bluuebunny/crossref_metadata_2025 huggingface dataset:
Synthetic GPR84 Agonists in Colorectal Cancer: Effective in THP-1 Cells but Ineffective in BMDMs and MC38 Mouse Tumor Models
Authors: Schwarzfischer Marlene , Walker Maria Rae , Curcio Michele , Boshta Nader M. , Marchand Arnaud , Soons Erik , Pöhlmann Doris , Wawrzyniak Marcin , Morsy Yasser , Lang Silvia , Spalinger Marianne Rebecca , Versele Matthias , Scharl Michael
Published: January 2025

Tumor-associated macrophages (TAMs) in the colorectal cancer (CRC) microenvironment promote tumor progression but can be reprogrammed into a pro-inflammatory state with anti-cancer properties. Activation of the G protein-coupled receptor 84 (GPR84) is associated with pro-inflammatory macrophage polarization, making it a potential target for CRC therapy. This study evaluates the effects of the GPR84 agonists 6-OAU and ZQ-16 on macrophage activation and anti-cancer efficacy. GPR84 expression on THP-1 macrophages and murine BMDMs was analyzed using flow cytometry. Macrophages were treated with 6-OAU or ZQ-16, and pro-inflammatory cytokine levels, reactive oxygen species (ROS) production, and phagocytosis were assessed using qPCR and functional assays. Anti-cancer effects were tested in a subcutaneous MC38 tumor model, with oral or intraperitoneal agonist administration. Pharmacokinetics and compound stability were also evaluated. In THP-1 macrophages, 6-OAU increased pro-inflammatory cytokines and ROS production, with ZQ-16 showing similar effects. However, neither agonist induced pro-inflammatory responses, ROS production, or phagocytosis in murine macrophages. In vivo, both agonists failed to inhibit tumor growth in the MC38 model despite systemic exposure. Current GPR84 agonists lack efficacy in promoting anti-cancer macrophage activity, limiting their potential as CRC therapies.
Neoadjuvant Chemotherapy for T3 Tumors in the Era of Precision Medicine—Biology Is Still King
Authors: Rahman Rakhshanda Layeequr , Santillan Alfredo , Habibi Mehran , Beitsch Peter , Whitworth Pat , Ramaswamy Harshini , Chmielewski-Stivers Nicole , Menicucci Andrea , Audeh William , O’Shaughnessy Joyce
Published: January 2025

Clinical T3 (cT3) breast cancer (BC) presents a challenge for achieving cosmetically acceptable breast conservation, and neoadjuvant chemotherapy (NAC) is commonly used for cytoreduction in these high-risk cancers. MammaPrint® risk-of-recurrence and BluePrint® molecular subtyping genomic signatures have demonstrated high accuracy in predicting chemotherapy benefits. Here, we examined the utility of MammaPrint/BluePrint for predicting pathological Complete Response (pCR) rates to NAC among 404 patients diagnosed with cT3 early-stage BC. The association of genomic subtype and clinical features with the likelihood of pCR was evaluated by multivariate logistic regression. Differences in pCR rates between genomic risk categories were evaluated by a two-sided proportional z-test and stratified by nodal status. MammaPrint/BluePrint subtyping was associated with significantly higher odds ratios (ORs) for pCR in MammaPrint High-Risk/BluePrint Basal-Type (OR = 3.06, 95% CI: 1.15–8.19, p = 0.025) and HER2-Type (OR = 6.27, 95% CI: 2.19–19.38, p = 0.001) compared to BluePrint Luminal-Type. Of the 209 patients with hormone receptor-positive, HER2-negative disease, 6.7% achieved pCR, and MammaPrint High-Risk was associated with a significantly higher pCR rate (9.3%) compared to MammaPrint Low-Risk cancers (0%), regardless of nodal involvement (p = 0.036). These data show that for patients with MammaPrint Low-Risk, cT3 tumors are less likely to have clinically impactful cytoreduction from NAC, regardless of nodal involvement.
Metabolic Reprogramming at the Edge of Redox: Connections Between Metabolic Reprogramming and Cancer Redox State
Authors: Serrano José J. , Medina Miguel Ángel
Published: January 2025

The importance of redox systems as fundamental elements in biology is now widely recognized across diverse fields, from ecology to cellular biology. Their connection to metabolism is particularly significant, as it plays a critical role in energy regulation and distribution within organisms. Over recent decades, metabolism has emerged as a relevant focus in studies of biological regulation, especially following its recognition as a hallmark of cancer. This shift has broadened cancer research beyond strictly genetic perspectives. The interaction between metabolism and redox systems in carcinogenesis involves the regulation of essential metabolic pathways, such as glycolysis and the Krebs cycle, as well as the involvement of redox-active components like specific amino acids and cofactors. The feedback mechanisms linking redox systems and metabolism in cancer highlight the development of redox patterns that enhance the flexibility and adaptability of tumor processes, influencing larger-scale biological phenomena such as circadian rhythms and epigenetics.
Molecular Epidemiology and In-Depth Characterization of Klebsiella pneumoniae Clinical Isolates from Armenia
Authors: Sedrakyan Anahit , Gevorgyan Zaruhi , Zakharyan Magdalina , Arakelova Karine , Hakobyan Shoghik , Hovhannisyan Alvard , Aminov Rustam
Published: January 2025

The global dissemination of Klebsiella pneumoniae pathotypes with multidrug-resistant (MDR) and hypervirulent traits poses a threat to public health. The situation in Armenia is unclear, and we performed a comprehensive characterisation of 48 clinical isolates of K. pneumoniae, collected from 2018 to 2024. The majority of the isolates (64.58%) were extensively drug-resistant (XDR) and MDR. Genomic analysis of 21 isolates revealed the presence of international high-risk MDR clones (ST395, ST15, and ST307). The ST395 strains were isolated from children and resisted the first-line drugs such as beta-lactams. These isolates harboured a range of virulence determinants, from capsule polysaccharides to siderophores to regulators of the mucoid phenotype. The ST395 strains are enriched by ICEs, plasmids, and prophages, on which antimicrobial resistance (AMR) and virulence genes are located and which may lead to the convergence of MDR and hypervirulent traits. There is a widespread non-specific AMR mechanism among our K. pneumoniae strains. These are mutations in the porin genes, which reduce permeability to antimicrobials, and mutations in the regulators of efflux pumps, which lead to overexpression of drug efflux pumps such as AcrAB. These mechanisms may contribute to the elevated MICs and confer AMR to strains with no specific AMR genes.
Special Issue: Recent Advances in Microglia Research
Authors: Lana Daniele , Giovannini Maria Grazia
Published: January 2025

This Editorial introduces the new Special Issue, published in the International Journal of Molecular Sciences and entitled “Recent Advances in Microglia Research”, which covers this important topic with a collection of five valuable contributions: three Original Research Articles and two Reviews [...]
IgG-NR2B—A Potentially Valuable Biomarker in the Management of Refractory Anti-NMDAR Encephalitis
Authors: Števková Zuzana , Krastev Georgi , Mako Miroslav , Čierna Zuzana
Published: January 2025

The autoantibodies against the NR1 subunit are well known in the pathomechanism of NMDAR encephalitis. The dysfunction of the NR2 subunit could be a critical factor in this neurological disorder due to its important role in the postsynaptic pathways that direct synaptic plasticity. We report a case of paraneoplastic anti-NMDAR encephalitis presented alongside very severe illness. Computed tomography (CT) of the brain, as well as FLAIR and T2-weighted MRI, was performed to rule out any other acute brain processes. A semi-quantitative method was applied to detect the presence of anti-NMDAR antibodies in the serum and CSF. A CT chest–abdomen–pelvis scan was performed that detected an ovarian teratoma. A histopathological examination was performed after a laparoscopic right-ovary cystectomy. Subsequent immunofluorescence immunohistochemical staining showed the expression of NMDA receptors of type NR2B. Treatment included first-line immunotherapy, second-line immunotherapy, tumor removal, and intrathecal injections with methotrexate and dexamethasone. The histological finding for our patient after tumor removal was ovarian teratoma. Hematoxylin–eosin (HE) staining revealed a characteristic spectrum of elements, including stratified squamous epithelium and fat tissue accompanied by neuroglial cells. Subsequent immunohistochemical staining showed an expression of NMDA receptors of type NR2B in different structures of the teratoma, including the neuroglial cells. The first-line immunotherapy following the tumor removal was insufficient in our patient. The paraneoplastic anti-NMDAR encephalitis with a coexpressed NR2B subunit on the neural cells of the ovarian teratoma may suggest a different inflammation process and could be the key factor in the pathomechanism and treatment of the refractory anti-NMDAR encephalitis.
Targeting Triple NK Cell Suppression Mechanisms: A Comprehensive Review of Biomarkers in Pancreatic Cancer Therapy
Authors: Fanijavadi Sara , Thomassen Mads , Jensen Lars Henrik
Published: January 2025

Pancreatic ductal adenocarcinoma (PDAC) is an aggressive cancer with poor outcomes due to frequent recurrence, metastasis, and resistance to treatment. A major contributor to this resistance is the tumor’s ability to suppress natural killer (NK) cells, which are key players in the immune system’s fight against cancer. In PDAC, the tumor microenvironment (TME) creates conditions that impair NK cell function, including reduced proliferation, weakened cytotoxicity, and limited tumor infiltration. This review examines how interactions between tumor-derived factors, NK cells, and the TME contribute to tumor progression and treatment resistance. To address these challenges, we propose a new “Triple NK Cell Biomarker Approach”. This strategy focuses on identifying biomarkers from three critical areas: tumor characteristics, TME factors, and NK cell suppression mechanisms. This approach could guide personalized treatments to enhance NK cell activity. Additionally, we highlight the potential of combining NK cell-based therapies with conventional treatments and repurposed drugs to improve outcomes for PDAC patients. While progress has been made, more research is needed to better understand NK cell dysfunction and develop effective therapies to overcome these barriers.
An FGF2-Derived Short Peptide Attenuates Bleomycin-Induced Pulmonary Fibrosis by Inhibiting Collagen Deposition and Epithelial–Mesenchymal Transition via the FGFR/MAPK Signaling Pathway
Authors: Wang Mengwei , Sun Yuanmeng , Zhao Yanzhi , Jiang Xinyi , Wang Teng , Xie Junye , Yu Xiuling , Guo Shujun , Zhang Yibo , Chen Xiaojia , Hong An
Published: January 2025

Following the COVID-19 pandemic, the prevalence of pulmonary fibrosis has increased significantly, placing patients at higher risk and presenting new therapeutic challenges. Current anti-fibrotic drugs, such as Nintedanib, can slow the decline in lung function, but their severe side effects highlight the urgent need for safer and more targeted alternatives. This study explores the anti-fibrotic potential and underlying mechanisms of an endogenous peptide (P5) derived from fibroblast growth factor 2 (FGF2), developed by our research team. Using a bleomycin-induced pulmonary fibrosis mouse model, we observed that P5 alleviated fibrosis by inhibiting collagen deposition, as confirmed by CT scans and histological staining. In TGF-β-induced cell models, P5 effectively suppressed collagen deposition and epithelial–mesenchymal transition (EMT). Transcriptome analysis highlighted pathways related to receptor binding, extracellular matrix organization, and cell adhesion, with KEGG analysis confirming FGFR/MAPK signaling inhibition as the primary mechanism underlying its anti-fibrotic effects. In summary, our study demonstrates that P5 significantly attenuates pulmonary fibrosis through the inhibition of EMT, collagen deposition, and FGFR/MAPK signaling, providing a promising therapeutic approach for fibrosis.
Genome-Wide Identification, Phylogenetic Evolution, and Abiotic Stress Response Analyses of the Late Embryogenesis Abundant Gene Family in the Alpine Cold-Tolerant Medicinal Notopterygium Species
Authors: Wu Xuanye , He Xiaojing , Wang Xiaoling , Liu Puyuan , Ai Shaoheng , Liu Xiumeng , Li Zhonghu , Wang Xiaojuan
Published: January 2025

Late embryogenesis abundant (LEA) proteins are a class of proteins associated with osmotic regulation and plant tolerance to abiotic stress. However, studies on the LEA gene family in the alpine cold-tolerant herb are still limited, and the phylogenetic evolution and biological functions of its family members remain unclear. In this study, we conducted genome-wide identification, phylogenetic evolution, and abiotic stress response analyses of LEA family genes in Notopterygium species, alpine cold-tolerant medicinal herbs in the Qinghai–Tibet Plateau and adjacent regions. The gene family identification analysis showed that 23, 20, and 20 LEA genes were identified in three Notopterygium species, N. franchetii, N. incisum, and N. forrestii, respectively. All of these genes can be classified into six LEA subfamilies: LEA_1, LEA_2, LEA_5, LEA_6, DHN (Dehydrin), and SMP (seed maturation protein). The LEA proteins in the three Notopterygium species exhibited significant variations in the number of amino acids, physical and chemical properties, subcellular localization, and secondary structure characteristics, primarily demonstrating high hydrophilicity, different stability, and specific subcellular distribution patterns. Meanwhile, we found that the members of the same LEA subfamily shared similar exon–intron structures and conserved motifs. Interestingly, the chromosome distributions of LEA genes in Notopterygium species were scattered. The results of the collinearity analysis indicate that the expansion of the LEA gene family is primarily driven by gene duplication. A Ka/Ks analysis showed that paralogous gene pairs were under negative selection in Notopterygium species. A promoter cis-acting element analysis showed that most LEA genes possessed multiple cis-elements connected to plant growth and development, stress response, and plant hormone signal transduction. An expression pattern analysis demonstrated the species-specific and tissue-specific expression of NinLEAs. Experiments on abiotic stress responses indicated that the NinLEAs play a crucial role in the response to high-temperature and drought stresses in N. franchetii leaves and roots. These results provide novel insights for further understanding the functions of the LEA gene family in the alpine cold-tolerant Notopterygium species and also offer a scientific basis for in-depth research on the abiotic stress response mechanisms and stress-resistant breeding.
Evaluation of Damage to Existing Buildings Induced by Tunnel Excavation
Authors: Laçin Akşit Ekin Evrim , Güler Kadir
Published: January 2025

This study emphasizes the significance of employing systematic approaches and precise modeling techniques to evaluate potential building damage from metro tunnel excavations. Mair et al. (1996) proposed a three-stage assessment framework comprising preliminary assessment, second-stage assessment, and detailed assessment to analyze the damage to buildings inflicted by tunnel excavation. For preliminary and second-stage assessments, parametric calculation methods have been examined; however, detailed assessment requires using a 3D numerical analysis model. This study selected a school building, to examine this three-stage assessment method. For the preliminary and second stage assessments, a “greenfield” analysis approach was utilized using the PLAXIS 2D to determine the ground settlement curve caused by tunnel excavation. Based on the obtained settlement values, the evaluation was conducted using the boundary conditions proposed by Mair et al. (1996). Since the obtained settlement values did not meet the proposed boundary conditions, a three-dimensional finite element model was generated using the SAP2000 analysis program. This paper offers practical guidance on the nonlinear modeling principles of structural elements during the detailed assessment of a building subjected to vertical settlement. It provides a framework for assessing buildings near tunnel construction sites.
Assessing Genetic Diversity and Population Structure of Western Honey Bees in the Czech Republic Using 22 Microsatellite Loci
Authors: Knoll Aleš , Šotek Martin , Prouza Jan , Langová Lucie , Přidal Antonín , Urban Tomáš
Published: January 2025

To date, no study has been conducted to investigate the diversity in honeybee populations of Apis mellifera in the Czech Republic. Between 2022 and 2023, worker bees were collected from colonies distributed throughout the Czech Republic in 77 districts, and their genetic differences were examined using 22 microsatellite loci. The samples were obtained from hives (n = 3647) and through the process of capture on flowers (n = 553). Genetic diversity parameters were assessed for both populations in all 77 districts. The findings demonstrated that honeybee populations exhibit moderate genetic diversity, as evidenced by the number of observed alleles, the Shannon index, and heterozygosity values. There was no discrepancy in diversity between hive and flower samples. Diversity characteristics were determined: mean observed heterozygosity 0.55 (hives) and 0.56 (flowers), and fixation index 0.58 for both populations. The average number of alleles per locus was 13.77 and 11.18 from hives and flowers, respectively. The low FST and FIS values (they measured the level of genetic differentiation between populations and the level of inbreeding, respectively) suggest the absence or minimal genetic diversity within and among studied populations. The genetic variation was calculated as 2% and 1% between populations, 8% and 6% between individuals within populations, and 91% and 93% between all individuals in samples from hives and flowers, respectively. Cluster and DAPC (discriminant analysis principal component) analysis classified the bee samples collected from across the country into three and five to six distinguishable groups, respectively. The honeybee population in the Czech Republic displays sufficient diversity and a partial structure. However, there appears to be no correlation between the genetic groups and the geographic regions to which they are assigned.
Navigating the Semiochemical Landscape: Attraction of Subcortical Beetle Communities to Bark Beetle Pheromones, Fungal and Host Tree Volatiles
Authors: Crandall Leah , Zaman Rashaduz , Duthie-Holt Marnie , Jarvis Wade , Erbilgin Nadir
Published: January 2025

Subcortical beetle communities interact with a wide range of semiochemicals released from different sources, including trees, fungi, and bark beetle pheromones. While the attraction of bark beetles, their insect predators, and competitors to bark beetle pheromones is commonly studied, the attraction of these beetle communities to other sources of semiochemicals remains poorly understood. We tested the attraction of bark and wood-boring beetles and their predators to host stress volatiles, fungal volatiles, and a mountain pine beetle lure in the field. Host stress volatiles were derived from lodgepole pine trees stressed by three fungal symbionts of mountain pine beetle and two common phytopathogens. Our results showed that bark beetles, particularly mountain pine beetles, show a preference for a combination of fungal volatiles, particularly 2-methyl-1-butanol and its lures. Without the addition of lures, 2-methyl-1-butanol was also identified as a key fungal volatile in the attraction of mountain pine beetle competitors from the Cerambycidae and Buprestidae families. Predators in the Elateridae and Staphylinidae families showed attraction to host stress volatiles and the healthy tree volatile profiles. These findings suggest that these semiochemicals warrant further field testing for potential use in monitoring and management of subcortical beetle populations.
Exercise Training in Heart Failure: Current Evidence and Future Directions
Authors: Eleyan Loay , Gonnah Ahmed R. , Farhad Imran , Labib Aser , Varia Alisha , Eleyan Alaa , Almehandi Abdullah , Al-Naseem Abdulrahman O. , Roberts David H.
Published: January 2025

Heart Failure (HF) is a prevalent condition which places a substantial burden on healthcare systems worldwide. Medical management implemented with exercise training (ET) plays a role in prognostic and functional capacity improvement. The aim of this review is to determine the effect of exercise training (ET) on HFpEF and HFrEF patients as well as exercise modality recommendations in frail and sarcopenic subpopulations. Pharmacological therapy structures the cornerstone of management in HF reduced ejection fraction (HFrEF) and aids improved survival rates. Mortality reduction with pharmacological treatments in HF preserved ejection fraction (HFpEF) are yet to be established. Cardiac rehabilitation (CR) and ET can play an important role in both HFrEF and HFpEF. Preliminary findings suggest that CR significantly improves functional capacity, exercise duration, and quality of life. ET has shown beneficial effects on peak oxygen consumption (pVO2) and 6 min walk test distance in HFrEF and HFpEF patients, as well as a reduction in hospitalisation and mortality rates; however, the limited scope of larger trials reporting on this underscores the need for further research. ET also has been shown to have beneficial effects on depression and anxiety levels. High-intensity training (HIT) and moderate continuous training (MCT) have both shown benefits, while resistance exercise training and ventilatory assistance may also be beneficial. ET adherence rates are higher when enrolled to a supervised programme, but prescription rates remain low worldwide. Larger robust trials are required to determine ET’s effects on HF, as well as the most efficacious and personalised exercise prescriptions in HF subtypes.
Partial Loss of NEMO Function in a Female Carrier with No Incontinentia Pigmenti
Authors: Cifaldi Cristina , Sgrulletti Mayla , Cesare Silvia Di , Rivalta Beatrice , Emanuele Agolini , Colucci Lucia , Moscato Giusella Maria Francesca , Matraxia Marta , Perrone Chiara , Di Matteo Gigliola , Cancrini Caterina , Moschese Viviana
Published: January 2025

Background/Objectives: The nuclear factor (NF)-kB essential modulator (NEMO) has a crucial role in the NFκB pathway. Hypomorphic IKBKG pathogenic variants cause ectodermal dysplasia with immunodeficiency (EDA-ID) in affected males. However, heterozygous amorphic IKBKG variants could be responsible for Incontinentia Pigmenti (IP) in female carriers. Typically, IP patients do not exhibit immunodeficiency, although hypomorphic variants might lead to immunodeficiency in female IP patients. Here, we report the case of an IKBKG female carrier, with no IP but an unexpected picture of immunodeficiency. She had a positive family history for the same genetic condition. Methods: We performed immunological, molecular, and functional analysis to evaluate NEMO contribution. Results: The patient was healthy until the age of 25 when severe asthma and Hashimoto thyroiditis occurred. She had HLAB27-positive ankylosing spondylitis, non-tubercular mycobacteriosis, and pulmonary aspergillosis infections. We found CD19+ B cell lymphopenia and T cell subset alterations. Sanger sequencing revealed a heterozygous IKBKG variant at position +1 of the 5′ UTR of the gene which disrupted the normal pre-mRNA splicing. We observed a decreased NEMO protein expression, a reduced level of mRNA, and a defective NF-κB pathway. Conclusions: These findings suggest a possible correlation between the partial loss of NEMO function and the immunodeficiency observed in this patient. This case could expand our understanding of NEMO deficiency in female carriers.
Risk-Stratified Venous Thromboembolism Chemoprophylaxis After Total Joint Arthroplasty: Evaluation of an Institutional Approach
Authors: Hyland Sara J. , Fada Maria J. , Secic Michelle , Fada Robert A. , Lockhart Marie M. , Parrish Richard H.
Published: January 2025

Background/Objectives: The optimal venous thromboembolism (VTE) chemoprophylaxis approach after hip or knee total joint arthroplasty (TJA) remains controversial. This study aimed to characterize antithrombotic-related complications associated with various chemoprophylaxis regimens after TJA and to assess our current institutional risk-stratified prescribing tool. Methods: This retrospective case–control study and regression analysis included elective unilateral TJA patients at a single institution between 1 July 2015 and 31 December 2021. The primary outcome was a composite of antithrombotic-related complications within 30 days of surgery, including thrombotic and hemorrhagic/wound-related adverse events. The duration of anticoagulant chemoprophylaxis prescribed prior to aspirin monotherapy (0–28 days) was compared between patients who did vs. did not experience a complication, with stratification by institutionally defined VTE risk categories (Routine, Moderate, or High Risk). The complication rate was then assessed as a function of anticoagulant duration within each risk subgroup. Results: The study included 5420 patients, with 279 (5.2%) experiencing ≥1 complication. Routine VTE risk patients experienced few complications, with no significant difference between aspirin monotherapy and various initial anticoagulant durations (p = 0.6118). Moderate and High VTE Risk patients saw significantly lower complication rates with initial anticoagulant prophylaxis of increasing durations (p = 0.0090 and p = 0.0050), with a significant overall effect of VTE Risk strata observed (p = 0.0006). Conclusions: When both bleeding and thrombotic events are considered, anticoagulant-to-aspirin regimens were associated with lower complication rates than aspirin monotherapy in higher risk patients, while routine patients saw no significant benefit over aspirin. Our risk-stratified prescribing approach should be prospectively evaluated.
Metabolic Sequelae and Quality of Life in Early Post-Treatment Period in Adolescents with Hodgkin Lymphoma
Authors: Pranjić Ines , Sila Sara , Lulić Kujundžić Sara , Dodig Mateja , Vestergaard Larsen Anna , Kranjčec Izabela
Published: January 2025

Background/Objectives: The long-term consequences of intensive treatment for Hodgkin lymphoma (HL), including metabolic syndrome (MetS) and cardiovascular diseases, but also deteriorated quality of life (QoL), are present in many survivors of childhood HL. Methods: Adolescents and young adults diagnosed with HL who continued the follow-up after successful treatment for HL were included. Anthropometric parameters, body composition, laboratory data, blood pressure values, compliance to the Mediterranean diet (MD), QoL and lifestyle habits were evaluated at the follow-up. Available data were also extracted retrospectively at the time of diagnosis. The primary objective was to determine metabolic sequelae in the early post-treatment period in adolescents treated for HL. Additionally, QoL and compliance with MD were explored, and the correlation of MetS with QoL was investigated. Results: Sixty percent of patients had at least one risk factor for metabolic syndrome, with obesity/abdominal obesity, high blood pressure and low HDL being most commonly observed, present in 66.7%, 44.4% and 44.4% of patients, respectively. The number of obese patients increased from 6.3% at the diagnosis to 31.3% at the follow-up. The majority of patients (53.3%) had low adherence to the MD. Participants had comparable quality-of-life domains to those of the healthy population at the follow-up. The physical health domain of QoL was positively correlated with compliance to the MD in young adults (r = 0.8, p = 0.032) and negatively correlated with obesity/overweight in adolescents (r = −0.85, p = 0.008). Conclusions: Healthy lifestyle choices can impact not only the metabolic health of survivors but also their quality of life, and therefore should be encouraged in these patients.
Remifentanil-Propofol-Ketamine- Based Total Intravenous Anesthesia with Spontaneous Breathing for Adult Rigid Bronchoscopy
Authors: Frasca Luca , Sarubbi Antonio , Longo Filippo , Costa Fabio , Sarubbi Domenico , Strumia Alessandro , Marziali Valentina , Crucitti Pierfilippo
Published: January 2025

Background: Rigid bronchoscopy (RB) is the gold standard for managing central airway obstruction (CAO), a life-threatening condition caused by both malignant and benign etiologies. Anesthetic management is challenging as it requires balancing deep sedation with maintaining spontaneous breathing to avoid airway collapse. There is no consensus on the optimal anesthetic approach, with options including general anesthesia with neuromuscular blockers or spontaneous assisted ventilation (SAV). Methods: This case series presents our anesthetic protocol using remifentanil–propofol–ketamine total intravenous anesthesia (TIVA) with SAV in four patients with airway obstructions. Muscle relaxants were avoided in all cases. Results: Ketamine’s ability to preserve respiratory drive and airway reflexes, along with its bronchodilating properties, made it ideal for managing CAO. All procedures successfully restored airway patency without complications or drug-related side effects. Conclusions: Our findings suggest that remifentanil–propofol–ketamine TIVA combined with SAV is a viable anesthetic approach for therapeutic RB, offering effective sedation, maintaining airway patency, and minimizing perioperative complications.
Long COVID in Children and Adolescents: Mechanisms, Symptoms, and Long-Term Impact on Health—A Comprehensive Review
Authors: Basaca Diana-Georgiana , Jugănaru Iulius , Belei Oana , Nicoară Delia-Maria , Asproniu Raluca , Stoicescu Emil Robert , Mărginean Otilia
Published: January 2025

Long COVID, also known as post-acute sequelae of SARS-CoV-2 infection (PASC), is increasingly recognized as a condition affecting not only adults but also children and adolescents. While children often experience milder acute COVID-19 symptoms compared to adults, some develop persistent physical, psychological, and neurological symptoms lasting for weeks or months after initial infection. The most commonly reported symptoms include debilitating fatigue, respiratory issues, headaches, muscle pain, gastrointestinal disturbances, and cognitive difficulties, which significantly impact daily activities, schooling, and social interactions. Additionally, many children with long COVID experience psychological symptoms, such as anxiety, depression, mood swings, and irritability, likely exacerbated by prolonged illness and lifestyle disruptions. Risk factors for long COVID in children include pre-existing health conditions such as asthma, obesity, and neurological disorders, with adolescents and females seemingly more affected. Hypothesized mechanisms underlying long COVID include chronic immune dysregulation, persistent viral particles stimulating inflammation, autonomic nervous system dysfunction, and mitochondrial impairment, which may collectively contribute to the variety of observed symptoms. Long-term outcomes remain uncertain; however, long COVID can lead to school absenteeism, social withdrawal, and psychological distress, potentially affecting cognitive development. Severe cases may develop chronic conditions such as postural orthostatic tachycardia syndrome (POTS) and reduced exercise tolerance. This review synthesizes the existing literature on long COVID in children, examining its prevalence, symptomatology, risk factors, and potential mechanisms, with an emphasis on the need for further clinical studies. While existing research largely relies on surveys and self-reported data, clinical assessments are essential to accurately characterize long COVID in pediatric populations and to guide effective management strategies.
Impact of Obesity on Hospitalization Burden of Urolithiasis in Spain Between 1997 and 2021
Authors: Rodríguez-Monsalve María , Durán-Poveda Manuel , Gómez Dos Santos Victoria , Burgos Revilla Javier , García-Criado Elena , Prieto Dolores , Gil de Miguel Ángel , Sáenz-Medina Javier
Published: January 2025

Background/Objective: The prevalence of kidney stones has increased, especially in industrialized countries. Obesity and metabolic syndrome have also risen significantly and are considered factors driving this trend. Our goal was to assess the hospitalization burden of kidney stones and identify epidemiological trends in Spain over the past 25 years. Additionally, this study analyzed the relationship between the data of kidney stone patients and obesity-coded diagnoses in hospital discharges. Methods: A retrospective observational study was conducted with the data from 1,070,192 patients hospitalized for urolithiasis between 1997 and 2021 using the Minimum Basic Data System. The hospitalization burden of lithiasis and its association with obesity was analyzed, alongside trend evaluations. The incidence of lithiasis in obese hospitalized patients versus all hospitalizations was compared. Mortality rates, length of stay, and the costs of lithiasis hospitalizations were evaluated to determine obesity’s impact on lithiasis patients. Results: Kidney stone cases increased by 1.8% annually (CI 95%: 0.2–3.3), with a more pronounced 10.7% (CI 95%: 7.3–14.2) increase in obesity-related hospitalizations. Obesity increased the likelihood of lithiasis hospitalization by 15.6 times and was associated with higher hospitalization costs. However, obesity did not significantly affect hospital stay duration or mortality rates. Conclusions: The increasing burden of kidney stone hospitalizations in Spain is linked to rising obesity rates. Obesity contributes to higher hospitalization costs. Preventive strategies targeting obesity should be implemented to reduce the burden on healthcare systems.
Is It Feasible to Apply a Virtual Box and Block Test in Children with Unilateral Cerebral Palsy?: A Pilot Study
Authors: Pérez-Nombela Soraya , Merino-Andrés Javier , Gómez-Soriano Julio , Álvarez-Rodríguez María , Ceruelo-Abajo Silvia , López-Muñoz Purificación , Palomo-Carrión Rocío , de los Reyes-Guzmán Ana
Published: January 2025

Background: With technological advancements, virtual versions of the Box and Block Test (BBT) employing the Leap Motion Controller have been developed for evaluating hand dexterity. Currently, there are no studies about the usefulness of this system in children with unilateral cerebral palsy (UCP). Thus, our main objective is to apply a virtual BBT based on the Leap Motion Controller in children with UCP compared with the real BTT for assessing upper limb function within a pilot study. Methods: Seven children between the ages of 4 and 8 years who were diagnosed with UCP were assessed three times using the real and virtual BBT. Results: For all the participants, performance was greater in the real BBT than in the virtual BBT. During the last assessment, the participants reached 28.17 (SD:6.31) blocks in the real test and 9.00 (SD:5.90) in the virtual test. The correlation index between the two modalities of the BBT was moderate (r = 0.708). Conclusions: The results obtained in this study suggest that the application of the virtual BBT in children with UCP is feasible. Future studies are needed to validate the application of the virtual BBT in children with UCP.
An Updated Design Formula for Predicting the Compressive Strength of Plate: Elastic Buckling and Ultimate Compressive Strength
Authors: Kim Do Kyun , Yang Hee Yeong , Li Shen , Kim Seungjun
Published: January 2025

In the present study, a simplified and useful design formula is proposed to predict the ultimate strength of a plate under longitudinal compression. The shape of the elastic buckling strength (σxE) equation is utilised and adjusted to predict the ultimate compressive strength of the plate. In total, 600 cases of reasonable plate scenarios are selected to update the design formula by broadly considering the plate geometry (i.e., plate length, breadth, and thickness), material property (i.e., elastic modulus and yield strength), and initial deflection. The proposed formula, including the factor or coefficient for correction (Cf) may help ocean and shore (including onshore, offshore and nearshore) structural engineers improve safety and design the unstiffened plate element used in shipbuilding and oil and gas.
The Nexus of Research and Development Intensity with Earnings Management: Empirical Insights from Jordan
Authors: Farah Freihat Abdelrazaq , Farhan Ayda , Khatatbeh Ibrahim
Published: January 2025

Driven by positive accounting, agency, and political and economic theories, this study examines the relationship between research and development (R&D) intensity and earnings management for listed pharmaceutical companies in the Amman Stock Exchange (ASE) between 2008 and 2021. Employing panel regression methods, the results reveal a positive association between R&D investment and earnings manipulation. Specifically, after two or three R&D delays, the association survived. Moreover, firm size negatively affects earnings management, showing that larger firms have less tendencies to conduct earning manipulation. Furthermore, financial leverage and earnings management are strongly connected, showing that firms may utilize earnings management to avoid credit covenants. The findings emphasize distortions in R&D reporting and profit management within Jordan’s financial reporting practices. Enhancing the accuracy of R&D investment disclosures, minimizing profit manipulation, and fostering greater transparency are crucial. Jordan’s regulators should improve capitalization standards, transparency, auditing, and shareholder activism.
Fair Taxes, Better Revenue: A Case Study on Spatial Approaches to Land Taxation in Lebak Regency, Indonesia
Authors: Hernandi Andri , Meilano Irwan , Saptari Asep Yusup , Suwardhi Deni , Abdulharis Rizqi , Handayani Alfita P. , Nurmaulia Sella L. , Putri Nabila S. E. , Widyastuti Ratri , Merdekawati Putri , Cahyani Fitri N.
Published: January 2025

Land taxation, mainly the Land and Building Tax (LBT), is a critical revenue source for local governments in Indonesia, yet its contribution remains suboptimal due to inefficiencies in assessment and administration. This study focuses on the Lebak Regency to optimize the Sales Value of Taxable Objects (SVTO) assessment, a key determinant of LBT revenue. Using spatial analysis, Land Value Zones (LVZ), and socio-economic data, the research evaluates assessment ratios to identify discrepancies between SVTO and market values. Adjustments to SVTO are proposed based on spatial patterns, such as land use and infrastructure, and the Index of Developing Villages (IDV). Findings reveal significant disparities between assessed and market values, with assessment ratios ranging from 1% to 267%. Simulations indicate potential LBT revenue of IDR 224.7 billion under full compliance, compared to IDR 44.22 billion, the 2024 target. Adjustments based on spatial patterns from land use planning and village development indices enhance equity and accuracy in tax assessments, optimizing local revenues. Despite these improvements, the study’s limitations lie in the lack of community validation for the proposed methodology, which is essential to confirm its practicality and acceptance. Future research should address this gap and explore household-level dynamics, including tax affordability and spending patterns, to enhance policy inclusivity and align taxation systems with local socio-economic realities.
Cabozantinib Cutaneous Toxicity—Comprehensive Review
Authors: Tutunaru Cristina Violeta , Alexandru Dragos Ovidiu , Dracea Sanda Amelia , Ungureanu Loredana , Popa Liliana Gabriela , Beiu Cristina
Published: January 2025

Background: In the context of modern cancer therapy, the management of adverse effects of systemic therapies can lead to the avoidance of underdosing and withdrawal and increases in the quality of the therapeutic act and the quality of life. This review offers an overview of the skin-related toxicities associated with Cabozantinib, a multikinase inhibitor (MKI) that is approved for treating advanced kidney cancer, hepatocellular carcinoma, and medullary thyroid cancer. It covers the most common dermatological side effects, such as palmar–plantar erythrodysesthesia, stomatitis, hair alterations, xerosis, scrotal erythema, and subungual splinter hemorrhages. Additionally, this review includes suggested preventive strategies and management approaches based on the severity of these adverse effects.
Research on Two-Layer Polymer Composites Alternatively Obtained in a Constant Magnetic Field
Authors: Miękoś Ewa , Zieliński Marek , Cichomski Michał , Klepka Tomasz , Czarnecka-Komorowska Dorota , Drzewiecka Dominika , Sroczyński Dariusz , Fenyk Anna
Published: January 2025

The aim of this research was to obtain two-layer polymer composites with favorable mechanical and functional properties. The composites consisted of one lower layer of polymer with less elastic properties, containing no admixtures, and one upper layer of polymer with more elastic properties, containing plant admixtures, in the amount of 10% by weight of either goldenrod (Solidago virgaurea L.), or of turmeric (Curcuma longa L.). The admixtures S. virgaurea and C. longa were intended to introduce new biodegradable and medicinal properties without causing too much deterioration of physical or mechanical properties. Some polymer composites additionally contained magnetic particles in the form of carbonyl iron (Fe) in the amount of 20% by weight. The tests of mechanical tensile strength of the composites, water absorption, frost resistance, and surface contact angle were performed. Microscopic examinations determined the roughness of the cross-sectional surfaces. A constant magnetic field with magnetic induction B, which was an additional external factor changing the properties and structure of two-layer polymer composites, was also used in the research.
Magnetite Nanoparticles Encapsulated with PBS-PEG for AMF Hyperthermia
Authors: Souto Carlos Augusto Zanoni , de Souza Junior Fernando Gomes , da Silva André Romero , Pal Kaushik
Published: January 2025

Novel studies on typical synthesized magnetite nanoparticles were encapsulated into a poly (butylene succinate)/poly (ethylene glycol) copolymer (PBS-PEG). PBS was chosen because of its biocompatibility characteristics necessary for biomedical applications. PEG, as part of the macromolecular structure, increases the hybrid system’s solubility in an aqueous environment, increasing the circulation time of the material in the bloodstream. The immune system has difficulty recognizing particles with good solubility in an aqueous medium and with a diameter until 200 nm, preventing the body from eliminating the nanoparticles before the magnetic hyperthermia is performed. All the prepared materials were characterized by Fourier transform infrared spectroscopy (FTIR), scanning electron microscopy (SEM), energy dispersive spectroscopy (EDS), X-ray powder diffraction (XRD), thermogravimetric analysis (TGA), differential scanning calorimetry (DSC), dynamic light scattering (DLS), and zeta potential. The detailed investigated result executes the formulation developed in this work, showing it has potential and that further studies and analyses can be carried out so that the formulation can be improved, thus obtaining even better results.
Numerical Simulation of Compressive Testing of Sandwich Structures with Novel Triply Periodic Minimal Surface Cores
Authors: Vasile Alexandru , Constantinescu Dan Mihai , Indreș Andrei Ioan , Coropețchi Iulian Constantin , Sorohan Ștefan , Apostol Dragoş Alexandru
Published: January 2025

Sandwich structures with triply periodic minimal surface (TPMS) cores have garnered research attention due to their potential to address challenges in lightweight solutions, high-strength designs, and energy absorption capabilities. This study focuses on performing finite element analyses (FEAs) on eight novel TPMS cores and one stochastic topology. It presents a method of analysis obtained through implicit modeling in Ansys simulations and examines whether the results obtained differ from a conventional method that uses a non-uniform rational B-spline (NURBS) approach. The study further presents a sensitivity analysis and a qualitative analysis of the meshes and four material models are evaluated to find the best candidate for polymeric parts created by additive manufacturing (AM) using a stereolithography (SLA) method. The FEA results from static and explicit simulations are compared with experimental data and while discrepancies are identified in some of the specimens, the failure mechanism of the proposed topologies can generally be estimated without the need for an empirical investigation. Results suggest that implicit modeling, while more computationally expensive, is as accurate as traditional methods. Additionally, insights into numerical simulations and optimal input parameters are provided to effectively validate structural designs for sandwich-type engineering applications.
The Influence of Fiber Dispersion on the Properties of MgO Concrete and Engineering Applications
Authors: Jiang Feifei , Deng Wencong , Wang Qi , Gu Zihan , Wang Jialei
Published: January 2025

Adding expansion agents to compensate for concrete shrinkage is a common crack resistance technique, but excessive expansion can also increase the porosity of concrete and reduce its strength. The addition of fibers can reduce expansion and improve the compactness of concrete. However, too little fiber will not be effective in inhibition, while too much fiber will cause aggregation. In this study, steel fiber and MgO expansive agent were used at the same time, and the effect of fiber on the mechanical properties of MgO concrete was studied. The results showed that the appropriate amount of MgO (8%) could compensate for the shrinkage of concrete and slightly improve the strength of concrete. When the content reached 10%, MgO produced excessive expansion under free conditions, which reduced the strength of the concrete. After using MgO and steel fiber at the same time, steel fiber could restrain the expansion of MgO, improve the compactness of concrete, produce a “super superposition” benefit, and increase the strength of concrete by 20%. In addition, the reinforcing effect of steel fiber on MgO was closely related to its distribution. In the composite system, steel fiber not only played a “bridge role” but also needed steel fiber to effectively restrain the expansion of MgO and produce self-stress. Only when the steel fibers were evenly distributed could reliable bonding be ensured between the fibers and the matrix, and at this time, the fibers could restrain the expansion of MgO. Considering the uniformity of steel fiber distribution and construction cost, adding 8% MgO and 1% steel fiber has the maximum benefit.