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Background: Hypersensitivity to the new dermal injectable porcine-based collagen with lidocaine featuring a novel cross-linking technology (test filler) for nasolabial fold correction was compared to the commercially available traditional cross-linked dermal injectable porcine-based collagen with lidocaine (control filler). Methods: Recruited participants (n = 279) received a single 0.1 mL intradermal injection of either test filler or control filler in the left forearm as a screening skin allergy test. Injection sites were assessed clinically at 24 h post-implant. Treatment was given to 252 successfully screened participants, and injection sites were monitored for 21 days. Immunological examinations were performed at screening and then at 4 and 24 weeks post-treatment. Observations for adverse events continued until the 52nd week. Results: Intradermal allergy testing results were negative for all the test recipients (0/124) and positive for two control recipients (2/132, 1.5%). Most of the participants exhibited no changes in serum immunoglobulin (IgG, IgM) and complement (C3, C4) levels. No serious adverse events related to the device were recorded. Most adverse events were common complications of dermal filler treatment and were related to the injection site. Most adverse effects were resolved or under control by 52 weeks. Conclusions: Hypersensitivity reactions with the test filler were lower than those with the control filler, validating the safe use of test filler for nasolabial fold correction without the need for pretreatment skin testing. [ABSTRACT FROM AUTHOR]

Background: The ligamentum flavum (LF) degeneration is a critical factor in spinal stenosis, leading to nerve compression and pain. Even with new treatment options becoming available, it is vital to have a better understanding of LF degeneration to ensure the effectiveness of these treatments. Objective: This study aimed to provide insight into LF degeneration by examining the connections between various aspects of LF degeneration, including histology, microstructure, chemical composition, and biomechanics. Method: We analyzed 30 LF samples from 27 patients with lumbar vertebrae, employing magnetic resonance imaging (MRI) to link lumbar disc degeneration grades with fibrosis levels in the tissue. X‐ray diffraction (XRD) analysis assessed microstructural alterations in the LF matrix component due to degeneration progression. Instrumented nanoindentation combined with Raman spectroscopy explored the spatial microbiomechanical and biochemical characteristics of the LF's ventral and dorsal regions. Results: Our outcomes revealed a clear association between the severity of LF fibrosis grades and increasing LF thickness. XRD analysis showed a rise in crystalline components and hydroxyapatite molecules with progressing degeneration. Raman spectroscopy detected changes in the ratio of phosphate, proteoglycan, and proline/hydroxyproline over the amide I band, indicating alterations in the extracellular matrix composition. Biomechanical testing demonstrated that LF tissue becomes stiffer and less extensible with increasing fibrosis. Discussion: Notably, the micro‐spatial assessment revealed the dorsal side of the LF experiencing more significant mechanical stress, alongside more pronounced biochemical and biomechanical changes compared to the ventral side. Degeneration of the LF involves complex processes that affect tissue histology, chemical composition, and biomechanics. It is crucial to fully understand these changes to develop new and effective treatments for spinal stenosis. These findings can improve diagnostic accuracy, identify potential biomarkers and treatment targets, guide personalized treatment strategies, advance tissue engineering approaches, help make informed clinical decisions, and educate patients about LF degeneration. [ABSTRACT FROM AUTHOR]

Purpose: Porcine-based dermal injectable collagen is effective for nasolabial fold correction. In the present study, a new dermal injectable collagen, incorporating a novel cross-linking technology and premixed with lidocaine, was introduced. The study aimed to determine the efficacy of the new dermal injectable collagen in improving bilateral nasolabial fold wrinkles, and reducing pain during injection. Patients and Methods: This prospective, double-blind, multicenter, parallel-group, randomized trial enrolled participants with moderate-to-severe bilateral nasolabial fold wrinkles from February 2019 to March 2021. Participants were randomly assigned to the test group (new dermal injectable collagen with lidocaine featuring a novel cross-linking technology) or control group (traditionally cross-linked dermal injectable collagen with lidocaine). Participants were monitored for adverse events (AEs), and for pain using the Thermometer Pain Scale (TPS) and a visual analog scale (VAS). Efficacy was measured using the Wrinkle Severity Rating Scale (WSRS) and the Global Aesthetic Improvement Scale (GAIS). Results: On the poor or better sides, the 2 groups exhibited a significant decrease in WSRS scores at 4, 12, 24, and 36 weeks after treatment, compared to baseline WSRS scores (all, p < 0.05). Compared to the control group, the test group had a greater decrease in WSRS score (poor or better sides) at 12, 24, 36, and 52 weeks after treatment (all, p < 0.05). A similar observation was also found in the WSRS response rate and GAIS score of the 2 groups. VAS and TPS scores were not significantly different between the 2 groups (p > 0.05), indicating that pain reduction was similar in the 2 groups. All AEs were anticipated AEs associated with facial aesthetic injections, and most recovered within 0 to 30 days without sequelae. There were no differences in AEs between the 2 groups (all, p > 0.05). Conclusion: The new dermal injectable collagen with lidocaine exhibited better efficacy for correcting nasolabial fold wrinkles compared to the control group. Both relieved pain and produced only transient and tolerable AEs. [ABSTRACT FROM AUTHOR]

This study aims to identify a secure and efficient trading approach for investors in highly volatile cryptocurrency markets. While pairs trading is a promising strategy, the available literature on this topic in cryptocurrency markets is limited and primarily based on traditional methods. This study compares six statistical approaches for selecting trading pairs: Cointegration, Correlation, Distance, Fluctuation Behaviour, Hurst Exponent, and Stochastic Differential Residual. We utilise intraday data from 30 cryptocurrencies on the Binance exchange during a three-month period from 1 January 2022 to 31 March 2022. The trading results are measured by 11 criteria covering return, risk, and trade aspects. The findings show that Distance performs well at all three frequencies of 1 minute, 5 minutes, and 60 minutes, with a total return of 208.12%, 236.31%, and 210.36%, respectively. At the 60-minute frequency, this method exhibits low risk and performs impressively even when all other techniques generate negative returns, as well as displays the lowest number of expired counts and the highest success ratio among the methods. At 1-minute and 5-minute frequencies, Cointegration and Hurst Exponent produce results comparable to those of Distance. The Student t-test conducted confirms these conclusions. [ABSTRACT FROM AUTHOR]

In 2022, two novel classification systems for myelodysplastic syndromes/neoplasms (MDS) have been proposed: the International Consensus Classification (ICC) and the 2022 World Health Organization (WHO-2022) classification. These two contemporary systems exhibit numerous shared features but also diverge significantly in terminology and the definition of new entities. Thus, we retrospectively validated the ICC and WHO-2022 classification and found that both systems promoted efficient segregation of this heterogeneous disease. After examining the distinction between the two systems, we showed that a peripheral blood blast percentage ≥ 5% indicates adverse survival. Identifying MDS/acute myeloid leukemia with MDS-related gene mutations or cytogenetic abnormalities helps differentiate survival outcomes. In MDS, not otherwise specified patients, those diagnosed with hypoplastic MDS and single lineage dysplasia displayed a trend of superior survival compared to other low-risk MDS patients. Furthermore, the impact of bone marrow fibrosis on survival was less pronounced within the ICC framework. Allogeneic transplantation appears to improve outcomes for patients diagnosed with MDS with excess blasts in the ICC. Therefore, we proposed an integrated system that may lead to the accurate diagnosis and advancement of future research for MDS. Prospective studies are warranted to validate this refined classification. [ABSTRACT FROM AUTHOR]

Background: Whether the etiology of chronic liver disease (CLD) impacts the overall survival (OS) of patients with hepatocellular carcinoma (HCC) remains unclear. We aim to clarify this issue. Materials and methods: Between 2011 and 2020, 3941 patients who were newly diagnosed with HCC at our institution were enrolled in this study. In patients with multiple CLD etiologies, etiology was classified using the following hierarchy: hepatitis C virus (HCV) > hepatitis B virus (HBV) > alcohol-related > all negative. All negative was defined as negative for HCV, HBV, and alcohol use disorder. Results: Among 3941 patients, 1407 patients were classified with HCV-related HCC, 1677 patients had HBV-related HCC, 145 patients had alcohol-related HCC, and 712 patients had all-negative HCC. Using the all-negative group as the reference group, multivariate analysis showed that HBV is an independent predictor of mortality (hazard ratio: 0.856; 95% confidence interval: 0.745–0.983; p = 0.027). Patients with HBV-related HCC had superior OS compared with patients with other CLD etiologies (p<0.001). Subgroup analyses were performed, for Barcelona Clinic Liver Cancer (BCLC) stages 0–A (p<0.001); serum alpha-fetoprotein (AFP) levels≧20 ng/ml (p<0.001); AFP levels < 20 ng/ml (p<0.001); age > 65 years (p<0.001); and the use of curative treatments (p = 0.002). No significant difference in OS between HBV and other etiologies was observed among patients aged ≤ 65 years (p = 0.304); with BCLC stages B–D (p = 0.973); or who underwent non-curative treatments (p = 0.1). Conclusion: Patients with HBV-related HCC had superior OS than patients with other HCC etiologies. [ABSTRACT FROM AUTHOR]

Background: The risk of first recurrence of hepatocellular carcinoma (HCC) within years 5 to 10 after curative hepatectomy remains unknown. We aimed to assess the incidence and prognostic factors for very late recurrence among patients who achieved 5 years' recurrence-free survival (RFS) after primary resection. Methods: We retrospectively analyzed 337 patients with early-stage HCC underwent primary tumor resection and achieved more than 5 years' RFS. Results: A total of 77 patients (22.8%) developed very late recurrence. The cumulative very late recurrence rate increased from 6.9% and 11.7% to 16.6% at 6, 7, and 8 years, respectively. Patients stopped smoking had a higher rate of very late RFS. Conclusions: The high rates of very late recurrence in HCC indicate that patients warrant continued surveillance, even after 5 recurrence-free years. Moreover, smoking is a risk factor for very late HCC recurrence, and quitting smoking may reduce the risk of very late recurrence. [ABSTRACT FROM AUTHOR]

A nationwide population-based database was utilized in a nested case–control study to explore the association between ambient air pollution exposure and the likelihood of developing connective tissue sarcoma. The study examined 280 cases of connective tissue sarcoma diagnosed between 2000 and 2012. A random sample of 1120 control subjects was selected from a subpopulation of claim records without a connective tissue sarcoma diagnosis in a 1:4 ratio. The control subjects were selected based on similar characteristics as the connective tissue sarcoma patients, including gender, birth year, and the year of diagnosis of the case group with medical records. Risk factors for connective tissue sarcoma were collected for analysis. Our data on exposure to air pollutants was collected from Taiwan's Air Quality Monitoring Network, which has been gathering air quality data from a growing network of sampling stations (now 76) throughout the country since 1997. It was discovered that the risk of connective tissue sarcoma was significantly increased by the Charlson comorbidity index (CCI), elevated levels of specific air pollution indices (e.g., total hydrocarbons (THC), fine particulate matter (PM2.5), and O3_8 (the annual mean of the daily maximum 8-h average concentration of O3), the High Pollutant Standards Index (hPSI) (the percentage of days in a given year in Taiwan where the PSI exceeds 100), and an insurable monthly wage over US$1100. Further investigation is needed to explore the involvement of these air pollutants in the formation of connective tissue sarcoma. [ABSTRACT FROM AUTHOR]

One of the most important organic molecules is metol [4-(methylamino)-phenol sulfate], which finds extensive usage in various applications as a monochromatic material. People, plants, and animals are all affected by it, and it raises serious environmental concerns. Developing a straightforward, quick, affordable, sensitive, and hands-on technique for metol determination in water bodies is of the utmost importance in the current scenario. A low-cost fabrication strategy is presented in this work for the synthesis of a zinc oxide nanoplatelet (ZnO) embedded into boron-doped carbon nitride nanosheet materials (ZnO/2D-BCN) utilizing a high-performance electrochemical sensor. The quantitative and qualitative information about the nanostructure of ZnO/2D-BCN were systematically analyzed further by using standard spectroscopic techniques such as XPS, XRD, FT-IR, EDAX, and Raman spectroscopy. 2D-nonstructural was observed to have a nanoplatelet/nanosheet through FE-SEM and TEM. Furthermore, electrochemical sensors' performance was analyzed by using cyclic and differential pulsed voltammetry techniques. The fabricated ZnO/2D-BCN has peculiar intrinsic structural features, both connectivity and characteristic synergistic effect of B-dopants 2D-structure, which perturb mass transport with highly efficient electrochemical pathways. In addition, the electrochemical sensors of metol and its electrocatalytic mechanism were scrutinized further, which confirmed a fast electron transfer event. The as-prepared ZnO/2D-BCN exposed superior sensing conclusion through LOD (8.6 nM) in a wide-ranging linear 0.039–1617 (μM) as well as a remarkable sensitivity of 0.804 μA μM–1 cm–2. Additionally, other sensing parameters such as remarkable repeatability, electrodes' reproducibility, materials' stability, and a remarkable selectivity toward metol have been performed. Furthermore, the practical feasibility of as-made ZnO/2D-BCN/GCE has been inspected with biological and environment samples such as blood serum, human urine, river, pond, industry, and tap samples as a real sample, revealing excellent rational recovery outcomes. [ABSTRACT FROM AUTHOR]

Acute myeloid leukemia (AML) with CEBPA bZIP in-frame mutations (CEBPAbZIP-inf) is classified within the favorable-risk group by the 2022 European LeukemiaNet (ELN-2022). However, heterogeneous clinical outcomes are still observed in these patients. In this study, we aimed to investigate the mutation profiles and transcriptomic patterns associated with poor outcomes in patients with CEBPAbZIP-inf. One hundred and thirteen CEBPAbZIP-inf patients were identified in a cohort of 887 AML patients homogeneously treated with intensive chemotherapy. Concurrent WT1 or DNMT3A mutations significantly predicted worse survival in AML patients with CEBPAbZIP-inf. RNA-sequencing analysis revealed an enrichment of interferon (IFN) signaling and metabolic pathways in those with a shorter event-free survival (EFS). CEBPAbZIP-inf patients with a shorter EFS had higher expression of IFN-stimulated genes (IRF2, IRF5, OAS2, and IFI35). Genes in mitochondrial complexes I (NDUFA12 and NDUFB6) and V (ATP5PB and ATP5IF1) were overexpressed and were associated with poorer survival, and the results were independently validated in the TARGET AML cohort. In conclusion, concurrent WT1 or DNMT3A mutations and a dysregulated immune and metabolic state were correlated with poor survival in patients with CEBPAbZIP-inf, and upfront allogeneic transplantation may be indicated for better long-term disease control. [ABSTRACT FROM AUTHOR]

A proposed model is used to account for both the recovery rate and regime-switching uncertainties for pricing credit-risky bonds. A two-factor hazard rate model (TFHRM) is also considered, where the dynamics of both instantaneous forward rates and asset values are modeled using Markov-modulated geometric Brownian motions (MMGBMs). Moreover, a macroeconomic factor is incorporated into the MMGBMs. The model complexity is resolved through the introduction of an endogenous intensity function and a recovery rate under the TFHRM. A semi-closed-form solution for pricing defaultable bonds is derived along with a pricing formula for credit spread. A credit cycle is constructed to reflect changes in industry characteristics and macroeconomic factors. The empirical study demonstrates that the inclusion of a stochastic recovery rate increases the model's pricing accuracy, and the results indicate a close interaction among business cycles, recovery rates, and credit ratings. [ABSTRACT FROM AUTHOR]

Simple Summary: Our study elucidates a genetic differentiation of F. taiwana populations across the central mountain ranges of Taiwan, which stands out as a significant geographical feature shaping these populations' genetic landscape. The mountain range acts as a significant topographic barrier, influencing gene flow and contributing to distinct genetic clusters in eastern and western regions. Despite potential mechanisms for passive dispersal, such as human-mediated transportation and monsoon winds, the genetic divergence remains pronounced. These findings provide crucial insights for understanding the species' molecular ecology and can inform targeted pest management strategies. Future research, involving more detailed genomic analyses, will be pivotal in exploring specific genetic adaptations and further elucidating gene flow across these geographical divisions. Forcipomyia (Lasiohelea) taiwana, a small bloodsucking midge, thrives in moderately moist habitats and is commonly found in grassy and bushy areas at an elevation below 250 m. This species exhibits a diurnal biting pattern and shows a marked preference for human blood. Although not known to transmit arthropod-borne diseases, the bites of F. taiwana can induce severe allergic reactions in some individuals. As a significant nuisance in Taiwan, affecting both daily life and the tourism industry, comprehensive studies on its population genetics across different geographical regions remain scarce. The central mountain ranges in Taiwan, comprising more than two hundred peaks above 3000 m in elevation, extend from the north to the south of the island, creating distinct eastern and western geographical divisions. This study utilizes microsatellite markers to explore the genetic differentiation of F. taiwana populations located in the eastern and western regions of the mountain ranges. Our findings reveal substantial genetic differentiation among populations inhabiting Taiwan's western region compared to those in the eastern region. This indicates that the topographical barriers presented by the mountain ranges significantly restrict gene flow, particularly given the species' limited active flight ability and habitat preferences. Although passive dispersal mechanisms, like wind or human activity, could contribute, this study concludes that the gene flow of F. taiwana between the western and eastern regions is primarily influenced by topographical constraints. [ABSTRACT FROM AUTHOR]

Lenvatinib has been approved as one of the first‐line treatments for advanced hepatocellular carcinoma (HCC) due to its high treatment efficacy being non‐inferior to sorafenib. Previous studies have shown well‐controlled viremia contributes to the prognosis of HCC patients receiving first‐line sorafenib; hence, we postulated this association might also exist in HCC patients with lenvatinib treatment. From April 2018 to December 2021, 201 unresectable HCC patients with first‐line lenvatinib treatment in our institute were assessed. High‐effect nucleoside analogues were administered for hepatitis B virus (HBV) control, while direct‐acting antivirals were used for hepatitis C virus (HCV) elimination. Based on our previous study, well‐controlled viremia was defined as patients who had undetectable viremia, or who had been receiving antivirals at least 6 months before lenvatinib. This study enrolled 129 patients, including 85 patients with HBV‐related HCC (HBV‐HCC) and 44 patients with HCV‐related HCC (HCV‐HCC), respectively. Progression‐free survival (PFS) and overall survival (OS) rates between the two groups were not different. Before administration of lenvatinib, 57.1% of the HBV‐HCC patients and 88.4% of the HCV‐HCC patients had well‐controlled viremia, and their PFS (8.8 vs. 3.1 months, p < 0.001) and OS (30.2 vs. 12.8 months, p = 0.041) were better than those who had uncontrolled viremia; moreover, well‐controlled viremia reduced tumor progression in multivariate analysis (Hazard ratio: 0.41, 95% confidence interval: 0.25–0.68, p = 0.001) after adjusting for albumin–bilirubin grade and concurrent treatment. HBV or HCV infection was not associated with tumor progression of HCC patients receiving lenvatinib, but viremia, controlled or not, was. [ABSTRACT FROM AUTHOR]

Congenital heart disease (CHD) represents a significant contributor to both morbidity and mortality in neonates and children. There's currently no analogous dried blood spot (DBS) screening for CHD immediately after birth. This study was set to assess the feasibility of using DBS to identify reliable metabolite biomarkers with clinical relevance, with the aim to screen and classify CHD utilizing the DBS. We assembled a cohort of DBS datasets from the California Department of Public Health (CDPH) Biobank, encompassing both normal controls and three pre-defined CHD categories. A DBS-based quantitative metabolomics method was developed using liquid chromatography with tandem mass spectrometry (LC-MS/MS). We conducted a correlation analysis comparing the absolute quantitated metabolite concentration in DBS against the CDPH NBS records to verify the reliability of metabolic profiling. For hydrophilic and hydrophobic metabolites, we executed significant pathway and metabolite analyses respectively. Logistic and LightGBM models were established to aid in CHD discrimination and classification. Consistent and reliable quantification of metabolites were demonstrated in DBS samples stored for up to 15 years. We discerned dysregulated metabolic pathways in CHD patients, including deviations in lipid and energy metabolism, as well as oxidative stress pathways. Furthermore, we identified three metabolites and twelve metabolites as potential biomarkers for CHD assessment and subtypes classifying. This study is the first to confirm the feasibility of validating metabolite profiling results using long-term stored DBS samples. Our findings highlight the potential clinical applications of our DBS-based methods for CHD screening and subtype classification. [ABSTRACT FROM AUTHOR]

Electrochemical sensors, due to their excellent and unique features, are of high interest nowadays for the detection and monitoring of several biological compounds. In such a case, serotonin (SRN), an important neurotransmitter, was herein studied for its detection in biological fluids since its presence is more crucial to be monitored and detected in clinical and medical applications. Several study strategies have been used to determine the chemical and physical properties. The crystalline size of the constructed copper sulfide (Cu2S) material was measured to be 25.92 nm. The Cu2S was fabricated over the working surface and further analyzed for several sensor parameters to be optimized. The charge transfer resistance of the copper sulfide-modified glassy carbon electrode (Cu2S/GCE) was determined to be about 277.0 Ω. With the linear range from about 0.029 μM to 607.6 μM for SRN, the limit of detection (LOD) was calculated as 3.2 nM, with a good sensitivity of 13.23 μA μM−1 cm2. The sensor experienced excellent repeatability, reproducibility, and long-term stability. The fabricated electrode was selective with the presence of different interfering compounds. The real sample analysis, as determined with the regular addition method with human serum and urine samples, revealed a good recovery percentage. Thus, the employed fabricated electrode material will be highly effective in sensing other analytes of choice. [ABSTRACT FROM AUTHOR]

Purpose: To elucidate whether pro-inflammatory cytokines might influence the commitment of intervertebral disc (IVD)- and ligamentum flavum (LF)-derived progenitor cells toward either osteogenesis or adipogenesis, specifically Interleukin-1β (IL-1β), IL-19, and IL-20. Methods: Sixty patients with degenerative spondylolisthesis and lumbar or lumbosacral spinal stenosis were included in the study. Injuries to the spine, infections, and benign or malignant tumors were excluded. From nine patient samples, IVD- and LF-derived cells were isolated after primary culture, and two clinical samples were excluded due to mycoplasma infection. The effects of IL-1β, IL-19, as well as IL-20 in regulating osteogenic and adipogenic differentiation in vitro were investigated. Results: Primary IVD- and LF-derived cells were found to have a similar cell morphology and profile of surface markers (CD44, CD90, and CD105) as placenta-derived mesenchymal stem cells (MSCs). Primary IVD/LF cells have a high capacity to differentiate into osteocytes and adipocytes. IL-19 had a tendency to promote adipogenesis. IL-20 inhibited osteogenesis and promoted adipogenesis; IL-1β promoted osteogenesis but inhibited adipogenesis. Conclusion: IL-1β, IL-19, and IL-20 impact the adipogenic and osteogenic differentiation of IVD-derived and LF-derived cells. Modulating the expression of IL-1β, IL-19, and IL-20 provides a potential avenue for controlling cell differentiation of IVD- and LF-derived cells, which might have beneficial effect for degenerative spondylolisthesis and spinal stenosis. [ABSTRACT FROM AUTHOR]

Background: Nivolumab and pembrolizumab have not been directly compared in clinical trials, and the aim of this study is to investigate the efficacy and safety of nivolumab versus pembrolizumab in patients with advanced hepatocellular carcinoma (HCC) in real-world practice. Methods: We retrospectively reviewed patients with HCC who received intravenous nivolumab or pembrolizumab alone as second-line and later therapy. The objective response was determined according to the Response Evaluation Criteria in Solid Tumors criteria version 1.1. Adverse events (AEs) were graded based on the National Cancer Institute Common Terminology Criteria for Adverse Events, version 5.0. The Kaplan–Meier method was used to analyze progression-free survival (PFS) and overall survival (OS). Prognostic values were estimated using hazard ratios with 95% confidence intervals (CIs). Results: In total, 120 patients were enrolled, including 95 who received nivolumab and 25 who received pembrolizumab. All patients were staged as Barcelona Clinic Liver Cancer stage C, and 29 patients were classified as Child-Pugh classification B (7). The response rate of the pembrolizumab and nivolumab groups were 8.0% and 7.4%, respectively. There was no significant difference in the median PFS between the pembrolizumab and nivolumab groups (2.7 months versus 2.9 months). The median OS in the nivolumab group was longer than that in the pembrolizumab group (10.8 months versus 8.1 months); however, the difference was not statistically significant. The effects of pembrolizumab and nivolumab on the median PFS and OS were consistent across the subgroups based on baseline characteristics. The severity of all AEs was grades 1–2 without treatment interruption or dose adjustment; there was no statistically significant difference in the incidence of treatment-related AEs between these two groups. Additionally, the percentage of patients receiving subsequent therapy was consistent between the two groups. Conclusion: The efficacy and safety of pembrolizumab and nivolumab were comparable in the management of patients with pretreated HCC in real-world practice. [ABSTRACT FROM AUTHOR]

Myelodysplastic syndromes (MDS) have varied prognoses and require a risk-adapted treatment strategy for treatment optimization. Recently, a molecular prognostic model (Molecular International Prognostic Scoring System [IPSS-M]) that combines clinical parameters, cytogenetic abnormalities, and mutation topography was proposed. This study validated the IPSS-M in 649 patients with primary MDS (based on the 2022 International Consensus Classification [ICC]) and compared its prognostic power to those of the IPSS and revised IPSS (IPSS-R). Overall, 42.5% of the patients were reclassified and 29.3% were up-staged from the IPSS-R. After the reclassification, 16.9% of the patients may receive different treatment strategies. The IPSS-M had greater discriminative potential than the IPSS-R and IPSS. Patients with high, or very high-risk IPSS-M might benefit from allogeneic hematopoietic stem cell transplantation. IPSS-M, age, ferritin level, and the 2022 ICC categorization predicted outcomes independently. After analyzing demographic and genetic features, complementary genetic analyses, including KMT2A-PTD, were suggested for accurate IPSS-M categorization of patients with ASXL1, TET2, STAG2, RUNX1, SF3B1, SRSF2, DNMT3A, U2AF1, and BCOR mutations and those classified as MDS, not otherwise specified with single lineage dysplasia/multi-lineage dysplasia based on the 2022 ICC. This study confirmed that the IPSS-M can better risk-stratified MDS patients for optimized therapeutic decision-making. [ABSTRACT FROM AUTHOR]

Myelodysplastic syndromes (MDS) are a group of clinically and genetically diverse diseases that impose patients with an increased risk of leukemic transformation. While MDS is a disease of the elderly, the interplay between aging and molecular profiles is not fully understood, especially in the Asian population. Thus, we compared the genetic landscape between younger and older patients in a cohort of 698 patients with primary MDS to advance our understanding of the distinct pathogenesis and different survival impacts of gene mutations in MDS according to age. We found that the average mutation number was higher in the older patients than younger ones. The younger patients had more WT1 and CBL mutations, but less mutated ASXL1, DNMT3A, TET2, SF3B1, SRSF2, STAG2, and TP53 than the older patients. In multivariable survival analysis, RUNX1 mutations with higher variant allele frequency (VAF) and U2AF1 and TP53 mutations were independent poor prognostic indicators in the younger patients, whereas DNMT3A and IDH2 mutations with higher VAF and TP53 mutations conferred inferior outcomes in the older patients. In conclusion, we demonstrated the distinct genetic landscape between younger and older patients with MDS and suggested that mutations impact survival in an age‐depended manner. [ABSTRACT FROM AUTHOR]

Pairs trading is a popular quantitative trading strategy with the advantage of a similarity in price movement to financial assets. Assuming that the price spreads of trading pairs are mean-reverting, this strategy exploits the disequilibrium in financial markets to find arbitrage investment opportunities. Pairs trading has been widely applied to stock, ETF, and commodity markets. However, the effectiveness of this method for cryptocurrency markets has yet to be properly explored. Therefore, we examine the profitability of pairs trading for 26 cryptocurrencies traded on the Binance exchange at high frequencies of 1, 5, and 60 min. In addition to the traditional statistical methods of distance, correlation, cointegration, and stochastic differential residual (SDR), we focus on two evolutionary algorithms: genetic algorithm (GA) and non-dominated sorting genetic algorithm II (NSGA-II). During the 79-trading-day period from 11 January to 31 March 2018, NSGA-II showed the best results at all frequencies, with an average return of 2.84%. Among the statistical models, SDR ranks first, whereas Correlation ranks last, with average returns of 1.63% and −0.48%, respectively. The z-test results show that the models are statistically significantly different. We propose NSGA-II as the best candidate for use in pairs trading strategies in cryptocurrency markets. [ABSTRACT FROM AUTHOR]

Intervertebral disc degeneration (IDD) is closely related to changes in the intervertebral disc (IVD) composition and the resulting viscoelastic properties. IDD is a severe condition because it decreases the disc's ability to resist mechanical loads. Our research aims to understand IDD at the cellular level, specifically the changes in the viscoelastic properties of the nucleus pulposus (NP), which are poorly understood. This study employed a system integrating nanoindentation with Raman spectrometry to correlate biomechanics with subtle changes in the biochemical makeup of the NP. The characterization was, in turn, correlated with the degenerative severity of IVD as assessed using magnetic resonance imaging (MRI) of different patients with spinal stenosis, degenerative spondylolisthesis, and degenerative scoliosis. It is shown that there is an increase in the crosslinking ratio in collagen, a reduction in proteoglycan, and a build‐up of minerals upon the rise in the severity level of the disc damage in the NP. Assessment of mechanical characteristics reveals that the increasing disc degeneration makes the NP lose its elasticity, becoming more viscous. This shows that the tissue undergoes abnormalities in weight‐bearing ability, which contributes to spinal instability. The correlation of the individual discs shows that grades III and IV have similarities in the changes of Amide I and III toward the storage modulus. In contrast, grades IV and V correlate with mineralization toward the storage modulus. Reduction of proteoglycan has the highest impact on the changes of the storage modulus in all grades of IDD. Connecting compositional alterations to IVD micromechanics at various degrees of degeneration expands our understanding of tissue behavior and provides critical insight into clinical diagnostics, treatment, and tissue engineering. [ABSTRACT FROM AUTHOR]

Simple Summary: Radiofrequency ablation is a curative treatment for early-stage hepatocellular carcinoma (HCC), but many factors influence the survival of these patients and should be taken into consideration during treatment planning. Our retrospective study reports the outcome of radiofrequency ablation (RFA) as primary treatment and analyzes seven factors related to a poorer prognosis: Age greater than 65 years, albumin-bilirubin (ALBI) grades 2 and 3, AST-to-platelet ratio index (APRI) greater than 1, tumor size larger than 3 cm, diabetes mellitus, end-stage renal disease, and tumor number greater than 1. By incorporating these variables, we developed a simplified nomogram that enables personalized predictions of overall survival following RFA for HCC. This tool can support physicians in clinical decision-making by providing individualized prognostic information. Our objective was to develop a predictive nomogram that could estimate the long-term survival of patients with very early/early-stage hepatocellular carcinoma (HCC) undergoing radiofrequency ablation (RFA). For this retrospective study, we enrolled 950 patients who initially received curative RFA for HCC at Barcelona Clinic Liver Cancer (BCLC) stages 0 and A between 2002 and 2016. Factors predicting poor survival after RFA were investigated through a Cox proportional hazard model. The nomogram was constructed using the investigated variables influencing overall survival (OS). After a median follow-up time of 6.25 years, 400 patients had died, and 17 patients had received liver transplantation. The 1-,3-,5-,7-, and 10-year OS rates were 94.5%, 73.5%, 57.9%, 45.7%, and 35.8%, respectively. Multivariate analysis showed that age greater than 65 years, albumin-bilirubin (ALBI) grades 2 and 3, AST-to-platelet ratio index (APRI) greater than 1, tumor size larger than 3 cm, diabetes mellitus, end-stage renal disease, and tumor number greater than 1 were significantly associated with poor OS. The nomogram was constructed using these seven variables. The validation results showed a good concordance index of 0.683. When comparing discriminative ability to tumor, node, and metastasis (TNM), BCLC, and Cancer of the Liver Italian Program (CLIP) staging systems, our nomogram had the highest C-index for predicting mortality. This nomogram provides useful information on prognosis post-RFA as a primary treatment and aids physicians in decision-making. [ABSTRACT FROM AUTHOR]

Introduction: High-dose dual therapy (HDDT) can attain acceptable eradication rates provided that the optimal doses, timing and treatment duration are applied. The existing evidence still shows inconsistent reports (< 90%) on HDDT therapy except in some Asian countries. We aimed to assess and compare the efficacy of 14-day HDDT by comparing it to 14-day rabeprazole-containing hybrid therapy (HT) and to investigate the host and bacterial factors predicting the treatment outcomes of eradication therapies. Methods: In this open-label, randomized controlled trial, we recruited 243 naïve Helicobacter pylori-infected patients from September 1, 2018, to November 30, 2021. They were randomly allocated (1:1) to the HDDT group (rabeprazole 20 mg and amoxicillin 750 mg q.i.d for 14 days, n = 122) and the HT group (rabeprazole 20 mg and amoxicillin 1 g b.i.d. for 7 days, followed by rabeprazole 20 mg, amoxicillin 1 g, clarithromycin 500 mg and metronidazole 500 mg b.i.d. for 7 days, n = 121). Twelve patients were absent during follow-up in the HDDT group and 4 in the HT group, resulting in 110 for the HDDT group and 117 for HT group in the per protocol (PP) study. The outcome was determined by urea breath tests 8 weeks later. Results: The eradication rates for the HDDT and HT groups were 77.0% (95% confidence interval [CI]: 68.5% to 84.1%) and 94.2% (95% CI: 88.4% to 97.6%) (P < 0.001) in intention-to-treat analysis; 85.5% (95% CI: 77.5% to 91.5%) and 97.4% [95% CI: 92.6% to 99.5%] (P = 0.001) in per protocol analysis. The adverse event rates were 7.3% in the HDDT group and 14.5% in the HT group (P = 0.081). The habit of coffee drinking was the dependent factor for eradication failure in the HDDT group (88.2% vs. 68.8%, P = 0.040), but had no influence in the HT group (97.9% versus 95.0%, P = 0.449) in the univariate analysis. Conclusion: This study demonstrated that 14-day rabeprazole-containing HDDT did not achieve > 90% eradication rates for first-line H. pylori eradication as 14-day rabeprazole-containing HT did. HDDT is a potentially beneficial combination, which involves only two drugs with mild adverse effects; more precise studies are urged to find answers regarding these failures. This clinical trial was registered retrospectively on 28 November, 2021, as ClinicalTrials.gov identifier: NCT05152004. [ABSTRACT FROM AUTHOR]

Introduction: Open reduction and internal fixation with plates is the most widespread surgery in traumatic pubic symphysis diastasis. However, implant failure or recurrent diastasis was commonly observed during follow-up. The aim of our study was to evaluate the radiologic findings and clinical outcomes. Materials and methods: Sixty-five patients with traumatic pubic symphysis diastasis treated with plating between 2008 and 2019 were retrospectively reviewed. The exclusion criteria were a history of malignancy and age under 20 years. Radiographic outcomes were determined by radiograph findings, including pubic symphysis distance (PSD) and implant failure. Clinical outcomes were assessed according to the Majeed score at the final follow-up. Results: Twenty-eight patients were finally included. Nine patients (32%) experienced implant failure, including four (14%) with screw loosening and five (18%) with plate breakage. Only one patient underwent revision surgery. Postoperatively, a significant increase in PSD was observed at 3 months and 6 months. Postoperative PSD was not significantly different between patients with single plating and double plating, but it was significantly greater in the implant-failure group than in the non-failure group. The Majeed score was similar between patients with single plating and double plating or between the implant-failure group and the non-failure group. Body mass index, number of plates, age, and initial injured PSD were not significantly different between the implant-failure group and the non-failure group. Only a significant male predominance was observed in the implant-failure group. Conclusion: A gradual increase in the symphysis distance and a high possibility of implant failure may be the distinguishing features of traumatic pubic symphysis diastasis fixation. The postoperative symphyseal distance achieved stability after 6 months, even after implant failure. Radiographic outcomes, such as increased symphysis distance, screw loosening, and plate breakage, did not affect clinical functional outcomes. [ABSTRACT FROM AUTHOR]

Simple Summary: Hepatocellular carcinoma (HCC) is a highly aggressive and lethal form of liver cancer, and most patients with HCC die due to HCC-related causes. Although most patients die of HCC-related causes, non–HCC-related death represents a competing event among patients who engage in alcohol use and receive curative treatment and among patients 75 years and older in the hepatitis B virus and all-negative groups who receive curative treatments. All negative was defined as negative for hepatitis C virus, hepatitis B virus, and alcohol-related causes. The results of the current study underscore the importance of assessing and managing underlying comorbidities, especially among certain subgroups of patients with HCC. This study was conducted to determine whether the causes of death among patients with hepatocellular carcinoma (HCC) differ according to chronic liver disease (CLD) etiology. Between 2011 and 2020, 3977 patients who were newly diagnosed with HCC at our institution were enrolled in this study. We determined whether the cause of death was HCC-related and non-HCC-related. For patients with multiple CLD etiologies, etiology was classified using the following hierarchy: hepatitis C virus (HCV) > hepatitis B virus (HBV) > alcohol-related causes > all negative. All negative was defined as negative for HCV, HBV, and alcohol-related causes. Among 3977 patients, 1415 patients were classified as HCV-related, 1691 patients were HBV-related, 145 patients were alcohol-related, and 725 patients were all negative. HCC-related mortality was the leading cause of death, irrespective of etiology. Among patients who underwent curative treatment, HCC-related mortality was the leading cause of death for patients in the HCV, HBV, and all-negative groups, but not for patients in the alcohol-related group. Among patients 75 years and older who underwent curative treatment, HCC-related mortality was the leading cause of death in the HCV but not HBV or all-negative groups. In conclusion, although most patients with HCC die due to HCC-related causes, non-HCC-related mortality represents a competing event in certain patient subgroups. The current study results underscore the importance of assessing and managing underlying comorbidities, particularly among patients with HCC at risk of non-HCC-related mortality. [ABSTRACT FROM AUTHOR]

A tissue preparation method will inevitably alter the tissue content. This study aims to evaluate how different common sample preparation methods will affect the tissue morphology, biomechanical properties, and chemical composition of samples. The study focuses on intervertebral disc (IVD) tissue; however, it can be applied to other soft tissues. Raman spectroscopy synchronized with nanoindentation instrumentation was employed to investigate the compositional changes of IVD, specifically, nucleus pulposus (NP) and annulus fibrosus (AF), together with their biomechanical properties of IVD. These properties were examined through the following histological specimen types: fresh cryosection (control), fixed cryosection, and paraffin-embedded. The IVD tissue could be located using an optical microscope under three different preparation methods. Paraffin-embedded samples showed the most explicit details where the lamellae structure of AF could be identified. In terms of biomechanical properties, there was no significant difference between the fresh and fixed cryosection (p > 0.05). In contrast, the fresh cryosection and paraffin-embedded samples showed a significant difference (p < 0.05). It was also found that the tissue preparations affected the chemical content of the tissues and structure of the tissue, which are expected to contribute to biomechanical properties changes. Fresh cryosection and fixed cryosection samples are more promising to work with for biomechanical assessment in histological tissues. The findings fill essential gaps in the literature by providing valuable insight into the characteristics of IVD at the microscale. This study can also become a reference for a better approach to assessing the mechanical properties and chemical content of soft tissues at the microscale. [ABSTRACT FROM AUTHOR]

Background: The role of des-γ-carboxy prothrombin (DCP) in patients undergoing radiofrequency ablation (RFA) for hepatocellular carcinoma (HCC) needs to be clarified. Materials and methods: 174 HCC patients that underwent RFA were enrolled. We calculated the HLs of DCP from the available values before and on first day after ablation and assessed the correlation between HLs of DCP and RFA efficacy. Results: Of 174 patients, 63 with pre-ablation DCP concentrations of ≥80 mAU/mL were analyzed. The ROC analysis showed the optimal cut-off value of HLs of DCP for predicting RFA response was 47.5 h. Therefore, we defined short HLs of DCP < 48 h as a predictor of favorable treatment response. Of 43 patients with a complete radiological response, 34 (79.1%) had short HLs of DCP. In 36 patients with short HLs of DCP, 34 (94.4%) had a complete radiologic response. The sensitivity, specificity, accuracy, positive predictive value, and negative predictive value were 79.1%, 90.0%, 82.5%, 94.4%, and 66.7%. During the 12-month follow-up, patients who had short HLs of DCP had a better disease-free survival rate than patients with long HLs of DCP (p < 0.001). Conclusions: Short HLs of DCP < 48 h calculated on the first day post-RFA are a useful predictor for treatment response and recurrence-free survival after RFA. [ABSTRACT FROM AUTHOR]

The influenza-specific antibody repertoire is continuously reshaped by infection and vaccination. The host immune response to contemporary viruses can be redirected to preferentially boost antibodies specific for viruses encountered early in life, a phenomenon called original antigenic sin (OAS) that is suggested to be responsible for diminished vaccine effectiveness after repeated seasonal vaccination. Using a new computational tool called Neutralization Landscapes, we tracked the progression of hemagglutination inhibition antibodies within ferret antisera elicited by repeated influenza A/H3 infections and deciphered the influence of prior exposures on the de novo antibody response to evolved viruses. The results indicate that a broadly neutralizing antibody signature can nevertheless be induced by repeated exposures despite OAS induction. Our study offers a new way to visualize how immune history shapes individual antibodies within a repertoire, which may help to inform future universal influenza vaccine design. [ABSTRACT FROM AUTHOR]

A set of myelodysplasia-related (MDS-R) gene mutations are incorporated into the 2022 European LeukemiaNet risk classification as adverse genetic factors for acute myeloid leukemia (AML) based on their poor prognostic impact on older patients. The impact of these mutations on younger patients (age < 60 years) remains elusive. In the study of 1213 patients with de novo non-M3 AML, we identified MDS-R mutations in 32.7% of the total cohort, 44.9% of older patients and 23.4% of younger patients. The patients with MDS-R mutations had a significantly lower complete remission rate in both younger and older age groups. With a median follow-up of 9.2 years, the MDS-R group experienced shorter overall survival (P = 0.034 for older and 0.035 for younger patients) and event-free survival (P = 0.004 for older and 0.042 for younger patients). Furthermore, patients with MDS-R mutations more frequently harbored measurable residual disease that was detectable using next generation sequencing at morphological CR than those without MDS-R mutations. Allogeneic hematopoietic stem cell transplantation (allo-HSCT) might ameliorate the negative impact of MDS-R mutations. In summary, AML patients with MDS-R mutations have significantly poorer outcomes regardless of age. More intensive treatment, such as allo-HSCT and/or novel therapies, is warranted for AML patients with MDS-R mutations. [ABSTRACT FROM AUTHOR]

A tissue preparation method will inevitably alter the tissue content. This study aims to evaluate how different common sample preparation methods will affect the tissue morphology, biomechanical properties, and chemical composition of samples. The study focuses on intervertebral disc (IVD) tissue; however, it can be applied to other soft tissues. Raman spectroscopy synchronized with nanoindentation instrumentation was employed to investigate the compositional changes of IVD, specifically, nucleus pulposus (NP) and annulus fibrosus (AF), together with their biomechanical properties of IVD. These properties were examined through the following histological specimen types: fresh cryosection (control), fixed cryosection, and paraffin-embedded. The IVD tissue could be located using an optical microscope under three different preparation methods. Paraffin-embedded samples showed the most explicit details where the lamellae structure of AF could be identified. In terms of biomechanical properties, there was no significant difference between the fresh and fixed cryosection (p > 0.05). In contrast, the fresh cryosection and paraffin-embedded samples showed a significant difference (p < 0.05). It was also found that the tissue preparations affected the chemical content of the tissues and structure of the tissue, which are expected to contribute to biomechanical properties changes. Fresh cryosection and fixed cryosection samples are more promising to work with for biomechanical assessment in histological tissues. The findings fill essential gaps in the literature by providing valuable insight into the characteristics of IVD at the microscale. This study can also become a reference for a better approach to assessing the mechanical properties and chemical content of soft tissues at the microscale. [ABSTRACT FROM AUTHOR]

In the present study, we have designed a highly conductive electrode material niobium carbide (NbC) entangled with copper phosphate (Cu3P2O8). The combined features of the efficient electrocatalyst with improved electrical conductivity, more active sites, with a high surface area were employed for the electrochemical sensing of melatonin (MLT). MLT is a naturally secreted hormone in our brain responsible for maintaining our daily circadian cycle. The detection of such hormones in clinical studies can help maintain several problems. The Cu3P2O8/NbC was initially characterized to analyze the physicochemical properties. The high crystalline Cu3P2O8 resembled a self-assembled flake ball-like structure entangled with NbC sheets. The synergistic effect between the catalyst enhances the electrochemical performance of MLT. The Cu3P2O8/NbC fabricated glassy carbon electrode obtained an enhanced oxidation response of MLT. The linearity range of MLT was about 0.014–1517.68 μM with a low limit of detection of about 0.0083 μM. The fabricated electrode showed high selectivity to the interfering compounds added and the sensitivity was about 5.137 μA μM–1 cm–2. The real samples showed good results at the Cu3P2O8/NbC/GCE. The Cu3P2O8/NbC/GCE will be more efficient and reliable in detecting the employed drugs or any other analytes of choice. Thus, the low cost, with improved electrochemical performances and significant features of the prepared electrode will be of great interest. [ABSTRACT FROM AUTHOR]

Saliency-based position sensorless machine drive with the pulsewidth modulation (PWM) voltage switching frequency injection has advantages of high estimation bandwidth and low acoustic noise. However, multiple currents must be sampled every PWM cycle for spatial saliency calculation. Besides, the switching frequency voltage injection distorts the symmetric PWM voltage pattern. For these saliency-based drives, the PWM injection is the tradeoff between the transient estimation bandwidth and steady state estimation error. This article proposes a modified PWM voltage injection through the measurement vector insertion (MVI) for sensorless position estimation. By integrating the MVI with discontinuous PWM, the proposed injection maintains the symmetric PWM voltage for machine control. This MVI-based PWM (MVIPWM) improves the saliency-based drive among voltage harmonics, current harmonics, and position estimation error. The proposed MVIPWM injection is compared to other PWM injection methods on an interior permanent magnet machine. All advantages of MVIPWM on the saliency-based drive are verified by experimental results. [ABSTRACT FROM AUTHOR]

Background: The approved dose of nivolumab is 3 mg/kg or a flat dose of 240 mg for indications. There is no dose-response relationship for nivolumab; therefore, a low-dose regimen may be an option to reduce financial toxicity. This study was designed to investigate the efficacy and safety of low-dose nivolumab in the management of hepatocellular carcinoma (HCC).Methods: We retrospectively reviewed patients with HCC who received 20 or 100 mg of nivolumab intravenously every 2 weeks. The objective response rate was determined in accordance with the Response Evaluation Criteria in Solid Tumors criteria version 1.1. The Cox regression model and Kaplan-Meier method were used to analyze hazard factors, progression-free survival (PFS), and overall survival (OS). Adverse events (AEs) were assessed according to the National Cancer Institute Common Terminology Criteria for Adverse Events version 5.0.Results: In total, 78 patients were enrolled, including 49 with hepatitis B virus (HBV) and 23 with hepatitis C virus (HCV). All patients were staged as Barcelona Clinic Liver Cancer stage C, and 20 patients were classified as having Child-Pugh classification B (7). Nivolumab 20 mg was an independent prognostic factor for better PFS, and albumin-bilirubin grade 1 was the independent prognostic factor for superior OS in the multivariate analyses. Patients with better HBV (HBV DNA < 500 IU/ml) and HCV (HCV RNA undetectable) controls had superior OS. All AEs were grade 1-2 in severity, and all patients tolerated nivolumab without treatment interruption or dose adjustment. Additionally, 31 patients underwent subsequent therapy after nivolumab treatment.Conclusion: Low-dose nivolumab may be effective with manageable toxicity and can be an alternative option to reduce financial toxicity in patients with advanced HCC who cannot afford the high cost of immune checkpoint inhibitors in real-world practice. [ABSTRACT FROM AUTHOR]

In this paper, a bidirectional converter with multi-mode control strategies is proposed for a battery energy storage system (BESS). This proposed converter, which is composed of a half-bridge-type dual-active-bridge (HBDAB) converter and an H-bridge inverter, is able to operate the BESS with different power conditions and achieve the DC–AC function for lower input DC voltage applications. For the HBDAB converter, the variable-frequency control (VFC) and phase-shift control (PSC) are both adopted to achieve zero-voltage switching over a wider power range and the battery module balance control capability for BESS, respectively. In addition, the interleaved configuration is used to reduce the current ripple and increase the overall current rating. For the H-bridge inverter, the unipolar control mode (UCM) and totem-pole control mode (TPCM) are adopted to manage the real and reactive current control under different AC grid conditions. The UCM offers a reduction in current ripple for real and reactive power control. The TPCM is able to eliminate switching losses and achieve higher conversion efficiency for pure real power control. Considering applications for battery energy storage systems, the principle of operation and voltage gain analysis are described. Finally, computer simulations and hardware experimental results from a prototype system are presented to verify the performance of the proposed converter with the different control strategies. [ABSTRACT FROM AUTHOR]

The management strategies of thoracolumbar (TL) burst fractures include posterior, anterior, and combined approaches. However, the rigid constructs pose a risk of proximal junctional failure. In this study, we aim to systemically evaluate the biomechanical performance of different TL reconstruction constructs using finite element analysis. Furthermore, we investigate the motion and the stress on the proximal junctional level adjacent to the constructs. We used a T10-L3 finite element model and simulated L1 burst fracture. Reconstruction with posterior instrumentation (PI) alone (U2L2 and U1L1+(intermediate screw) and three-column spinal reconstruction (TCSR) constructs (U1L1+PMMA and U1L1+Cage) were compared. Long-segment PI resulted in greater global motion reduction compared to constructs with short-segment PI. TCSR constructs provided better stabilization in L1 compared to PI alone. Decreased intradiscal and intravertebral pressure in the proximal level were observed in U1L1+IS, U1L1+PMMA, and U1L1+Cage compared to U2L2. The stress and strain energy of the pedicle screws decreased when anterior reconstruction was performed in addition to PI. We showed that TCSR with anterior reconstruction and SSPI provided sufficient immobilization while offering additional advantages in the preservation of physiological motion, the decreased burden on the proximal junctional level, and lower risk of implant failure. [ABSTRACT FROM AUTHOR]

The coincident downregulation of NR4A1 and NR4A3 has been implicated in myeloid leukemogenesis, but it remains unknown how these two genes function in myeloid cells and how their combined downregulation promotes myeloid leukemogenesis. Since NR4A1 abrogation is thought to confer a survival and proliferation advantage to myeloid cells, we hypothesized that downregulation of NR4A3 may have a complementary effect on myeloid cell differentiation. First, we tested the association between differentiation status of leukemic cells and NR4A3 expression using two large clinical datasets from patients with different acute myeloid leukemia (AML) subtypes. The analysis revealed a close association between differentiation status and different subtypes of AML Then, we probed the effects of differentiation-inducing treatments on NR4A3 expression and NR4A3 knockdown on cell differentiation using two myeloid leukemia cell lines. Differentiation-inducing treatments caused upregulation of NR4A3, while NR4A3 knockdown prevented differentiation in both cell lines. The cell culture findings were validated using samples from chronic myeloid leukemia (CML) patients at chronic, accelerated and blastic phases, and in acute promyelocytic leukemia (APL) patients before and after all trans-retinoic acid (ATRA)-based differentiation therapy. Progressive NR4A3 downregulation was coincident with impairments in differentiation in patients during progression to blastic phase of CML, and NR4A3 expression was increased in APL patients treated with ATRA-based differentiating therapy. Together, our findings demonstrate a tight association between impaired differentiation status and NR4A3 downregulation in myeloid leukemias, providing a plausible mechanistic explanation of how myeloid leukemogenesis might occur upon concurrent downregulation of NR4A1 and NR4A3. [ABSTRACT FROM AUTHOR]

Featured Application: At present, there is no relevant research which explores possible lesions in ultrasound images that may exist in acoustic shadow; only a differential diagnosis can be made. This current work addresses the use of a reliable posterior restoration algorithm for possible acoustic shadowed lesions. Our results reveal the potential for a SAFT-based restorative application that may provide diagnostic information in medical sonography. The phenomenon of acoustic shadowing on ultrasonography is characterized by an echo signal void behind structures that strongly absorb or reflect ultrasonic energy. In medical ultrasonography, once the ultrasound energy is shielded, acoustic shadowing makes it difficult to create an image, leading to misinterpretations and obscure diagnoses. Hence, instead of dealing with the defocused problem encountered in an ultrasound scan (US), this current research focuses on revealing the existence of an acoustically shadowed target (or a potential lesion) using a well-known restoration algorithm, i.e., the synthetic aperture focusing technique (SAFT). To demonstrate the effects of an acoustic shadow on an ultrasound scan (US), a forward model study is carried out. In laboratory manipulations, a purposely designed physical model is created and then scanned using B-mode and pitch/catch arrangements to carry out shadowed and shadow-free scans in a water tank. Thereafter, making use of a delay-and-sum (DAS) operation, the echo signals are processed by the synthetic aperture focusing technique (SAFT) to perform image restoration. The results of the restoration process show that the SAFT algorithm performs well with respect to directional shadowing. Once the target or lesion is positioned in a total anechoic zone, or even in a multi-channel scan, it will fail. [ABSTRACT FROM AUTHOR]

Simple Summary: Previous studies reported hepatitis C virus-related hepatocellular carcinoma (HCV-HCC) patients might have better prognosis than hepatitis B virus-related HCC (HBV-HCC) patients at using sorafenib. However, the information about status of viremia was limited in these studies. We defined well-controlled viremia as patients who had undetectable viremia, or who had been receiving antivirals at least six months before sorafenib. We reported 116 (65.2%) HBV-HCC patients and 62 (34.8%) HCV-HCC patients who received sorafenib, and progression-free survival and overall survival (OS) rates between these two groups were not different. Before sorafenib, 56% of HBV-HCC patients and 54.8% of HCV-HCC patients had well-controlled viremia and their OS was superior to those who had uncontrolled viremia (15.5 vs. 11.1 months, p = 0.001). Besides, well-controlled viremia was associated with mortality in multivariate analysis (Hazard ratio: 0.63, 95% confidence interval: 0.42–0.93, p = 0.022). The significance of our study is the first research to confirm the prognostic value of well-controlled viremia between HBV-HCC and HCV-HCC patients receiving sorafenib. Besides, HBV or HCV infection was not associated with the outcome, neither in univariate nor in multivariate analysis. Without analyzing the status of viremia, hepatitis C virus-related hepatocellular carcinoma (HCV-HCC) patients are proposed to have better prognosis than hepatitis B virus-related HCC (HBV-HCC) patients using sorafenib. We aimed to elucidate the efficacy of concurrent sorafenib and anti-viral treatment for HCC patients with HBV or HCV infection in real world. Between January 2018 and January 2021, 256 unresectable HCC patients receiving first-line sorafenib were evaluated. High-potency nucleoside analogs were used for HBV control, whereas direct-acting antivirals were administered for HCV eradication. Well-controlled viremia was defined as patients who had undetectable viremia, or who had been receiving antivirals at least 6 months before sorafenib. We recruited 116 (65.2%) HBV-HCC patients and 62 (34.8%) HCV-HCC patients. Using sorafenib, progression-free survival and overall survival (OS) rates between these two groups were not different. Before sorafenib, 56% of HBV-HCC patients and 54.8% of HCV-HCC patients had well-controlled viremia and their OS was superior to those who had uncontrolled viremia (15.5 vs. 11.1 months, p = 0.001). Dividing our patients into four subgroups as well-controlled HCV viremia, well-controlled HBV viremia, uncontrolled HCV viremia, and uncontrolled HBV viremia, their OS rates were distributed with a significantly decreasing trend as 21.9 months, 15.0 months, 14.2 months, and 5.7 months (p = 0.009). Furthermore, well-controlled viremia was associated with mortality in multivariate analysis (Hazard ratio: 0.63, 95% confidence interval: 0.42–0.93, p = 0.022). In real-life, HBV or HCV infection did not contribute to the prognosis of HCC patients receiving sorafenib; however, whether viremia was controlled or not did contribute. [ABSTRACT FROM AUTHOR]

Degenerative disc disease (DDD) is an important cause of low back pain. Repetitive tensile stress from the daily motion of the spine predisposes it to injury of the annulus fibrosus (AF) which causes IVD degeneration. This study aims to determine the causal relationship between mechanical stretch and osteogenesis in the AF cells of IVD as affected by bone morphogenic proteins (BMPs), specifically BMP-2/6 heterodimers. Our results found that 15% tensile stress (high cyclic stretching, HCS) may induce the expression of osteogenesis-related markers (Runx2, osterix) by upregulating BMP-2/6 heterodimeric ligands and their receptors on the human AF cell line. HCS also induced transient phosphorylation of p38 mitogen-activated protein (MAP) kinase and SMAD1/5/8. Neutralizing antibodies to the BMP-2/6 receptor (ALK3) blocked the expression of Runx2 and osterix, as well as the phosphorylation of p38 and SMAD1/5/8. In addition, treatment with a p38 MAPK inhibitor (SB203580) or siRNA to neutralize the effects of SMAD1/5/8 suppressed tensile stress-induced Runx2 and osterix expression. Mechanical stretching induces activation of p38 MAP kinase and SMAD1/5/8 signaling pathways, followed by the upregulation of BMP-2/6 heterodimer expression, thereby stimulating osteogenic Runx2 and osterix expression on AF cells. HCS may accelerate the progression of IVD degeneration by promoting an osteogenic response. [ABSTRACT FROM AUTHOR]

A20FMDV2 is a 20-mer peptide that exhibits high selectivity and affinity for the tumour-related αvβ6 integrin that can compete with extracellular ligands for the crucial RGD binding site, playing a role as a promising αvβ6-specific inhibitor for anti-cancer therapies. Unfortunately, the clinical value of A20FMDV2 is limited by its poor half-life in blood caused by rapid renal excretion and its reported high susceptibility to serum proteases. The incorporation of poly (ethylene glycol) chains, coined PEGylation, is a well-established approach to improve the pharmacokinetic properties of drug molecules. Here, we report a systematic study on the incorporation of a varying number of ethylene glycol units (1–20) into the A20FMDV2 peptide to establish the effects of PEGylation size on the peptide stability in both rat serum and human plasma. In addition, the effect of acetyl and propionyl PEGylation handles on peptide stability is also described. Selected peptide analogues were assessed for integrin-αvβ6-targeted binding, showing good specificity and activity in vitro. Stability studies in rat serum established that all of the PEGylated peptides displayed good stability, and an A20FMDV2 peptide containing twenty ethylene glycol units (PEG20) was the most stable. Surprisingly, the stability testing in human plasma identified shorter PEGs (PEG2 and PEG5) as more resistant to degradation than longer PEGs, a trend which was also observed with affinity binding to integrin αvβ6. [ABSTRACT FROM AUTHOR]

Excessive mechanical loading is a major cause of spinal degeneration, typically originating from a tear in the annulus fibrosus (AF). Endoplasmic reticulum (ER) stress and NLRP3 (NOD-, LRR- and pyrin domain-containing protein 3) inflammasome have been implicated in the pathogenesis of intervertebral disc (IVD) degeneration. However, the causal relationship between the mechanical stretching of AF cells and the NLRP3 inflammasome response associated with ER stress remains scarce. To elucidate the pathogenesis and regulatory mechanisms of mechanical stretch-induced IVD degeneration, human AF cell lines were subjected to different degrees of cyclic stretching to simulate daily spinal movements. Our results indicated that 15% high cyclic stretch (HCS) induced the expression of NLRP3 and interleukin-1 beta (IL-1β) and was also responsible for the increased expression of NADPH (nicotinamide adenine dinucleotide phosphate) oxidase 2 (NOX2) and reactive oxygen species (ROS) in human AF cells. In addition, HCS increased the expression of glucose-regulated protein 78 (GRP78), an ER stress chaperone, which was neutralized with tauroursodeoxycholic acid (TUDCA), an ER stress inhibitor. In addition, HCS was found to induce thioredoxin-interacting protein (TXNIP) expression and NLRP3 inflammasome activation, which can be suppressed by si-NOX2 or the NOX2 inhibitor GSK2795039. Consequently, HCS upregulated ER stress and ROS production, leading to increased NLRP3 and IL-1β expression in human AF cells, and may further accelerate IVD degeneration. [ABSTRACT FROM AUTHOR]

This article presents a robust passivity-based control (PBC) strategy to mitigate the instability effect of the dc–dc boost power converter supplying a constant power load and a constant voltage load in dc microgrid systems. The control robustness of the PBC against both line and load variation is significantly improved by adding the nonlinear disturbance observer (NDO). Using the disturbance estimation technique, this observer works in parallel with the PBC strategy to compensate the disturbances of the system through a feed-forward compensation channel. Based on the dissipation property, the PBC strategy ensures the system stability, whereas the NDO guarantees global trajectory tracking to the reference voltage during disturbances. This control strategy not only ensures large-signal stability of the system, but also provides a fastest recovery performance during disturbances of the system as compared with other PBC strategies. The hardware-in-loop and real-hardware experimental results are provided to verify the control robustness of the proposed control strategy. [ABSTRACT FROM AUTHOR]

Background: This study investigated the incidence and predictors of hepatitis B virus (HBV) relapse in patients with hepatitis B e antigen (HBeAg)-positive chronic hepatitis B who discontinued entecavir (ETV) or tenofovir disoproxil fumarate (TDF).Methods: A total of 205 and 111 HBeAg-positive patients without cirrhosis who had stopped ETV or TDF treatment, respectively, for at least 6 months were recruited.Results: In the entire cohort, patients with HBeAg seroconversion during treatment, and propensity score-matched patients, those who discontinued TDF had significantly higher rates of virological and clinical relapse than patients who discontinued ETV therapy. Multivariate analysis identified that TDF was independently associated with virological and clinical relapse in the entire cohort and subgroup analysis. Patients with HBeAg loss without anti-HBe antibody formation during treatment had significantly higher rates of off-therapy HBV relapse and HBeAg seroreversion than patients with HBeAg seroconversion during treatment. The hepatitis B core-related antigen (HBcrAg) level at end of treatment (EOT) was independently associated with HBV relapse and HBeAg seroreversion in all patients and patients with HBeAg seroconversion during treatment.Conclusions: TDF therapy, HBeAg loss without seroconversion during treatment, and higher HBcrAg levels at EOT are significant predictors of HBV relapse in HBeAg-positive patients who discontinued ETV or TDF. [ABSTRACT FROM AUTHOR]

This study investigated the kinetics in HBsAg and the HBsAg loss rate after entecavir or tenofovir disoproxil fumarate (TDF) cessation in patients with chronic hepatitis B (CHB) who achieved virological suppression after virological relapse without clinical relapse. A total 504 HBeAg-negative, non-cirrhotic patients who previously received entecavir or TDF with post-treatment and who were followed up for at least 30 months were included. Of the 504 patients, 128 achieved sustained virological suppression (Group I), and 81 experienced virological relapse without clinical relapse. Of the 81 patients, 52 had intermittent or persistent HBV DNA > 2000 IU/mL (Group II), and 29 achieved persistent virological suppression (HBV DNA < 2000 IU/mL) for at least 1.5 years (Group III) after virological relapse. A generalized estimating equations analysis showed that Groups I and III experienced larger off-treatment HBsAg declines than Group II (both, p < 0.001). The post-treatment HBsAg declines of Group I and Group III were similar (p = 0.414). A multivariate analysis showed that there were no differences in the HBsAg change and HBsAg decline (p = 0.920 and 0.886, respectively) or HBsAg loss rate (p = 0.192) between Group I and Group III. The patients who achieved persistent viral suppression after HBV relapse without clinical relapse have a similar decline in HBsAg and the HBsAg loss rate as the sustained responders. [ABSTRACT FROM AUTHOR]

We present an inexpensive fabrication method in preparing one-dimensional gadolinium oxide (GdO) nanorods through hydrothermal synthesis and graphitic carbon nitride–g-C3N4, by a rapid calcination process. X-ray diffraction (XRD) patterns of GdO nanorods displayed a cubic crystal phase with an average crystalline size of 5–6.2 nm. Through high-resolution transmission electron microscopy micrographs, GdO exhibited a diameter of ∼20 nm. The GdO nanorods/g-C3N4 nanocomposite was analyzed using XRD, Fourier transmission-infrared spectroscopy, X-ray photoelectron spectroscopy, transmission electron microscopy, field-emission scanning electron microscopy with elemental mapping, and energy-dispersive X-ray spectrometry. The GdO/g-C3N4 nanocomposite was fabricated on a screen-printed carbon paste electrode for the electrochemical determination of clioquinol, which demonstrated rapid electron and ion transfer. The sensor was studied for its dual-modality detection using differential pulse voltammetry (DPV) and amperometry (i–t) techniques, which showed a wide detection range for DPV from 0.099 to 448.30 μM and i–t from 0.008 to 78.7 μM, and the lateral limit of detection for DPV was 4.8 nM and i–t was 1.2 nM with ultra-low sensitivity for DPV of 16.39 μA μM–1 cm–2 and i–t of 15.6 μA μM–1 cm–2 (S/N = 3). The prepared electrochemical sensor exhibited stability, selectivity, and sensitivity, which were markedly reported by DPV and i–t tests, and its use was further studied in real-time analysis using pharmaceutical and biological samples. [ABSTRACT FROM AUTHOR]