Search Results (713)

The growing application of 3D concrete printing (3DCP) in construction has raised important questions regarding its long-term durability under freeze–thaw (F–T) exposure, particularly in cold climates. This review paper presents a comprehensive examination of recent research focused on the F–T performance of 3D-printed concrete (3DPC). Key material and process parameters influencing durability, such as print orientation, admixtures, and layer bonding, are critically evaluated. Experimental findings from mechanical, microstructural, and imaging studies are discussed, highlighting anisotropic vulnerabilities and the potential of advanced additives like nanofillers and air-entraining agents. Notably, air-entraining agents (AEA) reduced the compressive strength loss by 1.4–5.3% after exposure to F–T cycles compared to control samples. Additionally, horizontally cored specimens with AEA incorporated into their mixture design showed a 15% higher dynamic modulus after up to 300 F–T cycles. Furthermore, optimized printing parameters, such as reduced nozzle standoff distance and minimized printing time gap, reduced surface scaling by over 50%. The addition of a nanofiller such as nano zinc oxide in 3DPC can result in compressive strength retention rates exceeding 95% even after aggressive F–T cycling. The lack of standard testing protocols and the geometry dependence of degradation are emphasized as key research gaps. This review provides insights into optimizing mix designs and printing strategies to improve the F–T resistance of 3DPC, aiming to support its reliable implementation in cold-region infrastructure. Full article

Background: The coexistence of sickle cell disease (SCD), vascular Ehlers–Danlos syndrome (vEDS), primary ciliary dyskinesia (PCD), and Phelan–McDermid syndrome (PMS) in a single pediatric patient is extremely rare and poses substantial diagnostic and management challenges. Case presentation: We report an 8-year-old male from Jazan, Saudi Arabia, born to consanguineous parents, with early-onset SCD, followed by the identification of vEDS, PCD, and PMS through clinical presentation and whole exome sequencing. His disease course has been exceptionally severe, marked by monthly hospitalizations, multiple PICU admissions, and a wide spectrum of systemic complications. Conclusions: The coexistence of SCD, vEDS, PCD, and PMS may lead to synergistic vascular, pulmonary, and neurodevelopmental compromise, demanding multidisciplinary long-term management. This case underscores the need for a comprehensive targeted genetic assessment in patients with unusually aggressive or syndromic SCD phenotypes, particularly in regions with high levels of consanguineous marriages. Full article

It has been shown previously that repeated positive fighting experience in daily agonistic interactions is accompanied by the development of psychosis-like behavior, with signs of an addiction-like state associated with changes in the expression of genes encoding the proteins involved in the main neurotransmitter events in some brain regions of aggressive male mice. Fighting deprivation (a no-fight period of 2 weeks) causes a significant increase in their aggressiveness. This paper is aimed at studying—after a period of fighting deprivation—the involvement of genes (associated with neurotransmitter systems within the nucleus accumbens) in the above phenomena. The nucleus accumbens is known to participate in reward-related mechanisms of aggression. We found the following differentially expressed genes (DEGs), whose expression significantly differed from that in controls and/or mice with positive fighting experience in daily agonistic interactions followed by fighting deprivation: catecholaminergic genes Th, Drd1, Drd2, Adra2c, Ppp1r1b, and Maoa; serotonergic genes Maoa, Htr1a, Htr1f, and Htr3a; opioidergic genes Oprk1, Pdyn, and Penk; and glutamatergic genes Grid1, Grik4, Grik5, Grin3a, Grm2, Grm5, Grm7, and Gad1. The expression of DEGs encoding proteins of the GABAergic system in experienced aggressive male mice mostly returned to control levels after fighting deprivation, except for Gabra5. In light of the conceptual paradigm for analyzing data that was chosen in our study, the aforementioned DEGs associated with the behavioral pathology can be considered responsible for consequences of aggression followed by fighting deprivation, including mechanisms of an aggression relapse. Full article

Background: The hypopharyngeal region is among the most aggressive sites of head and neck squamous cell carcinoma, often presenting at an advanced stage with poor survival outcomes. However, there are only a limited number of biomarkers available to predict the prognosis of this aggressive disease. Recent interest has focused on immunonutritional biomarkers that may improve prognostication. The C-reactive protein–albumin–lymphocyte (CALLY) index has emerged as a composite biomarker integrating systemic inflammation, nutritional status, and immune competence. However, its clinical relevance in hypopharyngeal cancer has not been established. Methods: This retrospective, single-center study included patients with histologically confirmed hypopharyngeal squamous cell carcinoma treated with definitive chemoradiotherapy between 2010 and 2024. Patients were excluded from the study if they had incomplete laboratory data, had a concomitant malignancy, were undergoing induction chemotherapy, or had diseases affecting inflammatory and immunological markers. The CALLY index was calculated using pre-treatment laboratory values. Receiver operating characteristic (ROC) analysis determined the optimal cut-off value for overall survival (OS). Kaplan–Meier survival estimates and Cox regression analyses were used to assess associations between the CALLY index and progression-free survival (PFS), local recurrence-free survival (LRFS), and OS. Results: A total of 71 patients were included. The optimal CALLY cut-off was 1.47 (AUC = 0.70, p = 0.006). Patients with a CALLY index ≥ 1.47 had significantly improved median PFS (37 vs. 9 months, p = 0.003), LRFS (39 vs. 9 months, p = 0.002), and OS (61 vs. 11 months, p = 0.002). In multivariate analysis, the CALLY index and T stage remained independent prognostic factors of all three survival outcomes. Conclusions: The pretreatment CALLY index is a practical, accessible biomarker that independently predicts survival in hypopharyngeal cancer. Its integration into clinical practice may enhance risk stratification and guide individualized management strategies. Full article

Monilinia fructigena, a causal agent of brown rot in apple and other fruit crops, poses a significant threat to fruit production and postharvest quality in temperate regions. This study reports on the molecular and morphological identification of M. fructigena isolates obtained from symptomatic apple fruits in the Almaty region of Kazakhstan. Nine isolates were characterized through a combination of morphological assessment, real-time PCR, target locus (ITS and TEF1-α gene) sequencing, and whole genome sequencing using nanopore sequencings. Morphological analysis revealed typical features of M. fructigena, including blastoconidia and microconidia. Pathogenicity tests on ‘Idared’ and ‘Golden Delicious’ apples confirmed the high aggressiveness of the isolates, with lesion development observed within 24–48 h post-inoculation. Molecular identification via real-time PCR and target sequencing confirmed all isolates as M. fructigena with high mapping quality and sequence identity. The whole genome sequencing of a representative isolate further validated the species identity based on comparative alignment with Monilinia reference genomes. Thus, the combination of the used traditional and molecular methods allowed us to unambiguously identify the isolated fungus as M. fructigena. This integrative approach enhances the understanding of Monilinia species in Central Asia and supports the implementation of modern molecular tools for phytopathogen surveillance and agricultural biosecurity. Full article

Background: Intrahepatic cholangiocarcinoma (ICC) is an aggressive malignancy with very poor survival. Prior research suggests rural–urban disparities on a regional scale. We aimed to elucidate these disparities in treatment and disease-specific survival (DSS) for ICC patients on a national scale using the SEER database. Methods: The SEER database was queried to identify biopsy-confirmed cases of ICC from 2000 to 2021. Differences in clinicopathologic features and treatment between rural and urban patients were assessed using Chi-square and Fischer’s exact tests. Disease-specific survival was compared using Kaplan–Meier and log-rank tests as well as multivariable Cox regressions. Results: A total of 14,940 ICC patients were identified. Rural patients were less likely than urban patients to receive chemotherapy (789 of 1588 [49.7%] vs. 7112 of 13,352 [53.3%], p = 0.006) and surgical treatment (305 of 1588 [19.2%] vs. 2922 of 13,352 [21.9%], p = 0.013). Rural patients experienced reduced 5- and 10-year DSS rates (7.0% and 4.0%) compared to urban patients (9.0% and 6.0%, p < 0.001). In multivariable analysis, rural residence independently demonstrated a 17% increased risk of disease-specific mortality compared to their urban counterparts (aHR 1.17, 95% CI 1.03–1.32). Conclusions: This study demonstrates significant rural–urban disparities in ICC treatment and survival throughout the US, independent of other prognostic factors. Further investigation into factors driving these disparities is warranted to improve outcomes for rural ICC patients. Full article

Advanced Gastric Signet Ring Cell Carcinoma (SRCC) is characterized by aggressive behavior, high metastatic potential, and extremely poor prognosis. There is an urgent need for effective imaging modalities to evaluate systemic metastatic lesions and to dynamically monitor disease progression during treatment. We report a rare case of a 26-year-old female with advanced SRCC presenting with extensive systemic metastases, clinically staged as IV (cT4N3M1). High-frequency and conventional ultrasound imaging revealed metastatic lesions involving the scalp soft tissues, cervical lymph nodes, intercostal soft tissues, pancreatic-splenic hilum region, pelvic cavity, peritoneum and omentum. The ultrasonographic findings were highly consistent with contrast-enhanced computed tomography (CT) and magnetic resonance imaging (MRI) results. The patient received seven cycles of a modified BEMA regimen (oxaliplatin, leucovorin and 5-fluorouracil) combined with nivolumab. Serial ultrasound monitoring indicated continuous disease progression. Due to poor therapeutic response, the patient succumbed to acute obstructive renal failure caused by tumor progression seven months after diagnosis. This report provided a comprehensive ultrasonographic assessment of widespread and rare metastatic sites in advanced SRCC, a scenario seldom documented. The combination of high-frequency ultrasound and Super Microvascular Imaging (SMI) offered precise, radiation-free, and repeatable evaluation of both superficial and deep lesions, proving particularly valuable for real-time monitoring of treatment response in critically ill patients. These findings underscore the unique role of systemic ultrasound in enhancing metastatic detection and therapeutic evaluation for advanced SRCC. Full article

Regulatory T cells (Tregs) have anti-inflammatory immunomodulatory activity and hold therapeutic potential for chronic neuroinflammatory neurodegenerative diseases, such as amyotrophic lateral sclerosis (ALS). We are developing engineered human Tregs with enhanced disease-modifying activity for treating ALS. A combination of a disease-specific chimeric antigen receptor (CAR) recognizing misfolded human superoxide dismutase-1 (hSOD1) and constitutive expression of brain-derived neurotrophic factor (BDNF) was tested. The scFv region of CAR demonstrated binding to anterior horn tissues of ALS patients with and without familial ALS mutations in SOD1. Tregs transduced to express BDNF showed the ability to secrete BDNF and protect co-cultured neuronal cells from peroxidase toxicity. Co-expression of BDNF did not inhibit CAR Treg expansion, Treg markers, or CAR-mediated anti-inflammatory cytokine production. Human Tregs co-expressing CAR and BDNF were tested for activity in G93A hSOD1-NSG transgenic mice, which develop an early-onset and aggressive ALS-like disease and do not reject human cells. Human Tregs expressing CAR and BDNF delayed the onset of disease development, extended survival, and decreased spinal cord neuroinflammation. The engineered Tregs showed enhanced disease-modifying activity and hold promise as a therapy for ALS. Full article

Introduction: Achieving LDL cholesterol (LDL-C) targets is critical in secondary cardiovascular prevention. Despite clinical guidelines promoting aggressive lipid-lowering strategies, many patients fail to reach recommended LDL-C levels. This study aimed to evaluate lipid profile management among secondary prevention patients in Spain using the Spanish Primary Care Clinical Database (BDCAP) registry. Methods: A repeated cross-sectional study was conducted using 2019–2023 data from the BDCAP. Patients with prior diagnoses of ischemic heart disease, stroke, or peripheral artery disease, and receiving lipid-lowering therapy, were included. Data on therapy type (monotherapy or combination therapy with lipid-lowering drugs), LDL-C serum levels, and demographic and socioeconomic factors were analyzed. Trends from 2019 to 2023 and regional differences were also explored. Results: In 2023, 1,565,429 patients received lipid-lowering drugs for secondary prevention (678.3 per 1000 attended), with higher rates in men. Combination therapy increased over time, from 88.9 to 191.1 per 1000 between 2019 and 2023. Regional disparities were notable, with treatment coverage ranging from 53.9% to 87.9%. Only 33.7% of treated patients achieved LDL-C < 70 mg/dL, and 65.6% achieved <100 mg/dL. Combination therapy was significantly more effective than monotherapy in reaching both LDL-C thresholds. Conclusions: Despite the growing use of combination lipid-lowering therapy, a substantial proportion of secondary prevention patients in Spain do not meet LDL-C targets. These findings highlight the need for more intensive lipid management strategies and improved adherence to clinical guidelines to optimize cardiovascular risk reduction. Full article

Background: Glioblastoma (GBM) is an aggressive brain tumor, with surgery being an integral part of treatment. Aggressive resections improve clinical outcomes but need to be balanced against potential functional impairment. Neuropsychological (NP) testing is an important tool neurosurgeons use to assess cognitive functioning. Importantly, associations between NP test scores and imaging biomarkers could enable a testable baseline by which to track patient outcomes over time and aid in presurgical counseling. Methods: We identified 44 patients diagnosed with primary GBM and who had detailed NP testing and presurgical imaging. Regression models for NP indices were created with tumor size, hemisphere, and lobar location as predictors. Lesion–symptom mapping (LSM) analyses were used to identify more detailed structure–function relationships. Results: Larger tumor volumes predicted worse attention, immediate memory, language, visuospatial, and overall NP performance (p < 0.05 for all). Left hemisphere involvement predicted worse attention, language, and immediate memory NP performance (p < 0.01 for all). Only visuospatial testing had lobar location significantly associated with worse scores (occipital lobe; p < 0.05). The LSM analyses identified areas around the left sagittal stratum as significantly associated with language performance (p < 0.05), with no other structure–function relationships being identified. Conclusions: These findings support the growing evidence that outside of a small number of truly critical regions, high-grade gliomas impair cognition generally, likely due to progressive tumor infiltration-associated neuroplasticity of complex parallel and interconnected networks. To investigate this, future studies should incorporate larger cohort sizes and should examine the relationship of glioma-induced network-level perturbations on cognitive decline. Full article

The impact of invasive alien species (IAS) is one of the direct factors causing global biodiversity decline and economic losses, and predicting the potential invasion risks of invasive species is crucial for developing prevention and control strategies. In recent years, an increasing number of studies have shown that invasive species undergo rapid shifts in climate niche in invaded areas. Accurately quantifying the dynamic shifts in the climate niche of invasive species in invaded areas is crucial for developing a more accurate framework for early warning of invasive species risks. Pomacea canaliculata is a freshwater snail found in South America and has become one of the most aggressive aquatic species in the world. Since its introduction to China in 1981, it has rapidly spread and caused multiple serious damages to agriculture, ecology, and public health. Therefore, based on multi-source distribution data of P. canaliculata, this study calculated the climate niche overlap by Schoener’ s D, quantified the niche shifts between the P. canaliculata in native and invaded areas (China) via the COUE scheme (a unified terminology representing niche centroid shift, overlap, unfilling, and expansion), and analyzed their changes on a time scale. The results revealed that there have been significant climate niche shifts (Schoener’s D < 0.2, niche similarity tests p > 0.01, niche equivalence tests p < 0.01) between the native and invaded areas (China) of P. canaliculata, which does not support the climate niche conservation hypothesis. The minimum temperature of the coldest month (Bio 6) and precipitation seasonality (Bio 15) were the key climate variables driving the climatic niche shift, and P. canaliculata can survive in colder and more arid regions than their native counterparts. The changes in the niche shifts in P. canaliculata on a time scale show significant temporal heterogeneity, and its invasion behavior in China presents a discontinuous and phased expansion pattern, with strong adaptability to new environments. The results are of great significance for the future development of more accurate ecological niche model (ENM), the formulation of more targeted prevention and control strategies, and the study of adaptive evolution mechanisms of invasive species. Full article

Perineuriomas are a rare form of peripheral nerve sheath tumors, with occurrences in the oral cavity being exceptionally uncommon. This scarcity underscores the clinical significance of each documented case, as it facilitates enhanced diagnostic precision among oral health professionals. We hereby present a case involving a 68-year-old female patient with an extraneural perineurioma (EPN) located on the mandibular region. A laser-assisted excisional biopsy was performed, and the diagnosis of EPN was confirmed through histopathological examination complemented by immunohistochemical analysis. The lesion was surgically excised, and no recurrence was observed during a one-year follow-up period. Accurate recognition of EPNs in the oral cavity is crucial to prevent unnecessary aggressive surgical interventions. Misdiagnoses may occur in cases of fibromas, neurofibromas, schwannomas, ossifying fibromas, or low-grade malignancies, which can potentially result in overtreatment that may compromise both function and aesthetics. Given the rarity of oral EPN, precise diagnosis and appropriate management are essential to avoid unwarranted invasive procedures and to mitigate potential medico-legal implications originating from misdiagnosis or suboptimal treatment. Ensuring comprehensive informed consent and meticulous documentation is also vital in minimizing medico-legal risks. Full article

Background: chordomas are characterized as locally aggressive yet infrequently metastasizing malignant neoplasms of bone, primarily arising in the axial skeleton, with a notable prevalence in the sacral region. En bloc resection is recognized as the standard treatment for sacral chordoma; however, its feasibility is not universally guaranteed. Therefore, definitive proton, carbon ion, or photon therapy is often utilized as an alternative to surgical intervention or as a (neo-)adjuvant measure in conjunction with surgery, owing to their role in enhancing local control. Methods: a search of PubMed yielded 127 articles, with 18 that were ultimately included in the review. This review aims to systematically evaluate clinical outcomes and complications associated with hadron therapy in cases of sacral chordomas. The review followed the PRISMA (Preferred Reporting Items for Systematic Reviews and Meta-Analyses) guidelines, including publication dates up to January 2025. Results: data extraction showed promising outcomes for patients treated with hadron therapy alone or when hadron therapy was used as an adjuvant for surgery, even if complications are described. The 5-year overall survival estimated from evaluating 10 of 18 articles was 82.4%, although some articles reported different results in shorter follow-up periods. Skin ulceration and pain were described in 323 (29%) and 186 (16%) patients, respectively. Chronic complications reported were sacral fractures, metastasis, rectal disorders, urinary disorders, and peripheral motor and sensory neuropathy. Conclusions: hadron therapy represents a highly effective and promising treatment for sacral chordomas. In cases of inoperable tumors, it has demonstrated outcomes comparable to surgery while significantly reducing treatment-related morbidity. Hadron therapy is also viable as adjuvant therapy and provides superior outcomes for patients who undergo surgery with positive margins compared to those treated with surgery alone, improving local control and overall prognosis. Full article

Invasive weeds pose a growing threat to global biodiversity, ecosystem stability, and agricultural productivity with significant ecological and economic consequences. In Iran, the rapid spread of invasive species such as Boreava orientalis, Azolla spp., Ibicella lutea, Physalis divaricata, Picnomon acarna, Cynanchum acutum, Vicia hyrcanica, Eichhornia crassipes, and Ambrosia psilostachya has severely affected native ecosystems, disrupted ecological processes, and threatened food security. These species exhibit aggressive traits such as rapid maturity, high reproductive rates, seed dormancy, and allelopathy that enable them to outcompete native species and successfully invade and dominate delicate habitats. Despite their documented impacts, a critical gap remains in understanding their biology, ecology, and management, particularly in understudied regions like Iran. This review synthesizes current knowledge on major invasive weeds affecting Iranian agroecosystems, with a focus on their ecological impacts and the urgent need for sustainable management strategies. It presents an integrated framework that combines ecological, biological, and management perspectives to address invasiveness, particularly in highly adaptable species like B. orientalis and A. psilostachya. This review highlights the critical role of interdisciplinary collaboration, advanced technology, and community involvement in developing effective strategies. It offers practical guidance for researchers, policymakers, and agricultural stakeholders, serving as a model for managing invasive species in other vulnerable regions. Ultimately, it supports global efforts to safeguard biodiversity, improve crop productivity, and strengthen ecological resilience against the growing threat of invasive species. Full article

Upon transferal from plastic to Matrigel, melanoma cells demonstrate growth in three dimensions and form de novo vascular networks—known as vasculogenic mimicry—that are characteristic of the stemness phenotype of aggressive tumors. It has been reported that during malignant transformation, stress, or differentiation, the long-range inter-chromosomal interactions between numerous developmental genes and nucleoli are changed. The aim of this work was to study the potential mechanisms behind the development of the vasculogenic mimicry phenotype in melanoma cells and whether the formation of these 3D structures is connected with the reorganization of inter-chromosomal contacts of rDNA clusters. Here, we show that after 15 h of growth on Matrigel, and following the formation of the vasculogenic mimicry phenotype, dramatic changes occur in Mel Z cells in rDNA contacts with different genomic regions that possess mainly developmental genes. Approximately 400 genes that retained stable contacts with nucleoli were co-expressed with different lincRNAs and were highly associated with H3K27me3 marks and simultaneously regulated by different transcription factors. These genes are involved in development and cell adhesion and may control the basic stage of differentiation. The genes that acquired or increased contacts with rDNA clusters during growth on Matrigel are associated with cell morphogenesis, cell junctions, and the cytoskeleton. Here, we present the first evidence that nucleoli may be involved in both the activation and repression of particular groups of developmental rDNA-contacting genes in melanoma cells forming the vasculogenic mimicry phenotype. We conclude that the inter-chromosomal interactions between developmental genes and rDNA clusters are dynamic, and that nucleoli play an important role in the development of vasculogenic mimicry and stemness phenotypes in aggressive tumor genes. Full article