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As young adults transition into adulthood they must develop effective self-regulation techniques to help them navigate the heightened expectations of independence placed upon them. During this challenging developmental stage, mentors and other supportive individuals can facilitate co-regulation processes that help young adults reach self-regulation. This qualitative research identifies and characterizes supportive processes of regulation that graduate student mentors engaged in as part of their mentorship interactions with undergraduate mentees with learning disabilities and attention-deficit hyperactivity disorder (LD/ADHD). Participants were part of a larger campus-based study with 52 undergraduate mentees with LD/ADHD and 57 graduate student mentors. Data were transcripts from mentor group meetings (N = 20) discussing LD/ADHD and the mentorship experiences, undergraduate group meetings (N = 13) discussing LD/ADHD experiences and supports, and an instrumental mentor case study. Structural coding was used to identify content related to mentorship experiences; process coding was used to describe the actions and roles undertaken by mentors; content analysis was used to examine relative salience of topics discussed during mentor group meetings. Four themes emerged describing the ways in which mentors acted as co-regulators for mentees including: Fostering Positive Relationships, Guidance Based on a Similar Path, Supporting Strategy Generation, and Supporting Mentees by Setting Limits. Findings highlight key actions and processes for effective co-regulation techniques used by disability-informed mentors, that support the self-regulation practices of undergraduate students with LD/ADHD to reach their educational, career, and personal goals.

Background: The SARS-CoV-2 virus has been a global public health threat since December 2019. This study aims to investigate the neurological characteristics and risk factors of coronavirus disease 2019 (COVID-19) in Taiwanese children, using data from a collaborative registry. Methods: A retrospective, cross-sectional, multi-center study was done using an online network of pediatric neurological COVID-19 cohort collaborative registry. Results: A total of 11160 COVID-19-associated emergency department (ED) visits and 1079 hospitalizations were analyzed. Seizures were the most common specific neurological symptom, while encephalitis and acute disseminated encephalomyelitis (ADEM) was the most prevalent severe involvement.In ED patients with neurological manifestations, severe neurological diagnosis was associated with visual hallucination, seizure with/without fever, behavior change, decreased GCS, myoclonic jerk, decreased activity/fatigue, and lethargy. In hospitalized patients with neurological manifestations, severe neurological diagnosis was associated with behavior change, visual hallucination, decreased GCS, seizure with/without fever, myoclonic jerk, fatigue, and hypoglycemia at admission. Encephalitis/ADEM was the only risk factor for poor neurological outcomes at discharge in hospitalized patients. Conclusion: Neurological complications are common in pediatric COVID-19. Visual hallucination, seizure, behavior change, myoclonic jerk, decreased GCS, and hypoglycemia at admission are the most important warning signs of severe neurological involvement such as encephalitis/ADEM.

Bottom-up and top-down are two main computing models in granular computing by which the granule set including granules with different granularities. The top-down hyperbox granular computing classification algorithm based on isolation, or IHBGrC for short, is proposed in the framework of top-down computing model. Algorithm IHBGrC defines a novel function to measure the distance between two hyperbox hgranules, which is used to judge the inclusion relation between two hyperbox granules, the meet operation is used to isolate the i th class data from the other class data, and the hyperbox granule is partitioned into some hyperbox granules which include the i th class data. We compare the performance of IHBGrC with support vector machines and HBGrC, for a number of two-class problems and multiclass problems. Our computational experiments showed that IHBGrC can both speed up training and achieve comparable generalization performance.

Objectives: This research aims to explain the impact of flow’s antecedents on flow experience. Furthermore, this research explores the intention of students to continue using online AI-powered English learning platforms. Methodology: This study gathered data from 300 online students enrolled in AI-powered English learning platforms in Taiwan, with data collection facilitated by a research company in the country. Findings: According to the findings, flow was significantly associated with continuous intention. In terms of antecedents of flow, information quality, service support quality, and intrinsic motivation were significant, whereas confirmation, service quality, and instructor quality were not significant. Flow was found to have significant associations with perceived usefulness and satisfaction. Furthermore, confirmation significantly impacted perceived usefulness and satisfaction. Moreover, perceived usefulness was significantly associated with satisfaction but had no association with continuous intention. Lastly, both intrinsic motivation and satisfaction were associated with continuous intention. Novelty/Improvement:This research delves into the dynamic interplay between students' experiences and the adoption of AI-powered online English learning platforms. The study employed a comprehensive framework, including flow, a technology acceptance model, motivation, and an expectation confirmation model. Doi: 10.28991/HIJ-2024-05-02-011 Full Text: PDF

The investigation was motivated by the widespread use of ultra-high-strength steels in cable-stayed bridges and armor steel plates. These structures are exposed to elevated risks from extreme loads, including vehicle impacts and blast loadings. The study aimed to investigate the mechanical properties of 1770 steel for applications in extreme conditions. The strain rates and temperatures ranged from 0.00095 s−1 to 1303 s−1 and 20 °C–900 °C, respectively. Tensile tests were conducted at various strain rates using a Split Hopkinson Tension Bar for dynamic testing and a universal testing machine for quasi-static testing at room temperature (20 °C). Quasi-static tension at elevated temperatures was carried out using an electromechanical testing machine coupled with a heating device. A uniform temperature distribution inside the specimens was ensured by a 30-min holding time. The results of the tensile test indicate that the 1770 steel displays notable thermal softening effects and strain rate hardening that differ from mild steel. The standard Johnson-Cook (J-C) model was found to be inadequate in accurately predicting the strain rate effects of this specimen. To address this issue, the strain rate parameter C in the standard model was adjusted to create the modified J-C model, which demonstrated good agreement with the experimental results. To further demonstrate the modified model and the identified parameters, drop hammer impact tests and corresponding numerical simulations were conducted. The impact test and numerical simulation results showed good agreement in terms of deformation and contact force. The mechanical properties and the constitutive models can serve as a design reference for the ultra-high-strength 1770 steel in extreme envirnments, as well as a theoretical basis for fitting material models of similar ultra-high-strength steels.

Smart materials represent an emerging and highly exploited category, particularly in the creation of textiles that can sense and respond to various external stimuli, such as temperature or humidity. This study introduces for the first time the hygroscopic elongation and drying shrinkage properties of stimulus-responsive single-component polyamide (PA) fibers copolymerized with polyetherdiamine and diethylenetriamine (DETA). PA copolymers containing 5–15% polyetherdiamine were comprehensively characterized, including nuclear magnetic resonance spectroscopy (NMR), Fourier transform infrared spectroscopy (FT-IR), relative viscosity, and differential scanning calorimetry (DSC) analyses. Subsequently, these PA copolymers were successfully melt-spun into fibers and knitted into double-layered fabrics. PA fibers containing 15% polyetherdiamine showed significant results, with a moisture-absorbing elongation of 15.6% and a drying shrinkage of 94.9%. The Qmax and moisture regain of the PA fabric are 0.206 W·cm–2 and 4.4%, respectively. These moisture-driven, fiber-based smart textiles exhibit changes in breathability and shape retention at different humidity levels, thereby maintaining a more comfortable microclimate. Such textiles have great potential for widespread use in clothing, helping to improve comfort and adaptability.

Classification of data with imbalanced class distribution has encountered a significant drawback by most conventional classification learning methods which assume a relatively balanced class distribution. This paper proposes a novel classification method based on data-partition and SMOTE for imbalanced learning. The proposed method differs from conventional ones in both the learning and prediction stages. For the learning stage, the proposed method uses the following three steps to learn a class-imbalance oriented model: (1) partitioning the majority class into several clusters using data partition methods such as K-Means, (2) constructing a novel training set using SMOTE on each data set obtained by merging each cluster with the minority class, and (3) learning a classification model on each training set using convention classification learning methods including decision tree, SVM and neural network. Therefore, a classifier repository consisting of several classification models is constructed. With respect to the prediction stage, for a given example to be classified, the proposed method uses the partition model constructed in the learning stage to select a model from the classifier repository to predict the example. Comprehensive experiments on KEEL data sets show that the proposed method outperforms some other existing methods on evaluation measures of recall, g-mean, f-measure and AUC.

Abstract The incidence of melanoma, the most lethal form of skin cancer, has increased due to ultraviolet exposure. The treatment of advanced melanoma, particularly metastatic cases, remains challenging with poor outcomes. Targeted therapies involving BRAF/MEK inhibitors and immunotherapy based on anti-PD1/anti-CTLA4 antibodies have achieved long-term survival rates of approximately 50% for patients with advanced melanoma. However, therapy resistance and inadequate treatment response continue to hinder further breakthroughs in treatments that increase survival rates. This review provides an introduction to the molecular-level pathogenesis of melanoma and offers an overview of current treatment options and their limitations. Cells can die by either accidental or regulated cell death (RCD). RCD is an orderly cell death controlled by a variety of macromolecules to maintain the stability of the internal environment. Since the uncontrolled proliferation of tumor cells requires evasion of RCD programs, inducing the RCD of melanoma cells may be a treatment strategy. This review summarizes studies on various types of nonapoptotic RCDs, such as autophagy-dependent cell death, necroptosis, ferroptosis, pyroptosis, and the recently discovered cuproptosis, in the context of melanoma. The relationships between these RCDs and melanoma are examined, and the interplay between these RCDs and immunotherapy or targeted therapy in patients with melanoma is discussed. Given the findings demonstrating melanoma cell death in response to different stimuli associated with these RCDs, the induction of RCD shows promise as an integral component of treatment strategies for melanoma.

Abstract This work investigates a switchable 4G/5G dual‐antenna system designed for laptops. The dual open‐slot antenna structure is straightforward, with a slot width of only 2 mm. Each individual antenna features two different feed sections located in two separate regions between the slots. Port 1 is a direct‐feeding design with 3.6 pF chip capacitance, while Port 2 is only a direct‐feeding design. When Port 1 is excited and Port 2 is terminated to 50‐Ω, the antenna is functional in long‐term evolution (LTE) low‐band (617–960 MHz) and 5G sub‐6 GHz band (3300–5000 MHz). On the other hand, when Port 2 is excited and Port 1 is terminated to 50‐Ω, the antenna is functional in the LTE medium/high bands between 1710 and 2690 MHz. The measured isolation consistently exceeded 30 dB, and the efficiency remained above 48% across the entire frequency range. The calculated envelope correlation coefficients derived from the complex E‐field radiation pattern measurements were consistently below 0.02. These findings indicate that the system is exceptionally well‐suited for applications characterised by integrated metallic environments and a high display‐to‐body ratio.

Background: To investigate Pfizer-BioNTech 162b2 mRNA COVID-19 vaccine (BNT162b2) immunization-related myocarditis and describe the risk factors for consequent hospitalization in the pediatric intensive care unit (PICU) in children between 12 and 18 years. Methods: Children and adolescents 12 years of age and older who presented with discomfort after BNT162b2 immunization (BNTI) and visited pediatric emergency room (PER) at Chang Gung Memorial Hospital from September 22, 2021 to March 21, 2022, were included for analysis. Results: 681 children presented with discomfort after BNTI and visited our PER. The mean age was 15.1 ± 1.7 years. Three hundred and ninety-four (57.9%) and 287 (42.1%) events were after 1st and 2nd dose, respectively. 58.4% (n = 398) were male. The most common complaints were chest pain (46.7%) and chest tightness (27.0%). The median (interquartile range [IQR]) interval of discomfort after BNTI was 3.0 (1.0−12.0) days. BNTI-related pericarditis, myocarditis and myopericarditis were diagnosed in 15 (2.2%), 12 (1.8%) and 2 (0.3%) patients, respectively. Eleven (1.6%) needed hospitalization in PICU. The median (IQR) hospital stay was 4.0 (3.0−6.0) days. There was no mortality. More patients were diagnosed myocarditis (p = 0.004) after 2nd dose BNTI. PICU admission occurred more commonly after 2nd dose BNTI (p = 0.007). Risk factors associated with hospitalization in PICU were abnormal EKG findings (p = 0.047) and abnormal serum troponin levels (p = 0.003) at PER. Conclusion: Myocarditis in children aged 12−18 years occurred more commonly following 2nd dose BNTI. Most cases were of mild or intermediate severity without death. Factors predicting BNTI-related myocarditis and consequent hospitalization in PICU were abnormal EKG findings and abnormal serum troponin levels at PER in this study.

Lung cancer and cachexia are the leading causes of cancer-related deaths worldwide. Cachexia is manifested by weight loss and white adipose tissue (WAT) atrophy. Limited nutritional supplements are conducive to lung cancer patients, whereas the underlying mechanisms are poorly understood. In this study, we used a murine cancer cachexia model to investigate the effects of a nutritional formula (NuF) rich in fish oil and selenium yeast as an adjuvant to enhance the drug efficacy of an EGFR inhibitor (Tarceva). In contrast to the healthy control, tumor-bearing mice exhibited severe cachexia symptoms, including tissue wasting, hypoalbuminemia, and a lower food efficiency ratio. Experimentally, Tarceva reduced pEGFR and HIF-1α expression. NuF decreased the expression of pEGFR and HIF-2α, suggesting that Tarceva and NuF act differently in prohibiting tumor growth and subsequent metastasis. NuF blocked LLC tumor-induced PTHrP and expression of thermogenic factor UCP1 and lipolytic enzymes (ATGL and HSL) in WAT. NuF attenuated tumor progression, inhibited PTHrP-induced adipose tissue browning, and maintained adipose tissue integrity by modulating heat shock protein (HSP) 72. Added together, Tarceva in synergy with NuF favorably improves cancer cachexia as well as drug efficacy.

Abstract Background Studies comparing the effectiveness of either adjuvant oral uracil‐tegafur (UFT) or intravenous chemotherapy on early‐stage (stage I and II) non‐small cell lung cancer (NSCLC) patients treated with complete surgical treatment remain limited. Methods From January 2011 to December 2017, patients with early‐stage NSCLC (defined as tumor size >3 cm without mediastinal lymph node involvement or any distant metastasis) receiving either adjuvant oral UFT or intravenous chemotherapy after surgical resection were identified from the Taiwan Cancer Registry. Overall survival (OS) and relapse‐free survival (RFS) were the primary and secondary outcomes, respectively. Propensity matching was used for controlling confounders. Results A total of 840 patients receiving adjuvant therapy after surgery (including 595 oral UFT and 245 intravenous chemotherapy) were enrolled. Before matching, patients using oral UFT had significantly longer OS (HR: 0.69, 95% CI: 0.49–0.98, p = 0.0387) and RFS (HR: 0.79, 95% CI: 0.61–0.97, p = 0.0392) than those with intravenous chemotherapy. A matched cohort of 352 patients was created using 1:1 propensity score‐matching. In the Cox regression analysis, the UFT and the matched chemotherapy groups had similar OS (HR: 0.80, 95% CI: 0.48–1.32, p = 0.3753) and RFS (HR: 0.98, 95% CI: 0.72–1.34, p = 0.9149). Among subgroup analysis, oral UFT use was associated with longer RFS among the subgroups of non‐drinker (HR: 0.66, 95% CI: 0.34–0.99, p = 0.0478) and patients with stage IB disease (HR: 0.67, 95% CI: 0.42–0.97, p = 0.0341). Conclusions This population‐based study in the real‐world setting of Taiwan demonstrates comparable effectiveness between oral UFT and intravenous chemotherapy in terms of clinical outcomes for early‐stage NSCLC patients after surgery.

Background Passive suicidal ideation is a predictor of subsequent suicidal behavior, and the predictive value of objective biomarkers for suicidal ideation is attracting increasing attention. The incidence of passive suicidal ideation is relative high in elderly patients with schizophrenia. However, studies on passive suicidal ideation and biomarkers in this population are lacking. Objective To investigate the correlation of passive suicidal ideation with thyroid stimulating hormone (TSH) and prolactin (PRL) among elderly schizophrenia inpatients. Methods A total of 248 schizophrenia inpatients aged 60 years and above from Shenzhen Kangning Hospital were retrospective included from January 2014 to October 2018 and divided into the passive suicidal ideation group (n=37) and non-passive suicidal ideation group (n=211) according to the first item of the Suicide Subscale of the Chinese Version of Mini-International Neuropsychiatric Interview. The sociodemographic characteristics, TSH, free triiodothyronine (FT3) , free total-thyroxine (FT4) and PRL levels in the two groups were collected separately. Results Univariate analysis showed that the proportions of female patients, history of attempted suicide and PRL level inpassive suicidal ideation group were higher than non-passive suicidal ideation group, while the TSH level was lower than non-passive suicidal ideation group (P

Background: This study investigated the mechanism by which tazarotene-induced gene 1 (TIG1) inhibits melanoma cell growth. The main focus was to analyze downstream genes regulated by TIG1 in melanoma cells and its impact on cell growth. Methods: The effects of TIG1 expression on cell viability and death were assessed using water-soluble tetrazolium 1 (WST-1) mitochondrial staining and lactate dehydrogenase release assays. RNA sequencing and Western blot analysis were employed to investigate the genes regulated by TIG1 in melanoma cells. Additionally, the correlation between TIG1 expression and its downstream genes was analyzed in a melanoma tissue array. Results: TIG1 expression in melanoma cells was associated with decreased cell viability and increased cell death. RNA-sequencing (RNA-seq), quantitative reverse transcription PCR (reverse RT-QPCR), and immunoblots revealed that TIG1 expression induced the expression of Endoplasmic Reticulum (ER) stress response-related genes such as Homocysteine-responsive endoplasmic reticulum-resident ubiquitin-like domain member 1 (HERPUD1), Binding immunoglobulin protein (BIP), and DNA damage-inducible transcript 3 (DDIT3). Furthermore, analysis of the melanoma tissue array revealed a positive correlation between TIG1 expression and the expression of HERPUD1, BIP, and DDIT3. Additionally, attenuation of the ER stress response in melanoma cells weakened the impact of TIG1 on cell growth. Conclusions: TIG1 expression effectively hinders the growth of melanoma cells. TIG1 induces the upregulation of ER stress response-related genes, leading to an increase in caspase-3 activity and subsequent cell death. These findings suggest that the ability of retinoic acid to prevent melanoma formation may be associated with the anticancer effect of TIG1.

Padina minor is a seaweed rich in polysaccharides often used in food, feed, fertilizers, and antibacterial drugs. This study is the first to evaluate the effect of feeding zebrafish with Padina minor extract on preventing and treating C. albicans infections. This study evaluated the growth, survival, and disease resistance effects of P. minor extract on zebrafish. The fish were divided into four groups: three groups treated with 1%, 5%, or 10% P. minor extract and one untreated group (c, control). Subsequently, we analyzed how the extract affected the immune function of zebrafish infected with C. albicans. Based on the lethal concentration (LC50) calculated in the first stage, 1% was used as the effective therapeutic concentration. The results showed that the growth rate of the 1% feed group was the best, and no significant difference in survival rates between the four groups was observed. Feeding with 1% P. minor extract downregulated the expression of key inflammatory genes like tumor necrosis factor-alpha (TNF-α), interleukin-1β (IL-1β), and IL-10, effectively preventing and treating C. albicans infections in zebrafish. This study is a preliminary evaluation of the therapeutic efficacy of P. minor extracts against C. albicans.

OBJECTIVES/GOALS: Our goal is to determine whether microplastic fibers (MPFs) provide signals for dendritic cell-induced Th2 polarization via epithelial-cell-derived thymic stromal lymphopoietin (TSLP). We seek to highlight a potential mechanism for MPF-induced airway toxicity associated with asthma exacerbation. METHODS/STUDY POPULATION: Primary human bronchial epithelial cells (NHBEs) were grown and differentiated at an air-liquid interface. Dyed and undyed polyester MPFs (14x45 µm) generated using a cryomicrotome were delivered to NHBEs through a custom designed mesh-hopper system. After the exposure period (6, 12, 24 hrs), cell viability was assessed using alamarBlue, and RT-qPCR was performed to determine mRNA expression of asthma associated genes (i.e., TSLP, IL-13, IL-33, etc.,) in NHBEs. Bulk mRNA-sequencing followed by bioinformatics will be performed to observe other plausible pathways tweaked by lung cell exposure to MPFs. RESULTS/ANTICIPATED RESULTS: Through gravimetric analysis, it was determined that the mesh-hopper system can achieve delivery efficiencies of at least 85% for as low as 500 fibers. Following exposure, results show polyester MPFs (500 - 1,000 fibers) exposed to NHBEs at multiple time points (6, 12, 24 hrs) did not result in a statistically significant decrease in cell viability. Treatment with 500 undyed MPFs resulted in a slight increase in TSLP expression at 6 hrs that decreased over time, whereas all other treatment groups resulted in TSLP downregulation. Similarly, 500 undyed MPFs resulted in an increase in IL-13 expression at both 6 and 12 hrs with all other treatment groups leading to IL-13 downregulation. We anticipate the RNA-seq results will show pro-inflammatory pathways are highly targeted following NHBE exposure to MPFs. DISCUSSION/SIGNIFICANCE: This study is one of the first to mechanistically assess the impact of MPFs on lung cells while simultaneously addressing the need for a reliable system that delivers MPFs to ALI cultures to better mimic inhalation and avoid inadequate resuspension of particles in liquid medium.

Abstract Introduction Neonatal sepsis is a major cause of health loss and mortality worldwide. Without proper treatment, neonatal sepsis can quickly develop into multisystem organ failure. However, the signs of neonatal sepsis are non-specific, and treatment is labour-intensive and expensive. Moreover, antimicrobial resistance is a significant threat globally, and it has been reported that over 70% of neonatal bloodstream infections are resistant to first-line antibiotic treatment. Machine learning is a potential tool to aid clinicians in diagnosing infections and in determining the most appropriate empiric antibiotic treatment, as has been demonstrated for adult populations. This review aimed to present the application of machine learning on neonatal sepsis treatment. Methods PubMed, Embase, and Scopus were searched for studies published in English focusing on neonatal sepsis, antibiotics, and machine learning. Results There were 18 studies included in this scoping review. Three studies focused on using machine learning in antibiotic treatment for bloodstream infections, one focused on predicting in-hospital mortality associated with neonatal sepsis, and the remaining studies focused on developing machine learning prediction models to diagnose possible sepsis cases. Gestational age, C-reactive protein levels, and white blood cell count were important predictors to diagnose neonatal sepsis. Age, weight, and days from hospital admission to blood sample taken were important to predict antibiotic-resistant infections. The best-performing machine learning models were random forest and neural networks. Conclusion Despite the threat antimicrobial resistance poses, there was a lack of studies focusing on the use of machine learning for aiding empirical antibiotic treatment for neonatal sepsis.

Abstract Background With its high nutritional value and productivity, Italian ryegrass as a biomass feedstock constantly supplies rumen degradable nitrogen and digestible fiber to ruminants. However, biofuel production is easily reduced during ensiling due to the high-moisture content of Italian ryegrass, leading to economic losses. Lactic acid bacteria inoculants could improve lignocellulosic degradation and fermentation quality and decrease dry matter loss during the bioprocessing of silage. Therefore, this study analyzed the effects of Lactobacillus buchneri TSy1-3 (HE), Lactobacillus rhamnosus BDy3-10 (HO), and the combination of HE and HO (M) on fermentation quality, bacterial community and metabolome in high-moisture Italian ryegrass silage during ensiling. Results The results showed that the pH value was significantly lower in the HO groups than in the other treatments at the end of ensiling, and the dry matter and acetic acid contents were significantly higher in the HO group than in the other inoculated groups. All inoculants decreased the diversity of the bacterial community and significantly increased the relative abundance of Lactobacillus. Inoculation with HO significantly improved the concentrations of organic acids, dipeptides, ferulic acid, apigenin, and laricitrin. Compared with Lactobacillus buchneri TSy1-3 (HE), HO significantly upregulated the flavonoid compounds in the flavone and flavonol biosynthesis pathway. Conclusions Overall, these findings suggest that inoculation with HO was beneficial for the development of Italian ryegrass as a biomass feedstock, improving fermentation quality, accelerating changes in bacterial community composition and increasing biofunctional metabolites in high-moisture Italian ryegrass silage.

Structural change can alter the energy absorption ability of constituent materials. Carbon organic framework (COF)-inspired structures printed with fusion deposition modeling (FDM) using polylactic acid (PLA) and acrylonitrile butadiene styrene (ABS) polymers are used to analyze the structural effect. Structures were characterized for specific energy absorption under static compression. The best structures from the static testing results were further characterized for dynamic compression using sinusoidal displacement to calculate the dynamic elastic recovery (DER), hysteresis work, and tan δ. Based on the results, the bending-dominated structure absorbed the highest energy, and the surface structure provided the best DER. The structure which failed by the pure collapsing of the layer showed the best specific values. The delamination of printed layers during loading reduced the performance of structures despite of the materials.

Based on the idea of crowdsourcing,mobile crowdsensing(MCS) collects mobile sensing devices to sense the surroun-ding environment,which can make environment sensing and information collection more flexible,convenient and efficient.Whe-ther the task allocation strategy is reasonable or not directly affects the success of the sensing task.Therefore,formulating a reasonable task allocation strategy is a hotspot and focus in the research of MCS.At present,most of the task allocation methods in MCS systems are offline and targeted at single type tasks.However,in practice,online multi-type task allocation is more common.Therefore,this paper studies the task allocation method in MCS for multiple types of tasks,and proposes an online task allocation strategy oriented to system benefits combined with the characteristics of MCS technology in the military field.In this paper,a long-term,dynamic online task allocation system model is established,and the problem is solved based on Lyapunov optimization theory with the system benefit as the optimization goal,so that the online dynamic control of task admission strategy and task allocation scheme is realized.Experiment shows that the online task allocation algorithm proposed in this paper is effective and feasible.It can reasonably allocate the tasks arriving at the MCS system online,ensure the stability of the task queue,and increase the system utility by adjusting the parameter value.

Abstract Background This study was designed to analyze the clinical follow-up results (minimum of 2 years) in patients with stable nonunion, unstable nonunion, or nonunion of the scaphoid with early degenerative radioscaphoid arthritis (Lichtman classification stage I–III) treated with arthroscopic osteosynthesis with autogenous bone graft. Methods We retrospectively recruited 44 consecutive patients with scaphoid fracture nonunion treated with arthroscopy-assisted percutaneous internal fixation with autogenous bone grafts from January 2010 to November 2019. We recorded union and return to activity and analyzed data with regular clinical follow-up at a mean duration of 33 months (range 24–46 months). Clinical (i.e., visual analog scale pain score, grip strength, and range of motion), radiographic, and functional (Mayo Modified Wrist Score (MMWS)) outcomes at the final follow-up were compared with the preoperative assessments and analyzed in patients with different stages. Results We confirmed union in 39 of the 44 patients (88.6%) after a mean 15.4 weeks post-operatively according to clinical examinations and standard radiography. All clinical parameters improved significantly. For the MMWS, there were 25 excellent and 14 good results. Of the 44 patients, 40 (90.9%) returned to work or sports activities at their preinjury levels. Comparisons of the outcomes between patients in different stages of scaphoid nonunion revealed no significant difference in the aspect of union rate, VAS pain score, and functional score improvement. Conclusions Arthroscopic osteosynthesis with autogenous bone grafts is a reliable and minimally invasive method for achieving nonunion healing and improving clinical outcomes in stage I–III scaphoid nonunion. Level of Evidence: Level IV, case series.

Subharmonic oscillation stands as a critical concern in the context of ripple-based constant-on-time (COT) controllers. While this issue can be mitigated through the application of the virtual inductor current (VIC) technique, it comes at the cost of load transient response. To achieve both high stability and rapid transient response, this paper introduces an Output Capacitor Voltage Ripple Compensation (VRC) technique. This technique minimizes the phase delay attributed to output capacitance by introducing a virtual output ripple ( $\text{V}_{\mathrm {VOR}})$ inversely related to the feedback voltage. The VVOR serves to expedite the load transient response by counteracting the additional virtual inductor current injection during load transients. Utilizing a $0.13\mu \text{m}$ BCD technology, a synchronous buck converter is integrated with the proposed VRC-COT controller, showcasing exceptional stability across a load current range of 0 to 8A, even when equipped with a 30% $88\mu \text{F}$ ceramic output capacitor. Additionally, the load transient response exhibits reduced overshoot and undershoot, measuring at 120mV and 130mV, respectively, in response to load steps from 0A to 8A within a $10\mu \text{S}$ timeframe.

Sleep has attracted extensive attention due to its significance in health. However, its association with erectile dysfunction (ED) is insufficiently investigated. To investigate the potential causal links between sleep traits (insomnia, sleep duration, and chronotype) and ED, this study was performed. The single-nucleotide polymorphisms (SNPs) associated with insomnia, sleep duration, and chronotype were retrieved from previous genome-wide association studies (GWAS). A conventional two-sample Mendelian randomization (MR) was used to estimate the causal links between sleep traits and ED. The summary statistics of ED were from individuals of European ancestry (6175 cases vs 217 630 controls). As shown by the random effect inverse-variance-weighting (IVW) estimator, genetically predicted insomnia was causally associated with a 1.15-fold risk of ED (95% confidence interval: 1.07–1.23, P < 0.001). Sleep duration and morningness were not causally associated with ED, as indicated by the IVW (all P > 0.05). These findings were consistent with the results of sensitivity analyses. Based on genetic data, this study provides causal evidence that genetically predicted insomnia increases the risk of ED, whereas sleep duration and chronotype do not.

AIM: To evaluate the changes in macular morphology and function after a single intravitreal injection of aflibercept in diabetic macular edema (DME) using optical coherence tomography angiography (OCTA) and MP-3 microperimetry. METHODS: Twenty-eight patients (42 eyes) diagnosed with DME were treated with intravitreal injection of aflibercept. The changes in best corrected visual acuity (BCVA), central retinal thickness (CRT), foveal avascular zone (FAZ) area, vessel density of superficial retinal capillary plexus (SVD), vessel density of deep retinal capillary plexus (DVD), mean light sensitivity (MLS), 2° fixation rate (P1), 4° fixation rate (P2), and other indicators 1mo after treatment were compared; of these, BCVA was converted into logarithm of the minimum angle of resolution (logMAR), and the correlation among the factors was analyzed. RESULTS: After treatment, logMAR BCVA was 0.47±0.24, which was significantly better than that before treatment (0.63±0.28, P

Indoor air quality (IAQ) in schools has received attention over the past decades but still lacks specific standards and regulations. This study aimed to review the impact of bioaerosol activity in indoor environments on acute respiratory diseases and explore whether carbon dioxide can be used as an indicator of bioaerosol and respiratory diseases in indoor environments in K-12 school systems. Findings suggest a lack of a consensual approach to evaluate bioaerosols impacting IAQ in indoor infrastructures, particularly in school environments; an elevated CO _2 concentration inside the school classrooms was not uncommon, and the evidence of unsatisfactory and degraded IAQ (surpassing ASHRAE standards) at public schools in rural and urban settings in one of the North Central County, Florida. It was found that CO _2 levels can be associated with bioaerosol activity, and sufficient ventilation within the space substantially reduces the airborne time of respiratory droplets and CO _2 levels. CO _2 monitoring can act as an effective, low-cost alternative to surveying or detecting the prevalence of respiratory diseases, which may hold strength through establishing critical CO _2 thresholds and, thereafter associating it with the infectious doses of pathogen activity.

This study aimed to provide environmental surveillance data for evaluating the risk of acquiring SARS-CoV-2 in public areas with high foot traffic in a university. Air and surface samples were collected at a university that had the second highest number of COVID-19 cases among public higher education institutions in the U.S. during Fall 2020. A total of 60 samples were collected in 16 sampling events performed during Fall 2020 and Spring 2021. Nearly 9800 students traversed the sites during the study period. SARS-CoV-2 was not detected in any air or surface samples. The university followed CDC guidance, including COVID-19 testing, case investigations, and contact tracing. Students, faculty, and staff were asked to maintain physical distancing and wear face coverings. Although COVID-19 cases were relatively high at the university, the possibility of acquiring SARS-CoV-2 infections at the sites tested was low.

CeO2 and CuO nanoparticles (NPs) are used as additives in petrodiesel to enhance engine performance leading to reduced diesel combustion emissions. Despite their benefits, the additive application poses human health concerns by releasing inhalable NPs into the ambient air. In this study, a bioinspired lung cell exposure system, Dosimetric Aerosol in Vitro Inhalation Device (DAVID), was employed for evaluating the toxicity of aerosolized CeO2 and CuO NPs with a short duration of exposure (≤10 min vs. hours in other systems) and without exerting toxicity from non-NP factors. Human epithelial A549 lung cells were cultured and maintained within DAVID at the air-liquid interface (ALI), onto which aerosolized NPs were deposited, and experiments in submerged cells were used for comparison. Exposure of the cells to the CeO2 NPs did not result in detectable IL-8 release, nor did it produce a significant reduction in cell viability based on lactate dehydrogenase (LDH) assay, with a marginal decrease (10%) at the dose of 388 μg/cm2 (273 cm2/cm2). In contrast, exposure to CuO NPs resulted in a concentration dependent reduction in LDH release based on LDH leakage, with 38% reduction in viability at the highest dose of 52 μg/cm2 (28.3 cm2/cm2). Cells exposed to CuO NPs resulted in a dose dependent cellular membrane toxicity and expressed IL-8 secretion at a global dose five times lower than cells exposed under submerged conditions. However, when comparing the ALI results at the local cellular dose of CuO NPs to the submerged results, the IL-8 secretion was similar. In this study, we demonstrated DAVID as a new exposure tool that helps evaluate aerosol toxicity in simulated lung environment. Our results also highlight the necessity in choosing the right assay endpoints for the given exposure scenario, e.g., LDH for ALI and Deep Blue for submerged conditions for cell viability.

BackgroundResection of a giant retroperitoneal liposarcoma is difficult and technically demanding, especially for large retroperitoneal tumors accompanied by a diaphragmatic hernia. Technically, the open abdominal approach can be time-consuming and difficult to perform, with possible intraoperative complications and other factors bringing psychological and physical difficulties to the patient. This study reports a safe and feasible approach for the complete resection of a large retroperitoneal tumor complicated by a diaphragmatic hernia.MethodsA 58-year-old male patient with persistent upper abdominal pain and distension was treated at a local hospital on 4 July 2022. Computed tomography showed a mixed-density mass on the right retroperitoneum, and liposarcoma was considered. On 6 July 2022, the patient was transferred to our hospital for further treatment. Computed tomography showed a mass with low-density fatty shadow in the right adrenal region. The boundary with the right adrenal gland was unclear. The mass was 102 mm × 74 mm, and the right lobe of the liver was compressed. Insufficiency of the right middle lobe of the liver was seen due to a right diaphragmatic hernia and left mediastinal deviation. We considered the traditional approach for tumor resection via laparotomy, but we opted to perform a comprehensive evaluation first. The tumor was close to the back of the right kidney and liver, causing the diaphragm to rise because of its proximity to these organs. Exposing the tumor through laparotomy would be difficult, making it challenging to remove. The patient had a diaphragmatic hernia and moderate pulmonary dysfunction; therefore, we decided to enter the abdomen through a thoracotomy of the ninth rib.ResultsUsing our technique, the tumor was easily visualized and completely removed in approximately 30 min. The intraoperative blood loss was 100 ml, and no postoperative bleeding, pneumothorax, intestinal fistula, infection, or other complications occurred.ConclusionThe transthoracic approach may be a safer and more feasible resection method than the traditional open approach for patients with giant retroperitoneal liposarcoma with a diaphragmatic hernia.

Summary: We investigated the influence of hydroxyl groups on the anti-quorum-sensing (anti-QS) and anti-biofilm activity of structurally similar cyclic dipeptides, namely cyclo(L-Pro-L-Tyr), cyclo(L-Hyp-L-Tyr), and cyclo(L-Pro-L-Phe), against Pseudomonas aeruginosa PAO1. Cyclo(L-Pro-L-Phe), lacking hydroxyl groups, displayed higher virulence factor inhibition and cytotoxicity, but showed less inhibitory ability in biofilm formation. Cyclo(L-Pro-L-Tyr) and cyclo(L-Hyp-L-Tyr) suppressed genes in both the las and rhl systems, whereas cyclo(L-Pro-L-Phe) mainly downregulated rhlI and pqsR expression. These cyclic dipeptides interacted with the QS-related protein LasR, with similar binding efficiency to the autoinducer 3OC12-HSL, except for cyclo(L-Pro-L-Phe) which had lower affinity. In addition, the introduction of hydroxyl groups significantly improved the self-assembly ability of these peptides. Both cyclo(L-Pro-L-Tyr) and cyclo(L-Hyp-L-Tyr) formed assembly particles at the highest tested concentration. The findings revealed the structure-function relationship of this kind of cyclic dipeptides and provided basis for our follow-up research in the design and modification of anti-QS compounds.

Objective: To present the detailed history of three cervical cancer patients with rectovaginal fistula, who had undergone radiotherapy. Cases report: A 74-year-old patient with end-stage renal disease undergoing hemodialysis had radiotherapy for her advanced cervical cancer. Colonoscopic biopsy showed radiation sigmoid colitis and ulcers. Laparotomy revealed colon perforation and rectovaginal fistula. The second case is a 54-year-old cervical cancer patient, who had received concurrent chemoradiation therapy and further systemic therapy with cisplatin, paclitaxel, and bevacizumab. She suffered from bloody stool and abdominal pain. Rectovaginal fistula was found during exploratory laparotomy. The third case is a 35-year-old cervical cancer patient, who had received concurrent chemoradiation therapy. Systemic therapy was then prescribed with platinum, paclitaxel, and bevacizumab for her lung metastasis, and a rectovaginal fistula was found later. All three patients did not survive later. Conclusions: Fatal rectovaginal fistula may occur in post-radiation advanced cervical cancer patients. Unnecessary colonoscopic biopsy may cause significant sequelae. In patients with high risk for rectovaginal fistulas, chemotherapy without adding bevacizumab might be suggested in patients with low risk of poor response to chemotherapy. In addition, three-dimensional conformal radiation therapy or intensity-modulated radiation therapy should be used for patients with high risk for fistulas.

With the increasing demand for green and renewable energy, piezoelectric nanogenerators (PENGs) are in the infant stage for the next generation of wearable energy supplies. In this study, we synthesize an electrospun poly (vinylidene fluoride) zinc oxide (PVDF@ZnO) PENG device with different particle sizes of ZnO by solution electrospinning and study the effect of incorporation of ZnO and its particle size on the piezoelectric properties of the PVDF PENG device. We evaluate the piezoelectric properties of the PENG device under different mechanical conditions of tension, compression, and bending. The incorporation of ZnO nanoparticles remarkably enhances the piezoelectric response of PVDF under all the study conditions. In particular, the device with large-particle ZnO (PVDF@L-ZnO) PENG generates an electrical output current, voltage, and power density of 1308 nA, 5.6 V, and 2160 μW/m2, respectively, at a loading resistance of 10 MΩ under compression; 42 mV, 82 nA, and 28 μW/m2, respectively, at a loading resistance of 20 MΩ under tension; 2.8 V, 323 nA, and 320 μW/m2, respectively, at a loading resistance of 20 MΩ under bending, and we choose the compression result for further practical applications. In addition, we use the PENG device to harvest waste vibration mechanical energy from an air compressor machine with a frequency of 60 Hz. It harvests waste mechanical energy that turns on a liquid crystal display (LCD). The PVDF@L-ZnO PENG device also shows stable cyclic discharging and charging properties, which are crucial for practical applications. Therefore, the fabricated PENG device is a favorable candidate for wasted mechanical energy and converting it to electrical energy. We expect that it can play an important role in the problems related to renewable and green energy utilization.

Objective To evaluate the effect of icariin on sevoflurane-induced postoperative cognitive dysfunction (POCD),and to explore its potential mechanism. Methods The mice were divided into control group, model group(sevoflurane anesthesia + laparotomy were used to establish a mouse POCD model), icariin group, PI3K inhibitor group, icariin + inhibitor group, PI3K activator group, with 12 rats in each group. Conditional fear test and Y maze test were used to evaluate cognitive dysfunction in mice; ELISA method was used to detect the levels of serum TNF-α, IL-1β and BDNF; the hippocampal tissue was taken, Nissl staining was used to observe the changes of neuron morphology; TUNEL staining was used to detect neuronal apoptosis rate; the expression levels of M1 and M2 activated microglia and their markers were detected by immunofluorescence method; Western blot was used to detect the expression of TNF-α, IL-1β,IL-10, GSK-3β phosphorylated protein and Bcl-2. Results Compared with the control group, mice of model group showed cognitive impairment, severe hippocampal neuron impairment and apoptosis, the pro-inflammatory response mediated by M1 polarization of microglia in the hippocampus was more intensive than the anti-inflammatory response mediated by M2 polarization. The expression of PI3K/Akt-GSK-3β pathway and its mediated anti-inflammatory and anti-apoptotic proteins decreased (P＜0.05). Icariin and PI3K activator intervention promoted the PI3K/Akt-GSK-3β pathway and its anti-inflammatory and anti-apoptotic responses, and promote the anti-inflammatory response mediated by M2 polarization of hippocampal microglia, alleviated the impairment and apoptosis of hippocampal neurons, and improved cognitive function impairment of mice (P＜0.05). PI3K inhibitors could weaken the above-mentioned effects of icariin (P＜0.05). Conclusions The effect of icariin on improving the apoptosis of hippocampal neurons and cognitive impairment in POCD mice may be related to promoting the activation of PI3K/Akt pathway and enhancing the anti-inflammatory response mediated by M2 polarization of microglia.

Background: Flatfoot (Pes Planus), often regarded as a physiological deviation in children, is of concern to parents because there is no test to predict the development of foot arch. This study aimed to use a new diagnostic flatfoot criterion to determine 1) how the footprint index changes during the development of foot arches, 2) what factors can predict a foot arch development, and 3) whether foot arch development could be a process of body growth. Methods: 572 children were enrolled in a prospective longitudinal study of anthropometrical parameters and physical fitness twice at age of 6.7 and 8.2 years. The bimodal frequency distribution of the Chippaux-Smirak index (CSI) of the footprint was used to define flatfoot as CSI 0.61. Body measurements and physical fitness tests were compared between children with flatfeet who developed foot arches and children who did not. Results: Of 263 children with flatfeet, the CSI significantly changed from 0.72 to 0.46 in 70 children who developed foot arches over 1.5 years and the others had minimal change in the index. Children with foot arch development had a lower initial CSI, improved boys' performance in one-leg balance, and less increase in girls’ body height than children who remained flatfooted, whereas sex and weight were similar in both groups. Conclusion: This longitudinal study with the bimodal distribution of the CSI investigated how the development of foot arch advances in children around age 7. A significant and unique pattern in change of the CSI suggests involvement of a maturational stage in foot arch development. Along with the improved performance in one-leg balance, the unidirectional transition from flatfoot to non-flatfoot is associated with improvement in motor control of the ankle. Trial registration: Chinese Clinical Trial Registry (ChiCTR–OCS–14004300).

Abstract Background Owing to the heterogeneity of microbiota among individuals and populations, only Fusobacterium nucleatum and Bacteroides fragilis have been reported to be enriched in colorectal cancer (CRC) in multiple studies. Thus, the discovery of additional bacteria contributing to CRC development in various populations can be expected. We aimed to identify bacteria associated with the progression of colorectal adenoma to carcinoma and determine the contribution of these bacteria to malignant transformation in patients of Han Chinese origin. Methods Microbiota composition was determined through 16S rRNA V3–V4 amplicon sequencing of autologous adenocarcinomas, adenomatous polyps, and non-neoplastic colon tissue samples (referred to as “tri-part samples”) in patients with CRC. Enriched taxa in adenocarcinoma tissues were identified through pairwise comparison. The abundance of candidate bacteria was quantified through genomic quantitative polymerase chain reaction (qPCR) in tissue samples from 116 patients. Associations of candidate bacteria with clinicopathological features and genomic and genetic alterations were evaluated through odds ratio tests. Additionally, the effects of candidate bacteria on CRC cell proliferation, migration, and invasion were evaluated through the co-culture of CRC cells with bacterial cells or with conditioned media from bacteria. Results Prevotella intermedia was overrepresented in adenocarcinomas compared with paired adenomatous polyps. Furthermore, co-abundance of P. intermedia and F. nucleatum was observed in tumor tissues. More notably, the coexistence of these two bacteria in adenocarcinomas was associated with lymph node involvement and distant metastasis. These two bacteria also exerted additive effects on the enhancement of the migration and invasion abilities of CRC cells. Finally, conditioned media from P. intermedia promoted the migration and invasion of CRC cells. Conclusion This report is the first to demonstrate that P. intermedia is enriched in colorectal adenocarcinoma tissues and enhances the migration and invasion abilities of CRC cells. Moreover, P. intermedia and F. nucleatum exert additive effects on the malignant transformation of colorectal adenomas into carcinomas. These findings can be used to identify patients at a high risk of malignant transformation of colorectal adenomas or metastasis of CRC, and they can accordingly be provided optimal clinical management.

The regulation of the distinct intrinsic phenotypic states in melanoma remain poorly characterised. Here, multi-omics analysis for a panel of 68 early passage melanoma cell lines reveals that cancer cell intrinsic transcriptomic programs are associated with distinct immune features.

Identification of germline pathogenic variants in cancer patients is critical for treatment planning, genetic counseling, and health policymaking. However, previous estimates of the prevalence of germline etiology of pancreatic ductal adenocarcinoma (PDAC) were biased because they were based only on sequencing data of protein-coding regions of known PDAC candidate genes. To determine the percentage of patients with PDAC carrying germline pathogenic variants, we enrolled the inpatients from the digestive health clinics, hematology and oncology clinics, and surgical clinics of a single tertiary medical center in Taiwan for whole genome sequencing (WGS) analysis of genomic DNA. The virtual gene panel of 750 genes comprised PDAC candidate genes and those listed in the COSMIC Cancer Gene Census. The genetic variant types under investigation included single nucleotide substitutions, small indels, structural variants, and mobile element insertions (MEIs). In 8 of 24 (33.3%) patients with PDAC, we identified pathogenic/likely pathogenic variants, including single nucleotide substitutions and small indels in ATM, BRCA1, BRCA2, POLQ, SPINK1 and CASP8, as well as structural variants in CDC25C and USP44. We identified additional patients carrying variants that could potentially affect splicing. This cohort study demonstrates that an extensive analysis of the abundant information yielded by the WGS approach can uncover many pathogenic variants that could be missed by traditional panel-based or whole exome sequencing-based approaches. The percentage of patients with PDAC carrying germline variants might be much higher than previously expected.

Damage to the nervous system can lead to functional impairment, including sensory and motor functions. Importantly, neuropathic pain (NPP) can be induced after nerve injury, which seriously affects the quality of life of patients. Therefore, the repair of nerve damage and the treatment of pain are particularly important. However, the current treatment of NPP is very weak, which promotes researchers to find new methods and directions for treatment. Recently, cell transplantation technology has received great attention and has become a hot spot for the treatment of nerve injury and pain. Olfactory ensheathing cells (OECs) are a kind of glial cells with the characteristics of lifelong survival in the nervous system and continuous division and renewal. They also secrete a variety of neurotrophic factors, bridge the fibers at both ends of the injured nerve, change the local injury microenvironment, and promote axon regeneration and other biological functions. Different studies have revealed that the transplantation of OECs can repair damaged nerves and exert analgesic effect. Some progress has been made in the effect of OECs transplantation in inhibiting NPP. Therefore, in this paper, we provided a comprehensive overview of the biology of OECs, described the possible pathogenesis of NPP. Moreover, we discussed on the therapeutic effect of OECs transplantation on central nervous system injury and NPP, and prospected some possible problems of OECs transplantation as pain treatment. To provide some valuable information for the treatment of pain by OECs transplantation in the future.

Osteoarthritis (OA) is a progressive disease that causes pain, stiffness, and inflammation in the affected joints. Currently, there are no effective treatments for preventing the worst outcomes, such as synovitis or cartilage degradation. Sarcodia montagneana and Corbicula fluminea are common species found in the ocean or in freshwater areas. Their extracts are demonstrated to possess both antioxidative and anti-inflammatory functions. This study aimed to investigate the synergistic effects of the extracts of Sarcodia montagneana (SME) and Corbicula fluminea (FCE) on reducing local and systemic inflammation, as well as their efficacy in OA symptom relief. An in vitro monocytic LPS-treated THP-1 cell model and in vivo MIA-induced mouse OA model were applied, and the results showed that the combinatory usage of SME and FCE effectively suppressed IFN-γ and TNF-α production when THP-1 cells were treated with LPS. SME and FCE also significantly decreased the systemic TNF-α level and joint swelling and prevented the loss of proteoglycan in the cartilage within the joints of OA mice. The data shown here provide a potential solution for the treatment of osteoarthritis.

Hepatocellular carcinoma (HCC) usually recurs after curative surgical resection. Currently, no approved adjuvant therapy has been shown to reduce HCC recurrence rates. In this study, the in vivo effect of sequential combination treatment with recombinant mouse interferon-alpha (rmIFN-α) and an anti-mouse-PD1 antibody on hepatitis B virus (HBV) clearance in mice was evaluated. A Phase I clinical trial was then conducted to assess the safety, tolerability, and inhibitory activity of sequential therapy with ropeginterferon alfa-2b and nivolumab in patients with HCC recurrence who underwent curative surgery for HBV-related HCC. The animal modeling study showed that HBV suppression was significantly greater with the rmIFN-α and anti-PD1 sequential combination treatment in comparison with sole treatment with rmIFN-α or anti-PD1. In the Phase I study, eleven patients completed the sequential therapy with ropeginterferon alfa-2b every two weeks for six doses at 450 µg, followed by three doses of nivolumab every two weeks up to 0.75 mg/kg. A notable decrease in or clearance of HBV surface antigen was observed in two patients. The dose-limiting toxicity of grade 3 alanine transaminase and aspartate aminotransferase increases was observed in one patient. The maximum tolerated dose was then determined. To date, no HCC recurrence has been observed. The treatment modality was well tolerated. These data support the further clinical development of sequential combination therapy as a post-surgery prophylactic measure against the recurrence of HBV-related HCC.