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The frozen elephant trunk (FET) technique can be applied to extensive aortic pathology, including lesions in the aortic arch and proximal descending thoracic aorta. FET is useful for tear-oriented surgery in dissections, managing malperfusion syndrome, and promoting positive aortic remodeling. Despite these benefits, complications such as distal stent-induced new entry and spinal cord ischemia can pose serious problems with the FET technique. To prevent these complications, careful sizing and planning of the FET are crucial. Additionally, since the FET technique involves total arch replacement, meticulous surgical skills are essential, particularly for young surgeons. In this article, we propose several techniques to simplify surgical procedures, which may lead to better outcomes for patients with extensive aortic pathology. In the era of precision medicine, the next-generation FET device could facilitate the treatment of complex aortic diseases through a patient-tailored approach.

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BACKGROUND: ChatGPT, a recently developed artificial intelligence (AI) chatbot, has demonstrated improved performance in examinations in the medical field. However, thus far, an overall evaluation of the potential of ChatGPT models (ChatGPT-3.5 and GPT-4) in a variety of national health licensing examinations is lacking. This study aimed to provide a comprehensive assessment of the ChatGPT models' performance in national licensing examinations for medical, pharmacy, dentistry, and nursing research through a meta-analysis. METHODS: Following the PRISMA protocol, full-text articles from MEDLINE/PubMed, EMBASE, ERIC, Cochrane Library, Web of Science, and key journals were reviewed from the time of ChatGPT's introduction to February 27, 2024. Studies were eligible if they evaluated the performance of a ChatGPT model (ChatGPT-3.5 or GPT-4); related to national licensing examinations in the fields of medicine, pharmacy, dentistry, or nursing; involved multiple-choice questions; and provided data that enabled the calculation of effect size. Two reviewers independently completed data extraction, coding, and quality assessment. The JBI Critical Appraisal Tools were used to assess the quality of the selected articles. Overall effect size and 95% confidence intervals [CIs] were calculated using a random-effects model. RESULTS: A total of 23 studies were considered for this review, which evaluated the accuracy of four types of national licensing examinations. The selected articles were in the fields of medicine (n = 17), pharmacy (n = 3), nursing (n = 2), and dentistry (n = 1). They reported varying accuracy levels, ranging from 36 to 77% for ChatGPT-3.5 and 64.4-100% for GPT-4. The overall effect size for the percentage of accuracy was 70.1% (95% CI, 65-74.8%), which was statistically significant (p < 0.001). Subgroup analyses revealed that GPT-4 demonstrated significantly higher accuracy in providing correct responses than its earlier version, ChatGPT-3.5. Additionally, in the context of health licensing examinations, the ChatGPT models exhibited greater proficiency in the following order: pharmacy, medicine, dentistry, and nursing. However, the lack of a broader set of questions, including open-ended and scenario-based questions, and significant heterogeneity were limitations of this meta-analysis. CONCLUSIONS: This study sheds light on the accuracy of ChatGPT models in four national health licensing examinations across various countries and provides a practical basis and theoretical support for future research. Further studies are needed to explore their utilization in medical and health education by including a broader and more diverse range of questions, along with more advanced versions of AI chatbots.

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Multifunctional structural batteries promise advancements in structural energy storage technologies by seamlessly integrating load-bearing and energy-storage functions within a single material, reducing weight, and enhancing safety. Yet, commercialization faces challenges in materials processing, assembly, and design optimization. Here, we report a systematic approach to develop a carbon fiber (CF)-based structural battery impregnated with epoxy-based solid polymer electrolyte (SPE) via robust vacuum-assisted compression molding (VACM). Informed by cure kinetics, SPE processing enhances the multifunctional performance with no fillers or additives. The thin flexible CF-based laminae impregnated under high pressure achieved a substantial enhancement of ∼160% in the fiber volume fraction (FVF) as although thin and strip-shaped, the fibers were optimally packed with low void. A CF/SPE-based battery was fabricated, with a hybrid layered ionic liquid (IL)/ carbonate electrolyte (CE) showing enhanced safety and multifunctional performance. Enhanced by thin, uniform, and stiff CF-based composites, this study propels the development of advanced multifunctional structures, thereby expediting sustainable commercialization.

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Alloys of platinum with alkaline earth metals promise to be active and highly stable for fuel cell applications, yet their synthesis in nanoparticles remains a challenge due to their high negative reduction potentials. Herein, we report a strategy that overcomes this challenge by preparing platinum-magnesium (PtMg) alloy nanoparticles in the solution phase. The PtMg nanoparticles exhibit a distinctive structure with a structurally ordered intermetallic core and a Pt-rich shell. The PtMg/C as a cathode catalyst in a hydrogen-oxygen fuel cell exhibits a mass activity of 0.50 A mgPt-1 at 0.9 V with a marginal decrease to 0.48 A mgPt-1 after 30,000 cycles, exceeding the US Department of Energy 2025 beginning-of-life and end-of-life mass activity targets, respectively. Theoretical studies show that the activity stems from a combination of ligand and strain effects between the intermetallic core and the Pt-rich shell, while the stability originates from the high vacancy formation energy of Mg in the alloy.

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BACKGROUND: We recently reported that the dopamine (DA) analogue CA140 modulates neuroinflammatory responses in lipopolysaccharide-injected wild-type (WT) mice and in 3-month-old 5xFAD mice, a model of Alzheimer's disease (AD). However, the effects of CA140 on Aß/tau pathology and synaptic/cognitive function and its molecular mechanisms of action are unknown. METHODS: To investigate the effects of CA140 on cognitive and synaptic function and AD pathology, 3-month-old WT mice or 8-month-old (aged) 5xFAD mice were injected with vehicle (10% DMSO) or CA140 (30 mg/kg, i.p.) daily for 10, 14, or 17 days. Behavioral tests, ELISA, electrophysiology, RNA sequencing, real-time PCR, Golgi staining, immunofluorescence staining, and western blotting were conducted. RESULTS: In aged 5xFAD mice, a model of AD pathology, CA140 treatment significantly reduced Aß/tau fibrillation, Aß plaque number, tau hyperphosphorylation, and neuroinflammation by inhibiting NLRP3 activation. In addition, CA140 treatment downregulated the expression of cxcl10, a marker of AD-associated reactive astrocytes (RAs), and c1qa, a marker of the interaction of RAs with disease-associated microglia (DAMs) in 5xFAD mice. CA140 treatment also suppressed the mRNA levels of s100ß and cxcl10, markers of AD-associated RAs, in primary astrocytes from 5xFAD mice. In primary microglial cells from 5xFAD mice, CA140 treatment increased the mRNA levels of markers of homeostatic microglia (cx3cr1 and p2ry12) and decreased the mRNA levels of a marker of proliferative region-associated microglia (gpnmb) and a marker of lipid-droplet-accumulating microglia (cln3). Importantly, CA140 treatment rescued scopolamine (SCO)-mediated deficits in long-term memory, dendritic spine number, and LTP impairment. In aged 5xFAD mice, these effects of CA140 treatment on cognitive/synaptic function and AD pathology were regulated by dopamine D1 receptor (DRD1)/Elk1 signaling. In primary hippocampal neurons and WT mice, CA140 treatment promoted long-term memory and dendritic spine formation via effects on DRD1/CaMKIIα and/or ERK signaling. CONCLUSIONS: Our results indicate that CA140 improves neuronal/synaptic/cognitive function and ameliorates Aß/tau pathology and neuroinflammation by modulating DRD1 signaling in primary hippocampal neurons, primary astrocytes/microglia, WT mice, and aged 5xFAD mice.

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van der Waals (vdW) layered materials have been shown to have excellent optoelectronic properties relevant to photovoltaics. Despite their promise, the demonstrated efficiencies of vdW material solar cells remain low and are seldom supported by statistics or spectral quantum efficiency analysis. In this study, we utilize a p-type WSe2 absorber, forming a solar cell with a transparent front InOx electron contact, and a rear Pd reflector/hole contact. We fabricate multiple devices providing statistics for 10 devices with an average 1 sun conversion efficiency above 5%, among which a champion efficiency of 6.37% is achieved. This is the highest AM 1.5G 1 sun efficiency reported for a vdW material solar cell, with a current density supported by external quantum efficiency analysis. This cell is also shown to have near unity quantum efficiency around λ = 600 nm. This work provides support to vdW materials being considered as serious candidates for future thin-film solar cells.

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In this study, a multiple-resonance (MR) core structure is developed with a spin-flip-restricted emission mechanism based on a fused indolo[3,2,1-jk]carbazole (ICz) framework as emitters to improve the lifetime of blue organic light-emitting diodes. The molecular skeleton modulation approach applied to the conjugated π-system effectively stabilizes the triplet energy of the fused ICz emitters and narrows the full-width-at-half maximum (<20 nm). In addition, the emitters exhibit higher exciton stability than conventional boron-based MR emitters. The fused ICz-based blue fluorescent device exhibits a high external quantum efficiency of 7.2%, a blue index of 68.6 cd A-1 at a Commission internationale de l'éclairage y coordinate (CIEy) of 0.075, and a device lifetime 1.8 times longer than that of a boron-based emitter. In addition, a phosphor-sensitized fluorescent device based on the ICz emitter exhibited an improved external quantum efficiency of 20.6% with a CIEy coordinate of 0.076.

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Combinatorial interactions between different regulators diversify and enrich the chance of transcriptional regulation in eukaryotic cells. However, a dose-dependent functional switch of homologous transcriptional repressors has rarely been reported. Here, we show that SHY2, an auxin/indole-3-acetic acid (Aux/IAA) repressor, exhibits a dose-dependent bimodal role in auxin-sensitive root-hair growth and gene transcription in Arabidopsis, whereas other Aux/IAA homologs consistently repress the auxin responses. The co-repressor (TOPLESS [TPL])-binding affinity of a bimodal Aux/IAA was lower than that of a consistently repressing Aux/IAA. The switch of a single amino acid residue in the TPL-binding motif between the bimodal form and the consistently repressing form switched their TPL-binding affinity and transcriptional and biological roles in auxin responses. Based on these data, we propose a model whereby competition between homologous repressors with different co-repressor-binding affinities could generate a bimodal output at the transcriptional and developmental levels.

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Synthesis of silver nanoparticles (AgNPs) using plant extracts has been proposed as a more advantageous and environmentally friendly alternative compared to existing physical/chemical methods. In this study, AgNPs were synthesized from silver nitrate using black mulberry (BM) extract. The biosynthesized AgNPs were characterized through an UV-visible spectrometer, X-ray diffraction, and transmission electron microscopy. Additionally, BM-AgNPs were subjected to antioxidant, antibacterial, anti-inflammatory, and anticancer activities. AgNPs biosynthesized from BM extract were dark brown in color and showed a strong peak at 437 nm, confirming that AgNPs were successfully synthesized. The size of AgNPs was 170.17 ± 12.65 nm, the polydispersity index was 0.281 ± 0.07, and the zeta potential value was -56.6 ± 0.56 mV, indicating that the particles were stable. The higher total phenol, flavonoid, and anthocyanin content of BM-AgNPs compared to BM extract indicates that the particles contain multiple active substances due to the formation of AgNPs. The DPPH and ABTS assays showed decreased IC50 values compared to BM extract, demonstrating improved antioxidant activity. AgNPs inhibited the growth of S. aureus and E. coli at 600 µg/mL, with minimum bactericidal concentrations determined to be 1000 and 1200 µg/mL, respectively. The anti-inflammatory activity was 64.28% at a BM-AgNPs concentration of 250 µg/mL. As the concentration increased, the difference from the standard decreased, indicating the inhibitory effect of AgNPs on bovine serum albumin denaturation. The viability of MCF-7 cells treated with BM-AgNPs was found to be significantly lower than that of cells treated with BM extract. The IC50 value of BM-AgNPs was determined to be 96.9 µg/mL. This study showed that BM-AgNPs have the potential to be used in the pharmaceutical industry as antioxidant, antibacterial, anti-inflammatory, and anticancer agents.

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BACKGROUND: Cognitive behavioral therapy for insomnia (CBTi) is the first-line therapy for chronic insomnia. Mobile app-based CBTi (MCBTi) can enhance the accessibility of CBTi treatment; however, few studies have evaluated the effectiveness of MCBTi using a multicenter, randomized controlled trial design. OBJECTIVE: We aimed to assess the efficacy of Somzz, an MCBTi that provides real-time and tailored feedback to users, through comparison with an active comparator app. METHODS: In our multicenter, single-blind randomized controlled trial study, participants were recruited from 3 university hospitals and randomized into a Somzz group and a sleep hygiene education (SHE) group at a 1:1 ratio. The intervention included 6 sessions for 6 weeks, with follow-up visits over a 4-month period. The Somzz group received audiovisual sleep education, guidance on relaxation therapy, and real-time feedback on sleep behavior. The primary outcome was the Insomnia Severity Index score, and secondary outcomes included sleep diary measures and mental health self-reports. We analyzed the outcomes based on the intention-to-treat principle. RESULTS: A total of 98 participants were randomized into the Somzz (n=49, 50%) and SHE (n=49, 50%) groups. Insomnia Severity Index scores for the Somzz group were significantly lower at the postintervention time point (9.0 vs 12.8; t95=3.85; F2,95=22.76; ηp2=0.13; P<.001) and at the 3-month follow-up visit (11.3 vs 14.7; t68=2.61; F2,68=5.85; ηp2=0.03; P=.01) compared to those of the SHE group. The Somzz group maintained their treatment effect at the postintervention time point and follow-ups, with a moderate to large effect size (Cohen d=-0.62 to -1.35; P<.01 in all cases). Furthermore, the Somzz group showed better sleep efficiency (t95=-3.32; F2,91=69.87; ηp2=0.41; P=.001), wake after sleep onset (t95=2.55; F2,91=51.81; ηp2=0.36; P=.01), satisfaction (t95=-2.05; F2,91=26.63; ηp2=0.20; P=.04) related to sleep, and mental health outcomes, including depression (t95=2.11; F2,94=29.64; ηp2=0.21; P=.04) and quality of life (t95=-3.13; F2,94=54.20; ηp2=0.33; P=.002), compared to the SHE group after the intervention. The attrition rate in the Somzz group was 12% (6/49). CONCLUSIONS: Somzz outperformed SHE in improving insomnia, mental health, and quality of life. The MCBTi can be a highly accessible, time-efficient, and effective treatment option for chronic insomnia, with high compliance. TRIAL REGISTRATION: Clinical Research Information Service (CRiS) KCT0007292; https://cris.nih.go.kr/cris/search/detailSearch.do?seq=22214&search_page=L.

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The method presented herein is associated with the Lab Resource article titled "Generation of αMHC-EGFP knock-in in human pluripotent stem cell line, SNUe003-A-3, using CRISPR/CAS9-based gene targeting" [1]. The cardiac muscle-specific protein, α-myosin heavy chain (αMHC), is encoded by the human MYH6 gene, which is expressed in both the atria and ventricles during embryonic development and is predominantly expressed in the atria after birth [2]. Herein, the methods used to achieve CRISPR/SpCas9-mediated introduction of an EGFP reporter into αMHC, the target locus in human pluripotent stem cells (hPSCs) for cardiac lineage tracing and clinical cell sorting are described. The CRISPR-Cas9 system enables efficient replacement of the stop codon in the last exon of αMHC with a 2A non-joining peptide (T2A)-EGFP cassette. First, hPSCs are transfected with the donor construct and Cas9/sgRNA plasmids via electroporation and selected with neomycin for approximately 3 weeks. Thereafter, the established cell line exhibits typical characteristics of human embryonic stem cells (hESCs). When these cells differentiate into cardiomyocytes, the expression of EGFP is confirmed using confocal microscopy, flow cytometry analysis, and immunostaining.•The line enables monitoring of cell maturation events during human cardiac development.•The line is a valuable platform for cardiotoxicity tests and drug screening.•This method has already been employed in two original studies, as previously reported for reporter cell line generation using CRISPR/Cas9.

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The clustered regularly interspaced short palindromic repeat/Cas (CRISPR/Cas) system is a powerful tool for nucleic acid detection owing to specific recognition as well as cis- and trans-cleavage capabilities. However, the sensitivity of CRISPR/Cas-based diagnostic approaches is determined by nucleic acid preamplification, which has several limitations. Here, we present a method for direct nucleic acid detection without preamplification, by combining the CRISPR/Cas12a system with signal enhancement based on light-up RNA aptamer transcription. We first designed two DNA templates to transcribe the light-up RNA aptamer and kleptamer (Kb) RNA: the first DNA template encodes a Broccoli RNA aptamer for fluorescence signal generation, and the Kb DNA template comprises a dsDNA T7 promoter sequence and an ssDNA sequence that encodes an antisense strand for the Broccoli RNA aptamer. Hepatitis B virus (HBV) target recognition activates a CRISPR/Cas12a complex, leading to the catalytic cleavage of the ssDNA sequence. Transcription of the added Broccoli DNA template can then produce several Broccoli RNA aptamer transcripts for fluorescence enhancement. The proposed strategy exhibited excellent sensitivity and specificity with 22.4 fM detection limit, good accuracy, and stability for determining the target HBV dsDNA in human serum samples. Overall, this newly designed signal enhancement strategy can be employed as a universal sensing platform for ultrasensitive nucleic acid detection.

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BACKGROUND & AIMS: Chronic HCV infection results in abnormal immunological alterations, which are not fully normalized after viral elimination by direct-acting antiviral (DAA) treatment. Herein, we longitudinally examined phenotypic, transcriptomic, and epigenetic alterations in peripheral blood regulatory T (Treg) cells from patients with chronic HCV infection before, during, and after DAA treatment. METHODS: Patients with chronic genotype 1b HCV infection who achieved sustained virologic response by DAA treatment and age-matched healthy donors were recruited. Phenotypic characteristics of Treg cells were investigated through flow cytometry analysis. Moreover, the transcriptomic and epigenetic landscapes of Treg cells were analyzed using RNA sequencing and ATAC-seq (assay for transposase-accessible chromatin with sequencing) analysis. RESULTS: The Treg cell population - especially the activated Treg cell subpopulation - was expanded in peripheral blood during chronic HCV infection, and this expansion was sustained even after viral clearance. RNA sequencing analysis revealed that viral clearance did not abrogate the inflammatory features of these Treg cells, such as Treg activation and TNF signaling. Moreover, ATAC-seq analysis showed inflammatory imprinting in the epigenetic landscape of Treg cells from patients, which remained after treatment. These findings were further confirmed by intracellular cytokine staining, demonstrating that Treg cells exhibited inflammatory features and TNF production in chronic HCV infection that were maintained after viral clearance. CONCLUSIONS: Overall, our results showed that during chronic HCV infection, the expanded Treg cell population acquired inflammatory features at phenotypic, transcriptomic, and epigenetic levels, which were maintained even after successful viral elimination by DAA treatment. Further studies are warranted to examine the clinical significance of sustained inflammatory features in the Treg cell population after recovery from chronic HCV infection. IMPACT AND IMPLICATIONS: During chronic HCV infection, several immune components are altered both quantitatively and qualitatively. The recent introduction of direct-acting antivirals has led to high cure rates. Nevertheless, we have demonstrated that inflammatory features of Treg cells are maintained at phenotypic, transcriptomic, and epigenetic levels even after successful DAA treatment. Further in-depth studies are required to investigate the long-term clinical outcomes of patients who have recovered from chronic HCV infection.

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RATIONALE AND OBJECTIVES: To assess a deep learning application (DLA) for acute ischemic stroke (AIS) detection on brain magnetic resonance imaging (MRI) in the emergency room (ER) and the effect of T2-weighted imaging (T2WI) on its performance. MATERIALS AND METHODS: We retrospectively analyzed brain MRIs taken through the ER from March to October 2021 that included diffusion-weighted imaging (DWI) and fluid-attenuated inversion recovery (FLAIR) sequences. MRIs were processed by the DLA, and sensitivity, specificity, accuracy, and area under the receiver operating characteristic curve (AUROC) were evaluated, with three neuroradiologists establishing the gold standard for detection performance. In addition, we examined the impact of axial T2WI, when available, on the accuracy and processing time of DLA. RESULTS: The study included 947 individuals (mean age ± standard deviation, 64 years ± 16; 461 men, 486 women), with 239 (25%) positive for AIS. The overall performance of DLA was as follows: sensitivity, 90%; specificity, 89%; accuracy, 89%; and AUROC, 0.95. The average processing time was 24 s. In the subgroup with T2WI, T2WI did not significantly impact MRI assessments but did result in longer processing times (35 s without T2WI compared to 48 s with T2WI, p < 0.001). CONCLUSION: The DLA successfully identified AIS in the ER setting with an average processing time of 24 s. The absence of performance acquire with axial T2WI suggests that the DLA can diagnose AIS with just axial DWI and FLAIR sequences, potentially shortening the exam duration in the ER.

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BACKGROUND: Ebola virus disease (EVD) survivors experience ocular sequelae including retinal lesions, cataracts, and vision loss. While monoclonal antibodies targeting the Ebola virus glycoprotein (EBOV-GP) have shown promise in improving prognosis, their effectiveness in mitigating ocular sequelae remains uncertain. METHODS: We developed and characterized a BSL-2-compatible immunocompetent mouse model to evaluate therapeutics targeting EBOV-GP by inoculating neonatal mice with vesicular stomatitis virus expressing EBOV-GP (VSV-EBOV). To examine the impact of anti-EBOV-GP antibody treatment on acute retinitis and ocular sequelae, VSV-EBOV-infected mice were treated with polyclonal antibodies or monoclonal antibody preparations with antibody-dependent cellular cytotoxicity (ADCC-mAb) or neutralizing activity (NEUT-mAb). FINDINGS: Treatment with all anti-EBOV-GP antibodies tested dramatically reduced viremia and improved survival. Further, all treatments reduced the incidence of cataracts. However, NEUT-mAb alone or in combination with ADCC-mAb reduced viral load in the eyes, downregulated the ocular immune and inflammatory responses, and minimized retinal damage more effectively. INTERPRETATION: Anti-EBOV-GP antibodies can improve survival among EVD patients, but improved therapeutics are needed to reduce life altering sequelae. This animal model offers a new platform to examine the acute and long-term effect of the virus in the eye and the relative impact of therapeutic candidates targeting EBOV-GP. Results indicate that even antibodies that improve systemic viral clearance and survival can differ in their capacity to reduce acute ocular inflammation, and long-term retinal pathology and corneal degeneration. FUNDING: This study was partly supported by Postgraduate Research Fellowship Awards from ORISE through an interagency agreement between the US DOE and the US FDA.

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Two-dimensional (2D) materials have emerged as promising building blocks for next generation memristive devices, owing to their unique electronic, mechanical, and thermal properties, resulting in effective switching mechanisms for charge transport. Memristors are key components in a wide range of applications including neuromorphic computing, which is becoming increasingly important in artificial intelligence applications. Crossbar arrays are an important component in the development of hardware-based neural networks composed of 2D materials. In this paper, we summarize the current state of research on 2D material-based memristive devices utilizing different switching mechanisms, along with the application of these devices in neuromorphic crossbar arrays. Additionally, we discuss the challenges and future directions for the field.

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Acute necrotizing encephalopathy (ANE) is a rare immune-mediated complication of a viral infection commonly involving the bilateral thalamus and has been reported mainly in children. Here, we describe the MRI findings of coronavirus disease 2019 (COVID-19)-associated ANE in two pediatric patients, including a 7-year-old girl with fever and mental change, and a 6-year-old girl with fever and generalized seizures. Brain MRI revealed symmetrical T2 fluid attenuated inversion recovery high-signal intensity lesions in the bilateral thalamus with central hemorrhage. In one patient, the thalamic lesions showed a trilaminar pattern on the apparent diffusion coefficient map. This report emphasizes the importance of creating awareness regarding these findings in patients with COVID-19, particularly in children with severe neurological symptoms. Furthermore, it provides a literature review of several documented cases of COVID-19 presenting with bilateral thalamic hemorrhagic necrosis, suggesting a diagnosis of ANE.