bluuebunny/crossref_metadata_2025 huggingface dataset:
Deriving Verified Vehicle Trajectories from LiDAR Sensor Data to Evaluate Traffic Signal Performance
Authors: Saldivar-Carranza Enrique D. , Bullock Darcy M.
Published: July 2024

Advances and cost reductions in Light Detection and Ranging (LiDAR) sensor technology have allowed for their implementation in detecting vehicles, cyclists, and pedestrians at signalized intersections. Most LiDAR use cases have focused on safety analyses using its high-fidelity tracking capabilities. This study presents a methodology to transform LiDAR data into localized, verified, and linear-referenced trajectories to derive Purdue Probe Diagrams (PPDs). The following four performance measures are then derived from the PPDs: arrivals on green (AOG), split failures (SF), downstream blockage (DSB), and control delay level of service (LOS). Noise is filtered for each detected vehicle by iteratively projecting each sample’s future location and keeping the subsequent sample that is close enough to the estimated destination. Then, a far side is defined for the analyzed intersection’s movement to linear reference sampled trajectories and to remove those that do not cross through that point. The technique is demonstrated by using over one hour of LiDAR data at an intersection in Utah to derive PPDs. Signal performance is then estimated from these PPDs. The results are compared to those obtained from comparable PPDs derived from connected vehicle (CV) trajectory data. The generated PPDs from both data sources are similar, with relatively modest differences of 1% AOG and a 1.39 s/veh control delay. Practitioners can use the presented methodology to estimate trajectory-based traffic signal performance measures from their deployed LiDAR sensors. The paper concludes by recommending that unfiltered LiDAR data are used for deriving PPDs and extending the detection zones to cover the largest observed queues to improve performance estimation reliability.
Carbon Market for Climate Projects in Russia: An Overview of Nature-Based and Technological Carbon Offsets
Authors: Nevzorova Tatiana
Published: July 2024

Climate projects can become one of the key tools for decarbonization in Russia. They have powerful potential in terms of solving the problems of reducing emissions and increasing the absorption of greenhouse gases, as well as monetization potential for businesses. Despite the geopolitical crisis and sanctions imposed on Russia, certain opportunities for implementing climate projects have remained accessible. This study aims to provide a comprehensive analysis of the current status, including the regulations and approved methodologies, prospects, and challenges for climate projects in the carbon market in Russia. It also offers an overview of international carbon market mechanisms and analyses the advantages and disadvantages of the nature-based and technological solutions of climate projects for carbon sequestration. This, in turn, can facilitate the realization of future strategies for realizing the bigger potential of Russian climate projects in the domestic and international carbon markets. This research also provides up-to-date data on the current situation of the carbon market in Russia.
Analysis of Codon Usage Bias in Chloroplast Genomes of Dryas octopetala var. asiatica (Rosaceae)
Authors: Ling Lizhen , Zhang Shudong , Yang Tao
Published: July 2024

Dryas octopetala var. asiatica, a dwarf shrub belonging to the Rosaceae family and native to Asia, exhibits notable plasticity in photosynthesis in response to temperature variations. However, the codon usage patterns and factors influencing them in the chloroplast genome of this species have not yet been documented. This study sequenced and assembled the complete genome of D. octopetala var. asiatica. The annotated genes in the chloroplast genome were analyzed for codon composition through multivariate statistical methods including a neutrality plot, a parity rule 2 (PR2) bias plot, and an effective number of codons (ENC) plot using CodonW 1.4.2 software. The results indicated that the mean GC content of 53 CDSs was 38.08%, with the average GC content at the third codon base position being 27.80%, suggesting a preference for A/U(T) at the third codon position in chloroplast genes. Additionally, the chloroplast genes exhibited a weak overall codon usage bias (CUB) based on ENC values and other indicators. Correlation analysis showed a significant negative correlation between ENC value and GC2, an extremely positive correlation with GC3, but no correlation with GC1 content. These findings highlight the importance of the codon composition at the third position in influencing codon usage bias. Furthermore, our analysis indicated that the CUB of the chloroplast genome of D. octopetala var. asiatica was primarily influenced by natural selection and other factors. Finally, this study identified UCA, CCU, GCU, AAU, GAU, and GGU as the optimal codons. These results offer a foundational understanding for genetic modification and evolutionary dynamics of the chloroplast genome of D. octopetala var. asiatica.
Domain Adaptation from Drilling to Geophysical Data for Mineral Exploration
Authors: Shin Youngjae
Published: July 2024

This study utilizes domain adaptation to enhance the integration of diverse geoscience datasets, aiming to improve the identification of ore bodies. Traditional mineral exploration methods often face challenges in merging different geoscience data types, which leads to models that do not perform well across varying domains. Domain adaptation is a deep learning strategy aimed at adapting a model developed in one domain (source) to perform well in a different domain (target). To adapt models trained on detailed, labeled drilling data (source) to interpret broader, unlabeled geophysical data (target), Domain-Adversarial Neural Networks (DANNs) were applied, chosen for their robust performance in scenarios where the target domain does not provide labels. This approach was indirectly validated through the minimal overlap between regions identified as candidate ore and borehole locations marked as host rocks, with qualitative validation provided by t-Distributed Stochastic Neighbor Embedding (t-SNE) visualizations showing improved data integration across domains.
Association of Overweight and Obesity with Impaired Executive Functioning in Mexican Adolescents: The Importance of Inhibitory Control
Authors: Ruiz-Molina Yatzeny Guadalupe , Herrera-Ávila Josué , Espinosa-Juárez Josué Vidal , Esquinca-Avilés Héctor Armando , Tejas-Juárez Juan Gabriel , Flores-Guillén Elena , Morales-Martínez Luis Alberto , Briones-Aranda Alfredo , Jiménez-Ceballos Betsabé , Sierra-Ramírez José Alfredo , Cruz-Trujillo Refugio
Published: July 2024

Overweight and obesity are major public health issues worldwide, including in Mexico, particularly among adolescents. This study aimed to analyze the associations between nutritional status and impaired executive function (EF) in Mexican adolescents. A case–control study was conducted with 98 male and female adolescents, categorized into normal weight and overweight/obese groups based on body mass index. EF was assessed using the BANFE-2 test. The prevalence of overweight and obesity was 54.3%. The EF assessment revealed that 82.45% of the overweight/obese group exhibited mild-to-severe impairment, compared to only 36.58% in the normal weight group (X2 = 21.69, p < 0.0001). In the inhibitory control assessment, adolescents with overweight and obesity performed worse than their normal-weight counterparts. Specifically, females with overweight/obesity scored lower than females with normal weight on the risk–benefit processing test. The risk of severe EF impairment significantly increased with the presence of overweight/obesity (OR = 7.8, p < 0.0001). These findings indicate that EF, particularly inhibitory control and risk–benefit processing, is impaired in adolescents with overweight or obesity.
Blood Microbiota and Its Products: Mechanisms of Interference with Host Cells and Clinical Outcomes
Authors: Santacroce Luigi , Charitos Ioannis Alexandros , Colella Marica , Palmirotta Raffaele , Jirillo Emilio
Published: July 2024

In healthy conditions, blood was considered a sterile environment until the development of new analytical approaches that allowed for the detection of circulating bacterial ribosomal DNA. Currently, debate exists on the origin of the blood microbiota. According to advanced research using dark field microscopy, fluorescent in situ hybridization, flow cytometry, and electron microscopy, so-called microbiota have been detected in the blood. Conversely, others have reported no evidence of a common blood microbiota. Then, it was hypothesized that blood microbiota may derive from distant sites, e.g., the gut or external contamination of blood samples. Alteration of the blood microbiota’s equilibrium may lead to dysbiosis and, in certain cases, disease. Cardiovascular, respiratory, hepatic, kidney, neoplastic, and immune diseases have been associated with the presence of Gram-positive and Gram-negative bacteria and/or their products in the blood. For instance, lipopolysaccharides (LPSs) and endotoxins may contribute to tissue damage, fueling chronic inflammation. Blood bacteria can interact with immune cells, especially with monocytes that engulf microorganisms and T lymphocytes via spontaneous binding to their membranes. Moreover, LPSs, extracellular vesicles, and outer membrane vesicles interact with red blood cells and immune cells, reaching distant organs. This review aims to describe the composition of blood microbiota in healthy individuals and those with disease conditions. Furthermore, special emphasis is placed on the interaction of blood microbiota with host cells to better understand disease mechanisms.
Stationary Steam Engines in Puerto Rico and the U.S. Virgin Islands
Authors: Nance R. Damian
Published: July 2024

In Puerto Rico and each of the U.S. Virgin Islands, stationary steam engines survive on their original foundations and stand in testament to the long history of sugar production in the American territories of the Caribbean. In total, six beam engines, seven horizontal engines, one vertical engine, and a compound engine exist on the islands in various states of preservation, many amid the ruins of the plantations (haciendas) whose output they made possible. The whereabouts of an eighth horizontal engine recorded in 1976 remains unknown. Most were imported from Britain in the second half of the nineteenth century, but at least one is of American build. These machines not only provide unique examples of the adaption of steam technology to the needs of nineteenth-century sugar production but are also lasting symbols of an industry that once dominated the economy of these islands and remain deeply entwined in their history.
Acute Toxicity of Malathion, Permethrin, and Roundup on the Tropical Freshwater Shrimp Xiphocaris elongata (Guérin-Méneville, 1855)
Authors: Torres-Pérez Wesley X. , Pérez-Reyes Omar
Published: July 2024

Urban and agricultural runoffs can transport contaminants and pesticides into freshwater ecosystems, particularly in the developing tropics. For instance, organophosphate and pyrethroids pesticides, such as Roundup, Malathion, and Permethrin, have been found in tropical streams. The uncontrolled application of these pesticides has become a growing concern due to their adverse effects on various non-targeted organisms. Unfortunately, most studies have focused on a few selected model species, ignoring the effects on other non-target organisms, which may play an important role in tropical lotic ecosystems. In addition, the biological characteristics of aquatic crustaceans, including their morphology, physiology, and behavior, make them susceptible to toxic chemicals. For this reason, this study used the widely distributed freshwater shrimp Xiphocaris elongata as a model organism to determine the acute toxicity of Permethrin, Malathion, and Roundup. Our results show that the proportion of mortality of X. elongata in each concentration group became progressively higher as the concentration of exposure increased. We also found that the synthetic pyrethroid Permethrin was the most toxic pesticide tested, with a median lethal concentration (LC50) value for 96 h of 3.96 × 10−6 µg·L−1, followed by organophosphate Malathion (8.87 µg·L−1) and Roundup (748.92 µg·L−1). Experiments with this freshwater shrimp showed a good control performance and reproducibility for the tested pesticides. This study demonstrated that X. elongata is a suitable test organism that can be a representative bioindicator of pesticide toxicity in tropical streams.
Mental Health, Declining Physical Activity and Social Connection during Transitions into Fatherhood in the UK
Authors: Lovett Emily , Smith Andy
Published: July 2024

This paper addresses an under-explored area of sociologically oriented health research, namely, the mental health and physical activity (PA) experiences of new fathers. Drawing upon responses to an online qualitative survey from 32 fathers, aged 18 or over, and living in the UK, we show how the decline in these fathers’ overall PA was associated with poor mental health and the changing constraints that characterised their increasingly complex networks of interdependence. These constraints corresponded with shifts in fathers’ PA engagement from team sports towards individualised, flexible, and more recreationally oriented lifestyle activities like running and the gym. Fathers’ engagement in these activities appeared to exacerbate the complex feelings of guilt and isolation that they already encountered as new fathers. These experiences were simultaneously associated with feelings of shame associated with being insufficiently active and fearing judgement about their engagement in fathering responsibilities. The paper has important policy implications, highlighting the need for tailored support for new fathers in the perinatal period, and implications for practice, suggesting that co-produced community-based PA programmes are potentially effective settings for engaging new fathers in PA and promoting their mental health.
Assessing the Impact of Non-Exhaust Emissions on the Asthmatic Airway (IONA) Protocol for a Randomised Three-Exposure Crossover Study
Authors: Scales James , Hajmohammadi Hajar , Priestman Max , McIlvenna Luke C. , de Boer Ingrid E. , Hassan Haneen , Tremper Anja H. , Chen Gang , Wood Helen E. , Green David C. , Katsouyanni Klea , Mudway Ian S. , Griffiths Christopher
Published: July 2024

Background: People living with asthma are disproportionately affected by air pollution, with increased symptoms, medication usage, hospital admissions, and the risk of death. To date, there has been a focus on exhaust emissions, but traffic-related air pollution (TRAP) can also arise from the mechanical abrasion of tyres, brakes, and road surfaces. We therefore created a study with the aim of investigating the acute impacts of non-exhaust emissions (NEEs) on the lung function and airway immune status of asthmatic adults. Methods: A randomised three-condition crossover panel design will expose adults with asthma using a 2.5 h intermittent cycling protocol in a random order at three locations in London, selected to provide the greatest contrast in the NEE components within TRAP. Lung function will be monitored using oscillometry, fractional exhaled nitric oxide, and spirometry (the primary outcome is the forced expiratory volume in one second). Biomarkers of inflammation and airborne metal exposure will be measured in the upper airway using nasal lavage. Symptom responses will be monitored using questionnaires. Sources of exhaust and non-exhaust concentrations will be established using source apportionment via the positive matrix factorisation of high-time resolution chemical measures conducted at the exposure sites. Discussion: Collectively, this study will provide us with valuable information on the health effects of NEE components within ambient PM2.5 and PM10, whilst establishing a biological mechanism to help contextualise current epidemiological observations.
Spectroscopic Study of a Novel Binaphthyl Amine Fluorescent Probe for Chiral Recognition of D/L-Lysine
Authors: Wu Liji , Lu Xiangyu , Cai Wentao , Zou Yajun , Zhang Xiaoyu , Yang Jialiang , Zhao Gang
Published: July 2024

Lysine plays a crucial role in promoting development, enhancing immune function, and improving the function of central nervous system tissues. The two configurational isomers of amino acids have significantly different effects. Currently, methods for chiral recognition of lysine have been reported; however, previous detection methods have drawbacks such as expensive equipment and complicated detection processes. Fluorescence analysis, on the other hand, boasts high sensitivity, strong selectivity, and simple operation. In this study, we synthesized four novel Binaphthyl-Amine (BINAM)-based fluorescent probes capable of specifically identifying the L-configuration of lysine among the twenty amino acids that constitute human proteins. The enantiomeric fluorescence enhancement ratio (ef or ΔIL/ΔID) reached up to 15.29, demonstrating high enantioselectivity. In addition, we assessed the probe’s recognition capabilities under varying pH levels, reaction times, and metal ion conditions, along with its limit of detection (LOD) and quantum yield. Our results suggest that this probe serves as a highly stable tool for the detection of chiral lysine.
In Vitro Antiviral Activity of Kalanchoe daigremontiana Extract against Human Herpesvirus Type 1
Authors: Chodkowski Marcin , Nowak Sylwia , Janicka Martyna , Sobczak Marcin , Granica Sebastian , Bańbura Marcin W. , Krzyzowska Malgorzata , Cymerys Joanna
Published: July 2024

Plant polyphenols possess diverse bioactivities, including antiviral activity against a broad spectrum of viruses. Here, we investigated the virucidal properties of an Kalanchoe daigremontiana extract using an in vitro model of human herpesvirus type 1 (HHV-1) infection. Chromatographic analysis indicated that the extract of Kalanchoe daigremontiana is rich in various compounds, among which are polyphenols with virucidal activity confirmed in the literature. We found that Kalanchoe daigremontiana extract shows an ability to prevent HHV-1 infection by direct inhibition of the virus attachment, penetration, and blocking of infection when used in pretreatment or post-entry treatment. Our results indicate that Kalanchoe daigremontiana extract may be a good candidate drug against HHV-1, both as a substance to prevent infection and to treat an already ongoing infection. Our findings illustrate that Kalanchoe daigremontiana could be a potential new candidate for clinical consideration in the treatment of HHV-1 infection alone or in combination with other therapeutics.
Enhancing Dendritic Cell Cancer Vaccination: The Synergy of Immune Checkpoint Inhibitors in Combined Therapies
Authors: Zanotta Serena , Galati Domenico , De Filippi Rosaria , Pinto Antonio
Published: July 2024

Dendritic cell (DC) cancer vaccines are a promising therapeutic approach, leveraging the immune system to fight tumors. These vaccines utilize DCs’ ability to present tumor-associated antigens to T cells, triggering a robust immune response. DC vaccine development has progressed through three generations. The first generation involved priming DCs with tumor-associated antigens or messenger RNA outside the body, showing limited clinical success. The second generation improved efficacy by using cytokine mixtures and specialized DC subsets to enhance immunogenicity. The third generation used blood-derived DCs to elicit a stronger immune response. Clinical trials indicate that cancer vaccines have lower toxicity than traditional cytotoxic treatments. However, achieving significant clinical responses with DC immunotherapy remains challenging. Combining DC vaccines with immune checkpoint inhibitors (ICIs), such as anticytotoxic T-lymphocyte Antigen 4 and antiprogrammed death-1 antibodies, has shown promise by enhancing T-cell responses and improving clinical outcomes. These combinations can transform non-inflamed tumors into inflamed ones, boosting ICIs’ efficacy. Current research is exploring new checkpoint targets like LAG-3, TIM-3, and TIGIT, considering their potential with DC vaccines. Additionally, engineering T cells with chimeric antigen receptors or T-cell receptors could further augment the antitumor response. This comprehensive strategy aims to enhance cancer immunotherapy, focusing on increased efficacy and improved patient survival rates.
Identification of Apple Flower Development-Related Gene Families and Analysis of Transcriptional Regulation
Authors: Mei Chuang , Li Xianguo , Yan Peng , Feng Beibei , Mamat Aisajan , Wang Jixun , Li Ning
Published: July 2024

Apple (Malus domestica Borkh.) stands out as a globally significant fruit tree with considerable economic importance. Nonetheless, the orchard production of ‘Fuji’ apples faces significant challenges, including delayed flowering in young trees and inconsistent annual yields in mature trees, ultimately resulting in suboptimal fruit yield due to insufficient flower bud formation. Flower development represents a pivotal process influencing plant adaptation to environmental conditions and is a crucial determinant of successful plant reproduction. The three gene or transcription factor (TF) families, C2H2, DELLA, and FKF1, have emerged as key regulators in plant flowering regulation; however, understanding their roles during apple flowering remains limited. Consequently, this study identified 24 MdC2H2, 6 MdDELLA, and 6 MdFKF1 genes in the apple genome with high confidence. Through phylogenetic analyses, the genes within each family were categorized into three distinct subgroups, with all facets of protein physicochemical properties and conserved motifs contingent upon subgroup classification. Repetitive events between these three gene families within the apple genome were elucidated via collinearity analysis. qRT-PCR analysis was conducted and revealed significant expression differences among MdC2H2-18, MdDELLA1, and MdFKF1-4 during apple bud development. Furthermore, yeast two-hybrid analysis unveiled an interaction between MdC2H2-18 and MdDELLA1. The genome-wide identification of the C2H2, DELLA, and FKF1 gene families in apples has shed light on the molecular mechanisms underlying apple flower bud development.
How to Survive without Water: A Short Lesson on the Desiccation Tolerance of Budding Yeast
Authors: Robison Zoe L. , Ren Qun , Zhang Zhaojie
Published: July 2024

Water is essential to all life on earth. It is a major component that makes up living organisms and plays a vital role in multiple biological processes. It provides a medium for chemical and enzymatic reactions in the cell and is a major player in osmoregulation and the maintenance of cell turgidity. Despite this, many organisms, called anhydrobiotes, are capable of surviving under extremely dehydrated conditions. Less is known about how anhydrobiotes adapt and survive under desiccation stress. Studies have shown that morphological and physiological changes occur in anhydrobiotes in response to desiccation stress. Certain disaccharides and proteins, including heat shock proteins, intrinsically disordered proteins, and hydrophilins, play important roles in the desiccation tolerance of anhydrobiotes. In this review, we summarize the recent findings of desiccation tolerance in the budding yeast Saccharomyces cerevisiae. We also propose that the yeast under desiccation could be used as a model to study neurodegenerative disorders.
Novel Brassinosteroid Analogues with 3,6 Dioxo Function, 24-Nor-22(S)-Hydroxy Side Chain and p-Substituted Benzoate Function at C-23—Synthesis and Evaluation of Plant Growth Effects
Authors: Jorquera Sebastián , Soto Mauricio , Díaz Katy , Nuñez María , Cuellar Mauricio A. , Olea Andrés F. , Espinoza-Catalán Luis
Published: July 2024

Brassinosteroids (BRs) are an important group of polyhydroxylated naturally occurring steroidal phytohormones found in the plant kingdom in extremely low amounts. Due to the low concentrations in which these compounds are found, much effort has been dedicated to synthesizing these compounds or their structural analogs using natural and abundant sterols. In this work, we report the synthesis of new brassinosteroid analogs obtained from hyodeoxycholic acid, with a 3,6 dioxo function, 24-Nor-22(S)-hydroxy side chain and p-substituted benzoate function at C-23. The plant growth activities of these compounds were evaluated by two different bioassays: rice lamina inclination test (RLIT) and BSI. The results show that BRs’ analog with p-Br (compound 41f) in the aromatic ring was the most active at 1 × 10−8 M in the RLIT and BSI assays. These results are discussed in terms of the chemical structure and nature of benzoate substituents at the para position. Electron-withdrawing and size effects seems to be the most important factor in determining activities in the RLIT assay. These results could be useful to propose a new structural requirement for bioactivity in brassinosteroid analogs.
Mutual Inhibition of Antithrombin III and SARS-CoV-2 Cellular Attachment to Syndecans: Implications for COVID-19 Treatment and Vaccination
Authors: Hudák Anett , Pusztai Dávid , Letoha Annamária , Letoha Tamás
Published: July 2024

Antithrombin III (ATIII) is a potent endogenous anticoagulant that binds to heparan sulfate proteoglycans (HSPGs) on endothelial cells’ surfaces. Among these HSPGs, syndecans (SDCs) are crucial as transmembrane receptors bridging extracellular ligands with intracellular signaling pathways. Specifically, syndecan-4 (SDC4) has been identified as a key receptor on endothelial cells for transmitting the signaling effects of ATIII. Meanwhile, SDCs have been implicated in facilitating the cellular internalization of SARS-CoV-2. Given the complex interactions between ATIII and SDC4, our study analyzed the impact of ATIII on the virus entry into host cells. While ATIII binds to all SDC isoforms, it shows the strongest affinity for SDC4. SDCs’ heparan sulfate chains primarily influence ATIII’s SDC attachment, although other parts might also play a role in ATIII’s dominant affinity toward SDC4. ATIII significantly reduces SARS-CoV-2′s cellular entry into cell lines expressing SDCs, suggesting a competitive inhibition mechanism at the SDC binding sites, particularly SDC4. Conversely, the virus or its spike protein decreases the availability of SDCs on the cell surface, reducing ATIII’s cellular attachment and hence contributing to a procoagulant environment characteristic of COVID-19.
Controlled Hypoxia Acutely Prevents Physical Inactivity-Induced Peripheral BDNF Decline
Authors: Duderstadt Yves , Schreiber Stefanie , Burtscher Johannes , Schega Lutz , Müller Notger G. , Brigadski Tanja , Braun-Dullaeus Rüdiger C. , Leßmann Volkmar , Müller Patrick
Published: July 2024

Brain-derived neurotrophic factor (BDNF) is a crucial mediator of neuronal plasticity. Here, we investigated the effects of controlled normobaric hypoxia (NH) combined with physical inactivity on BDNF blood levels and executive functions. A total of 25 healthy adults (25.8 ± 3.3 years, 15 female) were analyzed in a randomized controlled cross-over study. Each intervention began with a 30 min resting phase under normoxia (NOR), followed by a 90 min continuation of NOR or NH (peripheral oxygen saturation [SpO2] 85–80%). Serum and plasma samples were collected every 15 min. Heart rate and SpO2 were continuously measured. Before and after each exposure, cognitive tests were performed and after 24 h another follow-up blood sample was taken. NH decreased SpO2 (p < 0.001, ηp2 = 0.747) and increased heart rate (p = 0.006, ηp2 = 0.116) significantly. The 30-min resting phase under NOR led to a significant BDNF reduction in serum (p < 0.001, ηp2 = 0.581) and plasma (p < 0.001, ηp2 = 0.362). Continuation of NOR further significantly reduced BDNF after another 45 min (p = 0.018) in serum and after 30 min (p = 0.040) and 90 min (p = 0.005) in plasma. There was no significant BDNF decline under NH. A 24 h follow-up examination showed a significant decline in serum BDNF, both after NH and NOR. Our results show that NH has the potential to counteract physical inactivity-induced BDNF decline. Therefore, our study emphasizes the need for a physically active lifestyle and its positive effects on BDNF. This study also demonstrates the need for a standardized protocol for future studies to determine BDNF in serum and plasma.
The Induction of G2/M Phase Cell Cycle Arrest and Apoptosis by the Chalcone Derivative 1C in Sensitive and Resistant Ovarian Cancer Cells Is Associated with ROS Generation
Authors: Salanci Šimon , Vilková Mária , Martinez Lola , Mirossay Ladislav , Michalková Radka , Mojžiš Ján
Published: July 2024

Ovarian cancer ranks among the most severe forms of cancer affecting the female reproductive organs, posing a significant clinical challenge primarily due to the development of resistance to conventional therapies. This study investigated the effects of the chalcone derivative 1C on sensitive (A2780) and cisplatin-resistant (A2780cis) ovarian cancer cell lines. Our findings revealed that 1C suppressed cell viability, induced cell cycle arrest at the G2/M phase, and triggered apoptosis in both cell lines. These effects are closely associated with generating reactive oxygen species (ROS). Mechanistically, 1C induced DNA damage, modulated the activity of p21, PCNA, and phosphorylation of Rb and Bad proteins, as well as cleaved PARP. Moreover, it modulated Akt, Erk1/2, and NF-κB signaling pathways. Interestingly, we observed differential effects of 1C on Nrf2 levels between sensitive and resistant cells. While 1C increased Nrf2 levels in sensitive cells after 12 h and decreased them after 48 h, the opposite effect was observed in resistant cells. Notably, most of these effects were suppressed by the potent antioxidant N-acetylcysteine (NAC), underscoring the crucial role of ROS in 1C-induced antiproliferative activity. Moreover, we suggest that modulation of Nrf2 levels can, at least partially, contribute to the antiproliferative effect of chalcone 1C.
Associations between Microglia and Astrocytic Proteins and Tau Biomarkers across the Continuum of Alzheimer’s Disease
Authors: Doroszkiewicz Julia , Kulczyńska-Przybik Agnieszka , Dulewicz Maciej , Mroczko Jan , Borawska Renata , Słowik Agnieszka , Zetterberg Henrik , Hanrieder Jörg , Blennow Kaj , Mroczko Barbara
Published: July 2024

Recent investigations implicate neuroinflammatory changes, including astrocyte and microglia activation, as crucial in the progression of Alzheimer’s disease (AD) Thus, we compared selected proteins reflecting neuroinflammatory processes to establish their connection to AD pathologies. Our study, encompassing 80 subjects with (n = 42) AD, (n = 18) mild cognitive impairment (MCI) and (n = 20) non-demented controls compares the clinical potential of tested molecules. Using antibody-based methods, we assessed concentrations of NGAL, CXCL-11, sTREM1, and sTREM2 in cerebrospinal fluid (CSF). Proinflammatory proteins, NGAL, and CXCL-11 reached a peak in the early stage of the disease and allowed for the identification of patients with MCI. Furthermore, the concentration of the anti-inflammatory molecule sTREM2 was highest in the more advanced stage of the disease and permitted differentiation between AD and non-demented controls. Additionally, sTREM2 was biochemically linked to tau and pTau in the AD group. Notably, NGAL demonstrated superior diagnostic performance compared to classical AD biomarkers in discriminating MCI patients from controls. These findings suggest that proteins secreted mainly through microglia dysfunction might play not only a detrimental but also a protective role in the development of AD pathology.
Technology-Driven Intergenerational Physical Activity Intervention: An Instrumental Case Study
Authors: Knight Rachel L. , Chalabaev Aïna , Mackintosh Kelly A. , McNarry Melitta A. , Hudson Joanne
Published: July 2024

Intergenerational contact offers an under-explored strategic approach to challenging age stereotypes and positively influencing health behaviors in older adults and children. It is postulated that through the application of the constructs of Contact Theory, an effective platform for change could be established. Using an instrumental case study, the experiential effects of the intergenerational contact phenomenon were pragmatically explored from the perspective of a single familial dyad (61-year-old woman; 9-year-old boy). Semi-structured interviews were conducted with each participant, both during and following engagement with a remote, 12-week, technology-driven physical activity intervention focused on using daily step counts (acquired via any activity of their choice, using physical activity trackers) to collaboratively complete virtual walk routes during the COVID-19 pandemic. Through reflexive thematic analysis and interpretation of the data in line with the study’s aim and propositions, four core themes were identified: Reciprocal Encounter; Opportunity for Reflection and Re-evaluation; Platform for Change; and COVID-19. In addition to the perceived positive effects on targeted health outcomes (physical activity, sedentary behavior, health-related quality of life), facilitating intergenerational contact through virtual methods could also, through opportunities to nurture and build relationships, challenge age stereotypes.
Understanding Gastric GIST: From Pathophysiology to Personalized Treatment
Authors: Moga Doru-Florian-Cornel , Vlădoiu Gabriela , Frățilă Anca-Maria , Dan Andreea-Alina , Popa Daniel , Oprea Valentin
Published: July 2024

Background: Gastric gastrointestinal stromal tumors (GISTs) represent a subset of gastrointestinal tumors predominantly found in the stomach. Despite their rarity, these tumors carry significant implications for patient health and management. GISTs are potentially malignant tumors with unpredictable progression. They originate from the interstitial cells of Cajal, which are positioned between the intramural neurons and the smooth muscle cells of the digestive tract. These tumors are characterized primarily by mutations in the c-Kit gene, as well as other mutations such as those in the platelet-derived growth factor receptor alpha (PDGFRA) gene. Methods: Our comprehensive search across five databases initially yielded 2976 articles. After eliminating 197 duplicates, we screened the titles and abstracts of 2779 articles, excluding 2692 for not meeting the inclusion criteria. During the full-text screening, 16 more articles were excluded. Ultimately, 71 papers met the inclusion criteria and were included in our analysis. Results: Due to differences in study designs, inclusion criteria for patients, and reported outcomes, a meta-analysis was not conducted. The accurate diagnosis of GIST is established through histopathological examination and immunohistochemistry. Histopathologically, GISTs are classified into three main types: spindle cell, epithelioid, and mixed. The therapeutic management of GIST involves surgery, endoscopic treatment, and chemotherapy. Conclusions: The prognosis for GIST patients depends on various factors, including risk category, disease stage, applied treatments, and recurrence post-treatment. A significant recent advancement comes from artificial intelligence, which can be increasingly involved in both the diagnosis and treatment of this tumor.
Treatment Outcomes of Patients with Orbital Inflammatory Diseases: Should Steroids Still Be the First Choice?
Authors: Al-Ghazzawi Karim , Neumann Inga , Knetsch Mareile , Chen Ying , Wilde Benjamin , Bechrakis Nikolaos E. , Eckstein Anja , Oeverhaus Michael
Published: July 2024

Objective: To clarify the therapy response in orbital inflammatory diseases (OID), we analyzed the treatment effects of steroid therapy, the use of disease-modifying antirheumatic drugs (DMARDS), and biologicals in our tertiary referral center cohort. Methods: We collected the clinical and demographic data of all patients treated for non-specific orbital inflammation (NSOI) (n = 111) and IgG4-ROD (n = 13), respectively at our center from 2008 to 2020 and analyzed them with descriptive statistics. NSOI were sub-grouped according to the location into either idiopathic dacryoadenitis (DAs) (n = 78) or typical idiopathic orbital myositis (n = 32). Results: Mean age at first clinical manifestation was significantly different between subgroups (IOI: 49.5 ± 18, IgG4-ROD: 63.2 ± 14, p = 0.0171). Among all examined OID, 63 patients (50%) achieved full remission (FR) with corticosteroids (NSOI 53%/IgG4-ROD 31%). In contrast, classic myositis showed a significantly higher response (76%). Disease-modifying drugs (DMARDS) for myositis accomplished only 33% FR (NSOI 57%) and 66% did not respond sufficiently (NSOI 43%). The biologic agent (Rituximab) was significantly more efficient: 19 of 23 patients (82%) achieved full remission and only 4 (17%) did not respond fully and needed orbital irradiation or orbital decompressive surgery.
Developments in the Use of Indocyanine Green (ICG) Fluorescence in Colorectal Surgery
Authors: Khalafi Shayan , Botero Fonnegra Cristina , Reyes Ana , Hui Vanessa W.
Published: July 2024

Indocyanine Green (ICG) has significantly advanced minimally invasive surgery. It is widely recognized for its ability to visualize blood vessel patency in real-time across various surgical specialties. While its primary use in colorectal surgery is to evaluate anastomoses for leaks, numerous other applications have been documented in the literature. In this review, we aim to explore both established and emerging applications of ICG fluorescence in colorectal surgery, with the goal of improving patient outcomes. This includes preoperative tumor marking and the detection of metastatic disease. Some applications, such as lymphatic mapping, require further research to determine their impact on clinical practices. Conversely, others, like the intraoperative localizations of ureters, necessitate additional procedures and are not yet widely accepted by the surgical community. However, the development of alternative compounds could offer better solutions. Future research should focus on areas like quantitative ICG and protocol standardization in prospective multicenter studies.
Clinical and Genetic Characterization of a Cohort of Small-for-Gestational-Age Patients: Cost-Effectiveness of Whole-Exome Sequencing and Effectiveness of Treatment with GH
Authors: Arroyo-Ruiz Ramón , Urbano-Ruiz Cristina , García-Berrocal María Belén , Marcos-Vadillo Elena , Isidoro-García María , Martín-Alonso M. Montserrat , Bajo-Delgado Ana Fe , Prieto-Matos Pablo , López-Siguero Juan Pedro
Published: July 2024

Background/Objectives: Develop a clinical and genetic characterization, in a group of small-for-gestational-age (SGA) patients who did not experience catch-up growth Methods: In an ambispective cohort study with (SGA) patients. These patients received one treatment with growth hormone (GH) over 14 years. This study analyzes their response to treatment and conducts a genetic analysis in order to identify cases with specific phenotypic and auxological characteristics, defined as presenting two or more dysmorphic traits and/or a stature below −3 SDS (standard deviation score). Whole-exome sequencing (WES) was performed on selected patients. Results: Forty-four SGA patients were examined, with an average age of 6.4 (2.49) years and an initial size of −3.3 SDS. The pubertal growth was 24.1 (5.2) cm in boys and 14.7 (4.3) cm in girls. WES in 11 SGA patients revealed conclusive genetic variants in eight, including two pathogenic ACAN variants, one 15q26.2-q26.3 deletion, and four variants of uncertain significance in other genes. Conclusions: Treatment with GH in SGA patients was shown to be effective, with a similar response in the group with positive genetic results and in the group who did not undergo a genetic study. Genetic testing based on auxological and clinical criteria proved highly cost-effective.
Percutaneous Transluminal Angioplasty for Atherosclerotic Stenosis of Vertebral Artery Origin
Authors: Krajíčková Dagmar , Krajina Antonín , Herzig Roman , Chovanec Vendelín , Lojík Miroslav , Raupach Jan , Renc Ondřej , Vyšata Oldřich , Šimůnek Libor
Published: July 2024

Background: In patients with vertebral artery origin (VAO) stenosis and concomitant stenoses of other cerebral feeding arteries, data on the risk of percutaneous transluminal angioplasty (PTA) alone and with stent placement (PTAS) for VAO stenosis are limited. We aimed to determine how the presence of polystenotic lesions in other cerebral feeding arteries and concomitant carotid artery stenting (CAS) affect the periprocedural risk and long-term effect of PTA/S for atherosclerotic VAO stenosis. Methods: In a retrospective descriptive study, consecutive patients treated with PTA/S for ≥70% VAO stenosis were divided into groups with isolated VAO stenosis and multiple stenoses. We investigated the rate of periprocedural complications in the first 72 h and the risk of restenosis and ischemic stroke (IS)/transient ischemic attack (TIA) during the follow-up period. Results: In a set of 66 patients aged 66.1 ± 9.1 years, polystenotic lesions were present in 56 (84.8%) patients. 21 (31.8%) patients underwent endovascular treatment for stenosis of one or more other arteries in addition to VAO stenosis (15 underwent CAS). During the periprocedural period, no patient suffered from an IS or died, and, in the polystenotic group with concomitant CAS, there was one case of TIA (1.6%). During a mean follow-up period of 36 months, we identified 8 cases (16.3%) of ≥50% asymptomatic VA restenosis, and, in the polystenotic group, 4 (8.9%) cases of IS. Conclusion: The presence of severe polystenotic lesions or concomitant CAS had no adverse effect on the overall low periprocedural risk of PTA/S of VAO stenosis or the risk of restenosis during the follow-up period.
Comparison of Inflammatory Marker Scoring Systems and Conventional Inflammatory Markers in Patients over 65 Years of Age Admitted to the Intensive Care Unit: A Multicenter, Retrospective, Cohort Study
Authors: Çakin Özlem , Karaveli Arzu , Yüce Aktepe Melike , Gümüş Ayça , Yildirim Özlem Esra
Published: July 2024

Background: The aim of the current study is to evaluate the effects of inflammation markers on infection and mortality in patients over 65 years of age monitored in the intensive care unit (ICU). In this study, we attempted to determine the significance of the pan-immune–inflammation value (PIV); the neutrophil–lymphocyte ratio (NLR); the platelet–lymphocyte ratio (PLR); the monocyte–lymphocyte ratio (MLR); the systemic immune–inflammatory index (SII); the systemic immune response index (SIRI); multi-inflammatory indices (MIIs) 1, 2, and 3; and the CRP/albumin ratio (a new biomarker) as prognostic and mortality markers in patients over 65 years of age being monitored in the ICU. Methods: This multicenter, retrospective, cohort study was conducted on patients aged 65 and over who were admitted to two tertiary-level ICUs. Patients with cirrhosis, bone marrow transplantation, hematologic malignancy, steroid intake, current chemotherapy treatment, and neutropenia upon admission to the ICU were excluded from this study. Results: A total of 333 patients were included in this study. The group’s 28-day mortality was found to be 31.8%. When each inflammatory marker associated with 28-day mortality was examined, the CRP/albumin ratio was found to be a better indicator than both the NLR and the SIRI, and the results were statistically significant (AUC: 0.665, 95% CI: 0.604–0.726, and p < 0.001). The NLR showed moderate discriminative ability in distinguishing mortality risk (AUC: 0.593, 95% CI: 0.526–0.660, and p = 0.006). Although the SIRI was lower than the NLR, it produced a statistically significant result (AUC: 0.580, 95% CI: 0.514–0.646, and p = 0.019). The CRP/albumin ratio was the most effective inflammatory marker in predicting mortality risk in older patients admitted to the ICU. Conclusions: It is important to monitor inflammatory markers (especially CRP/albumin ratio, NLR, SIRI, and MII 1-2-3) in older patients admitted to the ICU in order to accurately predict 28-day mortality. In the current study, the effects of PIV, MLR, PLR, and SII on the prediction of 28-day mortality in older ICU patients could not be demonstrated. We believe that more clinical studies are needed to determine the effects of PIV, MLR, PLR, and SII on short- and long-term prognoses and survival in older ICU patients.
Electrophoretic Deposition of Chitosan Coatings on the Porous Titanium Substrate
Authors: Flesińska Julia , Szklarska Magdalena , Matuła Izabela , Barylski Adrian , Golba Sylwia , Zając Julia , Gawlikowski Maciej , Kurtyka Przemysław , Ilnicka Barbara , Dercz Grzegorz
Published: July 2024

Medicine is looking for solutions to help implant patients recover more smoothly. The porous implants promote osteointegration, thereby providing better stabilization. Introducing porosity into metallic implants enhances their biocompatibility and facilitates osteointegration. The introduction of porosity is also associated with a reduction in Young’s modulus, which reduces the risk of tissue outgrowth around the implant. However, the risk of chronic inflammation remains a concern, necessitating the development of coatings to mitigate adverse reactions. An interesting biomaterial for such modifications is chitosan, which has antimicrobial, antifungal, and osteointegration properties. In the present work, a porous titanium biomaterial was obtained by powder metallurgy, and electrophoretic deposition of chitosan coatings was used to modify its surface. This study investigated the influence of ethanol content in the deposition solution on the quality of chitosan coatings. The EPD process facilitates the control of coating thickness and morphology, with higher voltages resulting in thicker coatings and increased pore formation. Ethanol concentration in the solution affects coating quality, with higher concentrations leading to cracking and peeling. Optimal coating conditions (30 min/10 V) yield high-quality coatings, demonstrating excellent cell viability and negligible cytotoxicity. The GIXD and ATR-FTIR analysis confirmed the presence of deposited chitosan coatings on Ti substrates. The microstructure of the chitosan coatings was examined by scanning electron microscopy. Biological tests showed no cytotoxicity of the obtained materials, which allows for further research and the possibility of their use in medicine. In conclusion, EPD offers a viable method for producing chitosan-based coatings with controlled properties for biomedical applications, ensuring enhanced patient outcomes and implant performance.
Design of Ship Trajectory Control Method Integrating Self Disturbance Rejection and Neural Network
Authors: Luo Luyu , Zhang Lei , Gu Zheng
Published: July 2024

To reduce the ship trajectory control difficulty, a ship trajectory control method based on active disturbance rejection control and radial basis function neural network is designed. Firstly, a separated model structure is proposed to model the ship’s navigation system, followed by the introduction of active disturbance rejection control technology to control the ship’s trajectory, and the fusion of radial basis function to improve the parameter adjustment effect. It was found that on the AIS and MSSIS datasets when the system was iterated 25 and 22 times, respectively, the fitness values of the research method were as high as 99.46 and 99.51. In addition, when the accuracy of all algorithms was 0.900, the recall rate of the research method was significantly the highest, at 0.752. When the recall rate was 0.900, the accuracy of the research method was significantly the highest, reaching 0.869. In practical applications, when there was no external interference, the heading was a square wave signal, and when the time reached 90.11, the proposed method operated with a small difference between the planned heading and the actual heading. In addition, it was found that the control effect of the research method on ship operation remains highly stable when external interference is added during ship operation. The above results indicate that the designed method has significant advantages in ship trajectory control tasks and can effectively enhance the navigation safety and stability of ships.