formation, microstructure, and mechanical property between different paths were studied. The results showed that pure laser and ∞-shaped patterns produced welding defects such as spatters and collapse during the welding process, while the O-shaped pattern exhibited good macroscopic formation at varying laser powers. The O-shaped pattern promoted the finest grain in the weld center and reduced the heat input during the welding process. The equiaxed grain zone (EQZ) width of the O-shaped pattern is the smallest compared to the other two patterns at high laser power. In addition to this, the O-shaped pattern could effectively reduce the porosity in the weld. When an O-shaped scanning pattern was adopted at the ideal laser power parameter of 3000 W, the microhardness of the weld center increased by approximately 5.6% compared to pure laser mode.
Immunotherapy-Based Combinations in First-Line Urothelial Cancer: A Systematic Review and Individual Patient Data (IPD) Meta-Analysis
Authors: Di Civita Mattia Alberto , Torchia Andrea , Santini Daniele , Marinelli Daniele , Magro Virginia , Cerro Marianna , Pappalardo Laura , Maltese Giulia , Santamaria Fiorenza , Zacco Luca , Buccilli Dorelsa , Dehghanpour Ailin , Speranza Iolanda , Sciarra Alessandro , Panebianco Valeria , Roberto Michela
Published: August 2024

Introduction. Platinum-based chemotherapy represents the standard of care (SoC) for the first-line treatment of advanced urothelial carcinoma (mUC). The benefit of adding immune checkpoint inhibitors (ICIs) to platinum-based chemotherapy was recently investigated. We performed an individual patient data (IPD) meta-analysis of phase 3 clinical trials comparing ICI-based treatments. Methods. A systematic literature search was conducted on the MEDLINE and CENTRAL databases. The results were filtered by including only reports on clinical trials or randomized clinical trials from 2018 to 2023, including 3047 patients from four clinical trials (EV302, CHECKMATE-901, IMVIGOR130, KEYNOTE-361). An IPD meta-analysis was performed by reconstructing IPD from Kaplan–Meier curves. The primary endpoints were overall survival (OS) and progression-free survival (PFS) of Pembrolizumab + EV compared to experimental arms of the other trials of immunotherapy + chemotherapy. Results. The OS analysis showed an advantage of IPD from EV302 vs. all the other trials. For EV302 vs. KEYNOTE-361, the HR was 0.51; for EV302 vs. IMVIGOR130, the HR was 0.47; and for EV302 vs. CHECKMATE-901, the HR was 0.66 (CI 95% 0.51–0.85). In the PFS analysis, the EV302 arm showed a statistically significant advantage compared to CHECKMATE-901 (HR 0.66) and versus IMVIGOR130 (HR 0.51). Limitations: By using reconstructed IPD curves, it was not possible to adjust patient-level covariates, and the heterogeneity of the included population may have affected the pooled results. Conclusions: The EV302 experimental arm showed better OS and PFS when compared to the other immunochemotherapy combinations. An immunochemotherapy combination strategy at the beginning of treatment in mUC seems to be superior in terms of OS and PFS compared to platinum-based chemotherapy alone. EV–Pembrolizumab resulted to have better outcomes compared to avelumab, rather than other immunochemotherapy combinations. However, given the heterogeneity of these studies, a longer follow up and prospective trials are needed to confirm these data.