Browse Articles

Runx2 takes center stage in regulating HSC expansion

Evaluating dental student competency in forensic rugoscopy for human identification

LEF1 and CLL: a matter of quantity and quality

Clinical predictive fusion network for accurate disease prediction in patient cohorts

NMNAT3 deficiency: a novel red blood cell enzymopathy causing hemolysis by altering NAD levels and glycolysis

Abstract We describe, to our knowledge, the first case of nicotinamide mononucleotide adenylyl transferase 3 (NMNAT3) deficiency, a novel red cell enzymopathy that causes reduced NAD levels and mild hemolytic anemia, which improved upon NAD precursor supplementation. We therefore propose testing for NMNAT3 variants in unexplained hereditary hemolytic anemia.

Optimal compilation strategies for QFT circuits in neutral-atom quantum computing

Armed and SAVVY: CAR T cells combat AML

Wear behaviour and statistical assessment of organomodified nanoclay reinforced glass fiber epoxy nanocomposites

Genome-wide analysis defines genetic determinants of MPN subtypes and identifies a sex-specific association at <i>CDH22</i> / <i>CD40</i>

Abstract To identify genetic variants that influence myeloproliferative neoplasm (MPN) phenotypes, we undertook a 2-stage patient-only genome-wide association study. MPN subtypes (essential thrombocythemia [ET]; polycythemia vera [PV]) were compared with each other to healthy controls and stratified analyses was performed for chromosome 9p aberrations, JAK2 V617F mutation burden, and sex. The ET vs PV analysis identified known associations: (1) at HBS1L-MYB that increased ET risk (Pmeta = 7.93 × 10–6, odds ratio [OR] = 1.28) and reduced PV risk (Pmeta = 9.43 × 10–5, OR = 0.81) and (2) at GFI1B-GTF3C5 that predisposed to PV only (Pmeta = 1.43 × 10–9, OR = 1.38). Two further linked intronic variants, rs2425786 and rs2425788, at CDH22/CD40 were significant in females only (Pmeta = 2.67 × 10–8), with predisposition to PV (Pmeta = .0006, OR = 1.3) and reduction of ET risk (Pmeta = 7.82 × 10–5, OR = 0.75). A polygenic risk score consisting of 48 variants from 31 loci demonstrated moderate discriminative performance for ET and PV (area under the curve [AUC] = 0.718) and was improved by optimization for disease subtype (AUCET = 0.724 and AUCPV = 0.755). Overall, our results reveal that multiple germline variants influence MPN phenotype, with HBS1L-MYB and a novel sex-specific association with CDH22/CD40 being the strongest determinants.

Decoding the molecular mechanism via systems biology-based insights into neoschaftoside from Ailanthus altissima targeting lung cancer

Abstract The epidermal growth factor receptor (EGFR) is a critical regulator of multiple oncogenic signaling cascades, including MAPK, PI3K/AKT/mTOR, and JAK–STAT pathways, which collectively contribute to enhanced proliferation, angiogenesis, and resistance to apoptosis in cancer. Aberrant EGFR activation has been strongly associated with tumor progression and therapeutic resistance, underscoring its importance as a molecular target for anticancer interventions. Ailanthus altissima ( A. altissima ), is known for its broad-spectrum anticancer potential although the underlying mechanism has not yet been clearly defined. Therefore, in present study, bioactive constituents of A. altissima were systematically analyzed for their ability to modulate proteins implicated in cancer pathogenesis and subsequently overlapped with hub genes differentially expressed across cancer grades. The common targets were mapped to lung cancer associated signaling pathways, revealing EGFR as a highly modulated node. Among the identified metabolites, neoschaftoside emerged as the top-ranked bioactive interacting with EGFR-related hub genes. Later, Molecular docking and molecular dynamics (MD) simulations demonstrated strong binding affinity and conformational stability of the EGFR neoschaftoside complex. Post-MD analyses, including principal component analysis (PCA) and dynamic cross-correlation matrix (DCCM) analysis, further indicated restricted global motions and enhanced correlated dynamics, confirming structural stabilization upon ligand binding. Collectively, these findings suggest that neoschaftoside may function as a promising lead compound capable of inhibiting EGFR activity through modulation of EGFR signaling, thereby suppressing oncogenic progression.

Acalabrutinib treatment for older (aged ≥80 years) and/or frail patients with CLL: primary end point analysis of the CLL-Frail trial

Abstract Because frail patients and patients aged ≥80 years with chronic lymphocytic leukemia (CLL) are still underrepresented in clinical trials, the CLL-Frail trial aimed to evaluate the efficacy and safety of acalabrutinib in these patients. The primary end point was the overall response rate (ORR) after 6 cycles of treatment to test the null hypothesis of ORR ≤65%. Fifty-three patients were included in the trial, and 34 patients are still on therapy. Adverse events (AEs) were the most frequent reason for early discontinuation (10 patients), whereas 5 patients stopped treatment because of death. Median age was 81 years, and 47.2% of patients were frail. The ORR for the 46 patients receiving ≥3 cycles of treatment was 93.5% (95% confidence interval, 82.1-98.6) meeting the primary end point of this trial (P &amp;lt; .001). The estimated 12-month progression-free and overall survival rates were 93.3% and 95.7%, respectively, after a median follow-up of 19 months. 53.5% of patients reported an improvement in their self-perceived frailty. Although all patients experienced AEs, and severe (Common Terminology Criteria of ≥3) events were reported in 63.5% of patients, there were no events of severe bleeding and atrial fibrillation was rare (2 cases of Common Terminology Criteria Grades 2 and 3). Five patients died, of which 4 deaths happened during or &amp;lt;28 days after treatment. Infections/COVID-19 were the cause of death in 3 cases. To our knowledge, this is the first prospective trial in older and/or frail patients with CLL demonstrating a high efficacy and safe treatment with acalabrutinib monotherapy. This trial was registered at www.ClinicalTrials.gov as #NCT04883749.

Optimized deep learning for Indian Classical Dance Classification a novel application based on a refined version of chameleon swarm algorithm

Silkenstedt E, Dreyling M. Treatment of relapsed/refractory MCL. <i>Blood</i> . 2025;145(7):673-682.

Wildfire-Induced alterations in soil physical, chemical, and micromorphological properties in forest ecosystems of Yunnan, Southwestern China

Feasibility and safety of anti-PD1 first-line treatment of classic Hodgkin lymphoma: do we see the full picture?

Abstract Classic Hodgkin lymphoma (cHL) is highly curable with risk-adapted first-line treatment. Due to exceptional efficacy, antiprogrammed cell death protein 1 antibodies (aPD1) are increasingly incorporated into first-line treatment. However, the short- and long-term immune-related adverse event burden in this setting is insufficiently understood. Here, we review the currently available evidence on the feasibility and safety of aPD1 first-line cHL treatment. A more harmonized and complete reporting is critical to enable a detailed understanding and comprehensive assessment of aPD1-related morbidity.

Redox reactions in subducted CaCO3–Fe–SiO2 as a potential source of superdeep diamond inclusions

Increased LEF1 protein levels and isoform switching drive cell proliferation in chronic lymphocytic leukemia

Abstract The transcription factor lymphoid enhancer-binding factor 1 (LEF1) is aberrantly expressed across all subtypes and stages of chronic lymphocytic leukemia (CLL), yet the molecular mechanisms underlying its contribution to CLL pathogenesis remain poorly defined. Here, we conducted a comprehensive mechanistic dissection of LEF1 function in CLL using extensive functional analyses of patient-derived samples. We identified that, although LEF1 messenger RNA levels remain stable, patients with clinically aggressive disease show elevated LEF1 protein levels due to enhanced protein stability. LEF1 protein abundance is selectively modulated by lymph node–derived stimuli, including T-cell interactions and B-cell receptor signaling. Importantly, we uncovered a dual, context-dependent role for LEF1 that is determined by its protein levels. Low LEF1 protein, characteristic of indolent disease, supports B-cell activation, whereas increased protein abundance in aggressive disease promotes proliferation through the binding and induction of cell cycle and metabolic gene networks. We further showed that LEF1 exon 6 skipping is enriched in proliferative and aggressive CLL. Both in vitro and in vivo experiments revealed that LEF1-driven proliferation is mediated by these short, alternative spliced isoforms. Although all LEF1 isoforms bind to a core set of proliferation- and activation-related genes, they induce distinct transcriptional programs; full-length LEF1 promotes a quiescence gene signature and limits leukemic growth, whereas exon 6-skipping isoforms drive proliferation. Our findings establish LEF1 as an oncogenic transcription factor in CLL whose biological and clinical effects are modulated posttranscriptionally by both protein abundance and isoform composition.

Inverse design of cellular structures with the targeted nonlinear mechanical response

MPN predisposition: shared roots, split branches

Density functional study of barium and strontium boron hydrides for hydrogen storage and optoelectronic applications