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Real-world validation study of the LSC17 score for risk prediction in patients with newly diagnosed acute myeloid leukemia

The identification of patients with acute myeloid leukemia (AML) who may have resistant disease when treated with standard induction chemotherapy is still challenging: Murphy and colleagues present the first prospective, multicenter study aiming to evaluate the prognostic value of the leukemic stem cell 17-gene (LSC17) score in patients with newly diagnosed AML.


Acute myeloid leukemia (AML) patients exhibit diverse molecular and cytogenetic changes with heterogeneous outcomes. The functionally-derived LSC17 gene expression score has demonstrated strong prognostic significance in retrospective analyses of adult and pediatric AML cohorts, where above-median scores are associated with worse outcomes compared to below-median scores in intensively-treated patients. Here we used a laboratory-developed clinically-validated NanoString-based LSC17 assay to test the prognostic value of the LSC17 score in a prospective multicenter study of 276 newly-diagnosed AML patients. Each patient’s score was classified as high or low by comparison to a previously-established reference score. In the entire cohort, a high LSC17 score was associated with poor risk features, including advanced age and unfavorable genetic mutations. In the subset of 190 patients treated intensively, a high LSC17 score was associated with lower remission rates (63% vs. 94% after induction; P0.0001), presence of measurable residual disease (46% vs. 10%; P0.0001), and shorter overall survival (OS, 606 days vs. not reached; P=0.0004; hazard ratio


=2.16; 95% confidence interval [CI]: 1.39−3.35) and relapse-free survival (RFS, 541 days vs. not reached; P=0.001; HR=1.99; 95% CI: 1.29−3.08). In multivariable analysis considering age, white blood cell count and European LeukemiaNet 2022 risk groups, the LSC17 score remained an independent predictor of RFS and OS. Allogeneic stem cell transplantation improved OS for patients with a high but not a low LSC17 score. This study establishes the real-world value of the LSC17 score as a robust tool for risk assessment in AML and paves the way for its incorporation into routine clinical practice.

Acute myeloid leukemia (AML) is a heterogeneous malignancy with multiple subtypes and variable clinical outcomes driven by disease characteristics as well as the clinical status of the patient.1 2,3 While genomic classification has further rationalized risk stratification in AML, many challenges remain.4 The accurate assessment of survival outcomes in AML subtypes driven by various combinations of driver mutations and cytogenetic abnormalities presents a challenge to the treating physician.5

AML is sustained by a rare subpopulation of leukemia stem cells (LSC) believed to drive therapy resistance and relapse.6,7 The LSC17 gene expression score was developed based on functionally-defined LSC populations across the spectrum of AML subtypes.8 In multiple independent retrospective cohorts, the LSC17 score has been found to robustly discriminate between patients with significantly different outcomes.9–12 Higher-than-median LSC17 scores were associated with poor treatment response and survival outcomes in both uni-and multi-variable survival analyses, independent of commonly used prognostic factors including cytogenetic and molecular risk groups.

New strategy to fight chronic kidney inflammation

Mayo Clinic researchers have identified a drug-and-supplement combination therapy that is capable of reducing the harmful effects of senescent cells – also known as “zombie cells” – in diabetic kidney disease.

In eBioMedicine, a publication of The Lancet, the team reported that the combination of the cancer drug dasatanib and a naturally occurring substance known as quercetin decreased inflammation and boosted protective factors in the kidney.

Diabetic kidney disease affects more than 12 million people in the U.S. and is the leading cause of kidney failure. While newer treatments can delay loss of kidney function, there is currently no cure.

Alzheimer’s Disease: From Molecular Mechanisms to Promising Therapeutic Strategies

Brain vasculature in ischemic stroke.

Ischemic stroke induces dynamic cellular structural changes in the neurovascular unit, leading to disrupted structural integrity of the blood–brain barrier, neuronal degeneration, and responsive angiogenesis coordinated by endothelial cells, reactive astrocytes, and pericytes.

After ischemic stroke, the neurovascular coupling function of the neurovascular unit is also disrupted, manifested by the metabolic dysregulation of glucose, lipid/fatty acid, and amino acids.

Neurovascular unit dynamic structural remodeling and metabolic dysfunction following ischemic stroke show cellular states and spatiotemporal heterogeneities, revealing new perspectives on ischemic stroke pathogenesis and future therapeutic strategies.

Multidimensional approach aiming to repair neurovascular unit structural disorganization and restore metabolic homeostasis with cellular and spatiotemporal precision is the optimal therapeutic strategy for ischemic stroke. sciencenewshighlights ScienceMission https://sciencemission.com/neurovascular-unit-in-ischemia


The neurovascular unit (NVU) is a multicellular system functioning to maintain healthy brain homeostasis and regulate the exchange of essential elements between the blood and the brain. Recent studies have shown that, in response to ischemic stroke (IS), the NVU undergoes dynamic structural remodeling and metabolic dysfunction, revealing new features of IS pathogenesis. Recent breakthroughs in single-cell multiomics provide emerging evidence regarding the spatiotemporal heterogeneity of NVU responses to IS. To date, clinical treatments for IS-induced brain injury remain very limited. These new studies have advanced our knowledge of the dynamic cellular and molecular changes of the NVU after IS, paving the way for new therapeutic strategies.

Physicists Finally Realize Long-Predicted 2D Topological Crystal in the Lab

Researchers in Finland have experimentally realized a long-predicted class of quantum material: a two-dimensional topological crystalline insulator. Physicists at the University of Jyväskylä and Aalto University (Finland) have successfully created a two-dimensional topological crystalline insulat

Largest ever radio sky survey maps the universe in unprecedented detail

An international collaboration using the Low Frequency Array (LOFAR) has published an exceptionally detailed radio sky map, revealing 13.7 million cosmic sources and delivering the most complete census yet of actively growing supermassive black holes. It showcases an extraordinary variety of systems powered by these black holes, whose radio emission can extend for millions of light-years.

The newly released LOFAR Two-meter Sky Survey (LoTSS-DR3) marks a major milestone in radio astronomy and international scientific collaboration. The results will be published in Astronomy & Astrophysics.

By observing the sky at low radio frequencies, the survey reveals a dramatically different view of the universe than that seen at optical wavelengths. Much of the detected emission arises from relativistic particles moving through magnetic fields, allowing astronomers to trace energetic phenomena such as powerful jets from supermassive black holes and galaxies undergoing extreme star formation across cosmic time.

Closing in on a universal vaccine: Nasal spray protects mice from respiratory viruses, bacteria and allergens

In the realm of medical advancements, a universal vaccine that can protect against any pathogen has long been a Holy Grail—and about as elusive as a mythological vessel. But Stanford Medicine researchers and collaborators have taken an astonishing step forward in that quest, surprising even themselves.

In a new study in mice, they have developed a universal vaccine formula that protects against a wide range of respiratory viruses, bacteria and even allergens. The vaccine is delivered intranasally—such as through a nasal spray—and provides broad protection in the lungs for several months.

In the study, published in Science, researchers show that vaccinated mice were protected against SARS-CoV-2 and other coronaviruses, Staphylococcus aureus and Acinetobacter baumannii (common hospital-acquired infections), and house dust mites (a common allergen).

The macroecology of immunity: predominant influence of climate on invertebrate immune response

https://vist.ly/4u8bp Macroecology Odonates Parasites

The immune system is the primary defense against parasites. With the ever-increasing rate of disease, epidemiologic models considering geographic variation in immune responses could prove useful. Despite increasing interest in the macroecology of parasitism and infectious diseases, we know little about the macroecology of immune responses (i.e. macroimmunology). Host characteristics, parasite exposure, and environmental factors can all affect immunity, but how these factors shape spatial variation in the strength of immune responses remains underexplored. We captured odonates (dragonflies and damselflies) and their conspicuous ectoparasitic mites from 42 sites spread across a geographic area spanning the temperate and boreal forest biomes in eastern Canada. We then conducted immune response bioassays on 1237 individuals from 63 odonate species. We used generalized additive models and structural equation models to relate immune responses to host body size, parasite load, pH, temperature and precipitation while accounting for spatial autocorrelation in immune ability and evolutionary relationships among host species. We found significant differences in the strength of immune response among host individuals, and this variation was best explained by climatic conditions, specifically strongly decreasing with precipitation. While host species significantly differed in immune response strength, we found no effect of host body size, evolutionary relationships among hosts, or parasitism on immune response. Our study investigating the drivers of immune response across dozens of species spread across two biomes is the most comprehensive to date. Climatic conditions have a strong influence on host immune response, regardless of host characteristics or parasitism rates. Strong immune responses were associated with low levels of annual precipitation, which could relate to the role of cuticular melanin content in desiccation resistance, and the melanin-based encapsulation response being a byproduct of this adaptation. A spatially explicit understanding of the biological processes affecting immunity could improve epidemiological models of disease risk that inform disease management globally.


Predicting parasite and pathogen spread is increasingly relevant and challenging in a highly connected world (Tsiotas and Tselios 2022), and an animal’s immune system is the first line of defense against attack by parasites and pathogens. Yet, the factors driving variation in immunity among individuals, populations, and species are poorly studied and rarely factored into epidemiologic models (Becker et al. 2019). Characteristics of the host, exposure to parasites or pathogens, and the abiotic environment can interact in complex ways to affect immunity (Sweeny and Albery 2022), but their interactions are challenging to elucidate (Johnson et al. 2019).

As the immune system is the primary line of defense against infection by parasites, pathogens, and disease, it is assumed to be costly in terms of fitness and should therefore lead to tradeoffs with life-history traits (e.g. fecundity, fertility, Albery et al. 2021). Although a plethora of studies have provided key evidence of immune variation due to such tradeoffs, most studies emphasize the role of biotic factors such as predation (Duong and McCauley 2016) and resource availability (Hasik et al. 2025a) without considering that of abiotic factors (Lazzaro and Little 2008). A relationship between immune response and temperature is expected in both invertebrate ectotherms (Mastore et al. 2019) and vertebrate endotherms (Butler et al. 2013), due to the thermal sensitivity of the enzymes involved in immune responses (Catalán et al. 2012). When one scales this temperature-dependent immunity to explore the effect of climate (specifically, temperature and humidity), then climate is expected to be a clear driver of geographic variation in immunity (Li et al. 2024).

Parasites are a leading cause of disease and death around the world and thus are drivers of life-history evolution via their effects on host fitness (Hasik and Siepielski 2022a) that have the potential to affect host macroevolutionary dynamics (Hasik et al. 2025b). The majority of organisms on earth are infected by at least one parasite (Price 1980), and yet, we have a very limited understanding of the multifarious factors governing the intensity of infection and, therefore, the health cost. Immune responses are necessary to defend organisms from the deleterious and fitness-reducing effects of parasites (and disease in general, Hasik and Siepielski 2022a). Although there is increasing interest in the macroecology of parasites and infectious diseases (Stephens et al. 2016), we know very little about macroimmunology (Becker et al. 2020). Both among-individual and interspecific variation in immune response surely plays a central role, but the factors regulating immunity in natural settings are poorly understood, which can interfere with the accuracy of predictive epidemiologic models. Environmental factors and local parasite pressure can independently drive differences in immunity across space, but they could also act in concert (Becker et al. 2020). Parasitism varies among host populations distributed across large-scale environmental gradients (LoScerbo et al. 2020, Hasik and Siepielski 2022b) and at fine spatial scales, within populations (Albery et al. 2019, Hasik et al. 2025a). To date, however, the focus on a limited set of taxa, specifically vertebrates (Becker et al. 2020), limits our ability to identify generalities regarding the relative influence of environmental conditions and parasitism on immune defenses that would apply across host–parasite systems (Rolff and Siva-Jothy 2003).

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