Genetic and clinical characteristics of acute B-cell lymphoblastic leukemia with MEF2D fusions and report of two novel MEF2D rearrangements.

The MEF2D rearrangement is a recurrent chromosomal abnormality detected in approximately 2.4-5.3% of patients with acute B-cell lymphoblastic leukemia (B-ALL). Currently, MEF2D-rearranged B-ALL is not classified as an independent subtype in the WHO classification. Consequently, the clinical significance of MEF2D rearrangement in B-ALL remains largely unexplored. In this study, we retrospectively screened 260 B-ALL patients with RNA sequencing data collected between November 2018 and December 2022. Among these, 10 patients were identified with MEF2D rearrangements (4 with MEF2D::HNRNPUL1, 3 with MEF2D::BCL9, 1 with MEF2D::ARID1B, 1 with MEF2D::DAZAP1 and 1 with MEF2D::HNRNPM). Notably, HNRNPM and ARID1B are reported as MEF2D fusion partners for the first time. The patient with the MEF2D::HNRNPM fusion was resistant to chemotherapy and chimeric antigen receptor T-cell therapy and relapsed early after allogenic stem cell transplantation. The patient with MEF2D::ARID1B experienced early extramedullary relapse after diagnosis. All 10 patients achieved complete remission after induction chemotherapy. However, 9/10 (90%) of whom experienced relapse. Three of the 9 patients relapsed with aberrant expression of myeloid antigens. The median overall survival of these patients was only 11 months. This small cohort showed a high incidence of early relapse and short survival in patients with MEF2D rearrangements.

Clonal evolution from B-cell acute lymphoblastic leukemia with BCR::ABL1 multilineage involvement to acute myeloid leukemia after multiple anti-CD19 chimeric antigen receptor T-cell therapy.

Not available.

Weathering the storm: diagnosis and treatment of a life-threatening disseminated Nocardia otitidiscaviarum infection.

Nocardiosis demonstrates a temporal categorization that includes acute, subacute, and chronic stages alongside distinct typical localizations such as pulmonary, cutaneous, and disseminated forms. Disseminated nocardiosis, commonly caused by Nocardia asteroides, N. brasiliensis, and N. farcinica, continues to result in substantial morbidity and mortality. Herein, we report a life-threatening disseminated nocardiosis caused by Nocardia otitidiscaviarum in a patient with minimal change disease. This study emphasizes the difficulty in the diagnosis and treatment of unknown infections in clinical settings and highlights the important role played by laboratories in solving infectious diseases caused by rare pathogens.

Virulence Factors and Carbapenem-Resistance Mechanisms in Hypervirulent Klebsiella Pneumoniae.

Hypervirulent Klebsiella pneumoniae (hvKP) has emerged as a novel variant of K. pneumoniae, exhibiting distinct phenotypic and genotypic characteristics that confer increased virulence and pathogenicity. It is not only responsible for nosocomial infections but also community-acquired infections, including liver abscesses, endophthalmitis, and meningitis, leading to significant morbidity and mortality. HvKP has been reported all over the world, but it is mainly prevalent in Asia Pacific, especially China. Moreover, hvKP can acquire carbapenemase genes resulting in the emergence of carbapenem-resistant hypervirulent K. pneumoniae (CR-hvKP), which possesses both high virulence and drug resistance capabilities. Consequently, CR-hvKP poses substantial challenges to infection control and presents serious threats to global public health. In this paper, we provide a comprehensive summary of the epidemiological characteristics, virulence factors, and mechanisms underlying carbapenem resistance in hvKP strains with the aim of offering valuable insights for practical prevention strategies as well as future research.

Investigations of the prognostic value of RUNX1 mutation in acute myeloid leukemia patients: Data from a real-world study.

RUNX1 is one of the recurrent mutated genes in newly diagnosed acute myeloid leukemia (AML). Although historically recognized as a provisional distinct entity, the AML subtype with RUNX1 mutations (AML-RUNX1mut) was eliminated from the 2022 WHO classification system. To gain more insight into the characteristics of AML-RUNX1mut, we retrospectively analyzed 1065 newly diagnosed adult AML patients from the First Affiliated Hospital of Soochow University between January 2017 and December 2021. RUNX1 mutations were identified in 112 patients (10.5%). The presence of RUNX1 mutation (RUNX1mut) conferred a lower composite complete remission (CRc) rate (40.2% vs. 58.4%, P＜0.001), but no significant difference was observed in the 5-year overall survival (OS) rate (50.2% vs. 53.9%; HR=1.293; P=0.115) and event-free survival (EFS) rate (51.5% vs. 49.4%; HR=1.487, P=0.089), even within the same risk stratification. Multivariate analysis showed that RUNX1mut was not an independent prognostic factor for OS (HR=1.352, P=0.068) or EFS (HR=1.129, P=0.513). When patients were stratified according to induction regimen, RUNX1mut was an unfavorable factor for CRc both on univariate and multivariate analysis in patients receiving conventional chemotherapy, and higher risk stratification predicted worse OS. In those who received venetoclax plus hypomethylating agents, RUNX1mut was not predictive of CRc and comparable OS and EFS were seen between intermediate-risk and adverse-risk groups. The results of this study revealed that the impact of RUNX1mut is limited. Its prognostic value depended more on treatment and co-occurrent abnormalities. VEN-HMA may abrogate the prognostic impact of RUNX1, which merits a larger prospective cohort to illustrate.

Classification and prediction of Klebsiella pneumoniae strains with different MLST allelic profiles via SERS spectral analysis.

The Gram-negative non-motile Klebsiella pneuomoniae is currently a major cause of hospital-acquired (HA) and community-acquired (CA) infections, leading to great public health concern globally, while rapid identification and accurate tracing of the pathogenic bacterium is essential in facilitating monitoring and controlling of K. pneumoniae outbreak and dissemination. Multi-locus sequence typing (MLST) is a commonly used typing approach with low cost that is able to distinguish bacterial isolates based on the allelic profiles of several housekeeping genes, despite low resolution and labor intensity of the method. Core-genome MLST scheme (cgMLST) is recently proposed to sub-type and monitor outbreaks of bacterial strains with high resolution and reliability, which uses hundreds or thousands of genes conserved in all or most members of the species. However, the method is complex and requires whole genome sequencing of bacterial strains with high costs. Therefore, it is urgently needed to develop novel methods with high resolution and low cost for bacterial typing. Surface enhanced Raman spectroscopy (SERS) is a rapid, sensitive and cheap method for bacterial identification. Previous studies confirmed that classification and prediction of bacterial strains via SERS spectral analysis correlated well with MLST typing results. However, there is currently no similar comparative analysis in K. pneumoniae strains. In this pilot study, 16 K. pneumoniae strains with different sequencing typings (STs) were selected and a phylogenetic tree was constructed based on core genome analysis. SERS spectra (N = 45/each strain) were generated for all the K. pneumoniae strains, which were then comparatively classified and predicted via six representative machine learning (ML) algorithms. According to the results, SERS technique coupled with the ML algorithm support vector machine (SVM) could achieve the highest accuracy (5-Fold Cross Validation = 100%) in terms of differentiating and predicting all the K. pneumoniae strains that were consistent to corresponding MLSTs. In sum, we show in this pilot study that the SERS-SVM based method is able to accurately predict K. pneumoniae MLST types, which has the application potential in clinical settings for tracing dissemination and controlling outbreak of K. pneumoniae in hospitals and communities with low costs and high rapidity.

Targeted therapy and immunotherapy for T cell acute lymphoblastic leukemia/lymphoma.

T cell acute lymphoblastic leukemia/lymphoma (T-ALL/LBL) is an aggressive malignancy of progenitor T cells. Despite significant improvements in survival of T-ALL/LBL over the past decades, treatment of relapsed and refractory T-ALL (R/R T-ALL/LBL) remains extremely challenging. The prognosis of R/R T-ALL/LBL patients who are intolerant to intensive chemotherapy remains poor. Therefore, innovative approaches are needed to further improve the survival of R/R T-ALL/LBL patients. With the widespread use of next-generation sequencing in T-ALL/LBL, a range of new therapeutic targets such as NOTCH1 inhibitors, JAK-STAT inhibitors, and tyrosine kinase inhibitors have been identified. These findings led to pre-clinical studies and clinical trials of molecular targeted therapy in T-ALL/LBL. Furthermore, immunotherapies such as CD7 CAR T cell therapy and CD5 CAR T cell therapy have shown profound response rate in R/R T-ALL/LBL. Here, we review the progress of targeted therapies and immunotherapies for T-ALL/LBL, and look at the future directions and challenges for the further use of these therapies in T-ALL/LBL.

Ultra-Low-Density Carbon Nanotube Aerogel Film for Fast and Sensitive Bolometric Sensing.

In various applications, infrared (IR) detectors with quick responses and high sensitivity at room temperature are essential. This work synthesizes carbon nanotube aerogel films (CAFs) with an ultra-low density of 1.33 mg cm-3. Transient electrothermal (TET) technology is used to characterize the thermal and electrical transport of CAFs in the temperature range of 320 to 10 K. CAF has record-low thermal conductivity (2.5 mW m-1 K-1 at 320 K) and thermal diffusivity (2.24 × 10-6 m2 s-1 at 320 K) in vacuum. The TCR of CAF is -0.11%/K at 295 K, which is 57% higher than that of the MWCNT films. In addition, the comprehensive bolometric performance of carbon nanotube aerogels is tested and analyzed, including the photothermal response, resistivity responsivity, and response time to lasers of a broad spectrum from ultraviolet to near-infrared. The relative responsivity of CAF to lasers of different wavelengths is found to be consistent. The response time of CAF with 200 µm suspended length is measured to be as short as 2.95-3.03 ms (framing rate of 330-339 per second). In addition, the resistive response of the CAF sample to a blackbody radiator and the radiation of the human hand also shows good sensitivity and repeatability. These results demonstrate the promising application of CAF as a sensitive and fast-response uncooled bolometer.

Anisodamine ameliorates ischemia/reperfusion-induced renal injury in rats through activation of the extracellular signal-regulated kinase (ERK) pathway and anti-apoptotic effect.

Anisodamine exerts significant protective effect on ischemia/reperfusion (I/R) injury in various organs. However, little is known about the mechanisms of anisodamine in renal I/R injury. Activation of extracellular regulated protein kinases (ERK) pathway promotes the repair of renal epithelial cells following oxidant injury. The present study investigated whether the renoprotective role of anisodamine against renal I/R injury in rats was associated with the activation of ERK signaling pathway. Male Sprague-Dawley (SD) rats were separated into the following groups: Sham-operated group, I/R group, anisodamine-treated group, PD98059 (MEK-1/ERK inhibitor)-treated group and anisodamine plus PD98059-treated group. A rat model of renal I/R was established by excising the right kidney and then clamping the left renal pedicle for 45 min followed by reperfusion for 24 h. Serum and renal tissue samples were obtained for assays of the associated morphological, molecular and biochemical parameters. Treatment with anisodamine ameliorated renal I/R injury, as evidenced by improvements of renal histology and kidney function, a decrease in paller's score and apoptosis index. Anisodamine also upregulated the phosphorylation levels of ERK1/2 and its downstream targets, including 90 ribosomal S6 kinase (p90rsk) and Bad, as well as the expression of antiapoptotic Bcl-2 protein, downregulated the expression levels of proapoptotic proteins Bax and cleaved-caspase-3, whereas these effects were greatly abolished by administration of PD98059. In conclusion, the results suggest that anisodamine prevents renal I/R injury in rats as a result of an activation of the ERK signaling pathway and anti-apoptotic properties.

Homophobic bullying victimization trajectories: The roles of perpetration, sex assigned at birth, and sexuality.

There is a paucity of research on developmental trajectories of bias-based aggression. We examined homophobic bullying victimization trajectories among high school students (N = 3,064; M age = 13.67; Girls = 50.2%) and how these developmental pathways vary as a function of factors like homophobic bullying perpetration, sex assigned at birth, and sexuality. Using data from a 3-wave longitudinal investigation over a 2-year period, we utilized latent growth mixture modeling to explore the aforementioned trajectories. Findings suggested that there were three distinct classes characterized by high initial rates and declines over time, low initial rates, and increases over time, and low, stable, rate across time. Furthermore, results indicated that homophobic bullying perpetration, sex assigned at birth, and sexuality all predicted class membership.

Sexual harassment victimization, school belonging, and depressive symptoms among LGBTQ adolescents: Temporal insights.

Peer victimization and the associated poor outcomes among lesbian, gay, bisexual, transgender, and questioning (LGBTQ) youth have been the focus of countless studies. School climate is a factor that has garnered significant attention. Perceptions of school contexts may even be mechanisms that define how victimization relates to poor outcomes. However, there is a lack of rigorous scholarship that could demonstrate directionality and therefore further augment our understanding of these relations. Specifically, it is not clear if victimization is strictly an antecedent to mental health issues like depressive symptoms. This longitudinal study examined the associations among sexual harassment victimization, school belonging, and depressive symptoms among LGBTQ high school students (n = 404). Self-report measures were completed at 3 time points across 3 school years in 6 Midwest high schools. Structural equation modeling indicated that peer victimization was an antecedent to depressive symptoms, and that school belonging mediated the association. Implications and future directions are discussed. (PsycINFO Database Record