bluuebunny/crossref_metadata_2025 huggingface dataset:
Indian Hedgehog (IHh) Protein and COX-2 as Biomarkers to Define the Mechanism of Epilepsy and Gastrointestinal Problems as Comorbid Medical Illnesses in Autism Spectrum Disorder: Combining ROC Curves to Improve Diagnostic Values
Authors: El-Ansary Afaf , Alhakbany Manan , Alfawaz Hanan A. , Al-Ayadhi Laila Y.
Published: November 2024

Background/Objectives: Autism spectrum disorder (ASD) is a neurodevelopmental disorder that is increasing throughout the world. Nevertheless, no specific diagnostic or even risk assessment marker is available. Combining more than one marker can improve the diagnostic value of each marker alone and maximize the AUC for ROC curve. Hedgehog (Hh) signaling modulates both intestinal inflammation and immunity. Cyclooxygenase-2 (COX-2) is required for inflammation, and it has been related to epileptic seizures. COX-2 generates prostaglandins-EP2 (PGE2) in the brain, which plays a major role in neuropathology and epilepsy. This study aims to understand the pathophysiology of ASD by investigating the diagnostic value of COX-2 and IHh using independent and combined ROC curves. Methods: COX-2 and IHh were measured in 40 children with ASD and 41 age and sex-matched controls using ELISA. Statistical analyses were performed using ROC curves, odds ratios, and multiple logistic regression models. Results: Higher levels of COX-2 and IHh were observed in the plasma of patients with autism than in controls. The ROC curve of HIh and COX-2 independently showed poor and fair AUCs of 0.662 and 0.776, respectively, while the combined ROC for both variables in relation to the control group increased the AUC = 0.831 significantly (p < 0.001). Conclusions: Thus, combining these variables could be a useful diagnostic marker for ASD.
Transforming Breast Cancer Care: Cutting-Edge Insights and Future Directions
Authors: De Sanctis Rita , Tiberio Paola , Zambelli Alberto , Santoro Armando
Published: November 2024

Breast cancer (BC) continues to be the most prevalent malignancy affecting women globally, with 2 [...]
Ischemic Risks Induced by Larger Orthodontic Forces on Dental Pulp and Neuro-Vascular Bundle in Reduced Periodontium
Authors: Moga Radu-Andrei , Olteanu Cristian Doru , Delean Ada Gabriela
Published: November 2024

Background/Objectives: There are few data about the ischemic risks induced by the large orthodontic forces during periodontal breakdown in dental pulp and neuro-vascular bundle (NVB) and none on the individual tissular stress distribution, despite their great importance for orthodontic treatment planning. Our aim was to assess, by a numerical analysis, the biomechanical behavior of dental pulp and the NVB during a simulated horizontal periodontal breakdown (1–8 mm), under 2–4 N of applied orthodontic forces and five movements (rotation, translation, tipping, intrusion, and extrusion). Additionally, the ischemic and degenerative-resorptive risks were assessed. Methods: The analysis involved 72 3D models of nine patients, totaling 720 simulations. The models were CBCT-based, having the second lower premolar and surrounding periodontium, and they suffered 1 mm of gradual horizontal periodontal breakdown (up to 8 mm loss). Results: Both forces displayed a similar qualitative stress distribution in all five movements, but with a quantitative increase (doubling of stress amounts for 4 N when compared with 2 N). The highest amounts of stress were displayed at 8 mm of periodontal loss, which is lower than the 16 KPa of the maximum hydrostatic pressure. The NVB stress was higher than the pulpal stress. Rotation was the most stressful, closely followed by tipping, intrusion, and extrusion. Conclusions: A total of 4 N of applied force seems to not induce any ischemic or degenerative-resorptive risks for healthy intact teeth, in up to 8 mm of periodontal breakdown. Intrusion and extrusion determined the highest visible tissular deformation in the NVB, with potential ischemic and resorptive-generative risks for previously traumatized/injured teeth (i.e., occlusal trauma). Rotation and translation (in particular) showed the highest coronal and radicular pulpal stress with potential ischemic and resorptive-generative risks for previously injured/traumatized dental pulp (i.e., direct-indirect pulp capping). It seems that 4 mm of periodontal breakdown could signal a clinical stress increase with potential ischemic and degenerative-resorptive risks for the previously traumatized/injured tissues.
Unlocking Better Asthma Control: A Narrative Review of Adherence to Asthma Therapy and Innovative Monitoring Solutions
Authors: Poplicean Emanuel , Crișan Alexandru Florian , Tudorache Emanuela , Hogea Patricia , Mladin Roxana , Oancea Cristian
Published: November 2024

This review addresses the ongoing challenges in asthma management, particularly focusing on patient adherence to inhaler therapy. Asthma, a chronic condition characterized by variable respiratory symptoms and airflow obstruction, can lead to significant morbidity and mortality if not properly managed. Despite advances in inhaler technology and therapeutic options, non-adherence remains a significant barrier to optimal asthma control. This review explores both intentional and unintentional non-adherence, influenced by factors such as age, socioeconomic status, and the complexity of inhaler devices. The Global Initiative for Asthma (GINA) provides guidelines aimed at improving adherence through targeted interventions, and this review examines their application. Common inhaler technique errors, including incorrect inhalation speed, not exhaling before inhaling, and failure to hold breath post-inhalation, are identified as major contributors to inadequate asthma control. Furthermore, the review explores the emerging role of electronic monitoring devices (EMDs), such as CapMedic and DigiHaler, which offer real-time feedback to enhance inhaler technique and adherence. The role of biomarkers in assessing adherence and the potential of personalized treatment strategies, including biologic therapies, are also discussed. Overall, addressing adherence requires a comprehensive approach that integrates patient education, tailored interventions, and technological innovations to achieve better clinical outcomes in asthma management.
Prognosis of Cirrhotic Patients After Osteoporotic Femoral Neck Fracture
Authors: Muallem Aviya , Kandel Leonid , Ackerman Zvi
Published: November 2024

Introduction and Objectives: Osteoporotic hip fractures in cirrhotic subjects are associated with increased post-fracture mortality. Our aim was to identify unfavorable factors that were associated with increased post-fracture mortality. Patients and Methods: We employed a retrospective evaluation of the short- and long-term prognosis of cirrhotic patients that were admitted with a hip fracture to our institution. Results: A total of 77 cirrhotic and 81 control patients were included. The majority of the patients who died either during the initial three months or during one year of follow-up after the hip fracture were cirrhotic. The patients that did not survive the three-month period suffered from decompensated cirrhosis. The variables that were associated upon multivariate analysis with increased one-year all-cause mortality in both the control and cirrhotic patients were the presence of either cirrhosis, congestive heart failure or low hemoglobin levels upon admission. The variables that were associated upon univariate analysis with increased one-year all-cause mortality only in the cirrhotic patients were the patient’s age, the presence of hepatic encephalopathy, as well as the levels of serum albumin, PT (in %) and FIB-4. Our multivariate analysis disclosed that the admission level of PT (in %) was the only parameter that was associated with one-year all-cause mortality among the cirrhotic patients (adjusted OR 0.962, CI: 0.928–0.996, p = 0.029). Conclusions: Patients with decompensated cirrhosis are at an increased risk of dying during the first year after an osteoporotic hip fracture. Cirrhotic patients with osteoporosis who are at risk of hip fractures should be identified and measures to prevent this complication should be implemented.
Relationship Between the Risk of Obstructive Sleep Apnea and Cardiovascular Health in Middle-Aged Korean Men and Women: A Nationwide Study
Authors: Kang Seo Young , Kim Jung Hwan , Kim Yunmi
Published: November 2024

Background/Objectives: Cardiovascular health (CVH) can be conceptualized as encompassing seven health behaviors and metabolic factors that contribute to cardiovascular disease. We explored the relationship between the risk of obstructive sleep apnea (OSA) and CVH among middle-aged Korean adults. Methods: Data from 5909 participants, aged between 40 and 64 years, in the Korea National Health and Nutrition Examination Survey (2019–2021) were analyzed. The risk of OSA was assessed using STOP-Bang questionnaire. CVH metrics, including smoking status, diet, physical activity, body mass index (BMI), blood pressure, total cholesterol level, and fasting glucose concentration, were evaluated using American Heart Association criteria. Multivariate logistic regression analysis was employed to investigate the association between OSA risk and CVH. Results: Among study participants, 78.6% of men and 16.3% of women displayed moderate-to-high risk of OSA, while 45.4% of men and 17.2% of women exhibited poor CVH. The ORs (95% CIs) for poor CVH were 2.69 (2.08–3.49) for men at moderate risk of OSA and 6.54 (4.81–8.90) for those at high risk, compared to men at low risk. For women, the ORs were 3.21 (2.47–4.19) for those with moderate risk and 12.88 (6.29–26.38) for those with high risk of OSA, compared to women at low risk. CVH metrics associated with moderate-to-high OSA risk included high BMI, high blood pressure, elevated fasting glucose, and smoking. Conclusions: The risk of OSA was associated with poor CVH, while various CVH components were linked to moderate-to-high OSA risk. Managing both OSA and components of CVH is essential to minimize poor CVH.
Applying Neural Networks to Predict Offshore Platform Dynamics
Authors: Martzikos Nikolas , Ruzzo Carlo , Malara Giovanni , Fiamma Vincenzo , Arena Felice
Published: November 2024

Integrating renewable energy sources with aquaculture systems on floating multi-use platforms presents an innovative approach to developing sustainable and resilient offshore infrastructure, utilizing the ocean’s considerable potential. From March 2021 to January 2022, a 1:15-scale prototype was tested in Reggio Calabria, Italy, which gave crucial insights into how these structures behave under different wave conditions. This study investigates the application of Artificial Neural Networks (ANNs) to predict changes in mooring loads, particularly at key points of the structure. By analyzing metocean data, several ANN models and optimization techniques were evaluated to identify the most accurate predictive model. With a Normalized Root Mean Square Error (NRMSE) of 1.7–4.7%, the results show how ANNs can effectively predict offshore platform dynamics. This research highlights the potential of machine learning in developing and managing sustainable ocean systems, setting the stage for future advancements in data-driven marine resource management.
Experimental Study of Wave Load Distributions on Pile Groups Affected by Cap Structures and Pile Spacings Under Varied Wave Conditions
Authors: Han Wanshui , Zhou Kai , Wang Jiajia , Xiao Lili , Xu Xin , Xiang Yuheng , Yu Xi
Published: November 2024

Wave-induced forces pose significant challenges to marine structures, especially pile groups, where cap structures and pile spacings play critical roles in load distribution and structural stability. A physical wave flume experiment was conducted to investigate the influences of cap structures and pile spacings on wave load distributions under different wave conditions. Spatial and temporal variations in wave load distributions, including temporal variations in horizontal force, were measured as wave pressure rather than force. The results demonstrate that cap structures significantly alter the distributions of wave loads on pile groups. The integration of the cap increases the horizontal forces on the front pile and slightly reduces the vertical pressures across the pile group, particularly on the rear pile at relatively low elevations. The cap also delays the peak moment of horizontal force, especially in shallow water depths, where impact loads are more prominent and the cap induces water splash-back. Additionally, reducing pile spacing mitigates interference effects, optimizing the load distribution across piles by modulating flow velocity and pressure. The vertical pressure distribution exhibits a tiered pattern, with lower sections experiencing consistent loading, middle sections being subjected to higher loads at larger spacings, and upper sections being more affected by the cap at smaller spacings. As wave velocity and water depth increase, the differences in pressure intensity between pile groups with and without cap structures decrease, indicating the stabilizing effect of wave characteristics on structural response. This study provides insights into the design of marine pile group structures to optimize their performance characteristics under dynamic wave loading conditions.
The Long-Term Impact of Polysaccharide-Coated Iron Oxide Nanoparticles on Inflammatory-Stressed Mice
Authors: Göring Julia , Schwarz Claudia , Unger Eric , Quaas Rainer , Hilger Ingrid
Published: November 2024

Since iron oxide nanoparticles (IONPs) are expected to be important tools in medical care, patients with inflammatory diseases will be increasingly exposed to IONPs in the future. Here, we assessed the short- and long-term impact of polysaccharide (PS)-coated IONPs on mice with persistent systemic inflammation. To this end, PS-IONPs were synthetized by a core-shell method. Mice were regularly injected with sterile zymosan. PS-IONPs were administered intravenously. At specific nanoparticle injection post-observation times, the organ iron concentration was determined via atomic absorption spectrometry, the expression of NF-κB-related proteins using SDS-PAGE and immunoblotting, as well as body weight and haemograms. Finally, the mediator secretion in blood plasma was analysed using multiplexed ELISA. Our data show that PS-IONPs induce short-term changes of iron levels in distinct organs and of NF-κB p65 and p50, p100, COX-2s, and Bcl-2 protein expression in the liver of inflammatory stressed mice. In the long term, there was an attenuated expression of several NF-κB–related proteins and attenuated features of inflammatory-based anaemia in blood. PS-IONPs weakly influenced the blood cytokine levels. PS-IONPs are biocompatible, but given their short-term pro-inflammatory impact, they should prospectively be applied with caution in patients with inflammatory diseases of the liver.
Classification, Chemical, and Toxicological Properties of Carbamate Nerve Agents
Authors: Pampalakis Georgios
Published: November 2024

Nerve agents are usually identified as exceedingly toxic organophosphate compounds like VX and sarin. Nevertheless, although carbamate nerve agents (CNAs) have been developed they constitute the least studied class of nerve agents outside military literature. Recently, CNAs gained popularity after the inclusion of a small subset of carbamate agents in the Chemical Weapons Convention (CWC) list of Schedule 1 chemicals. Here, a holistic approach was used to identify and categorize the developed CNAs. It is demonstrated that CNAs encompass a highly diverse class of compounds. Their main characteristics include an aromatic group that carries the carbamate moiety. Based on their chemical structure, CNAs were categorized into two generations that are further divided into various subclasses. The second generation of CNAs includes some members that exhibit higher toxicity than VX. CNAs have not been used in any conflict, which may be related to their solid nature that requires sophisticated delivery systems. Since, however, CNAs can be applied as poisons in individualized cases, understanding their chemistry and toxicological properties is important for the development of effective countermeasures.
How Accurately Is Topsoil Texture Shown on Agricultural Soil Maps? A Case Study of Eleven Fields Located in Poland
Authors: Stępień Michał , Gozdowski Dariusz , Samborski Stanisław
Published: November 2024

Agricultural soil maps (ASMs) showing the agricultural land of Poland were prepared at a 1:5000 scale in the 1960s and 1970s. These maps show land suitability groups, soil type, and soil texture (ST) to a depth of 150 cm. Nowadays, these maps are being digitalized and might be a basis for the preparation of modern soil maps at the local, regional, national, and international levels. The agreement between the ST of the topsoil derived from ASMs and the recently evaluated one for eleven fields located in three voivodeships (regions) of Poland was studied. This study considered the examination of soil profiles or augerings and the laboratory analysis of the ST. The agreement between the ST status in the field and that according to the ASMs was field-specific. A complete agreement (purity) within the field was assessed for 5–79% of ST classes and for 23–100% of agronomic categories (ACs), i.e., groupings of similar ST classes. However, the averaged agreement, which treated adjacent ST classes as having a partial agreement, varied from 37 to 88% for ST classes and from 61 to 100% for the ACs among studied fields. These results indicate the variable quality of the information shown on ASMs and the necessity of improving these maps.
Study on the Population Carrying Scale of Arable Land in Southern Xinjiang, China
Authors: Liu Huanran , Ding Jianli , Li Xiang , Wang Jinjie
Published: November 2024

Research on the carrying capacity of land resources and their outputs to population size will be able to better serve the ecological governance of food security. This paper analyzes the population carrying capacity level of southern Xinjiang by using the population carrying capacity model of land resources, and ANOVA analyzes the significance difference between the newly added arable land and the original arable land. At the same time, the demand of cultivated land development is discussed. The results showed that the sown area of grain crops in all the prefectures showed an overall increase from 2009 to 2019. The population carrying scale is more optimistic under subsistence and well-off conditions. From 2009 to 2019, cropland in Aksu region increased the most, followed by Kashgar region, with both regions exceeding 300,000 ha. ANOVA results show that the new arable land is comprehensively lower than the original arable land in terms of quality grade and agricultural output, and salinization and desertification are more serious than on the original arable land. At the same time, the subsistence type requires the least amount of arable land development while the affluent type requires the most. Therefore, we should adapt to local conditions and develop modern agriculture scientifically and reasonably.
Evaluation of Tree Object Segmentation Performance for Individual Tree Recognition Using Remote Sensing Techniques Based on Urban Forest Green Structures
Authors: Sung Uk-Je , Eum Jeong-Hee , Chung Kyung-Jin
Published: November 2024

This study evaluated whether tree object segmentation using remote sensing techniques could be effectively conducted according to the green structures of urban forests. The remote sensing techniques used were handheld LiDAR and UAV-based photogrammetry. The data collected from both methods were merged to complement each other’s limitations. The green structures of the study area were classified into three types based on the distance between canopy trees and the presence of shrubs. The ability to individually classify trees within each of the three types of green structures was then evaluated. The evaluation method was to assess the success rate by comparing the actual number of trees, which were visually counted in the field, with the number of tree objects classified in the study. To perform semantic segmentation of tree objects, a preprocessing step was conducted to extract only the data related to tree structures from the data collected through remote sensing techniques. The preprocessing steps included data merging, noise removal, separation of DTM and DSM, and separation of green areas and structures. The analysis results showed that tree object recognition was not efficient when the green structures were complex and mixed, and the recognition rate was highest when only canopy trees were present, and the canopies did not overlap. Therefore, when observing in high-density areas, the semantic segmentation algorithm’s variables should be adjusted to narrow the object recognition range, and additional observations in winter are needed to compensate for areas obscured by leaves. By improving data collection methods and systematizing the analysis methods according to the green structures, the object recognition process can be enhanced.
Sustainability Assessment of Geotourism Consumption Based on Energy–Water–Waste–Economic Nexus: Evidence from Zhangye Danxia National Geopark
Authors: Xia Bing
Published: November 2024

The development of geotourism and the establishment of geoparks can generate new job opportunities, new economic activities, and additional sources of income, with great significance in achieving the United Nations Sustainable Development Goals. Tourists often consume more energy and water and generate more waste in order to seek a more comfortable state during their travels. This research took Zhangye Danxia National Geopark in the north slope of the Qinghai–Tibet Plateau in China as an example and combined field research with questionnaires to construct a non-radial model (SBM) based on energy-water-waste-economic nexus. From the perspective of consumption, this research focuses on the consumer characteristics of geotourism sustainability based on the energy–water–waste–economic nexus (GTS-EWWE) and the driving factors behind them under different degrees of consumption. The elderly, children, and high-income tourists can contribute more to the sustainability of geotourism. Stay duration in the geopark and energy consumption are the native driving factors behind the sustainability of geotourism. However, with the improvement of the tourism consumption level, the marginal effect of the negative influence of both factors is diminishing gradually. While tourism expenditure is a positive driving factor, the tourist’s travel mode and the consumer’s awareness of ecological–environmental actions will contribute more to the sustainability of geotourism. New energy technologies to promote the green development of geoparks is significant. This research aims to provide a reference for the sustainability assessment of geoheritage sights and to provide evidence for the appropriate management policy with respect to their sustainable development.
Spatial Patterns and Influencing Factors of People’s Commune Sites: A Case Study of Henan Province, China
Authors: Zhu Yi , Tian Yasi , Tang Guoyan , Zheng Dantong , Yu Fei
Published: November 2024

The people’s commune was a social practice for achieving a communist society after the establishment of New China, but they were dismantled in the early 1980s, along with their legacy. This paper analyzes people’s commune sites, offering guidance for their protection and development. This study used the historical place names of the communes recorded in the Overview of People’s Commune, compiled a comprehensive database of people’s commune sites, and mathematically analyzed the quantity and type of communes. The spatial pattern of people’s commune sites was described via average nearest neighbors, spatial variability, kernel density analysis, and spatial correlation. Moreover, the driving mechanism was measured using the geodetector model. The survey results revealed 327 points related to people’s communes, which were categorized into three main types: agriculture-oriented, industry-oriented, and integrated. Agriculture-oriented communes are the most significant type of people’s commune, accounting for 87.0%. Communes in the northern region of Henan Province are more densely clustered, whereas those in the southeastern region are less concentrated. Moreover, precipitation is the most critical factor affecting the spatial pattern of people’s commune sites, followed by railroad accessibility. A comprehensive literature analysis revealed that water conservancy projects limited the development of communes during the people’s commune period. This paper analyzes the spatial distribution patterns of the sites that have existed historically according to historical gazetteers, revealing the factors that influenced the development of this particular political system. It enriches the spatial scope of the study of people’s communes and provides theoretical references for the future preservation of communal heritage from the perspective of regional heritage.
Spatiotemporal Analysis of High-Quality Development and Coordination in Cities Along the Lower Yellow River
Authors: Zhai Ge , Zhang Maoxin , He Tingting , Ren Peng
Published: November 2024

The current urban development in cities along the Lower Yellow River is in tension regarding human–land relations. To achieve the goals of ecological protection and high-quality development (HQD), it is urgent to scientifically measure and analyse the region’s function development and development coordination (DC). This study focuses on cities along the Lower Yellow River, constructs a three-dimensional HQD assessment framework based on urban functions through multiple remote sensing data, and evaluates DCs by feature classification. The results show the following: (1) The HQD of the study area shows a trend of decreasing and then increasing during 2000–2020 and reaches its highest level at the end. HQD shows a spatial trend of decreasing from south to north and from east to west. (2) The overall agricultural function of the study area declined slightly; the ecological function declined first and then increased, with the highest value occurring in 2000; and the urban function increased steadily and improved significantly after 2015. (3) DCs under different administrative levels are polarised, with high-level DCs exhibiting a spatial leader effect. (4) Urban development preferences in the study area are divergent, and the functional type with the highest share under different administrative scales is agro-ecological, which is mainly influenced by differences in natural base. This study reveals the characteristics of HQD and functional changes in cities along the Lower Yellow River, combined with a hierarchical classification of DCs and the types of development preferences, providing a reference for the formulation of spatial governance strategies.
Effects of Blood Flow Restriction Training on Muscle Strength and Hypertrophy in Untrained Males: A Systematic Review and Meta-Analysis Based on a Comparison with High-Load Resistance Training
Authors: Chang Hualong , Zhang Jie , Yan Jing , Yang Xudong , Chen Biao , Zhang Jianli
Published: November 2024

This meta-analysis examined the efficacy of low-load resistance training with blood flow restriction (LL-BFR) versus high-load resistance training (HL-RT) on muscle strength and hypertrophy, exploring factors affecting outcomes. We searched Embase, CNKI, Wanfang, PubMed, Ovid Medline, ProQuest, Cochrane Library, Embase, and Scopus from inception to July 2024. After assessing the risk of bias using the Cochrane tool, a meta-analysis was conducted to calculate the overall effect size. Subgroup analyses were performed to explore the impact of different modulating factors on training effects. LL-BFR was found to be inferior to HL-RT with regard to muscle strength gains (SMD = −0.33, 95% CI: −0.49 to −0.18, p < 0.0001). However, subgroup analyses revealed that LL-BFR achieved muscle strength gains comparable to HL-RT under individualized pressure (SMD = −0.07, p = 0.56), intermittent cuff inflation (SMD = −0.07, p = 0.65), and a higher number of training sessions (SMD = −0.12, p = 0.30). No significant difference in muscle mass gains was observed between LL-BFR and HL-RT (SMD = 0.01, p = 0.94), and this conclusion remained consistent after controlling for modulating variables. HL-RT is superior to LL-BFR in enhancing muscle strength gains. Nevertheless, under appropriate conditions, including individualized pressure prescription, intermittent cuff inflation, and a higher number of training sessions, LL-BFR can achieve muscle strength gains comparable to HL-RT, emphasizing the importance of tailored training programs. Both methods exhibit similar effects on muscle mass gains, indicating that LL-BFR serves as an effective alternative for individuals who cannot perform HL-RT because of physical limitations or injury concerns.
Niemann–Pick C1-like 1 as a Prognostic Marker in Renal Cell Carcinoma: A Retrospective Cohort Study
Authors: Kwon Ryuk Jun , Kim Ho Jun , Lee Young-Shin , Lee Hye Sun , Lee Sang Yeoup , Park Eun-Ju , Lee Youngin , Lee Sae Rom , Choi Jung-In , Son Soo Min , Lee Jeong Gyu , Yi Yu Hyeon , Tak Young Jin , Lee Seung-Hun , Kim Gyu Lee , Ra Young Jin , Cho Young Hye
Published: November 2024

Background: Renal cell carcinoma (RCC) is a highly aggressive malignancy accounting for the majority of kidney cancers. Despite recent advancements in therapeutic options, the prognosis for advanced-stage RCC remains poor. Niemann–Pick C1-Like 1 (NPC1L1) plays a crucial role in cholesterol absorption and has been implicated in cancer progression across various cancers. However, its expression patterns and prognostic significance in RCC remain unclear. Methods: In this study, NPC1L1 expression in normal and RCC tissues, including subtypes, was compared using TCGA, GEPIA2, and The Human Protein Atlas. Clinical correlations were assessed, and the impact of NPC1L1 on overall survival (OS) and progression-free survival (PFS) was evaluated. Gene effect scores were analyzed using the DepMap tool to determine the involvement of NPC1L1 in RCC progression. Results: NPC1L1 expression was significantly lower in RCC tissues compared to normal tissues, particularly in the clear cell RCC (ccRCC), papillary RCC (pRCC), and chromophobe RCC (chRCC) subtypes, but increased in advanced tumor stages. Higher NPC1L1 expression was associated with worse OS and PFS in RCC patients. Multivariable Cox regression confirmed NPC1L1 as an independent prognostic marker. Additionally, gene effect scores showed that NPC1L1 is essential for the survival of specific RCC cell lines. Conclusions: This study determines NPC1L1 as an independent prognostic indicator in RCC, with higher expression associated with poor survival outcomes. These findings suggest that NPC1L1 could serve as a valuable marker for identifying high-risk RCC patients. Further research is required to investigate the molecular mechanisms underlying the role of NPC1L1 in RCC progression.
Effect of the Complex Allele p.[Ile148Thr;Ile1023_Val1024del] in Cystic Fibrosis and Tracing of a Founder Effect in Mexican Families
Authors: Mendiola-Vidal Namibia Guadalupe , Contreras-Cubas Cecilia , Barajas-Olmos Francisco , Villafan-Bernal José Rafael , Yañez-Felix Ana Lucia , García-Ortiz Humberto , Centeno-Cruz Federico , Mendoza-Caamal Elvia , Alaez-Verson Carmen , Jiménez-Ruíz Juan Luis , Monge-Cázares Tulia , Lieberman Esther , Baca Vicente , Lezana José Luis , Martínez-Hernández Angélica , Orozco Lorena
Published: November 2024

Cystic fibrosis (CF) is a rare autosomal recessive disease most commonly affecting the Caucasian population. CF diagnosis can be a challenge due to the large spectrum of pathogenic variants in the CFTR gene and the effects of complex alleles. Next-generation sequencing has improved our understanding of the contribution of these complex alleles to the wide spectrum of CF clinical symptoms and to the response to medications. Herein, we studied nine CF patients from six unrelated families carrying the complex allele p.[Ile148Thr;Ile1023_Val1024del] with a frequency of 0.18%. All patients were from Central Mexico. This complex allele was found in trans with Class I and II pathogenic variants such as p.(Phe508del), and p.(Phe1078Profs*77)]. A targeted search of a dataset of 2217 exomes from healthy individuals revealed that eight individuals (0.18%) carried the p.(Ile148Thr) variant, but only one (0.022%), who was also born in Central Mexico, was a carrier of the complex allele. These findings show an enrichment of this p.[Ile148Thr;Ile1023_Val1024del] complex allele in Mexican CF patients in this region of Mexico. Finally, protein modeling revealed that this complex allele disrupts the secondary structure of the CFTR protein and might alter the ion flow.
Hemodialysis Patients May Benefit from Cholecalciferol Treatment Targeting High Level of 25(OH)D
Authors: Tarasewicz Agnieszka , Dąbrowska Małgorzata , Komorniczak Michał , Zakrzewska Agnieszka , Biedunkiewicz Bogdan , Małgorzewicz Sylwia , Jankowska Magdalena , Jasiulewicz Katarzyna , Płonka Natalia , Dębska-Ślizień Alicja , Tylicki Leszek
Published: November 2024

(1) Background and Objectives: Vitamin D is implicated in the pathogenesis of Chronic Kidney Disease—Mineral and Bone Disorder (CKD-MBD) in hemodialysis (HD) patients, including the development of secondary hyperparathyroidism (SHP). While cholecalciferol supplementation is recommended for vitamin D deficiency correction, its impact on CKD-MBD remains inconsistent. The aim of this observational prospective study was to assess the effect of cholecalciferol in achieving high–normal serum 25-hydroxycholecalciferol (25(OH)D > 75 ng/mL) levels and its impact on CKD-MBD biochemical markers, including 1,25-dihydroxycholecalciferol (1,25(OH)2D) and parathormone (PTH) in HD patients. The study also evaluated the maintenance dosage required to sustain 25(OH)D levels within the 50–75 ng/mL range. (2) Materials and Methods: A total of 22 HD patients with baseline 25(OH)D levels 30–50 ng/mL received cholecalciferol (70,000 IU/week) to achieve the target serum 25(OH)D > 75 ng/mL. Baseline data on calcium, phosphate, 1–84 PTH, 25(OH)D, and 1,25(OH)2D serum levels were compared with the data when 25(OH)D > 75 ng/mL was targeted or when the highest 25(OH)D levels were noted. (3) Results: Cholecalciferol significantly improved vitamin D status in HD patients, with 73% reaching the target 25(OH)D level >75 ng/mL in a median time of 7.5 weeks, with a median total dose of 525,000 IU. This was associated with a significant rise in 1,25(OH)2D, decrease in 1–84 PTH, and no significant effect on calcium and phosphate levels. The median maintenance dose of cholecalciferol was established at 30,000 IU/week. (4) Conclusions: The findings support the use of cholecalciferol targeting high normal 25(OH)D levels to improve biochemical markers of CKD-MBD in HD patients.
Self-Powered Photoelectrochemistry Biosensor for Ascorbic Acid Determination in Beverage Samples Based on Perylene Material
Authors: Zhang Wei , Sun Xinyang , Liu Hong , Shang Lei , Ma Rongna , Li Xiaojian , Jia Liping , He Shuijian , Li Chuan , Wang Huaisheng
Published: November 2024

Ascorbic acid plays an important role in the synthesis and metabolism of the human body. However, it cannot be synthesized by the human body and needs to be supplemented from exogenous food intake. Ascorbic acid is easily degraded during storage and heating, often causing its content in food to change. It is important to develop a sensitive and accurate photoelectrochemistry (PEC) biosensor for detecting ascorbic acid. The shortage of PEC materials with long illumination wavelengths and low bias voltages impedes the development of ascorbic acid biosensors. Herein, a 3,4,9,10-perylenetetracarboxylic dianhydride (PDA) self-assembly rod material was firstly reported to show significant photocurrent increases to ascorbic acid at 630 nm illumination and 0 V vs. Ag/AgCl. Moreover, the PDA self-assembly rod material was used as a PEC platform to detect ascorbic acid. This self-powered PEC biosensor exhibited a linear response for ascorbic acid from 5 μM·L−1 to 400 μM·L−1; the limit of detection was calculated to be 4.1 μM·L−1. Compared with other ascorbic acid biosensors, the proposed self-powered PEC biosensor shows a relatively wide linear range. In addition, the proposed self-powered PEC biosensor exhibits good practicability in beverage samples.
When Chirality Makes the Difference: The Case of Novel Enantiopure N-Heterocyclic Carbene–Gold and –Silver Complexes
Authors: Marra Maria , Mariconda Annaluisa , Iacopetta Domenico , Ceramella Jessica , D’Amato Assunta , Rosano Camillo , Tkachenko Kateryna , Pellegrino Michele , Aquaro Stefano , Sinicropi Maria Stefania , Longo Pasquale
Published: November 2024

N-heterocyclic carbene (NHC)–gold and –silver complexes have attracted the interest of the scientific community because of their multiple applications and their versatility in being chemically modified in order to improve their biological properties. However, most of these complexes contain one or more chiral centers, and have been obtained and studied as racemic mixture. In particular, concerning the interesting biological and medicinal properties, many questions about how the chirality may influence these properties still remain unanswered. Aiming at a better understanding, herein a series of enantiopure NHC–gold and –silver complexes was synthesized, characterized and biologically evaluated in different in vitro systems. The individuated complexes exerted different properties based on the complexed metal and the specific configuration, with the (R)-gold–NHC complexes being the most active, particularly as anti-inflammatory molecules. Docking simulations indicated a different binding mode for each enantiomer. Moreover, anticancer and antibacterial activities were also evaluated for the considered enantiomers. Overall, the reported data may contribute to a better understanding of the different biological properties exerted by the enantiopure gold and silver complexes.
Anchoring and Catalytic Performance of Co@C2N Monolayer for Rechargeable Li-SexSy Batteries: A First-Principles Calculations
Authors: Li Xiaojing , Zhang Yingbo , Liu Chenchen , Tang Shuwei
Published: November 2024

SexSy composite cathode materials, which offer superior theoretical capacity compared to pure selenium and improved electrochemical properties relative to pure sulfur, have aroused considerable interest in recent decades on account of their applications in electric vehicles and energy storage grids. In the current work, the feasibility of a Co@C2N monolayer as a promising host candidate for the cathode material of Li-SexSy batteries has been evaluated using first-principles calculations, and particular efforts have been devoted to underscoring the anchoring mechanism and catalytic performance of the Co@C2N monolayer. The pronounced synergistic effects of Co-S and Li-N bonds lead to increased anchoring performance for Li2SexSy/SexSy clusters on the surface of Co@C2N monolayer, which effectively inhibit the shuttle effect. The charge density difference and Mulliken charge analysis underscores a substantial charge transfer from the Li2SexSy and SexSy clusters to the Co@C2N monolayer, which indicates a noticeable chemical interaction between them. Further electronic property calculations show that the Co@C2N monolayer can improve the electrical conductivity of cathode materials for Li-SexSy batteries by maintaining semi-metallic characteristics after anchoring of Li2SexSy/SexSy clusters. Additionally, the catalytic performance of the Co@C2N monolayer is evaluated in terms of the reduction pathway of Se8 and the decomposition energy barrier of the Li2SeS cluster, which highlights the catalytic role of the Co@C2N monolayer in the formation and decomposition of the Li2SeS cluster during the cycle processes. Overall, the Co@C2N monolayer emerges as a promising host material and catalyst for Li-SexSy batteries with remarkable anchoring and catalytic performance.
Cytotoxic Effects of Plant Secondary Metabolites and Naturally Occurring Bioactive Peptides on Breast Cancer Model Systems: Molecular Mechanisms
Authors: Zasheva Diana , Mladenov Petko , Zapryanova Silvina , Gospodinova Zlatina , Georgieva Mariyana , Alexandar Irina , Velinov Valentin , Djilianov Dimitar , Moyankova Daniela , Simova-Stoilova Lyudmila
Published: November 2024

Breast cancer is the second leading cause of death among women, and the number of mortal cases in diagnosed patients is constantly increasing. The search for new plant compounds with antitumor effects is very important because of the side effects of conventional therapy and the development of drug resistance in cancer cells. The use of plant substances in medicine has been well known for centuries, but the exact mechanism of their action is far from being elucidated. The molecular mechanisms of cytotoxicity exerted by secondary metabolites and bioactive peptides of plant origin on breast cancer cell lines are the subject of this review.
In Situ Nitrate Monitoring for Improved Fertigation in On-Demand Coupled Aquaponic Systems
Authors: Faliagka Sofia , Naounoulis Ioannis , Pechlivani Eleftheria Maria , Katsoulas Nikolaos
Published: November 2024

Fertigation practices in soilless crop cultivation often rely on predetermined recipes, which may lead to suboptimal nutrient concentrations due to inherent human error or environmental fluctuations. To address this challenge, the integration of in situ real-time nutrient analyzers becomes imperative for ensuring the delivery of high-quality supply solutions. This study assesses the effectiveness of a real-time nitrate (NO3−) analyzer in optimizing the mineral composition of the nutrient solution for fertigating a decoupled aquaponic cucumber crop. The analyzer was integrated into the programmable logic controller of the greenhouse’s hydroponic system. The NO3− analyzer was activated during solution preparation, dynamically adjusting the NO3− concentration based on real-time measurements from either the aquaculture or drainage solution by adding the necessary water or/and nutrients in order to prepare a solution to meet the needs of the crop. Four treatments were evaluated: hydroponics (HP), coupled aquaponics (CAP), decoupled aquaponics (DCAP) with EC adjustment, and decoupled aquaponics with NO3− adjustment (DCAP_N). Results indicated that the DCAP_N treatment, with NO3− adjustment, yielded the highest crop productivity, outperforming DCAP, HP, and CAP treatments by 7.4%, 21.2%, and 56.1%, respectively. Additionally, DCAP_N demonstrated superior water use efficiency (WUE) and fertilizer use efficiency (FUE), exhibiting a 21.5% and 52.5% increase over the HP treatment, respectively. These findings align with the European Green Deal’s objectives by enhancing nutrient management practices, which are crucial for minimizing nutrient loss and ensuring the sustainable and efficient use of fertilizers.
Synthesis of Thieno[3,2-b]thiophenes from 2,5-Dicarbonyl 3-Nitrothiophenes via Nucleophilic Aromatic Substitution of the Nitro Group with Thiolates
Authors: Irgashev Roman A. , Kazin Nikita A.
Published: November 2024

In this study, we developed an efficient strategy for constructing thieno[3,2-b]thiophene molecules from 3-nitrothiophenes, containing carbonyl fragments at the C-2 and C-5 atoms, by nucleophilic aromatic substitution of the nitro group in these substrates. It was shown that the reaction of 3-nitrothiophene-2,5-dicarboxylates with thiophenols, thioglycolates and 2-mercaptoacetone in the presence of K2CO3 proceeds rapidly via nucleophilic displacement of the nitro group with the formation of 3-sulfenylthiophene-2,5-dicarboxylates. Further treatment of the resulting thiophene-2,5-dicarboxylates, which have -SCH2CO2Alk or -SCH2COMe moiety at C-3 atom, with sodium alcoholates afford obtaining 2,3,5-trisubstituted thieno[3,2-b]thiophene derivatives according to the Dieckman condensation. In turn, the reaction of methyl 5-formyl-4-nitrothiophene-2-carboxylate with methyl thioglycolate or 2-mercaptoacetone in the presence of K2CO3 proceeds to directly form 2,5-disubstituted thieno[3,2-b]thiophenes.
Depuration of Aliarcobacter butzleri and Malaciobacter molluscorum in Comparison with Escherichia coli in Mussels (Mytilus galloprovincialis) and Oysters (Crassostrea gigas)
Authors: Salas-Massó Nuria , Fernández-Bravo Ana , Bertomeu Edgar , Andree Karl B. , Figueras Maria José , Furones Dolors
Published: November 2024

Arcobacter-related species are considered emerging food-borne and waterborne pathogens, with shellfish being a suggested reservoir. In a published study that investigated 204 shellfish samples and 476 isolates, the species Arcobacter butzleri (now known as Aliarcobacter butzleri) and Arcobacter molluscorum (now known as Malaciobacter molluscorum) have been isolated as the most dominant species. However, the efficiency of depuration for eliminating A. butzleri and M. molluscorum in comparison with Escherichia coli from mussels and oysters is unknown and is therefore the objective of this investigation. The shellfish depuration process was evaluated in the laboratory, in summer and winter, using mussels and oysters collected from the Ebro Delta harvesting areas after performing a natural contamination and an artificial contamination using the same conditions for both mollusk and seasons. The natural contamination was performed by exposing the shellfish to a freshwater channel that receives untreated sewage from the village of Poble Nou (PNC) and that had a salinity of 10.7–16.8‰. The artificial contamination exposed the shellfish to A. butzleri and E. coli (in one tank) and to M. molluscorum and E. coli in another tank under controlled conditions of salinity (34.5‰) and temperature (20 °C summer and 14 °C winter). When evaluating the reduction in the bacteria load (every 24 h) throughout 120 h, the naturally contaminated shellfish at the PNC showed a higher reduction than the shellfish contaminated at the laboratory, with the exception of M. molluscorum, that at 24 h could not be detected in summer, neither in mussels nor in oysters. This may be attributed to the fact that the bacteria from the PNC were less adapted to the conditions of high salinity (34.5‰) in which the depuration process was performed. Although temperature did not statistically make a difference in depuration, at 20 °C a higher elimination of all bacteria was recorded relative to 14 °C. In general, E. coli survived more in mussels than in oysters, and M. molluscorum suffered in both mollusks a higher reduction than A. butzleri. New studies are required to determine further the safety of bivalves regarding the presence of Arcobacter-related species.
Multidrug Resistant Pseudomonas aeruginosa in Clinical Settings: A Review of Resistance Mechanisms and Treatment Strategies
Authors: Schwartz Beth , Klamer Katherine , Zimmerman Justin , Kale-Pradhan Pramodini B. , Bhargava Ashish
Published: November 2024

Pseudomonas aeruginosa is causing increasing concern among clinicians due to its high mortality and resistance rates. This bacterium is responsible for various infections, especially in hospital settings, affecting some of the most vulnerable patients. Pseudomonas aeruginosa has developed resistance through multiple mechanisms, making treatment challenging. Diagnostic techniques are evolving, with rapid testing systems providing results within 4–6 h. New antimicrobial agents are continuously being developed, offering potential solutions to these complex clinical decisions. This article provides a review of the epidemiology, at-risk populations, resistance mechanisms, and diagnostic and treatment options for Pseudomonas aeruginosa.