Transcutaneous auricular vagus nerve stimulation (taVNS) has shown promise as a non-invasive alternative to vagus nerve stimulation (VNS) with implantable devices, which has been used to treat ...drug-resistant epilepsy and treatment-resistant depression. Prior work has used functional MRI to investigate the brain response to taVNS, and more recent work has also demonstrated potential therapeutic effects of high-frequency sub-threshold taVNS in rheumatoid arthritis. However, no studies to date have measured the effects of high-frequency sub-threshold taVNS on cerebral blood flow (CBF). The objective of this study was to determine whether high-frequency (20 kHz) sub-threshold taVNS induces significant changes in CBF, a promising metric for the assessment of the sustained effects of taVNS. Arterial spin labeling (ASL) MRI scans were performed on 20 healthy subjects in a single-blind placebo-controlled repeated measures experimental design. The ASL scans were performed before and after 15 min of either sub-threshold taVNS treatment or a sham control. taVNS induced significant changes in CBF in the superior posterior cerebellum that were largely localized to bilateral Crus I and Crus II. Post hoc analyses showed that the changes were driven by a treatment-related decrease in CBF. Fifteen minutes of high-frequency sub-threshold taVNS can induce sustained CBF decreases in the bilateral posterior cerebellum in a cohort of healthy subjects. This study lays the foundation for future studies in clinical populations, and also supports the use of ASL measures of CBF for the assessment of the sustained effects of taVNS.
Circumnutation (Darwin et al., Sci Rep 10(1):1-13, 2000) is the side-to-side movement common among growing plant appendages but the purpose of circumnutation is not always clear. Accurately tracking ...and quantifying circumnutation can help researchers to better study its underlying purpose.
In this paper, a deep learning-based model is proposed to track the circumnutating flowering apices in the plant Arabidopsis thaliana from time-lapse videos. By utilizing U-Net to segment the apex, and combining it with the model update mechanism, pre- and post- processing steps, the proposed model significantly improves the tracking time and accuracy over other baseline tracking methods. Additionally, we evaluate the computational complexity of the proposed model and further develop a method to accelerate the inference speed of the model. The fast algorithm can track the apices in real-time on a computer without a dedicated GPU.
We demonstrate that the accuracy of tracking the flowering apices in the plant Arabidopsis thaliana can be improved with our proposed deep learning-based model in terms of both the racking success rate and the tracking error. We also show that the improvement in the tracking accuracy is statistically significant. The time-lapse video dataset of Arabidopsis is also provided which can be used for future studies on Arabidopsis in various takes.
Transcutaneous auricular vagus nerve stimulation (taVNS), a non-invasive alternative to vagus nerve stimulation (VNS) with implantable devices, has shown promise in treating disorders such as ...depression, migraine, and insomnia. Studies of these disorders with resting-state functional magnetic resonance imaging (MRI) (rsfMRI) have found sustained changes in resting-state functional connectivity (rsFC) in patients treated with low frequency (1-20 Hz) taVNS. A recent study has reported reductions in pain scores in patients with rheumatoid arthritis after a 12-week treatment of high-frequency (20 kHz) sub-threshold taVNS. However, no studies to date have examined the effects of high-frequency sub-threshold taVNS on rsFC. The objective of this study was to determine whether high-frequency sub-threshold taVNS induces changes in rsFC using seed regions from the cingulate cortex and insula, brain regions that play a key role in interoception and processing of pain. With a single-blind placebo-controlled repeated measures experimental design, rsfMRI scans were acquired before and after 15 min of either sub-threshold taVNS treatment or a sham control. Significant taVNS-related changes in functional connections to the cingulate cortex were detected between the anterior cingulate cortex and right superior temporal gyrus and between the midcingulate cortex and right inferior parietal lobule. In addition, significant changes in functional connections to the insula were detected between the posterior insula and right precuneus and between the anterior insula and right cuneus gyrus. These results suggest that high-frequency sub-threshold taVNS can lead to sustained effects on the rsFC of brain regions involved in interoception and processing of pain in a cohort of healthy subjects. This study lays the foundation for future rsfMRI studies of high-frequency sub-threshold taVNS in clinical populations.
This paper develops a new divergence that generalizes relative entropy and can be used to compare probability measures without a requirement of absolute continuity. We establish properties of the ...divergence, and in particular derive and exploit a representation as an infimum convolution of optimal transport cost and relative entropy. Also included are examples of computation and approximation of the divergence, and the demonstration of properties that are useful when one quantifies model uncertainty.
Background
The JACOB trial (NCT01774786) was a double‐blinded, placebo‐controlled, randomized, multicenter, international, phase III trial evaluating the efficacy and safety of adding pertuzumab to ...trastuzumab and chemotherapy in first‐line treatment of human epidermal growth factor receptor 2 (HER2)‐positive metastatic gastric cancer/gastroesophageal junction cancer (GEJC). The aim of this analysis was to investigate efficacy and safety outcomes in the Chinese subpopulation from the JACOB trial.
Methods
This post hoc subpopulation analysis included all patients recruited in mainland China (n= 163; 20.9%) between June 2013 and January 2016. The patients were randomly assigned in a 1:1 ratio to receive pertuzumab plus trastuzumab and chemotherapy (pertuzumab group; n= 82) or placebo plus trastuzumab and chemotherapy (control group; n= 81). Intravenous pertuzumab (840 mg) and trastuzumab (8 mg/kg loading and 6 mg/kg maintenance doses) were given every 3 weeks until disease progression or unacceptable toxicity. Chemotherapy was given as per standard regimens/doses of capecitabine or 5‐fluorouracil plus cisplatin. The primary endpoint was overall survival (OS); secondary efficacy endpoints included progression‐free survival (PFS), and overall objective response rate (ORR).
Results
The median OS was 18.7 months in the pertuzumab group and 16.1 months in the control group (hazard ratio HR 0.75; 95% confidence interval CI 0.49 to 1.14). The median PFS was 10.5 and 8.6 months in the pertuzumab and control groups, respectively (HR 0.85; 95% CI 0.60 to 1.21), and the median ORRs were 68.9% and 55.7%, respectively. The treatment effect in this Chinese subpopulation showed consistency with that in the global ITT population with numerically lower HR for OS and PFS compared with the control group. The safety profiles of the pertuzumab and control groups in this Chinese subpopulation analysis were generally comparable. The most common grade 3–5 adverse events were neutropenia, anemia, and leukopenia. However, due to the nature of being a post hoc subgroup analysis, the results presented here are descriptive only and need to be interpreted with caution.
Conclusions
OS and PFS were numerically improved by adding pertuzumab to trastuzumab and chemotherapy as first‐line treatment in Chinese HER2‐positive gastric cancer/GEJC patients, and this regimen demonstrated an acceptable safety profile.
Trial registration ClinicalTrials.gov. NCT01774786. Registered on 24 January 2013, https://clinicaltrials.gov/ct2/show/NCT01774786
Streaming of live 360-degree video allows users to follow a live event from any view point and has already been deployed on some commercial platforms. However, the current systems can only stream the ...video at relatively low-quality because the entire 360-degree video is delivered to the users under limited bandwidth. Streaming video falling into user field of view (FoV) can improve bandwidth efficiency of 360-degree video delivery. In this paper, we propose to use the idea of "flocking" to simultaneously improve the accuracy of user FoV prediction and video delivery efficiency for live 360-degree video streaming. By assigning variable playback latencies to users in a streaming session based on their network conditions, a "streaming flock" is formed and led by "strong" users with low playback latencies in the front of the flock. We propose a long short-term memory (LSTM) based collaborative FoV prediction scheme where the FoV traces of users in the front of the flock are utilized to predict the FoV of users behind them. Given a predicted FoV, we develop an optimal rate allocation strategy to maximize the perceptual quality. By conducting experiments using real-world user FoV traces and LTE/5 G network bandwidth traces, we evaluate the gains of the proposed strategies over several benchmarks. Our experimental results demonstrate that the proposed streaming system can increase the overall quality dramatically by about 10 dB compared with heuristic FoV prediction strategy. In addition, the network-aware flocking formation can further reduce the video freeze without influencing video quality.
Streaming of live 360-degree video allows users to follow a live event from any view point and has already been deployed on some commercial platforms. However, the current systems can only stream the ...video at relatively low-quality because the entire 360-degree video is delivered to the users under limited bandwidth. In this paper, we propose to use the idea of "flocking" to improve the performance of both prediction of field of view (FoV) and caching on the edge servers for live 360-degree video streaming. By assigning variable playback latencies to all the users in a streaming session, a "streaming flock" is formed and led by low latency users in the front of the flock. We propose a collaborative FoV prediction scheme where the actual FoV information of users in the front of the flock are utilized to predict of users behind them. We further propose a network condition aware flocking strategy to reduce the video freeze and increase the chance for collaborative FoV prediction on all users. Flocking also facilitates caching as video tiles downloaded by the front users can be cached by an edge server to serve the users at the back of the flock, thereby reducing the traffic in the core network. We propose a latency-FoV based caching strategy and investigate the potential gain of applying transcoding on the edge server. We conduct experiments using real-world user FoV traces and WiGig network bandwidth traces to evaluate the gains of the proposed strategies over benchmarks. Our experimental results demonstrate that the proposed streaming system can roughly double the effective video rate, which is the video rate inside a user's actual FoV, compared to the prediction only based on the user's own past FoV trajectory, while reducing video freeze. Furthermore, edge caching can reduce the traffic in the core network by about 80%, which can be increased to 90% with transcoding on edge server.
Background.
Diabetic patients with breast cancer receiving metformin and neoadjuvant chemotherapy have a higher pathologic complete response rate than do diabetic patients not receiving metformin, ...but findings on salvage treatment have been inconsistent. We performed a meta‐analysis to assess the effect of adding metformin to standard therapy on the prognosis of breast cancer patients with diabetes.
Methods.
We searched PubMed, Embase, Web of Science (Thomson Scientific), China Knowledge Resource Integrated Database, VIP journal integration platform, and Chinese BioMedical Literature Database from inception to January 10, 2015, without language restrictions, including references related to metformin, breast cancer, and prognosis. We performed the meta‐analysis using a random‐effects model, with hazard ratios (HRs) and 95% confidence intervals (95% CIs) as effect measures.
Results.
A total of 11 studies consisting of 5,464 breast cancer patients with diabetes were included, comprising 2,760 patients who had received metformin and 2,704 patients who had not. The meta‐analysis showed that metformin was associated with better overall survival times (HR: 0.53; 95% CI: 0.39‐0.71) and cancer‐specific survival times (HR: 0.89; 95% CI: 0.79‐1.00). Subgroup analysis revealed that metformin improved the overall survival by 65% after adjusting for hormone receptor expression (HR: 0.35; 95% CI: 0.15–0.84). Taking metformin after the diagnosis of breast cancer was still associated with prolonged overall survival.
Conclusion.
The use of metformin in standard cancer therapy might improve both overall and cancer‐specific survivals of diabetic patients with breast cancer.
Implications for Practice:
Diabetic patients with breast cancer receiving metformin and neoadjuvant chemotherapy have a higher pathologic complete response rate than diabetic patients not receiving metformin, but findings on salvage treatment have been inconsistent. The meta‐analysis showed that metformin was associated with better overall survival times and cancer‐specific survival times. Subgroup analysis revealed that metformin improved the overall survival by 65% after adjusting for hormone receptor expression. Taking metformin after the diagnosis of breast cancer was still associated with prolonged overall survival. The findings of this study highlight the potential usage of metformin in diabetic patients with breast cancer.
摘要
背景. 合并糖尿病的乳腺癌患者中,接受二甲双胍与新辅助化疗者的病理学完全缓解率优于未接受二甲双胍治疗者,但有关挽救性治疗的研究结果并不一致。我们开展了一项 meta 分析,目的是在合并糖尿病的乳腺癌患者中,评估标准治疗基础上添加二甲双胍治疗对预后的影响。
方法. 我们在 PubMed、Embase、Web of Science (汤普森科技)、中国知识资源总库、维普期刊资源整合服务平台和中国生物医学文献数据库中,对起始至 2015 年 1 月 10 日的数据进行了检索。检索对象包括与二甲双胍、乳腺癌和预后相关的参考文献,未设语种限制。我们的 meta 分析使用了随机效应模型,使用风险比 (HR) 和 95%可信区间 (CI) 进行效应测量。
结果. 共纳入 11 项研究,涉及 5 464 例合并糖尿病的乳腺癌患者,包括 2 760 例接受二甲双胍治疗的患者和 2 704 例未接受二甲双胍治疗的患者。Meta 分析显示二甲双胍治疗患者的总生存时间(HR: 0.53, 95%CI: 0.39 ∼ 0.71)和癌症相关生存时间较长 (HR: 0.89, 95%CI: 0.79 ∼ 1.00)。亚组分析显示,校正激素受体表达状态后,二甲双胍治疗使总生存时间延长了65% (HR: 0.35, 95%CI: 0.15 ∼ 0.84)。在诊断为乳腺癌之后才开始二甲双胍治疗仍然与总生存时间延长相关。
结论. 在标准抗癌治疗方案基础上加用二甲双胍,可改善合并糖尿病的乳腺癌患者的总生存及癌症相关生存。The Oncologist 2015;20:1236–1234
对临床实践的提示:合并糖尿病的乳腺癌患者中,接受二甲双胍与新辅助化疗的患者病理学完全缓解率高于未接受二甲双胍治疗的患者,但有关挽救性治疗的研究结果并不一致。本项 meta 分析显示二甲双胍与总生存时间和癌症相关生存时间较长相关。亚组分析显示,校正激素受体表达状态后,二甲双胍使总生存时间延长了 65%。在诊断为乳腺癌之后才开始二甲双胍治疗仍然与总生存时间延长相关。本研究的结果强调了二甲双胍在合并糖尿病的乳腺癌患者中的潜在应用。
This meta‐analysis showed that metformin was associated with better overall survival times and cancer‐specific survival times in diabetic patients with breast cancer. Subgroup analysis revealed that metformin improved the overall survival by 65% after adjusting for hormone receptor expression. The findings of this study highlight the potential usage of metformin in diabetic patients with breast cancer.
Efficient coding and streaming of 360-degree video and point cloud video are critical for the continued development of lifelike virtual reality (VR) experiences.Interactive 360-degree video ...applications, e.g. video conferencing, require an extremely low delay in video delivery and robustness to both network dynamics and field of view (FoV) prediction errors. We propose a frame-level FoV-adaptive coding structure that varies the bit rates for different regions of a coded frame based on the predicted FoV. Integrating such frame-level FoV adaptation with temporal predictive coding is challenging due to the temporal variations of the FoV. We propose novel ways for modeling the influence of FoV dynamics on the quality-rate performance of temporal predictive coding. Compared with other benchmark systems, our system shows significantly improved rendered video quality, while achieving very low end-to-end delay and low frame-freeze probability.Octree-based point cloud representation and compression have been adopted by the MPEG G-PCC standard. However, it only uses handcrafted methods to predict the probability that a leaf node is non-empty, which is used for entropy coding. We propose a 3D convolution-based machine learning model to predict such probabilities for geometry coding using the context information from the previous and currently coded octree level. We further propose a convolution-based model to upsample the decoded point cloud at a coarse resolution on the decoder side. Integration of the two approaches significantly improves the octree-based geometry coding performance. A key advantage of our work from the prior related studies is that our octree-based entropy coding model is naturally scalable. This benefits the future design of the point cloud streaming system.
B7-H1 and B7-H3, two members of the B7 family that are thought to regulate T-cell activation, are expressed in human non-small cell lung cancer (NSCLC). However, their prognostic significance is ...poorly understood. In the present study we reported that B7-H1 and B7-H3 were expressed in 96/128 (72.7%) and 89/128 (69.5%) samples, respectively. B7-H1 and B7-H3 expression and the number of infiltrating T-cell intracellular antigen-1+ and interferon-γ+ cells in NSCLC tissues were significantly higher than those in the adjacent tissues (p<0.01). High B7-H1 or B7-H3 expression was associated with lymph node metastasis and TNM stage (p<0.05, respectively). Sex, TNM stage, B7-H1, B7-H3, and T-cell intracellular antigen-1 expression remained significant prognostic factors after adjusting for other prognostic factors in a multivariate Cox proportional hazards regression model. In vitro studies revealed that knockdown of B7-H3 on tumor cells enhanced T-cell growth and interferon-γ secretion when stimulated by anti-CD3 and anti-CD28 monoclonal antibodies. Interferon-γ reduced CXCR4 expression on cancer cells and inhibited the CXCL12-induced cell migration.B7-H1 and B7-H3 are independent predictors of poorer survival in patients with NSCLC. Interference of the signal pathways of these negative regulatory molecules might be a new strategy for treating NSCLC.
PDF
