Search Results (192)

Understanding the physical mechanisms of extreme weather and climate events often relies on identifying typical large-scale circulation patterns associated with such extremes. Self-organizing maps (SOMs) have therefore been widely applied in atmospheric and climate studies as an objective clustering tool for circulation pattern classification. However, because SOM necessarily assigns all events to a limited number of representative nodes, individual extreme events with atypical large-scale circulation patterns may be grouped into clusters that do not adequately represent their underlying dynamics. In this study, we examine this interpretational issue using 223 severe January cold events over South Korea during 1949–2021. We show that a substantial fraction of cold events exhibits weak or even conflicting similarity with their assigned SOM node patterns, indicating pronounced within-node heterogeneity. Although optimizing the SOM node configuration and cluster number reduces the proportion of atypical cases, such heterogeneity cannot be fully eliminated. We further apply a pattern-correlation–based post-processing approach (SOM-PC) to explicitly identify and exclude atypical cases, which reduces the number of atypical cold events by approximately 27%. Rather than pointing to limitations of SOM itself, our results underscore potential interpretational pitfalls that can arise when SOM-derived circulation patterns are directly linked to extreme events without evaluating the representativeness of individual cluster members. These findings highlight the importance of applying explicit diagnostics for within-cluster heterogeneity when using SOM or similar data-driven tools to elucidate large-scale circulation patterns underlying localized extreme weather and climate events. Full article

Objectives: Atypical teratoid/rhabdoid tumors (ATRTs) are rare, malignant central nervous system (CNS) neoplasms that predominantly affect infants and young children. While ATRT arises throughout the CNS, its extracranial counterpart, malignant rhabdoid tumor, occurs in other organs. A single-institutional cohort is reviewed to map anatomic distribution of pediatric ATRTs and to integrate a literature review to contextualize ATRT histogenesis from anatomical and embryological perspectives. Methods: A retrospective review was conducted on a cohort of 50 pediatric patients with ATRT treated over 20 years. Demographic, surgical, and neuroimaging data were correlated to define tumor location, extent, and compartmental involvement. A focused literature review synthesized molecular subclassifications and proposed cells of origin/cytogenesis. Results: Of the 50 ATRTs, 18 (36%) were infratentorial, 15 (30%) supratentorial, 11 (22%) in the pineal region, and 6 (12%) in the spinal compartment. Among infratentorial tumors, 10 were centered in the fourth ventricle, with or without extension into the cerebellopontine angle (CPA) cistern; the remainder arose in the CPA. Among ATRTs of the cerebral hemispheres, 3 showed bi-hemispheric involvement crossing the falx cerebri. ATRTs of the pineal region predominantly originated from the superior medullary velum. These topographic data were corelated with embryological and molecular information available in the literature. Conclusions: ATRTs arise across diverse neuroanatomical compartments—including intraparenchymal, intraventricular, extra-axial, and extradural sites—underscoring biological heterogeneity. Inactivation of SMARCB1 is the defining molecular event and principal oncogenic driver, although the upstream mechanisms precipitating these alterations remain incompletely resolved. Molecular subgroups—ATRT-TYR, ATRT-SHH, and ATRT-MYC—display distinct age distributions and anatomic predilections, implicating developmental context in tumor initiation. The characteristic cellular admixture of rhabdoid cells with mesenchymal and/or epithelial differentiation, together with intra- and extra-axial and occasional extradural presentations, supports a model in which at least a subset of ATRTs may originate from neural crest-derived lineages, despite little or no neural crest contribution to brain parenchyma development. Neural plate border progenitors with bipotent features represent a plausible intraparenchymal cell of origin. Definitive resolution of these origins and the mechanisms of SMARCB1 disruption will require integrated approaches. Further investigations are warranted to clarify these mechanisms. Full article

Ferritin heavy chain (FTH1) is a key subunit of ferritin and serves as a core regulator of iron metabolism, playing an important role in alleviating cellular damage caused by oxidative stress or regulating programmed cell death. This study identified 7 FTH1 homologs (AgFTH1-1 to AgFTH1-7) across the entire genome of Anadara granosa and investigated their expression responses during Vibrio infection. The 7 AgFTH1 genes are arranged in tandem across 6 chromosomes, with AgFTH1-5 and AgFTH1-6 undergoing gene amplification via a local duplication event. Among these homologous genes, 5 genes contain a single conserved ferritin domain (PF00210) and retain key ferroxidase center residues (Glu23, His65). Following Vibrio infection, these 5 genes exhibit downregulated expression, which may increase intracellular free iron and be consistent with ferroptosis-like cell death contributing to pathogen clearance, as suggested by previous studies. AgFTH1-5 contains a signal peptide and exhibits increased expression, suggesting it may regulate extracellular local iron storage. AgFTH1-4 (synaptonemal N-terminal SNARE) and AgFTH1-7 (GTPase domain) lack signal peptides, exhibit atypical structures, and show no significant expression changes under bacterial stress, indicating they may be associated with vesicle trafficking rather than classical iron storage. This study systematically analyzed the genomic features and expression patterns of the FTH1 gene family in A. granosa, laying a foundation for further revealing its role in shellfish immune defense. Full article

Neurofibromatosis type 1 (NF1) predisposes to a spectrum of peripheral nerve sheath tumors, ranging from benign plexiform neurofibromas (PN) to atypical neurofibromatous neoplasms of uncertain biological potential (ANNUBP) and malignant peripheral nerve sheath tumors (MPNST). Tumorigenesis follows a multistep molecular cascade initiated by biallelic NF1 inactivation, followed by CDKN2A loss and disruption of the Polycomb Repressive Complex 2 (PRC2). These events guide chromatin remodeling, widespread epigenetic dysregulation, and activation of oncogenic pathways such as RAS/MAPK and PI3K/AKT. Here, we integrate genomic, transcriptomic, and epigenomic studies to delineate the molecular trajectories underlying tumor progression and to define promising biomarkers for the early detection of malignant transformation. Emerging liquid biopsy approaches, based on circulating tumor DNA (ctDNA) analyses, reveal distinctive copy number variations (CNVs) and methylation patterns that mirror tissue-derived profiles, enabling the detection of malignant transformation. Together, these findings support a model in which cumulative genetic and epigenetic alterations drive the PN–ANNUBP–MPNST continuum. They also underscore the value of multi-omics and liquid biopsy-based strategies to improve early diagnosis, patient risk stratification, and personalized management of NF1-associated tumors, thereby advancing precision medicine in this complex disease spectrum. Full article

Background: Endometrial hyperplasia (EH) represents a precursor lesion in the development of endometrial carcinoma, particularly the endometrioid subtype. Among the molecular pathways involved, microsatellite instability (MSI) resulting from DNA mismatch repair (MMR) deficiency has gained increasing attention as an early event in endometrial carcinogenesis. Objective: This study aimed to evaluate the expression of key MMR proteins (MLH1, PMS2, MSH2, and MSH6) in endometrial hyperplasia without atypia and endometrial atypical hyperplasia/endometrioid intraepithelial neoplasia (EAH/EIN) to determine the prevalence and potential implications of MMR deficiency at the precancerous stage. Methods: Fifty-six cases of EH were analyzed, including 28 endometrial hyperplasia without atypia and 28 EAH/EIN. Immunohistochemical (IHC) analysis was performed to assess the nuclear expression of MMR proteins. Loss of expression was defined as complete absence of epithelial nuclear staining with retained stromal positivity. Results: MMR protein expression was retained in all cases of endometrial hyperplasia without atypia, while total loss of one or more MMR proteins was observed in 3 of 28 (10.7%) EAH/EIN. The most frequent pattern involved concurrent MLH1/PMS2 loss, consistent with sporadic MLH1 promoter hypermethylation. One case exhibited isolated MSH6 loss, suggesting a potential Lynch syndrome, and another showed combined MSH6/PMS2 loss. Conclusions: MMR deficiency appears confined to atypical EH, supporting its role as an early molecular alteration in the neoplastic sequence leading to endometrioid carcinoma. Identification of abnormal MMR expression in EH may facilitate risk stratification, guide reflex testing for MLH1 methylation, and prompt genetic counseling for hereditary cancer predisposition. Full article

Background and Clinical Significance: Creutzfeldt–Jakob disease (CJD) is a rare and fatal neurodegenerative disorder caused by prion protein misfolding. The disease poses significant diagnostic challenges, particularly when its initial symptoms mimic other conditions, such as transient ischemic attacks. Early recognition and differentiation from other neurological conditions are critical, as misdiagnosis may lead to unnecessary interventions. This case highlights a unique presentation of CJD in a male Caucasian patient with a history of cardiac surgery and mitral valve prosthesis, emphasizing the role of multidisciplinary evaluation in complex neurological cases. Case Presentation: A male patient in his mid-sixties with a history of mitral valve mechanical prosthesis and prior infective endocarditis presented with progressive cognitive decline, memory impairment, and episodes of confusion. Initial cardiovascular investigations suggested mitral valve prosthesis thrombosis, while neurological assessment pointed toward transient brain ischemia. However, brain imaging remained inconclusive. Given the rapid deterioration of cognitive and motor functions, further diagnostic workup was performed. MRI findings revealed cortical diffusion restrictions consistent with probable CJD. Despite symptomatic management, the patient’s condition worsened, leading to akinetic mutism and death within eight days of diagnosis. Conclusions: This case underscores the diagnostic complexity of CJD, particularly when initial symptoms overlap with transient ischemic events. It highlights the importance of comprehensive neuroimaging and an interdisciplinary approach in recognizing atypical neurodegenerative diseases to improve diagnostic accuracy and patient management. Full article

Objectives: To evaluate reports of diabetic ketoacidosis (DKA) associated with antipsychotic drug (APD) use submitted to the U.S. Food and Drug Administration’s Adverse Event Reporting System (FAERS). Methods: A retrospective pharmacovigilance analysis was conducted using FAERS data from January 2000 to December 2022. DKA cases were identified using the MedDRA preferred term “diabetic ketoacidosis” in reports listing antipsychotic drugs as suspect medications. Disproportionality analyses, including the proportional reporting ratio (PRR) and empirical Bayes geometric mean (EBGM), were used to assess reporting patterns. Multiple analyses were performed, including those restricted to primary suspect listed drugs only, expanded to incorporate secondary suspect drugs, and sensitivity analyses excluding reports submitted by legal professionals. Results: Among 19,961 DKA reports in FAERS, 2489 (12.5%) listed atypical antipsychotics as the primary suspect drug, whereas reports involving typical APDs were rare. The majority of reports were submitted by healthcare professionals (74.1%), and nearly half originated from the United States (45.4%). Hospitalization was a frequent outcome, reported in 74.3% of cases. Quetiapine and olanzapine were the most frequently reported atypical APDs, with disproportionality analyses demonstrating strong safety signals when compared to all other drugs in FAERS: olanzapine PRR 13.2 (95% CI: 12.4–14.2) and quetiapine PRR 11.8 (95% CI: 11.1–12.5). The findings remained consistent across multiple sensitivity analyses, including incorporating secondary suspect drugs, when the comparator group was restricted to only psychotropic drugs, and excluding reports submitted by lawyers. Conclusions: This pharmacovigilance analysis highlights a potential safety signal for DKA with atypical antipsychotic drugs, notably quetiapine and olanzapine. While these findings do not establish causality, they underscore the need for further investigation using clinical and epidemiological data. Full article

The Altun Orogenic Belt (AOB) has undergone multiple complex subduction–collision events. However, there are numerous disagreements regarding the Early Paleozoic tectonic–magmatic evolution of the AOB, primarily due to differing interpretations of magmatic rock types and their sources. As a result, we conducted detailed geochemical analyses of granite samples obtained from several exploration wells in the Dongping area (DPA) of the South Altun Orogenic Belt (SAOB) at the western boundary of the Qaidam Basin. This approach differs from previous studies that mainly relied on outcrop samples. The granites in the study area are metaluminous and have high alkali contents (avg. 7.63%) and high TFe₂O₃/MgO ratios (avg. 4.50). Their rare-earth elements are enriched in light REEs and show weak to moderate negative Eu anomalies (δEu = 0.49–1.11). These geochemical signatures indicate an affinity to A-type granites. Through comprehensive diagram analysis, the rocks plot near the upper crustal composition in a Ta/Yb-Th/Yb diagram, indicating that they primarily originated from a mixed source of recycled and juvenile crustal material. A comprehensive analysis of the regional tectonic background shows that the Early Paleozoic granites in the SAOB formed in post-collisional extensional environments and syn-collisional volcanic arc tectonic settings. The majority formed in post-collisional extensional thinning environments, whereas a minority formed in syn-collisional volcanic arc tectonic settings, closely related to the subduction and collision of the Qaidam Block beneath the Central Altun Block. Full article

Hydropower is the primary source of electricity in several countries in Latin America. Hydropower provides approximately 80% of Ecuador’s electricity; however, it remains highly vulnerable to climate change, resulting in uncertainties in power generation due to altered precipitation patterns, runoff, and systematic failures. Consequently, Ecuadorians are becoming increasingly reliant on diesel generators during crises, resulting in public health, safety, and economic impacts, as well as social and political disruptions. This study evaluated noise pollution in the central urban area of the city of Loja for the first time during the 2024–2025 electricity crisis in Ecuador. A Type 1 integrating sound-level meter was used to monitor noise pollution (LAeq, 10min) at 20 locations during periods of generator operation and non-operation. At each location, the number of generators, the density of commercial activities along the streets, as well as traffic and other urban characteristics, were recorded. Results revealed that the presence of generators, street width, and the number of generators significantly increased the LAeq, 10min, often exceeding the limits set by the World Health Organization and Ecuador’s environmental regulations. Frequency spectrum analysis revealed that medium frequencies increased with A-weighting, while low frequencies rose with C-weighting, suggesting potential health risks to the local population. The thematic noise map during generator inactivity showed lower noise levels, averaging around 71.5 dBA. Conversely, when the generators were operational, noise levels exceeded 79.6 dBA, indicating a significant increase in environmental noise exposure associated with their use. This highlights an urgent need to implement and expand renewable energy sources, as existing options like wind power, photovoltaic energy, and biomass are insufficient to meet community demands. Full article

Background: Atypical teratoid rhabdoid tumor (ATRT) is a highly aggressive, rare pediatric central nervous system malignancy. Prognostic factors for optimizing risk stratification and management in a large uniformly treated cohort are lacking. Methods: We conducted a single-center retrospective cohort study analyzing clinical and outcome data for 100 newly diagnosed ATRT patients aged <18 years treated at the Children’s Cancer Hospital, Egypt, from 2008 to 2022. They were treated uniformly as per the Dana-Farber Cancer Institute modified IRS-III protocol. Molecular subgroups (MYC, SHH, and TYR) were determined via a DNA methylation array for patients who had sufficient DNA material available for the methylation analysis. Treatment toxicities were graded per the Common Terminology Criteria for Adverse Events (CTCAE) v5.0. Results: The median age at diagnosis was 1.88 years (IQR 0.99, 3.01); 28% were under 1 year of age, 45% were between 1 and 3 years old, and 26% were above 3 years of age. At diagnosis, 39% of patients had metastatic disease. A total of 60% of patients had gross residual disease following surgical excision. In multivariable analysis, age < 1 year and metastatic disease had a significant impact on event-free survival (EFS) (p = 0.047 and p = 0.002, respectively); however, only metastatic disease had a significantly negative effect on overall survival (OS) and cumulative incidence of relapse (CIR) (p = 0.002 for OS and p < 0.001 for CIR). DNA methylation was performed for 69 patients who were classified as having a TYR (n = 13), SHH (n = 34), MYC (n = 17), or non-ATRT diagnosis (n = 5). In the cohort of the 64 patients with ATRT defined by methylation, no significant survival differences were observed. Treatment-related deaths were reported in 28% of our studied group. Gram-negative septicemia was the most common cause of toxic death. The 5-year EFS and OS of the whole cohort were 12% and 13%, respectively. Conclusions: In this cohort, no significant survival differences were observed among the methylation subgroups. The higher treatment-related mortality in our cohort compared to the original protocol’s toxic-related deaths suggested that intensive and lengthy chemotherapy regimens may need modification for our population. The need for a short intensified approach, including a limited induction cycle followed by an intensified high-dose consolidation therapy, may be more appropriate for our patients with low socioeconomic status to avoid a repeated and prolonged course of protracted neutropenia. Full article

Background/Objectives: Fluorescence in situ hybridization (FISH) is a standard diagnostic tool for detecting gene fusions and rearrangements in lymphomas but is limited by incomplete genomic coverage, dependence on predefined probes, and difficulty identifying atypical or noncanonical fusion partners. These constraints often result in inconclusive diagnoses in complex lymphoma cases. This study evaluates a novel Hi-C-based sequencing assay from formalin-fixed paraffin-embedded (FFPE) samples to detect clinically significant gene fusions and rearrangements in cases where conventional FISH was inconclusive or expected biomarkers were not detected. Methods: Five diffuse large B-cell lymphoma cases with previously atypical gene fusions or rearrangements by FISH were analyzed using both standard FISH and a Hi-C-based lymphoma assay. Standard FISH was performed using break-apart probes targeting MYC, BCL2, and BCL6, and dual-fusion probes targeting IGH::MYC and IGH::BCL2. The Hi-C assay utilized high-resolution sequencing of FFPE tissue to map chromatin interactions and identify structural variations across the genome and assessment of their clinical relevance. Results: In this series of five lymphoma cases, Hi-C detected additional structural variants beyond those identified by FISH. It identified typical and atypical translocation partners of key oncogenes (MYC, BCL2, BCL6), cryptic breakpoints, and novel genomic events, including TP53 loss, KMT2A amplification, and complex rearrangements, which were undetectable by FISH. The Hi-C assay’s whole-genome coverage enabled comprehensive profiling. Conclusions: The Hi-C-based lymphoma assay offers a transformative diagnostic tool, overcoming FISH limitations by providing unbiased, high-resolution detection of structural variations. This approach enhances diagnostic accuracy and supports personalized therapeutic strategies in lymphoma management, warranting further validation for clinical adoption. Full article

Chromosomal BCR-ABL1 fusions are the defining molecular lesions of chronic myeloid leukemia (CML) and Philadelphia-positive acute lymphoblastic leukemia, and are rarely observed in acute myeloid leukemia. Their detection have transformed treatment paradigms by enabling effective use of specific tyrosine kinase inhibitors (TKIs). Although many BCR-ABL1 rearrangements are identified by standard cytogenetics, a clinically relevant subset is cryptic and can escape detection. High-depth RNA sequencing assays have improved our capacity to detect expressed fusion transcripts. Here, we introduce two myeloid cases in which cryptic BCR-ABL1 rearrangements and precise breakpoints detection required an integrated molecular approach: we describe the initial diagnostic pitfalls, detail the downstream therapeutic and prognostic implications and offer practical recommendations for integrating targeted sequencing and cytogenetics into routine practice. In the first case, a patient initially diagnosed with a myelodysplastic/myeloproliferative neoplasm was reclassified as CML following the discovery of a cryptic e13a2 BCR-ABL1 rearrangement, enabling effective TKI treatment. In the second case, a previously undetected BCR-ABL1 fusion was identified in a relapsed AML patient, along with additional molecular lesions, underscoring the aggressive nature of the disease. Our findings support a systematic, multimodal screening strategy in patients with atypical presentations to ensure the timely detection of clinically actionable fusion events. Full article

This paper reviews the apparent impact of how changes in nitrate, sulphate activities, and moisture affect the surface pH of rock art paintings at Cueva del Ratón, in the Sierra de San Francisco in Baja California Sur, Mexico. The data was collected after atypical weather events caused rain and mist in this normally arid area. The rock art paintings had been previously examined over several years and observed the unexpected formation of silica skins over some surfaces; such coatings are not often experienced in arid environments. The local geology of the cave and the availability of moisture can dramatically alter the microbiological activity on faecal material and development of surface acidity from such reactions which interacts with both the host rock and the pigments. Through a series of surface pH measurements and localised measurements on chloride, sulphate and nitrate it appears that both nitrate and sulphate concentrations have a significant impact on the surface pH, which is controlled by a diffusion-based movement of moisture from the closed to the open end of the shelter. The exfoliation of the rock surface and formation of the silica skins involves chemical reactions as contrasted with diffusion-controlled reactions which distribute the metabolites of the yeasts, moulds and bacteria, which are dominated by the availability of water through drip lines. The results are particularly relevant due to changing weather patterns in the last decade, caused by climate change, with an increase in hurricanes directly affecting the Baja California peninsula. The use of disposable test strips for semi-quantitative assessment of how these major anions impact on the decay mechanisms was a novel response to budget constraints and the remoteness of the location. Full article

This study presents the results of preliminary documentation and radon tracer investigations conducted at the “Aurelia” Mine in Złotoryja. Measurements of ²²²Rn activity concentrations were carried out between 17 March and 26 August 2023, while terrestrial laser scanning (TLS) for mapping purposes was performed on 16 November 2024. The radon data exhibited a consistently right-skewed distribution, with skewness coefficients ranging from 0.9 to 8.2 and substantial standard deviations, indicating significant data dispersion. Outliers and extreme outliers were identified as key factors influencing average radon activity concentrations from April through August, whereas data from March displayed homogeneity, with no detected anomalies. The average ²²²Rn activity concentrations recorded from March to July ranged from 51.4 Bq/m³ to 65.9 Bq/m³. In contrast, July and August showed elevated average values (75.8 Bq/m³ and 5784.8 Bq/m³, respectively) due to the presence of outliers and extreme values. Upon removal of these anomalies, the adjusted means were 73.8 Bq/m³ and 1003.6 Bq/m³, respectively, resulting in reduced skewness and improved representativeness. These findings suggest that the annual average radon concentrations at the “Aurelia” Mine remain compliant with the regulatory threshold of 300 Bq/m³ set by the Atomic Law Act, with exceedances likely related to atypical or rare geophysical phenomena requiring further statistical validation. August exhibited a significant occurrence of outliers and extreme outliers in ²²²Rn activity concentration data, particularly concentrated between the 13th and 17th days of the month. This anomaly is hypothesized to be associated with geological processes, notably mining-induced seismic events within the LGOM (Legnica–Głogów Copper District) region. It is proposed that periodic transitions between tensional and compressional phases within the rock mass, triggered by mining activity, may lead to abrupt increases in radon exhalation, potentially occurring before or after seismic events with a magnitude exceeding 2.5. Although the presented data provide preliminary evidence supporting the influence of tectonic kinematic changes on subsurface radon dynamics, further systematic observations are required to confirm this relationship. At the current stage, the hypothesis remains speculative but may contribute to the broader understanding of radon behavior in geologically active underground environments. Complementing the geochemical analysis, TLS enabled detailed geological mapping and 3D spatial modeling of the mine’s underground tourist infrastructure. The resulting simplified linked data model—integrating radon activity concentrations, geological structures, and spatial parameters—provides a foundational framework for developing a comprehensive GIS database. This integrative approach highlights the feasibility of combining tracer studies with spatial and cartographic data to improve radon risk assessment models and ensure regulatory compliance in underground occupational settings. Full article

Objectives: We sought to document interim methodologic improvements and preliminary results for pulmonary suffusion. Methods: A Phase I/II trial of thoracoscopic lung suffusion for resectable sarcoma and colorectal carcinoma metastases followed a pilot study on oligometastatic lung malignancy at a comprehensive cancer center. Primary-specific chemotherapy doses (cisplatin, oxaliplatin, doxorubicin, or gemcitabine) suffused unilaterally for 30 min were escalated to amplify regional deliveries three-fold. Drug delivery was measured with tissue, blood samples, and ⁹⁹Tc; pulmonary function tests and clinical adverse events (AEs) assessed safety and tolerance. Results: From 2008–2025, 31 ECOG 0–2 patients (10 male) aged 33–75 years had unilateral lung suffusion (16 right, 14 left, 1 aborted, and 8 sides selected randomly). Vascular occlusion intolerance was immediate or delayed (25 min) in two cases. Two catheter-positioning grade 3 AEs occurred: hypotension with troponin leak (1) and atrial fibrillation (1). Patients averaged 1.3 ± 1.2 metastasectomies (17 sub-lobar, 8 lobar resections, and 2 intentional open cytoreductive metastasectomies). Hospitalizations were brief (1–4 days) except for 6–7 day stays in the only two open cases and one doxorubicin (grade 4 hypoxic respiratory failure) case. Ninety-day survival was 100%, and the Phase I delivery goal of 12.75 mg/m² 65 (15% systemic) was achieved for oxaliplatin. Lung function was preserved according to ⁹⁹Tc differentials within 6.1 ± 7.1% of the predicted reductions at 30 days. Sampling delays, tracer discordances, and atypical pharmacokinetics reduced tissue drug detections. Recent pulmonary artery snaring cases (two) demonstrated in-flow control more stable than that of balloon occlusions. Conclusions: Suffusion for metastatic malignancies appears safe and warrants further investigation. Full article