MSE of 3-cycles N-of-1 trials (<i>n</i> = 1, 3, 5, 10, 20, 30).

<p>M1: Model 1; M2: Model 2; M3: Model 3; M4: Model 4. N/A: Meta-analysis was not available for <i>n</i> = 1 subject.</p

A Comparison of Four Methods for the Analysis of N-of-1 Trials

<div><p>Objective</p><p>To provide a practical guidance for the analysis of N-of-1 trials by comparing four commonly used models.</p><p>Methods</p><p>The four models, paired t-test, mixed effects model of difference, mixed effects model and meta-analysis of summary data were compared using a simulation study. The assumed 3-cycles and 4-cycles N-of-1 trials were set with sample sizes of 1, 3, 5, 10, 20 and 30 respectively under normally distributed assumption. The data were generated based on variance-covariance matrix under the assumption of (i) compound symmetry structure or first-order autoregressive structure, and (ii) no carryover effect or 20% carryover effect. Type I error, power, bias (mean error), and mean square error (MSE) of effect differences between two groups were used to evaluate the performance of the four models.</p><p>Results</p><p>The results from the 3-cycles and 4-cycles N-of-1 trials were comparable with respect to type I error, power, bias and MSE. Paired t-test yielded type I error near to the nominal level, higher power, comparable bias and small MSE, whether there was carryover effect or not. Compared with paired t-test, mixed effects model produced similar size of type I error, smaller bias, but lower power and bigger MSE. Mixed effects model of difference and meta-analysis of summary data yielded type I error far from the nominal level, low power, and large bias and MSE irrespective of the presence or absence of carryover effect.</p><p>Conclusion</p><p>We recommended paired t-test to be used for normally distributed data of N-of-1 trials because of its optimal statistical performance. In the presence of carryover effects, mixed effects model could be used as an alternative.</p></div

Bias (PE, %) of 3-cycles N-of-1 trials (<i>n</i> = 1, 3, 5, 10, 20, 30).

<p>M1: Model 1; M2: Model 2; M3: Model 3; M4: Model 4. N/A: Meta-analysis was not available for <i>n</i> = 1 subject.</p

Power of 3-cycles N-of-1 trials (<i>n</i> = 1, 3, 5, 10, 20, 30).

*<p>M1: Model 1; M2: Model 2; M3: Model 3; M4: Model 4. N/A: Meta-analysis was not available for <i>n</i> = 1 subject.</p

3-cycles N-of-1 trials. (There is a washout period between successive treatment periods).

<p>3-cycles N-of-1 trials. (There is a washout period between successive treatment periods).</p

Data_Sheet_1_Characteristics and duties of clinical research nurses: a scoping review.docx

IntroductionThe characteristics and duties of clinical research nurses (CRNs) are constantly developing and changing with the progress of medical technology and increasing needs in patient care. With the continuous deepening and standardization of clinical trials, the importance and status of CRNs during the whole process of clinical trials are also increasingly valued.MethodsA scoping review of studies related to the characteristics and duties of CRNs was conducted to clarify relevant roles and concepts. An electronic search was conducted on three English databases (PubMed, Web of Science, Embase) and two Chinese databases (CNKI and Wanfang database) in December 2023. Two authors independently screened the literature, extracted information from the included literature, and summarized and reported the findings.ResultsA total of 26 articles published between 1991 and 2023 were analyzed, and four characteristics of CRNs were identified as participants and managers of clinical trials, caregivers and protectors of subjects, coordinators of research teams, and educators. Basic knowledge, skills and literacy, communication and coordination ability, and advanced research ability are the competencies required for CRNs.ConclusionFurther studies should focus on the importance of various characteristics of CRNs, so as to improve the quality of clinical trials and promote clinical evidence-based practice.</p

Giant enhancement of higher-order harmonics of an optical-tweezer phonon laser

Phonon lasers, as mechanical analogues of optical lasers, are unique tools for not only fundamental studies of phononics but also diverse applications such as acoustic imaging and force sensing. Very recently, by levitating a micro-size sphere in an optical tweezer, higher-order mechanical harmonics were observed in the phonon-lasing regime, as the first step towards nonlinear levitated optomechanics [Nat. Phys. 19, 414 (2023)]. However, both the lasing strengths and the quality factors of the observed harmonics are typically very low, thus severely hindering their applications. Here we show that, by applying a simple but powerful electronic control to such a levitated micro-sphere, three orders of magnitude enhancement are achievable in the brightness of the phonon lasers, including both the fundamental mode and all its higher-order harmonics. Also, giant improvements of their linewidth and frequency stability are realized in such an electro-optomechanical system, together with further improved higher-order phonon coherence. These results, as a significant step forward for enhancing and controlling micro-object phonon lasers, can be readily used for a wide range of applications involving nonlinear phonon lasers, such as acoustic frequency comb, ultra-sound sensing, atmospherical monitoring, and even bio-medical diagnosis of levitated micro-size objects

Presentation_1_Activity of Metabotropic Glutamate Receptor 4 Suppresses Proliferation and Promotes Apoptosis With Inhibition of Gli-1 in Human Glioblastoma Cells.PDF

<p>Glioblastoma multiforme (GBM) is the most lethal glioma variant in the adult brain and among the deadliest of human cancers. Increasing evidence has shown that metabotropic glutamate receptor subtype 4 (mGluR4) expression may play roles in regulating the growth of neural stem cells as well as several cancer cell lines. Here, we investigated the effects of mGluR4 on the growth and apoptosis of the LN229 GBM cell line. Involvement of Gli-1, one of the key transcription factors in the sonic Hedgehog (SHH) signaling pathway, was further explored. In this study, mGluR4 was activated using selective agonist VU0155041; and gene-targeted siRNAs were used to generate loss of function of mGluR4 and Gli-1 in LN229 cells. The results demonstrated that LN229 cells expressed mGluR4 and the agonist VU0155041 decreased cell viability in a dose- and time-dependent manner. Activation of mGluR4 inhibited cyclin D1 expression, activated pro-caspase-8/9/3, and disrupted the balance of Bcl-2/Bax expression, which indicated cell cycle arrest and apoptosis of LN229 cells, respectively. Furthermore, Gli-1 expression was reduced by mGluR4 activation in LN229 cells, and downregulation of Gli-1 expression by gene-targeted siRNA resulted in both inhibition of cell proliferation and promotion of apoptosis. Moreover, VU0155041 treatment substantially blocked SHH-induced cyclin D1 expression and cell proliferation, while increasing TUNEL-positive cells and the activation of apoptosis-related proteins. We concluded that activation of mGluR4 expressed in LN229 cells could inhibit GBM cell growth by decreasing cell proliferation and promoting apoptosis. Further suppression of intracellular Gli-1 expression might be involved in the action of mGluR4 on cancer cells. Our study suggested a novel role of mGluR4, which might serve as a potential drug target for control of GBM cell growth.</p