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Overweight and Obesity — Capturing the Whole Picture
Progress through Persistence — Turning the Page in Pulmonary Fibrosis Clinical Trials
Metformin reduces the competitive advantage of Dnmt3aR878H HSPCs
Patient-Specific In Vivo Gene Editing to Treat a Rare Genetic Disease
Nerandomilast in Patients with Idiopathic Pulmonary Fibrosis
Case 4-2025: A Man with Syncope, Ankle Swelling, and Abnormal Chest Imaging
John Collins Warren — <i>Journal</i> Founder, Institution Builder, and Racial Theorist
Perturbing LSD1 and WNT rewires transcription to synergistically induce AML differentiation
Abstract Impaired differentiation is a hallmark of myeloid malignancies1,2. Therapies that enable cells to circumvent the differentiation block, such as all-trans retinoic acid (ATRA) and arsenic trioxide (ATO), are by and large curative in acute promyelocytic leukaemia3, but whether ‘differentiation therapy’ is a generalizable therapeutic approach for acute myeloid leukaemia (AML) and beyond remains incompletely understood. Here we demonstrate that simultaneous inhibition of the histone demethylase LSD1 (LSD1i) and the WNT pathway antagonist GSK3 kinase4 (GSK3i) robustly promotes therapeutic differentiation of established AML cell lines and primary human AML cells, as well as reducing tumour burden and significantly extending survival in a patient-derived xenograft mouse model. Mechanistically, this combination promotes differentiation by activating genes in the type I interferon pathway via inducing expression of transcription factors such as IRF7 (LSD1i) and the co-activator β-catenin (GSK3i), and their selective co-occupancy at targets such as STAT1, which is necessary for combination-induced differentiation. Combination treatment also suppresses the canonical, pro-oncogenic WNT pathway and cell cycle genes. Analysis of datasets from patients with AML suggests a correlation between the combination-induced transcription signature and better prognosis, highlighting clinical potential of this strategy. Collectively, this combination strategy rewires transcriptional programs to suppress stemness and to promote differentiation, which may have important therapeutic implications for AML and WNT-driven cancers beyond AML.
Blinatumomab in Childhood B-Cell Acute Lymphoblastic Leukemia
Sustained Clinical Benefit of AAV Gene Therapy in Severe Hemophilia B
Happy birthday quantum mechanics! I got a ticket to the ultimate physics party
Daily briefing: Physical masks created using AI can restore damaged paintings
Author Correction: Chromosome end protection by RAP1-mediated inhibition of DNA-PK
How to address gender equity in science in Africa
Author Correction: Global methane emissions from rivers and streams
Publisher Correction: Multi-zonal liver organoids from human pluripotent stem cells
A metagenomics survey of viral diversity in mosquito vectors allows the first detection of Sindbis virus in Burkina Faso
Arboviruses (i.e., Arthropod-borne viruses) pose a threat to human health worldwide. This taxonomically-diverse group includes numerous viruses that recurrently spread into new regions. Therefore, periodic surveys of the arboviral diversity in a given region can help optimize the diagnosis of arboviral infections. However, such surveys are infrequent, especially in low-income countries. Consequently, case investigation is often limited to a fraction of the arboviral diversity. This situation is likely to result in undiagnosed cases. Here, we investigated the diversity of mosquito-borne arboviruses in two regions of Burkina Faso. To this end, we used untargeted metagenomics to screen mosquitoes collected over three years in six urban and rural areas. The analysis focused on two mosquito species, Aedes aegypti and Culex quinquefasciatus, considered to be among the most important vectors of arboviruses worldwide. The screening detected Sindbis virus (SINV, Togaviridae) for the first time in Burkina Faso. This zoonotic arbovirus has spread from Africa to Europe. SINV causes periodic outbreaks in Europe but its distribution and epidemiology in Africa remains largely unstudied. SINV was detected in one of the six areas, and at a single year. Detection was validated with isolation in cell culture. SINV was only detected in Cx. quinquefasciatus, adding to the list of potential vectors of SINV in nature. The SINV infection rate in mosquitoes was similar to those observed in European regions experiencing SINV outbreaks. Phylogenetic analysis placed the nearly-full genome within a cluster of Central African strains of lineage I. This cluster is thought to be at the origin of the SINV strains introduced into Europe. Our results call for studies on the prevalence of SINV infections in the region to estimate the disease burden and the interest of SINV diagnostic in case investigation.
Development and validation of a cardiac surgery-associated acute kidney injury prediction model using the MIMIC-IV database
Objective This study aimed to develop an innovative early prediction model for acute kidney injury (AKI) following cardiac surgery in intensive care unit (ICU) settings, leveraging preoperative and postoperative clinical variables, and to identify key risk factors associated with AKI. Methods Retrospective data from 1,304 cardiac surgery patients (1,028 AKI cases and 276 non-AKI controls) were extracted from the MIMIC-IV database. We analyzed three datasets: preoperative 48-hour averages, preoperative 48-hour maxima, and postoperative 24-hour maxima of critical physiological parameters. Using logistic regression, LASSO regression, and random forest (RF) algorithms, we constructed nine prediction models, evaluating their performance via AUROC, sensitivity, specificity, Youden’s index, decision curve analysis (DCA), and calibration curves. Results Our findings demonstrate that all models achieved AUROC values >0.7, with three models exceeding 0.75. Notably, the logistic regression model incorporating preoperative 48-hour maximum values and postoperative 24-hour maximum values exhibited the highest predictive accuracy (AUROC = 0.755, 95%CI: 0.7185–0.7912), outperforming other configurations. This model’s superiority lies in its integration of dynamic preoperative and postoperative variables, capturing both baseline risks and acute postoperative changes. By systematically comparing multiple machine learning approaches, our study highlights the utility of combining temporal physiological metrics to enhance AKI risk stratification. These results offer a robust, clinically applicable tool for early AKI prediction, enabling proactive interventions to improve outcomes in cardiac surgery patients.
Viewing of abstract art follows a gist to survey gaze pattern over time regardless of broad categorical titles
Artworks are often shown alongside informative contextual text. This can be as simple as its title and date, or it can be a more descriptive or elaborative explanation of the piece, such as describing its content or explaining the symbolism of the work. Contextual information has been shown to have no impact on early viewing behaviour. A consistent impact on observer eye movement scan paths and fixations is only found in the later periods of looking. One explanation for this is that early eye movement responses to artworks support automatic low-level visual processing that quickly extracts a broad, holistic gist or sense of the works, allowing rapid categorization. The influence of contextual information may only be felt in later periods as it concentrates fixations on descriptive or elaborative elements more quickly and for longer periods. To examine this explanation, we recorded eye movement responses to abstract paintings that were preceded by basic-level categorical labels. In Experiment 1, abstract works were preceded by the labels Landscape, Portrait or Abstract, while in Experiment 2 the labels Action, Still Life or Abstract were given. We found that saccadic eye movements were more common in the first 2 seconds of viewing and were spread over a large portion of the artworks. They became less frequent and were spatially clustered over time. This changing pattern of saccades and their fixation periods was not affected by the contextual information provided by the category labels suggesting a minimal role for top-down control of eye movements when viewers are faced with abstract artworks.