Radiographic and neurological outcomes of Gamma Knife radiosurgery for lower cranial nerve schwannomas: a single-institution experience.

OBJECTIVE: Gamma Knife radiosurgery (GKRS) is widely used for treating small- to medium-sized or postoperative residual, recurrent lower cranial nerve schwannomas (LCNSs). This study aimed to evaluate the radiographic and neurological outcomes of GKRS for LCNS. METHODS: A total of 60 patients with 47 jugular foramen schwannomas (JFSs) and 13 hypoglossal nerve schwannomas (HNSs) who underwent GKRS were included. Dysphagia (40.4%) and hoarseness (23.4%) were the most common preexisting symptoms associated with JFS, whereas tongue deviation (53.8%) was prevalent in HNS. The median tumor volumes were 3.2 cm3 and 2.2 cm3 for JFSs and HNSs, respectively. The median marginal dose administered to the tumor was 13 Gy (range 12-15 Gy). The median follow-up duration was 52.8 months. RESULTS: Local tumor control was achieved in 91.5% of JFSs and 92.3% of HNSs. The preexisting neurological symptoms improved in 48.9% of patients with JFS and remained stable in 29.8%. However, 10 patients (21.3%) experienced exacerbation of symptoms associated with cranial nerves VII, VIII, IX, X, and XI. Among these, 3 patients (6.4%) exhibited persistent symptomatic deterioration. Patients with HNSs demonstrated a stable trajectory without symptom aggravation. Larger tumor volume and cystic portion were significantly associated with tumor progression (p = 0.017 and 0.003, respectively), and post-GKRS transient swelling was associated with neurological deterioration (p = 0.044). CONCLUSIONS: GKRS is an alternative treatment option for LCNS that reduces surgical morbidity and enhances tumor control. However, GKRS can potentially lead to neurological deterioration, necessitating extreme caution throughout the procedure, specifically for JFSs.

Long-term outcomes of CNS WHO grade 2 oligodendroglioma in adult patients: a single-institution experience.

PURPOSE: Oligodendrogliomas (ODGs) are a subtype of diffuse lower-grade gliomas with overall survival of > 10 years. This study aims to analyze long-term outcomes and identify prognostic factors in patients with WHO grade 2 ODG. METHODS: We retrospectively reviewed 138 adult patients diagnosed with 1p/19q co-deleted ODG who underwent surgical resection or biopsy between 1994 and 2021, analyzing clinical data, treatment details, and outcomes. Progression-free survival (PFS) and overall survival (OS) were evaluated using Kaplan-Meier analysis. Univariate and multivariate Cox regression analyses were utilized to identify significant prognostic factors. RESULTS: In the gross total resection (GTR) group, 63 (45.7%) underwent observation and 5 (3.6%) received postoperative treatment; in the non-GTR group, 37 (26.8%) were observed and 33 (23.9%) received postoperative treatment. The median PFS and OS were 6.8 and 18.4 years, respectively. Between adjuvant treatment and observation, there was no significant difference in PFS or OS. However, GTR or STR with less than 10% residual tumor exhibited significantly better PFS and OS compared to PR or biopsy (p = 0.022 and 0.032, respectively). Multivariate analysis revealed that contrast enhancement on MRI was associated with worse PFS (HR = 2.36, p < 0.001) and OS (HR = 5.89, p = 0.001). And the presence of seizures at presentation was associated with improved OS (HR = 0.28, p = 0.006). CONCLUSION: This study underscores favorable long-term outcomes for patients with 1p/19q co-deleted ODG WHO grade 2. Our findings indicate that the EOR plays a crucial role as a significant prognostic factor in enhancing PFS and OS outcomes in WHO grade 2 ODG.

Delay characteristics of quasi-nonvolatile memory devices operating in positive feedback mechanism.

This study examines the memory and read delay characteristics of quasi-nonvolatile memory (QNVM) devices operating in a positive feedback mechanism through technology computer-aided design simulation. The QNVM devices exhibit a rapid operation speed of 5 ns, a significant sensing margin of approximately 8.0µA, and a retention time of around 1 s without any external bias. These devices showcase an exceptionally brief read delay of 0.12 ns. The energy band diagrams during the memory operation are analyzed to clarify the factors influencing the read delay. The write and standby conditions modulate the potential barrier height during the standby operation, thereby affecting the read delay. Moreover, the shorter rising time causes the reduction of the read delay. This study demonstrates that the QNVM device has the potential to resolve energy consumption and speed issues in nonvolatile memory devices.

Generation and Storage of Random Voltage Values via Ring Oscillators Comprising Feedback Field-Effect Transistors.

In this study, we demonstrate the generation and storage of random voltage values using a ring oscillator consisting of feedback field-effect transistors (FBFETs). This innovative approach utilizes the logic-in-memory function of FBFETs to extract continuous output voltages from oscillatory cycles. The ring oscillator exhibited uniform probability distributions of 51.6% for logic 0 and 48.4% for logic 1. The generation of analog voltages provides binary random variables that are stored for over 5000 s. This demonstrates the potential of the ring oscillator in advanced physical functions and true random number generator technologies.

Surgical Strategy for Petroclival Meningioma-Related Trigeminal Neuralgia: The Role of Porus Trigeminus Opening.

OBJECTIVE: Petroclival meningiomas invade Meckel's cave through the porus trigeminus, leading to secondary trigeminal neuralgia. Microsurgery and stereotactic radiosurgery (SRS) are the typical treatment options. This study investigated symptom control, outcomes, and surgical strategies for PC meningioma-induced TN. METHODS: We retrospectively analyzed 28 TN patients with PC meningiomas who underwent microsurgical nerve decompression between January 2021 and February 2023. In all patients undergoing a transpetrosal approach, the porus trigeminus was opened to enable the removal of the entire tumor within Meckel's cave. Clinical outcomes were assessed using the Barrow Neurologic Institute (BNI) pain intensity scale. Risk factors for poor TN outcomes and poor facial numbness were analyzed. RESULTS: Among 28 patients, 21 (75%) underwent the transpetrosal approach, 5 (17.9%) underwent the retrosigmoid approach, and 2 (7.1%) underwent the Dolenc approach. Following microsurgery, 23 patients (82.1%) experienced TN relief without further medication (BNI I or II). TN recurrence occurred in 2 patients (7.1%), and 3 patients (10.7%) did not achieve TN relief. Cavernous sinus invasion was significantly correlated with poor TN outcomes (P = 0.047). A history of previous SRS (P = 0.011) and upper clivus type tumor (P = 0.018) were significantly associated with poor facial numbness. CONCLUSIONS: Microsurgical nerve decompression is effective in improving BNI scores in patients with TN associated with PC meningiomas. Considering the results of our study, the opening of the porus trigeminus can be considered as a suggested procedure in the treatment of PC meningiomas, especially in cases accompanied by TN.

Exploring prognostic factors and treatment strategies for long-term survival in pleomorphic xanthoastrocytoma patients.

Pleomorphic xanthoastrocytomas (PXA) are rare, accounting for < 1% of all astrocytomas. Literature on the clinical course and treatment outcomes of PXAs is limited. The study aimed to determine prognosis and treatment strategies for PXAs. Patients who had PXAs surgery between 2000-2021 were retrospectively analyzed for demographics and radiological characteristics. Initial and salvage treatment outcomes were recorded. Overall, 40 and 9 patients had grade 2 and 3 PXAs; their 5-year progression-free survival (PFS) rates were 75.8% and 37.0%, respectively (p = 0.003). Univariate analysis revealed that strong T1 enhancement (p = 0.036), infiltrative tumor margins (p < 0.001), peritumoral edema (p = 0.003), WHO grade (p = 0.005), and gross total resection (p = 0.005) affected the PFS. Multivariate analysis revealed that the WHO grade (p = 0.010) and infiltrative tumor margins (p = 0.008) influenced the PFS. The WHO grade (p = 0.027) and infiltrative tumor margins (p = 0.027) also affected the overall survival (OS). Subgroup analysis for grade 2 PXAs revealed no significant associations between adjuvant radiation therapy and the PFS and OS. This study highlighted the heterogeneous nature of PXAs and its impact on patient prognosis. Infiltrative tumor margins emerged as a key prognostic factor. Our findings have emphasized the prognostic relevance of radiological features and the need for larger studies on comprehensive management.

Read Operation Mechanism of Feedback Field-Effect Transistors with Quasi-Nonvolatile Memory States.

In this study, the read operation of feedback field-effect transistors (FBFETs) with quasi-nonvolatile memory states was analyzed using a device simulator. For FBFETs, write pulses of 40 ns formed potential barriers in their channels, and charge carriers were accumulated (depleted) in these channels, generating the memory state "State 1 (State 0)". Read pulses of 40 ns read these states with a retention time of 3 s, and the potential barrier formation and carrier accumulation were influenced by these read pulses. The potential barriers were analyzed, using junction voltage and current density to explore the memory states. Moreover, FBFETs exhibited nondestructive readout characteristics during the read operation, which depended on the read voltage and pulse width.

Evaluation of the Regulatory Required Post-Authorization Safety Study for Propacetamol: Nested Case-Control and Case-Time-Control Studies.

PURPOSE: Following the withdrawal of propacetamol in Europe owing to safety issues, the regulatory authority of South Korea requested a post-marketing surveillance study to investigate its safety profile. MATERIALS AND METHODS: We conducted nested case-control and case-time-control (CTC) analyses of cases and controls identified for outcomes of interest, including anaphylaxis, thrombosis, and Stevens-Johnson syndrome (SJS), using the claims database of South Korea, 2010-2019. Risk-set sampling was used to match each case with up to 10 controls for age, sex, cohort entry date, and follow-up duration. Exposure to anaphylaxis, thrombosis, and SJS was assessed within 7, 90, and 30 days of the index date, respectively. We calculated odds ratios (OR) with 95% confidence intervals (CIs) using conditional logistic regression to assess the risk of outcomes associated with propacetamol. RESULTS: We identified cases of anaphylaxis (n=61), thrombosis (n=95), and SJS (n=1) and matched them to controls (173, 268, and 4, respectively). In the nested case-control analysis, the ORs for anaphylaxis and SJS were inestimable given the small number of propacetamol users during the risk period; meanwhile, the OR for thrombosis was 1.60 (95% CI 0.71-3.62). In the CTC design, the effect estimate was only estimated for thrombosis (OR 0.56, 95% CI 0.09-3.47). CONCLUSION: In both nested case-control and CTC analyses, propacetamol was not associated with an increased risk of anaphylaxis, thrombosis, or SJS. The findings from this study, which used routinely collected clinical data, provide reassuring real-world evidence regarding the safety of propacetamol in a nationwide population to support regulatory decision-making.

Novel Chlorin e6-Curcumin Derivatives as a Potential Photosensitizer: Synthesis, Characterization, and Anticancer Activity.

Novel series of chlorin e6-curcumin derivatives were designed and synthesized. All the synthesized compounds 16, 17, 18, and 19 were tested for their photodynamic treatment (PDT) efficacy against human pancreatic cancer cell lines: AsPC-1, MIA-PaCa-2, and PANC-1. The cellular uptake study was performed in the aforementioned cell lines using fluorescence-activated cell sorting (FACS). 17, among the synthesized compounds with IC50 values of 0.27, 0.42, and 0.21 µM against AsPC-1, MIA PaCa-2, and PANC-1 cell lines, respectively, demonstrated excellent cellular internalization capability and exhibited higher phototoxicity relative to the parent Ce6. The quantitative analyses using Annexin V-PI staining revealed that the 17-PDT-induced apoptosis was dose-dependent. In pancreatic cell lines, 17 reduced the expression of the anti-apoptotic protein, Bcl-2, and increased the pro-apoptotic protein, cytochrome C, which indicates the activation of intrinsic apoptosis, the primary cause of cancer cell death. Structure-activity relationship studies have shown that the incorporation of additional methyl ester moiety and conjugation to the enone moiety of curcumin enhances cellular uptake and PDT efficacy. Moreover, in vivo PDT testing in melanoma mouse models revealed that 17-PDT greatly reduced tumor growth. Therefore, 17 might be an effective photosensitizer for PDT anticancer therapy.

Disturbance Characteristics of 1T DRAM Arrays Consisting of Feedback Field-Effect Transistors.

Challenges in scaling dynamic random-access memory (DRAM) have become a crucial problem for implementing high-density and high-performance memory devices. Feedback field-effect transistors (FBFETs) have great potential to overcome the scaling challenges because of their one-transistor (1T) memory behaviors with a capacitorless structure. Although FBFETs have been studied as 1T memory devices, the reliability in an array must be evaluated. Cell reliability is closely related to device malfunction. Hence, in this study, we propose a 1T DRAM consisting of an FBFET with a p+-n-p-n+ silicon nanowire and investigate the memory operation and disturbance in a 3 × 3 array structure through mixed-mode simulations. The 1T DRAM exhibits a write speed of 2.5 ns, a sense margin of 90 µA/µm, and a retention time of approximately 1 s. Moreover, the energy consumption is 5.0 × 10-15 J/bit for the write '1' operation and 0 J/bit for the hold operation. Furthermore, the 1T DRAM shows nondestructive read characteristics, reliable 3 × 3 array operation without any write disturbance, and feasibility in a massive array with an access time of a few nanoseconds.

Prediction of Device Characteristics of Feedback Field-Effect Transistors Using TCAD-Augmented Machine Learning.

In this study, the device characteristics of silicon nanowire feedback field-effect transistors were predicted using technology computer-aided design (TCAD)-augmented machine learning (TCAD-ML). The full current-voltage (I-V) curves in forward and reverse voltage sweeps were predicted well, with high R-squared values of 0.9938 and 0.9953, respectively, by using random forest regression. Moreover, the TCAD-ML model provided high prediction accuracy not only for the full I-V curves but also for the important device features, such as the latch-up and latch-down voltages, saturation drain current, and memory window. Therefore, this study demonstrated that the TCAD-ML model can substantially reduce the computational time for device development compared with conventional simulation methods.

A study of the regional differences in propacetamol-related adverse events using VigiBase data of the World Health Organization.

Upon withdrawal of propacetamol, an injectable formulation of the paracetamol prodrug, in Europe due to safety concerns, South Korea's regulatory body requested a post-marketing surveillance study exploring its safety profile. We characterized regional disparities in adverse events (AE) associated with propacetamol between Asia and Europe using the World Health Organization's pharmacovigilance database, VigiBase. We performed disproportionality analyses using reporting odds ratios (rOR) and information component (IC) to determine whether five AEs (anaphylaxis, Stevens-Johnson syndrome, thrombosis, contact dermatitis/eczema, injection site reaction [ISR]) were associated with propacetamol versus non-propacetamol injectable antipyretics in Asia and Europe, separately. In Asia, there was a high reporting ratio of propacetamol-related ISR (rOR 5.72, 95% CI 5.19-6.31; IC025 1.27), satisfying the signal criteria; there were no reports of thrombosis and contact dermatitis/eczema. Two signals were identified in Europe, with higher reporting ratios for thrombosis (rOR 7.45, 95% CI 5.19-10.71; IC025 1.92) and contact dermatitis/eczema (rOR 16.73, 95% CI 12.48-22.42; IC025 2.85). Reporting ratios of propacetamol-related anaphylaxis were low for Asia and Europe. While signals were found for thrombosis and contact dermatitis/eczema in Europe, these were not detected in Asia. These findings suggest potential ethnic differences in propacetamol-related AEs between Asia and Europe, which could serve as supportive data for future decision-making.

Logic and memory functions of an inverter comprising reconfigurable double gated feedback field effect transistors.

In this study, we propose an inverter consisting of reconfigurable double-gated (DG) feedback field-effect transistors (FBFETs) and examine its logic and memory operations through a mixed-mode technology computer-aided design simulation. The DG FBFETs can be reconfigured to n- or p-channel modes, and these modes exhibit an on/off current ratio of ~ 1012 and a subthreshold swing (SS) of ~ 0.4 mV/dec. Our study suggests the solution to the output voltage loss, a common problem in FBFET-based inverters; the proposed inverter exhibits the same output logic voltage as the supply voltage in gigahertz frequencies by applying a reset operation between the logic operations. The inverter retains the output logic '1' and '0' states for ~ 21 s without the supply voltage. The proposed inverter demonstrates the promising potential for logic-in-memory application.

NAND and NOR logic-in-memory comprising silicon nanowire feedback field-effect transistors.

The processing of large amounts of data requires a high energy efficiency and fast processing time for high-performance computing systems. However, conventional von Neumann computing systems have performance limitations because of bottlenecks in data movement between separated processing and memory hierarchy, which causes latency and high power consumption. To overcome this hindrance, logic-in-memory (LIM) has been proposed that performs both data processing and memory operations. Here, we present a NAND and NOR LIM composed of silicon nanowire feedback field-effect transistors, whose configuration resembles that of CMOS logic gate circuits. The LIM can perform memory operations to retain its output logic under zero-bias conditions as well as logic operations with a high processing speed of nanoseconds. The newly proposed dynamic voltage-transfer characteristics verify the operating principle of the LIM. This study demonstrates that the NAND and NOR LIM has promising potential to resolve power and processing speed issues.

Host tp53 mutation induces gut dysbiosis eliciting inflammation through disturbed sialic acid metabolism.

BACKGROUND: Host tp53 mutations are frequently found during the early stages of colitis-associated colorectal cancer (CAC), but whether such mutations induce gut microbiota dysbiosis and chronic intestinal inflammation that contributes to the development of CAC, remains unknown. RESULTS: We found that zebrafish tp53 mutant larvae exhibited elevated intestinal inflammation, by monitoring the NFκB activity in the mid-distal intestines of zebrafish larvae using an NFκB:EGFP transgenic reporter line in vivo as well as neutrophil infiltration into the intestine. This inflammation was due to dysbiotic gut microbiota with reduced diversity, revealed using both 16S rRNA amplicon sequencing and a germfree larva model. In this dysbiosis, Aeromonas spp. were aberrantly enriched as major pathobionts and exhibited the capacity for aggressive colonization in tp53 mutants. Importantly, the ex-germfree experiments supported the causality of the host tp53 mutation for inducing the inflammation. Transcriptome and high-performance liquid chromatography analyses of the host gastrointestinal tracts identified dysregulated sialic acid (SA) metabolism concomitant with increased host Neu5Gc levels as the key determinant of aberrant inflammation, which was reversed by the sialidase inhibitors oseltamivir and Philippin A. CONCLUSIONS: These results demonstrate a crucial role for host tp53 in maintaining symbiosis and immune homeostasis via SA metabolism. Disturbed SA metabolism via a tp53 mutation may be exploited by specific elements of the gut microbiome, eliciting both dysbiosis and inflammation. Manipulating sialometabolism may therefore provide an efficacious therapeutic strategy for tp53 mutation-induced dysbiosis, inflammation, and ultimately, related cancers. Video Abstract.

Correction: Yun et al. Prion Protein of Extracellular Vesicle Regulates the Progression of Colorectal Cancer. Cancers 2021, 13, 2144.

The authors wish to make the following corrections to this paper [...].

Prion Protein of Extracellular Vesicle Regulates the Progression of Colorectal Cancer.

Colorectal cancer (CRC) is one of the leading causes of cancer-related death due to its aggressive metastasis in later stages. Although there is a growing interest in the tumorigenic role of cellular prion protein (PrPC) in the process of metastasis, the precise mechanism behind the cellular communication involving prion proteins remains poorly understood. This study found that hypoxic tumor microenvironment increased the PrPC-expressing exosomes from CRC, and these exosomes regulate the CRC cell behavior and tumor progression depending on the expression of PrPC. Hypoxic exosomes from CRC cells promoted sphere formation, the expression of tumor-inducing genes, migration, invasion, and tumor growth. Furthermore, these exosomes increased endothelial permeability, migration, invasion, and angiogenic cytokine secretion. These effects were associated with PrPC expression. Application of anti-PrPC antibody with 5-fluorouracil significantly suppressed the CRC progression in a murine xenograft model. Taken together, these findings indicate that PrP-expressing exosomes secreted by hypoxic CRC cells are a key factor in the tumorigenic CRC-to-CRC and CRC-to-endothelial cell communication. Significance: These findings suggest that inhibiting PrPC in hypoxic exosomes during chemotherapy may be an effective therapeutic strategy in colorectal cancer.

Effect of Ge Mole Fraction on Performance of Underlapped Gate-All-Around SiGe-Source Tunneling Field-Effect Transistors.

In this paper, we propose the design optimization of underlapped Si1-xGex-source tunneling field-effect transistors (TFETs) with a gate-all-around structure. The band-to-band tunneling rates, tunneling barrier widths, I-V transfer characteristics, threshold voltages, on/off current ratios, and subthreshold swings (SSs) were analyzed by varying the Ge mole fraction of the Si1-xGex source using a commercial device simulator. In particular, a Si0.2Ge0.8-source TFET among our proposed TFETs exhibits an on/off current ratio of approximately 1013, and SS of 27.4 mV/dec.

Bovine milk extracellular vesicles induce the proliferation and differentiation of osteoblasts and promote osteogenesis in rats.

Bone is constantly balanced between the formation of new bone by osteoblasts and the absorption of old bone by osteoclasts. To promote bone growth and improve bone health, it is necessary to promote the proliferation and differentiation of osteoblasts. Although bovine milk is known to exert a beneficial effect on bone formation, the study on the effect of bovine milk extracellular vesicles (EVs) on osteogenesis in osteoblasts is limited. In this study, we demonstrated that bovine milk EVs promoted the proliferation of human osteogenic Saos-2 cells by increasing the expression of cell cycle-related proteins. In addition, bovine milk EVs also induced the differentiation of Saos-2 cells by increasing the expression of RUNX2 and Osterix which are key transcription factors for osteoblast differentiation. Oral administration of milk EVs did not cause toxicity in Sprague-Dawley rats. Furthermore, milk EVs promoted longitudinal bone growth and increased the bone mineral density of the tibia. Our findings suggest that milk EVs could be a safe and powerful applicant for enhancing osteogenesis. PRACTICAL APPLICATIONS: Until now, calcium and vitamin D have been prescribed to promote bone formation or to prevent bone diseases such as osteoporosis. Recently, several studies to find bioactive molecules that regulate cellular functions of osteoblasts or osteoclasts are actively underway. Milk basic proteins and lactoferrin present in milk are known to promote bone formation, but they exist in small quantities and the isolation of these proteins is complicated making mass production difficult. Recently, it has been found that milk contains large quantities of EVs, and that they promote bone formation. Studies on the effect of Milk EVs on osteoblasts during osteogenesis will help in the development of biomaterials for osteogenesis.

Inverting logic-in-memory cells comprising silicon nanowire feedback field-effect transistors.

In this paper, we propose inverting logic-in-memory (LIM) cells comprising silicon nanowire feedback field-effect transistors with steep switching and holding characteristics. The timing diagrams of the proposed inverting LIM cells under dynamic and static conditions are investigated via mixed-mode technology computer-aided design simulation to verify the performance. The inverting LIM cells have an operating speed of the order of nanoseconds, an ultra-high voltage gain, and a longer retention time than that of conventional dynamic random access memory. The disturbance characteristics of half-selected cells within an inverting LIM array confirm the appropriate functioning of the random access memory array.