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Chen L, Monti S, Juszczynski P, et al. SYK-dependent tonic B-cell receptor signaling is a rational treatment target in diffuse large B-cell lymphoma, <i>Blood</i> . 2008;111(4):2230-2237.

Impact of polygeneration topology on the technoeconomic performance of green hydrogen production utilizing integrated CPVT systems

Abstract This paper presents a year-long hour-by-hour dynamic comparative analysis of solar-driven polygeneration configurations at three Egyptian Sea coast locations — Hurghada, Suez, and Port Said. A MATLAB/SIMSCAPE computational framework is developed and validated, coupling a concentrating parabolic trough collector (PTC) to two receiver technologies: a conventional concentrating photovoltaic-thermal (CPVT), receiver-A, and a high-efficiency GaInP/GaInAs/Ge triple-junction photovoltaic-thermal (C3JT), receiver-B. Both are integrated with proton exchange membrane (PEM) electrolyzer and multi-effect evaporation (MEE) desalination units. Four configurations are evaluated: Polygeneration-I (Cases I-A and I-B) producing hydrogen and freshwater, and Polygeneration-II (Cases II-A and II-B) producing hydrogen and exporting electricity. The results show that the C3JT architecture consistently outperforms CPVT by 57.1–57.7% in annual hydrogen production across all configurations and locations. A global minimum levelized cost of hydrogen (LCOH) of 2.909 USD/kg is achieved by Case II-B at Hurghada, representing a 32.6% reduction relative to the Polygeneration-I CPVT baseline (Case I-A) at the same location. MEE thermal integration introduces an energy partitioning trade-off that reduces system-to-hydrogen HHV efficiency to 4.53–7.43% across Polygeneration-I configurations, yet this is more than offset by freshwater revenue credits in the economic framework. The results also demonstrate the economic viability of concentrating solar polygeneration in Egypt without requiring gigawatt-scale deployment.

Discovery and preclinical activity of the menin-KMT2A inhibitor ziftomenib in acute leukemia models

Abstract The protein-protein interaction between menin and KMT2A (histone lysine methyltransferase 2A) plays a critical role in acute leukemia with KMT2A rearrangements, nucleophosmin 1 (NPM1) mutations, and nucleoporin 98 rearrangements and represents an emerging opportunity for therapeutic intervention. Here, we report the development and comprehensive evaluation of the activity of ziftomenib as an orally bioavailable, highly potent, and selective small-molecule inhibitor of the menin-KMT2A interaction. In leukemia cells and primary patient samples with the menin-KMT2A dependency, ziftomenib profoundly inhibited proliferation, reduced clonogenic potential, and induced differentiation, which was associated with strong downregulation of the menin-KMT2A target genes, including MEIS1, HOXA9, and HOXB2. In xenografts and patient-derived xenograft models of KMT2A-rearranged leukemia, ziftomenib induced leukemia regression or reduced leukemia burden, accompanied by a pronounced reduction in the menin-KMT2A target genes. We next assessed ziftomenib against 4 MEN1 (gene encoding menin) mutants (T349M, M327I, G331R, G331D) associated with clinical resistance to another menin inhibitor, revumenib. Ziftomenib retained antileukemic activity against T349M mutant cells and demonstrated low nanomolar potency (50% growth inhibition ≤ 25nM) against G331R cells, despite several-fold reduced potency relative to MEN1 wild-type cells, whereas the M327I and G331D mutants were resistant. The crystal structures of ziftomenib in complex with menin wild-type, T349M, or G331R mutants revealed a similar binding mode of ziftomenib to these menin variants, rationalizing the potent inhibitory activity toward these mutants. Ziftomenib has recently received US Food and Drug Administration approval for adult patients with NPM1-mutated acute myeloid leukemia and continues to be evaluated clinically in leukemias with NPM1 or KMT2A alterations, both as monotherapy and in combinations.

OCT angiography vessel density loss and rates of visual field progression in glaucoma and glaucoma suspects

Abstract To evaluate the relationship between rates of retinal vessel density (VD) loss and rates of central and peripheral standard automated perimetry (SAP) progression. In this prospective cohort study, 116 eyes (85 glaucoma, 31 suspects) from 60 participants (mean age 68.6 ± 7.6 years) were followed at 4-month intervals. Participants underwent comprehensive ophthalmic evaluation, blood pressure assessment, SAP, and optical coherence tomography angiography (OCTA) of the optic nerve head (ONH) and peripapillary retina. OCTA scans (4.5 × 4.5 mm) were centered on the ONH, and VD was quantified using a custom fractal analysis algorithm. Over 33.3 ± 6.6 months, eyes completed an average of 7.9 ± 2.0 SAP and OCTA exams. The median SAP MD slope was 0.19 dB/year (range –2.99 to 2.74 dB/year), with 4.3% of eyes showing moderate to fast progression (≤ –0.50 dB/year). Faster SAP deterioration, across MD, central 5°, central 10°, and peripheral MS, was significantly associated with faster RPC VD loss (β = –1.63 to –2.17%/year; all p  ≤ 0.01) after adjusting for confounding factors. Rates of RPC VD loss measured by OCTA are strongly correlated with both central and peripheral SAP progression, supporting RPC VD loss as a biomarker associated with glaucomatous functional decline in this predominantly mild, slow-progressing cohort.

Two birds with one stone: faster, fitter CAR T cells

Lightweight multi-task network for synchronous fatigue detection and ankle instability gait analysis in football training with edge deployment

How soon is now for new treatments for mantle cell lymphoma?

An explainable hybrid Generative Adversarial Network framework for data augmentation in imbalanced medical image classification

Consensus recommendations for CAR T-cell administration in adult acute lymphoblastic leukemia: a modified Delphi study

Abstract The use of chimeric antigen receptor (CAR) T-cell therapy is increasing for adult B-cell acute lymphoblastic leukemia (B-ALL), with 3 CD19 CAR T-cell products commercially available. Several key clinical questions related to best practices for CAR T-cell administration in this population exist, and limited prospective randomized trials have been conducted to fill these knowledge gaps. Thus, to help guide clinical practice, we conducted a modified Delphi study to develop and validate consensus recommendations on the administration of commercially available CAR T-cell therapy for adults with B-ALL. Consensus panelists (n = 9) included principal investigators (PIs) from Real World Outcomes Collaborative of CAR T-Cell Therapy in Adult ALL (ROCCA) consortium sites and were selected based on expertise and CAR T-cell center volume. Final panel consensus recommendations were distributed for rating by the remaining PIs from ROCCA consortium sites, which served as the validation group (n = 27). Consensus topics included patient selection, bridging and pre–CAR T-cell leukemia staging, lymphodepletion, and CAR T-cell treatment setting, specific toxicity prevention and management, post–CAR T-cell response assessment and disease monitoring, and the role of consolidation and/or maintenance therapies after CAR T-cell therapy. Initially, 58 recommendation statements were evaluated for consensus. After 2 panel meetings, a total of 34 statements achieved consensus rating among the expert panel. After rating by the validation group, all but 1 recommendation statement continued to meet consensus, for a total of 33 consensus recommendation statements on the administration of CAR T-cell therapy in adult B-ALL.

Correction: EneA of Aspergillus fumigatus is a regulator of secondary metabolism and enhances nscA expression in presence of polyenes and Streptomyces

Disseminated cryptococcal lymphadenitis mimicking lymphoma and masked by prozone effect

Fine-root biomass in relation to soil properties in regenerating Norway spruce stands following large-scale bark beetle outbreaks in mountain and lowland forests

A tumor suppressor role of the miR-15b/16-2 cluster in T-cell acute lymphoblastic leukemia

Abstract T-cell acute lymphoblastic leukemia (T-ALL) is an aggressive hematological malignancy arising from the neoplastic transformation of immature T cells during their development in the thymus. Deciphering the developmental programs whose dysregulation drives T-ALL pathogenesis is critical for the development of novel targeted therapies, which remain an urgent unmet need for the treatment of this disease. MicroRNAs (miRNAs) have emerged as key posttranscriptional regulators of numerous physiological processes, including cancer. However, the specific role of miRNAs in human T-cell development and T-ALL pathogenesis remains largely unexplored. In this study, we comprehensively evaluated miRNA expression profiles across human T-cell development using microarray analysis and identified a dynamic expression pattern of miR-16-2, which is upregulated during early pre–T-cell proliferative stages up to the resting stage of immature thymocytes immediately preceding T-cell receptor αβ expression and is subsequently downregulated. We also confirmed the coordinated regulation of miR-15b expression, consistent with the reported clustered genomic location of both miRNAs. Notably, functional studies identified the miR-15b/16-2 cluster as a negative regulator of early thymocyte proliferation and demonstrated that overexpression of miR-15b/16-2 in T-ALL cells impaired leukemic growth in vitro and tumor progression in patient-derived xenotransplantation assays. Mechanistically, miR-15b/16-2 represses the expression of the genes encoding BCL-2 and cyclin D3, thereby promoting apoptosis and cell cycle dysregulation in T-ALL cells, characterized by an accumulation of G0-phase cells and a defective transition to the G2/M phase. Overall, these findings support a novel tumor-suppressive function for miR-15b/16-2 in T-ALL and highlight its potential as a promising therapeutic target.

Comparative assessment of municipal solid waste management and community vulnerability in peri-urban India

Drugging smart: molecular glue degraders rise in T-ALL

Enhancing scene text super-resolution via dense residual reconstruction and asymmetric recurrent modeling

Lysozyme-associated nephropathy heralding leukemic transformation in myelofibrosis

Elevated circulating growth differentiation factor-15 in asthma is associated with fixed airway obstruction and future exacerbations

Chrono-atlas of cell-type specific daily gene expression rhythms in the regenerating colon

Diagnostic performance of plasma pTau217 in genetically admixed South American populations

Abstract Plasma pTau217 is a leading biomarker for Alzheimer’s disease, but evidence from genetically admixed populations in low- and middle-income countries remains limited. We evaluated the diagnostic performance of pTau217 and pTau217/Aβ42 measured using Simoa technology in memory-clinic cohorts from Brazil (Cog-Aging-Study, n  = 353) and Argentina (GeNED.ar, n  = 134). Here we show that both biomarkers accurately identified cerebrospinal fluid (CSF)-defined amyloid pathology in Cog-Aging-Study-Brazil and showed high concordance with clinical diagnosis across both cohorts. Classification performance was improved using two-cut-off approaches that account for diagnostic uncertainty. We further show that APOE-ε4 , lower body mass index, and reduced kidney function were associated with higher pTau217 in Cog-Aging-Study-Brazil, whereas education also influenced biomarker levels in GeNED.ar-Argentina. African ancestry modified APOE-ε4 effect on CSF but not plasma biomarkers. These findings support the use of plasma pTau217-based biomarkers in genetically admixed South American populations and in settings with limited access to CSF testing and brain imaging.