226 research outputs found
The Physician in the 21st Century
From Hippocrates to Osler, the sacrosanct physician-patient relationship has been paramount. Hippocrates is best remembered for the Oath that bears his name(1), often recited at medical school graduations, which places the patient first and foremost in the physician encounter. More than two thousand years later, William Osler, the renowned professor of medicine at Johns Hopkins Hospital and Oxford, wrote that the premier quality of a good physician is “aequanimitas”, meaning calmness and patience(2). The foundational idea of the personal, caring relationship between physicians and patients has clearly withstood the test of time. Perhaps it can serve as a guidepost for the enormous changes coming in medical care in the 21st century. Indeed, across the ages of advances in scientific discovery, the special nature of the physician-patient relationship, exemplified by compassion, has been the mainstay of medicine.[...
Reimagining Medical Education in the Age of AI
Available medical knowledge exceeds the organizing capacity of the human mind, yet medical education remains based on information acquisition and application. Complicating this information overload crisis among learners is the fact that physicians\u27 skill sets now must include collaborating with and managing artificial intelligence (AI) applications that aggregate big data, generate diagnostic and treatment recommendations, and assign confidence ratings to those recommendations. Thus, an overhaul of medical school curricula is due and should focus on knowledge management (rather than information acquisition), effective use of AI, improved communication, and empathy cultivation
The effect of meninges on the electric fields in TES and TMS: Numerical modeling with adaptive mesh refinement
Background When modeling transcranial electrical stimulation (TES) and transcranial magnetic stimulation (TMS) in the brain, the meninges – dura, arachnoid, and pia mater – are often neglected due to high computational costs. Objective We investigate the impact of the meningeal layers on the cortical electric field in TES and TMS while considering the headreco segmentation as the base model. Method We use T1/T2 MRI data from 16 subjects and apply the boundary element fast multipole method with adaptive mesh refinement, which enables us to accurately solve this problem and establish method convergence at reasonable computational cost. We compare electric fields in the presence and absence of various meninges for two brain areas ( and ) and for several distinct TES and TMS setups. Results Maximum electric fields in the cortex for focal TES consistently increase by approximately 30% on average when the meninges are present in the CSF volume. Their effect on the maximum field can be emulated by reducing the CSF conductivity from 1.65 S/m to approximately 0.85 S/m. In stark contrast to that, the TMS electric fields in the cortex are only weakly affected by the meningeal layers and slightly (∼6%) decrease on average when the meninges are included. Conclusion Our results quantify the influence of the meninges on the cortical TES and TMS electric fields. Both focal TES and TMS results are very consistent. The focal TES results are also in a good agreement with a prior relevant study. The solver and the mesh generator for the meningeal layers (compatible with SimNIBS) are available online
A common founding clone with TP53 and PTEN mutations gives rise to a concurrent germ cell tumor and acute megakaryoblastic leukemia
We report the findings from a patient who presented with a concurrent mediastinal germ cell tumor (GCT) and acute myeloid leukemia (AML). Bone marrow pathology was consistent with a diagnosis of acute megakaryoblastic leukemia (AML M7), and biopsy of an anterior mediastinal mass was consistent with a nonseminomatous GCT. Prior studies have described associations between hematological malignancies, including AML M7 and nonseminomatous GCTs, and it was recently suggested that a common founding clone initiated both cancers. We performed enhanced exome sequencing on the GCT and the AML M7 from our patient to define the clonal relationship between the two cancers. We found that both samples contained somatic mutations in PTEN (C136R missense) and TP53 (R213 frameshift). The mutations in PTEN and TP53 were present at ∼100% variant allele frequency (VAF) in both tumors. In addition, we detected and validated five other shared somatic mutations. The copy-number analysis of the AML exome data revealed an amplification of Chromosome 12p. We also identified a heterozygous germline variant in FANCA (S858R), which is known to be associated with Fanconi anemia but is of uncertain significance here. In summary, our data not only support a common founding clone for these cancers but also suggest that a specific set of distinct genomic alterations (in PTEN and TP53) underlies the rare association between GCT and AML. This association is likely linked to the treatment resistance and extremely poor outcome of these patients. We cannot resolve the clonal evolution of these tumors given limitations of our data
Street View Data Collection Design for Disaster Reconnaissance
Over the last decade, street-view type images have been used across
disciplines to generate and understand various place-based metrics. However
efforts to collect this data were often meant to support investigator-driven
research without regard to the utility of the data for other researchers. To
address this, we describe our methods for collecting and publishing
longitudinal data of this type in the wake of the COVID-19 pandemic and discuss
some of the challenges we encountered along the way. Our process included
designing a route taking into account both broad area canvassing and community
capitals transects. We also implemented procedures for uploading and publishing
data from each survey. Our methods successfully generated the kind of
longitudinal data that can be beneficial to a variety of research disciplines.
However, there were some challenges with data collection consistency and the
sheer magnitude of data produced. Overall, our approach demonstrates the
feasibility of generating longitudinal street-view data in the wake of a
disaster event. Based on our experience, we provide recommendations for future
researchers attempting to create a similar data set.Comment: 11 pages, 2 figures, 1 tabl
A case of acute myeloid leukemia with promyelocytic features characterized by expression of a novel RARG-CPSF6 fusion
Key Points
Novel RARG-CPSF6 fusion in an AML case with promyelocytic features and no evidence of PML-RARA or X-RARA fusion. Gene fusions involving RARG can initiate AML with promyelocytic morphological features.</jats:p
Patterns of infectious complications in acute myeloid leukemia and myelodysplastic syndromes patients treated with 10-day decitabine regimen
Kdm6a deficiency restricted to mouse hematopoietic cells causes an age- and sex-dependent myelodysplastic syndrome-like phenotype
Kdm6a/Utx, a gene on the X chromosome, encodes a histone H3K27me3 demethylase that has an orthologue on the Y chromosome (Uty) (Zheng et al. 2018). We previously identified inactivating mutations of Kdm6a in approximately 50% of mouse acute promyelocytic leukemia samples; however, somatic mutations of KDM6A are more rare in human AML samples, ranging in frequency from 2-15% in different series of patients, where their role in pathogenesis is not yet clear. In this study, we show that female Kdm6aflox/flox mice (with allele inactivation initiated by Vav1-Cre in hematopoietic stem and progenitor cells (HSPCs) have a sex-specific phenotype that emerges with aging, with features resembling a myelodysplastic syndrome (MDS). Female Kdm6a-knockout (KO) mice have an age-dependent expansion of their HSPCs with aberrant self-renewal, but they did not differentiate normally into downstream progeny. These mice became mildly anemic and thrombocytopenic, but did not develop overt leukemia, or die from these cytopenias. ChIP-seq and ATAC-seq studies showed only minor changes in H3K27me3, H3K27ac, H3K4me, H3K4me3 and chromatin accessibility between Kdm6a-WT and Kdm6a-KO mice. Utilizing scRNA-seq, Kdm6a loss was linked to the transcriptional repression of genes that mediate hematopoietic cell fate determination. These data demonstrate that Kdm6a plays an important role in normal hematopoiesis, and that its inactivation may contribute to AML pathogenesis
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