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Copy number aberrations (CNA) are the core determinants for diagnosis, risk stratification and prognosis in acute myeloid leukemia (AML) and myelodysplastic syndrome (MDS). In this study, a shallow whole-genome sequencing-based assay, LeukoPrint, was utilized to depict genomic CNA profiles from the bone marrow of 137 newly diagnosed AML/MDS patients. It demonstrated 98.1% concordance of CNA profiles with cytogenetics and/or fluorescence in situ hybridization (FISH). It is advantageous in detecting CNAs of short segments (1 Mb) and from samples with low leukemic cell content, more accurate for describing complex karyotypes and less confounded by subjective bias. LeukoPrint improved the overall diagnostic yield by redefining the risk categories for 16 patients by presenting new information. In summary, LeukoPrint provided an automated, convenient, and cost-effective approach to describe genomic CNA profiles. It brought greater diagnostic yield and risk stratification information by incorporating into the routine cytogenetics based on the CNA-related criteria of standard ELN/IPSS-R guidelines. [ABSTRACT FROM AUTHOR]

The integration of cyber technologies is transforming the power distribution network into a cyber-physical active distribution system (CPADS), and brings more flexibility to its operation. However, various uncertainties from the cyber space and physical space are emerging and coupled with each other, which results in significant challenges for the distribution network planning and operation. Thus, a bilevel integrated planning model accounting for multidimensional uncertainties from both the cyber space and physical space is proposed for the CPADS in this paper. With the goal of minimizing the annual investment and operation costs, the model comprehensively considers the location and selection of active-management elements (e.g., electrical storage systems, capacitor banks, and switches), investment constraints, power flow constraints, and operation constraints for all the active-management elements, etc. Moreover, based on the typical cyber system failure scenario represented by information link failure (ILF), a novel N-k uncertainty set considering the failure probability distribution is proposed, while the uncertainties of renewable energy and load demand are characterized by box-like uncertainty sets. Finally, the proposed planning model is recast into a multi-stage robust optimization model which can be divided into a master problem and two-step subproblems (SP-1 and SP-2) to be solved by the column and constraint generation (CCG) algorithm. Case studies and comparative analysis on the PG 69 distribution system are performed to verify the effectiveness of the proposed method. [ABSTRACT FROM AUTHOR]

This paper proposes a marker-based motion capture system for rat motion detection and gait analysis. Motion capture in small animals such as rodents is more challenging than in humans because of their small bodies and rapid motion. Existing algorithms have poor applicability in rat motion capture in environments outside the studio. Moreover, gait analysis targeting on the rat is not performed by existing motion capture software. Our method consists of four procedures. First, Region of Interest (ROI) is extracted from the background using the inter-frame difference method and a depth filter. Second, a double-threshold marker detection method is used to detect markers in ROI and a marker shape filter is used to classify the markers. Third, a marker corrector is designed to modify missing and incorrect markers. Finally, a deep learning network is used to analyse the gait trajectory to classify rat as healthy, injured, or rehabilitated. The experimental result shows that marker recognition accuracy is 99.33%, higher than that of most existing software. The validation accuracy of the network is 100% and the loss is 0.0001. This method is conductive to the development of motion capture systems for small animals and research into the gait kinematics of rodents. [ABSTRACT FROM AUTHOR]

Based on the cluster analysis technique, the prediction technology of mineral resources in the mining area is studied and the collected geochemical data are sorted out. Thirty-nine chemical elements of the data are clustered and six relatively stable regions are obtained. Correlation analysis of the geochemical data in four regions is carried out. Through the correlation between the elements and the characteristic elements of each deposit, predicting the possible resources and types in each region, a line chart of the content of 39 elements at different sampling points in each region is drawn. The results of the preliminary prediction and the results of the relevant analysis are combined to obtain the possible resources and resource types of the four regions. Finally, by combining the occurrence environment of each deposit with the geological data of each area, the types of mineral resources and resources in the area are further determined more accurately. [ABSTRACT FROM AUTHOR]

Chromosomal aberrations are useful in assessing treatment options and clinical outcomes of acute myeloid leukemia (AML) patients. However, 40∼50% of the AML patients showed no chromosomal abnormalities, i.e., with normal cytogenetics aka the CN-AML patients. Testing of molecular aberrations such as FLT3 or NPM1 can help to define clinical outcomes in the CN-AML patients but with various successes. Goal of this study was to test the possibility of Wilms’ tumor 1 (WT1) gene overexpression as an additional molecular biomarker. A total of 103 CN-AML patients, among which 28% had overexpressed WT1, were studied over a period of 38 months. Patient’s response to induction chemotherapy as measured by the complete remission (CR) rate, disease-free survival (DFS) and overall survival (OS) were measured. Our data suggested that WT1 overexpression correlated negatively with the CR rate, DFS and OS. Consistent with previous reports, CN-AML patients can be divided into three different risk subgroups based on the status of known molecular abnormalities, i.e., the favorable (NPM1mt/no FLT3ITD), the unfavorable (FLT3ITD) and the intermediate risk subgroups. The WT1 overexpression significantly reduced the CR, DFS and OS in both the favorable and unfavorable groups. As the results, patients with normal WT1 gene expression in the favorable risk group showed the best clinical outcomes and all survived with complete remission and disease-free survival over the 37 month study period; in contrast, patients with WT1 overexpression in the unfavorable risk group displayed the worst clinical outcomes. WT1 overexpression by itself is an independent and negative indicator for predicting CR rate, DFS and OS of the CN-AML patients; moreover, it increases the statistical power of predicting the same clinical outcomes when it is combined with the NPM1mt or the FLT3ITD genotypes that are the good or poor prognostic markers of CN-AML. [ABSTRACT FROM AUTHOR]

Basic soil productivity (BSP) is the ability of a soil, in its normal environment to support plant growth. However, the assessment of BSP remains controversial. The aim of this study is to quantify and analyze the trends of BSP in winter wheat seasons using the decision support system for agrotechnologie transfer (DSSAT) model under a long-term fertilization experiment in the dark loessal soil region of the Loess Plateau of China. In addition, we evaluated the contribution percentage of BSP to yield and its influencing factors. A long-term fertilization experiment with a winter wheat/spring maize rotation was established in 1979 in a field of the Gaoping Agronomy Farm, Pingliang, Gansu, China, including six treatments: (1) no fertilizer as a control (CK), (2) chemical nitrogen fertilizer input annually (N), (3) chemical nitrogen and phosphorus fertilizer input annually (NP), (4) straw return and chemical nitrogen fertilizer input annually plus phosphorus fertilizer added every second year (SNP), (5) manure input annually (M), and (6) M plus N and P fertilizers added annually (MNP). The application of the DSSAT-CERES-Wheat model showed a satisfactory performance with good Wilmott d-index (0.78~0.95) and normalized root mean square error (NRMSE) (7.03%~18.72%) values for the tested genetic parameters of winter wheat. After the 26-years experiment, the yield by BSP of winter wheat under the M and MNP treatment significantly increased, at the rate of 2.7% and 3.82% a year, respectively, whereas that of CK and N treatments significantly decreased, at the rate of 0.23% and 3.03%. Moreover, the average contribution percentage of BSP to yield was 47.0%, 39.4%, 56.3%, 50.0%, and 61.9% in N, NP, SNP, M, and MNP treatments, respectively. In addition, soil organic carbon contents were the main controls of BSP under the different fertilization conditions in the dark loessial soil area. As a result, the combined application of organic fertilizer or straw and chemical fertilizer can be an effective form of fertilization management to greatly enrich basic soil productivity, continually promote the contribution percentage of BSP, and ultimately increase crop yield. [ABSTRACT FROM AUTHOR]

• The combined application of EENFs with water and fertilizer management significantly reduced N 2 O emissions. • The combined application of EENFs with water and fertilizer management had no significant effect on CH 4 and CO 2 emission. • The combined application of EENFs with water and fertilizer management can maintain yield while minimize GWP and GHGI. Enhanced efficiency nitrogen fertilizers (EENFs), including nitrification inhibitors (NIs) and slow-release fertilizers (SRFs), are considered a feasible pathway for improving grain yield and mitigating greenhouse gas (GHG) emissions. However, the usage of EENFs in an intensified spring wheat system has not been well documented. The combined application of EENFs with water and fertilizer management (EENFs-WFM) was investigated in an irrigated spring wheat cropping system over two years. Measurements of soil nitrous oxide (N 2 O), methane (CH 4) and carbon dioxide (CO 2) fluxes were taken across five treatments: no N fertilizer as a control (CK), conventional N fertilization and irrigation (Con), optimum N fertilization and irrigation (Opt), optimum N fertilization and irrigation plus nitrification inhibitor (Opt + NI), and optimum N fertilization as slow-release fertilizer and irrigation (Opt-SRF). The cumulative N 2 O emissions in both growing seasons were significantly (P < 0.05) higher than the fallow seasons and accounted for 56–83% of total emissions. The Opt, Opt-SRF, and Opt + NI treatments significantly reduced the cumulative N 2 O emissions by 25%, 34%, and 45%, respectively, relative to the Con treatment, while the fertilizer N input decreased by 36%. The soil acted as a tiny sink for atmospheric CH 4 , with no significant effect in any treatment. Moreover, global warming potential (GWP) and greenhouse gas intensity (GHGI) declined by ∼45% and ∼33%, respectively, in the Opt + NI treatment and ∼46% and ∼34%, respectively, in the Opt-SRF treatment, relative to the Con treatment, with almost no effect on grain yield. Our results highlight that EENFs-WFM is a promising management system for maintaining yield while minimizing GWP and GHGI. [ABSTRACT FROM AUTHOR]

Background: X-linked lymphoproliferative syndrome type 1 (XLP1) is an X-linked recessive genetic disorder with a strong resemblance to hemophagocytic lymphohistiocytosis (HLH). Causative mutations for XLP1 have been identified in SH2D1A, located on chromosome Xq25. Case presentation: We report a case of an 18-month-old male with a novel nonsense mutation in SH2D1A. The patient presented the typical phenotype of HLH, including splenomegaly and hemophagocytosis in the bone marrow. Thus, he was initially diagnosed with HLH based on HLH-2004 guidelines. High-throughput amplicon sequencing was performed to detect mutations in the most commonly reported causative genes of HLH, i.e., PRF1, UNC13D, STX11, STXBP2, SH2D1A, and XIAP. A likely pathogenic nonsense mutation was detected in SH2D1A (NM_002351.4:c.300T>A). The mutation was inherited from the patient's mother, and an X-linked recessive mode of inheritance was confirmed by a two-generation pedigree analysis based on Sanger sequencing results. Conclusions: The nonsense mutation in SH2D1A (NM_002351.4:c.300T>A) was reported for the first time in a case of XLP1 and was considered to be likely pathogenic based on the truncation of the mRNA sequence. This finding expands the spectrum of known XLP-related mutations in Chinese patients and indicates the utility of amplicon sequencing for XLP and HLH diagnosis. [ABSTRACT FROM AUTHOR]

Background and Objective: The bone marrow microenvironment is closely related to normal hematopoiesis and hematologic tumors. Adipocytes are an important part of the bone marrow microenvironment, in which they can release free fatty acids (FFAs) through lipolysis and secrete adipocytokines, etc., and participate in normal hematopoiesis, which is closely related to the occurrence and treatment of hematological tumors. In this review, we aim to discuss how bone marrow adipocytes (BMAs) can influence the proliferation, apoptosis, and chemotherapy resistance of cancer cells by reprogramming lipid metabolism and the secretion of various adipocytokines., Methods: Studies from 2000 to July 2024 were reviewed from PubMed, Springer Link, and the Web of Science using the keywords bone marrow microenvironment, adipocytes, lipid metabolism, adipocytokines, hematological tumor, cancer, and their combinations. Unreliable articles such as those that are old and have a low impact factor are excluded, and there is no restriction on language., Key Content and Findings: Adipocytes can regulate the proliferation and differentiation of hematopoietic stem cells (HSCs) by secreting inflammatory factors and adipocytokines to maintain hematopoietic homeostasis. Adipocytes can also stimulate and accelerate the occurrence and progression of hematological tumors by secreting adipocytokines and mediating the reprogramming of lipid metabolism. Moreover, abundant adipocytes in bone marrow can protect tumor cells by physically blocking and/or secreting cytokines, leading to chemotherapy resistance., Conclusions: Therefore, the targeted inhibition of related lipid metabolism pathways and adipocytokines might be a potential therapeutic target for hematological tumors, which would be helpful to inhibit tumor growth and correct chemotherapy resistance., Competing Interests: Conflicts of Interest: All authors have completed the ICMJE uniform disclosure form (available at https://tcr.amegroups.com/article/view/10.21037/tcr-24-52/coif). All authors report that this study was supported by the Key Project of Medical Science and Technology Co-Construction in Henan Province (No. SBGJ202002026). The authors have no other conflicts of interest to declare., (2024 AME Publishing Company. All rights reserved.)

Rapid and accurate pathogen identification is essential for timely and effective treatment of pneumonia. Here, we describe the use of metagenomic next-generation sequencing (mNGS) of bronchoalveolar lavage (BALF) fluid to identify pathogens in patients with hematologic comorbid respiratory symptoms in a retrospective study with 84 patients. In the transplantation group, 8 cases (19.5%) and 47 cases (97.9%) were positive for BALF by conventional method detection and mNGS detection, respectively, and 6 cases (14.0%) and 41 cases (91.1%) in chemotherapy group, respectively. The detection rate of mNGS in both groups was significantly higher than that of conventional detection methods (all P<0.05). Pseudomonas aeruginosa and Streptococcus pneumoniae were the most common bacterial infections in the transplantation and chemotherapy groups, respectively. Aspergillus was the most common fungal infection in both groups. Human betaherpesvirus 5 (HHV-5), torque teno virus and human betaherpesvirus 7 (HHV-7) were the most common pathogen species in both groups. The most common type of infection in patients in the transplantation and chemotherapy groups was the mixed infection of bacteria-virus. Most patients in the transplantation group had mixed infections based on multiple viruses, with 42 cases of viral infections in the transplantation group and 30 cases of viral infections in the chemotherapy group, which were significantly higher in the transplantation group than in the chemotherapy group (χ2 = 5.766, P=0.016). and the mixed infection of virus-virus in the transplantation group was significantly higher than that in the chemotherapy group (27.1% vs 4.4%, P=0.003). The proportion of death due to pulmonary infection was significantly higher in the transplantation group than in the chemotherapy group (76.9% vs 16.7%, χ2 = 9.077, P=0.003). This study demonstrated the value of mNGS of BALF in improving the diagnosis and prognosis of hematologic comorbid pneumonia, helping patients to obtain timely and effective treatment, and giving guidance on the overall treatment plan for patients, with particular benefit for patients with hematologic chemotherapy comorbid pneumonia., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest. The handling editor [LA] declared a shared parent affiliation with the author(s) [BZ, RG, QW, XJ, ZL, JW, LH, LZ, XL, JZ] at the time of review., (Copyright © 2022 Zhang, Gui, Wang, Jiao, Li, Wang, Han, Zhou, Wang, Wang, Fan, Lyu, Song and Zhou.)

C1qTNF-related protein 1 (CTRP1) is independently associated with type 2 diabetes. However, the relationship between CTRP1 and insulin resistance is still not established. This study aimed to explore the role of CTRP1 under the situation of insulin resistance in adipose tissue. Plasma CTRP1 level was investigated in type 2 diabetic subjects (n = 35) and non-diabetic subjects (n = 35). The relationship between CTRP1 and phosphorylation of multi insulin receptor substrate 1 (IRS-1) serine (Ser) sites was further explored. Our data showed that Plasma CTRP1 was higher and negative correlation with insulin resistance in diabetic subjects (r = -0.283, p = 0.018). Glucose utilisation test revealed that the glucose utilisation rate of mature adipocytes was improved by CTRP1 in the presence of insulin. CTRP1 was not only related to IRS-1 protein, but also negatively correlated with IRS-1 Ser1101 phosphorylation (r = -0.398, p = 0.031). Furthermore, Phosphorylation levels of IRS-1 Ser1101 were significantly lower after incubation with 40 ng/mL CTRP1 in mature adipocytes than those with no intervention (p < 0.05). There was no significant correlation between CTRP1 and other IRS-1 serine sites (Ser302, Ser307, Ser612, Ser636/639, and Ser789). Collectively, our results suggested that CTRP1 might improve insulin resistance by reducing the phosphorylation of IRS-1 Ser1101, induced in the situation of insulin resistance as a feedback adipokine.

Background: Fusion genes generated from chromosomal translocation play an important role in hematological malignancies. Detection of fusion genes currently employ use of either conventional RT-PCR methods or fluorescent in situ hybridization (FISH), where both methods involve tedious methodologies and require prior characterization of chromosomal translocation events as determined by cytogenetic analysis. In this study, we describe a real-time quantitative reverse transcription PCR (qRT-PCR)-based multi-fusion gene screening method with the capacity to detect 22 fusion genes commonly found in leukemia. This method does not require pre-characterization of gene translocation events, thereby facilitating immediate diagnosis and therapeutic management., Methods: We performed fluorescent qRT-PCR (F-qRT-PCR) using a commercially-available multi-fusion gene detection kit on a patient cohort of 345 individuals comprising 108 cases diagnosed with acute myeloid leukemia (AML) for initial evaluation; remaining patients within the cohort were assayed for confirmatory diagnosis. Results obtained by F-qRT-PCR were compared alongside patient analysis by cytogenetic characterization., Results: Gene translocations detected by F-qRT-PCR in AML cases were diagnosed in 69.4% of the patient cohort, which was comparatively similar to 68.5% as diagnosed by cytogenetic analysis, thereby demonstrating 99.1% concordance. Overall gene fusion was detected in 53.7% of the overall patient population by F-qRT-PCR, 52.9% by cytogenetic prediction in leukemia, and 9.1% in non-leukemia patients by both methods. The overall concordance rate was calculated to be 99.0%. Fusion genes were detected by F-qRT-PCR in 97.3% of patients with CML, followed by 69.4% with AML, 33.3% with acute lymphoblastic leukemia (ALL), 9.1% with myelodysplastic syndromes (MDS), and 0% with chronic lymphocytic leukemia (CLL)., Conclusions: We describe the use of a F-qRT-PCR-based multi-fusion gene screening method as an efficient one-step diagnostic procedure as an effective alternative to lengthy conventional diagnostic procedures requiring both cytogenetic analysis followed by targeted quantitative reverse transcription (qRT-PCR) methods, thus allowing timely patient management.

The chromosomal translocation t(7;11)(p15;p15) and the resulting nucleoporin 98-homeobox A9 ( NUP98-HOXA9 ) gene fusion is rare but recurrent genetic abnormity in acute myeloid leukemia (AML). The present study describes a case of AML plus maturation (-M2) with multilineage dyspoiesis in a 30-year-old male in whom a 46,XY,t(7;11)(p15;p15) karyotype was detected through chromosome analysis. Subsequent molecular and sequencing analysis demonstrated a NUP98-HOXA9 fusion gene with a type I fusion between NUP98 exon 12 and HOXA9 exon 1b, and mutations in neuroblastoma V-Ras oncogene homolog and Wilms tumor 1. The patient achieved hematological complete remission (CR) following two courses of induction chemotherapy. However, the NUP98-HOXA9 fusion gene remained detectable during the hematological CR period and following intensive consolidation chemotherapy. The disease relapsed 11 months after diagnosis, and the patient became refractory, with complications from an infection causing eventual mortality. The present case and literature review suggest that patients with AML and t(7;11) may have unique biological and clinical characteristics, and a poor prognosis.

Complement C1q tumor necrosis factor-related protein 1 (CTRP1), an adipose tissue-derived adipokine has been shown to decrease blood glucose levels and to improve metabolism of glucose in mice. In addition, CTRP1 has exhibited significant association with BMI, adiponectin and TNF-α in diabetic animal models. However, there are no published studies addressing CTRP1 levels in type 2 diabetic patients. Therefore, it was of interest to evaluate plasma CTRP1 levels and associated clinical parameters and biomarkers in patients with type 2 diabetes. 135 subjects were recruited to this study, including 62 type 2 diabetic patients (DM group) and 73 healthy subjects (control group). We measured biochemical parameters, CTRP1, TNF-α and adiponectin using enzyme-linked immunosorbent assay (ELISA). Plasma CTRP1 levels showed a significant difference between the DM group and the control group (646.3 ± 154.4 ng/mL vs. 442.6 ± 165.4 ng/mL, p < 0.01). In addition, CTRP1 was strongly positively associated with BMI, glucose levels, HbA1c, HOMA-IR and TNF-α in diabetic patients. CTRP1 showed negative correlation with adiponectin. In Multivariate regression analysis, CTRP1 was strongly independently associated with diabetes when CTRP1 levels were analyzed by both as a continuous variable and quartile (OR: 1.009, 95% CI: 1.004-1.015, p < 0.05; OR: 2.443, 95% CI: 1.379-4.182, p < 0.01, respectively). Increased plasma CTRP1 was independently associated with type 2 diabetes. Profiling of plasma adipokines such as CTRP1 is particularly important to obtain a greater understanding of their contribution to the type 2 diabetic state.