bluuebunny/crossref_metadata_2025 huggingface dataset:
Beyond Correlation to Causation in Hunter–Gatherer Ritual Landscapes: Testing an Ontological Model of Site Locations in the Mojave Desert, California
Authors: Whitley David S. , Lancaster JD , Catacora Andrea
Published: February 2025

Why are rock art sites found in certain places and not others? Can locational or environmental variables inform an understanding of the function and meaning of the art? How can we move beyond observed patterning in spatial associations to a credible explanation of such meanings and ensure that we are not confusing correlation with causation? And what variables were most relevant in influencing site locational choices? These and related problems, whether recognized or not, are the subtext of the last three decades of rock art site distributional and landscape studies. They are now especially important to resolve given the need for accurate predictive modeling due to the rapid transformation of certain regions from undeveloped rural areas into rural industrial landscapes. Partly with this problem in mind, Whitley developed a descriptive model that provides an explanation for the location of Native Californian rock art in the Mojave Desert. It identifies the variables most relevant to site locations based on ethnographic Indigenous ontological beliefs about the landscape. These concern the geographical distribution of supernatural power and its association with certain landforms, natural phenomena and cultural features. His analysis further demonstrated that this model can account for two unusually large concentrations of sites and motifs: the Coso Range petroglyphs and the Carrizo Plain pictographs. But unanswered was the question of whether the model is applicable more widely, especially to smaller sites and localities made by different cultural groups. We documented and analyzed three petroglyph localities with seven small petroglyph sites in the southern Mojave Desert, California, to test this model. These sites are attributed to the Takic-speaking Cahuilla and Serrano tribes. Our study revealed a good fit between the expected natural and cultural variables associated with rock art site locations, with the number of such variables present at any given locale potentially correlated with the size of the individual sites. In addition to the research value of these results, this suggests that the model may be useful in the predictive modeling of rock art site locations for heritage management purposes.
Future Climate Trends in the Wine-Growing Regions of the Western Cape of South Africa
Authors: Chauke Helga , Pongrácz Rita
Published: February 2025

The Western Cape province is among the best wine-producing regions; however, the province has been facing environmental challenges due to the rapidly changing climate. This study analyses the projected changes in temperature and precipitation patterns across seven wine-producing districts in the Western Cape using high-resolution regional climate model (RCM) simulations from the CORDEX-Africa framework. The model simulations highlight spatial variability due to variable topography and microclimates within the province wherein variable changes in climate conditions are projected over the selected wine-producing regions. The Olifants River is projected to experience the most substantial temperature increases—greater than 5 °C—under the very high baseline emission scenario at the end of the century, while regions closer to the coast, such as Cape Agulhas, are projected to experience moderate changes in both temperature and precipitation changes. The projected changes in precipitation indicate a strong drying trend, especially over regions that are farther from the south coast. The results highlight the vulnerability of vinicultural practices due to climate change; therefore, this study can be used to provide stakeholders with information needed so that they can adapt to the changing climate conditions across wine regions.
CNPY2 in Solid Tumors: Mechanisms, Biomarker Potential, and Therapeutic Implications
Authors: Mullick Chowdhury Sayan , Hong Feng , Rolfo Christian , Li Zihai , He Kai , Wesolowski Robert , Mortazavi Amir , Meng Lingbin
Published: February 2025

Canopy FGF signaling regulator 2 (CNPY2) has emerged as a crucial player in cancer development by promoting cell proliferation, tissue repair, and angiogenesis. This review synthesizes the current understanding of CNPY2’s role in solid tumors, particularly renal cell carcinoma, prostate cancer, hepatocellular carcinoma, and non-small-cell lung cancer. CNPY2 modulates key pathways such as p53, MYLIP, NF-κB, and AKT/GSK3β, thereby driving tumor growth and progression. In renal cell carcinoma, CNPY2 paradoxically promotes tumor growth through p53 upregulation, while in hepatocellular carcinoma, CNPY2 drives cell cycle progression via p53 destabilization. In prostate cancer, it enhances tumor progression by stabilizing androgen receptors through MYLIP interaction, and in non-small-cell lung cancer, it contributes to chemoresistance and metastasis through NF-κB and AKT/GSK3β signaling. Additionally, CNPY2 influences the tumor microenvironment, impacting immune function and metastatic potential. As a potential biomarker, CNPY2 shows promise for cancer detection and prognosis, particularly when used in combination with other markers. Early therapeutic strategies, including siRNA and miRNA approaches, are under exploration, though challenges remain due to CNPY2’s expression in normal tissues and potential off-target effects. This review underscores the need for further research to fully elucidate CNPY2’s oncogenic mechanisms and develop targeted therapies. Improved understanding of CNPY2’s diverse roles may lead to novel diagnostic and therapeutic approaches in solid tumors.
A Narrative Review on Manufacturing Methods Employed in the Production of Mesenchymal Stromal Cells for Knee Osteoarthritis Therapy
Authors: Aabling Rasmus Roost , Rusan Maria , Møller Anaïs Marie Julie , Munk-Pedersen Naija , Holm Carsten , Elmengaard Brian , Pedersen Michael , Møller Bjarne Kuno
Published: February 2025

Knee osteoarthritis (OA) is a chronic, progressive, inflammatory, and degenerative whole-joint disease. Early-stage OA treatments typically include physiotherapy, weight-loss, pain relief medications, and intra-articular knee injections, such as corticosteroids, hyaluronic acid, or platelet-rich plasma. These treatments primarily provide symptomatic relief rather than reversing or halting disease progression. Recently, mesenchymal stromal cell (MSC) injections have garnered attention due to their immunomodulatory and regenerative capacities. MSCs, which can be derived from sources such as bone marrow, umbilical cord, or adipose tissue, and can be allogeneic or autologous, have demonstrated promising results in both animal models and several human studies. However, different protocols have been employed, presenting challenges for comparing outcomes. In this review, we address these variable settings, evaluate current practices, and identify key factors critical in optimizing MSC-based therapies by critically reviewing clinical trials of ex vivo expanded MSC therapies for OA undertaken between 2008 and 2023. Specific attention was given to two key aspects: (1) the cell culture process employed in manufacturing of autologous or allogeneic MSC products, and (2) the post-culture methods employed in storage, reconstitution and administration of the MSCs. Our findings suggest that standardizing MSC production for clinical applications remains a significant challenge, primarily due to variations in tissue sources, harvesting techniques, and manufacturing protocols, and due to broad discrepancies in reporting. Thus, we propose a set of minimal reporting criteria to guide future clinical trials. A common reporting guideline is a critical step towards a more standardized MSC production across different laboratories and clinical settings, thereby enhancing reproducibility and advancing the field of regenerative medicine for knee OA, as well as other disease settings.
Radiation Retinopathy: Microangiopathy-Inflammation-Neurodegeneration
Authors: Davids Anja-Maria , Pompös Inga-Marie , Kociok Norbert , Heufelder Jens , Skosyrski Sergej , Reichhart Nadine , Joussen Antonia M. , Wolf Susanne A.
Published: February 2025

Purpose: Proton irradiation is used to treat choroidal melanoma of the eye. The impact on non-malignant retinal cells is currently understudied. Therefore, we here report a mouse model to investigate the impact of proton irradiation on the retina. Methods: We performed a proton beam irradiation of 5–15 Cobalt-Gray-Equivalent (CGE) of the eyes of female C57Bl6/J (Cx3cr1+/+), Cx3cr1gfp/+ and Cx3cr1gfp/gfp mice mimicking the clinical situation and evaluated the structure, function and cellular composition of the retina up to 24 weeks after irradiation. Results: Proton beam irradiation of the eye with 15 CGE leads to cataract formation after 24 weeks without affecting the gross anatomy of the retinal vasculature as shown by Fundus imaging in all genotypes respectively. However, 10 and 15 CGE, lead to a significant decrease in NG2 positive cell numbers and all three dosages induced an increase in GFAP immunoreactivity. At 24 weeks a dosage of 15 CGE resulted in functional impairment and a decrease of NG2 positive cells in both WT and Cx3cr1 animals. Iba1 cell immunoreactivity was increased in all genotypes. However, in the Cx3cr1 animals the invasion of Iba1 cells into the deep vascular layer was partially prevented. This was accompanied by a less severe functional impairment in the irradiated Cx3cr1gfp/gfp vs. WT. Conclusions: Although the gross anatomy of the retina does not seem to be affected by proton beam irradiation, the cellular composition and retinal function changed significantly in both WT and Cx3cr1 mice reflecting the clinical situation. Moreover, cataract formation was one of the major long-term effects of irradiation. We conclude that the murine model (WT and Cx3cr1 genotype) can be used to investigate proton-beam associated side effects in vivo as well as to test prospective interventions. Moreover, the loss of Cx3cr1 seems to be partially protective.
Seasonal Influences on Human Placental Transcriptomes Associated with Spontaneous Preterm Birth
Authors: Akram Khondoker M. , Dodd Eleanor , Anumba Dilly O. C.
Published: February 2025

Demographic studies have revealed a strong association between exposure to high ambient temperatures during pregnancy and increased risks of preterm birth (PTB). The mechanism underlying this association is unclear, but it is plausible that altered placental function may contribute to it. In this study, we conducted differential gene expression analysis, gene set enrichment analysis (GSEA), and gene ontology (GO) analysis on bulk RNA-seq data from human placentas delivered at term and preterm during the warmer months compared to placentas delivered at term and preterm during the colder months in the UK. We detected 48 differentially expressed genes in preterm placentas delivered during the warmer months compared to preterm placentas delivered during the colder months, the majority of which were inflammatory cytokines and chemokines, including SERPINA1, IL1B, CCL3, CCL3L3, CCL4, CCL4L2, CCL20, and CXCL8. The GSEA positively enriched 17 signalling pathways, including the NF-κB, IL17, Toll-like receptor, and chemokine signalling pathways in preterm placentas delivered during warmer months. These results were not observed in the placentas delivered at term during the same times of the year. The GO analysis revealed several enhanced biological processes, including neutrophil, granulocyte, monocyte, and lymphocyte chemotaxis, as well as inflammatory and humoral immune responses in preterm placentas, but not in placentas delivered at term in the summer. We conclude that maternal exposure to warm environmental temperatures during pregnancy likely alters the placental transcriptomes towards inflammation and immune regulation, potentially leading to PTB.
Systemic Drivers of Electric-Grid-Caused Catastrophic Wildfires: Implications for Resilience in the United States
Authors: Eagleston Holly , Bester Michelle , Yusuf Jubair , Damodaran Adit , Reno Matthew J.
Published: February 2025

Wildfires are projected to increase in severity and frequency due to climate change, and the electric grid is both a cause of wildfires and is vulnerable to wildfires. Equipment from the electric grid accounts for 10% of fires burned in California and 3% of fires nationally. Recent catastrophic wildfires, such as the Lahaina Fire, Camp Fire, Marshall Fire, and Smokehouse Creek fires, were all started by electrical equipment and show how devastating these events can be because they threaten lives and structures. Vegetation structure, weather and winds, climate and vegetation response, land use, and human activities all impact the likelihood of severe wildfires. We explore the relationship between the built environment, electric grid infrastructure specifically, and its role in causing catastrophic wildfires to find lessons learned for increasing resilience. Electric grid utility companies currently employ multiple methods to mitigate fire, including (1) early detection, (2) grid hardening, (3) vegetation management, and (4) pre-emptive shutoffs. Utility companies need to consider the conditions for wildfire and the impact that each mitigation strategy has on drivers of wildfire behavior, as a single solution will not be adequate. Utility companies need to work with stakeholders to develop a holistic strategy to reduce ignition likelihood and spread likelihood to reduce catastrophic wildfires and improve resiliency.
Updating the Distribution and Conservation Status of the Endemic Nabatean Thyme (Thymbra nabateorum)
Authors: Abdulkarem Ayman , Elgharib Ahmed , Darwish Mohammed , Assaeed Abdulaziz , Alenezi Ali , Van Essen Lourens , Soultan Alaaeldin
Published: February 2025

Nabatean thyme (Thymbra nabateorum (Danin & Hedge) Bräuchler) is a perennial herb species under the Lamiaceae family, first described in 1998. The species is thought to be endemic to Jordan with only six known records. However, recent fieldwork has uncovered new patches of Nabatean thyme in northwestern Saudi Arabia. This study aimed to determine the global conservation status and update the distribution of Nabatean thyme. To achieve this, we conducted extensive fieldwork and used the collected occurrences to calculate species Extent of Occurrence (EOO) and Area of Occupancy (AOO). We recorded Nabatean thyme in sandstone grooves within open plains at altitudes of 850 to 1350 m, with its largest population occurring outside its historical range, rendering it endemic to northwest Arabia. The primary threats to Nabatean thyme across its range include overgrazing, excessive harvesting for medicinal purposes, and habitat fragmentation. Nabatean thyme has an EOO of 47,585 km² and an AOO of 136 km². Accordingly, we recommend considering Nabatean thyme as an Endangered species under the B2ab(iii) and C2a(ii) IUCN criteria. We recommend integrating both in situ and ex situ conservation programs to improve the conservation status and ensure the sustainability of Nabatean thyme.
Blue Light Therapy in Dermatological Practice: A Review
Authors: Lodi Giuseppe , Cassalia Fortunato , Sannino Mario , Cannarozzo Giovanni , Baroni Adone , Amato Simone , Zappia Elena , Pellacani Giovanni , Nisticò Steven Paul
Published: February 2025

For some years, blue light at a wavelength of 400–500 nm has emerged as a non-invasive and innovative treatment in dermatology. This narrative review provides a comprehensive exploration of the mechanisms by which blue light exerts therapeutic effects on various skin disorders including treatment of acne vulgaris, psoriasis, atopic dermatitis, vitiligo, androgenetic alopecia, ulcers and photoaging. We delve into the antimicrobial properties of blue light, highlighting its ability to generate reactive oxygen species that target and destroy pathogenic microorganisms such as Cutibacterium acnes. Additionally, we examine its anti-inflammatory effects, which involve the modulation of cytokine production and reduction in inflammatory cell infiltration, contributing to symptom relief in chronic inflammatory conditions. Blue light, through interaction with some photoreceptors, belonging to the Opsin family, is able to stimulate and prolong the anagen phase in the hair’s life cycle and stimulate repigmentation in vitiligoid patches. The photobiomodulation properties of blue light are also discussed, emphasizing how it influences cellular activities like proliferation and differentiation, thereby aiding in skin rejuvenation and healing processes. By assessing the clinical efficacy, safety profiles, and potential adverse effects reported in the current literature, we aim to present a balanced perspective on the utility of blue light therapy. The review also discusses advancements in light-emitting diode (LED) technology that have enhanced treatment delivery and patient outcomes. Furthermore, we outline future directions for research and clinical applications, emphasizing the need for standardized treatment protocols and long-term safety studies to fully integrate blue light therapy into dermatological practice.
Railroad Cybersecurity: A Systematic Bibliometric Review
Authors: Abudu Ruhaimatu , Bridgelall Raj , Quayson Bright Parker , Tolliver Denver , Dadson Kwabena
Published: February 2025

Cybersecurity challenges are increasing in the rail industry because of constant technological evolution that includes the Internet of Things, blockchains, automation, and artificial intelligence. Consequently, many railroads and supply chain stakeholders have implemented strategies and practices to address these challenges. However, the pace of cybersecurity implementation in the railroad industry is slow even as cyberthreats escalate. This study uniquely integrates bibliometric analysis with a systematic literature review to provide a holistic view of cybersecurity trends in rail freight. The study analyzes 70 articles focusing on cybersecurity practices in the rail freight industry, structured around four research questions relating to: (1) challenges, (2) measures, (3) emerging trends, and (4) innovations. Key findings are that implementing cybersecurity practices in the rail freight industry comes with numerous challenges and risks. The study concludes that new threats will constantly emerge with technological advancements. Therefore, there is a need for continuous human training, collaboration, and coordination with stakeholders. This study also highlights research gaps and recommends how stakeholders can most appropriately execute cybersecurity strategies and best coordinate them with the various technological functions in the rail freight industry.
A Secure and Efficient Access-Control Scheme Based on Blockchain and CP-ABE for UAV Swarm
Authors: Han Pengbin , Sui Aina , Wu Jiang
Published: February 2025

With the continuous development of UAV technology, the application of UAV swarm has gradually become the focus of research all over the world. Although UAV swarm provides some advantages in terms of autonomous collaboration, the traditional UAV management technology suffers from security challenges, including the risk of single points of failure due to centralized control, which makes UAV swarm susceptible to hacker attacks. Due to some advantages of blockchain, such as decentralization, tamper-proof characteristics, and traceability, it is applied to the drone swarm to solve some security challenges brought about by centralized management. However, blockchain cannot achieve secure access control on the data it stores, which may leak some crucial data. Therefore, a secure and efficient access-control model based on blockchain and ciphertext-policy attribute-based encryption (CP-ABE) is proposed, and a secure data-access scheme is designed under this model, which can not only prevent the leakage of critical data but also realize lightweight access control. Moreover, to improve the decryption efficiency of the data user, an outsourcing-based data decryption scheme is also studied, in which the complex calculations are completed by the data user agency. The experiments show that when the number of attributes is 60, the computation cost of the proposed scheme is 0.404 s, which is much lower than the existing research, and is more suitable for the UAV swarm with limited computing power. Moreover, the communication cost of the proposed scheme is reduced by about 30% compared with the existing scheme under the same conditions. The security analysis also shows that the proposed scheme is secure and reliable, and can resist a variety of attacks such as collusion attacks, man-in-the-middle attacks, and forgery attacks.
Performance Monitoring of a Double-Slope Passive Solar-Powered Desalination System Using Arduino Programming
Authors: Radhakrishnan Ganesh , Karthikeyan Kadhavoor R.
Published: February 2025

Solar energy is one of the promising renewable energies; it is clean, green, and accepted worldwide for targeting sustainable development through applications such as power generation, desalination, food preservation, etc. Solar-powered desalination has received more attention in recent times to meet the demand of pure water in the rural places of many countries where solar energy is abundant. In the present work, a double-slope passive solar desalination system was fabricated with readily available materials that can be installed and used in rural places, either for domestic purposes or in small-scale industries. The capacity of the desalination system fabricated to be filled with saline water is ~15 L. The performance of the desalination system is continuously monitored by recording the temperatures at various locations around the system, such as the outer surface of the glass, the inner surface of the glass, inside the basin, and outside the basin, through DHT11 sensors controlled by Arduino programming fed in the Arduino UNO board. The influence of solar radiation intensity and temperatures at various locations on the solar still on the thermal performance and production of desalination unit is analyzed by the data recorded by the Arduino program. A cumulative yield of fresh water of around 0.7–0.9 L is recorded every day, and the lowest yield of around 0.55 L was obtained on the third day of experimentation.
Judicial Innovation in Enhancing Forest Carbon Sinks: Evidence from China
Authors: Que Zhanwen , Zhang Yixuan , Cheng Xiaoya
Published: February 2025

Sustainable forest management plays a crucial role in climate change mitigation and adaption, as well as the achievement of the 2030 Sustainable Development Goals (SDGs). Recognizing the significance of sustainable forest management, China has implemented a range of the legislative measures and policies for the conservation and restoration of key forest ecosystems and has launched the Three-North Shelterbelt Forest Program and other key forest programs, resulting in an increase in forest coverage and forest carbon sinks. In addition to forestry ecological restoration projects (FERPs) initiated by the administration and project developers, the Chinese courts have also actively engaged in exploring various strategies to enhance forest carbon sinks. In both criminal and civil cases, afforestation and reforestation activities, buying forest carbon credits, and participation in forest management and other restoration activities by offenders have been regarded as factors in determining legal responsibility. Moreover, the courts have also established forest restoration centers, either independently or in collaboration with local governments. These judicial innovations in China have provided positive incentives for the conservation, restoration, and sustainable management of forests, thereby significantly contributing to the achievement of the Climate Action Goals (SDG 13). However, these developments also raise several concerns, particularly the fair application of forest carbon sink mechanisms, the comparability in ecosystem service between damaged natural resources and compensatory measures, and the interconnection of the various SDGs. It is imperative to establish clear guidance on buying forest carbon credits, to develop standards and procedures to assess forest carbon sinks, and to strengthen cooperation between the judiciary and governmental agencies. Additionally, it is essential to integrate the forest carbon sink with broad economic development goals and social justice frameworks to ensure sustainable and inclusive outcomes.
Determination of the Probiotic and Functional Properties of Yeasts Isolated from Different Dairy Products
Authors: Kanak Eda Kılıç , Öztürk Yılmaz Suzan
Published: February 2025

This study aimed to explore new probiotic yeast strains, considering that Saccharomyces cerevisiae is the only yeast used industrially. To this end, yeasts were isolated from various dairy products and their probiotic potential was investigated. All yeast strains demonstrated survival potential under simulated gastrointestinal conditions, mimicking the stomach and intestinal passage. Among the isolates, 13.04% were identified as moderate biofilm producers, 34.78% as weak biofilm producers, and 52.17% exhibited no biofilm-forming ability. Catalase enzyme production was detected in all isolates, and it was determined that their hydrophobicity varied depending on hydrocarbon interactions. In this study, the percentage of autoaggregation increased with prolonged incubation times across all strains. After 24 h, the percentage of autoaggregation exceeded 60% for all isolates. It was concluded that the coaggregation ability depended on incubation time and strain type. Most of the isolated yeasts exhibited antimicrobial activity against E. coli ATCC 25922, E. coli O157:H7, B. cereus, C. sakazakii ATCC 29544, L. monocytogenes ATCC 7644, S. aureus ATCC 25923, and S. typhimurium ATCC 140828. Furthermore, the yeast strains were resistant to all tested antibiotics. The 1,1-diphenyl-2-picrylhydrazyl radical scavenging activity revealed that the antioxidant activity of the cells was higher than that of their intracellular extracts for all tested strains. The yeasts were initially identified using MALDI-TOF and further characterized through 18S-28S rRNA analysis. There are not many recent studies on the selection of probiotic yeasts for use in the dairy industry. Therefore, in this study we wanted to investigate some functional properties of different yeasts to be proposed as probiotic cultures in this specific sector. In particular, the antimicrobial and antioxidant properties and enzymatic activity highlighted by isolates have promising implications for food safety and health. These preliminary results provide a valuable basis for the future industrial application of probiotic yeasts in the dairy sector.
Multiple Lenses to Unearth Hidden Voices: Living with Diabetic Foot Ulceration in an Afro-Caribbean Community
Authors: Lovell Laura , Campbell Michael H. , Greaves Natalie
Published: February 2025

(1) Background: This study was conducted in the small island developing state of Barbados, which has dubiously earned the title of “amputation capital of the world”, to understand perspectives of persons living with diabetic foot ulceration. (2) Methods: An exploratory multi-lens approach was used (focus groups; dyads; and triads) to gather indigenous Afro-Caribbean perspectives of living with diabetic foot ulceration that may be obscured by using a single method. (3) Results: Findings in this group highlighted the necessity of creating culturally sensitive education tools, as well as understanding how mistrust of local health systems may play a role in decisions to delay seeking health services despite ease of access with no cost at point of care. Problematic historical relationships with health systems among Afro-Caribbean people, for whom oral traditions motivate preference for traditional medicines instead of Western/colonial treatments from North America or Europe, may be deeply entrenched in this population and contribute to health beliefs and behaviors. (4) Conclusions: This paper addresses the gap in the literature regarding the use of qualitative methodologies to explore the beliefs of Afro-Caribbean people within their native context to inform design of culturally responsive self-education programs.
NAD+ Boosting Through NRH Supplementation Enhances Treatment Efficacy in EOC In Vitro
Authors: Lee Kevin J. , Chokshi Sagar , Joshi Tanvi , Cummings Mackenzie , Lyons Catherine E. , Singleton Mary Howard , Catranis Elizabeth , Madiera da Silva Luciana , Hayat Faisal , Migaud Marie , Scalici Jennifer
Published: February 2025

Dihydronicotinamide rioside (NRH), the reduced form of nicotinamide riboside (NR), is a recently identified, naturally occurring precursor of arguably the most crucial cofactor for cellular function, nicotinamide adenine dinucleotide (NAD+). Recent investigation suggests that NRH is more adept at increasing NAD+ stores than traditional NAD+ precursors, and such extreme NAD+ boosting via NRH supplementation induces cytotoxicity in certain cellular contexts. It has also been shown that the lack of functional BRCA protein in epithelial ovarian cancer (EOC) directly impacts intracellular NAD+ levels. Given that altered cellular metabolism and DNA repair mechanisms are central alterations in EOC, and these processes are functionally dependent on NAD+, we sought to assess whether NRH supplementation in EOC cell lines enhanced cellular cytotoxicity alone and in combination with standard therapeutic agents. Significant cytotoxicity was noted in NRH treated cells (~40%) with minimal cell death in the nicotinic acid (NA)-treated lines. Levels of NAD(P)H were confirmed to have increased with NRH supplementation, albeit at different levels among the different cell lines. Overall, the cytotoxicity associated with NRH supplementation appears to be independent of ROS generation. Strikingly, NRH supplementation enhanced cytotoxicity of carboplatin in OVCAR8, but not ES2 or SKOV3. Paclitaxel cytotoxicity was also enhanced by the addition of NRH in OVCAR8, but not ES2 or SKOV3 cell lines. NA supplementation had no effect on baseline treatment-induced cytotoxicity. PARP inhibition by olaparib requires NAD+. Interestingly, NRH supplementation enhanced olaparib cytotoxicity in SKOV3 and OVCAR8, but not ES2 cells. NRH in combination with olaparib completely altered mitochondrial respiration, thereby shutting down energy consumption, which would lead to cell death. Coupled together with expression data of key enzymes required for NRH/NAD metabolism, this could be key in understanding mechanisms of cell death with NRH supplementation. Here, we showed that in the context of EOC, exploitation of the NAD+ bioenergetic phenotype through NRH supplementation is a biologically feasible strategy to enhance the response of traditional therapy with potentially minimal toxicity. These data suggest several potential mechanisms by which cellular NAD+ availability impacts treatment efficacy and resistance and highlights the potential utility of NAD+ metabolomics as a biomarker to guide treatment decisions.
Exploring the Effects and Mechanisms of Valerian Volatile Oil in Treating Insomnia Using Network Pharmacology, Molecular Docking, and Molecular Dynamics Simulation-Based Approaches
Authors: Muhetaer Halimulati , Li Huajian , Wang Bingna , Cai Xinyi , Zhang Yang , Li Yongxian , Li Chuwen , Wu Bo
Published: February 2025

Valerian possesses a multitude of pharmacological effects, including sedative and hypnotic properties, antihypertensive effects, antibacterial activity, and liver protection. Insomnia, one of the most prevalent disorders in contemporary society, significantly impacts people’s daily lives. This study aims to explore the anti-insomnia effects of valerian volatile oil (VVO) and investigate its potential mechanism of action through chemical analysis, network pharmacology, molecular docking, molecular dynamics simulations, and experimental validation. Through gas chromatography–mass spectrometry (GC-MS) analysis and drug-likeness screening, we identified 38 active compounds. Network pharmacology studies revealed that these 38 compounds might affect 103 targets associated with insomnia, such as monoamine oxidase B (MAOB), dopamine receptor D2 (DRD2), monoamine oxidase A (MAOA), interleukin 1β (IL1B), solute carrier family 6 member 4 (SLC6A4), prostaglandin-endoperoxide synthase 2 (PTGS2), and 5-hydroxytryptamine receptor 2A (HTR2A), which contribute to regulating the neuroactive ligand–receptor interaction, 5-hydroxytryptaminergic synapse, and calcium signaling pathways. The results of the molecular dynamics simulations indicated that bis[(6,6-dimethyl-3-bicyclo[3.1.1]hept-2-enyl)methyl] (E)-but-2-enedioate exhibited a stabilizing interaction with MAOB. The animal studies demonstrated that gavage administration of a high dose (100 mg/kg) of VVO significantly diminished autonomous activity, decreased sleep latency, and extended sleep duration in mice. Furthermore, the results of the Western blot experiment indicated that VVO interacts with MAOB, resulting in decreased expression levels of MAOB in the cerebral cortex. This study demonstrates the protective mechanism of VVO against insomnia through chemical analysis, network pharmacology, and experimental validation and extends the possible applications of VVO, which is a potential therapeutic ingredient for use in insomnia treatment.
AI vs. Human-Authored Headlines: Evaluating the Effectiveness, Trust, and Linguistic Features of ChatGPT-Generated Clickbait and Informative Headlines in Digital News
Authors: Gherheș Vasile , Fărcașiu Marcela Alina , Cernicova-Buca Mariana , Coman Claudiu
Published: February 2025

This study explores possible applications of AI technology in online journalism, given the predictions that speed and adaptation to the new medium will increase the penetration of automation in the production business. The literature shows that while the human supervision of journalistic workflow is still considered vital, the journalistic workflow is changing in nature, with the writing of micro-content being entrusted to ChatGPT-3.5 among the most visible features. This research assesses readers’ reactions to different headline styles as tested on a sample of 624 students from Timisoara, Romania, asked to evaluate the qualities of a mix of human-written vs. AI-generated headlines. The results show that AI-generated, informative headlines were perceived by more than half of the respondents as the most trustworthy and representative of the media content. Clickbait headlines, regardless of their source, were considered misleading and rated as manipulative (44.7%). In addition, 54.5% of respondents reported a decrease in trust regarding publications that frequently use clickbait techniques. A linguistic analysis was conducted to grasp the qualities of the headlines that triggered the registered responses. This study provides insights into the potential of AI-enabled tools to reshape headline writing practices in digital journalism.
Comparative Study of Mastectomy Surgical Techniques Followed by Reconstruction: Hydrodissection and Electrical Plasma Surgery
Authors: Actis Silvia , Lavalle Giulia , Agus Stefania , Paradiso Elena , Accomasso Francesca , Minella Carola , Sgro Luca Giuseppe , Boltri Mario , Balocco Paolo , Ferrero Annamaria , Bounous Valentina Elisabetta
Published: February 2025

Background/Objectives: Mastectomy is a surgical option for breast cancer when conservative treatment is unsuitable, and it is also performed prophylactically in high-risk women. Various surgical techniques can be used for mastectomy, including electrosurgery, which can cause thermal damage to tissues, reducing surgical precision and delaying wound healing. This study aims to compare electrical plasma surgery and hydrodissection, which appear to be the least traumatic methods, to determine the better option for performing mastectomy with immediate reconstruction. Methods: Conducted at the “Breast Unit” of AO “OrdineMauriziano Umberto I”, this study analyzed 56 patients undergoing 65 mastectomies (9 bilateral, 47 unilateral). A total of 16 were prophylactic, and 49 were oncologic. All patients received immediate subpectoral reconstruction. Data collected included preoperative medical history, pain, drain flow, blood transfusions, hemoglobin levels, and hospital stay duration. Complications were graded using the Clavien-Dindo classification. Results: Both groups were similar in age, body mass index (BMI), smoking habits, and comorbidities. Patients who underwent hydrodissection reported more pain on the first and second postoperative day and had longer hospital stays. The drop in hemoglobin from pre- to postoperative and the volume of surgical drains on the day of surgery and the first and second postoperative days were comparable between groups. Early complications and reintervention rates (Clavien-Dindo grade 3) were similar between techniques. Conclusions: Electrical plasma surgery offers better early postoperative outcomes in terms of pain and hospital stay, although overall complication and reintervention rates are unaffected by the technique used. Larger randomized studies are needed to confirm these findings and optimize patient management.
BRM: From Skin-Reducing Mastectomy to the New Concept of Breast Reshaping Mastectomy
Authors: Lorenzano Valerio , Lisa Andrea Vittorio Emanuele , Vinci Valeriano , Agnelli Benedetta , Lozito Alessia , Klinger Marco , Mela Alessandro , Caruso Martina , Klinger Francesco
Published: February 2025

Background: Macromastia is a well-known issue in breast reconstruction. Skin-reducing mastectomy (SRM) was introduced as a skin-sparing mastectomy that utilizes a skin reduction pattern similar to breast reduction or breast lift surgery, specifically to manage hypertrophic and pendulous breasts. Over time, numerous authors have contributed to refining the SRM technique, leading to the development of various technical variants. However, the diversity of approaches inspired by SRM has created confusion, and clear surgical indications are lacking. Methods: We propose a unifying concept called breast reshaping mastectomy (BRM), which encompasses all techniques based on SRM principles. The BRM aims not only to preserve and reduce the breast skin envelope but also to immediately reshape it for a more aesthetic outcome. This approach is applicable to all mastectomies where skin envelope preservation (with or without the nipple-areola complex) is oncologically safe, a modification of breast skin coverage is needed for better aesthetic results, and an implant-based reconstruction is planned. Results: To define the BRM concept, we reviewed the existing literature on SRM and its related techniques. Our analysis focused on four key elements: skin incision pattern, implant coverage strategy, nipple-areola complex (NAC) management, and the choice between two-stage and direct-to-implant reconstruction. Conclusions: By integrating these four components into a single surgical framework, BRM provides a structured approach to breast reconstruction that enhances both oncologic safety and aesthetic outcomes. Standardizing these techniques could help clarify surgical indications and improve reconstructive planning for patients undergoing skin-sparing mastectomy.
The 12-Year Experience of the Hungarian Pancreatic Study Group
Authors: Szentesi Andrea , Hegyi Péter ,   on behalf of the Hungarian Pancreatic Study Group
Published: February 2025

The Hungarian Pancreatic Study Group (HPSG) was established with the aim of advancing pancreatology. Our summary outlines the methodologies, key results, and future directions of the HPSG. Methodological elements included, the formation of strategic national and international collaborations, the establishment of patient registries and biobanks, and a strong focus on education and guideline development. Key results encompassed, pioneering research on pancreatic ductal function and the role of cystic fibrosis transmembrane conductance regulator (CFTR) in inflammation, significant advancements in understanding acute and chronic pancreatitis, and the execution of numerous clinical trials to explore new therapeutic approaches. Despite challenges, such as securing funding and translating research into clinical practice, the HPSG’s commitment to patient care and scientific innovation has been unwavering. The group aims to deepen research into pancreatic cancer and chronic pancreatitis, conduct more randomized controlled trials (RCTs), and expand its efforts internationally by involving global staff and patients. The authors hope that this summary inspires others to undertake similar initiatives and contribute to the global advancement of medical research and patient care in pancreatology.
Prediction of Seawater Intrusion Run-Up Distance Based on K-Means Clustering and ANN Model
Authors: Li Jiatao , Meng Zhenzhu , Zhang Junkang , Chen Yukai , Yao Jiewen , Li Xinyue , Qin Peng , Liu Xian , Cheng Chunmei
Published: February 2025

Coastal regions are increasingly vulnerable to sea-level rise and extreme storm events, making the accurate prediction of wave run-up on seawalls crucial for effective flood and erosion protection. This study presents a novel hybrid approach combining K-means clustering with artificial neural networks (ANNs) to predict wave run-up distance. The method begins with dimensionless analysis to scale all the variables, followed by data segmentation using K-means clustering to group wave characteristics such as the Froude number, scaled distance from the wave front to the shoreline, and wave nonlinearity. These clusters help to focus the ANN on more homogeneous wave conditions, significantly improving prediction accuracy. Two-dimensional flume experiments systematically varied wave height, period, and steepness, producing a robust dataset that accounts for a range of wave conditions. The model’s performance is demonstrated through a high R2 value of 0.97 and low mean squared error (MSE) of 0.0092, surpassing traditional ANN models in its ability to capture complex wave dynamics.
Galleria mellonella as an Invertebrate Model for Studying Fungal Infections
Authors: Marena Gabriel Davi , Thomaz Luciana , Nosanchuk Joshua Daniel , Taborda Carlos Pelleschi
Published: February 2025

The incidence of fungal infections continues to increase and one of the factors responsible for these high rates is the emergence of multi-resistant species, hospitalizations, inappropriate or prolonged use of medications, and pandemics, such as the ongoing HIV/AIDS pandemic. The recent pandemic caused by the severe acute respiratory syndrome virus (SARS-CoV-2) has led to a significant increase in fungal infections, especially systemic mycoses caused by opportunistic fungi. There is a growing and urgent need to better understand how these microorganisms cause infection and develop resistance as well as to develop new therapeutic strategies to combat the diverse diseases caused by fungi. Non-mammalian hosts are increasingly used as alternative models to study microbial infections. Due to their low cost, simplicity of care, conserved innate immunity and reduced ethical issues, the greater wax moth Galleria mellonella is an excellent model host for studying fungal infections and it is currently widely used to study fungal pathogenesis and develop innovative strategies to mitigate the mycoses studied. G. mellonella can grow at 37 °C, which is similar to the mammalian temperature, and the anatomy of the larvae allows researchers to easily deliver pathogens, biological products, compounds and drugs. The aim of this review is to describe how G. mellonella is being used as a model system to study fungal infections as well as the importance of this model in evaluating the antifungal profile of potential drug candidates or new therapies against fungi.
Citizen Science to Investigate the Ecophysiological Responses of Mediterranean Shrubland Vegetation in an Urban Open-Air Laboratory
Authors: Lazzeri Valerio , Bretzel Francesca , Rossini Graziella , Pellegrino Laura , Marchetti Laura , Panti Rosella , Talà Enrica , Martelli Antonio , Scartazza Andrea
Published: February 2025

Urban biodiversity is essential for enhancing liveability for both humans and wildlife by providing a range of ecosystem services. Therefore, it is crucial to raise awareness among citizens, particularly schoolchildren, about the significance of biodiversity in urban environments. To this end, an Open-Air Laboratory was established in an urban park of an Italian Mediterranean city (Livorno), where natural vegetation flourishes. This initiative engaged schoolchildren in experimental campaigns to collect ecophysiological data on local wild woody species. Specifically, the students were tasked with identifying various wild woody species and, under the guidance of researchers, recording specific leaf ecophysiological traits, such as leaf mass per area, leaf pigments, and chlorophyll fluorescence. The results, which highlighted seasonal variations in leaf ecophysiological traits and interspecific differences, were analysed in relation to the environmental conditions documented by the schoolchildren. This analysis revealed distinct plant strategies for coping with winter and summer stressful periods. The methodology employed in this project, which involved schoolchildren in research activities, not only fostered environmental awareness among young participants but also serves as a pilot model for public engagement in scientific research.
A Leverage Points Perspective on China’s Governance of Marine Protected Areas: Current State and Ways Forward
Authors: Wang Jinpeng , Mao Zhengkai , Zhang Zhijun
Published: February 2025

As a key element of spatial governance, marine protected areas (MPAs) have been increasingly established in various countries, with lessons learned from terrestrial environmental protection. Nevertheless, the development of MPAs in China continues to trail behind that of their land-based counterparts. Here, following the leverage points perspective of sustainability interventions, this article presents a systematic analysis of the governance and evolution of China’s MPAs, identifying key areas for improvement. The analysis encompasses the number, effectiveness, legal framework, governance structure, value, and paradigm of MPAs, and highlights the associated governance challenges facing China. Drawing on relevant experiences from the United States, Australia, and the European Union, the article offers valuable insights for informing China’s future MPA strategies. The study concludes that while China has made significant progress in the development of MPAs, further efforts are needed, including paradigm shifts, refinement of the legal system, optimization of governance structures, and enhancement of MPA effectiveness.