Comparison of Small (70-150 µm) and Intermediate (100-300 µm) Size Drug-Eluting Embolics for Transarterial Chemoembolization of Small Hepatocellular Carcinomas (≤3 cm).

PURPOSE: To compare oncologic outcomes of transarterial chemoembolization (TACE) using 70-150 µm and 100-300 µm drug-eluting beads (DEBs) to treat small hepatocellular carcinoma (HCC). METHODS: This retrospective study included 93 patients with small HCC (≤3cm) who underwent first TACE with DEB: 43 with 70-150 µm DEBs and 50 with 100-300 µm DEBs. Initial tumor response was assessed using per-patient and per-lesion analysis. Progression-free survival (PFS) and target tumor PFS were analyzed for patients and lesions with initial complete response (CR). Overall survival (OS) and safety outcomes were also evaluated. RESULTS: At 1 month, initial CR rates were 72.1% in the 70-150 µm group and 70.0% in the 100-300 µm group. PFS was significantly longer in the 70-150 µm group (median, 26 months) compared with the 100-300 µm group (median, 11 months; log-rank p=0.049), with comparable OS results (p=0.096). Per-lesion analysis found that target tumor PFS was significantly longer in the 70-150 µm group (median, 30 months) compared with the 100-300 µm group (median, 13 months; p=0.009). Subgroup analysis revealed the 70-150 µm group had significantly longer target tumor PFS compared with the 100-300 µm group in the 1.0-2.0 cm subgroup (p=0.017), but not in the 2.1-3.0 cm subgroup (p=0.117). No significant differences in adverse events were observed between the two groups. CONCLUSION: The 70-150 µm and 100-300 µm DEB-TACE resulted in comparable tumor response and short-term safety in small HCCs (≤3cm). However, in cases where CR was achieved, treatment with smaller beads demonstrated longer PFS and target tumor PFS.

Preclinical Evidence and Underlying Mechanisms of Polygonum multiflorum and Its Chemical Constituents Against Cognitive Impairments and Alzheimer's Disease.

Objectives: Cognitive impairments, ranging from mild to severe, adversely affect daily functioning, quality of life, and work capacity. Despite significant efforts in the past decade, more than 200 promising drug candidates have failed in clinical trials. Herbal remedies are gaining interest as potential treatments for dementia due to their long history and safety, making them valuable for drug development. This review aimed to examine the mechanisms behind the effect of Polygonum multiflorum on cognitive function. Methods: This study focused primarily on the effects of Polygonum multiflorum and its chemical constituents on cognitive behavioral outcomes including the Morris water maze, the passive avoidance test, and the Y maze, as well as pathogenic targets of cognitive impairment and Alzheimer's disease (AD) like amyloid deposition, amyloid precursor protein, tau hyperphosphorylation, and cognitive decline. Additionally, a thorough evaluation of the mechanisms behind Polygonum multiflorum's impact on cognitive function was conducted. We reviewed the most recent data from preclinical research done on experimental models, particularly looking at Polygonum multiflorum's effects on cognitive decline and AD. Results: According to recent research, Poligonum multiflorum and its bioactive components, stilbene, and emodin, influence cognitive behavioral results and regulate the pathological target of cognitive impairment and AD. Their mechanisms of action include reducing oxidative and mitochondrial damage, regulating neuroinflammation, halting apoptosis, and promoting increased neurogenesis and synaptogenesis. Conclusion: This review serves as a comprehensive compilation of current experiments on AD and other cognitive impairment models related to the therapeutic effects of Polygonum multiflorum. We believe that these findings can serve as a basis for future clinical trials and have potential applications in the treatment of human neurological disorders.

Transcriptome Analysis of the Striatum of Electroacupuncture-treated Naïve and Ischemic Stroke Mice.

Objectives: Electroacupuncture (EA) has been demonstrated to aid stroke recovery. However, few investigations have focused on identifying the potent molecular targets of EA by comparing EA stimulation between naïve and disease models. Therefore, this study was undertaken to identify the potent molecular therapeutic mechanisms underlying EA stimulation in ischemic stroke through a comparison of mRNA sequencing data obtained from EA-treated naïve control and ischemic stroke mouse models. Methods: Using both naïve control and middle cerebral artery occlusion (MCAO) mouse models, EA stimulation was administered at two acupoints, Baihui (GV20) and Dazhui (GV14), at a frequency of 2 Hz. Comprehensive assessments were conducted, including behavioral evaluations, RNA sequencing to identify differentially expressed genes (DEGs), functional enrichment analysis, protein-protein interaction (PPI) network analysis, and quantitative real-time PCR. Results: EA stimulation ameliorated the ischemic insult-induced motor dysfunction in mice with ischemic stroke. Comparative analysis between control vs. MCAO, control vs. control + EA, and MCAO vs. MCAO + EA revealed 4,407, 101, and 82 DEGs, respectively. Of these, 30, 7, and 1 were common across the respective groups. Gene Ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway analyses revealed upregulated DEGs associated with the regulation of inflammatory immune response in the MCAO vs. MCAO + EA comparison. Conversely, downregulated DEGs in the control vs. control + EA comparison were linked to neuronal development. PPI analysis revealed major clustering related to the regulation of cytokines, such as Cxcl9, Pcp2, Ccl11, and Cxcl13, in the common DEGs of MCAO vs. MCAO + EA, with Esp8l1 identified as the only common downregulated DEG in both EA-treated naïve and ischemic models. Conclusion: These findings underscore the diverse potent mechanisms of EA stimulation between naïve and ischemic stroke mice, albeit with few overlaps. However, the potent mechanisms underlying EA treatment in ischemic stroke models were associated with the regulation of inflammatory processes involving cytokines.

Does prior rotator cuff surgery influence the outcomes and complications after reverse total shoulder arthroplasty in patients with cuff tear arthropathy or massive rotator cuff tear? A propensity score-matched study.

BACKGROUND: The aim of this study was to compare outcomes and complications in patients with and without a history of prior rotator cuff surgery who underwent reverse total shoulder arthroplasty (RTSA). METHODS: Two-hundred and nine consecutive patients who had undergone RTSA for rotator cuff insufficiency with a minimum 12-months follow-up period were reviewed. A total of 35 patients with a history of prior rotator cuff surgery were made the study group (PS group). Using propensity score matching for age and sex, these patients were matched 1:3 with a control group of 105 patients with no history of prior surgery (NPS group). The mean follow-up period was 41.4 months. RESULTS: Both groups showed a significant improvement of clinical scores and range of motion after RTSA. The PS group showed a significantly higher final visual analog scale (VAS) pain score compared with the NPS group (P = 0.020). The PS group showed a significantly higher incidence of acromial stress fracture compared with the NPS group (17.1% vs 4.8%, P = 0.018), but no significant difference in the overall complication rate was observed (25.7% vs 13.3%, P > 0.05). The PS group showed a significantly higher reoperation rate compared with the NPS group (14.3% vs 1.9%, P = 0.004). CONCLUSIONS: Our study demonstrated that a history of prior rotator cuff surgery was associated with a high incidence of acromial stress fracture and reoperation after RTSA as well as a high final VAS pain score, although satisfactory clinical outcomes after RTSA were achieved in both groups.

Compound Heterozygous Mutations of SACS in a Korean Cohort Study of Charcot-Marie-Tooth Disease Concurrent Cerebellar Ataxia and Spasticity.

Mutations in the SACS gene are associated with autosomal recessive spastic ataxia of Charlevoix-Saguenay disease (ARSACS) or complex clinical phenotypes of Charcot-Marie-Tooth disease (CMT). This study aimed to identify SACS mutations in a Korean CMT cohort with cerebellar ataxia and spasticity by whole exome sequencing (WES). As a result, eight pathogenic SACS mutations in four families were identified as the underlying causes of these complex phenotypes. The prevalence of CMT families with SACS mutations was determined to be 0.3%. All the patients showed sensory, motor, and gait disturbances with increased deep tendon reflexes. Lower limb magnetic resonance imaging (MRI) was performed in four patients and all had fatty replacements. Of note, they all had similar fatty infiltrations between the proximal and distal lower limb muscles, different from the neuromuscular imaging feature in most CMT patients without SACS mutations who had distal dominant fatty involvement. Therefore, these findings were considered a characteristic feature in CMT patients with SACS mutations. Although further studies with more cases are needed, our results highlight lower extremity MRI findings in CMT patients with SACS mutations and broaden the clinical spectrum. We suggest screening for SACS in recessive CMT patients with complex phenotypes of ataxia and spasticity.

Self-Powered Electrical Bandage Based on Body-Coupled Energy Harvesting.

Self-powered electrical bandages (SEBs), integrated with wearable energy harvesters, can provide an effective and autonomous electrical stimulation (ES) solution for rapid and scarless wound healing. A continuously operating, wireless, and applicable-to-comprehensive-wound ES device is essential for the quick restoration of wounds and convenience. This work illustrates a SEB powered by body-coupled energy harvesting. The SEB continuously treats the wound with 60-Hz sinusoidal electrical potential gained from the coupling of the human body and ambient electrical waves. It is demonstrated that enough level of electrical potential can be applied to the wound, further enhanced by strong capacitive coupling arising from the use of high-permittivity poly(vinylidene fluoride-trifluoroethylene):CaCu3Ti4O12 (P(VDF-TrFE):CCTO) nanocomposite. The potential clinical efficacy of the SEB is illustrated by preclinical analysis of human fibroblasts and mouse wound model, thus confirming the successful expedition of wound recovery. This work suggests a new class of wearable devices to provide ES events and its potential for extension to other conventional wound care materials and device technology.

Dissatisfaction-considered waiting time prediction for outpatients with interpretable machine learning.

Long waiting time in outpatient departments is a crucial factor in patient dissatisfaction. We aim to analytically interpret the waiting times predicted by machine learning models and provide patients with an explanation of the expected waiting time. Here, underestimating waiting times can cause patient dissatisfaction, so preventing this in predictive models is necessary. To address this issue, we propose a framework considering dissatisfaction for estimating the waiting time in an outpatient department. In our framework, we leverage asymmetric loss functions to ensure robustness against underestimation. We also propose a dissatisfaction-aware asymmetric error score (DAES) to determine an appropriate model by considering the trade-off between underestimation and accuracy. Finally, Shapley additive explanation (SHAP) is applied to interpret the relationship trained by the model, enabling decision makers to use this information for improving outpatient service operations. We apply our framework in the endocrinology metabolism department and neurosurgery department in one of the largest hospitals in South Korea. The use of asymmetric functions prevents underestimation in the model, and with the proposed DAES, we can strike a balance in selecting the best model. By using SHAP, we can analytically interpret the waiting time in outpatient service (e.g., the length of the queue affects the waiting time the most) and provide explanations about the expected waiting time to patients. The proposed framework aids in improving operations, considering practical application in hospitals for real-time patient notification and minimizing patient dissatisfaction. Given the significance of managing hospital operations from the perspective of patients, this work is expected to contribute to operations improvement in health service practices.

Dosing Strategy of Ramosetron to Prevent Postoperative Nausea and Vomiting and Development of Prediction Models Using Data Obtained From Randomized Controlled Trials: A Comparative Study.

PURPOSE: The study aimed to compare the postoperative nausea and vomiting (PONV) preventive effect of repeated administration of ramosetron with the standard treatment group and compare models to predict the incidence of PONV using machine-learning techniques. METHODS: A total of 261 patients scheduled for breast surgery were analyzed to evaluate the effectiveness of repeated intravenous administration of ramosetron. All patients were administered 0.3 mg ramosetron just before the end of surgery. For the repeated dose of ramosetron group, an additional dose of 0.3 mg was administered at 4, 22, and 46 hours after the end of the surgery. Postoperative nausea, vomiting, and retching were evaluated using the Rhodes Index of Nausea, Vomiting, and Retching at 6, 24, and 48 hours postoperatively. Previously published randomized controlled data were combined with the data of this study to create a new dataset of 1390 patients, and machine-learning-based PONV prediction models (classification tree, random forest, extreme gradient boosting, and neural network) was constructed and compared with the Apfel model. FINDINGS: Fifty patients (38.5%) and 60 patients (45.8%) reported nausea, vomiting, or retching 48 hours postoperatively in the standard and repeated-dose groups, respectively (P = 0.317, χ2 test). Median sensitivity, specificity, and accuracy of the Apfel model analyzed using the training set were 0.815, 0.344, and 0.495, respectively. IMPLICATIONS: The repeated administration of ramosetron did not reduce the incidence of PONV. The Apfel model had high sensitivity, however, its specificity and accuracy were lower than that in machine-learning-based models.

Ventral Anterior Cingulate Atrophy as a Predisposing Factor for Transient Global Amnesia.

Background and Purpose: This study aimed to evaluate the brain magnetic resonance imaging (MRI) of patients with acute transient global amnesia (TGA) using volumetric analysis to verify whether the brains of TGA patients have pre-existing structural abnormalities. Methods: We evaluated the brain MRI data from 87 TGA patients and 20 age- and sex-matched control subjects. We included brain MRIs obtained from TGA patients within 72 hours of symptom onset to verify the pre-existence of structural change. For voxel-based morphometric analyses, statistical parametric mapping was employed to analyze the structural differences between patients with TGA and control subjects. Results: TGA patients exhibited significant volume reductions in the bilateral ventral anterior cingulate cortices (corrected p<0.05). Conclusions: TGA patients might have pre-existing structural changes in bilateral ventral anterior cingulate cortices prior to TGA attacks.

Obesity exacerbates ischemia-reperfusion injury and senescence in murine kidneys and perirenal adipose tissues.

Background: Obesity is a major worldwide health problem and can be related to cellular senescence. Along with the rise in obesity, the comorbidity of renal ischemia-reperfusion (IR) injury is increasing. Whether obesity accelerates the severity of IR injury and whether senescence contributes to these conditions remain unclear. We studied the degree of injury and cellular senescence in the IR kidneys and perirenal adipose tissues of high-fat-diet-induced obese mice. Methods: C57BL/6 mice fed standard chow or a high-fat diet for 16 weeks were randomized to renal IR or sham group (n = 6-10 each). Renal IR was performed by unilateral clamping of the right renal pedicle for 30 minutes. Six weeks after surgery, renal function, perirenal fat/renal senescence, and histology were evaluated ex vivo. Results: Obese mice showed more renal tubular damage and fibrosis in IR injury than control mice, even though the degree of ischemic insult was comparable. Renal expression of senescence and its secretory phenotype was upregulated in either IR injury or with a high-fat diet and was further increased in the IR kidneys of obese mice. Fat senescence and the expression of tumor necrosis factor alpha were also increased, especially in the perirenal depot of the IR kidneys, with a high-fat diet. Conclusion: A high-fat diet aggravates IR injury in murine kidneys, which is associated, at least in part, with perirenal fat senescence and inflammation. These observations support the exploration of therapeutic targets of the adipo-renal axis in injured obese kidneys.

Revised evaluation objectives of the Korean Dentist Clinical Skill Test: a survey study and focus group interviews

PURPOSE: This study aimed to propose a revision of the evaluation objectives of the Korean Dentist Clinical Skill Test by analyzing the opinions of those involved in the examination after a review of those objectives. METHODS: The clinical skill test objectives were reviewed based on the national-level dental practitioner competencies, dental school educational competencies, and the third dental practitioner job analysis. Current and former examinees were surveyed about their perceptions of the evaluation objectives. The validity of 22 evaluation objectives and overlapping perceptions based on area of specialty were surveyed on a 5-point Likert scale by professors who participated in the clinical skill test and dental school faculty members. Additionally, focus group interviews were conducted with experts on the examination. RESULTS: It was necessary to consider including competency assessments for "emergency rescue skills" and "planning and performing prosthetic treatment." There were no significant differences between current and former examinees in their perceptions of the clinical skill test's objectives. The professors who participated in the examination and dental school faculty members recognized that most of the objectives were valid. However, some responses stated that "oromaxillofacial cranial nerve examination," "temporomandibular disorder palpation test," and "space management for primary and mixed dentition" were unfeasible evaluation objectives and overlapped with dental specialty areas. CONCLUSION: When revising the Korean Dentist Clinical Skill Test's objectives, it is advisable to consider incorporating competency assessments related to "emergency rescue skills" and "planning and performing prosthetic treatment."

The natural history and genotype-phenotype correlations of TMPRSS3 hearing loss: an international, multi-center, cohort analysis.

TMPRSS3-related hearing loss presents challenges in correlating genotypic variants with clinical phenotypes due to the small sample sizes of previous studies. We conducted a cross-sectional genomics study coupled with retrospective clinical phenotype analysis on 127 individuals. These individuals were from 16 academic medical centers across 6 countries. Key findings revealed 47 unique TMPRSS3 variants with significant differences in hearing thresholds between those with missense variants versus those with loss-of-function genotypes. The hearing loss progression rate for the DFNB8 subtype was 0.3 dB/year. Post-cochlear implantation, an average word recognition score of 76% was observed. Of the 51 individuals with two missense variants, 10 had DFNB10 with profound hearing loss. These 10 all had at least one of 4 TMPRSS3 variants predicted by computational modeling to be damaging to TMPRSS3 structure and function. To our knowledge, this is the largest study of TMPRSS3 genotype-phenotype correlations. We find significant differences in hearing thresholds, hearing loss progression, and age of presentation, by TMPRSS3 genotype and protein domain affected. Most individuals with TMPRSS3 variants perform well on speech recognition tests after cochlear implant, however increased age at implant is associated with worse outcomes. These findings provide insight for genetic counseling and the on-going design of novel therapeutic approaches.

p62/sequestosome-1 as a severity-reflecting plasma biomarker in Charcot-Marie-Tooth disease type 1A.

Autophagy is a self-degradation system for recycling to maintain homeostasis. p62/sequestosome-1 (p62) is an autophagy receptor that accumulates in neuroglia in neurodegenerative diseases. The objective of this study was to determine the elevation of plasma p62 protein levels in patients with Charcot-Marie-Tooth disease 1A (CMT1A) for its clinical usefulness to assess disease severity. We collected blood samples from 69 CMT1A patients and 59 healthy controls. Plasma concentrations of p62 were analyzed by ELISA, and we compared them with Charcot-Marie-Tooth neuropathy score version 2 (CMTNSv2). A mouse CMT1A model (C22) was employed to determine the source and mechanism of plasma p62 elevation. Plasma p62 was detected in healthy controls with median value of 1978 pg/ml, and the levels were significantly higher in CMT1A (2465 pg/ml, p < 0.001). The elevated plasma p62 levels were correlated with CMTNSv2 (r = 0.621, p < 0.0001), motor nerve conduction velocity (r = - 0.490, p < 0.0001) and disease duration (r = 0.364, p < 0.01). In C22 model, increased p62 expression was observed not only in pathologic Schwann cells but also in plasma. Our findings indicate that plasma p62 measurement could be a valuable tool for evaluating CMT1A severity and Schwann cell pathology.

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.

Promotion of Probabilistic Bit Generation in Mott Devices by Embedded Metal Nanoparticles.

Considerable attention has been drawn to the use of volatile two-terminal devices relying on the Mott transition for the stochastic generation of probabilistic bits (p-bits) in emerging probabilistic computing. To improve randomness and endurance of bit streams provided by these devices, delicate control of the transient evolution of switchable domains is required to enhance stochastic p-bit generation. Herein, it is demonstrated that the randomness of p-bit streams generated via the consecutive pulse inputs of pump-probe protocols can be increased by the deliberate incorporation of metal nanoparticles (NPs), which influence the transient dynamics of the nanoscale metallic phase in VO2 Mott switches. Among the vertically stacked Pt-NP-containing VO2 threshold switches, those with higher Pt NP density show a considerably wider range of p-bit operation (e.g., up to ≈300% increase in ΔVprobe upon going from (Pt NP/VO2)0 to (Pt NP/VO2)11) and can therefore be operated under the conditions of high speed (400 kbit s-1), low power consumption (14 nJ per bit), and high stability (>105 200 bits) for p-bit generation. Thus, the study presents a novel strategy that exploits nanoscale phase control to maximize the generation of nondeterministic information sources for energy-efficient probabilistic computing hardware.

Clinical characteristics and hearing loss etiology of cochlear implantees undergoing surgery in their teens, 20s, and 30s.

PURPOSE: This study aimed to investigate the etiology of hearing loss, including genetic variants, in individuals who underwent cochlear implantation (CI) in their teens to thirties. It also sought to analyze post-CI speech performance and identify prognostic factors affecting CI outcomes in this age group. METHODS: We conducted a retrospective review of 421 cochlear implant patients at Seoul National University Bundang Hospital, focusing on 63 subjects aged 10-39 years who underwent their first CI by a single surgeon between July 2018 and June 2022. The study included audiologic evaluation, molecular genetic testing, and analysis of speech performance post-CI. Statistical analyses were performed using SPSS 25 and GraphPad Prism 7. RESULTS: Among 63 participants (M:F, 24:39), nine underwent CI in their teens, 24 in their 20 s, and 30 in their 30 s. Most of them (40, 63.5%) had postlingual deafness. The study found that 65.2% (40/63) of subjects received a genetic diagnosis, with DFNB4 being the most common etiology (37.5%, 15/40). Post-CI speech evaluation showed an average sentence score of 80% across all subjects. Factors such as the onset of hearing loss, duration of deafness (DoD), and preoperative Speech Intelligibility Rating (SIR) significantly influenced CI outcomes. Notably, longer DoD was associated with poorer CI outcomes, but this did not affect individuals with postlingual hearing loss as much. CONCLUSION: The study concludes that in individuals aged 10-39 undergoing CI, the onset of hearing loss and preoperative SIR are critical predictors of postoperative outcomes. CI is recommended for those with postlingual hearing loss in this age group, irrespective of the DoD. The study highlights the importance of genetic factors especially DFNB4 in hearing loss etiology and underscores the value of the relatively easy-to-evaluate factor, preoperative SIR in predicting CI outcomes.

Hepatic arterial infusion chemotherapy for hepatocellular carcinoma refractory to transarterial chemoembolization: exploring the influence of prior transarterial chemoembolization and additional transarterial chemoembolization on survival outcomes.

Background: The selection of an efficacious treatment modality for patients with hepatocellular carcinoma (HCC) diagnosed as refractory to transarterial chemoembolization (TACE) presents numerous challenges. In addition to systemic therapies, hepatic arterial infusion chemotherapy (HAIC) may serve as an alternative option. However, it is imperative to identify patients who are appropriate candidates for HAIC to confer a survival benefit. Our study aimed to evaluate the impact of the number of TACE sessions prior to HAIC treatment and the addition of TACE during HAIC on the survival of HCC patient's refractory to TACE. Methods: This retrospective study included 82 patients with HCC refractory to TACE (mean age 60.5 years, 75 males). Survival analysis was conducted using the Kaplan-Meier method, with comparison between two groups via the log-rank test; the Cox regression model was utilized to identify factors influencing survival. Results: The overall response rate (ORR) was observed to be 29.3%, with a disease control rate (DCR) of 56.1%. Patients receiving more than four TACE sessions prior to HAIC exhibited a significantly poorer survival prognosis compared to those receiving fewer than four TACE sessions, with a hazard ratio (HR) of 0.151 (P=0.02). The median overall survival (OS) was markedly different, being 3.4 (range, 0.5-13.6) months for the former group and 14 (range, 8.5-19.5) months for the latter (P=0.01). Furthermore, patients undergoing additional TACE while receiving HAIC treatment demonstrated improved survival outcomes compared to those who did not, with an HR of 0.491 (P=0.02); the respective OS for these groups was 14 (range, 3.6-14.4) and 6.7 (range, 2.8-11) months (P=0.02). Conclusions: HAIC can be a suitable alternative treatment for HCC patient's refractory to TACE. For those with a history of more than 4 TACE sessions, other alternative treatments should be considered. The addition of TACE during HAIC treatment may extend patient OS time, provided it is balanced with maintaining safe liver function.

Recessive GNE Mutations in Korean Nonaka Distal Myopathy Patients with or without Peripheral Neuropathy.

Autosomal recessive Nonaka distal myopathy is a rare autosomal recessive genetic disease characterized by progressive degeneration of the distal muscles, causing muscle weakness and decreased grip strength. It is primarily associated with mutations in the GNE gene, which encodes a key enzyme of sialic acid biosynthesis (UDP-N-acetylglucosamine 2-epimerase/N-acetylmannosamine kinase). This study was performed to find GNE mutations in six independent distal myopathy patients with or without peripheral neuropathy using whole-exome sequencing (WES). In silico pathogenic prediction and simulation of 3D structural changes were performed for the mutant GNE proteins. As a result, we identified five pathogenic or likely pathogenic missense variants: c.86T>C (p.Met29Thr), c.527A>T (p.Asp176Val), c.782T>C (p.Met261Thr), c.1714G>C (p.Val572Leu), and c.1771G>A (p.Ala591Thr). Five affected individuals showed compound heterozygous mutations, while only one patient revealed a homozygous mutation. Two patients revealed unreported combinations of combined heterozygous mutations. We observed some specific clinical features, such as complex phenotypes of distal myopathy with distal hereditary peripheral neuropathy, an earlier onset of weakness in legs than that of hands, and clinical heterogeneity between two patients with the same set of compound heterozygous mutations. Our findings on these genetic causes expand the clinical spectrum associated with the GNE mutations and can help prepare therapeutic strategies.

Quantum circuit mapping for universal and scalable computing in MZI-based integrated photonics.

Linear optical quantum computing (LOQC) offers a quantum computation paradigm based on well-established and robust technology and flexible environmental conditions following DiVincenzo's criteria. Within this framework, integrated photonics can be utilized to achieve gate-based quantum computing, defining qubits by path-encoding, quantum gates through the use of Mach-Zehnder interferometers (MZIs), and measurements through single-photon detectors. In particular, universal two-qubit gates can be achieved by suitable structures of MZIs together with post-selection or heralding. The most resource-efficient choice is given by the post-selected Controlled-Z (CZ) gate. However, this implementation is characterized by a design which has a non-regular structure and cannot be cascaded. This limits the implementation of large-scale LOQC. Starting from these issues, we suggest an approach to move toward a universal and scalable LOQC on the integrated photonic platform. First of all, choosing the post-selected CZ as a universal two-qubit gate, we extend the path-encoded dual-rail qubit to a triplet of waveguides, composed of an auxiliary waveguide and the pair of waveguides corresponding to the qubit basis states. Additionally, we introduce a swap photonic network that maps the regularly-labeled structure of the new path-encoded qubits to the structure needed for the post-selected CZ. We also discuss the optical swap gate that allows the connection of non-nearest neighbor path-encoded qubits. In this way, we can deterministically exchange the locations of the qubits and execute controlled quantum gates between any path-encoded qubits. Next, by truncating the auxiliary waveguides after any post-selected CZ, we find that it is possible to cascade this optical gate when it acts on different pairs that share only one qubit. Finally, we show the Bell state and the Greenberger-Horne-Zeilinger (GHZ) state generation circuits implementing the regular structure, the cascading procedure of post-selected CZ and the optical swap.

Association Between Multiple Heavy Metal Exposures and Cholesterol Levels in Residents Living Near a Smelter Plant in Korea.

BACKGROUND: Considering the interactions between heavy metals, a comprehensive evaluation of the effects of exposure to various types of co-interacting heavy metals on health is required. This study assessed the association between dyslipidemia markers and blood mercury, lead, cadmium, iron, zinc, and nickel levels in residents of an abandoned refinery plant. METHODS: A total of 972 individuals (exposed group: 567, control group: 405) living near the Janghang refinery plant in the Republic of Korea were included. Blood mercury, lead, cadmium, iron, zinc, nickel, cholesterol, and triglyceride levels were measured. The combined effect of the six heavy metals on dyslipidemia markers was evaluated using a Bayesian kernel machine regression (BKMR) model and compared with the results of a linear regression analysis. The BKMR model results were compared using a stratified analysis of the exposed and control groups. RESULTS: In the BKMR model, the combined effect of the six heavy metals was significantly associated with total cholesterol (TC) levels both below the 45th percentile and above the 55th percentile in the total population. The combined effect range between the 25th and 75th percentiles of the six metals on TC levels was larger in the exposed group than that in the total population. In the control group, the combined effects of the changes in concentration of the six heavy metals on the TC concentration were not statistically significant. CONCLUSION: These results suggest that the cholesterol levels of residents around the Janghang refinery plant may be elevated owing to exposure to multiple heavy metals.