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Deconstruction of a spino-brain–spinal cord circuit that drives chronic pain
Development of a model to predict nicotine pharmacokinetics from oral nicotine pouches
CSF-1R inhibition and lenalidomide synergize to promote myeloma control after autologous stem cell transplantation
Abstract Autologous stem cell transplantation (ASCT) with maintenance lenalidomide remains the mainstay of consolidation therapy for eligible patients with multiple myeloma, but preventing disease relapse remains a critical unmet need. Here, we investigated whether immunosuppressive myeloid populations in bone marrow correlated with ASCT outcomes. We identified a subset of CD64+CD169+CD163+ macrophages that expressed CSF-1R, PD-L1, and CD155 and were expanded in patients who relapsed after ASCT. Using a preclinical ASCT model with suboptimal endogenous antimyeloma activity, we demonstrated that although neither CSF-1R inhibition nor lenalidomide monotherapy significantly improved outcomes, their combination synergistically attenuated disease progression and prolonged survival. Single-cell RNA sequencing revealed that lenalidomide expanded natural killer (NK)–like CD8+ T cells but paradoxically also increased the frequency of Csf1r+ macrophages. Cell-cell communication analyses identified Csf1r+ macrophages as suppressors of these NK- and effector-like phenotypically exhausted (Tphex) CD8 T-cell populations through CD94/NKG2A and PD-L1/PD-1, respectively. CSF-1R blockade depleted these immunosuppressive macrophages, which correlated with decreased expression of inhibitory receptors and enhanced expression of activation markers in Tphex. Given the US Food and Drug Administration approval of axatilimab for chronic graft-versus-host disease, combining CSF-1R blockade with lenalidomide maintenance represents a readily testable strategy to improve progression-free survival after ASCT.
Design of a low-power RISC-V based intelligent endoscopy detection processor: EndoRISC-V
Methylation-based lineage tracing in cancer
Abstract The evolutionary history of cancers is encoded in molecular patterns that provide critical insights into the mechanisms of tumor progression. However, reconstructing cancer lineages in patient tumors remains challenging, because conventional sequencing captures only static snapshots of an ongoing evolutionary process. DNA methylation at CpG sites is a heritable epigenetic mark that accumulates stochastic errors, termed epimutations, at rates far exceeding those of somatic DNA mutations. These epimutations serve as a “molecular clock” and can be harnessed for retrospective lineage tracing. When applied at single-cell resolution, methylation-based lineage tracing enables the reconstruction of cancer phylogenies and provides a powerful framework for studying the dynamics of treatment resistance, cell-state heritability, and metastasis directly in human tumors. In this review, we outline the strengths and challenges of single-cell DNA methylation–based lineage tracing, highlight key insights gained from its application with an emphasis on hematologic cancers when relevant, and discuss its future potential in advancing our understanding of cancer evolution.
‘Virtual cells’ aim to turn raw data into predictive models of biology
Manganese recycling from zinc anode slime via SO2 reductive leaching in an integrated copper–zinc hydrometallurgical plant
Homeodomain-driven oncogenic diversion to a γδTCR phenotype in T-cell acute lymphoblastic leukemia
Abstract T-cell acute lymphoblastic leukemia (T-ALL) results from the malignant transformation of thymocytes blocked in their differentiation. Surface expression of the γδ T-cell receptor (γδTCR) is surprisingly frequent in T-ALLs, questioning the susceptibility of the γδ-lineage to leukemogenesis. Among 1233 T-ALLs phenotyped in our center, 33% (n = 403) expressed a TCR, of which 47% (n = 191; 113 adults, 78 children) were positive for γδTCR (γδTCR+). Using a comprehensive analysis, we were able to delineate 2 distinct γδTCR+ T-ALL subtypes, with distinct physiological counterparts. The first (75% of cases) was characterized by ectopic expression of homeodomain-containing oncogenes (HD+), Vβ-Jβ rearrangements, and phenotypic (including surface pre-TCRα chain) and transcriptional profiles reminiscent of cortical thymocytes and was, therefore, termed cortical-like γδ T-ALLs. Transduction of murine T-cell progenitors and human CD34+ cells with HOXA9 or TLX3 (HD+ oncogenes) led to a differentiation bias toward γδTCR-expressing thymocytes. The second subtype (25%) exhibited phenotypic and transcriptional profiles reminiscent of γδ thymocytes, and was termed bona fide γδ T-ALLs. These findings were validated in the COGAALL0434 cohort. Although bona fide γδ T-ALLs were enriched for early T-cell progenitor (ETP)–like and KMT2A-rearranged cases, they mostly eluded the phenotypic definition of ETP-ALLs. Similar to the ETP-like subtype, bona fide γδ T-ALLs were associated with a poor initial response to chemotherapy but were sensitive to the BCL2 inhibitor venetoclax. Our results reveal developmental heterogeneity behind γδTCR expression in T-ALLs and suggest that overrepresentation of this subtype reflects αβ-lineage commitment repression by HD+ oncogenes. These trials were registered at www.clinicaltrials.gov as NCT00222027 (GRAALL2003), NCT00327678 (GRAALL2005), NCT03709719 (GRAALL2014), and NCT00408005 (Children's Oncology Group AALL0434 trial).
Will AI ruin the social sciences — or revolutionize them?
A passive islanding detection method using deep neural bidirectional LSTM-CNN
The evolution of hematopoietic models through a clonal lens
Abstract Hematopoiesis is a tightly regulated process through which a small pool of stem cells sustains the lifelong production of all blood cell types in response to physiological demand. Understanding how this process is controlled and how hematopoietic stem cells commit to specific lineages is essential to understand blood and immune health and to treat their disorders. In this review, we examine the major conceptual frameworks that have been proposed to describe hematopoiesis and the underlying data that informed them, ranging from the classical discrete hierarchy to the continuous model, the punctuated continuum, and the multitrack model. Evidence from clonal lineage–tracing studies in mouse, nonhuman primates, and humans supports the idea that lineage fate is largely predetermined rather than stochastically acquired, and we highlight the importance of clonal multiomics approaches for identifying the molecular predictors of fate. We then discuss the computational models that have been developed to study hematopoietic development. Finally, we outline key challenges, including resolving native hematopoiesis in vivo, in both mouse and humans, and identifying the molecular programs that encode fate trajectories and how they are altered in disease. Looking at the hematopoietic process through a clonal lens is paramount to find the molecular signatures that truly can predict fate.
Effects of solution treatment, precipitation hardening, and shot peening on the cavitation erosion resistance of 17‑4PH steel produced by additive and conventional methods
United forces bring down menin resistance in AML
The future of science communication is not an article like this
Fecal carriage of multidrug-resistant Enterobacterales and its associated factors among hospital and non-hospital janitors at the University of Gondar, Northwest Ethiopia: a comparative cross-sectional study
Abstract Multidrug-resistant (MDR) Enterobacterales represent a severe global health challenge. Janitors, who are frequently in contact with contaminated surfaces, may become carriers and spreaders of these pathogens. This risk is especially acute in resource-constrained environments such as Ethiopia, where research into this potential transmission route remains scarce. The aim of this study was to assess fecal carriage rates of multidrug-resistant Enterobacterales and its associated factors among hospital and non-hospital janitors at the University of Gondar (UoG), Northwest Ethiopia. A comparative cross-sectional study was conducted from June 15 to September 25, 2025 at the UoG. A total of 385 janitors (203 hospital and 182 non-hospital) were selected using a stratified and simple random sampling techniques. Data on socio-demographic and associated factor were collected using a semi-structured questionnaire. Stool samples were collected aseptically, cultured on MacConkey agar, and identified using biochemical test results. Antimicrobial resistance (AMR) patterns were determined by the Kirby-Bauer disk diffusion method following Clinical and Laboratory Standards Institute (CLSI) 2024 guidelines. Quality control was ensured by using standard reference strain ( E. coli ATCC 25922). Data analysis was performed using SPSS version 27.0, employing chi-square tests and logistic regression. A p -value of < 0.05 was considered statistically significant. Among the 385 stool samples, a total of 416 Enterobacterales isolates were recovered, 229 from hospital janitors and 187 from non-hospital janitors. The overall fecal carriage rate of MDR Enterobacterales among janitors was 54.0% (95% CI 48.9, 59.1). This rate was significantly higher in hospital janitors compared to non-hospital janitors ((63.5% (95% CI 56.5, 70.2) vs. 43.4% (95% CI 36.1, 50.9), respectively; p < 0.001)). History of antibiotic use, urinary tract infection, and gastrointestinal tract symptom in the last three months were significantly associated with MDR Enterobacterales carriage among janitors. The high carriage rates of MDR Enterobacterales identified among janitors suggest that janitors may serve as a potential reservoir for resistant bacteria. To address this, we recommend their inclusion in national antimicrobial resistance surveillance programs and the implementation of tailored infection prevention and control training.