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Accurate modeling of intratumor heterogeneity presents a bottleneck against drug testing. Flexibility in a preclinical platform is also desirable to support assessment of different endpoints. We established the model system, OHC-NB1, from a bone marrow metastasis from a patient diagnosed with MYCN-amplified neuroblastoma and performed whole-exome sequencing on the source metastasis and the different models and passages during model development (monolayer cell line, 3D spheroid culture and subcutaneous xenograft tumors propagated in mice). OHC-NB1 harbors a MYCN amplification in double minutes, 1p deletion, 17q gain and diploid karyotype, which persisted in all models. A total of 80–540 single-nucleotide variants (SNVs) was detected in each sample, and comparisons between the source metastasis and models identified 34 of 80 somatic SNVs to be propagated in the models. Clonal reconstruction using the combined copy number and SNV data revealed marked clonal heterogeneity in the originating metastasis, with four clones being reflected in the model systems. The set of OHC-NB1 models represents 43% of somatic SNVs and 23% of the cellularity in the originating metastasis with varying clonal compositions, indicating that heterogeneity is partially preserved in our model system.  相似文献   
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Journal of Neuro-Oncology - Evidence supporting routine postoperative antiepileptic drug (AED) prophylaxis following oncologic neurosurgery is limited, and actual practice patterns are largely...  相似文献   
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目的:对氯氮平片在帕金森病(Parkinson’s disease,PD)合并精神障碍辅助治疗中的应用价值予以探讨。方法:选取50例我院2013年1月1日—2019年6月30日接诊的PD合并精神障碍患者进行研究,按照随机数表法分为对照组和观察组。对照组用多巴丝肼,观察组联合氯氮平片,对比治疗效果。结果:观察组疾病治疗总有效率96.00%(24/25)高于对照组68.00%(17/25),差异有统计学意义(P<0.05),不良反应发生率8.00%(2/25)与对照组20.00%(5/25)差异无统计学意义(P>0.05);观察组UPDRD评分、VGI-S评分和BPRS评分明显低于对照组,差异有统计学意义(P<0.05)。结论:氯氮平片辅助治疗PD合并精神障碍患者,既可提高临床疗效,也不会增加用药后不良反应,安全性高,值得推广。  相似文献   
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Purpose

Partial nephrectomy (PN) is standard for small renal masses, improving renal function by preserving renal parenchyma compared with radical nephrectomy. Recent work demonstrated that postoperative surgeon assessment of volume preservation (SAVP) and 3D imaging measurements agree and correlate with postoperative function. We hypothesize preoperative assessment of volume preservation (PAVP) with PN based on preoperative imaging will reliably indicate postoperative renal function.

Materials and Methods

Data were collected from 336 patients undergoing PN for suspected renal cancer by 40 surgeons at 12 centers in Europe and the United States within the Surface-Intermediate-Base International Consortium. Surgeons recorded PAVP and SAVP for individual patients; pre- and postoperative glomerular filtration rate (GFR) was estimated by Chronic Kidney Disease Epidemiology Collaboration equations. Correlations between PAVP, SAVP, and postoperative GFR were assessed with linear regression models. Bland–Altman analysis was used to assess agreement between PAVP and SAVP with a significant cutoff of 5%.

Results

Median PAVP was 90% (interquartile range [IQR] 85%–100%) and SAVP was 90% (IQR: 80%–94%). PAVP and SAVP were moderately correlated (R2?=?0.67, P < 0.0001) and deemed “interchangeable” by Bland–Altman analysis at a 5% acceptable rate of difference (95% CI: ?5.4, ?3.1). Median postoperative GFR was 77.3 (IQR: 56.2, 92.0). Both PAVP (R2?=?0.82, P < 0.0001) and SAVP (R2?=?0.83, P < 0.0001) were correlated with postoperative GFR. Multivariable models utilizing volume-adjusted GFR based on PAVP or SAVP significantly and similarly predicted postoperative GFR (R2?=?0.72 for each).

Conclusion

Renal function is closely linked to the amount of parenchymal volume preservation, whether estimated prior to surgery (PAVP) or afterward (SAVP). PAVP provides reasonably accurate information for decision-making in patients considering PN.  相似文献   
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The processes involved in value evaluation and self‐control are critical when making behavioral choices. However, the evidence linking these two types of processes to behavioral choices in intertemporal decision‐making remains elusive. As the ventromedial prefrontal cortex (vmPFC), striatum, and dorsolateral prefrontal cortex (dlPFC) have been associated with these two processes, we focused on these three regions. We employed functional magnetic resonance imaging during a delayed discounting task (DDT) using a relatively large sample size, three independent samples. We evaluated how much information about a specific choice could be decoded from local patterns in each brain area using multivoxel pattern analysis (MVPA). To investigate the relationship between the dlPFC and vmPFC/striatum regions, we performed a psychophysiological interaction (PPI) analysis. In Experiment I, we found that the vmPFC and dlPFC, but not the striatum, could determine choices in healthy participants. Furthermore, we found that the dlPFC showed significant functional connectivity with the vmPFC, but not the striatum, when making decisions. These results could be replicated in Experiment II with an independent sample of healthy participants. In Experiment III, the choice‐decoding accuracy in the vmPFC and dlPFC was lower in patients with addiction (smokers and participants with Internet gaming disorder) than in healthy participants, and decoding accuracy in the dlPFC was related to impulsivity in addicts. Taken together, our findings may provide neural evidence supporting the hypothesis that value evaluation and self‐control processes both guide the intertemporal choices, and might provide potential neural targets for the diagnosis and treatment of impulsivity‐related brain disorders.  相似文献   
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European Journal of Ageing - Fall prevention and management of behavioural and psychological symptoms of dementia (BPSD) in long-term care (LTC) facility is a major challenge. The objective of this...  相似文献   
10.
目的 比较改良分期尿道板纵切卷管尿道成形术(改良Duplay术)和一期横形带蒂岛状包皮皮瓣尿道成形术(Duckett术)治疗儿童中重度尿道下裂的疗效。方法 收集81例中重度尿道下裂患儿的临床资料,根据术式不同分为改良Duplay术式组45例和Duckett术式组36例。比较2组的手术时间、出血量、住院费用、术后并发症和患儿家属对手术的满意度及治愈率。结果 与Duckett术式组比较,改良Duplay术式组的手术时间较短,尿道狭窄和尿道憩室的发生率较低(P均< 0.05)。2组的出血量、住院费用、尿瘘和龟头裂开的发生率和治愈率比较差异均无统计学意义(P均> 0.05)。Duckett术式组患儿家属对手术的满意度高于改良Duplay术式组患儿家属对一期手术的满意度(P < 0.05),与改良Duplay术式组患儿家属对二期手术的满意度相近(P > 0.05)。结论 改良Duplay术治疗中重度尿道下裂手术时间短、尿道狭窄和尿道憩室的发生率低,其临床应用优于Duckett术。  相似文献   
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