Current status of advance care planning, palliative care consultation, and end-of-life care in patients with glioblastoma in South Korea.

BACKGROUND: Given the typical trajectory of glioblastoma, many patients lose decision-making capacity over time, which can lead to inadequate advance care planning (ACP) and end-of-life (EOL) care. We aimed to evaluate patients' current ACP and EOL care status. PATIENTS AND METHODS: We conducted a cohort study on 205 patients referred to oncologists at a Korean tertiary hospital between 2017 and 2022. We collected information on sociodemographic factors, cancer treatment, palliative care consultation, ACP, legal documents on life-sustaining treatment (LST) decisions, and aggressiveness of EOL care. RESULTS: With a median follow-up time of 18.3 months: 159 patients died; median overall survival: 20.3 months. Of the 159 patients, 11 (6.9%) and 63 (39.6%) had advance directive (AD) and LST plans, respectively, whereas 85 (53.5%) had neither. Among the 63 with LST plans, 10 (15.9%) and 53 (84.1%) completed their forms through self-determination and family determination, respectively. Of the 159 patients who died, 102 (64.2%) received palliative care consultation (median time: 44 days from the first consultation to death) and 78 (49.1%) received aggressive EOL care. Those receiving palliative care consultations were less likely to receive aggressive EOL care (83.3% vs 32.4%, P < .001), and more likely to use more than 3 days of hospice care at EOL (19.6% vs 68.0%, P < .001). CONCLUSIONS: The right to self-determination remains poorly protected among patients with glioblastoma, with nearly 90% not self-completing AD or LST plan. As palliative care consultation is associated with less aggressive EOL care and longer use of hospice care, physicians should promptly introduce patients to ACP conversations and palliative care consultations.

Feasibility study for the development of multilayered solar cells for proton linear energy transfer depth profile measurement.

BACKGROUND: Previous study proposed a method to measure linear energy transfer (LET) at specific points using the quenching magnitude of thin film solar cells. This study was conducted to propose a more advanced method for measuring the LET distribution. PURPOSE: This study focuses on evaluating the feasibility of estimating the proton LET distribution in proton therapy. The feasibility of measuring the proton LET and dose distribution simultaneously using a single-channel configuration comprising two solar cells with distinct quenching constants is investigated with the objective of paving the way for enhanced proton therapy dosimetry. METHODS: Two solar cells with different quenching constants were used to estimate the proton LET distribution. Detector characteristics (e.g., dose linearity and dose-rate dependency) of the solar cells were evaluated to assess their suitability for dosimetry applications. First, using a reference beam condition, the quenching constants of the two solar cells were determined according to the modified Birks equation. The signal ratios of the two solar cells were then evaluated according to proton LET in relation to the estimated quenching constants. The proton LET distributions of six test beams were obtained by measuring the signal ratios of the two solar cells at each depth, and the ratios were evaluated by comparing them with those calculated by Monte Carlo simulation. RESULTS: The detector characterization of the two solar cells including dose linearity and dose-rate dependence affirmed their suitability for use in dosimetry applications. The maximum difference between the LET measured using the two solar cells and that calculated by Monte Carlo simulation was 2.34 keV/µm. In the case of the dose distribution measured using the method proposed in this study, the maximum difference between range measured using the proposed method and that measured using a multilayered ionization chamber was 0.7 mm. The expected accuracy of simultaneous LET and dose distribution measurement using the method proposed in this study were estimated to be 3.82%. The signal ratios of the two solar cells, which are related to quenching constants, demonstrated the feasibility of measuring LET and dose distribution simultaneously. CONCLUSION: The feasibility of measuring proton LET and dose distribution simultaneously using two solar cells with different quenching constants was demonstrated. Although the method proposed in this study was evaluated using a single channel by varying the measuring depth, the results suggest that the proton LET and dose distribution can be simultaneously measured if the detector is configured in a multichannel form. We believe that the results presented in this study provide the envisioned transition to a multichannel configuration, with the promise of substantially advancing proton therapy's accuracy and efficacy in cancer treatment.

CXCL5/CXCL8 induces neutrophilic inflammation in peri-implantitis.

OBJECTIVE AND BACKGROUND: This research aimed to examine the role of C-X-C motif chemokine ligand 5 (CXCL5) and C-X-C motif chemokine ligand 8 (CXCL8; also known as IL-8) in neutrophilic inflammation triggered by peri-implantitis and to shed light on the underlying mechanisms that link them to the development of this condition. MATERIALS: This study included 40 patients who visited the Department of Periodontology at Kyungpook University Dental Hospital. They were divided into two groups based on their condition: healthy implant (HI) group (n = 20) and peri-implantitis (PI) group (n = 20). Biopsy samples of PI tissue were collected from the patients under local anesthesia. HI tissue was obtained using the same method during the second implant surgery. To construct libraries for control and test RNAs, the QuantSeq 3' mRNA-Seq Library Prep Kit (Lexogen, Inc., Austria) was used according to the manufacturer's instructions. Samples were pooled based on representative cytokines obtained from RNA sequencing results and subjected to Reverse transcription-quantitative polymerase chain reaction (RT-qPCR). Hematoxylin and eosin staining, and immunohistochemistry (IHC) analysis were performed to visually assess expression levels and analyze tissue histology. Student's t-test was employed to conduct statistical analyses. RESULTS: Initially, heatmaps were used to examine gene expression variations between the HI and PI groups based on the results of RNA sequencing. Notably, among various cytokines, CXCL5 and CXCL8 had the highest expression levels in the PI group compared with the HI group, and they are known to be associated with inflammatory responses. In the gingival tissues, the expression of genes encoding cytokines such as interleukin (IL)-1ß, tumor necrosis factor-alpha (TNF)-α, interleukin (IL)-6, and CXCL5/CXCL8 was assessed via RT-qPCR. The mRNA expression level of CXCL5/CXCL8 significantly increased in the PI group compared with the HI group (p < .045). Contrarily, the mRNA expression level of interleukin 36 receptor antagonist (IL36RN) significantly decreased (p < .008). IHC enabled examination of the distribution and intensity of CXCL5/CXCL8 protein expression within the tissue samples. Specifically, increased levels of CXCL5/CXCL8 promote inflammatory responses, cellular proliferation, migration, and invasion within the peri-implant tissues. These effects are mediated through the activation of the PI3K/Akt/NF-κB signaling pathway. CONCLUSIONS: This study found that the PI sites had higher gene expression level of CXCL8/CXCL5 in the soft tissue than HI sites, which could help achieve more accurate diagnosis and treatment planning.

Tumor Growth Kinetics Based on Initial Tumor Volume Doubling Time in Active Surveillance of Low-Risk Papillary Thyroid Carcinoma.

Background: During active surveillance (AS) of low-risk papillary thyroid carcinomas (PTCs), the majority remain stable, while some exhibit either an increase or a decrease in tumor diameter or tumor volume (TV). We aimed to evaluate the clinical outcomes and relevant parameters influencing tumor growth kinetics of low-risk PTCs. Methods: This retrospective cohort study evaluated clinical parameters of 402 patients with low-risk PTC sized <2 cm, with a follow-up duration over 3 years. Changes in maximum tumor diameter, TV, and initial TV doubling time (i-TVDT) calculated within 3 years were assessed. A significant change in TV was defined as a change of 75% or more. Results: Of the 402 patients with low-risk PTC, 93.3% (375/402) were diagnosed with papillary thyroid microcarcinoma. During a median follow-up of 5 years, 3.4% (14/402) of patients developed new cervical lymph node (LN) metastasis, and 8.2% (33/402) experienced a maximal diameter increase of ≥3 mm. The i-TVDT of <5 years emerged as an independent risk factor for both maximal diameter growth and new LN metastasis (p < 0.001 and p = 0.04, respectively). Based on TV changes and i-TVDT during AS, we identified four statistically significant tumor kinetic patterns (p < 0.001): Stable (±75% change in TV), Rapid growth (TV increase >75% and i-TVDT <5 years), Slow growth (TV increase >75% and i-TVDT ≥5 years), and Shrinkage (TV decrease >75%). Most of the PTCs remained stable (67.7%), but 17.2% were rapidly growing, with a median onset of growth of 2.0 years. Slowly growing PTCs, comprising 10.9%, grew at a median of 4.3 years. A minority, 4.2%, exhibited shrinkage. In total, 115 (28.6%) patients underwent delayed surgery >12 months after initiating AS. The reasons for delayed surgery included patient preference (51/115, 44.3%), disease progression (31/115, 27.0%), and suspected disease progression, which was referred to as tumor growth not meeting the criteria of an increase of ≥3 mm in maximal tumor diameter (17/115, 14.8%). Conclusion: An i-TVDT of <5 years serves as an important prognostic indicator for disease progression, including tumor growth and new LN metastasis. The four tumor kinetic patterns based on TV changes and i-TVDT assist in guiding personalized decisions early in AS.

Detection of EGFR exon 20 insertion mutations in non-small cell lung cancer: implications for consistent nomenclature in precision medicine.

Epidermal growth factor receptor (EGFR) exon 20 insertion mutations (E20ins) are the third most frequent mutations observed in non-small cell lung cancer, accounting for approximately 1-10% of all EGFR mutations. In the era of precision medicine and targeted therapies, consistent naming of genetic alterations is crucial to avoid confusion and errors. However, the annotation of EGFR E20ins mutations has been inconsistent, leading to confusion in the scientific literature and product documentation. In this study, our primary objective was to investigate the usage of different annotation related to EGFR E20ins in independent studies. Additionally, we assessed the distribution of EGFR E20ins mutations and estimated the detection coverage expected from each available EGFR E20ins detection assay. A total of 1,418 EGFR E20ins mutations were collected from six studies (FoundationInsights, Geneseeq Technology Inc, mobocertinib phase I/II trial, poziotinib phase II trial, sunvozertinib phase I trial, and Samsung Medical Center) and reorganised according to Human Genome Variation Society (HGVS) nomenclature. Our analysis revealed that the majority of EGFR E20ins mutations requiring correction were 'insertion' or 'deletion-insertion', which should be appropriately designated as 'duplication'. Additionally, duplicated variants were reported using different annotations in each study, and furthermore, even identical variant sequences were annotated differently within the same study. In all six studies, p.A767_V769dup and p.S768_D770dup were the most frequently observed EGFR E20ins. The Oncomine Dx Target Test showed the highest patient coverage at 77.2%, followed by the Droplex EGFR Mutation Test v2 with a patient coverage of 70.5% for EGFR E20ins patients. To ensure comprehensive coverage in real-world settings, it is essential to standardise the annotations for each variant, for example using the HGVS nomenclature. The accurate classification and analysis of drug responsiveness in EGFR E20ins necessitate consideration of the nomenclature, particularly with respect to the locations where the actual mutations occur.

Microbiome dynamics in immune checkpoint blockade.

Immune checkpoint blockade (ICB) is one of the leading immunotherapies, although a variable extent of resistance has been observed among patients and across cancer types. Among the efforts underway to overcome this challenge, the microbiome has emerged as a factor affecting the responsiveness and efficacy of ICB. Active research, facilitated by advances in sequencing techniques, is assessing the predominant influence of the intestinal microbiome, as well as the effects of the presence of an intratumoral microbiome. In this review, we describe recent findings from clinical trials, observational studies of human patients, and animal studies on the impact of the microbiome on the efficacy of ICB, highlighting the role of the intestinal and tumor microbiomes and the contribution of methodological advances in their study.

Prediction of treatment response after stereotactic radiosurgery of brain metastasis using deep learning and radiomics on longitudinal MRI data.

We developed artificial intelligence models to predict the brain metastasis (BM) treatment response after stereotactic radiosurgery (SRS) using longitudinal magnetic resonance imaging (MRI) data and evaluated prediction accuracy changes according to the number of sequential MRI scans. We included four sequential MRI scans for 194 patients with BM and 369 target lesions for the Developmental dataset. The data were randomly split (8:2 ratio) for training and testing. For external validation, 172 MRI scans from 43 patients with BM and 62 target lesions were additionally enrolled. The maximum axial diameter (Dmax), radiomics, and deep learning (DL) models were generated for comparison. We evaluated the simple convolutional neural network (CNN) model and a gated recurrent unit (Conv-GRU)-based CNN model in the DL arm. The Conv-GRU model performed superior to the simple CNN models. For both datasets, the area under the curve (AUC) was significantly higher for the two-dimensional (2D) Conv-GRU model than for the 3D Conv-GRU, Dmax, and radiomics models. The accuracy of the 2D Conv-GRU model increased with the number of follow-up studies. In conclusion, using longitudinal MRI data, the 2D Conv-GRU model outperformed all other models in predicting the treatment response after SRS of BM.

Induction of indoleamine 2,3-dioxygenase 1 expression in neurons of the central nervous system through inhibition of histone deacetylases blocks the progression of experimental autoimmune encephalomyelitis.

BACKGROUND: A wide array of histone deacetylase (HDAC) inhibitors and aryl hydrocarbon receptor (AHR) agonists commonly arrest experimental autoimmune encephalomyelitis (EAE). However, it is not known whether HDAC inhibition is linked to the AHR signaling pathway in EAE. METHODS: We investigated how the pan-HDAC inhibitor SB939 (pracinostat) exerted immunoregulatory action in the myelin oligodendrocyte glycoprotein 35-55 (MOG35-55)-induced EAE mouse model by evaluating changes in of signal transducer and activator of transcription 3 (STAT3) acetylation and the expression of indoleamine 2,3-dioxygenase 1 (IDO1) and AHR in inflamed spinal cords during EAE evolution. We proved the involvement of IDO1 and the AHR in SB939-mediated immunosuppression using Ido1-/- and Ahr-/- mice. RESULTS: Administration with SB939 halted EAE progression, which depended upon IDO1 expression in neurons of the central nervous system (CNS). Our in vitro and in vivo studies demonstrated that SB939 sustained the interleukin-6-induced acetylation of STAT3, resulting in the stable transcriptional activation of Ido1. The therapeutic effect of SB939 also required the AHR, which is expressed mainly in CD4+ T cells and macrophages in CNS disease lesions. Finally, SB939 was shown to markedly reduce the proliferation of CD4+ T cells in inflamed neuronal tissues but not in the spleen or draining lymph nodes. CONCLUSIONS: Overall, our results suggest that IDO1 tryptophan metabolites produced by neuronal cells may act on AHR in pathogenic CD4+ T cells in a paracrine fashion in the CNS and that the specific induction of IDO1 expression in neurons at disease-afflicted sites can be considered a therapeutic approach to block the progression of multiple sclerosis without affecting systemic immunity.

Prognostic Roles of Inflammatory Biomarkers in Radioiodine-Refractory Thyroid Cancer Treated with Lenvatinib.

BACKGRUOUND: Inflammatory biomarkers, such as the neutrophil-to-lymphocyte ratio (NLR), lymphocyte-to-monocyte ratio (LMR), and platelet-to-lymphocyte ratio (PLR), serve as valuable prognostic indicators in various cancers. This multicenter, retrospective cohort study assessed the treatment outcomes of lenvatinib in 71 patients with radioactive iodine (RAI)-refractory thyroid cancer, considering the baseline inflammatory biomarkers. METHODS: This study retrospectively included patients from five tertiary hospitals in Korea whose complete blood counts were available before lenvatinib treatment. Progression-free survival (PFS) and overall survival (OS) were evaluated based on the median value of inflammatory biomarkers. RESULTS: No significant differences in baseline characteristics were observed among patients grouped according to the inflammatory biomarkers, except for older patients with a higher-than-median NLR (≥2) compared to their counterparts with a lower NLR (P= 0.01). Patients with a higher-than-median NLR had significantly shorter PFS (P=0.02) and OS (P=0.017) than those with a lower NLR. In multivariate analysis, a higher-than-median NLR was significantly associated with poor OS (hazard ratio, 3.0; 95% confidence interval, 1.24 to 7.29; P=0.015). However, neither the LMR nor the PLR was associated with PFS. A higher-than-median LMR (≥3.9) was significantly associated with prolonged OS compared to a lower LMR (P=0.036). In contrast, a higher-than-median PLR (≥142.1) was associated with shorter OS compared to a lower PLR (P=0.039). CONCLUSION: Baseline inflammatory biomarkers can serve as predictive indicators of PFS and OS in patients with RAI-refractory thyroid cancer treated with lenvatinib.

Evaluating Novel SP-B and SP-C Synthetic Analogues for Pulmonary Surfactant Efficacy.

Pulmonary surfactants, a complex assembly of phospholipids and surfactant proteins such as SP-B and SP-C, are critical for maintaining respiratory system functionality by lowering surface tension (ST) and preventing alveolar collapse. Our study introduced five synthetic SP-B peptides and one SP-C peptide, leading to the synthesis of CHAsurf candidates (CHAsurf-1 to CHAsurf-5) for evaluation. We utilized a modified Wilhelmy balance test to assess the surface tension properties of the surfactants, measuring spreading rate, surface adsorption, and ST-area diagrams to comprehensively evaluate their performance. Animal experiments were performed on New Zealand white rabbits to test the efficacy of CHAsurf-4B, a variant chosen for its economic viability and promising ST reduction properties, comparable to Curosurf®. The study confirmed that higher doses of SP-B in CHAsurf-4 are associated with improved ST reduction. However, due to cost constraints, CHAsurf-4B was selected for in vivo assessment. The animal model revealed that CHAsurf-4B could restore alveolar structure and improve lung elasticity, akin to Curosurf®. Our research highlights the significance of cysteine residues and disulfide bonds in the structural integrity and function of synthetic SP-B analogues, offering a foundation for future surfactant therapy in respiratory disorders. This study's findings support the potential of CHAsurf-4B as a therapeutic agent, meriting further investigation to solidify its role in clinical applications.

Central neurocytoma exhibits radial glial cell signatures with FGFR3 hypomethylation and overexpression.

We explored the genomic events underlying central neurocytoma (CN), a rare neoplasm of the central nervous system, via multiomics approaches, including whole-exome sequencing, bulk and single-nuclei RNA sequencing, and methylation sequencing. We identified FGFR3 hypomethylation leading to FGFR3 overexpression as a major event in the ontogeny of CN that affects crucial downstream events, such as aberrant PI3K-AKT activity and neuronal development pathways. Furthermore, we found similarities between CN and radial glial cells based on analyses of gene markers and CN tumor cells and postulate that CN tumorigenesis is due to dysregulation of radial glial cell differentiation into neurons. Our data demonstrate the potential role of FGFR3 as one of the leading drivers of tumorigenesis in CN.

Nucleolin-Targeting AS1411 Aptamer-Conjugated Nanospheres for Targeted Treatment of Glioblastoma.

Post-operative chemotherapy is still required for the treatment of glioblastoma (GBM), for which nanocarrier-based drug delivery has been identified as one of the most effective methods. However, the blood-brain barrier (BBB) and non-specific delivery to non-tumor tissues can significantly limit drug accumulation in tumor tissues and cause damage to nearby normal tissues. This study describes a targeted cancer therapy approach that uses AS1411 aptamer-conjugated nanospheres (100-300 nm in size) loaded with doxorubicin (Dox) to selectively identify tumor cells overexpressing nucleolin (NCL) proteins. The study demonstrates that the active target model, which employs aptamer-mediated drug delivery, is more effective than non-specific enhanced permeability and maintenance (EPR)-mediated delivery and passive drug delivery in improving drug penetration and maintenance in tumor cells. Additionally, the study reveals the potential for anti-cancer effects through 3D spheroidal and in vivo GBM xenograft models. The DNA-protein hybrid nanospheres utilized in this study offer numerous benefits, such as efficient synthesis, structural stability, high drug loading, dye labeling, biocompatibility, and biodegradability. When combined with nanospheres, the 1411 aptamer has been shown to be an effective drug delivery carrier allowing for the precise targeting of tumors. This combination has the potential to produce anti-tumor effects in the active targeted therapy of GBM.

Beneficial Effect of Rapamycin on Liver Fibrosis in a Mouse Model (C57bl/6 Mouse).

BACKGROUND: Liver fibrosis is a chronic inflammatory disease that progresses and has a high mortality rate. This study was performed to investigate the protective effect of rapamycin on experimentally induced chronic liver injury in mice models using both biochemical parameters of liver function enzymes. METHODS: Twenty-four mice were divided randomly into 4 equal groups: [1] the normal group, n = 6; [2] the liver fibrosis (LF) group, n = 6; [3] the LF with the treatment of rapamycin group, n = 6; [4] the LF with the treatment of silimaryn, n = 6. RESULTS: In the group receiving oral administration of rapamycin, aspartate aminotransferase, alanine aminotransferase, urea, and creatinine were found to significantly decrease compared to the liver fibrosis group. Rapamycin, in the orally administered group, demonstrated a statistically significant decrease in the expression of interleukin (IL) 10, IL-1B, inducible nitric oxide synthase, and tumor necrosis factor alpha compared to the liver fibrosis group. CONCLUSIONS: In this study, we explored the potential therapeutic effects of rapamycin on liver fibrosis in an animal model.

Extracellular vesicle-mediated transfer of miRNA-1 from primary tumors represses the growth of distant metastases.

Metastases originate from primary tumors and reach distant organs. Growing evidence suggests that metastases are under the control of primary tumors even outside the primary site; however, the mechanisms by which primary tumors remotely control metastases remain unclear. Here, we discovered a molecular mechanism by which primary tumors suppress metastatic growth. Interestingly, we found that extracellular vesicles (EVs) derived from the primary tumor can inhibit the growth of metastases both in vitro and in vivo. miR-1 was particularly enriched in primary tumor-derived EVs (pTDEs) and was found to be responsible for the suppression of metastatic growth. Mechanistically, intracellular reactive oxygen species (ROS) production and DNA damage were induced, which led to cell cycle arrest. Collectively, our data demonstrate that primary tumors restrict the growth of distant metastases via miR-1 in pTDEs and that miR-1 could potentially be used as an antimetastatic agent.

Eye Drop with Fas-Blocking Peptide Attenuates Age-Related Macular Degeneration.

Age-related macular degeneration (AMD), characterized by macular retinal degeneration, poses a significant health concern due to the lack of effective treatments for prevalent dry AMD. The progression of AMD is closely linked to reactive oxygen species and Fas signaling, emphasizing the need for targeted interventions. In this study, we utilized a NaIO3-induced retinal degeneration mouse model to assess the efficacy of Fas-blocking peptide (FBP). Intravitreal administration of FBP successfully suppressed Fas-mediated inflammation and apoptosis, effectively arresting AMD progression in mice. We developed a 6R-conjugated FBP (6R-FBP) for eye drop administration. 6R-FBP, administered as an eye drop, reached the retinal region, attenuating degeneration by modulating the expression of inflammatory cytokines and blocking Fas-mediated apoptosis in rodent and rabbit NaIO3-induced retinal degeneration models to address practical concerns. Intravitreal FBP and 6R-FBP eye drops effectively reduced retinal degeneration and improved retinal thickness in rodent and rabbit models. This study highlights the therapeutic potential of FBP, particularly 6R-FBP as an eye drop, in inhibiting Fas-mediated cell signaling and protecting against retinal cell death and inflammation in dry AMD. Future investigations should explore the translational prospects of this approach in primates with eye structures comparable to those of humans.

Validation of Korean Olfactory Questionnaire for Perioperative Olfactory Assessment in Endoscopic Endonasal Skull Base Surgery.

Objective: To analyze changes in olfactory function after endoscopic endonasal skull base surgery and compare performance of the olfactory questionnaire with those of conventional psychophysical tests. Methods: Patients were classified into 5 categories for olfactory function evaluation (normal, mild hyposmia, moderate hyposmia, severe hyposmia, and anosmia) based on a self-assessment. Patients also underwent the butanol threshold test (BTT), Cross-Cultural Smell Identification Test (CCSIT), and 11-item olfactory questionnaire. Subjects with normosmia preoperatively and who were followed up at least 6 months after surgery were analyzed. Receiver operating characteristic curves and confusion matrix analysis were performed for BTT, CCSIT, and olfactory questionnaire to compare their diagnostic abilities. The effects of age, preoperative olfaction, septal flap, tumor pathology, and tumor size on postoperative olfaction were evaluated using multivariate linear regression analysis. Results: Data from 108 patients were analyzed. Postoperative changes in the olfactory questionnaire were significantly associated with changes in the BTT and CCSIT. The area under the curve for postoperative self-olfactory function classification was highest for olfactory questionnaire (0.894), followed by BTT (0.767) and CCSIT (0.688). Patient age at the time of surgery and preoperative BTT score were significantly related to postoperative olfactory outcomes. Conclusion: The olfactory questionnaire correlated well with conventional psychosomatic olfactory function tests. In combination with clinical parameters and preoperative psychosomatic olfactory function tests, the olfactory questionnaire is suitable for assessing subjective olfactory function after endoscopic endonasal skull base surgery.

Detection of prions in matching post-mortem skin and cerebrospinal fluid samples using second-generation real-time quaking-induced conversion assay.

Real-time quaking-induced conversion assay (RT-QuIC) exploits templating activity of pathogenic prion protein for ultrasensitive detection of prions. We have utilized second generation RT-QuIC assay to analyze matching post-mortem cerebrospinal fluid and skin samples of 38 prion disease patients and of 30 deceased neurological controls. The analysis of cerebrospinal fluid samples led to 100% sensitivity and 100% specificity, but some samples had to be diluted before the analysis to alleviate the effect of present RT-QuIC inhibitors. The analysis of the corresponding skin samples provided 89.5% sensitivity and 100% specificity. The median seeding dose present in the skin was one order of magnitude higher than in the cerebrospinal fluid, despite the overall fluorescent signal of the skin samples was comparatively lower. Our data support the use of post-mortem cerebrospinal fluid for confirmation of prion disease diagnosis and encourage further studies of the potential of skin biopsy samples for intra-vitam prion diseases´ diagnostics.

Hearing preservation after stereotactic radiosurgery for sporadic intracanalicular vestibular schwannomas classified as Koos grade 1.

INTRODUCTION: The mechanism of hearing loss following stereotactic radiosurgery (SRS) for vestibular schwannomas (VSs) remains unclear. There is conflicting evidence regarding cochlear nerve damage by transient volume expansion of VSs after radiosurgery and radiation-induced cochlear damage. This study aimed to investigate whether there is a specific patient population that can achieve definite hearing preservation after SRS for VSs. METHODS: A total of 37 consecutive patients with sporadic unilateral intracanalicular VSs and serviceable hearing (Gardner-Roberson [G-R] class I or II) were treated with SRS from 2009 to 2023. This is a retrospective study. Survival analysis with Cox regression for hearing deterioration was performed. RESULTS: The median age was 55 years old. The median tumor volume was 0.089 cm3 , and the median marginal dose was 12.0 Gy. Nonserviceable hearing deterioration occurred in 9 patients (24.3%), with a median onset of 11.9 months after SRS. The actuarial rates of serviceable hearing preservation were 86%, 82%, and 70% at 1, 2, and 3 years after SRS, respectively. In a multivariate analysis, only baseline pure tone average > 30 dB increased the risk of nonserviceable hearing deterioration with significant hazard ratio. There were 13 patients with petit VSs whose tumor volume was smaller than 0.05 cm3 , and 11 of them were treated by a 4-mm single shot with a marginal dose of 12 Gy. None of the 13 patients had nonserviceable hearing deterioration. CONCLUSIONS: Petit VSs that can be treated with 4-mm single or double shots with a marginal dose of 12 Gy may achieve hearing preservation after SRS.

Imatinib inhibits oral squamous cell carcinoma by suppressing the PI3K/AKT/mTOR signaling pathway.

Oral squamous cell carcinoma (OSCC) is a prevalent oral and maxillofacial cancer with high mortality as OSCC cells readily invade tissues and metastasize to cervical lymph nodes. Although imatinib exhibits potential anticancer and remarkable clinical activities that therapeutically affect several cancer types, its specific impact on OSCC has yet to be fully explored. Therefore, this study investigated the potential anticancer effect of imatinib on OSCC cells and the underlying mechanisms. The Cell Counting Kit-8 was used to determine the impact of imatinib on cell viability. Then, morphological cell proliferation analysis was conducted to examine how imatinib impacted OSCC cell growth. Moreover, OSCC cell migration was determined through wound-healing assays, and colony formation abilities were investigated through the soft agar assay. Lastly, the effect of imatinib on OSCC cell apoptosis was verified with flow cytometry, and its inhibitory mechanism was confirmed through Western blot. Our results demonstrate that imatinib effectively inhibited OSCC cell proliferation and significantly curtailed OSCC cell viability in a time- and concentration-dependent manner. Furthermore, imatinib suppressed migration and colony formation while promoting OSCC cell apoptosis by enhancing p53, Bax, and PARP expression levels and reducing Bcl-2 expression. Imatinib also inhibited the PI3K/AKT/mTOR signaling pathway and induced OSCC cell apoptosis, demonstrating the potential of imatinib as a treatment for oral cancer.

Lower Plasma Amyloid Beta - 42 Levels Associated With Worse Survival in Patients With Glioma.

BACKGROUND/AIM: Glioma is often refractory. The accumulation of amyloid beta (Aß) in the brain is commonly associated with Alzheimer's disease (AD), but there are studies suggesting that Aß has tumor suppressor potential. The aim of this study was to identify a novel, non-invasive candidate biomarker for histological prediction and prognostic assessment of glioma. PATIENTS AND METHODS: Serum was prepared from blood samples collected preoperatively from 48 patients with WHO grade II-IV glioma between October 2004 and December 2017 at a single tertiary institution. The concentration of Aß42 was measured using the SMCxPRO immunoassay (Merck). The clinical and histological characteristics of the patients, including molecular subtypes, were reviewed. RESULTS: The mean age of the patients was 52.2±12.5 years. The mean value of serum Aß42 concentration was 7.6±7.8 pg/ml in the anaplastic astrocytoma (WHO grade III) group and 6.4±6.5 pg/ml in the glioblastoma multiforme (WHO grade IV) group. The Negative epidermal growth factor receptor (EGFR) expression was associated with higher serum Aß42 levels (p=0.020). Kaplan-Meier analysis demonstrated that patients with high serum Aß42 (>11.78 pg/ml) had significantly longer progression-free survival (PFS) (p=0.038) and overall survival (OS) (p=0.018). CONCLUSION: This study investigated serum Aß42 levels as a potential biomarker for glioma. The results showed that low serum Aß42 levels were associated with EGFR expression and poor PFS and OS. Overall, these findings suggest a potential role of Aß42 as a prognostic marker in astrocytomas.