The acute myeloid leukemia (AML) treatment landscape has changed substantially since 2017. New targeted drugs have emerged, including venetoclax to target B-cell lymphoma 2, midostaurin and ...gilteritinib to target FLT3, and ivosidenib and enasidenib to target mutant isocitrate dehydrogenase 1 and 2, respectively. Other additions include reapproval of gemtuzumab ozogomycin to target CD33, glasdegib to target the hedgehog pathway, and a liposomal formulation of daunorubicin and cytarabine (CPX-351). Genomically heterogeneous AML has a tendency to evolve, particularly under selective treatment pressure. For decades, treatment decisions have largely centered around chemotherapy drug intensity. Physicians now have access to an increasing number of drugs with novel mechanisms of action and distinctive side-effect profiles. Key issues faced by hematologists in this era of new drugs include (1) the timely identification of actionable mutations at diagnosis and at relapse; (2) deciding which drug to use among several therapeutic options; and (3) increasing awareness of how to anticipate, mitigate, and manage common complications associated with these new agents. This article will use 3 case presentations to discuss some of the new treatment challenges encountered in AML management, with the goal of providing practical guidance to aid the practicing physician.
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While short-read sequencing technology has resulted in a sharp increase in the number of species with genome assemblies, these assemblies are typically highly fragmented. Repeats pose the largest ...challenge for reference genome assembly, and pericentromeric regions and the repeat-rich Y chromosome are typically ignored from sequencing projects. Here, we assemble the genome of Drosophila miranda using long reads for contig formation, chromatin interaction maps for scaffolding and short reads, and optical mapping and bacterial artificial chromosome (BAC) clone sequencing for consensus validation. Our assembly recovers entire chromosomes and contains large fractions of repetitive DNA, including about 41.5 Mb of pericentromeric and telomeric regions, and >100 Mb of the recently formed highly repetitive neo-Y chromosome. While Y chromosome evolution is typically characterized by global sequence loss and shrinkage, the neo-Y increased in size by almost 3-fold because of the accumulation of repetitive sequences. Our high-quality assembly allows us to reconstruct the chromosomal events that have led to the unusual sex chromosome karyotype in D. miranda, including the independent de novo formation of a pair of sex chromosomes at two distinct time points, or the reversion of a former Y chromosome to an autosome.
Sleep stage classification is essential for sleep assessment and disease diagnosis. Although previous attempts to classify sleep stages have achieved high classification performance, several ...challenges remain open: 1) How to effectively utilize time-varying spatial and temporal features from multi-channel brain signals remains challenging. Prior works have not been able to fully utilize the spatial topological information among brain regions. 2) Due to the many differences found in individual biological signals, how to overcome the differences of subjects and improve the generalization of deep neural networks is important. 3) Most deep learning methods ignore the interpretability of the model to the brain. To address the above challenges, we propose a multi-view spatial-temporal graph convolutional networks (MSTGCN) with domain generalization for sleep stage classification. Specifically, we construct two brain view graphs for MSTGCN based on the functional connectivity and physical distance proximity of the brain regions. The MSTGCN consists of graph convolutions for extracting spatial features and temporal convolutions for capturing the transition rules among sleep stages. In addition, attention mechanism is employed for capturing the most relevant spatial-temporal information for sleep stage classification. Finally, domain generalization and MSTGCN are integrated into a unified framework to extract subject-invariant sleep features. Experiments on two public datasets demonstrate that the proposed model outperforms the state-of-the-art baselines.
MIMIC-III ('Medical Information Mart for Intensive Care') is a large, single-center database comprising information relating to patients admitted to critical care units at a large tertiary care ...hospital. Data includes vital signs, medications, laboratory measurements, observations and notes charted by care providers, fluid balance, procedure codes, diagnostic codes, imaging reports, hospital length of stay, survival data, and more. The database supports applications including academic and industrial research, quality improvement initiatives, and higher education coursework.
MIT's (magnetic induction tomography) low-cost and noninvasive features can offer great excitement and potential to address many challenging problems that exist in the current industrial/medical ...applications. The foundation development of MIT has been made in the past ten years. Many more advancements can be expected in the next decade, including the first commercialized MIT system for industrial or medical application. It will certainly contribute some impact to the current imaging technology.
Digital data collection during routine clinical practice is now ubiquitous within hospitals. The data contains valuable information on the care of patients and their response to treatments, offering ...exciting opportunities for research. Typically, data are stored within archival systems that are not intended to support research. These systems are often inaccessible to researchers and structured for optimal storage, rather than interpretability and analysis. Here we present MIMIC-IV, a publicly available database sourced from the electronic health record of the Beth Israel Deaconess Medical Center. Information available includes patient measurements, orders, diagnoses, procedures, treatments, and deidentified free-text clinical notes. MIMIC-IV is intended to support a wide array of research studies and educational material, helping to reduce barriers to conducting clinical research.
Striking differences in the solidification textures of a nickel based alloy owing to changes in laser scanning pattern during additive manufacturing are examined based on theory and experimental ...data. Understanding and controlling texture are important because it affects mechanical and chemical properties. Solidification texture depends on the local heat flow directions and competitive grain growth in one of the six preferred growth directions in face centered cubic alloys. Therefore, the heat flow directions are examined for various laser beam scanning patterns based on numerical modeling of heat transfer and fluid flow in three dimensions. Here we show that numerical modeling can not only provide a deeper understanding of the solidification growth patterns during the additive manufacturing, it also serves as a basis for customizing solidification textures which are important for properties and performance of components.
Recent studies indicate that intestinal oxidative stress and microbiota imbalance is involved in weaning-induced intestinal dysfunction in piglets. We have investigated the effect of feeding a ...carvacrol-thymol blend supplemented diet on intestinal redox status, selected microbial populations and the intestinal barrier in weaning piglets. The piglets (weaned at 21 days of age) were randomly allocated to two groups with six pens per treatment and 10 piglets per pen. At weaning day (21 days of age), six piglets were sacrificed before weaning to serve as the preweaning group. The weaned group was fed with a basal diet, while the weaned-CB group was fed with the basal diet supplemented with 100 mg/kg carvacrol-thymol (1 : 1) blend for 14 days. On day 7 post-weaning, six piglets from each group were sacrificed to determine intestinal redox status, selected microbial populations, messenger RNA (mRNA) transcript levels of proinflammatory cytokines and biomarkers of intestinal barrier function. Weaning resulted in intestinal oxidative stress, indicated by the increased concentration of reactive oxygen species and thiobarbituric acid-reactive substances present in the intestine. Weaning also reduced the population of Lactobacillus genus and increased the populations of Enterococcus genus and Escherichia coli in the jejunum, and increased mRNA levels of tumor necrosis factor α (TNF-α), interleukin 1β and interleukin 6 (IL-6). In addition, decreased mRNA levels of zonula occludens and occludin in the jejunal mucosa and increased plasma diamine oxidase concentrations indicated that weaning induced dysfunction of the intestinal barrier. On day 7 post-weaning, supplementation with the carvacrol-thymol blend restored weaning-induced intestinal oxidative stress. Compared with the weaned group, the weaned-CB group had an increased population of Lactobacillus genus but reduced populations of Enterococcus genus and E. coli in the jejunum and decreased mRNA levels of TNF-α. The results indicated that weaning induced intestinal oxidative stress and dysfunction of the intestinal barrier. Dietary supplementation with 100 mg/kg carvacrol-thymol (1 : 1) decreased the intestinal oxidative stress and influenced selected microbial populations without changing the biomarkers of intestinal barrier in weaning piglets.
The key physics of the spin valve involves spin-polarized conduction electrons propagating between two magnetic layers such that the device conductance is controlled by the relative magnetization ...orientation of two magnetic layers. Here, we report the effect of a magnon valve which is made of two ferromagnetic insulators (YIG) separated by a nonmagnetic spacer layer (Au). When a thermal gradient is applied perpendicular to the layers, the inverse spin Hall voltage output detected by a Pt bar placed on top of the magnon valve depends on the relative orientation of the magnetization of two YIG layers, indicating the magnon current induced by the spin Seebeck effect at one layer affects the magnon current in the other layer separated by Au. We interpret the magnon valve effect by the angular momentum conversion and propagation between magnons in two YIG layers and conduction electrons in the Au layer. The temperature dependence of the magnon valve ratio shows approximately a power law, supporting the above magnon-electron spin conversion mechanism. This work opens a new class of valve structures beyond the conventional spin valves.
In 2017, 4 drugs received US Food and Drug Administration marketing approval for acute myeloid leukemia (AML) treatment: targeted therapies for mutant FLT3 and IDH2, a liposomal ...cytarabine-daunorubicin formulation for therapy-related AML and AML with myelodysplasia-related changes, and resurgence of an antibody-drug conjugate designed to target CD33. Promising results also emerged for the BCL-2 inhibitor venetoclax combined with low-intensity therapy in older patients unfit for intensive chemotherapy. This quintet of new drugs is likely to reshape the therapeutic landscape of AML.
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