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The assessment of bone marrow iron stores is typically performed on an aspirate smear slide that has been manually stained by a technologist using a commercially available kit. This approach can contribute to inconsistent results and limit the broad use of iron staining in bone marrow specimens, particularly when laboratories have low staffing and/or high specimen volumes. Here, we describe the adaptation and validation of the Ventana Benchmark automated stainer and iron stain kit for routine clinical use of staining iron in bone marrow aspirate smear slides. We assessed accuracy and precision of the Ventana automated iron staining protocol compared to the Perls Prussian blue manual iron staining index method. Hematopathologists assigned Gale scores and enumerated the percentages of erythroid sideroblasts on paired patient bone marrow aspirate smear slides stained by the automated method and the manual iron staining method. We found a similar level of performance of the Ventana automated iron stain relative to the index manual method (as assessed by Pearson correlation and Bland–Altman analyses). In addition, there was low imprecision between replicates performed via the automated iron stain protocol. We also report superior qualitative findings of the automated method in ease of localization of iron storage, visualization of sideroblasts, and counterstain consistency. Automated iron staining of bone marrow aspirate smear slides performed similarly to the manual method and may allow for accurate routine evaluation of bone marrow iron stores as part of bone marrow analysis. [ABSTRACT FROM AUTHOR]

Achieving selective hydrodeoxygenation of α, β-unsaturated carbonyl groups to alkenes poses a substantial challenge due to the presence of multiple functional groups. In this study, we develop a ZnNC-X catalyst (X represents the calcination temperature) that incorporates both Lewis acidic-basic sites and Zn-Nx sites to address this challenge. Among the catalyst variants, ZnNC-900 catalyst exhibits impressive selectivity for alkenes in the hydrodeoxygenation of α, β-unsaturated carbonyl compounds, achieving up to 94.8% selectivity. Through comprehensive mechanism investigations and catalyst characterization, we identify the Lewis acidic-basic sites as responsible for the selective hydrogenation of C=O bonds, while the Zn-Nx sites facilitate the subsequent selective hydrodeoxygenation step. Furthermore, ZnNC-900 catalyst displays broad applicability across a diverse range of unsaturated carbonyl compounds. These findings not only offer valuable insights into the design of effective catalysts for controlling alkene selectivity but also extend the scope of sustainable transformations in synthetic chemistry. The selective reduction of α, β-unsaturated carbonyls remains a challenge. Here the authors report a zinc-based catalyst for this reaction, converting α, β-unsaturated carbonyl compounds into unsaturated alcohols followed by hydrodeoxygenation to form alkenes. [ABSTRACT FROM AUTHOR]

This study aims to assess the role of methotrexate-related gene polymorphisms in children with acute lymphoblastic leukemia (ALL) during high-dose methotrexate (HD-MTX) therapy and to explore their effects on serum metabolites before and after HD-MTX treatment. The MTHFR 677C>T, MTHFR 1298A>C, ABCB1 3435C>T, and GSTP1 313A>G genotypes of 189 children with ALL who received chemotherapy with the CCCG-ALL-2020 regimen from January 2020 to April 2023 were analyzed, and toxic effects were reported according to the Common Terminology Criteria for Adverse Events (CTCAE, version 5.0). Fasting peripheral blood serum samples were collected from 27 children before and after HD-MTX treatment, and plasma metabolites were analyzed by liquid chromatography-tandem mass spectrometry (LC–MS). The results of univariate and multivariate analyses showed that MTHFR 677C>T and ABCB1 3435 C>T gene polymorphisms were associated with the delayed MTX clearance (P < 0.05) and lower platelet count after treatment in children with MTHFR 677 mutation compared with wild-type ones (P < 0.05), and pure mutations in ABCB1 3435 were associated with higher serum creatinine levels (P < 0.05). No significant association was identified between MTHFR 677C>T, MTHFR 1298A>C, ABCB1 3435 C>T, and GSTP1 313A>G genes and hepatotoxicity or nephrotoxicity (P > 0.05). However, the serum metabolomic analysis indicated that the presence of the MTHFR 677C > T gene polymorphism could potentially contribute to delayed MTX clearance by influencing L-phenylalanine metabolism, leading to the occurrence of related toxic side effects. Conclusion: MTHFR 677C>T and ABCB1 3435 C>T predicted the risk of delayed MTX clearance during HD-MTX treatment in children with ALL. Serum L-phenylalanine levels were significantly elevated after HD-MTX treatment in children with the MTHFR 677C>T mutation gene. Trial registration: This study was registered at the Chinese Clinical Trial Registry (registration number: ChiCTR2000035264; registration: 2020/08/05; https://www.chictr.org.cn/). What is Known: • MTX-related genes play an important role in MTX pharmacokinetics and toxicity, but results from different studies are inconsistent and the mechanisms involved are not clear. What is New: • Characteristics, prognosis, polymorphisms of MTX-related genes, and metabolite changes were comprehensively evaluated in children treated with HD-MTX chemotherapy. • Analysis revealed that both heterozygous and pure mutations in MTHFR 677C>T resulted in a significantly increased risk of delayed MTX clearance, and that L-phenylalanine has the potential to serve as a predictive marker for the metabolic effects of the MTHFR 677C>T polymorphism. [ABSTRACT FROM AUTHOR]

The artificial intelligence methods might be applied to see through the education problems, and make effective prediction and decision. The transformation from data to decision are inseparable from the learning analytics. In order to solve the dynamic multi-objective decision problems, a decision learning algorithm is designed to analyze the learning behavior and learning achievement based on the particle swarm optimization mechanism, which ensures the global optimization of data analysis. Compared with the performance indicators of several approximate algorithms, this algorithm has the advantage of association analysis, which improves the accuracy and robustness; Furthermore, three tested problems are constructed by GeoDa tool, and through data training and analysis, the dynamic multi-objective decision rules are obtained. The whole research can provide theoretical and technical support for other related or similar issues. [ABSTRACT FROM AUTHOR]

Introduction: Spinal muscular atrophy (SMA) is an inherited neuromuscular disorder and regarded as one of the most frequent genetic causes of infant mortality. The aim of this study is to develop a cost-effectiveness analysis of AVXS-101 (Onasemnogene Abeparvovec/Zolgensma®) and nusinersen (Spinraza®) for SMA to inform decision-making on reimbursement policies in Australia. Methods: A Markov model was developed with five health states to evaluate the costs and effects for patients with SMA Type I from a healthcare system perspective over a time-horizon of 100 years. The model parameters were based on clinical trials, parametric distributions, published literature, and Australian registries. One-way and probabilistic sensitivity analysis were performed to appraise the uncertainties of the parameters in the model. A threshold analysis was conducted to estimate the cost of AVXS-101 of being cost-effective. Results: The incremental cost-effectiveness ratio (ICER) of AVXS-101 was $1,808,471 per quality-adjusted life year (QALY) and that of nusinersen was $2,772,798 per QALY, compared to standard of care, respectively. The ICER of AVXS-101 was $1,238,288 per QALY compared to nusinersen. The key drivers influencing on ICERs were costs of using treatments and utility values of sitting and walking independently. Conclusion: Both nusinersen and AVXS-101 resulted in health benefits, but they were not cost-effective with a commonly used willingness-to-pay (WTP) threshold of $50,000 per QALY. Developing high-quality clinical data and exploring appropriate WTP thresholds are critical for decision-making on reimbursement policies in the treatment of rare diseases. [ABSTRACT FROM AUTHOR]

Sika deer (Cervus nippon) are large ruminants distributed throughout northeastern Asia. The phylogenetic relationship of the sika deer subspecies remains unclear. The complete mitochondrial genomes of 287 sika deer from eight subspecies (C. n. hortulorum, C. n. sichuanicus, C. n. kopschi, C. n. taiouanus, C. n. yesoensis, C. n. centralis, C. n. nippon and C. n. yakushimae) were obtained. Haplotype network and development of a phylogenetic tree revealed China clusters and Japan clusters that were well separated based on the mitochondrial whole-genome level. Our studies indicate that China sika deer are genetically distinguishable from Japanese samples. Our findings increase the understanding of the phylogenetic relationships of sika deer and could provide useful information for sika deer conservation projects as well as for sika deer genomics, emergence and geographical distribution. [ABSTRACT FROM AUTHOR]

We investigate the spatio-temporal characteristics of the austral spring Ross Ice Shelf Polynya (RISP) and its relationship with atmospheric circulation anomalies based on the sea ice concentration data from the National Snow and Ice Data Center (NSIDC) and the ERA5 reanalysis data. The RISP area series is derived by choosing 25% sea ice concentration as the threshold. Then the principal spatial patterns of the RISP are acquired by using the empirical orthogonal function (EOF) analysis. The leading EOF (EOF1) has a spatial distribution of a strong negative core in the northeastern RISP with a weak positive core near the Cape Adare, explaining 48.1% of the variance. This mode matches the wind pattern of the northwesterly on the western Ross Sea while southwesterly on the eastern Ross Sea, which reflects the zonal variation of the RISP. There is also a strong positive correlation between the RISP area and the PC1. The EOF2 explains 27.4% of the variance, and is mainly characterized by a large region of low values in the northwestern Ross Sea with a small region of high value near Cape Colbeck. Matching the strong southerly over the western Ross Sea, the EOF2 partly depicts the meridional variation of the RISP. We further explored the connections between the RISP and sea level pressure, and found that a deeper and more eastward Amundsen Sea Low (ASL) in November often coincides with a larger and more eastward RISP in December. This lagged response is partly generated through the influence of the ASL on the RISP in November. [ABSTRACT FROM AUTHOR]

Electrically responsive electrochemical actuators that contain a polymer electrolyte membrane laminated between two electrodes have attracted great attention due to their potential applications in smart electronics, wearable devices, and soft robotics. However, some challenges such as the achievement of large bending strain under low applied voltage and fast ion diffusion and accumulation still exist to be resolved. The key to the solution lies in the choice of electrode materials and the design of electrode structures. In this study, an engineering electrochemical actuator that presents large bending strain under low applied voltage based on MXene/polystyrene-MXene hybrid electrodes is developed. The developed electrochemical actuator based on the MXene/polystyrene-MXene 3D-structure is found to exhibit large bending strain (ca. 1.18%), broad frequency bandwidth, good durability (90% retention after 10,000 cycles) and considerable Young's modulus (ca. 246 MPa). The high-performance actuation mainly stems from the excellent properties of MXene and 3D-structure of the electrode. The MXene provides excellent mechanical strength and high electrical conductivity which facilitate strong interaction and rapid electron transfer in electrodes. The 3D architectures formed by polystyrene microspheres generate unimpeded ion pathways for ionic short diffusion and fast injection. This study reveals that the 3D-structure hybrid electrodes play a crucial role in promoting the performance of such electrochemical actuators. [ABSTRACT FROM AUTHOR]

In practice, a variety of composite indicators are created using the arithmetic average of different sub-indicators. However, this scheme is typically criticized of the possibility of compensation. For this reason, this paper re-constructs these composite indicators by means of a new methodology. Comprehensive individual judgements among the sub-indicators have been considered to determine the maximum total utilities. Then the best–worst method is introduced to determine the preference associated with various individual judgements. An illustration of Value Measure of health systems is presented to demonstrate the validity and usefulness of our methodology. [ABSTRACT FROM AUTHOR]

Given the serious work hardening phenomenon, high chemical activity, severe tool wear, and poor workpiece surface quality during the cutting of titanium alloys, placing micro-texture on the tool surface decreases the tool-chip contact area and friction and plays the role of wear resistance and friction reduction. In order to improve the cutting performance of cutting tools, the present study examins the effect of micro-texture parameters of a cemented carbide ball-end milling cutter on cutting force, tool wear, and workpiece surface roughness and establishes a regression analysis model via regression analysis. We consider the cutting performance of a cemented carbide micro-texture ball-end milling cutter as an evaluation standard. A genetic algorithm is applied to the multi-objective optimization of micro-texture parameters, and a regression analysis model of micro-texture design criteria is established. This provides a standardised reference to select standard micro-texture parameters in the design and preparation of a cemented carbide micro-texture ball-end milling cutter. [ABSTRACT FROM AUTHOR]

Titanium alloys is a typical difficult-to-cut material with many machining problems, build-up-edge, large cutting force, and high cutting heat. Previous research has shown that micro-texture on the tool surface can solve the above problems potentially, and that a blunt round edge of the cutting tool can enhance its strength and improve the tool wear resistance. Therefore, towards an optimal parameter of micro-texture and blunt round radius, a finite element method (FEM) simulation and an experiment are carried out, where the test result provides a set of data for a genetic algorithm–based prediction model. The optimized parameter combinations of the micro-textured ball-end milling cutter with a blunt round edge are obtained and compared in a set of experiments. The optimized parameters refer to a 40-μm radius of the blunt round edge, a 40-μm micro-texture diameter, a 175-μm spacing, a 120-μm distance from the cutting edge, and an 80-μm depth. [ABSTRACT FROM AUTHOR]

Introduction: Progression of pulmonary fibrosis, characterized by the deterioration of lung tissue's mechanical properties, is affected by respiratory motion-induced dynamic loading. Since the development of anti-fibrosis drugs faces major hurdles in animal tests and human clinical trials, preclinical models that can recapitulate fibrosis progression under physiologically-relevant cyclic loading hold great promise. However, the integration of these two functions has not been achieved in existing models. Methods: Recently we developed static human lung microtissue arrays that recapitulate the progressive changes in tissue mechanics during lung fibrogenesis. In the current study, we integrate the lung microtissue array with a membrane stretching system to enable dynamic loading to the microtissues. The effects of a pro-fibrotic agent and anti-fibrosis drugs were tested under cyclic stretching. Results: Cyclic stretching that mimics respiratory motion was shown to affect the cytoskeletal organization and cellular orientation in the microtissue and cause the increase in microtissue contractility and stiffness. Fibrosis induction using TGF-β1 further promoted fibrosis-related mechanical activity of the lung microtissues. Using this system, we examined the therapeutic effects of two FDA approved anti-fibrotic drugs. Our results showed that Nintedanib was able to fully inhibit TGF-β1 induced force increase but only partially inhibited stretching induced force increase. In contrast, Pirfenidone was able to fully inhibit both TGF-β1 induced force increase and stretching-induced force increase. Conclusions: Together, these results highlight the pathophysiologically-relevant modeling capability of the current fibrotic microtissue system and demonstrated the potential of this system to be used for anti-fibrosis drug screening. [ABSTRACT FROM AUTHOR]

Velvet antler displays the fastest and most robust tissue proliferation in the animal world, it is a model for a complete organ development/regeneration, and alternative medicine, tonic made from velvet antler, was beneficial for human. The weight of velvet antler had high biomedical and economic value, but the related regulation mechanisms controlling velvet antler weight remain unclear. In this study, extremely heavy and light velvet antler groups were selected from a sika deer population of 100 individuals with extreme velvet antler weight. A combination of full-length transcriptome sequencing and microRNA sequencing to the proliferation zone in the tip of velvet antler was applied. A total of 55306 transcripts and 1082 microRNAs were identified. Some highly expressed genes (COL1A1, COL1A2, COL3A1, FN1, and ATP6) and microRNAs (miR-21, let-7i, and miR-27b) were highly correlated with the physiological and growth characteristics of velvet antlers. Among the 334 differentially expressed genes, we found that most of the genes were located in the developmental process, especially animal organ development process. It is exciting to see that more blood vessels were found in the growing tip of heavy velvet antler through histological observation, and GO term of blood vessel development was also significant different between two groups. The combination analysis with mRNA and microRNA data in velvet antler showed a specific regulation network involved in the development of bone, mesenchyme, cartilage, and blood vessel, and helped us clearly find out the candidate 14 genes and 6 microRNAs, which could be used for selecting significant DNA markers of velvet antler weight. [ABSTRACT FROM AUTHOR]

The concentrations, homologue, and congener profiles, as well as the gas/particle distribution of polychlorinated dibenzo- p-dioxins and furans (PCDD/Fs), chlorobenzenes (CBzs), chlorophenols (CPhs), and polyaromatic hydrocarbons (PAHs) from stack gas of two different municipal solid waste incinerators in China, were characterized. The incinerators were a stoker furnace incinerator equipped with the advanced air pollution control device (APCD) and a common circulating fluidized bed (CFB) furnace. The concentration of PCDD/Fs in the stack gas of the stoker incinerator ranged 0.011-0.109 ng international toxic equivalent factor (I-TEQ)/Nm and was below the current limit for PCDD/F emissions from the municipal solid waste incinerators (MSWIs) in China (0.1 ng I-TEQ/Nm) in most of the cases. Moreover, the concentration of PCDD/Fs in the stack gas of the stoker incinerator was significantly lower than that of the CFB incinerator (0.734 to 24.6 ng I-TEQ/Nm). In both incinerators, the majority of the total PCDD/F emissions (above 90%) ended up in the gas phase. 2,3,4,7,8-PeCDF, which occupied 24.3-43.6 and 32.5-75.6% of I-TEQ contribution in MSWIs A and B, respectively, was the most abundant congener. However, different types of incinerators and APCDs induced different congener and homologue distributions. The total concentration of CBzs from the stoker incinerator (0.05-3.2 μg/Nm) was also much lower than that formed from the CFB incinerator (10.9-75.2 μg/Nm). The phase distribution of CBzs followed the same pattern as with the PCDD/Fs. Moreover, the emission level of CBz was 100-1000 times higher than that of the PCDD/Fs, which determines the applicability of CBzs as indicators of PCDD/F emissions. High correlations between the emission concentrations of PCDD/Fs, TeCBz, and PCBz in specific ranges were revealed. Furthermore, high concentrations of CPhs (0.6-141.0 μg/Nm) and PAHs (148.6-4986.5 μg/Nm) were detected in the stack gases of MSWI B. In some cases, the concentrations were as high as the concentrations in the fumes exiting the boiler of one foreign stoker without flue gas purification indicating the abundance of CPh and PAH emissions in the stack gas of waste incinerators. [ABSTRACT FROM AUTHOR]

HER2 is a proto-oncogene frequently amplified in human breast cancer, its overexpression is correlated with tamoxifen resistance and decreased recurrence-free survival. Arenobufagin and bufalin are homogeneous bufadienolides of cardiac glycosides agents. In this research, we studied the effects of arenobufagin and bufalin on cellular survival and proliferation of HER2 overexpressing breast cancer cells and the mechanism under the results including the direct effect on HER2 downstream pathways. Our results showed that arenobufagin and bufalin could significantly inhibit the proliferation and survival of HER2 overexpressing breast cancer cells, along with the declination of SRC-1, SRC-3, nuclear transcription factor E2F1, phosphorylated AKT, and ERK. And the combination of each bufadienolide in low dose with tamoxifen could significantly enhance the inhibitory effect of tamoxifen on HER2 overexpressing breast cancer cells. All above suggest that arenobufagin and bufalin may be potential therapy adjuvants for HER2 overexpressing breast cancer therapy. [ABSTRACT FROM AUTHOR]

The mold-filling process has a determining effect on the quality of castings, and it has always been a hot but difficult research topic. The authors developed a wireless monitoring system for the mold-filling process of castings based on a contact time method and an observation system based on heat-resistant high-speed cameras. By using these two systems, the filling process of a turbine guide vane casting with a stepped gating system was investigated. The filling profile of the casting was recorded, and the filling time of nine typical positions was acquired. These results show that at the beginning, the liquid steel flowed out from the top ingate, which was designed to be the last to fill. The numerical simulation of the filling of the guide vane was performed, and the outflow from the top ingate were predicted. Finally, the gating system of the casting was improved with enlarged sprue. The new design features bigger sprue to ingate ratio; therefore, it could avoid the overflow from the top ingate and realize stable filling. [ABSTRACT FROM AUTHOR]

Heavy hydro turbine castings are made of martensitic stainless steel, which undergoes martensitic transformation during the casting process. Therefore, both residual stress and deformation are affected not only by uneven cooling but also by martensitic transformation. In this paper, a coupled thermo-martensitic phase transformation-stress model was established and it was implemented by further development with ABAQUS, which also incorporated the thermal and mechanical boundaries, and the contact pair between the casting and mold. The system was applied to the analysis of a heavy hydro blade casting. Results of stress, displacement, and martensite phase fraction were obtained. It is found that martensitic transformation has a significant effect on the stress and deformation results. The displacement in the normal direction of local areas was calculated to represent deformation in the x, y, and z directions. The deformation of the blade casting occurred mainly at the two thin corners with 18 and 22 mm in opposite tendency. The simulated results were compared with the measured machining allowance, and they are basically in agreement. [ABSTRACT FROM AUTHOR]

The design of arbitrarily controlled multi-beam antennas is investigated by using the technique of optical transformation. Based on the optical transformation, cylindrical waves emitted from a line source can be converted to plane waves through a metamaterial layer which has a circular shape in the inner outline and a polygon shape in the outer outline. Hence the line source together with the metamaterial layer constructs a high-performance multi-beam antenna. The number of sidelines and the shape of polygon are used to control the number and directions of beams. Analytical formulas of the permittivity and permeability tensors are presented for the metamaterial layer in the antenna. The designed multi-beam antennas are validated by full-wave simulations using the finite-element method. The proposed multi-beam antennas will be very useful in the intelligent traffic system. [ABSTRACT FROM AUTHOR]

Background: This study seeks to assess the utility of T1 and T2 mapping in distinguishing metastatic lymph nodes from reactive lymphadenopathy in patients with head and neck squamous cell carcinoma (HNSCC), using diffusion-weighted imaging (DWI) as a comparison., Methods: Between July 2017 and November 2019, 46 HNSCC patients underwent neck MRI inclusive of T1 and T2 mapping and DWI. Quantitative measurements derived from preoperative T1 and T2 mapping and DWI of metastatic and non-metastatic lymph nodes were compared using independent samples t-test or Mann-Whitney U test. Receiver operating characteristic curves and the DeLong test were employed to determine the most effective diagnostic methodology., Results: We examined a total of 122 lymph nodes, 45 (36.9%) of which were metastatic proven by pathology. Mean T2 values for metastatic lymph nodes were significantly lower than those for benign lymph nodes (p < 0.001). Conversely, metastatic lymph nodes exhibited significantly higher apparent diffusion coefficient (ADC) and standard deviation of T1 values (T1 SD ) (p < 0.001). T2 generated a significantly higher area under the curve (AUC) of 0.890 (0.826-0.954) compared to T1 SD (0.711 [0.613-0.809]) and ADC (0.660 [0.562-0.758]) (p = 0.007 and p < 0.001). Combining T2, T1 SD , ADC, and lymph node size achieved an AUC of 0.929 (0.875-0.983), which did not significantly enhance diagnostic performance over using T2 alone (p = 0.089)., Conclusions: The application of T1 and T2 mapping is feasible in differentiating metastatic from non-metastatic lymph nodes in HNSCC and can improve diagnostic efficacy compared to DWI., (© 2023. The Author(s).)