Mutations in the IDH1 and IDH2 genes encoding isocitrate dehydrogenases are frequently found in human glioblastomas and cytogenetically normal acute myeloid leukaemias (AML). These alterations are ...gain-of-function mutations in that they drive the synthesis of the ‘oncometabolite’ R-2-hydroxyglutarate (2HG). It remains unclear how IDH1 and IDH2 mutations modify myeloid cell development and promote leukaemogenesis. Here we report the characterization of conditional knock-in (KI) mice in which the most common IDH1 mutation, IDH1(R132H), is inserted into the endogenous murine Idh1 locus and is expressed in all haematopoietic cells (Vav-KI mice) or specifically in cells of the myeloid lineage (LysM-KI mice). These mutants show increased numbers of early haematopoietic progenitors and develop splenomegaly and anaemia with extramedullary haematopoiesis, suggesting a dysfunctional bone marrow niche. Furthermore, LysM-KI cells have hypermethylated histones and changes to DNA methylation similar to those observed in human IDH1- or IDH2-mutant AML. To our knowledge, our study is the first to describe the generation and characterization of conditional IDH1(R132H)-KI mice, and also the first report to demonstrate the induction of a leukaemic DNA methylation signature in a mouse model. Our report thus sheds light on the mechanistic links between IDH1 mutation and human AML.
Gastric cancer is one of the most aggressive cancers and is the second leading cause of cancer death worldwide. Approximately 40% of global gastric cancer cases occur in China, with peritoneal ...metastasis being the prevalent form of recurrence and metastasis in advanced disease. Currently, there are limited clinical approaches for predicting and treatment of peritoneal metastasis, resulting in a 6-month average survival time. By comprehensive genome analysis will uncover the pathogenesis of peritoneal metastasis. Here we describe a comprehensive whole-genome and transcriptome sequencing analysis of one advanced gastric cancer case, including non-cancerous mucosa, primary cancer and matched peritoneal metastatic cancer. The peripheral blood is used as normal control. We identified 27 mutated genes, of which 19 genes are reported in COSMIC database (ZNF208, CRNN, ATXN3, DCTN1, RP1L1, PRB4, PRB1, MUC4, HS6ST3, MUC17, JAM2, ITGAD, IREB2, IQUB, CORO1B, CCDC121, AKAP2, ACAN and ACADL), and eight genes have not previously been described in gastric cancer (CCDC178, ARMC4, TUBB6, PLIN4, PKLR, PDZD2, DMBT1and DAB1).Additionally,GPX4 and MPND in 19q13.3-13.4 region, is characterized as a novel fusion-gene. This study disclosed novel biological markers and tumorigenic pathways that would predict gastric cancer occurring peritoneal metastasis.
Devices for near-infrared light stimulation of autofluorescence (NIRAF) allow for intraoperative identification of parathyroid glands with high sensitivity in adults. However, their performance in ...the pediatric population is unknown. In this case series with chart review at a tertiary academic children's hospital, we investigated pediatric patients undergoing thyroid surgery and concurrent use of a probe-based NIRAF device. Thirteen patients (ages 6-18 years) underwent thyroid and/or neck dissection procedures, and 2 patients had revision procedures for a total of 15 cases with the NIRAF device. Eight cases had NIRAF values that matched surgeon opinion of parathyroid tissue or histology when available. Six cases had false positive NIRAF readings (40.0%) and 1 case had false negative readings (6.7%). Compared with surgeon opinion or histology, the NIRAF device confirmed 26 of 34 parathyroid gland candidates (76.5%). These devices need further investigation in pediatric patients, whose tissues may have different autofluorescence characteristics.
The primary goal of this study is to create and test a lecture‐capture system that can rearrange visual elements while recording is still taking place, in such a way that student performance can be ...positively influenced. The system we have devised is capable of integrating and rearranging multimedia sources, including learning content, the instructor and students' images, into lecture videos that are embedded in a website for students to review after school. The present study employed a two‐group experimental design, with 153 participants (145 females and 8 males) making up an experimental group in which lecture courses were recorded using the new lecture‐capture system, and 149 participants (140 females and 9 males) forming a control group whose lectures were recorded by traditional means. All participants were in the freshman college and studying Introduction to Computer and Information Science in one of six classes, and were randomly assigned to one of the two groups. The participants' midterm examination and final examination scores were collected as indicators of their academic performance, with their mathematics entrance scores used as a pre‐test. The findings obtained from analysis of covariance (ANCOVA) suggest that appropriate rearrangement of visual elements in lecture videos can significantly impact students' learning performance.
•Gray zone heterogeneity predicts cardiac events in patients with heart failure.•Heterogeneity can be quantified by the texture analysis technique.•Texture parameters of heterogeneity are prognostic ...predictors.•The net reclassification is improved by texture parameters.
Previous research showed that gray zone detected by late gadolinium enhancement cardiovascular magnetic resonance (LGE-CMR) imaging could help identify high-risk patients. In this study, we investigated whether LGE-CMR gray zone heterogeneity measured by image texture features could predict cardiovascular events in patients with heart failure (HF).
This is a retrospective cohort study. Patients with systolic HF undergoing CMR imaging were enrolled. Cine and LGE images were analyzed to derive left ventricular (LV) function and scar characteristics. Entropy and uniformity of gray zones were derived by texture analysis.
A total of 82 systolic HF patients were enrolled. After a median 1021 (25%–75% quartiles, 205–2066) days of follow-up, the entropy (0.60 ± 0.260 vs. 0.87 ± 0.28, p = 0.013) was significantly increased while the uniformity (0.68 ± 0.14 vs. 0.53±0.15, p = 0.016) was significantly decreased in patients with ventricular tachycardia or ventricular fibrillation (VT/VF). The percentage of core scar (21.9 ± 10.6 vs. 30.6 ± 10.4, p = 0.029) was higher in cardiac mortality group than survival group while the uniformity (0.55 ± 0.17 vs. 0.67 ± 0.14, p = 0.018) was lower in cardiac mortality group than survival group. A multivariate Cox regression model showed that higher percentage of gray zone area (HR = 8.805, 1.620−47.84, p = 0.045), higher entropy (>0.85) (HR = 1.391, 1.092−1.772, p = 0.024) and lower uniformity (≦0.54) (HR = 0.535, 0.340−0.842, p = 0.022) were associated with VT/VF attacks. Also, higher percentage of gray zone area (HR = 5.716, 1.379−23.68, p = 0.017), core scar zone (HR = 1.939, 1.056−3.561, p = 0.025), entropy (>0.85) (HR = 1.434, 1.076−1.911, p = 0.008) and lower uniformity (≦0.54) (HR = 0.513, 0.296−0.888, p = 0.009) were associated with cardiac mortality during follow-up.
Gray zone heterogeneity by texture analysis method could provide additional prognostic value to traditional LGE-CMR substrate analysis method.
Caregivers play a major role in providing care for patients with Alzheimer's disease (AD) and are themselves at higher risk of health comorbidities.
To address the impact of neuropsychiatric symptoms ...of patients in different stages of AD on their caregivers' burden.
This prospective study enrolled 260 AD patients with clinical dementia rating (CDR) of 0.5, 1 and 2 at a tertiary medical center.
All patients were tested using the mini-mental state examination (MMSE), the cognitive abilities screening instrument (CASI), the neuropsychiatric inventory (NPI) and the CDR scale. Data regarding therapeutic outcomes of anti-Alzheimer's drugs were also collected. Caregivers were tested using NPI.
The mean follow-up interval was 25.0 ± 12.2 months, and two patients died during follow-up. NPI-burden was positively correlated with NPI-sum ( r = 0.822, P < 0.001) but negatively correlated with years of education ( r = -0.140, P = 0.024), CASI score ( r = -0.259, P < 0.001) and MMSE score ( r = -0.262, P <0.001). Multiple linear regression analysis showed that only NPI-sum was independently associated with mean NPI-burden. Both higher mean CASI and MMSE scores had better therapeutic outcome of anti-Alzheimer's drugs ( P = 0.001 and P = 0.005, respectively).
The severity of neuropsychiatric symptoms in patients with AD was positively associated with caregiver's stress, and patients with better cognitive functions, under treatment with anti-Alzheimer's drugs, had better therapeutic outcomes. To reduce the impact of neuropsychiatric symptoms, it is crucial to detect dementia in its early phases and provide early intervention with anti-Alzheimer's drugs, which might help decrease the caregiver burden, thereby improving their quality of life.
We report on the MIT Epoch of Reionization (MITEoR) experiment, a pathfinder low-frequency radio interferometer whose goal is to test technologies that improve the calibration precision and reduce ...the cost of the high-sensitivity 3D mapping required for 21 cm cosmology. MITEoR accomplishes this by using massive baseline redundancy, which enables both automated precision calibration and correlator cost reduction. We demonstrate and quantify the power and robustness of redundancy for scalability and precision. We find that the calibration parameters precisely describe the effect of the instrument upon our measurements, allowing us to form a model that is consistent with X2 per degree of freedom <1.2 for as much as 80 per cent of the observations. We use these results to develop an optimal estimator of calibration parameters using Wiener filtering, and explore the question of how often and how finely in frequency visibilities must be reliably measured to solve for calibration coefficients. The success of MITEoR with its 64 dual-polarization elements bodes well for the more ambitious Hydrogen Epoch of Reionization Array project and other next-generation instruments, which would incorporate many identical or similar technologies.
Heparin is an anticoagulant which has been widely used in various clinical settings, from thromboprophylaxis to the treatment of thromboembolism. Heparin-induced thrombocytopenia (HIT) is a rare ...medical condition with severe complications if unrecognised, and it carries significant risks of co-morbidities and mortality. The incidence of HIT is relatively less common in low molecular weight heparin. HIT is more common in the venous system than the arterial circulatory system, and it is rare to see multi-vessel coronary artery thrombosis due to HIT. We hereby report a case of multi-vessel coronary thrombosis secondary to low molecular weight HIT, presenting as a case of ST-segment elevation myocardial infarction. We learned from the case that low molecular weight heparin can cause thrombosis secondary to HIT and HIT could be one of the differential diagnoses in those presenting with ST-elevation myocardial infarct and recent exposure to low molecular weight heparin.
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