To evaluate age-related changes in the orbital pulley array using magnetic resonance imaging (MRI) in older Japanese adults with acquired exotropia (XT) compared with young healthy participants (YHP). In this retrospective cross-sectional case series, MRI images of 30 eyes from fifteen patients (age ≥ 60 years) with distance XT and no high myopia were compared with those of 14 eyes from seven YHP. Rectus muscle (RM) pulley positions relative to the globe center were assessed. The lateral rectus muscle-superior rectus (LR-SR) band was evaluated for rupture. Mean age of patients with XT was 73.7 ± 5.5 years. Compared with YHP, patients with XT showed significant inferior displacement of the lateral rectus (LR) pulley (-3.6 ± 1.2 mm vs. - 2.0 ± 1.1 mm, p < 0.01) and temporal displacement of the superior rectus (SR) pulley (-0.4 ± 1.2 mm vs. - 1.6 ± 0.8 mm, p < 0.01). No significant differences were observed in medial rectus or inferior rectus pulley positions. Inferior LR pulley displacement correlated with inferior SR pulley displacement (r = 0.41, p = 0.03), whereas no significant relationship was observed between LR pulley position and MR or IR pulley position. Rupture of the LR-SR band was observed in 24 orbits (80.0%). Older Japanese adults with XT exhibit localized pulley displacement and LR-SR band rupture. These structural changes differ from the global sagging observed in sagging eye syndrome and may contribute to the pathogenesis of acquired exotropia in older adults.
To determine the incidence of hospital-acquired bloodstream infections (BSI), Ventilator-Associated Pneumonias (VAP) and the impact of Infectious Diseases (ID) referral on outcomes using data from the ACORN HAI surveillance network. Adults hospitalized ≥48 h in a tertiary hospital (3/2023-3/2024) were prospectively included if HA-BSI and VAP criteria were met. ID referral was defined as formal referral to, or consultation with an ID specialist. Clinical, laboratory parameters, and 28-day outcomes were collected. The incidence of HA-BSI and VAP was calculated using the number of patients with HA-BSI or VAP as numerator, and total hospitalized adult patients as denominator; incidence density per 1000 patient-days was computed using infection episodes as numerator, and total patient-days as denominator. Among 115 patients (mean age 62.4 ± 18.1 years), 58.3% were male, and 33. 91% diabetic. HA-BSI incidence density was higher compared to VAP (1.03 vs. 46 per 1000 patient-days). Mortality (BSI 24.7%, VAP 50%, combined infection 57.1%) differed across infection types. Majority of infection episodes were referred to ID (119/143, 83.21%). Although late referrals (9/143, 6.29%), had numerically higher mortality and prolonged hospitalization, these were not statistically significant. The timing of ID referral had no statistically significant association with clinical and functional outcomes, mortality, and length of stay. Overall HA-BSI and VAP rates were low, but still associated with high mortality and prolonged hospitalization. ID referral was not associated with better outcomes in this small study.
The mortality rate among patients in the intensive care units (ICUs) with severe community-acquired pneumonia (CAP) is high. Identification of severe CAP early in the course and transferring to appropriate setting seem favorable. This study aimed to identify clinical characteristics and the risk factors associated with mortality of severe CAP in the ICU (ICU-CAP). A multi-center, prospective study was conducted at 11 teaching hospitals in China from December 2017 to October 2021. Patients who met the inclusion criteria were assigned to the ICU group and the non-ICU group according to whether they were admitted to the ICU. A total of 170 patients with severe CAP were included, 111 patients were admitted to the ICU and 59 patients were admitted to the ward. Among patients in the ICU, 91.9% of patients were with respiratory failure, 65.8% of patients with consciousness disturbance, 23.4% were in shock state, and 73.0% (81/111) of patients had at least one comorbidity. In-hospital mortality for ICU-CAP was 34.2% (38/111), 28-day mortality was 27.9% (31/111), and 7-day mortality was 10.8% (12/111). Mortality in patients with pneumonia severity index class V (PSI-V) was 40.0% (18/45), mortality in patients with invasive mechanical ventilation was 40.2% (33/82). In the ICU subgroup, invasive mechanical ventilation [odds ratio (OR) =3.35; 95% confidence interval (CI): 1.14-9.81; P=0.02] and age ≥60 years (OR =2.64; 95% CI: 1.07-6.53; P=0.03) were independently associated with in-hospital mortality. In this multicenter prospective cohort, severe CAP patients admitted to the ICU exhibited substantial disease severity, with high rates of treatment failure and mortality. Invasive mechanical ventilation and age ≥60 years were associated with in-hospital mortality in the ICU subgroup.
to evaluate the healing evolution of pressure injuries developed in the hospital setting among adult patients in the post-discharge period, as well as the complications and care provided to these patients. prospective cohort study with patients who developed pressure injuries during hospitalization and were subsequently discharged. Data were collected at 7, 15, 30, and 60 days after hospital discharge. the sample included 113 patients, 63 men (55.8%), with a mean age of 64.6 years old (± 15.1). A total of 246 injuries occurred, predominantly in the sacral region (91; 37.0%) and classified as stage 2 (117; 47.6%). Readmission rates ranged from 10.6% to 16.8% over 60 days and 25 deaths (22.1%) occurred. At the last interview, 57 patients participated, of whom 29 (50.9%) remained bedridden or with very limited mobility, while 48 (84.2%) showed improvement or complete healing. Stroke occurred in 22 (19.5%) patients and was an unfavorable factor in the healing process (HR = 0.6; p = 0.021). during the 60 days after discharge, patients experienced unfavorable outcomes, including death, hospital readmission, and non-healing of pressure injuries. Stroke was associated with a slower progression of the healing process.
To determine whether COVID-19 is a risk factor for developing airway stenosis in intubated patients. Retrospective case-control study with planned chart review. Temple University Health Systems hospitals in Philadelphia, PA. Chart review of patients 18 to 90 years old diagnosed with COVID-19 who underwent endotracheal intubation and had a post-extubation CT scan at our institution between February 2020 and December 2022 was performed. Patients without COVID-19 matched for age, sex, and BMI who were intubated within one year served as a control group. Outcome variables included endoscopic and radiographic evidence of airway stenosis. Descriptive statistics were analyzed using Chi-squared and unpaired two-tailed T-test analyses for cohort comparison. One hundred five COVID-positive and 101 COVID-negative met inclusion criteria. The mean age was 58.6 years. Mean endotracheal tube size was 8.05 for COVID-positive and 7.72 for COVID-negative patients (P = .0075). Twenty-six (24.76%) COVID-positive and 45 (44.55%) COVID-negative patients had COPD (P = .0016). Length of intubation was 8.8 days in COVID-positive patients and 3.5 days for COVID-negative patients (P < .0001). Thirty-five (33.98%) COVID-positive and 1 (0.99%) COVID-negative patient were ventilated while prone (P = .0002). Seventy-eight (75%) COVID-positive and 38 (41.76%) COVID-negative patients received intravenous steroids (P = .0001). Mean length of stay was 38.81 days for COVID-positive and 17.16 days for COVID-negative patients (P < .0004). Six (5.77%) COVID-positive and 2 (1.3%) COVID-negative patients developed airway stenosis (P = .202). Patients with COVID-19 infection were not at an increased risk for intubation-related airway stenosis. IV.
Klebsiella pneumoniae (K. pneumoniae) is a major cause of urinary tract infections (UTIs) and poses a growing public health concern due to multidrug resistance and virulence potential. This study aimed to characterize antimicrobial resistance, biofilm formation, and virulence gene distribution among urinary K. pneumoniae isolates from North Lebanon and to explore correlations between these factors. A total of 153 non-duplicate isolates from hospital and community settings were analyzed for antibiotic susceptibility, hypermucoviscosity, biofilm formation, and presence of key virulence (fimH, mrkD, magA, rmpA, entB, iucA, iroN, kfu) and β-lactamase (blaTEM, blaSHV, blaCTX-M) genes. Adhesion-associated genes fimH and mrkD were highly prevalent, particularly in hospital-acquired and strong biofilm-producing isolates. Capsular and regulatory genes (magA) was more frequent in putative hypervirulent and community-acquired strains, while siderophore genes entB and iucA were strongly associated with biofilm formation and hospital-acquired infections. A significantly higher resistance to cephalosporins, along with an increased frequency of multidrug-resistant phenotypes, was detected in hospital-acquired, classical, and strong biofilm-forming isolates. ESBL production was significantly more common in hospital-acquired and biofilm-forming isolates. Strong biofilm formation was largely associated with classical K. pneumoniae and hospital-acquired infections, whereas putative hypervirulent strains were primarily weak biofilm producers and community-acquired. These findings highlight the interplay between virulence determinants, biofilm formation, and antibiotic resistance, emphasizing the need for targeted infection control and treatment strategies in North Lebanon.
Pregnancy can result in the development of antibodies to fetal HLA, and this humoral sensitization contributes to reduced access to transplantation. While desensitization protocols have enabled more sensitized patients to undergo transplantation, their efficacy is variable due in part to the persistence of donor-specific memory B cells. Better constraint of memory B cells through the induction of a B cell-intrinsic tolerant state may result in improved humoral desensitization. This study uses mouse models of semi-allogeneic pregnancy to show that, in the absence of fetus-specific antibodies (FSA), pregnancy-sensitized B cells can acquire a tolerant state that manifests as the inability to differentiate into germinal center B cells. Adoptive transfer of serum containing FSA prevented tolerance induction and reversed established B cell tolerance. Strikingly, B cells sensitized through skin rejection did not acquire this tolerant state even when donor-specific antibodies were absent. Furthermore, antepartum CTLA-4Ig treatment prevented humoral sensitization, induced B cell tolerance and preserved the ability of post-partum dams to accept F1 grafts with transient anti-CD154 treatment. Together, these findings reveal the distinct plasticity of pregnancy-induced memory B cells that may be leveraged towards new strategies to improve access to transplantation and outcomes in post-partum women.
Osimertinib is the standard of care in first-line therapy for advanced EGFR-mutant NSCLC, but resistance invariably develops through EGFR-dependent or independent mechanisms. Here, we report the case of a stage IVA adenocarcinoma patient with several metastases harboring an EGFR exon 19 deletion, which progressed locally after five years on osimertinib. Sequencing of the re-biopsy revealed the emergence of an acquired exon 20 mutation, p.(Cys797Ala), not previously characterized and absent from variant databases. Immunohistochemical analysis (IHC) showed phospho-EGFR positivity in the re-biopsy, indicating activation of the double mutant receptor and downstream pathways, while molecular modelling predicted resistance to osimertinib but sensitivity to fourth-generation TKIs. Based on these results, the patient was enrolled in a trial combining osimertinib with a SOS1 inhibitor, which targets a downstream effector of the EGFR pathway, deriving a clinical benefit. This report of a patient with the rare p.(Cys797Ala) EGFR acquired mutation highlights the role of molecular modelling and IHC for phosphorylated proteins as tools to functionally characterize variants of unknown significance and help clinical decisions.
Long-term dental implant success depends on a biologic "race to the surface," in which osteogenic cells, peri-implant soft-tissue cells, and bacterial pathogens compete for early dominance at the implant-tissue interface. Because implant surface design is often optimized for one objective at the expense of another (e.g., micro-roughness to accelerate osteoconductivity but with increased plaque-retention risk; relatively smooth transmucosal surfaces to discourage bacterial attachment despite uncertainty regarding optimal soft-tissue integration), strategies that enhance peri-implant health without forcing topographical trade-offs are needed. Ultraviolet (UV) photofunctionalization-by removing storage-acquired hydrocarbons ("biological aging") and converting surfaces to a high-energy, superhydrophilic state-has been proposed as a chairside, topography-preserving approach to improve interfacial biology. This systematic review evaluates whether UV photofunctionalization of titanium and zirconia surfaces provides clinically relevant advantages for (1) reduction of bacterial attachment and biofilm formation, (2) peri-implant soft-tissue responses relevant to mucosal sealing, and (3) human clinical outcomes. After systematic literature search, screening and full-text evaluation, a total of 34 articles, including 9 bacterial/biofilm, 13 soft-tissue (1 overlapping between bacterial and soft-tissue), and 13 clinical studies were selected. Findings were synthesized qualitatively with attention to protocol heterogeneity (UV wavelength band, exposure duration, device configuration, and material and surface types). Across experimental models, UV photofunctionalization most consistently reduced early bacterial attachment and/or early biofilm accumulation across several titanium surface topographies, supporting an early anti-adhesive and biofilm-suppressive phenotype. Soft-tissue studies generally demonstrated enhanced fibroblast/epithelial attachment, spreading, and functional behaviors relevant to sealing on both titanium and zirconia, although the optimal underlying topography for soft-tissue integration remains unresolved. Clinically, the most consistent signal was accelerated and enhanced implant stability development, while selected studies also suggested favorable trends in peri-implant soft-tissue parameters and/or crestal bone maintenance. However, clinical outcomes remained variable and were limited by heterogeneity in UV protocols, surface systems, endpoints, and follow-up duration. UV photofunctionalization can be conceptualized as a surface-agnostic physicochemical reactivation technology: a topography-preserving enhancement that restores high surface energy and favorable surface chemistry without altering the underlying surface architecture. Current evidence for this concept is strongest for titanium, whereas supportive evidence for zirconia is emerging primarily from soft-tissue and interface-focused models. This interface-first, positive-sum strategy may allow clinicians to select zone-specific topographies (e.g., smooth transmucosal regions and rough endosteal regions) while maximizing soft-tissue affinity and suppressing early colonization. Although current clinical evidence most strongly supports accelerated osseointegration/stability development, further longitudinal studies with standardized peri-implant health, microbiologic, and mucosal inflammatory endpoints are needed to clarify the long-term translational impact of UV photofunctionalization on peri-implant disease prevention.
Some plant-beneficial microbes, including bacteria and fungi, can induce plant defense, enabling plants to resist pathogen infections. Successful defense elicitation depends on compatible host-microbe interactions at multiple stages. The initial interaction begins with plant root exudates, which contain chemical cues that attract beneficial microbes by enhancing their motility, biofilm formation, and expression of symbiosis- and immunity-related genes. In turn, these microbes produce a diverse array of immune elicitors-such as proteins, carbohydrates, lipids, and volatile compounds-that are perceived by plants through various mechanisms. Some elicitors are recognized by membrane-bound pattern recognition receptors, whereas others interact with the plant plasma membrane or cytoplasmic targets such as MYB72 and LOX3. These interactions can either trigger local pattern-triggered immunity, characterized by reactive oxygen species production and activation of the mitogen-activated protein kinase signaling pathway, or generate long-distance signals such as oxylipins that induce systemic resistance in distal tissues. A central outcome of these interactions is induced systemic resistance, which primes plants for a heightened immune state, enabling faster and stronger defense responses upon a subsequent pathogen challenge. In some cases, beneficial microbes can also trigger salicylic acid-mediated systemic acquired resistance, particularly enhancing resistance against biotrophic pathogens. Furthermore, beneficial microbes must balance immune activation and immune evasion by suppressing microbe-associated molecular pattern-triggered immune responses and avoiding the formation of hyperbiofilm, which allows them to establish a long-term symbiotic relationship with the host.
The amygdala is the nucleus of the brain that is largely responsible for perceiving danger and plays a role in emotion, behavior, control and learning. A small amygdala has been associated to aggression. Horned ewes are expected to be more aggressive and have a smaller amygdala. Both horned and hornless ewes exhibit intraspecific head-butting behavior and both species are at risk for traumatic brain injury. The aim of this study was to investigate the neuronal density, glial cells and blood-brain barrier (BBB) of the amygdala in horned and hornless ewes. Four horned and six hornless ewe heads (age: 16.00 ± 4.00 months) were obtained from the abattoir. The brains were carefully removed and preserved in 10.00% formalin for 5 days. Bilateral amygdalae were sectioned. The samples were stained with Hematoxylin and Eosin, immunohistochemical (glial fibrillary acidic protein) and Terminal deoxynucleotidyl transferase deoxyuridine triphosphate nick end labeling methods, and the histological structures of the amygdala were examined by light microscopy. The Mann-Whitney U test was used to analyze the data. Neuronal density was estimated to be 143,230 ± 12,540 per mm3 in horned and 152,230 ± 18,430 per mm3 in hornless ewes. Horned subjects had reduced numbers of neurons, damaged BBB and localized inflammatory areas. More apoptotic neurons were observed in horned ewes. Further studies are needed to determine whether these differences in neuronal density, glial cells, and BBB are acquired (due to trauma) or congenital. The results of this study might need further similar studies to be conducted in the future.
Arsenic trioxide (ATO) is the hallmark therapy for acute promyelocytic leukemia (APL); however, its clinical utility is limited by severe cardiotoxicity. APL patients develop neutropenia and immunodeficiency due to bone marrow suppression, increasing susceptibility to community-acquired pneumonia (CAP). Levofloxacin (LFX) and moxifloxacin (MFX) serve as first-line antimicrobial agents for treating CAP in patients with APL. This study quantitatively detected plasma concentrations of inorganic arsenic (iAs), monomethylarsonic acid (MMAV), and dimethylarsinic acid (DMAV) in 96 APL patients undergoing ATO therapy using HPLC-HG-AFS. LFX significantly increased the incidence of QT interval prolongation and myocardial injury, while elevating plasma arsenic concentrations in ATO-treated APL patients; in contrast, MFX showed no significant effects. In vivo studies demonstrated that LFX significantly suppressed LVEF and FS, reduced renal arsenic excretion, and increased arsenic accumulation in systemic circulation, kidneys, and hearts of ATO-treated rats, concomitant with downregulated renal P-glycoprotein (P-gp) expression; conversely, MFX exhibited none of these effects. In vitro experiments revealed that LFX suppressed P-gp expression in HEK293T cells by inhibiting the PXR/AKT/FOXO3a pathway, thereby inhibiting cellular efflux of ATO; conversely, MFX exhibited no significant effects on this regulatory axis. Collectively, our results demonstrate that LFX exacerbates ATO cardiotoxicity by suppressing the PXR/AKT/FOXO3a signaling axis to downregulate renal P-gp, thereby reducing arsenic excretion and enhancing systemic and cardiac arsenic accumulation. In contrast, MFX exhibits a superior safety profile when co-administered with ATO.
Horizontal gene transfer (HGT) in plant mitochondria is frequent, yet acquired genes are rarely functional due to expression barriers. The holoparasitic plant Lophophytum mirabile (Balanophoraceae) is an exceptional case, having functionally replaced numerous native mitochondrial genes with host-derived xenologues. This system provides a unique opportunity to investigate the mechanisms of functional HGT assimilation. Here, we assembled mitochondrial genomes of the sister species L. pyramidale and their mimosoid hosts and analysed expression data from both holoparasites. We show that this extensive functional integration occurred without the co-transfer of nuclear regulatory factors; Lophophytum relies entirely on its pre-existing native machinery. Our results demonstrate that the primary mechanism enabling Lophophytum to overcome the transcription barrier is structural: most functional xenologues are chimaeric and retain native 5' regions that probably place foreign coding sequences under the control of a recognizable native promoter. This structural solution is complemented by post-transcriptional flexibility, as the RNA editing machinery efficiently processes novel host-specific sites. However, functional replacement appears biased towards genes with inherently low editing requirements and no introns, highlighting a strong selective filter. Taken together, our results show that functional integration is driven by a combination of structural integration and the flexibility of the native regulatory system.
To overcome the limitations of single remote-sensing features in estimating maize canopy leaf area index (LAI), this study developed a UAV-based estimation approach by integrating multispectral vegetation indices (VIs) with digital surface model (DSM) features and stacking ensemble learning. Field experiments were conducted in Dehong, Yunnan Province, China, during 2023-2024, and UAV multispectral images and DSM products were acquired for maize grown under three planting-density treatments. Five vegetation indices and three DSM-derived texture/structural features were retained according to their correlation with measured LAI, statistical significance, and complementary spectral or structural information. The VI-based random forest (VI-RF) model achieved an R2 of 0.835 and an NRMSE of 9.5%, whereas the DSM-based model showed lower performance (R2 = 0.641; NRMSE = 14.2%). Under the same random-forest modeling framework, fusing VIs with DSM features improved the overall model performance to R2 = 0.892 and NRMSE = 7.6%, indicating that DSM-derived structural information mainly enhanced the feature representation of maize LAI. Using the same VI-DSM feature set, the stacking model with support vector machine (SVM) as the meta-learner further improved the overall performance to R2= 0.930 and NRMSE = 6.3%. The additional gain from stacking was moderate but consistent, whereas feature fusion contributed the dominant improvement. The combined VI-DSM-Stacking workflow improved prediction stability across planting densities, especially under low- and high-density canopy conditions where soil background interference and spectral saturation were more evident. These results demonstrate that integrating spectral and DSM-derived structural information with stacking ensemble learning can improve the accuracy and robustness of UAV-based maize LAI estimation.
Multi-Source Unsupervised Domain Adaptation (MUDA) aims to leverage labeled data from multiple distinct source domains and unlabeled data from the target domain in training a model that can adapt to the target domain. Many classical methods have been proposed and utilized, nevertheless, alongside the emergence and progression of pre-trained Visual Language Models (VLMs), there is currently a dearth of effective methods based on VLMs to address the MUDA problem. To address this issue, we have constructed a novel CLIP-model-based framework for MUDA, which introduces a method that integrates category-specific prompts with a multimodal Low-Rank (LoRA) matrix adaptation approach. Our method employs learnable, class-specific prompts to extract and learn shared knowledge, while incorporating a multimodal LoRA matrix to acquire domain-specific knowledge. Furthermore, we introduce a modality interaction mechanism to foster the interplay between fine-tuning parameters across different modalities. Extensive experiments have demonstrated that our approach yields significant improvements on standard image classification benchmark datasets.
New drugs, devices, and other tools are essential to improving children's orthopaedic care. An often underappreciated aspect of new products is the amount of time and money needed to bring them to the bedside. While grants and other seed money have a role very early in the development of technology by start-ups, the bulk of the expense of such development is borne by private investors. We examined a quarter century of early-stage investments in pediatric orthopaedic start-ups and compared them with similar investments in adult-focused orthopaedic companies. Investor backing of pediatric enterprises was much less common, representing only 10% of investments in the field of orthopaedics. Yet, when pediatric companies were supported, the rate at which they acquired subsequent capital and the total amount of capital they raised were comparable with those of adult-focused companies. Investments in new pediatric orthopaedic innovations from 2000 to 2024 were far less common than adult orthopaedic investments. Our data underscore the unmet challenges of backing start-ups in the field and provide benchmark data against which founders and investors can judge their financial performance. The availability of new orthopaedic tools is tied to capital investment in the field's youngest companies. A more complete understanding of long-term trends in the private financing of pediatric orthopaedic start-ups is essential for founders, investors, and policymakers.
Common bean (Phaseolus vulgaris) is an important food and cash crop in Tanzania, where it contributes to household nutrition and income among smallholder farmers. Its production is, however, constrained by diseases such as bean rust and bean anthracnose, which can cause substantial yield losses and reduce crop quality. This article presents a labelled image dataset of common bean leaves collected under field conditions in Northern Tanzania to support research and application development in computer vision, machine learning and digital crop health. The dataset comprises 155,842 labelled multi-season images belonging to three classes: healthy leaves, bean rust and bean anthracnose. Images were acquired from farms in Arusha, Kilimanjaro and Manyara regions using smartphone cameras and were subsequently reviewed and validated with support from agricultural extension officers and plant pathologists to improve annotation reliability. The dataset is organized into class-specific compressed files and is publicly available through the Zenodo repository. By providing a large field-based image resource captured under variable real-world conditions, this dataset can support the development, training and evaluation of image-based models for common bean disease identification.
Malaria infection remains a potential health threat to U.S. service members located in or near endemic areas due to duty assignments, participation in contingency operations, or personal travel. This report summarizes findings from surveillance of malaria infections among U.S. service members in 2025 and analyzes trends for a 10-year period, from 2016 through 2025. In 2025, 36 cases of malaria were diagnosed among U.S. service members, representing a 12.5% increase from 32 cases reported in 2024. The majority of malaria cases occurred in service members who were male (94.4%), in the active component (80.6%), and serving in the Army (63.9%). Africa was the leading region of acquisition (n=14), primarily for P. falciparum infections. A significant 2025 finding is a shift in the predominant species to P. vivax, which accounted for 41.7% (n=15) of all cases, a notable increase from 10% of all cases in 2024. Most P. vivax cases (80.0%) were acquired in Korea. Seasonality of infection remained consistent, with 72.1% of cases diagnosed May through October. These findings underscore the critical need for continuous surveillance, strict command emphasis on personal protective measures, and region-specific prevention strategies to protect the health of the force and maintain military readiness. The rise of P. vivax from Korea along with persistent P. falciparum infection from Africa not only directly affect force health protection but demonstrate a dynamic, regionally specific threat that requires specialized prevention strategies to maintain military readiness.
Glioblastoma (GBM) is a notoriously lethal brain tumor, primarily owing to its inevitable resistance to temozolomide (TMZ), a frontline chemotherapy. Hypoxia-driven metabolic adaptations have been implicated in therapeutic failure; however, the role of circular RNAs remains largely underexplored. By integrating multiomics profiling with functional assays in patient-derived GBM cells, orthotopic xenografts, and clinical specimens, this study aimed to elucidate the role of hypoxia-induced hsa_circ_0000745 (circSPECC1) in mediating TMZ resistance. Mechanistic investigation included RNA pulldown, RIP, glycolysis flux analysis, and DNA damage assessment. The circSPECC1 is overexpressed in GBM and correlates with poor prognosis. Hypoxia triggers HIF-1α-mediated transcriptional upregulation of circSPECC1, which scaffolds insulin-like growth factor 2 mRNA-binding protein 2 (IGF2BP2) to stabilize phosphoglycerate kinase 1 (PGK1) mRNA. Importantly, circSPECC1/PGK1 axis activation enhances glycolytic flux, blunts TMZ-induced DNA damage, and confers chemoresistance. Targeting circSPECC1 disrupts PGK1-driven glycolysis, restores TMZ sensitivity, and synergizes with TMZ to extend survival in orthotopic GBM models. In conclusion, this study identifies a previously uncharacterized HIF-1α/circSPECC1/IGF2BP2/PGK1 axis that drives metabolic adaptation and TMZ resistance in GBM. Targeting this axis overcomes acquired chemoresistance, positioning circSPECC1 as both a prognostic biomarker and a therapeutic vulnerability in hypoxic GBM niches.
This study aimed to examine the spatiotemporal properties of resting‑state global brain network activity and their associations with emotional and behavioral functioning in children. Resting‑state electroencephalography (EEG) was acquired in 83 children aged 6-7 years. Microstate features were extracted via K‑means clustering, and partial least squares (PLS) regression was used to characterize multivariate associations between microstate temporal metrics (global explained variance, duration, occurrence, and coverage) and parent‑rated scores on the Child Behavior Checklist (CBCL). Results demonstrated that four canonical microstate classes were already present in 6-7-year-old children, with microstate C showing dominance across temporal parameters. PLS revealed that the temporal parameters of microstate C were positively associated with total CBCL scores, whereas no significant relationships were observed for the other microstate classes. These findings suggest that neural dynamics indexed by microstate C may be associated with individual differences in emotional and behavioral regulation in 6-7-year-old children, highlighting its potential as an electrophysiological marker of neurobehavioral development.