Mcguirelawson6298

Our results highlight the importance of ascorbate and iron metabolism in adult human cell fate specification. Radial glia (RG) cells are the first neural stem cells to appear during embryonic development. Adult human glioblastomas harbor a subpopulation of RG-like cells with typical RG morphology and markers. The cells exhibit the classic and unique mitotic behavior of normal RG in a cell-autonomous manner. Single-cell RNA sequencing analyses of glioblastoma cells reveal transcriptionally dynamic clusters of RG-like cells that share the profiles of normal human fetal radial glia and that reside in quiescent and cycling states. Functional assays show a role for interleukin in triggering exit from dormancy into active cycling, suggesting a role for inflammation in tumor progression. These data are consistent with the possibility of persistence of RG into adulthood and their involvement in tumor initiation or maintenance. They also provide a putative cellular basis for the persistence of normal developmental programs in adult tumors. Tumour lysis syndrome is a complication of chemotherapy for haematological malignancies; in particular, aggressive leukaemias and lymphomas. For haematological malignancies, targeted therapies, such as small molecule inhibitors and monoclonal antibodies, have a high anti-tumour activity, are well tolerated, and have a low incidence of associated tumour lysis syndrome. CMV inhibitor The BCL-2 inhibitor venetoclax has a high anti-tumour activity in chronic lymphocytic leukaemia, achieving deep remissions by potently inducing apoptosis and increasing the risk for tumour lysis syndrome. In this Viewpoint, we discuss the pathophysiology, risk factors, monitoring, changes in laboratory parameters, and clinical manifestations of tumour lysis syndrome, and the prophylaxis and treatments available for this complication. Prophylaxis and treatment strategies have been implemented as standard of care in patients receiving venetoclax to minimise the risk of both laboratory and clinical manifestations of tumour lysis syndrome. Graft-versus-host disease (GVHD) is a major factor contributing to mortality and morbidity after allogeneic stem-cell transplantation. Because of the small number of results from well designed, large-scale, clinical studies there is considerable variability in the prevention and treatment of GVHD worldwide. In 2014, to standardise treatment approaches the European Society of Blood and Marrow Transplantation published recommendations on the management of GVHD in the setting of HLA-identical sibling or unrelated donor transplantation in adult patients with haematological malignancies. Here we update these recommendations including the results of study published after 2014. Evidence was searched in three steps first, a widespread scan of published trials, meta-analyses, and systematic reviews; second, expert opinion was added for specific issues following several rounds of debate; and third, a refined search to target debated or rapidly updating issues. On the basis of this evidence and the 2014 recommendations,ion, we discuss specific aspects of GVHD prophylaxis and management in the setting of haploidentical transplantation and in paediatric patients, but no formal recommendations on those procedures have been provided in this Review. The European Society of Blood and Marrow Transplantation proposes to use these recommendations as a basis for the routine management of GVHD during stem-cell transplantation. OBJECTIVE We sought to identify and characterize examinations in women with a personal history of breast cancer likely performed for asymptomatic surveillance. METHODS We included surveillance mammograms (1997-2017) in asymptomatic women with a personal history of breast cancer diagnosed at age ≥18 years (1996-2016) from 103 Breast Cancer Surveillance Consortium facilities. We examined facility-level variability in examination indication. We modeled the relative risk (RR) and 95% confidence intervals (CIs) at the examination level of a (1) nonscreening indication and (2) surveillance interval ≤9 months using Poisson regression with fixed effects for facility, stage, diagnosis age, surgery, examination year, and time since diagnosis. RESULTS Among 244,855 surveillance mammograms, 69.5% were coded with a screening indication, 12.7% short-interval follow-up, and 15.3% as evaluation of a breast problem. Within a facility, the proportion of examinations with a screening indication ranged from 6% to 100% (median 86%, interquartile range 79%-92%). Facilities varied the most for examinations in the first 5 years after diagnosis, with 39.4% of surveillance mammograms having a nonscreening indication. link2 Within a facility, breast conserving surgery compared with mastectomy (RR = 1.64; 95% CI = 1.60-1.68) and less time since diagnosis (1 year versus 5 years; RR = 1.69; 95% CI = 1.66-1.72; 3 years versus 5 years = 1.20; 95% CI = 1.18-1.23) were strongly associated with a nonscreening indication with similar results for ≤9-month surveillance interval. Screening indication and >9-month surveillance intervals were more common in more recent years. CONCLUSION Variability in surveillance indications across facilities in the United States supports including indications beyond screening in studies evaluating surveillance mammography effectiveness and demonstrates the need for standardization. PURPOSE The aim of this study was to compare breast imaging subspecialists' follow-up recommendations for incidental liver lesions (ILLs) on breast MRI with abdominal subspecialty radiologists' opinions informed by best-practice recommendations. METHODS In this retrospective study at an academic medical center, natural language processing identified reports with ILLs among 2,181 breast MRI studies completed in 2015. Electronic health record and radiology report reviews abstracted malignancy presence or absence, prior imaging, and breast subspecialists' recommendations regarding ILLs for random sets of 30 patients ILLs with follow-up recommendations, ILLs without recommendations, and without ILLs. Two abdominal radiologists evaluated MRI liver findings and offered follow-up recommendations in consensus. The primary outcome was agreement between breast and abdominal subspecialists in patients with ILL follow-up recommendations compared with those without (χ2 analysis). Secondary outcomes were agreement between rovement opportunities may exist in other cross-subspecialty interpretation workflows. PURPOSE Natural language processing (NLP) enables conversion of free text into structured data. Recent innovations in deep learning technology provide improved NLP performance. We aimed to survey deep learning NLP fundamentals and review radiology-related research. METHODS This systematic review was reported according to the Preferred Reporting Items for Systematic Reviews and Meta-Analyses guidelines. We searched for deep learning NLP radiology studies published up to September 2019. MEDLINE, Scopus, and Google Scholar were used as search databases. RESULTS Ten relevant studies published between 2018 and 2019 were identified. Deep learning models applied for NLP in radiology are convolutional neural networks, recurrent neural networks, long short-term memory networks, and attention networks. Deep learning NLP applications in radiology include flagging of diagnoses such as pulmonary embolisms and fractures, labeling follow-up recommendations, and automatic selection of imaging protocols. Deep learning NLP models perform as well as or better than traditional NLP models. CONCLUSION Research and use of deep learning NLP in radiology is increasing. Acquaintance with this technology can help prepare radiologists for the coming changes in their field. The association between macrocephaly and autism spectrum disorder (ASD) suggests that the mechanisms underlying excessive neural growth could contribute to ASD pathogenesis. Consistently, neural progenitor cells (NPCs) derived from human induced pluripotent stem cells (hiPSCs) of ASD individuals with early developmental brain enlargement are inherently more proliferative than control NPCs. Here, we show that hiPSC-derived NPCs from ASD individuals with macrocephaly display an altered DNA replication program and increased DNA damage. When compared with the control NPCs, high-throughput genome-wide translocation sequencing (HTGTS) demonstrates that ASD-derived NPCs harbored elevated DNA double-strand breaks in replication stress-susceptible genes, some of which are associated with ASD pathogenesis. Our results provide a mechanism linking hyperproliferation of NPCs with the pathogenesis of ASD by disrupting long neural genes involved in cell-cell adhesion and migration. Alveolar epithelial type 2 cells (AEC2s) are the facultative progenitors responsible for maintaining lung alveoli throughout life but are difficult to isolate from patients. Here, we engineer AEC2s from human pluripotent stem cells (PSCs) in vitro and use time-series single-cell RNA sequencing with lentiviral barcoding to profile the kinetics of their differentiation in comparison to primary fetal and adult AEC2 benchmarks. We observe bifurcating cell-fate trajectories as primordial lung progenitors differentiate in vitro, with some progeny reaching their AEC2 fate target, while others diverge to alternative non-lung endodermal fates. We develop a Continuous State Hidden Markov model to identify the timing and type of signals, such as overexuberant Wnt responses, that induce some early multipotent NKX2-1+ progenitors to lose lung fate. Finally, we find that this initial developmental plasticity is regulatable and subsides over time, ultimately resulting in PSC-derived AEC2s that exhibit a stable phenotype and nearly limitless self-renewal capacity. Continual efferocytic clearance of apoptotic cells (ACs) by macrophages prevents necrosis and promotes injury resolution. How continual efferocytosis is promoted is not clear. Here, we show that the process is optimized by linking the metabolism of engulfed cargo from initial efferocytic events to subsequent rounds. We found that continual efferocytosis is enhanced by the metabolism of AC-derived arginine and ornithine to putrescine by macrophage arginase 1 (Arg1) and ornithine decarboxylase (ODC). Putrescine augments HuR-mediated stabilization of the mRNA encoding the GTP-exchange factor Dbl, which activates actin-regulating Rac1 to facilitate subsequent rounds of AC internalization. Inhibition of any step along this pathway after first-AC uptake suppresses second-AC internalization, whereas putrescine addition rescues this defect. Mice lacking myeloid Arg1 or ODC have defects in efferocytosis in vivo and in atherosclerosis regression, while treatment with putrescine promotes atherosclerosis resolution. Thus, macrophage metabolism of AC-derived metabolites allows for optimal continual efferocytosis and resolution of injury. Age-dependent loss of hypothalamic neural stem cells (htNSCs) is important for the pathological consequences of aging; however, it is unclear what drives the senescence of htNSCs. Here, we report that a long non-coding RNA, Hnscr, is abundantly expressed in the htNSCs of young mice but decreases markedly in middle-aged mice. We show that depletion of Hnscr is sufficient to drive the senescence of htNSCs and aging-like phenotypes in mice. Mechanistically, Hnscr binds to Y-box protein 1 (YB-1) to prevent its degradation and thus the attenuation of transcription of the senescence marker gene p16INK4A. link3 Through molecular docking, we discovered that a naturally occurring small compound, theaflavin 3-gallate, can mimic the activity of Hnscr. Treatment of middle-aged mice with theaflavin 3-gallate reduced the senescence of htNSCs while improving aging-associated pathology. These results point to a mediator of the aging process and one that can be pharmacologically targeted to improve aging-related outcomes.