Real-time clinical note monitoring to detect conditions for rapid follow-up: A case study of clinical trial enrollment in drug-induced torsades de pointes and Stevens-Johnson syndrome

Identifying acute events as they occur is challenging in large hospital systems. Here, we describe an automated method to detect 2 rare adverse drug events (ADEs), drug-induced torsades de pointes and Stevens-Johnson syndrome and toxic epidermal necrolysis, in near real time for participant recruitment into prospective clinical studies. A text processing system searched clinical notes from the electronic health record (EHR) for relevant keywords and alerted study personnel via email of potential patients for chart review or in-person evaluation. Between 2016 and 2018, the automated recruitment system resulted in capture of 138 true cases of drug-induced rare events, improving recall from 43% to 93%. Our focused electronic alert system maintained 2-year enrollment, including across an EHR migration from a bespoke system to Epic. Real-time monitoring of EHR notes may accelerate research for certain conditions less amenable to conventional study recruitment paradigms.     

MiR-634 sensitizes nasopharyngeal carcinoma cells to paclitaxel and inhibits cell growth both in vitro and in vivo

Resistance to chemotherapy is one of the key causal factors in cancer death and increasing evidence has revealed that microRNAs (miRNAs) are involved in chemoresistance in many kinds of human cancers. Paclitaxel has been used for treatment of advanced nasopharyngeal carcinoma (NPC); however, treatment failure often occurs due to development of acquired paclitaxel resistance. In this study, based on miRNA microarray screening and qRT-PCR validation, we found six differentially expressed miRNAs in our induced paclitaxel-resistant NPC CNE-1/Taxol cells. Furthermore, we clarified the role of miR-634, most significantly downregulated in the paclitaxel-resistant CNE-1/Taxol, in regulating the paclitaxel sensitivity in NPC cells. We restored miR-634 expression in the CNE-1/Taxol cells by lentivirus infection, and found restoration of miR-634 re-sensitized the CNE-1/Taxol cells to paclitaxel in vitro by MTT assay and colony formation assay. In xenograft mouse model, we found that miR-634 inhibited tumor growth and enhanced paclitaxel sensitivity. Thus, our findings provide important information for the development of targeted gene therapy for reversing paclitaxel resistance in NPC.     

Clinical Presentation of Paget’s Disease: Evaluation of a Contemporary Cohort and Systematic Review

Paget’s disease of bone (PDB) has become less common over recent decades but it is unclear if this has impacted on clinical presentation. Here we evaluated the presenting features of PDB in a contemporary cohort of UK patients and conducted a systematic review of studies in which the presenting features had been reported. The case series comprised 88 patients referred to a specialist clinic between 2005 and 2013. Bone pain was the most common presenting feature occurring in 73.8 % of patients. Others included bone deformity (18.1 %), deafness (7.9 %) and pathological fracture (5.7 %). The disease was asymptomatic in 22 % of cases. Antiresorptive treatment was given for pain in 34 cases and 61.7 % of patients responded. Patients with a shorter disease duration were more likely to respond (p = 0.047). In the systematic review, bone pain was the most common presenting feature (52.2 % of cases) followed by deformity (21.5 %), deafness (8.9 %) and fracture (8.5 %). Time trend analysis in subjects of European descent showed that fracture was less common in studies performed during the past 25 years as compared with older studies (5.5 vs. 10.8 % p < 0.001) whereas pain was more common (54.3 vs. 48.3 %, p = 0.003). While changes in the mode of presentation of PDB have occurred over recent years, many patients present with complications such as fracture and deformity. Further research is required to determine if early detection and therapeutic intervention might be of value in preventing the morbidity associated with this common disease.     

An ensemble with the chinese pentatonic scale using electroencephalogram from both hemispheres

To listen to brain activity as a piece of music,we previously proposed scale-free brainwave music（SFBM）technology,which translated the scalp electroencephalogram（EEG）into musical notes according to the power law of both the EEG and music.In this study,the methodology was further extended to ensemble music on two channels from the two hemispheres.EEG data from two channels symmetrically located on the left and right hemispheres were translated into MIDI sequences by SFBM,and the EEG parameters modulated the pitch,duration and volume of each note.Then,the two sequences were filtered into an ensemble with two voices：the pentatonic scale（traditional Chinese music）or the heptatonic scale（standard Western music）.We demonstrated differences in harmony between the two scales generated at different sleep stages,with the pentatonic scale being more harmonious.The harmony intervals of this brain ensemble at various sleep stages followed the power law.Compared with the heptatonic scale,it was easier to distinguish the different stages using the pentatonic scale.These results suggested that the hemispheric ensemble can represent brain activity by variations in pitch,tempo and harmony.The ensemble with the pentatonic scale sounds more consonant,and partially reflects the relations of the two hemispheres.This can be used to distinguish the different states of brain activity and provide a new perspective on EEG analysis.     

当归芍药散调控泛素-蛋白酶体途径改善SAMP8小鼠认知能力的作用及其机制

目的 探讨当归芍药散（DSS）调控泛素-蛋白酶体途径（UPP）改善SAMP8阿尔茨海默病（AD）模型小鼠认知能力的作用机制。方法 15只SAMR1小鼠为正常组，60只SAMP8小鼠随机分为模型组及DSS高、中、低剂量组（57.6、28.8、14.4 g·kg^-1·d^-1），连续灌胃给药8周。Morris水迷宫实验测试定位航行与空间探索能力；苏木素-伊红（HE）染色法检测海马CA1区神经元病理结构改变；免疫组化法（IHC）和酶联免疫吸附测定法（ELISA）检测海马β淀粉样蛋白（Aβ）和磷酸化（p）-Tau蛋白含量，实时荧光定量聚合酶链式反应（Real-time PCR）和蛋白免疫印迹法（Western blot）检测海马组织泛素（Ub）、泛素连接酶E3（E3）、26S蛋白酶体、泛素羧基端水解酶1（UCHL1）、UCHL3 mRNA和蛋白表达。结果 与正常组比较，模型组小鼠逃避潜伏期延长（P<0.05），穿越平台象限次数和平台象限停留百分比减少（P<0.05）；CA1区神经元明显减少、胞体聚缩；β-淀粉样前体蛋白（β-APP）和p-Tau阳性细胞数量明显增多（P<0.05）；Aβ和p-Tau蛋白水平升高（P<0.05）；Ub mRNA和蛋白表达升高（P<0.05）；E3、26S蛋白酶体、UCHL1、UCHL3 mRNA和蛋白表达下降（P<0.05）。与模型组比较，DSS高、中剂量组逃避潜伏期缩短（P<0.05），穿越平台象限次数和停留百分比增加（P<0.05）；DSS各剂量组CA1病理改变明显改善；各剂量组β-APP及中、低剂量组p-Tau阳性染色细胞数量减少（P<0.05）；各剂量组Aβ及p-Tau蛋白水平下降（P<0.05）；各剂量组 Ub mRNA表达降低（P<0.05），高、中剂量组26S、E3、UCHL3 mRNA表达水平升高（P<0.05），中剂量组UCHL1 mRNA表达升高（P<0.05）；各剂量组Ub蛋白表达降低，高、中剂量组26S、E3、UCHL1+3蛋白表达升高（P<0.05）。结论 DSS可改善SAMP8小鼠认知能力，其机制可能与降低UPP途径中Ub及升高E3、26S、UCHL1、UCHL3的表达，减少Aβ和p-Tau异常沉积有关。