Can Large Language Models (LLMs) Predict the Appropriate Treatment of Acute Hip Fractures in Older Adults? Comparing Appropriate Use Criteria With Recommendations From ChatGPT.

BACKGROUND: Acute hip fractures are a public health problem affecting primarily older adults. Chat Generative Pretrained Transformer may be useful in providing appropriate clinical recommendations for beneficial treatment. OBJECTIVE: To evaluate the accuracy of Chat Generative Pretrained Transformer (ChatGPT)-4.0 by comparing its appropriateness scores for acute hip fractures with the American Academy of Orthopaedic Surgeons (AAOS) Appropriate Use Criteria given 30 patient scenarios. "Appropriateness" indicates the unexpected health benefits of treatment exceed the expected negative consequences by a wide margin. METHODS: Using the AAOS Appropriate Use Criteria as the benchmark, numerical scores from 1 to 9 assessed appropriateness. For each patient scenario, ChatGPT-4.0 was asked to assign an appropriate score for six treatments to manage acute hip fractures. RESULTS: Thirty patient scenarios were evaluated for 180 paired scores. Comparing ChatGPT-4.0 with AAOS scores, there was a positive correlation for multiple cannulated screw fixation, total hip arthroplasty, hemiarthroplasty, and long cephalomedullary nails. Statistically significant differences were observed only between scores for long cephalomedullary nails. CONCLUSION: ChatGPT-4.0 scores were not concordant with AAOS scores, overestimating the appropriateness of total hip arthroplasty, hemiarthroplasty, and long cephalomedullary nails, and underestimating the other three. ChatGPT-4.0 was inadequate in selecting an appropriate treatment deemed acceptable, most reasonable, and most likely to improve patient outcomes.

Synthesis and Evaluation of Chloride-Substituted Ramalin Derivatives for Alzheimer's Disease Treatment.

Alzheimer's disease (AD) is a progressive neurodegenerative disorder marked by the accumulation of amyloid-beta plaques and hyperphosphorylated tau proteins, leading to cognitive decline and neuronal death. However, despite extensive research, there are still no effective treatments for this condition. In this study, a series of chloride-substituted Ramalin derivatives is synthesized to optimize their antioxidant, anti-inflammatory, and their potential to target key pathological features of Alzheimer's disease. The effect of the chloride position on these properties is investigated, specifically examining the potential of these derivatives to inhibit tau aggregation and beta-site amyloid precursor protein cleaving enzyme 1 (BACE-1) activity. Our findings demonstrate that several derivatives, particularly RA-3Cl, RA-4Cl, RA-26Cl, RA-34Cl, and RA-35Cl, significantly inhibit tau aggregation with inhibition rates of approximately 50%. For BACE-1 inhibition, Ramalin and RA-4Cl also significantly decrease BACE-1 expression in N2a cells by 40% and 38%, respectively, while RA-23Cl and RA-24Cl showed inhibition rates of 30% and 35% in SH-SY5Y cells. These results suggest that chloride-substituted Ramalin derivatives possess promising multifunctional properties for AD treatment, warranting further investigation and optimization for clinical applications.

Genome to phenome Association for Pork Belly Parameters Elucidates Three Regulation Distinctions: Adipogenesis, muscle formation, and their transcription factors.

Genome to phenome analysis is necessary in livestock areas because of its various and complex phenotypes. Pork belly is a favorable part of meat worldwide, including East Asia. A previous study has suggested that the three key transcription factors (ZNF444, NFYA and PPARG) affecting pork belly traits include total volume, the volume of total fat and muscle, and component muscles of the corresponding slice. However, other transcription factor genes affecting each slice other than pork belly component traits still needed to be identified. Thus, we aimed to analyze pork belly components at the genome to phenome level for identifying key transcription factor genes and their co-associated networks. The range of node numbers against each component trait via the association weight matrix was from 598 to 3020. Premised on the result, an in silico functional approach was performed. Each co-association network enriched three key transcription factors in adipogenesis and skeletal muscle proliferation, mesoderm development, metabolism, and gene transcription. The three key transcription factors and their related genes may be useful in comprehending their effect of pork belly construction.

Long-term liver-related outcomes and liver stiffness progression of statin usage in steatotic liver disease.

BACKGROUND: Statins have multiple benefits in patients with metabolic-associated steatotic liver disease (MASLD). AIM: To explore the effects of statins on the long-term risk of all-cause mortality, liver-related clinical events (LREs) and liver stiffness progression in patients with MASLD. METHODS: This cohort study collected data on patients with MASLD undergoing at least two vibration-controlled transient elastography examinations at 16 tertiary referral centres. Cox regression analysis was performed to examine the association between statin usage and long-term risk of all-cause mortality and LREs stratified by compensated advanced chronic liver disease (cACLD): baseline liver stiffness measurement (LSM) of ≥10 kPa. Liver stiffness progression was defined as an LSM increase of ≥20% for cACLD and from <10 kPa to ≥10 or LSM for non-cACLD. Liver stiffness regression was defined as LSM reduction from ≥10 kPa to <10 or LSM decrease of ≥20% for cACLD. RESULTS: We followed up 7988 patients with baseline LSM 5.9 kPa (IQR 4.6-8.2) for a median of 4.6 years. At baseline, 40.5% of patients used statins, and cACLD was present in 17%. Statin usage was significantly associated with a lower risk of all-cause mortality (adjusted HR=0.233; 95% CI 0.127 to 0.426) and LREs (adjusted HR=0.380; 95% CI 0.268 to 0.539). Statin usage was also associated with lower liver stiffness progression rates in cACLD (HR=0.542; 95% CI 0.389 to 0.755) and non-cACLD (adjusted HR=0.450; 95% CI 0.342 to 0.592), but not with liver stiffness regression (adjusted HR=0.914; 95% CI 0.778 to 1.074). CONCLUSIONS: Statin usage was associated with a relatively lower long-term risk of all-cause mortality, LREs and liver stiffness progression in patients with MASLD.

Bibliometric Patent Review of Minimally Invasive Spine Surgery.

STUDY DESIGN: This study analyzes patents associated with minimally invasive spine surgery (MISS) found on the Lens open online platform. OBJECTIVE: The goal of this research was to provide an overview of the most referenced patents in the field of MISS and to uncover patterns in the evolution and categorization of these patents. SUMMARY OF BACKGROUND DATA: MISS has rapidly progressed, with a core focus on minimizing surgical damage, preserving the natural anatomy, and enabling swift recovery, all while achieving outcomes that rival traditional open surgery. While prior studies have primarily concentrated on MISS outcomes, the analysis of MISS patents has been limited. METHODS: To conduct this study, we used the Lens platform to search for patents that included the terms "minimally invasive" and "spine" in their titles, abstracts, or claims. We then categorized these patents and identified the top 100 with the most forward citations. We further classified these patents into 4 categories: Spinal Stabilization Systems, Joint Implants or Procedures, Screw Delivery System or Method, and Access and Surgical Pathway Formation. RESULTS: Five hundred two MISS patents were identified initially, and 276 were retained following a screening process. Among the top 100 patents, the majority had active legal status. The largest category within the top 100 patents was Access and Surgical Pathway Formation, closely followed by Spinal Stabilization Systems and Joint Implants or Procedures. The smallest category was Screw Delivery System or Method. Notably, the majority of the top 100 patents had priority years falling between 2000 and 2009, indicating a moderate positive correlation between patent rank and priority year. CONCLUSIONS: Thus far, patents related to Access and Surgical Pathway Formation have laid the foundation for subsequent innovations in Spinal Stabilization Systems and Screw Technology. This study serves as a valuable resource for guiding future innovations in this rapidly evolving field.

Comparison of wrist range of motion and muscle strength in assembly workers with and without lateral epicondylitis.

BACKGROUND: Lateral epicondylitis (LE), also called tennis elbow, is a common musculoskeletal disorder that causes pain in the elbow area and is highly prevalent in assembly workers who repeatedly move their wrists. OBJECTIVE: The purpose of this study was to compare the wrist ROM and muscle strength of assembly workers with and without LE. METHODS: Forty-five male assembly line workers (23 with LE) participated in the study. Participants had their wrist range of motion (flexion, extension, ulnar deviation, and radial deviation) and strength (wrist flexors, extensors, and hand grip) measured using Smart KEMA sensors. RESULTS: Workers with LE showed significantly reduced wrist extension and radial deviation ROM compared to workers without LE, with no significant differences in wrist flexion and ulnar deviation ROM between groups. Workers with LE had significantly lower wrist extensor strength compared to workers without LE, and there was no significant difference in wrist flexor and grip strength between the two groups. CONCLUSIONS: For workers with LE, the difference in wrist ROM and muscle strength will be useful for planning intervention and evaluating treatment outcomes for assembly workers with LE.

Electrochemically Active MoO3/TiN Sulfur Host Inducing Dynamically Reinforced Built-in Electric Field for Advanced Lithium-Sulfur Batteries.

Although various electrocatalysts have been developed to ameliorate the shuttle effect and sluggish Li-S conversion kinetics, their electrochemical inertness limits the sufficient performance improvement of lithium-sulfur batteries (LSBs). In this work, an electrochemically active MoO3/TiN-based heterostructure (MOTN) is designed as an efficient sulfur host that can improve the overall electrochemical properties of LSBs via prominent lithiation behaviors. By accommodating Li ions into MoO3 nanoplates, the MOTN host can contribute its own capacity. Furthermore, the Li intercalation process dynamically affects the electronic interaction between MoO3 and TiN and thus significantly reinforces the built-in electric field, which further improves the comprehensive electrocatalytic abilities of the MOTN host. Because of these merits, the MOTN host-based sulfur cathode delivers an exceptional specific capacity of 2520 mA h g-1 at 0.1 C. Furthermore, the cathode exhibits superior rate capability (564 mA h g-1 at 5 C), excellent cycling stability (capacity fade rate of 0.034% per cycle for 1200 cycles at 2 C), and satisfactory areal capacity (6.6 mA h cm-2) under a high sulfur loading of 8.3 mg cm-2. This study provides a novel strategy to develop electrochemically active heterostructured electrocatalysts and rationally manipulate the built-in electric field for achieving high-performance LSBs.

Hyposalinity elicits physiological responses and alters intestinal microbiota in Korean rockfish Sebastes schlegelii.

Global warming significantly impacts aquatic ecosystems, with changes in the salt environment negatively affecting the physiological responses of fish. We investigated the impact of hyposalinity on the physiological responses and intestinal microbiota of Sebastes schlegelii under the context of increased freshwater influx due to climate change. We focused on the osmoregulatory capacity, oxidative stress responses, and alterations in the intestinal microbiome of S. schlegelii under low-salinity conditions. Our findings revealed compromised osmoregulatory capacity in S. schlegelii under low-salinity conditions, accompanied by the activation of oxidative stress responses, indicating physiological adaptations to cope with environmental stress. Specifically, changes in Na+/K+-ATPase (NKA) activity in gill tissues were associated with decreased osmoregulatory capacity. Furthermore, the analysis of the intestinal microbiome led to significant changes in microbial diversity. Exposure to low-salinity environments led to dysbiosis, with notable decreases in the relative abundance of Gammaproteobacteria at the class level and specific genera such as Enterovibrio, and Photobacterium. Conversely, Bacilli classes, along with genera like Mycoplasma, exhibited increased proportions in fish exposed to low-salinity conditions. These findings underscore the potential impact of environmental salinity changes on the adaptive capacity of fish species, particularly in the context of aquaculture. Moreover, they highlight the importance of considering both physiological and microbial responses in understanding the resilience of aquatic organisms to environmental stress. Additionally, they highlight the importance of intestinal microbiota analyses in understanding the immune system and disease management in fish.

Synergistic effect of SARS-CoV-2 infection and COVID-19 vaccination on the risk of venous thromboembolism.

BACKGROUND: Previous studies have reported a greater risk of venous thromboembolism among patients infected with SARS-CoV-2 and those who received COVID-19 vaccination. Nevertheless, there is a lack of understanding regarding the interaction effect on the risk of venous thromboembolism occurrence between SARS-CoV-2 infection and COVID-19 vaccination. METHODS: This was a retrospective cohort study including adult patients with confirmed SARS-CoV-2 infection between October 2020 and September 2021. Patients with confirmed SARS-CoV-2 infection were selected and matched 1:1 by age and sex with individuals who were not infected during the same period. A Cox proportional hazards model was used to analyze the venous thromboembolism risk. RESULTS: The study included 422546 individuals who were divided into four groups; the interaction group defined by having SARS-CoV-2 infection within 90 days following COVID-19 vaccination, the infection group defined by no vaccination before 90 days of SARS-CoV-2 infection, the vaccination group defined by COVID-19 vaccination without SARS-CoV-2 infection, and the reference group defined by neither COVID-19 vaccination nor SARS-CoV-2 infection. The results showed that the adjusted hazard ratio (aHR) of the interaction group was 29.71 (95% confidence interval [CI], 22.95-38.47), while the aHRs of the infection group and the vaccination group were 6.66 (95% CI, 5.18-8.58) and 2.31 (95% CI, 1.78-3.00), respectively. CONCLUSIONS: A synergistic effect on the risk of venous thromboembolism was suggested when individuals were infected with SARS-CoV-2 within 90 days following COVID-19 vaccination.

GCN2 is a determinant of the response to WEE1 kinase inhibition in small-cell lung cancer.

Patients with small-cell lung cancer (SCLC) are in dire need of more effective therapeutic options. Frequent disruption of the G1 checkpoint in SCLC cells creates a dependency on the G2/M checkpoint to maintain genomic integrity. Indeed, in pre-clinical models, inhibiting the G2/M checkpoint kinase WEE1 shows promise in inhibiting SCLC growth. However, toxicity and acquired resistance limit the clinical effectiveness of this strategy. Here, using CRISPR-Cas9 knockout screens in vitro and in vivo, we identified multiple factors influencing the response of SCLC cells to the WEE1 kinase inhibitor AZD1775, including the GCN2 kinase and other members of its signaling pathway. Rapid activation of GCN2 upon AZD1775 treatment triggers a stress response in SCLC cells. Pharmacological or genetic activation of the GCN2 pathway enhances cancer cell killing by AZD1775. Thus, activation of the GCN2 pathway represents a promising strategy to increase the efficacy of WEE1 inhibitors in SCLC.

Machine learning-assisted label-free colorectal cancer diagnosis using plasmonic needle-endoscopy system.

Early and accurate detection of colorectal cancer (CRC) is critical for improving patient outcomes. Existing diagnostic techniques are often invasive and carry risks of complications. Herein, we introduce a plasmonic gold nanopolyhedron (AuNH)-coated needle-based surface-enhanced Raman scattering (SERS) sensor, integrated with endoscopy, for direct mucus sampling and label-free detection of CRC. The thin and flexible stainless-steel needle is coated with polymerized dopamine, which serves as an adhesive layer and simultaneously initiates the nucleation of gold nanoparticle (AuNP) seeds on the needle surface. The AuNP seeds are further grown through a surface-directed reduction using Au ions-hydroxylamine hydrochloride solution, resulting in the formation of dense AuNHs. The formation mechanism of AuNHs and the layered structure of the plasmonic needle-based SERS (PNS) sensor are thoroughly analyzed. Furthermore, a strong field enhancement of the PNS sensor is observed, amplified around the edges of the polyhedral shapes and at nanogap sites between AuNHs. The feasibility of the PNS sensor combined with endoscopy system is further investigated using mouse models for direct colonic mucus sampling and verifying noninvasive label-free classification of CRC from normal controls. A logistic regression-based machine learning method is employed and successfully differentiates CRC and normal mice, achieving 100% sensitivity, 93.33% specificity, and 96.67% accuracy. Moreover, Raman profiling of metabolites and their correlations with Raman signals of mucus samples are analyzed using the Pearson correlation coefficient, offering insights for identifying potential cancer biomarkers. The developed PNS-assisted endoscopy technology is expected to advance the early screening and diagnosis approach of CRC in the future.

Pore-Free Single-Crystalline Particles for Durable Na-Ion Battery Cathodes.

The O3-type Na[Ni1-x-yCoxMny]O2 cathodes have received significant attention in sodium-ion batteries (SIBs) due to their high energy density. However, challenges such as structural instability and interfacial instability against an electrolyte solution limit their practical use in SIBs. In this study, the single-crystalline O3-type Na[Ni0.6Co0.2Mn0.2]O2 (SC-NCM) cathode has been designed and synthesized to effectively relieve the degradation pathways of the polycrystalline O3-type Na[Ni0.6Co0.2Mn0.2]O2 (PC-NCM) cathode for SIBs. The mechanically robust SC-NCM due to the absence of pores in the particles enhances tolerance to particle cracking, resulting in stable cycling performance with a cycle retention of 73% over 350 cycles. Moreover, the proposed SC-NCM is synthesized using a simple and cost-effective molten-salt synthetic route without the complex quenching process typically associated with PC-NCM synthesis methods, showing good practical applicability. This study will provide an innovative direction for the development of advanced cathode materials for practical SIBs.

Comparison of Midterm Outcomes between All-Inside Arthroscopic and Open Modified Broström Procedures as Treatment for Chronic Ankle Instability.

Background: Although the all-inside arthroscopic modified Broström operation (AMBO) and open modified Broström operation (OMBO) for chronic lateral ankle instability (CLAI) showed favorable outcomes up to 1-year short-term follow-up, concerns about the long-term stability of AMBO are still present. Therefore, we aimed to compare midterm outcomes between the 2 methods by extending the observation period. Methods: Fifty-four patients undergoing ankle surgery between August 2013 and July 2017 were included in the AMBO (n = 37) and OMBO (n = 17) groups. The American Orthopaedic Foot and Ankle Society (AOFAS) ankle-hindfoot scale and a visual analog scale (VAS) were used to evaluate the clinical outcomes. Anterior drawer test and talar tilt angle were used to evaluate the radiological outcomes. The mean follow-up duration was 59.69 months. Results: The 2 groups both showed improved clinical and radiological results statistically. In addition, they did not differ in age, sex, or preoperative AOFAS ankle-hindfoot scale score, VAS score, anterior drawer test, or talar tilt angle. No significant difference in the final follow-up postoperative clinical scores or radiological outcomes was observed. Conclusions: AMBO and OMBO as treatments for CLAI did not yield differing clinical or radiological outcomes at a mean follow-up time point of 59.69 months.

Quantitative proteomics and immunohistochemistry uncover NT5DC2 as a diagnostic biomarker for papillary urothelial carcinoma.

The accurate diagnosis of papillary urothelial carcinoma (PUC) is frequently challenging due to benign mimickers. Other than morphology-based diagnostic criteria, reliable biomarkers for differentiating benign and malignant papillary urothelial neoplasms remain elusive, so we sought to discover new markers to address this challenge. We first performed tandem mass spectrometry-based quantitative proteomics using diverse papillary urothelial lesions, including PUC, urothelial papilloma (UP), inverted urothelial papilloma, and cystitis cystica. We prioritized potential diagnostic biomarkers using machine learning, and subsequently validated through immunohistochemistry (IHC) in two independent cohorts. Metabolism, transport, cell cycle, development, and immune response functions were differentially enriched between malignant and benign papillary neoplasms. RhoB and NT5DC2 were shortlisted as optimal candidate markers for PUC diagnosis. In our pilot study using IHC, NT5DC2 was subsequently selected as its expression consistently differed in PUC (p = 0.007). Further validation of NT5DC2 using 49 low-grade (LG) urothelial lesions, including 15 LG-PUCs and 17 UPs, which are the most common mimickers, concordantly revealed lower IHC expression levels in LG-PUC (p = 0.0298). Independent external validation with eight LG-PUCs and eight UPs confirmed the significant downregulation of NT5DC2 in LG-PUC (p = 0.0104). We suggest that NT5DC2 is a potential IHC biomarker for differentiating LG-PUC from its benign mimickers, especially UP.

Proton-Coupled Electron Transfer on Cu2O/Ti3C2Tx MXene for Propane (C3H8) Synthesis from Electrochemical CO2 Reduction.

Electrochemical CO2 reduction reaction (CO2RR) to produce value-added multi-carbon chemicals has been an appealing approach to achieving environmentally friendly carbon neutrality in recent years. Despite extensive research focusing on the use of CO2 to produce high-value chemicals like high-energy-density hydrocarbons, there have been few reports on the production of propane (C3H8), which requires carbon chain elongation and protonation. A rationally designed 0D/2D hybrid Cu2O anchored-Ti3C2Tx MXene catalyst (Cu2O/MXene) is demonstrated with efficient CO2RR activity in an aqueous electrolyte to produce C3H8. As a result, a significantly high Faradaic efficiency (FE) of 3.3% is achieved for the synthesis of C3H8 via the CO2RR with Cu2O/MXene, which is ≈26 times higher than that of Cu/MXene prepared by the same hydrothermal process without NH4OH solution. Based on in-situ attenuated total reflection-Fourier transform infrared spectroscopy (ATR-FTIR) and density functional theory (DFT) calculations, it is proposed that the significant electrocatalytic conversion originated from the synergistic behavior of the Cu2O nanoparticles, which bound the *C2 intermediates, and the MXene that bound the *CO coupling to the C3 intermediate. The results disclose that the rationally designed MXene-based hybrid catalyst facilitates multi-carbon coupling as well as protonation, thereby manipulating the CO2RR pathway.

Identification of interactions between genetic risk scores and dietary patterns for personalized prevention of kidney dysfunction in a population-based cohort.

BACKGROUND & AIM: Chronic kidney disease (CKD) is a heterogeneous disorder that affects the kidney structure and function. This study investigated the effect of the interaction between genetic factors and dietary pattern on kidney dysfunction in Korean adults. METHODS: Baseline data were obtained from the Ansan and Ansung Study of the Korean Genome and Epidemiology Study involving 8230 participants aged 40-69 years. Kidney dysfunction was defined as an estimated glomerular filtration rate < 90 mL/minute/1.73 m2. Genomic DNAs genotyped on the Affymetrix® Genome-Wide Human SNP array 5.0 were isolated from peripheral blood. A genome-wide association study using a generalized linear model was performed on 1,590,162 single-nucleotide polymorphisms (SNPs). To select significant SNPs, the threshold criterion was set at P-value < 5 × 10-8. Linkage disequilibrium clumping was performed based on the R2 value, and 94 SNPs had a significant effect. Participants were divided into two groups based on their generic risk score (GRS): the low-GR group had GRS > 0, while the high-GR group had GRS ≤ 0. RESULTS: Three distinct dietary patterns were extracted, namely, the "prudent pattern," "flour-based and animal food pattern," and "white rice pattern," to analyze the effect of dietary pattern on kidney function. In the "flour-based and animal food pattern," higher pattern scores were associated with a higher prevalence of kidney dysfunction in both the low and high GR groups (P for trend < 0.0001 in the low-, high-GR groups of model 1; 0.0050 and 0.0065 in the low-, high-GR groups of model 2, respectively). CONCLUSIONS: The results highlight a significant association between the 'flour-based and animal food pattern' and higher kidney dysfunction prevalence in individuals with both low and high GR. These findings suggest that personalized nutritional interventions based on GR profiles may become the basis for presenting GR-based individual dietary patterns for kidney dysfunction.

Effects of structural variation in electrospray systems on spray characteristics.

Electrospraying is a method of atomizing fluids using a high voltage potential difference. Since the atomization of electrostatic atomization does not directly charge the nozzle but only uses the potential difference, various equipment structures are possible. In the case of this study, 12 different equipment structures of nozzle, ring electrode, and substrate were configured, and data on atomization characteristics of electrospray, such as spray modes applied voltage, coating area, coating current, spray velocity, and factors used in industrial processes, were verified. Data are provided for the generation process using uniform and continuous electrospray.

Engineered exosomes with a photoinducible protein delivery system enable CRISPR-Cas-based epigenome editing in Alzheimer's disease.

Effective intracellular delivery of therapeutic proteins can potentially treat a wide array of diseases. However, efficient delivery of functional proteins across the cell membrane remains challenging. Exosomes are nanosized vesicles naturally secreted by various types of cells and may serve as promising nanocarriers for therapeutic biomolecules. Here, we engineered exosomes equipped with a photoinducible cargo protein release system, termed mMaple3-mediated protein loading into and release from exosome (MAPLEX), in which cargo proteins can be loaded into the exosomes by fusing them with photocleavable protein (mMaple3)-conjugated exosomal membrane markers and subsequently released from the exosomal membrane by inducing photocleavage with blue light illumination. Using this system, we first induced transcriptional regulation by delivering octamer-binding transcription factor 4 and SRY-box transcription factor 2 to fibroblasts in vitro. Second, we induced in vivo gene recombination in Cre reporter mice by delivering Cre recombinase. Last, we achieved targeted epigenome editing in the brains of 5xFAD and 3xTg-AD mice, two models of Alzheimer's disease. Administration of MAPLEXs loaded with ß-site amyloid precursor protein cleaving enzyme 1 (Bace1)-targeting single guide RNA-incorporated dCas9 ribonucleoprotein complexes, coupled with the catalytic domain of DNA methyltransferase 3A, resulted in successful methylation of the targeted CpG sites within the Bace1 promoter. This approach led to a significant reduction in Bace1 expression, improved recognition memory impairment, and reduced amyloid pathology in 5xFAD and 3xTg-AD mice. These results suggest that MAPLEX is an efficient intracellular protein delivery system that can deliver diverse therapeutic proteins for multiple diseases.

Deep Network Regularization for Phase-based Magnetic Resonance Electrical Properties Tomography with Stein's Unbiased Risk Estimator.

Magnetic resonance imaging (MRI) can extract the tissue conductivity values from in vivo data using the so-called phase-based magnetic resonance electrical properties tomography (MR-EPT). However, this procedure suffers from noise amplification caused by the use of the Laplacian operator. To counter this issue, we propose a novel preprocessing denoiser for magnetic resonance transceive phase images, operating in an unsupervised manner. Inspired by the deep image prior approach, we apply the random initialization of a convolutional neural network, which enforces an implicit regularization. Additionally, we introduce Stein's unbiased risk estimator, which is the unbiased estimator of the mean square error for optimizing the network without the need for label images. This modification not only tackles the overfitting problem inherent in the deep image prior approach but also operates within a purely unsupervised framework. In addition, instead of using phase images, we use real and imaginary images, which aligns with the theoretical model of the risk estimator. Our generative model needs neither the preparation of training datasets nor prior training procedure, and it maintains adaptability across various resolutions and signal-to-noise ratio levels. In testing. our method significantly diminished residual error remaining in phase maps, quantitatively as well as qualitatively, for both phantom and simulated brain data. Furthermore, it outperformed other denoising methods in reducing noise amplification and boundary error. When applied to healthy volunteer and patient data, the proposed method revealed reduced error in the reconstructed conductivity maps, with conductivity values aligning well with established literature values. To the best of our knowledge, this is the first blind approach using a purely unsupervised denoising framework that can implement a 2D phase-based MR-EPT reconstruction algorithm. The source code is available at https://github.com/Yonsei-MILab/Implicit-Regularization-forMREPT-with-SURE.