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Minimal residual disease (MRD) based risk stratification criteria for specific genetic subtypes remained unclear in childhood acute lymphoblastic leukemia (ALL). Among 723 children with newly diagnosed ALL treated with the Chinese Children Leukemia Group CCLG-2008 protocol, MRD was assessed at time point 1 (TP1, at the end of induction) and TP2 (before consolidation treatment) and the MRD levels significantly differed in patients with different fusion genes or immunophenotypes (P all < 0.001). Moreover, the prognostic impact of MRD varied by distinct molecular subtypes. We stratified patients in each molecular subtype into two MRD groups based on the results. For patients carrying BCR::ABL1 or KMT2A rearrangements, we classified patients with MRD < 10–2 at both TP1 and TP2 as the low MRD group and the others as the high MRD group. ETV6::RUNX1+ patients with TP1 MRD < 10–3 and TP2 MRD-negative were classified as the low MRD group and the others as the high MRD group. For T-ALL, We defined children with TP1 MRD ≥ 10–3 as the high MRD group and the others as the low MRD group. The 10-year relapse-free survival of low MRD group was significantly better than that of high MRD group. We verified the prognostic impact of the subtype-specific MRD-based stratification in patients treated with the BCH-ALL2003 protocol. In conclusion, the subtype-specific MRD risk stratification may contribute to the precise treatment of childhood ALL. [ABSTRACT FROM AUTHOR]

Although pedestrian detection techniques are improving, this task is still challenging due to the problems of target occlusion, small targets, and complex pedestrian backgrounds in images of different scenes. As a result, the You Only Look Once algorithm exhibits lower detection accuracy. In this paper, a multisensor (MS) module that utilizes multiple dilated convolutions is proposed to sample feature images, avoiding information loss caused by repeated sampling, to improve the feature extraction and target detection performance of the algorithm. In addition, a lightweight shuffle-based efficient channel attention mechanism is introduced to conduct grouping in the channel dimension and perform parallel processing for each subfeature map channel. A new branch is introduced to enrich the channel feature information for multiscale feature representation. Finally, a distance intersection over union-based nonmaximum suppression (DIoU-NMS) method is introduced to minimize the occurrence of missed targets due to occlusion by taking the prediction box and ground truth box centroid locations information into account without increasing the computational cost over that of normal NMS. Our method is extensively evaluated on several challenging pedestrian detection datasets, achieving 87.73%, 34.7%, 93.96% and 95.23% mean average precision values on PASCAL VOC, MS COCO, Caltech Pedestrian and INRIA Person, which are respectively. The experimental results demonstrate the effectiveness of the method. [ABSTRACT FROM AUTHOR]

The immersive experience and diverse interaction modes provided by virtual digital technology match the spatial sensitivity and practical ability required in the field of architectural teaching, and its technological advantages can significantly enhance teaching outcomes. However, in the field of architecture teaching, there has been a lack of discussion on the suitability of different virtual technologies and teaching scenarios for historical buildings. Therefore, this study constructed a comprehensive adaptive evaluation system for virtual technology and selected 360-degree panoramic technology (360-degree PT), Immersive Virtual Reality (IVR) technology, and Desktop Virtual Reality (DVR) technology as representatives for empirical study. The research method used in this experiment is a questionnaire survey, involving a total of 60 students majoring in architecture and planning, with a certain foundation in historical architecture knowledge. Multiple statistical methods are employed to analyze the data. The experimental data indicates that IVR technology performs the best in terms of learning outcomes, learning autonomy, and sense of presence, making it suitable for immersive and interactive learning needs. 360-degree PT demonstrates the best perception of architectural features, catering to the demand for visual effects. DVR technology exhibits the highest learning efficiency, meeting the need for simplicity, efficiency, and widespread application. On the other hand, augmented reality (AR) technology and mixed reality (MR) technology have lower adaptability and do not meet the learning requirements for immersive spatial experiences. This study is expected to provide a new technical pathway for teaching historical buildings and serve as a systematic reference for selecting specific technologies. [ABSTRACT FROM AUTHOR]

HIV-1 envelope glycoproteins (Envs) of most primary HIV-1 strains exist in closed conformation and infrequently sample open states, limiting access to internal epitopes. Thus, immunogen design aims to mimic the closed Env conformation as preferred target for eliciting broadly neutralizing antibodies (bnAbs). Here we identify incompletely closed Env conformations of 6 out of 13 transmitted/founder (T/F) strains that are sensitive to antibodies that recognize internal epitopes typically exposed on open Envs. A 3.6 Å cryo-electron microscopy structure of unliganded, incompletely closed T/F Envs (1059-SOSIP) reveals protomer motion that increased sampling of states with incompletely closed trimer apex. We reconstruct de novo the post-transmission evolutionary pathway of a second T/F. Evolved viruses exhibit increased Env resistance to cold, soluble CD4 and 19b, all of which correlate with closing of the adapted Env trimer. Lastly, we show that the ultra-broad N6 bnAb efficiently recognizes different Env conformations and exhibits improved antiviral breadth against VRC01-resistant Envs isolated during the first-in-humans antibody-mediated-prevention trial. HIV-1 is a formidable target for vaccine development. Here, Parthasarathy et al. show that envelope glycoproteins of some HIV-1 primary strains exhibit inherent conformational flexibility that may contribute to HIV-1 evasion from neutralizing antibodies. [ABSTRACT FROM AUTHOR]

The seepage-stress coupling characteristics of fractured rock mass were studied theoretically in this paper. Based on the cubic law and the equivalent circuit principle, a modified multi-parallel plate equivalent model (MPPEM) for seepage analysis of a rough single-fracture and a modified equivalent seepage resistance model (ESRM) for seepage analysis of a fracture networks consisting of rough single-fracture combined in series and parallel were proposed. On this basis, the equation for the variation of fracture aperture of fractured rock masses under the action of the three-direction principal stresses and pore water pressure was derived, and the discrete element calculations of the seepage-stress coupling of the two-dimensional fractured rock mass were carried out under different ground stress coefficients. The results show that the error of the modified MPPEM characterizing the seepage in a rough single-fracture in a rock mass does not exceed 7%. The modified ESRM can better characterize the seepage in T-shaped combined fracture and × -shaped combined fracture. With the increase of normal stress applied to the fracture surface, the fracture aperture and seepage flow rate of the fractured rock mass decrease. The above study is of great theoretical significance for the analysis of the seepage evolution law of the fractured rock mass under the action of geostress. [ABSTRACT FROM AUTHOR]

Purpose: The importance of a TP53 mutation has been demonstrated in several tumor types, including breast cancer (BC). However, the accuracy of p53 protein expression as a predictor of gene mutation has not been well studied in BC. Therefore, we evaluated p53 protein expression associated with TP53 mutations in breast cancers from 64 patients. Methods: TP53 mutation was examined using next-generation sequencing (NGS). p53 protein expression was examined using immunohistochemistry (IHC). Results: Among the 64 BCs, 55% demonstrated abnormal expression patterns including 27% overexpression, 22% null, 6% equivocal with 45% having a wild-type pattern. A TP53 mutation was present in 53% (34/64) of tumors including 30% (19/64) demonstrating a missense mutation, 11% (7/64) with a frameshift mutation, 11% (7/64) with a nonsense mutation, and 3% (1/64) with a splice site mutation. Abnormal expression of p53 protein was present in 33 of 34 (97%) tumors carrying a TP53 mutation; conversely, a wild-type pattern was present in 28 of 30 (93%) tumors without a detectable mutation (p < 0.0001). The majority of BCs with a p53 IHC overexpression pattern (15/17, 88%) contained a missense TP53 mutation; while the majority of BCs with a null pattern (12/14, 86%) contained a truncating mutation (p < 0.0001). The BCs with a null pattern are associated with a high Nottingham histological grade and a triple-negative phenotype when compared to those demonstrating overexpression (p < 0.05). Conclusion: These findings suggest that p53 IHC can be a potential surrogate for TP53 mutations in BC. Different p53 expression patterns may correlate with specific TP53 genetic mutations in BC. [ABSTRACT FROM AUTHOR]

Background: While folic acid (FA) is widely used to treat elevated total homocysteine (tHcy), promoting vascular health by reducing vascular oxidative stress and modulating endothelial nitric oxide synthase, the optimal daily dose and individual variation by MTHFR C677T genotypes have not been well studied. Therefore, this study aimed to explore the efficacy of eight different FA dosages on tHcy lowering in the overall sample and by MTHFR C677T genotypes. Methods: This multicentered, randomized, double-blind, controlled clinical trial included 2697 eligible hypertensive adults with elevated tHcy (≥ 10 mmol/L) and without history of stroke and cardiovascular disease. Participants were randomized into eight dose groups of FA combined with 10 mg enalapril maleate, taken daily for 8 weeks of treatment. Results: The intent to treat analysis included 2163 participants. In the overall sample, increasing FA dosage led to steady tHcy reduction within the FA dosing range of 0–1.2 mg. However, a plateau in tHcy lowering was observed in FA dose range of 1.2–1.6 mg, indicating a ceiling effect. In contrast, FA doses were positively and linearly associated with serum folate levels without signs of plateau. Among MTHFR genotype subgroups, participants with the TT genotype showed greater efficacy of FA in tHcy lowering. Conclusions: This randomized trial lent further support to the efficacy of FA in lowering tHcy; more importantly, it provided critically needed evidence to inform optimal FA dosage. We found that the efficacy of FA in lowering tHcy reaches a plateau if the daily dosage exceeds 1.2 mg, and only has a small gain by increasing the dosage from 0.8 to 1.2 mg. ClinicalTrials.gov Identifier: NCT03472508 (Registration Date: March 21, 2018). [ABSTRACT FROM AUTHOR]

To investigate the role of co-stimulatory and co-inhibitory molecules on immune tolerance in immune thrombocytopenia (ITP), this study mapped the immune cell heterogeneity in the bone marrow of ITP at the single-cell level using Cytometry by Time of Flight (CyTOF). Thirty-six patients with ITP and nine healthy volunteers were enrolled in the study. As soluble immunomodulatory molecules, more sCD25 and sGalectin-9 were detected in ITP patients. On the cell surface, co-stimulatory molecules like ICOS and HVEM were observed to be upregulated in mainly central memory and effector T cells. In contrast, co-inhibitory molecules such as CTLA-4 were significantly reduced in Th1 and Th17 cell subsets. Taking a platelet count of 30×109 L−1 as the cutoff value, ITP patients with high and low platelet counts showed different T cell immune profiles. Antigen-presenting cells such as monocytes and B cells may regulate the activation of T cells through CTLA-4/CD86 and HVEM/BTLA interactions, respectively, and participate in the pathogenesis of ITP. In conclusion, the proteomic and soluble molecular profiles brought insight into the interaction and modulation of immune cells in the bone marrow of ITP. They may offer novel targets to develop personalized immunotherapies. [ABSTRACT FROM AUTHOR]

Different from rivers in humid areas, the variability of riverine CO2 system in arid areas is heavily impacted by anthropogenic disturbance with the increasing urbanization and water withdrawals. In this study, the water chemistry and the controls of carbonate system in an urbanized river (the Fenhe River) on the semi-arid Loess Plateau were analyzed. The water chemistry of the river water showed that the high dissolved inorganic carbon (DIC) concentration (about 37 mg L−1) in the upstream with a karst land type was mainly sourced from carbonate weathering involved by H2CO3 and H2SO4, resulting in an oversaturated partial pressure of CO2 (pCO2) (about 800 µatm). In comparison, damming resulted in the widespread appearance of non-free flowing river segments, and aquatic photosynthesis dominated the DIC and pCO2 spatiality demonstrated by the enriched stable isotope of DIC (δ13CDIC). Especially in the mid-downstream flowing through major cities in warm and low-runoff August, some river segments even acted as an atmospheric CO2 sink. The noteworthy is wastewater input leading to a sudden increase in DIC (> 55 mg L−1) and pCO2 (> 4500 µatm) in the downstream of Taiyuan City, and in cold November the increased DIC even extended to the outlet of the river. Our results highlight the effects of aquatic production induced by damming and urban sewage input on riverine CO2 system in semi-arid areas, and reducing sewage discharge may mitigate CO2 emission from the rivers. [ABSTRACT FROM AUTHOR]

Pancreatic ductal adenocarcinoma (PDAC) is a devastating cancer with dismal prognosis due to distant metastasis, even in the early stage. Using RNA sequencing and multiplex immunofluorescence, here we find elevated expression of mixed lineage kinase domain-like pseudo-kinase (MLKL) and enhanced necroptosis pathway in PDAC from early liver metastasis T-stage (T1M1) patients comparing with non-metastatic (T1M0) patients. Mechanistically, MLKL-driven necroptosis recruits macrophages, enhances the tumor CD47 'don't eat me' signal, and induces macrophage extracellular traps (MET) formation for CXCL8 activation. CXCL8 further initiates epithelial–mesenchymal transition (EMT) and upregulates ICAM-1 expression to promote endothelial adhesion. METs also degrades extracellular matrix, that eventually supports PDAC liver metastasis. Meanwhile, targeting necroptosis and CD47 reduces liver metastasis in vivo. Our study thus reveals that necroptosis facilitates PDAC metastasis by evading immune surveillance, and also suggest that CD47 blockade, combined with MLKL inhibitor GW806742X, may be a promising neoadjuvant immunotherapy for overcoming the T1M1 dilemma and reviving the opportunity for radical surgery. Early-stage liver metastasis of pancreatic ductal adenocarcinoma (PDAC) makes radical surgery not efficacious. Here, the authors show that MLKL-driven necroptosis contributes to PDAC early-stage metastasis by inducing tumour CD47 upregulation and macrophage extracellular traps formation. [ABSTRACT FROM AUTHOR]

In this paper, I advocate for a radical expansion of computational urban science to encompass a multidisciplinary, human-centered approach, addressing the inadequacies of traditional methodologies in capturing the complexities of urban life. Building on insights from Jane M. Jacobs and others, I argue that integrating computational tools with disciplines like sociology, anthropology, and urban planning can significantly enhance our understanding and management of urban environments. This integration facilitates a deeper analysis of cultural phenomena, improves urban policy design, and promotes more sustainable, inclusive urban development. By embracing qualitative research methods—such as ethnography and participatory observations—alongside computational analysis, I highlight the importance of capturing the nuanced social fabrics and subjective experiences that define urban areas. I also stress the necessity of including community stakeholders in the research process to ensure that urban science not only analyzes but also improves the lived experiences of urban populations. Furthermore, I underscore the need for ethical governance and the mitigation of biases inherent in computational tools, proposing rigorous model auditing and the inclusion of diverse perspectives in model development. Overall, this work champions a holistic approach to urban science, aiming to make cities smarter, more equitable, and responsive to their residents' needs. [ABSTRACT FROM AUTHOR]

High-entropy alloy nitride (HEN) coating of (AlCrTiVZr)N was deposited onto 17-4PH stainless steel substrates using the cathodic arc evaporation (CAE) technique. The composition and resulting microstructure were analyzed, and key mechanical properties including solid particle erosion resistance and sliding wear resistance were measured in the as-deposited condition. The coating had a relatively rough surface and contained small spherical droplets and large splats throughout the coating thickness. It had a single-phased solid solution B1 nitride phase with a preferred (111) orientation. The coating retained the as-deposited microstructure upon high temperature annealing, but experienced nitride phase decomposition at a temperature 800 °C or above. The hardness of the as-deposited nitride fell into the range of 27.5 ± 2.10 GPa and its elastic modulus was 284 ± 23 GPa. Dry sliding wear tests revealed the higher wear rates of the coating when compared with the wear rates of TiN coatings under various testing conditions. The coating had an erosion rate that increased with the impingement angle and demonstrated a combination of ductile and brittle erosion damage modes. Comparing to the CAE deposited TiN coating, the HEN nitride coating showed a lower wear and erosion resistance, which is attributed to the presence of a large quantity of defects in the coating. Reducing number of droplets/splats becomes very important for having better high-entropy nitride coating quality and hence the better coating performance against wear and erosion. [ABSTRACT FROM AUTHOR]

Highlights: Fundamental principles for designing synergistic composite catalysts are reviewed. The synergistic effect between various active sites, promoting electrocatalytic performance in different reactions are highlighted. The challenges and perspectives for multiple active sites catalysts are discussed. Combining single atoms with clusters or nanoparticles is an emerging tactic to design efficient electrocatalysts. Both synergy effect and high atomic utilization of active sites in the composite catalysts result in enhanced electrocatalytic performance, simultaneously provide a radical analysis of the interrelationship between structure and activity. In this review, the recent advances of single-atomic site catalysts coupled with clusters or nanoparticles are emphasized. Firstly, the synthetic strategies, characterization, dynamics and types of single atoms coupled with clusters/nanoparticles are introduced, and then the key factors controlling the structure of the composite catalysts are discussed. Next, several clean energy catalytic reactions performed over the synergistic composite catalysts are illustrated. Eventually, the encountering challenges and recommendations for the future advancement of synergistic structure in energy-transformation electrocatalysis are outlined. [ABSTRACT FROM AUTHOR]

This study aimed to identify possible pathogenic genes in a 90-member family with a rare combination of multiple neurodegenerative disease phenotypes, which has not been depicted by the known neurodegenerative disease. We performed physical and neurological examinations with International Rating Scales to assess signs of ataxia, Parkinsonism, and cognitive function, as well as brain magnetic resonance imaging scans with seven sequences. We searched for co-segregations of abnormal repeat-expansion loci, pathogenic variants in known spinocerebellar ataxia-related genes, and novel rare mutations via whole-genome sequencing and linkage analysis. A rare co-segregating missense mutation in the CARS gene was validated by Sanger sequencing and the aminoacylation activity of mutant CARS was measured by spectrophotometric assay. This pedigree presented novel late-onset core characteristics including cerebellar ataxia, Parkinsonism, and pyramidal signs in all nine affected members. Brain magnetic resonance imaging showed cerebellar/pons atrophy, pontine-midline linear hyperintensity, decreased rCBF in the bilateral basal ganglia and cerebellar dentate nucleus, and hypo-intensities of the cerebellar dentate nuclei, basal ganglia, mesencephalic red nuclei, and substantia nigra, all of which suggested neurodegeneration. Whole-genome sequencing identified a novel pathogenic heterozygous mutation (E795V) in the CARS gene, meanwhile, exhibited none of the known repeat-expansions or point mutations in pathogenic genes. Remarkably, this CARS mutation causes a 20% decrease in aminoacylation activity to charge tRNACys with L-cysteine in protein synthesis compared with that of the wild type. All family members carrying a heterozygous mutation CARS (E795V) had the same clinical manifestations and neuropathological changes of Parkinsonism and spinocerebellar-ataxia. These findings identify novel pathogenesis of Parkinsonism-spinocerebellar ataxia and provide insights into its genetic architecture. [ABSTRACT FROM AUTHOR]

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Currently, the issue of educational equity and balanced regional educational development for minority groups is receiving enormous attention. This study explored the influence of parental science expectations on science interests and related mediating effects on Yi junior high school students in China's largest Yi-inhabited region. The results of the study found that parental science expectations significantly predicted the science interests of Yi junior high school students; science interests, science experience, and science self-efficacy played a chain mediating role between parental science expectations and science interests; minority areas are likely to suffer from a lack of science resources due to economic and environmental factors, parents' failure to properly understand the value of science, and students' lack of extracurricular science experiences, thereby resulting in minority students' loss of interest in science. Therefore, there is a strong need to improve the science expectations of parents of minority students for their children, increase opportunities for minority students to participate in hands-on science activities and gain access to science media, and enhance their sense of science self-efficacy. These efforts are conducive to promoting increased interest in science among minority middle school students and enhancing educational equity and sustainable social development. [ABSTRACT FROM AUTHOR]

Through Smad3-dependent signalings, transforming growth factor-β (TGF-β) suppresses the development, maturation, cytokine productions and cytolytic functions of NK cells in cancer. Silencing Smad3 remarkably restores the cytotoxicity of NK-92 against cancer in TGF-β-rich microenvironment, but its effects on the immunoregulatory functions of NK cells remain obscure. In this study, we identified Smad3 functioned as a transcriptional repressor for CSF2 (GM-CSF) in NK cells. Therefore, disrupting Smad3 largely mitigated TGF-β-mediated suppression on GM-CSF production by NK cells. Furthermore, silencing GM-CSF in Smad3 knockout NK cells substantially impaired their anti-lung carcinoma effects. In-depth study demonstrated that NK-derived GM-CSF strengthened T cell immune responses by stimulating dendritic cell differentiation and M1 macrophage polarization. Meanwhile, NK-derived GM-CSF promoted the survival of neutrophils, which in turn facilitated the terminal maturation of NK cells, and subsequently boosted NK-cell mediated cytotoxicity against lung carcinoma. Thus, Smad3-silenced NK-92 (NK-92-S3KD) may serve as a promising immunoadjuvant therapy with clinical translational value given its robust cytotoxicity against malignant cells and immunostimulatory functions to reinforce the therapeutic effects of other immunotherapies. [ABSTRACT FROM AUTHOR]

The Hilbert transform (HT) is an important method for signal demodulation and instantaneous frequency (IF) estimation. The modulus of the analytic signal constructed by the HT is considered as the amplitude, and the derivative of the instantaneous phase of the extracted pure frequency modulation signal is the IF. When the spectra of the amplitude function and the oscillation term overlap each other and fail to satisfy the Bedrosian condition, the instantaneous amplitude and frequency calculated by the HT will contain errors. The recursive Hilbert transform (RHT) is an effective method to overcome this problem. The RHT considers the pure frequency modulation signal obtained by the previous HT as a new signal and recursively computes its HT until convergence. The final pure frequency modulation signal of the recursive procedure has the same zero-crossing points as the original signal, and its corresponding quadrature error signal vanishes. We emphasize the convergence analysis of the algorithm and study the convergent tendency of the quadrature error signal in each recursive step. The key to the proof is that the discrete Fourier transform value of the quadrature error signal is regarded as a vector, and the length/norm of the vector decreases with the recursion process. Finally, we used three examples to demonstrate the effectiveness of this method in signal demodulation, IF identification and damped vibrating signal analysis, which indicate the application potential of the RHT method in mono-component signal processing. [ABSTRACT FROM AUTHOR]

Loess, featured by its low permeability and cost-effectiveness, has become an increasingly popular material for landfill cover systems. However, the occurrence of cracks in loess caused by rainfall and evaporation poses challenges to the performance and durability of these cover systems. This study aims to comprehensively investigate variations in air permeability of compacted loess under normal and dry-wet cycle conditions. The conventional triaxial instrument was modified to meet the requirements of the air permeability test of loess. The influence of factors such as permeability pathway, water infiltration time, dry density, and water content as well as dry-wet cycles on the air permeability was thoroughly explored. And the applicability of established models in describing loess air permeability was assessed. The results confirmed that the airflow in compacted loess followed Darcy’s law, and there was a clear correlation between air permeability and these influencing factors. Loess samples with a diameter of 38 mm and a height of 76 mm were found to be more suitable for air permeability testing. Cracking in loess significantly increases air permeability, with longitudinal cracking having a greater effect than transverse cracking. Lower-density samples exhibit more pronounced cracking than higher-density samples. Both initial water content and humidification water content were identified as influential factors during dry-wet cycling and have a substantial impact on the variation of air permeability. These findings contribute to a better understanding of the air permeability characteristics of compacted loess in landfill cover systems, enabling improved design and performance evaluation for sustainable waste management practices. [ABSTRACT FROM AUTHOR]

Purpose: To predict the efficacy of high-intensity focused ultrasound (HIFU) ablation for uterine leiomyomas based on diffusion tensor imaging (DTI) indicators and imaging features. Methods: Sixty-two patients with 85 uterine leiomyomas were consecutively enrolled in this retrospective study and underwent DTI scanning before HIFU treatment. Based on whether the non-perfused volume ratio (NPVR) was greater than 70%, all patients were assigned to sufficient ablation (NPVR ≥ 70%) or insufficient ablation (NPVR < 70%) groups. The selected DTI indicators and imaging features were incorporated to construct a combined model. The predictive performance of DTI indicators and the combined model were assessed using receiver operating characteristic (ROC) curves. Results: There were 42 leiomyomas in the sufficient ablation group (NPVR ≥ 70%) and 43 leiomyomas in the insufficient ablation group (NPVR < 70%). The fractional anisotropy (FA) and relative anisotropy (RA) values were higher in the sufficient ablation group than in the insufficient ablation group (p < 0.05). Conversely, the volume ratio (VR) and mean diffusivity (MD) values were lower in the sufficient ablation group than those in the insufficient ablation group (p < 0.05). Notably, the combined model composed of the RA and enhancement degree values had high predictive efficiency, with an AUC of 0.915. The combined model demonstrated higher predictive performance than FA and MD alone (p = 0.032 and p < 0.001, respectively) but showed no significant improvement compared with RA and VR (p > 0.05). Conclusion: DTI indicators, especially the combined model incorporating DTI indicators and imaging features, can be a promising imaging tool to assist clinicians in predicting HIFU efficacy for uterine leiomyomas. [ABSTRACT FROM AUTHOR]

The issue of transgender education and equality has long been neglected in Pakistan, leading to a lack of awareness and acceptance of the transgender community. The present study focuses on the joint effort of the government, print media, and citizens toward breaking the stigma and promoting transgender education and equality. This study employed a mixed-methods approach, combining qualitative content analysis of articles from three prominent Pakistani media outlets with a quantitative public opinion survey to evaluate the extent of media coverage and public attitudes toward transgender education and equality. This coverage helped create awareness and understanding of the transgender community. The government also took significant steps (Transgender Act 2018) by passing policies favoring the transgender community. Furthermore, the study showed that citizens have a positive attitude toward transgender equality, a sign of creating an inclusive society. The study also concluded that joint efforts between the government, print media, and citizens can help people break the stigma and promote transgender education and equality. This approach will pave the way for a more inclusive society that recognizes and values the rights of all individuals, regardless of their gender identity. [ABSTRACT FROM AUTHOR]

Salt efflorescence is one of the critical problems for the preservation of immovable silicate relics. Salt efflorescence mainly comes from continuous cycles of crystallization/dissolution or hydration/dehydration of salts in confined pores in silicate relics. Many protocols have been developed in attempts to alleviate possible salt damages with minor success because of endless water and salt feed from underground. In this study, we propose and design a novel technique for salt damage prevention and protection of immovable relics. Materials with higher water-absorbing ability than matrix are applied to control the water and salt migration direction in simulated sand samples. The distribution of moisture content on the surface of sand is followed by hyperspectral imaging. It appears that water and salt molecules will preferentially transport towards positions containing higher water-absorbing material. Both organic and inorganic high water-absorbing materials show effective in controlling the water and salt migration direction, which provides a new approach for the prevention and protection of salt efflorescence in silicate cultural relics. [ABSTRACT FROM AUTHOR]

Anaplastic lymphoma kinase (ALK) fusion-positive colorectal cancer (CRC) is a rare and chemotherapy-refractory subtype that lacks established and effective treatment strategies. Additionally, the efficacy and safety of ALK inhibitors (ALKi) in CRC remain undetermined. Herein, we examined a series of ALK-positive CRC patients who underwent various lines of ALKi treatment. Notably, we detected an ALK 1196M resistance mutation in a CRC patient who received multiple lines of chemotherapy and ALKi treatment. Importantly, we found that Brigatinib and Lorlatinib demonstrated some efficacy in managing this patient, although the observed effectiveness was not as pronounced as in non-small cell lung cancer cases. Furthermore, based on our preliminary analyses, we surmise that ALK-positive CRC patients are likely to exhibit inner resistance to Cetuximab. Taken together, our findings have important implications for the treatment of ALK-positive CRC patients. [ABSTRACT FROM AUTHOR]

CircRNAs are covalently closed, single-stranded RNA that form continuous loops and play a crucial role in the initiation and progression of tumors. Cancer stem cells (CSCs) are indispensable for cancer development; however, the regulation of cancer stem cell-like properties in gastric cancer (GC) and its specific mechanism remain poorly understood. We elucidate the specific role of Circ-0075305 in GC stem cell properties. Circ-0075305 associated with chemotherapy resistance was identified by sequencing GC cells. Subsequent confirmation in both GC tissues and cell lines revealed that patients with high expression of Circ-0075305 had significantly better overall survival (OS) rates than those with low expression, particularly when treated with postoperative adjuvant chemotherapy for GC. In vitro and in vivo experiments confirmed that overexpression of Circ-0075305 can effectively reduce stem cell-like properties and enhance the sensitivity of GC cells to Oxaliplatin compared with the control group. Circ-0075305 promotes RPRD1A expression by acting as a sponge for corresponding miRNAs. The addition of LF3 (a β-catenin/TCF4 interaction antagonist) confirmed that RPRD1A inhibited the formation of the TCF4–β-catenin transcription complex through competitive to β-catenin and suppressed the transcriptional activity of stem cell markers such as SOX9 via the Wnt/β-catenin signaling pathway. This leads to the downregulation of stem cell-like property-related markers in GC. This study revealed the underlying mechanisms that regulate Circ-0075305 in GCSCs and suggests that its role in reducing β-catenin signaling may serve as a potential therapeutic candidate. Circular RNA Circ0075305 hinders gastric cancer stem cells by indirectly increasing the expression of RPRD1A. In turn, RPRD1A disrupts TCF4-β-catenin complex formation and promotes downregulation of SOX9 transcription. [ABSTRACT FROM AUTHOR]

Objective: To describe the features of ETV6::ABL1 AML as well as the clinical treatment and outcomes. Methods: Clinical data were collected from three patients diagnosed with ETV6::ABL1 AML at Hebei Yanda Lu Daopei Hospital and Beijing Lu Daopei Hospital. Their clinical and laboratory features were analyzed, and the treatment process and outcomes were described. Ten reported cases of ETV6::ABL1 AML from the literature were also included for analysis. Results: The median age of the patients was 34 years, and 2 patients were male. No patient had a history of blood disorders before diagnosis. After relapse, they were referred to our hospital, where the ETV6::ABL1 gene was detected. Unfortunately, Patient 1 died rapidly after leukemia relapse due to severe infection. Patients 2 and 3 received salvage therapy with a dasatinib-containing regimen, followed by allo-HSCT, and are currently alive and disease-free. Conclusion: ETV6::ABL1 is a rare but recurrent genetic aberration in AML, and the combined use of fluorescence in situ hybridization and PCR can better identify this fusion gene. Patients carrying ETV6::ABL1 have a high relapse rate and a poor prognosis. TKIs are a reasonable treatment option for this group, and allo-HSCT may be curative. [ABSTRACT FROM AUTHOR]

Metal oxides have been widely used in gas sensors. Metal oxides have the advantages of low cost, easy preparation and stable performance. However, the disadvantage of their high operating temperature limits their wider application. In this paper, a simple method based on hydrothermal reaction was developed to prepare ZnO/In2O3 composites with high response values capable of fast recovery. The chemical composition, microscopic morphology and structure of the ZnO/In2O3 composites were investigated by various characterization methods to determine the formation of ZnO/In2O3 heterojunction. The gas-sensitive properties of pure In2O3 and ZnO/In2O3 composites were tested at room temperature. The results showed that ZnO/In2O3 composites with different Zn/In molar ratios had short recovery time and high response value to NO2 at room temperature. Among them, the ZnO/In2O3 with Zn/In molar ratio of 2:1 showed the best gas-sensitive performance to NO2 at room temperature. The response values to NO2 were measured at concentrations of 5, 10, 20, and 30 ppm, resulting in values of 2.70, 3.26, 4.80, and 5.25, respectively. The response time to NO2 at 30 ppm was 267 s, with a recovery time of 7 s. In addition, ZnO/In2O3 composites have good long-term stability and selectivity to NO2 at room temperature. [ABSTRACT FROM AUTHOR]

Conventional liquid-phase methods lack precise control in synthesizing and processing materials with macroscopic sizes and atomic thicknesses. Water interfaces are ubiquitous and unique in catalyzing many chemical reactions. However, investigations on two-dimensional (2D) materials related to water interfaces remain limited. Here we report the growth of millimeter-sized 2D PbI2 single crystals at the water-air interface. The growth mechanism is based on an inherent ion-specific preference, i.e. iodine and lead ions tend to remain at the water-air interface and in bulk water, respectively. The spontaneous accumulation and in-plane arrangement within the 2D crystal of iodide ions at the water-air interface leads to the unique crystallization of PbI2 as well as other metal iodides. In particular, PbI2 crystals can be customized to specific thicknesses and further transformed into millimeter-sized mono- to few-layer perovskites. Additionally, we have developed water-based techniques, including water-soaking, spin-coating, water-etching, and water-flow-assisted transfer to recycle, thin, pattern, and position PbI2, and subsequently, perovskites. Our water-interface mediated synthesis and processing methods represents a significant advancement in achieving simple, cost-effective, and energy-efficient production of functional materials and their integrated devices. Here, the authors report the growth of millimetre-scale 2D PbI2 single crystals via the spontaneous accumulation and in-plane arrangement of iodide ions at the water-air interface. The metal iodide crystals could be thinned down to a single monolayer via water etching, and subsequently converted into perovskite optoelectronic devices. [ABSTRACT FROM AUTHOR]

Background: Liver fibrosis is a predisposing factor for liver cancer. This study will investigate the predictive role of the Triglyceride-glucose and Gamma-glutamyl transferase index (TyG-GGT) as a non-invasive indicator of advanced liver fibrosis in individuals with obesity or overweight. Method: We enrolled patients who underwent metabolic and bariatric surgery as well as intraoperative liver biopsies at Zhejiang provincial people's hospital from August 2020 to March 2023. Clinical characteristics, comorbidities, laboratory data, and pathological variables of patients were collected and analysed. Then, we conducted logistics regression model to compare the performance of the TyG-GGT index with other 4 non-invasive models. Results: A total of 65 patients were included in this study. 43(66.2%) of them were female, with the mean body mass index (BMI) of 39.0 ± 7.3 kg/m2. Meanwhile, 24(36.9%) patients were diagnosed with diabetes. Advanced liver fibrosis were observed in 16.9% of patients, while liver cirrhosis was found in 4.6% of patients. The multivariable logistics regression showed that TyG-GGT was an independent risk factor of advanced liver fibrosis (OR = 6.989, P = 0.049). Additionally, compared to another 4 non-invasive liver fibrosis models (NFS = 0.66, FIB4 = 0.65, METS-IR = 0.68, APRI = 0.65), TyG-GGT exhibits the highest AUC value of 0.75. Conclusions: More than one-third of patients undergoing metabolic and bariatric surgery are afflicted with nonalcoholic steatohepatitis (NASH), and a significant proportion exhibit advanced fibrosis. TyG-GGT was a potentially reliable predictor for screening individuals with overweight or obesity at high risk of advanced liver fibrosis, thus providing clinical guidance for early intervention in this targeted group. [ABSTRACT FROM AUTHOR]

In this article, we consider the existence of ground state sign-changing solutions to a class of Schrödinger–Poisson systems - Δ u + V λ (x) u + ϕ u = | u | 4 u + μ f (u) , in R 3 , - Δ ϕ = u 2 , in R 3 , where μ > 0 and V λ (x) = λ V (x) + 1 with λ > 0 . Under suitable conditions on f and V, by using the constraint variational method and quantitative deformation lemma, we prove that the above problem has one ground state sign-changing solution and the energy of ground state sign-changing solution is strictly more than twice the energy of the ground state solution. Furthermore, we also study the asymptotic behavior of ground state sign-changing solutions as λ → ∞ . [ABSTRACT FROM AUTHOR]

Superficial weathering in the form of granular disaggregation, powdering and flaking on stone surface is one of the most serious damages to stone heritages, since the surface carries most of the artistic, historical information. The determination of the thickness of the superficially weathered layer of historical stones is critical to their conservation. However, the methodology for quantitative analyses of such thickness remains very limited. In this study, we carefully study the vapor absorption and pore structure evolution of historical sandstones from Guanzhong area with respect to their weathering. We find out that the thickness of superficial weathered layer of Guanzhong sandstones can be derived by following the changes in vapor absorption or pore structure. Such data achieved from various methods developed in this work are consistent with each other and in good agreement with the results obtained by using current techniques such as drilling resistance measurement, the Ruxton method and ultrasonic testing. Among all methods used, pore size distribution analysis requires less sample preparation and measures the thickness of superficial weathered layer of Guanzhong sandstones around 7 mm. [ABSTRACT FROM AUTHOR]

The objective of this study is to optimise the process of supercritical water gasification of rice husk biomass utilising a low-cost catalyst made from alkaline-earth materials. The interactions between catalyst loading and Fe content on gasification yield were investigated using response surface methodology. The catalyst characterisation findings revealed that the catalysts' predominant reactive site is on iron oxide, calcium ferrite, and calcium oxide. Under all the conditions tested, the manufactured catalyst was highly active in promoting char gasification, gas volume, and gasification efficiency whilst the tar yield was substantially elevated. The maximum gasification efficiency of 69.57%, gas yield of 402.8 mL/g biomass, char yield 24.68 wt%, and gravimetric tar yield of 57.5 mg/g were obtained under the catalytic conditions of 15% catalyst loading with 5%Fe/limestone, 492 °C, 120-min residence time, and 9.5 wt% feed concentrations. Thus, the manufactured catalyst showed a potential for optimising gasification outputs. [ABSTRACT FROM AUTHOR]

One new seco-cyclic phorbol derivative and one new phorbol 12-monoester, named 13-oxo-14-isopropylphorbol (2), 12-angelylphorbol (5), together with four known compounds, named 4a-deoxyphorbol, 13-oxo-14-isopropenylphorbol, 12-isobutyrylphorbol, and phorbol-12-(2-methylbutyrate) were obtained by hydrolyzing croton oil. The structures of the compounds were elucidated by spectroscopic analysis. These compounds showed no cytotoxicity (CC50 > 200 μM). Phorbol-12-monoesters 4–6 showed the weak inhibitory activities on syncytia formation induced by HIV-1IIIB (4, EC50 = 56.05 μM; 5, EC50 = 72.97 μM; 6, EC50 = 52.58 μM). The seco-cyclic phorbol derivatives (2, 3) showed no anti-HIV-1 activities (EC50 > 200 μM), which indicated that chemical cleavage of cyclopropanols might affect anti-HIV-1 activity. [ABSTRACT FROM AUTHOR]

Biofouling on ships and offshore structures has always been a difficult problem to solve, which not only jeopardizes the structural strength but also brings great economic losses. Ultrasonic cavitation is expected to solve this problem due to its characteristics of no damage to structures and no pollution. Starting from the phenomenon and mechanism of ultrasonic cleaning, this paper introduces the application of ultrasonic cavitation in ship, pipeline and oil cleaning as well as ballast water treatment. By reviewing the existing studies, limitations such as insufficient ultrasonic parameter studies, lack of uniform cleanliness standards, and insufficient cavitation studies are summarized to provide traceable research ideas for improving ultrasonic cavitation technology and to guide the expansion and improvement of its applications. [ABSTRACT FROM AUTHOR]

Key message: Unreduced megagametophytes via second-division restitution were confirmed through heterozygosity analysis, and four candidate physical centromeres of rubber were located for the first time. The evaluation of maternal heterozygosity restitution (MHR) is vital in identifying the mechanism of 2n gametogenesis and assessing the utilization value of 2n gametes. In this study, three full-sib triploid populations were employed to evaluate the MHR of 2n female gametes of rubber tree clone GT1 and to confirm their genetic derivation. The 2n female gametes of GT1 were derived from second-division restitution (SDR) and transmitted more than half of the parental heterozygosity. In addition, low recombination frequency markers were developed, and four candidate physical centromeres of rubber tree were located for the first time. The confirmation that 2n female gametes of rubber tree clone GT1 are derived from SDR provides insights into the molecular mechanisms of 2n gametogenesis. In addition, the identified centromere location will aid in the development of centromeric markers for the rapid identification of the 2n gametogenesis mechanism. [ABSTRACT FROM AUTHOR]

This paper reports lithium concentrations and isotopic compositions of olivines in the oceanized subcontinental lithospheric mantle (SCLM) peridotites of the Tibetan Yunzhug ophiolite. The results show systematic Li isotope changes with distance from the rim of olivine grains. δ7Li values of olivine in dunites decrease from + 10.46 to + 1.33‰ with increasing distance to olivine rim from 26.15 to 124.71 μm. A negative correlation of δ7Li and Li content in olivine from dunite and harzburgite indicates recent diffusive ingress of Li into the peridotites. The extremely heavy Li isotopic composition requires the seawater or seawater alteration endmember in the mixing model, and reveals Li diffusion from seawater into olivine. As in dunites, olivines in a harzburgite sample show similar variations in δ7Li as a function of distance from the grain rim (e.g., 6.01 to 1.73 in sample 14YZ13). We suggest that the behavior of Li in the oceanized SCLM peridotites may be controlled by Li diffusion from seawater, as Li activity in the liquid state is higher than the solid state in transporting Li through the olivines in the peridotites. This study supports that seawater Li diffusion is one of the important factors for the heterogeneity of mantle Li isotopes in ophiolites. [ABSTRACT FROM AUTHOR]

With the rapid development of white LEDs, the research of new and efficient white light emitting materials has attracted increasing attention. Zero dimensional (0D) organic–inorganic hybrid metal halide perovskites with superior luminescent property are promising candidates for LED application, due to their abundant and tailorable structure. Herein, [(CH3)3S]2SnCl6·H2O is synthesized as a host for dopant ions Bi3+ and Sb3+. The Sb3+ doped, or Bi3+/Sb3+ co-doped, [(CH3)3S]2SnCl6·H2O has a tunable optical emission spectrum by means of varying dopant ratio and excitation wavelength. As a result, we can achieve single-phase materials suitable for emission ranging from cold white light to warm white light. The intrinsic mechanism is examined in this work, to clarify the dopant effect on the optical properties. The high stability of title crystalline material, against water, oxygen and heat, makes it promising for further application. [ABSTRACT FROM AUTHOR]

The efficacy of growth factor gene–modified stem cells in treating spinal cord injury (SCI) remains unclear. This study aims to evaluate the effectiveness of growth factor gene–modified stem cells in restoring motor function after SCI. Two reviewers searched four databases, including PubMed, Embase, Web of Science, and Scopus, to identify relevant records. Studies on rodents assessing the efficacy of transplanting growth factor gene–modified stem cells in restoring motor function after SCI were included. The results were reported using the standardized mean difference (SMD) with a 95% confidence interval (95% CI). Analyses showed that growth factor gene–modified stem cell transplantation improved motor function recovery in rodents with SCI compared to the untreated (SMD = 3.98, 95% CI 3.26–4.70, I2 = 86.8%, P < 0.0001) and stem cell (SMD = 2.53, 95% CI 1.93–3.13, I2 = 86.9%, P < 0.0001) groups. Using growth factor gene–modified neural stem/histone cells enhanced treatment efficacy. In addition, the effectiveness increased when viral vectors were employed for gene modification and high transplantation doses were administered during the subacute phase. Stem cells derived from the human umbilical cord exhibited an advantage in motor function recovery. However, the transplantation of growth factor gene–modified stem cells did not significantly improve motor function in male rodents (P = 0.136). Transplantation of growth factor gene–modified stem cells improved motor function in rodents after SCI, but claims of enhanced efficacy should be approached with caution. The safety of gene modification remains a significant concern, requiring additional efforts to enhance its clinical translatability. [ABSTRACT FROM AUTHOR]

Flocculent is commonly used in mining activities to improve the concentration of tailing slurry by enhancing the sedimentation process of small tailings particles. The presence of flocculent in thickened tailings is unavoidable, and it affects the heavy metal leaching performances and mechanical and rheological characteristics of tailing-based cemented paste backfill (CPB). This study is carried out to investigate the physicochemical and leachability of CPB amended with flocculants and lime-activated ground granulated blast-furnace slag (GGBS). The stabilized samples were subjected to a series of model tests, including toxicity characteristics leaching procedure (TCLP) and pH, unconfined compressive strength (UCS), scanning electron microscopy (SEM), and X-ray diffraction. Moreover, the CPB amended with anionic polyacrylamide (APAM) demonstrated better performance in terms of a decrease in heavy metal leachability besides higher mechanical strength than poly aluminum chloride (PAC) and poly ferric chloride (PFC) samples. Furthermore, the UCS results showed that increasing binder content up to 15% negatively influences strength improvement of all stabilized samples because of weak connections between soil particles and cementitious material, resulting in high leachability of heavy metals. The analysis of XRD and SEM showed that anionic polyacrylamide (APAM) cases exhibited more voluminous hydration products, resulting in a compact stabilized matrix and substantially reduced heavy metal leachability. [ABSTRACT FROM AUTHOR]

Geodynamic mechanism responsible for the generation of Silurian granitoids and the tectonic evolution of the Qilian orogenic belt remains controversial. In this study, we report the results of zircon U–Pb age, and systematic whole-rock geochemical data for the Haoquangou and Liujiaxia granitoids within the North Qilian orogenic belt and the Qilian Block, respectively, to constrain their petrogenesis, and the Silurian tectonic evolution of the Qilian orogenic belt. Zircon U–Pb ages indicate that the Haoquangou and Liujiaxia intrusions were emplaced at 423 ± 3 Ma and 432 ± 4 Ma, respectively. The Haoquangou granodiorites are calc-alkaline, while the Liujiaxia granites belong to the high-K calc-alkaline series. Both are peraluminous in composition and have relatively depleted Nd isotopic [εNd(t) = (− 3.9 – + 0.6)] characteristics compared with regional basement rocks, implying their derivation from a juvenile lower crust. They show adakitic geochemical characteristics and were generated by partial melting of thickened lower continental crust. Post-collisional extensional regime related to lithospheric delamination was the most likely geodynamic mechanism for the generation of the Haoquangou granodiorite, while the Liujiaxia granites were generated in a compressive setting during continental collision between the Qaidam and Qilian blocks. [ABSTRACT FROM AUTHOR]

This paper presents the analytical process of porous functionally graded graphene-reinforced truncated conical shells subjected to hydrostatic pressure and axial tension. Three types of graphene platelet (GPL) dispersion and three patterns of porous distribution were considered. A modified model, in which the volume fraction of the pores is regarded as the essential parameter, was built to evaluate the material properties. The static stability equations of the shells, coupled with the effect of the combined forces, were derived. The Galerkin integrate technique was employed to obtain the critical buckling hydrostatic pressure and axial tension. After the present method was validated, the influences of pores, GPLs, and shell geometrical characteristics were investigated in the parametric studies. The results show that the critical hydrostatic pressure and axial tension can be elevated by increasing the porous coefficient, semi-vertex, and length–thickness ratio. On the contrary, the critical pressure and tension are decreased with the rise of GPL mass fraction. [ABSTRACT FROM AUTHOR]

This meta-analysis compared the efficacy and safety of different antithrombotic regimens after left atrial appendage closure (LAAC). PubMed, Embase, Medline, Cochrane Library databases were systematically searched from their inception to March 2023. Patients were divided into short-term oral anticoagulation (OAC) group and antiplatelet therapy (APT) group. The incidence of events were performed using RevMan 5.4. The events including device-related thrombus (DRT), ischemic stroke/systemic embolization (SE), major bleeding, any bleeding, any major adverse event and all-cause mortality. Subgroup analysis were based on OAC alone or OAC plus single antiplatelet therapy (SAPT) in OAC group. Oral anticoagulants include warfarin and direct oral anticoagulant (DOAC). Fourteen studies with 35,166 patients were included. We found that the incidence of DRT (OR = 0.49, 95% CI 0.36–0.66, P＜0.0001) and all-cause mortality (OR = 0.71, 95% CI 0.57–0.89, P = 0.002) were significantly lower in OAC group than APT group. However, there was no statistical differences in the incidence rates of ischemic stroke/SE (OR = 0.77, 95% CI 0.49–1.20, P = 0.25), major bleeding (OR = 0.84, 95% CI 0.55–1.27, P = 0.84), any bleeding (OR = 0.83, 95% CI 0.56–1.22, P = 0.34) and any major adverse event (OR = 0.56, 95% CI 0.30–1.03, P = 0.06) in the two groups. Subgroup analysis found that the incidence of DRT, all-cause mortality and any major adverse event in OAC monotherapy were lower than that in APT group (P＜0.05), but not statistically different from other outcome. The incidence of DRT, all-cause mortality, any major adverse event and any bleeding in DOAC were significantly better than APT group (P＜0.05). While warfarin only has better incidence of DRT than APT (P＜0.05), there was no statistical difference between the two groups in other outcome (P＞0.05). The incidence of DRT was significantly lower than APT group (P＜0.05), major bleeding were higher, and the rest of the outcome did not show any statistically significant differences(P＞0.05) when OAC plus SAPT. Based on the existing data, short-term OAC may be favored over APT for patients who undergo LAAC. DOAC monotherapy may be favored over warfarin monotherapy or OAC plus APT, when selecting anticoagulant therapies. [ABSTRACT FROM AUTHOR]

Genetic diversity studies not only improve the understanding of the wild genetic resources of species but also provide a theoretical basis for the protection, development, and utilization of species and formulation of reasonable protection measures. Fishing pressure on the near threatened fish Harpadon nehereus has recently increased, leading to the aging and miniaturization of its population. We determined the gene sequences of mitochondrial cytochrome b (Cytb) and nuclear recombination-activating 1 (RAG1) in eight populations of H. nehereus in the Northwest Pacific, analyzed their genetic diversity levels, and compared the effectiveness of these two markers for analyzing genetic diversity and population structure. Sequence analysis of Cytb revealed that the eight populations showed low haplotype diversity (Hd = 0.110–0.356) and low nucleotide diversity (pi = 0.00015–0.00053). No significant genetic differentiation was observed among the populations (Fst = − 0.0197–0.000, P > 0.05). The haplotype network diagram did not exhibit evident geographical clustering or a pedigree structure. Molecular variance analysis revealed that variation primarily occurred within populations. Further comparative analysis of the RAG1 and Cytb sequences revealed two differences. RAG1 showed high haplotype diversity (Hd = 0.780–0.900) and low nucleotide diversity (pi = 0.00355–0.00463). The genetic differentiation index value revealed a significantly low level of genetic differentiation among some populations. [ABSTRACT FROM AUTHOR]

B cell acute lymphoblastic leukemia (ALL) is characterized by the highly heterogeneity of pathogenic genetic background, and there are still approximately 30–40% of patients without clear molecular markers. To identify the dysregulated genes in B cell ALL, we screened 30 newly diagnosed B cell ALL patients and 10 donors by gene expression profiling chip. We found that ECM1 transcription level was abnormally elevated in newly diagnosed B cell ALL and further verified in another 267 cases compared with donors (median, 124.57% vs. 7.14%, P < 0.001). ROC analysis showed that the area under the curve of ECM1 transcription level at diagnosis was 0.89 (P < 0.001). Patients with BCR::ABL1 and IKZF1 deletion show highest transcription level (210.78%) compared with KMT2A rearrangement (39.48%) and TCF3::PBX1 rearrangement ones (30.02%) (all P < 0.05). Also, the transcription level of ECM1 was highly correlated with the clinical course, as 20 consecutive follow-up cases indicated. The 5-year OS of patients (non-KMT2A and non-TCF3::PBX1 rearrangement) with high ECM1 transcription level was significantly worse than the lower ones (18.7% vs. 72.9%, P < 0.001) and high ECM1 transcription level was an independent risk factor for OS (HR = 5.77 [1.75–19.06], P = 0.004). After considering transplantation, high ECM1 transcription level was not an independent risk factor, although OS was still poor (low vs. high, 71.1% vs. 56.8%, P = 0.038). Our findings suggested that ECM1 may be a potential molecular marker for diagnosis, minimal residual disease (MRD) monitoring, and prognosis prediction of B cell ALL. Trial registration Trial Registration Registered in the Beijing Municipal Health Bureau Registration N 2007–1007 and in the Chinese Clinical Trial Registry [ChiCTR-OCH-10000940 and ChiCTR-OPC-14005546]; . [ABSTRACT FROM AUTHOR]

Background: Minimal residual disease (MRD) is proposed to be responsible for tumor recurrence. The role of circulating tumor DNA (ctDNA) to detect MRD, monitor recurrence, and predict prognosis in liver cancer patients undergoing liver transplantation (LT) remains unrevealed. Methods: Serial blood samples were collected to profile ctDNA mutational changes. Baseline ctDNA mutational profiles were compared with those of matched tumor tissues. Correlations between ctDNA status and recurrence rate (RR) and recurrence-free survival (RFS) were analyzed, respectively. Dynamic change of ctDNA was monitored to predict tumor recurrence. Results: Baseline mutational profiles of ctDNA were highly concordant with those of tumor tissues (median, 89.85%; range 46.2–100%) in the 74 patients. Before LT, positive ctDNA status was associated with higher RR (31.7% vs 11.5%; p = 0.001) and shorter RFS than negative ctDNA status (17.8 vs 19.4 months; p = 0.019). After LT, the percentage of ctDNA positivity decreased (17.6% vs 47.0%; p < 0.001) and patients with positive ctDNA status had higher RR (46.2% vs 21.3%; p < 0.001) and shorter RFS (17.2 vs 19.2 months; p = 0.010). Serial ctDNA profiling demonstrated patients with decreased or constant negative ctDNA status had lower RR (33.3% vs 50.0%; p = 0.015) and favorable RFS (18.2 vs 15.0 months, p = 0.003) than those with increased or constant positive ctDNA status. Serial ctDNA profiling predicted recurrence months ahead of imaging evidence and serum tumor biomarkers. Conclusions: ctDNA could effectively detect MRD and predict tumor recurrence in liver cancer patients undergone LT. [ABSTRACT FROM AUTHOR]