bluuebunny/crossref_metadata_2025 huggingface dataset:
Strategies to Target Chemoradiotherapy Resistance in Small Cell Lung Cancer
Authors: Yu Tony , Lok Benjamin H.
Published: October 2024

Background: Small cell lung cancer (SCLC) is a lethal form of lung cancer with few treatment options and a high rate of relapse. While SCLC is initially sensitive to first-line DNA-damaging chemo- and radiotherapy, relapse disease is almost universally therapy-resistant. As a result, there has been interest in understanding the mechanisms of therapeutic resistance in this disease. Conclusions: Progress has been made in elucidating these mechanisms, particularly as they relate to the DNA damage response and SCLC differentiation and transformation, leading to many clinical trials investigating new therapies and combinations. Yet there remain many gaps in our understanding, such as the effect of epigenetics or the tumor microenvironment on treatment response, and no single mechanism has been found to be ubiquitous, suggesting a significant heterogeneity in the mechanisms of acquired resistance. Nevertheless, the advancement of techniques in the laboratory and the clinic will improve our ability to study this disease, especially in patient populations, and identify methods to surmount therapeutic resistance.
Characteristics and Management of Children with Appendiceal Neuroendocrine Neoplasms: A Single-Center Study
Authors: Mastrangelo Stefano , Attinà Giorgio , Rindi Guido , Romano Alberto , Maurizi Palma , Ruggiero Antonio
Published: October 2024

Background/Objectives: Appendiceal neuroendocrine neoplasms (ANENs) are usually found incidentally during histology examination after appendectomy for appendicitis. Due to their rarity in pediatric populations, there is no consensus on treatment or follow-up. The analysis of patients with ANENs of our and other studies will increase the understanding of this tumor. Methods: Pediatric patients with ANENs were uniformly managed at our center between 1998 and 2023. Patients’ presenting symptoms, surgery, tumor histology, post-surgical work-up, follow-up and outcome were analyzed. Results: Our report describes 17 patients with a diagnosis of ANEN after appendectomy. The median age was 14 years (range of 4–17 years). Tumors were located at the tip of the appendix in 58.8% of cases and only one had a diameter >1 cm. All were well-differentiated tumors with free resection margins. The submucosa was invaded in five cases, muscularis propria in eight and subserosa in four. Post-appendectomy work-up included tumor marker measurement, abdominal ultrasound and computed tomography or magnetic resonance imaging, chest X-ray and octreotide scintigraphy. No residual tumors or metastases were detected. Additional surgery was not necessary. Follow-up was carried out for a median duration of 6 years (range of 1–10 years). Only one patient was lost to follow-up and all other patients are alive without tumor recurrence. Conclusions: The tumor characteristics of our patients confirmed data from the literature. With the lack of a sufficient number of large prospective trials, it is important to add more information to confirm the benign nature and excellent outcome of this tumor, even without additional surgery. Consensus guidelines are needed for ANENs in pediatric populations.
A Rare Endobronchial Tumor in a Pediatric Patient
Authors: Parekh Pooja , Wagh Ajay
Published: October 2024

A pediatric patient who presented with non-specific respiratory symptoms, including mild hemoptysis, wheezing, and eventual respiratory distress, was found to have a rare endobronchial inflammatory myofibroblastic tumor obstructing her right mainstem bronchus. It was diagnosed and initially debulked using bronchoscopy, which helped to stabilize the patient and eliminate the need for supplemental oxygen. The patient subsequently underwent successful removal of the residual tumor with parenchymal-sparing sleeve resection. This case highlights the importance of pursuing appropriate imaging along with diagnostic and therapeutic bronchoscopy for an endobronchial lesion to help manage pediatric patients with persistent respiratory symptoms.
New Section: Clinical Diagnosis and Prognosis
Authors: Kjaer Andreas
Published: October 2024

It is with pleasure that we introduce a new section of Diagnostics, named “Clinical Diagnosis and Prognosis” [...]
Sex Differences in Fat Distribution and Muscle Fat Infiltration in the Lower Extremity: A Retrospective Diverse-Ethnicity 7T MRI Study in a Research Institute Setting in the USA
Authors: Johnson Talon , Su Jianzhong , Andres Johnathan , Henning Anke , Ren Jimin
Published: October 2024

Background: Fat infiltration in skeletal muscle is related to declining muscle strength, whereas excess subcutaneous fat is implicated in the development of metabolic diseases. Methods: Using multi-slice axial T2-weighted (T2w) MR images, this retrospective study characterized muscle fat infiltration (MFI) and fat distribution in the lower extremity of 107 subjects (64M/43F, age 11–79 years) with diverse ethnicities (including White, Black, Latino, and Asian subjects). Results: MRI data analysis shows that MFI, evaluated by the relative intensities of the pixel histogram profile in the calf muscle, tends to increase with both age and BMI. However, statistical significance was found only for the age correlation in women (p < 0.002), and the BMI correlation in men (p = 0.04). Sex disparities were also seen in the fat distribution, which was assessed according to subcutaneous fat thickness (SFT) and the fibula bone marrow cross-sectional area (BMA). SFT tends to decrease with age in men (p < 0.01), whereas SFT tends to increase with BMI only in women (p < 0.01). In contrast, BMA tends to increase with age in women (p < 0.01) and with BMI in men (p = 0.04). Additionally, MFI is positively correlated with BMA but not with SFT, suggesting that compromised bone structure may contribute to fat infiltration in the surrounding skeletal muscle. Conclusions: The findings of this study highlight a sex factor affecting MFI and fat distribution, which may offer valuable insights into effective strategies to prevent and treat MFI in women versus men.
FedBeam: Reliable Incentive Mechanisms for Federated Learning in UAV-Enabled Internet of Vehicles
Authors: Hu Gangqiang , Zhu Donglin , Shen Jiaying , Hu Jialing , Han Jianmin , Li Taiyong
Published: October 2024

Unmanned aerial vehicles (UAVs) can be utilized as airborne base stations to deliver wireless communication and federated learning (FL) training services for ground vehicles. However, most existing studies assume that vehicles (clients) and UAVs (model owners) offer services voluntarily. In reality, participants (FL clients and model owners) are selfish and will not engage in training without compensation. Meanwhile, due to the heterogeneity of participants and the presence of free-riders and Byzantine behaviors, the quality of vehicles’ model updates can vary significantly. To incentivize participants to engage in model training and ensure reliable outcomes, this paper designs a reliable incentive mechanism (FedBeam) based on game theory. Specifically, we model the cooperation problem between model owners and clients as a two-layer Stackelberg game and prove the existence and uniqueness of the Stackelberg equilibrium (SE). For the cooperation among model owners, we formulate the problem as a coalition game and based on this, analyze and design a coalition formation algorithm to derive the Pareto optimal social utility. Additionally, to achieve reliable FL model updates, we design a weighted-beta (Wbeta) reputation update mechanism to incentivize FL clients to provide high-quality model updates. The experimental results show that compared to the baselines, the proposed incentive mechanism improves social welfare by 17.6% and test accuracy by 5.5% on simulated and real datasets, respectively.
Airfoil Optimization Using Deep Learning Models and Evolutionary Algorithms for the Case Large-Endurance UAVs Design
Authors: Minaev Evgenii , Quijada Pioquinto Jose Gabriel , Shakhov Valentin , Kurkin Evgenii , Lukyanov Oleg
Published: October 2024

This article presents the development of the AZTLI-NN network and the evaluation of this network as a set of evolutionary algorithms in airfoil optimization tasks. AZTLI-NN has the characteristic of predicting the aerodynamic coefficients of the airfoils in the form of images (graphs of the aerodynamic coefficients as a function of the angle of attack) from parameter vectors corresponding to the parameterization method CST. This feature allows the network to achieve good performance when generalizing the predictions of the aerodynamic coefficients, being on par with neural networks that have the aerodynamic coefficients encoded in the form of structured data, and has the ability to handle a wide range of usage airfoils in general aviation. In addition, a case of how AZTLI-NN together with an adaptive evolutionary algorithm and population size reduction methods achieve good performance in finding the airfoil that provides the highest possible endurance value is shown, so this work is considered as an option in the early stages of the design for the selection of airfoils in the design of large-endurance UAVs.
A Bidirectional Simultaneous Wireless Power and Data Transfer System with Non-Contact Slip Ring
Authors: Fan Yuanshuang , Chen Qiurui , Wu Sihan , Xiao Jing , Wang Zhihui
Published: October 2024

A non-contact slip ring is proposed in this paper. The bidirectional simultaneous wireless power and data transfer (BD-SWPDT) technology is utilized to transfer power and data bidirectionally. A bidirectional constant-voltage LC hybrid compensation topology is proposed, which utilizes the LC series parallel structure to have different equivalent models at different frequencies. By using different operating frequencies for forward and reverse power transfer, the system’s forward and reverse transfer can be equivalent to different constant-voltage output compensation topologies. The resonant parameters of the system are designed to achieve consistent voltage gain for forward and reverse power transfer. And based on this topology, a data carrier injection method is designed to achieve high Signal Noise Ratio (SNR) simultaneous data transfer. To improve the flexibility of non-contact slip ring installation, a caliper-type coupling structure is proposed. Finally, the feasibility of the proposed method is verified through experiments, achieving a forward and reverse output power of 200 W and half duplex communication with a data rate of 19.2 kbps.
A Software Defect Prediction Method That Simultaneously Addresses Class Overlap and Noise Issues after Oversampling
Authors: Wang Renliang , Liu Feng , Bai Yanhui
Published: October 2024

Software defect prediction datasets often suffer from issues such as class imbalance, noise, and class overlap, making it difficult for classifiers to identify instances of defects. In response, researchers have proposed various techniques to mitigate the impact of these issues on classifier performance. Oversampling is a widely used method to address class imbalance. However, in addition to inherent noise and class overlap in the datasets themselves, oversampling methods can introduce new noise and class overlap while addressing class imbalance. To tackle these challenges, we propose a software defect prediction method called AS-KDENN, which simultaneously improves the effects of class imbalance, noise, and class overlap on classification models. AS-KDENN first performs oversampling using the Adaptive Synthetic Sampling Method (ADASYN), followed by our proposed KDENN method to address noise and class overlap. Unlike traditional methods, KDENN takes into account both the distance and local density information of overlapping samples, allowing for a more reasonable elimination of noise and instances of overlapping. To demonstrate the effectiveness of the AS-KDENN method, we conducted extensive experiments on 19 publicly available software defect prediction datasets. Compared to four commonly used oversampling techniques that also address class overlap or noise, the AS-KDENN method effectively alleviates issues of class imbalance, noise, and class overlap, subsequently improving the performance of the classifier models.
Hybrid Feature Engineering Based on Customer Spending Behavior for Credit Card Anomaly and Fraud Detection
Authors: Alamri Maram , Ykhlef Mourad
Published: October 2024

For financial institutions, credit card fraud detection is a critical activity where the accuracy and efficiency of detection models are important. Traditional methods often use standard feature selection techniques that may ignore refined patterns in transaction data. This paper presents a new approach that combines feature aggregation with Exhaustive Feature Selection (EFS) to enhance the performance of credit card fraud detection models. Through feature aggregation, higher-order characteristics are created to capture complex relationships within the data, then find the most relevant features by evaluating all possible subsets of features systemically using EFS. Our method was tested using a public credit card fraud dataset, PaySim. Four popular learning classifiers—random forest (RF), decision tree (DT), logistic regression (LR), and deep neural network (DNN)—are used with balanced datasets to evaluate the techniques. The findings show a large improvement in detection accuracy, F1 score, and AUPRC compared to other approaches. Specifically, our method had improved F1 score, precision, and recall measures, which underlines its ability to handle fraudulent transactions’ nuances more effectively as compared to other approaches. This article provides an overall analysis of this method’s impact on model performance, giving some insights for future studies regarding fraud detection and related fields.
Study and Comparison of Hyperbolic and Pseudorange Positioning Algorithms in the eLoran System
Authors: Yang Man , Yan Baorong , Yang Chaozhong , Guo Wei , Li Shifeng
Published: October 2024

The positioning algorithms of the Enhanced Long-Range Navigation (eLoran) system primarily include the hyperbolic positioning algorithm and the pseudorange positioning algorithm. However, the calculations present in the existing literature are inaccurate and lack empirical data, and a thorough and precise comparison of the two algorithms has yet to be conducted. Therefore, this paper employs a combination of simulation analysis and empirical analysis to explore these two positioning algorithms in depth, with an optimization of the initial position calculation in the pseudorange algorithm. Under ideal conditions without observational errors, through precise calculations and analysis, the positioning errors of both algorithms are approximately zero, and full-area solutions can be achieved. Under conditions with observational errors, this study shows that both algorithms exhibit positioning errors, with the pseudorange algorithm achieving a level of accuracy comparable to that of the hyperbolic algorithm. At the same time, the empirical analysis further verified this conclusion. Additionally, this study found that the pseudorange positioning algorithm demonstrated better applicability in practical applications, as it successfully resolved the multivalued and singularity issues present in the hyperbolic positioning algorithm.
Organic Mulching Alters the Soil Microclimate, Increases Survival and Growth of Tree Seedlings in Restoration Planting
Authors: Machado Deivid Lopes , Dourado Murilo Nicolau , de Freitas Micael Silva , de Souza Letícia Moreira , da Silva Eder Marcos , Podadera Diego Sotto , Andrade Carlos Rogério , Ferreira Wendy Carniello , Guilherme Frederico Augusto Guimarães
Published: October 2024

Organic mulching has been suggested as an option for managing spontaneous species in restoration plantings and can promote improvements in soil properties and performance of planted species. The aim of this study was to test the effect of crowning techniques on soil microclimatic and performance of forest seedlings. The experiment was carried out in Goiás state, Brazil. Two study factors were used: crowning techniques (manual weeding, cardboard, wood chipping and control—without weed competition management), and six tree species: Anadenanthera peregrina, Ceiba speciosa, Dipteryx alata, Inga edulis, Genipa americana and Spondias mombin. Soil temperature and moisture assessments were performed within the crowning area (0.25 m2). Seedling survival and growth in height and diameter were evaluated over 219 days. Organic mulching treatments of wood chipping and cardboard provided increase in soil moisture and decrease in temperature, resulting in higher seedling survival rate. The increase in height and diameter differed among species under study, with A. peregrina standing out in height and C. speciosa in diameter. The crowning techniques did not influence the average height of species; however, wood chipping provided greater diameter increase. The findings of this study indicate that mulching treatments, by contributing to increase soil moisture and decrease soil temperature, can be used as crowning techniques to increase the survival rate and diameter growth of tree species in restoration plantings.
Mcan-YOLO: An Improved Forest Fire and Smoke Detection Model Based on YOLOv7
Authors: Liu Hongying , Zhu Jun , Xu Yiqing , Xie Ling
Published: October 2024

Forest fires pose a significant threat to forest resources and wildlife. To balance accuracy and parameter efficiency in forest fire detection, this study proposes an improved model, Mcan-YOLO, based on YOLOv7. In the Neck section, the asymptotic feature pyramid network (AFPN) was employed to effectively capture multi-scale information, replacing the traditional module. Additionally, the content-aware reassembly of features (CARAFE) replaced the conventional upsampling method, further reducing the number of parameters. The normalization-based attention module (NAM) was integrated after the ELAN-T module to enhance the recognition of various fire smoke features, and the Mish activation function was used to optimize model convergence. A real fire smoke dataset was constructed using the mean structural similarity (MSSIM) algorithm for model training and validation. The experimental results showed that, compared to YOLOv7-tiny, Mcan-YOLO improved precision by 4.6%, recall by 6.5%, and mAP50 by 4.7%, while reducing the number of parameters by 5%. Compared with other mainstream algorithms, Mcan-YOLO achieved better precision with fewer parameters.
Antibacterial Efficacy of Feline-Derived Lactic Acid Bacteria against Enteropathogenic Escherichia coli: A Comprehensive In Vitro Analysis
Authors: Wang Weiwei , Dong Hao , Chen Qianqian , Chang Xiaohan , Wang Longjiao , Miao Chengyi , Chen Shuxing , Chen Lishui , Wang Ran , Ge Shaoyang , Xiong Wei
Published: October 2024

This study evaluated the antibacterial efficacy of 700 feline-derived lactic acid bacteria (LAB) strains against enteropathogenic Escherichia coli (EPEC), a common cause of diarrhea in cats. Following comprehensive screening, strains ZY25 and ZY35 were identified as the most effective, with inhibition zones of ≥22 mm. These strains demonstrated strong tolerance against stress conditions, such as low pH, bile salts, and gastrointestinal fluids, alongside high hydrophobicity and auto-aggregation abilities. Safety evaluations confirmed the absence of hemolytic activity, virulence factors, and antibiotic resistance genes. The antibacterial activity of these strains is attributed to the production of organic acids, particularly lactic acid and acetic acid. These findings suggest that strains ZY25 and ZY35 have potential as natural and effective probiotic treatments for managing EPEC-induced diarrhea in cats, thus offering an alternative to conventional antibiotics.
The Averaging Principle for Caputo Type Fractional Stochastic Differential Equations with Lévy Noise
Authors: Ren Lulu , Xiao Guanli
Published: October 2024

In this paper, the averaging principle for Caputo type fractional stochastic differential equations with Lévy noise is investigated with consideration of a new method for dealing with singular integrals. Firstly, the estimate on higher moments for the solution is given. Secondly, under some suitable assumptions, we prove the averaging principle for Caputo type fractional stochastic differential equations with Lévy noise by using the Hölder inequality. Finally, a simulation example is given to verify the theoretical results.
The Rise and Decline of Settlement Sites and Traditional Rural Architecture on Therasia Island and Their Reciprocal Interaction with the Environment
Authors: Athanasiou Konstantinos
Published: October 2024

This study reconstructs the recent history of Therasia by examining the interplay between traditional settlements and the island’s natural and agricultural landscape. Through an interdisciplinary approach that integrates spatial and architectural analysis, historical records, and NDVI-based vegetation mapping, this research highlights the significant impact of agrarian structures like dry-stone walls and terraces on the environment. The unique dry-stone wall and terrace system is shown to have been crucial for both spatial organization and the survival of Therasia’s inhabitants. This study also addresses the challenges of dating these structures, employing a relative dating methodology to establish a timeline of habitation from the late medieval period to the present. This research reconstructs the island’s recent history, from early seasonal settlements to the eventual decline of rural architecture in the 20th century. The findings indicate that settlement patterns were closely linked to environmental and geomorphological factors, with the evolution of these sites driven by agricultural practices and broader socio-economic changes. This research not only reconstructs Therasia’s past, but also proposes a novel methodological framework combining remote sensing with traditional historical analysis, offering new insights into the relationship between human settlements and the environment in the Aegean region.
Recent Advancements in Postharvest Fruit Quality and Physiological Mechanism
Authors: Lv Yanrong , Ren Xiaolin , Ding Yuduan
Published: October 2024

Fresh fruits can provide people with various nutrients, including carbohydrates, vitamins, minerals, phenols, and other bioactive compounds, and they are an indispensable component of the human diet [...]
Effects of 4G Long-Term Evolution Electromagnetic Fields on Thyroid Hormone Dysfunction and Behavioral Changes in Adolescent Male Mice
Authors: Kim Hyun-Yong , Son Yeonghoon , Jeong Ye Ji , Lee Soo-Ho , Kim Nam , Ahn Young Hwan , Jeon Sang Bong , Choi Hyung-Do , Lee Hae-June
Published: October 2024

Radiofrequency electromagnetic fields (RF-EMFs) can penetrate tissues and potentially influence endocrine and brain development. Despite increased mobile phone use among children and adolescents, the long-term effects of RF-EMF exposure on brain and endocrine development remain unclear. This study investigated the effects of long-term evolution band (LTE) EMF exposure on thyroid hormone levels, crucial for metabolism, growth, and development. Four-week-old male mice (C57BL/6) were exposed to LTE EMF (whole-body average specific absorption rate [SAR] 4 W/kg) or a positive control (lead; Pb, 300 ppm in drinking water) for 4 weeks. Subsequently, the mice underwent behavioral tests including open field, marble burying, and nest building. Blood pituitary and thyroid hormone levels, and thyroid hormone-regulating genes within the hypothalamus–pituitary–thyroid (HPT) axis were analyzed. LTE exposure increased T3 levels, while Pb exposure elevated T3 and T4 and decreased ACTH levels. The LTE EMF group showed no gene expression alterations in the thyroid and pituitary glands, but hypothalamic Dio2 and Dio3 expressions were significantly reduced compared to that in the sham-exposed group. Pb exposure altered the hypothalamic mRNA levels of Oatp1c1 and Trh, pituitary mRNA of Trhr, and Tpo and Tg expression in the thyroid. In conclusion, LTE EMF exposure altered hypothalamic Dio2 and Dio3 expression, potentially impacting the HPT axis function. Further research is needed to explore RF-EMF’s impacts on the endocrine system.
Crosstalk of Hyperglycaemia and Cellular Mechanisms in the Pathogenesis of Diabetic Kidney Disease
Authors: Efiong Esienanwan Esien , Bazireh Homa , Fuchs Markéta , Amadi Peter Uchenna , Effa Emmanuel , Sharma Sapna , Schmaderer Christoph
Published: October 2024

Among all nephropathies, diabetic kidney disease (DKD) is the most common cause of kidney impairment advancement to end-stage renal disease (ESRD). Although DKD has no cure, the disease is commonly managed by strict control of blood glucose and blood pressure, and in most of these cases, kidney function often deteriorates, resulting in dialysis, kidney replacement therapy, and high mortality. The difficulties in finding a cure for DKD are mainly due to a poor understanding of the underpinning complex cellular mechanisms that could be identified as druggable targets for the treatment of this disease. The review is thus aimed at giving insight into the interconnection between chronic hyperglycaemia and cellular mechanistic perturbations of nephropathy in diabetes. A comprehensive literature review of observational studies on DKD published within the past ten years, with 57 percent published within the past three years was carried out. The article search focused on original research studies and reviews published in English. The articles were explored using Google Scholar, Medline, Web of Science, and PubMed databases based on keywords, titles, and abstracts related to the topic. This article provides a detailed relationship between hyperglycaemia, oxidative stress, and various cellular mechanisms that underlie the onset and progression of the disease. Moreover, it also shows how these mechanisms affect organelle dysfunction, resulting in fibrosis and podocyte impairment. The advances in understanding the complexity of DKD mechanisms discussed in this review will expedite opportunities to develop new interventions for treating the disease.
Genome-Wide Association Studies (GWAS) and Transcriptome Analysis Reveal Male Heterogametic Sex-Determining Regions and Candidate Genes in Northern Snakeheads (Channa argus)
Authors: Liu Haiyang , Zhang Jin , Cui Tongxin , Xia Weiwei , Luo Qing , Fei Shuzhan , Zhu Xinping , Chen Kunci , Zhao Jian , Ou Mi
Published: October 2024

The Northern snakehead (Channa argus) is a significant economic aquaculture species in China. Exhibiting sexual dimorphism in the growth rate between females and males, mono-sex breeding holds substantial value for aquaculture. This study employed GWAS and transcriptome analysis were applied to identify sex determination genomic regions and develop sex-specific markers. A total of 270 single-nucleotide polymorphisms (SNPs) and 31 insertion-deletions (InDels) were identified as being sexually dimorphic through GWAS and fixation index (Fst) scanning. Based on GWAS results, two sex-specific InDel markers were developed, effectively distinguishing genetic sex for XX females, XY males, and YY super-males via (polymerase chain reaction) PCR amplification. A major genomic segment of approximately 115 kb on chromosome 3 (Chr 03) was identified as the sex-determination region. A comparative transcriptome analysis of gonads for three sexes identified 158 overlapping differentially expressed genes (DEGs). Additionally, three sex-related candidate genes were identified near the sex determination region, including id2, sox11, and rnf144a. Further studies are required to elucidate the functions of these genes. Overall, two sex-specific InDel markers support a male heterogametic XX/XY sex-determination system in Northern snakeheads and three candidate genes offer new insights into sex determination and the evolution of sex chromosomes in teleost fish.
Proteomics Analysis on the Effects of Oxidative Stress and Antioxidants on Proteins Involved in Sterol Transport and Metabolism in Human Telomerase Transcriptase-Overexpressing-Retinal Pigment Epithelium Cells
Authors: Duncan R. Scott , Keightley Andrew , Lopez Adam A. , Hall Conner W. , Koulen Peter
Published: October 2024

Age-related macular degeneration (AMD) is the most prevalent ocular disease in the elderly, resulting in blindness. Oxidative stress plays a role in retinal pigment epithelium (RPE) pathology observed in AMD. Tocopherols are potent antioxidants that prevent cellular oxidative damage and have been shown to upregulate the expression of cellular antioxidant proteins. Here, we determined whether oxidative stress and tocopherols, using either normal cellular conditions or conditions of sublethal cellular oxidative stress, alter the expression of proteins mediating sterol uptake, transport, and metabolism. Human telomerase transcriptase-overexpressing RPE cells (hTERT-RPE) were used to identify differential expression of proteins resulting from treatments. We utilized a proteomics strategy to identify protein expression changes in treated cells. After the identification and organization of data, we divided the identified proteins into groups related to biological function: cellular sterol uptake, sterol transport and sterol metabolism. Exposure of cells to conditions of oxidative stress and exposure to tocopherols led to similar protein expression changes within these three groups, suggesting that α-tocopherol (αT) and γ-tocopherol (γT) can regulate the expression of sterol uptake, transport and metabolic proteins in RPE cells. These data suggest that proteins involved in sterol transport and metabolism may be important for RPE adaptation to oxidative stress, and these proteins represent potential therapeutic targets.
Intratumoral Heterogeneity and Metabolic Cross-Feeding in a Three-Dimensional Breast Cancer Culture: An In Silico Perspective
Authors: Arellano-Villavicencio Jorge E. , Vázquez-Jiménez Aarón , Oropeza-Valdez Juan José , Padron-Manrique Cristian , Prado-García Heriberto , Tovar Armando R. , Resendis-Antonio Osbaldo
Published: October 2024

Today, the intratumoral composition is a relevant factor associated with the progression and aggression of cancer. Although it suggests a metabolic interdependence among the subpopulations inside the tumor, a detailed map of how this interdependence contributes to the malignant phenotype is still lacking. To address this issue, we developed a systems biology approach integrating single-cell RNASeq and genome-scale metabolic reconstruction to map the metabolic cross-feeding among the subpopulations previously identified in the spheroids of MCF7 breast cancer. By calibrating our model with expression profiles and the experimental growth rate, we concluded that the reverse Warburg effect emerges as a mechanism to optimize community growth. Furthermore, through an in silico analysis, we identified lactate, alpha-ketoglutarate, and some amino acids as key metabolites whose disponibility alters the growth rate of the spheroid. Altogether, this work provides a strategy for assessing how space and intratumoral heterogeneity influence the metabolic robustness of cancer, issues suggesting that computational strategies should move toward the design of optimized treatments.
A Review of Biomarkers of Amyotrophic Lateral Sclerosis: A Pathophysiologic Approach
Authors: Alshehri Rawiah S. , Abuzinadah Ahmad R. , Alrawaili Moafaq S. , Alotaibi Muteb K. , Alsufyani Hadeel A. , Alshanketi Rajaa M. , AlShareef Aysha A.
Published: October 2024

Amyotrophic lateral sclerosis (ALS) is a neurodegenerative disease characterized by progressive degeneration of upper and lower motor neurons. The heterogeneous nature of ALS at the clinical, genetic, and pathological levels makes it challenging to develop diagnostic and prognostic tools that fit all disease phenotypes. Limitations associated with the functional scales and the qualitative nature of mainstay electrophysiological testing prompt the investigation of more objective quantitative assessment. Biofluid biomarkers have the potential to fill that gap by providing evidence of a disease process potentially early in the disease, its progression, and its response to therapy. In contrast to other neurodegenerative diseases, no biomarker has yet been validated in clinical use for ALS. Several fluid biomarkers have been investigated in clinical studies in ALS. Biofluid biomarkers reflect the different pathophysiological processes, from protein aggregation to muscle denervation. This review takes a pathophysiologic approach to summarizing the findings of clinical studies utilizing quantitative biofluid biomarkers in ALS, discusses the utility and shortcomings of each biomarker, and highlights the superiority of neurofilaments as biomarkers of neurodegeneration over other candidate biomarkers.
Circulating Immune Complexes and Complement Activation in Sensitized Kidney Transplant Recipients
Authors: Trivyza Maria Stella , Stergiopoulou Charikleia , Tsakas Sotiris , Ntrinias Theodoros , Papasotiriou Marios , Karydis Nikolaos , Papachristou Evangelos , Goumenos Dimitrios S.
Published: October 2024

Chronic antibody-mediated rejection in kidney transplantation is a common cause of graft loss in the late post-transplant period. In this process, the role of the classical complement activation pathway is crucial due to the formation of immune complexes between donor-specific antibodies (DSAs) and donor antigens and the attachment of the C1q complement fragment. This study aimed to determine the levels of circulating C1q immunocomplexes (CIC-C1q) and complement activation (CH50), in sensitized kidney transplant recipients (KTRs). In this cross-sectional study we used serum samples from KTRs with de novo or preformed DSAs (n = 14), KTRs without DSAs (n = 28), and 22 subjects with no history of chronic kidney disease (controls). C1q immunocomplexes and CH50 concentration in serum were measured with the enzyme immunoassay (EIA) kit MicroVue CIC-C1q (Quidel, Athens, OH, USA) and EIA kit MicroVue CH50 (Quidel, OH, USA), respectively. Higher concentrations of CIC-C1q was observed in KTRs with DSAs in comparison with controls and with KTRs with no DSAs (6.8 ± 2.7 and 4.8 ± 1.9 vs. 5.0 ± 1.2 μg Eq/mL, respectively, p < 0.01). We found no difference in CIC-C1q between KTRs with no DSAs and controls. CIC-C1q levels were positively correlated with DSA titer. CH50 levels were decreased in KTRs with DSAs in comparison with controls and KTRs with no DSAs (39 ± 15 vs. 68 ± 40 and 71 ± 34 U Eq/mL, respectively, p < 0.01). There was no difference in CH50 between DSA-negative KTRs and controls. Kidney transplant recipients with DSAs had increased serum levels of C1q immunocomplexes and increased classical pathway complement activation.
Assessing the Toxicity of Metal- and Carbon-Based Nanomaterials In Vitro: Impact on Respiratory, Intestinal, Skin, and Immune Cell Lines
Authors: Carrillo-Romero Juliana , Mentxaka Gartze , García-Salvador Adrián , Katsumiti Alberto , Carregal-Romero Susana , Goñi-de-Cerio Felipe
Published: October 2024

The field of nanotechnology has experienced exponential growth, with the unique properties of nanomaterials (NMs) being employed to enhance a wide range of products across diverse industrial sectors. This study examines the toxicity of metal- and carbon-based NMs, with a particular focus on titanium dioxide (TiO2), zinc oxide (ZnO), silica (SiO2), cerium oxide (CeO2), silver (Ag), and multi-walled carbon nanotubes (MWCNTs). The potential health risks associated with increased human exposure to these NMs and their effect on the respiratory, gastrointestinal, dermal, and immune systems were evaluated using in vitro assays. Physicochemical characterisation of the NMs was carried out, and in vitro assays were performed to assess the cytotoxicity, genotoxicity, reactive oxygen species (ROS) production, apoptosis/necrosis, and inflammation in cell lines representative of the systems evaluated (3T3, Caco-2, HepG2, A549, and THP-1 cell lines). The results obtained show that 3T3 and A549 cells exhibit high cytotoxicity and ROS production after exposure to ZnO NMs. Caco-2 and HepG2 cell lines show cytotoxicity when exposed to ZnO and Ag NMs and oxidative stress induced by SiO2 and MWCNTs. THP-1 cell line shows increased cytotoxicity and a pro-inflammatory response upon exposure to SiO2. This study emphasises the importance of conducting comprehensive toxicological assessments of NMs given their physicochemical interactions with biological systems. Therefore, it is of key importance to develop robust and specific methodologies for the assessment of their potential health risks.
Effect of Abelmoschus esculentus L. (Okra) on Dyslipidemia: Systematic Review and Meta-Analysis of Clinical Studies
Authors: Mokgalaboni Kabelo , Phoswa Wendy N. , Mokgalabone Tyson T. , Dlamini Sanele , Ndhlala Ashwell R. , Modjadji Perpetua , Lebelo Sogolo L.
Published: October 2024

The global prevalence of cardiovascular diseases (CVDs), including dyslipidemia and atherosclerosis, is rising. While pharmacological treatments for dyslipidemia and associated CVDs exist, not all individuals can afford them, and those who do often experience adverse side effects. Preclinical studies have indicated the potential benefits of Abelmoschus esculentus and its active phytochemicals in addressing dyslipidemia in rodent models of diabetes. However, there is limited clinical evidence on lipid parameters. Thus, this study aimed to assess the potential impact of Abelmoschus esculentus on dyslipidemia. A literature search was performed on PubMed, Scopus, and Cochrane Library for relevant trials published from inception until 11 August 2024. Data analysis was performed using Jamovi software version 2.4.8 and Review Manager (version 5.4), with effect estimates reported as standardized mean differences (SMDs) and 95% confidence intervals (CI). The evidence from eight studies with nine treatment arms showed that Abelmoschus esculentus reduces total cholesterol (TC), SMD = −0.53 (95% CI: −1.00 to −0.07), p = 0.025), compared to placebo. Additionally, triglyceride (TG) was reduced in Abelmoschus esculentus compared to placebo, SMD = −0.24 (95% CI: −0.46 to −0.02), p = 0.035. Furthermore, low-density lipoprotein (LDL) was also reduced, SMD = −0.35 (95% CI: −0.59 to −0.11), p = 0.004 in Abelmoschus esculentus versus placebo. This remedy substantially increased high-density lipoprotein (HDL), SMD = 0.34 (95% CI: 0.07 to 0.61), p = 0.014). Abelmoschus esculentus substantially improved lipid profile in prediabetes, T2D, obesity, and diabetic nephropathy. While the evidence confirms the potential benefits of Abelmoschus esculentus in reducing dyslipidemia, it is important for future clinical studies to standardize the effective dosage for more reliable results. Therefore, future trials should focus on these markers in well-designed trials with sufficient sample sizes. Furthermore, Abelmoschus esculentus can be supplemented to the diet of the relevant populations to alleviate dyslipidemia.
The Effect of Four-Month Training on Biochemical Variables in Amateur Cross-Country Skiers
Authors: Grzebisz-Zatońska Natalia
Published: October 2024

Background/Objectives: Research on the effects of training on the health of amateur cross-country skiers remains limited, particularly on biochemical parameters. Therefore, this study aimed to assess such changes in response to four months of training for amateur cross-country skiers. Methods: Blood samples were collected after spring training in May (active rest) and in September at the end of the preparatory period. The Wilcoxon signed-rank test was used for comparison of both measurements (initial and final). Results: Training in a group of amateur cross-country skiers exerts a statistically significant influence on the decrease in leukocyte count (thousand/µL) (p = 0.045) and the decrease in mean corpuscular hemoglobin concentration (MCHC) (g/dL) (p = 0.021). The other parameters did not show statistically significant changes. Conclusions: The change in MCHC and WBC can be attributed to adaptation to prolonged exercise, with a simultaneous increase in VO2 max. It should not be identified with pathology. The decrease in MCHC was likely attributable to changes in hydration status and a slight reduction in hemoglobin concentration. Similarly, it is recommended that other biochemical parameters be within the reference ranges.
Insight on Exercise-Induced Heart Remodeling in Different Track and Field Disciplines
Authors: Di Gioia Giuseppe , Ferrera Armando , Vespasiano Francesca , Maestrini Viviana , Monosilio Sara , Lemme Erika , Serdoz Andrea , Mango Federica , Casciani Emanuele , Pelliccia Antonio , Squeo Maria Rosaria
Published: October 2024

Background: The foot racing disciplines include sprints, middle distances, and long distances, which vary in terms of intensities, duration of training, and metabolic demands. The aim of our study was to evaluate the differences in morpho-functional parameters describing cardiac remodeling in a large cohort of Olympic athletes practicing the different track subspecialties. Methods: We evaluated 140 track and field (52.1% males, mean age 26.3 ± 4.3 years) Olympic athletes divided into four groups according to the distance performed: Group A (46, 32.9%): 100 and 200 mt; Group B (34, 24.3%): 400 mt; Group C (25, 17.9%): 800, 1500, and 3000 mt; Group D (35, 24.9%): 5000, 10,000 mt, and marathon distance. The athletes underwent a pre-participation screening, which included transthoracic echocardiography and exercise stress testing. Results: In Group A and in Group B, most athletes presented normal cardiac geometry (41/46, 89.1% in Group A and 31/34, 91.2% in Group B, p < 0.0001). Instead, in Groups C and D, more than half presented eccentric cardiac remodeling (13\25, 52% in Group C and 23\35, 65.7% in Group D). No significant differences were found between subspecialties in LVEF (p = 0.587), diastolic function (p = 0.431), and training hours/week (p = 0.078). Conclusions: In conclusion, the presence and extent of cardiac remodeling vary according to the distance of the discipline practiced, with the largest dimensional increase in both left and right ventricles and atria in mid- and long-distance runners and the lowest in sprinters.
Risk of Hepatitis B Virus Reactivation in COVID-19 Patients Receiving Immunosuppressive Treatment: A Prospective Study
Authors: Mihai Nicoleta , Olariu Mihaela Cristina , Ganea Oana-Alexandra , Adamescu Aida-Isabela , Molagic Violeta , Aramă Ștefan Sorin , Tilișcan Cătălin , Aramă Victoria
Published: October 2024

Objectives: This study aimed to evaluate the risk of hepatitis B virus reactivation (HBVr) in COVID-19 patients receiving immunosuppressive treatment, which has been insufficiently studied to date. Secondarily, we aimed to evaluate the seroprevalence of HBV infection in COVID-19 patients. Methods: We performed HBV screening on all Romanian adults hospitalized in four COVID-19 wards between October 2021 and September 2022. We enrolled patients with positive hepatitis B core antibody (anti-HBc) without protective hepatitis B surface antibody (anti-HBs), HBV treatment, or baseline immunosuppressive conditions, and we conducted a virological follow-up on these patients at 3 months. Results: We identified 333/835 (39.9%) anti-HBc-positive patients. Follow-up was performed for 13 patients with positive hepatitis B surface antigen (HBsAg) and 19 HBsAg-negative/anti-HBc-positive patients. Among those who received immunosuppressants, 4/23 (17.4%) patients experienced HBVr: 1 out of 8 (12.5%) HBsAg-positive patients (with 1.99 log increase in HBV DNA level) and 3 out of 15 (20%) HBsAg-negative/anti-HBc-positive patients (with a de novo detectable HBV DNA level). Conclusions: Administration of COVID-19 immunosuppressants may result in a significant risk of HBVr in co-infected patients. We recommend performing an HBV triple screen panel (HBsAg, anti-HBs, anti-HBc) for all COVID-19 patients receiving immunosuppressive treatment. HBV prophylaxis may be indicated in certain patients. Larger studies are needed in order to establish appropriate and cost-effective management for these patients.
From Bench to Bedside: A Team’s Approach to Multidisciplinary Strategies to Combat Therapeutic Resistance in Head and Neck Squamous Cell Carcinoma
Authors: Crossman Bridget E. , Harmon Regan L. , Kostecki Kourtney L. , McDaniel Nellie K. , Iida Mari , Corday Luke W. , Glitchev Christine E. , Crow Madisen T. , Harris Madelyn A. , Lin Candie Y. , Adams Jillian M. , Longhurst Colin A. , Nickel Kwangok P. , Ong Irene M. , Alexandridis Roxana A. , Yu Menggang , Yang David T. , Hu Rong , Morris Zachary S. , Hartig Gregory K. , Glazer Tiffany A. , Ramisetty Sravani , Kulkarni Prakash , Salgia Ravi , Kimple Randall J. , Bruce Justine Y. , Harari Paul M. , Wheeler Deric L.
Published: October 2024

Head and neck squamous cell carcinoma (HNSCC) is diagnosed in more than 71,000 patients each year in the United States, with nearly 16,000 associated deaths. One significant hurdle in the treatment of HNSCC is acquired and intrinsic resistance to existing therapeutic agents. Over the past several decades, the University of Wisconsin has formed a multidisciplinary team to move basic scientific discovery along the translational spectrum to impact the lives of HNSCC patients. In this review, we outline key discoveries made throughout the years at the University of Wisconsin to deepen our understanding of therapeutic resistance in HNSCC and how a strong, interdisciplinary team can make significant advances toward improving the lives of these patients by combatting resistance to established therapeutic modalities. We are profoundly grateful to the many scientific teams worldwide whose groundbreaking discoveries, alongside evolving clinical paradigms in head and neck oncology, have been instrumental in making our work possible.
Potentially Inappropriate Prescribing Identified Using STOPP/START Version 3 in Geriatric Patients and Comparison with Version 2: A Cross-Sectional Study
Authors: Szoszkiewicz Mikołaj , Deskur-Śmielecka Ewa , Styszyński Arkadiusz , Urbańska Zofia , Neumann-Podczaska Agnieszka , Wieczorowska-Tobis Katarzyna
Published: October 2024

Background: Multimorbidity, polypharmacy, and inappropriate prescribing are significant challenges in the geriatric population. Tools such as the Beers List, FORTA, and STOPP/START criteria have been developed to identify potentially inappropriate prescribing (PIP). STOPP/START criteria detect both potentially inappropriate medications (PIMs) and potential prescribing omissions (PPOs). The latest, third version of STOPP/START criteria expands the tool, based on the growing literature. The study aimed to evaluate the prevalence of PIP and the number of PIP per person identified by STOPP/START version 3 and to compare it to the previous version. Methods: This retrospective, cross-sectional study enrolled one hundred geriatric patients with polypharmacy from two day-care centers for partially dependent people in Poland. Collected data included demographic and medical data. STOPP/START version 3 was used to identify potentially inappropriate prescribing, whereas the previous version served as a reference. Results: STOPP version 3 detected at least one PIM in 73% of the study group, a significantly higher result than that for version 2 (56%). STOPP version 3 identified more PIMs per person than the previous version. Similarly, START version 3 had a significantly higher prevalence of PPOs (74% vs. 57%) and a higher number of PPOs per person than the previous version. The newly formed STOPP criteria with high prevalence were those regarding NSAIDs, including aspirin in cardiovascular indications. Frequent PPOs regarding newly formed START criteria were the lack of osmotic laxatives for chronic constipation, the lack of mineralocorticoid receptor antagonists, and SGLT-2 inhibitors in heart failure. Conclusions: This study showed the high effectiveness of the STOPP/START version 3 criteria in identifying potentially inappropriate prescribing, with a higher detection rate than version 2.