Interpretatively automated identification of circulating tumor cells from human peripheral blood with high performance.

The detection and analysis of circulating tumor cells (CTCs) would be of aid in a precise cancer diagnosis and an efficient prognosis assessment. However, traditional methods that rely heavily on the isolation of CTCs based on their physical or biological features suffer from intensive labor, thus being unsuitable for rapid detection. Furthermore, currently available intelligent methods are short of interpretability, which creates a lot of uncertainty during diagnosis. Therefore, we propose here an automated method that takes advantage of bright-field microscopic images with high resolution, so as to take an insight into cell patterns. Specifically, the precise identification of CTCs was achieved by using an optimized single-shot multi-box detector (SSD)-based neural network with integrated attention mechanism and feature fusion modules. Compared to the conventional SSD system, our method exhibited a superior detection performance with the recall rate of 92.2%, and the maximum average precision (AP) value of 97.9%. To note, the optimal SSD-based neural network was combined with advanced visualization technology, i.e., the gradient-weighted class activation mapping (Grad-CAM) for model interpretation, and the t-distributed stochastic neighbor embedding (T-SNE) for data visualization. Our work demonstrates for the first time the outstanding performance of SSD-based neural network for CTCs identification in human peripheral blood environment, showing great potential for the early detection and continuous monitoring of cancer progression.

Textbook outcomes of hepatocellular carcinoma patients with sarcopenia: A multicenter analysis.

BACKGROUND: The impact of sarcopenia on textbook outcome (TO) after hepatectomy in hepatocellular carcinoma (HCC) patients remains unclear. This study aimed to investigate the association between sarcopenia and TO, to clarify its long and short-term prognostic value, and to develop a nomogram model based on sarcopenia and TO for survival prediction. METHODS: Patients who underwent HCC resection between January 2012 and March 2017 in three large hospitals in Fujian were retrospectively recruited and divided into sarcopenia and non-sarcopenia groups based on skeletal muscle index (SMI) values. TO was defined as no 30-day morality, no 30-day readmission, negative margins, no prolonged hospital stay, and no major complications. Multivariate regression was used to screen for clinical factors associated with TO. Nomograms of overall survival (OS) and recurrence-free survival (RFS) after hepatectomy for HCC were developed. RESULTS: A total of 1172 patients were included in the study. The TO rates were 28.74% (121/421 patients) in the sarcopenia group and 43.4% (326/751 patients) in the non-sarcopenia group. The results showed that sarcopenia was an independent predictor of TO (p < 0.001), TO was an independent predictor of perioperative treatment-related sarcopenia (PTRS)(p = 0.002), and TO was an independent predictor of OS and RFS (p < 0.001). Nomogram models based on sarcopenia and TO were generated and accurately predicted OS and RFS at 1, 3, and 5 years. CONCLUSION: Both sarcopenia and TO are independent predictors of OS and RFS after HCC resection. Sarcopenia was an independent predictor of TO. Sarcopenia influenced long-term survival by affecting short-term postoperative outcomes.

Rosmarinic Acid Inhibits Mitochondrial Damage by Alleviating Unfolded Protein Response.

Mitochondria are essential organelles that perform important roles in cell biologies such as ATP synthesis, metabolic regulation, immunomodulatory, and apoptosis. Parkinson's disease (PD) is connected with mitochondrial neuronal damage related to mitochondrial unfolded protein response (mtUPR). Rosmarinic acid (RA) is a naturally occurring hydroxylated polyphenolic chemical found in the Boraginaceae and the Labiatae subfamily Nepetoideae. This study looked into RA's protective effect against mitochondrial loss in the substantia nigra (SN) caused by 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP), the underlying mechanism associated with the mtUPR. Pretreatment with RA reduced motor impairments and dopaminergic neuronal degeneration in the SN of a mouse model injected with MPTP. Pretreatment of SH-SY5Y cells from cell viability loss, morphological damage, and oxidative stress. Furthermore, RA pre-injection suppressed MPTP-induced mtUPR, lowered the expression of HSPA9, HSPE1, CLPP, LONP1, and SIRT 4, and protected the MPTP-mice and SH-SY5Y cells from mitochondrial failure. These findings imply that RA can prevent Parkinson's disease by preventing mitochondrial damage in dopaminergic neurons in Parkinson's disease via alleviating mitochondrial unfolded protein response.

Efficacy and safety of treatments for REM sleep behaviour disorder in Parkinson's disease: a systematic review and Bayesian network meta-analysis protocol.

INTRODUCTION: Sleep disorders are the main non-motor characteristics of Parkinson's disease (PD). The quality of life is significantly impacted by rapid eye movement sleep behaviour disorder (RBD). It is not clearly evidenced in the literature that some medications can reduce the dream activities of patients with PD and RBD and improve sleep quality. And, they have side effects that may increase the severity of this disease. To further understand which medication has better efficacy and fewer adverse effects for patients with PD and RBD, it is necessary to perform a network meta-analysis. METHODS AND ANALYSIS: This protocol is performed accordingly to the guidelines of the Preferred Reporting Items for Systematic Review and Meta-Analysis Protocols and the Cochrane Collaboration Handbook.A thorough literature selection will be conducted up to September 2021 using PubMed, Cochrane Library (The Cochrane Database of Systematic Reviews) and Embase. We will not only include randomised controlled trials, but prospective, retrospective cohort, case-control, nested case-control, case-cohort, cross-sectional and case series. We will use the Cochrane Collaboration tool to assess the risk of bias. Pairwise and network meta-analyses will be conducted using the R netmeta package and Stata V.14.0. The relative ranking probability of the best intervention will be estimated using the surface under the cumulative ranking curve. Additionally, sensitivity analysis, subgroup analysis, quality assessment and publication bias analysis will be performed. ETHICS AND DISSEMINATION: No research ethics approval is required for this systematic review, as no confidential patient data will be used. We will disseminate our findings through publication in a peer-reviewed journal and conference presentations, and our review will support development of a BMJ Rapid Recommendations providing contextualised clinical guidance based on this body of evidence. PROSPERO REGISTRATION NUMBER: CRD42020206958.

Comparative Efficacy and Safety of Dopamine Agonists in Advanced Parkinson's Disease With Motor Fluctuations: A Systematic Review and Network Meta-Analysis of Double-Blind Randomized Controlled Trials.

Background: Movement fluctuations are the main complication of Parkinson's disease (PD) patients receiving long-term levodopa (L-dopa) treatment. We compared and ranked the efficacy and safety of dopamine agonists (DAs) with regard to motor fluctuations by using a Bayesian network meta-analysis (NMA) to quantify information from randomized controlled trials (RCTs). Methods and Findings: We carried out a systematic review and meta-analysis, and only RCTs comparing DAs for advanced PD were included. Electronic databases (PubMed, Embase, and Cochrane Library) were systematically searched for relevant studies published until January 2021. Two reviewers independently extracted individual study data and evaluated studies for risk of bias using the Cochrane Risk of Bias tool. Network meta-analyses using a Bayesian framework were used to calculate the related parameters. The pre-specified primary and secondary outcomes were efficacy ("ON" time without troublesome dyskinesia, "OFF" time, "ON" time, "UPDRS-III," and "UPDRS-II") and safety [treatment-emergent adverse events (TEAE) and other adverse events] of DAs. The results are presented as the surface under the cumulative ranking (SUCRA) curve. A total of 20 RCTs assessing 6,560 patients were included. The general DA effects were ranked from high to low with respect to the amount of "ON" time without troublesome dyskinesia as follows: apomorphine (SUCRA = 97.08%), pramipexole_IR (probability = 79.00%), and ropinirole_PR (SUCRA = 63.92%). The general safety of DAs was ranked from high to low with respect to TEAE as follows: placebo (SUCRA = 74.49%), pramipexole_ER (SUCRA = 63.6%), sumanirole (SUCRA = 54.07%), and rotigotine (SUCRA = 53.84%). Conclusions: This network meta-analysis shows that apomorphine increased "ON" time without troublesome dyskinesia and decreased "OF" time for advanced PD patients. The addition of pramipexole, ropinirole, or rotigotine to levodopa treatment in advanced PD patients with motor fluctuations increased "ON" time without troublesome dyskinesia, improved the UPDRS III scores, and ultimately ameliorated the UPDRS II scores, thereby maximizing its benefit. This NMA of pramipexole, ropinirole, and rotigotine represents an effective treatment option and has an acceptable safety profile in patients with advanced PD.

Comparison of efficacy of deep brain stimulation and focused ultrasound in parkinsonian tremor: a systematic review and network meta-analysis.

To compare the efficacy of deep brain stimulation (DBS) and MRI-guided focused ultrasound (MRIgFUS) in parkinsonian tremor. We performed a network meta-analysis based on a Bayesian framework. We searched the literature for articles published between January 1990 and October 2020 using three databases: PubMed, Embase and Cochrane Library (The Cochrane Database of Systematic Reviews). A total of 24 studies were included in our analysis, comprising data from 784 participants. Our findings revealed similar efficacy of DBS and MRIgFUS in parkinsonian tremor suppression. Compared with internal globus pallidus (GPi)-MRIgFUS, GPi-DBS -1.84 (-6.44, 2.86), pedunculopontine nucleus (PPN)_DBS -3.28 (-9.28, 2.78), PPN and caudal zona incerta (cZI)-DBS 0.40 (-6.16, 6.87), subthalamic nucleus (STN)_DBS 0.89 (-3.48, 5.30), STN and cZI-DBS 1.99 (-4.74, 8.65), ventral intermediate nucleus(VIM)_DBS 1.75 (-2.87, 6.48), VIM_FUS 0.72 (-5.27, 6.43), cZI-DBS 0.27 (-4.75, 5.36) were no significantly difference. Compared with VIM-MRIgFUS, GPi-DBS -2.55(-6.94, 2.21), GPi-FUS -0.72 (-6.43, 5.27), PPN_DBS -4.01(-9.97, 2.11), PPN and cZI-DBS -0.32 (-6.73, 6.36), STN_DBS 0.16 (-3.98, 4.6), STN and cZI-DBS 1.31(-5.18,7.87), VIM-DBS 1.00(-3.41, 5.84)and cZI-DBS -0.43 (-5.07, 4.68) were no significantly difference. With respect to the results for the treatment of motor symptoms, GPi-DBS, GPi-MRIgFUS, STN-DBS and cZI-DBS were significantly more efficacious than baseline (GPi-DBS 15.24 (5.79, 24.82), GPi-MRIgFUS 13.46 (2.46, 25.10), STN-DBS 19.62 (12.19, 27.16), cZI-DBS 14.18 (1.73, 26.89). The results from the surface under the cumulative ranking results showed that STN-DBS ranked first, followed by combined PPN and cZI-DBS, and PPN-DBS ranked last. MRIgFUS, an efficacious intervention for improving parkinsonian tremor, has not demonstrated to be inferior to DBS in parkinsonian tremor suppression. Hence, clinicians should distinguish individual patients' symptoms to ensure that the appropriate intervention and therapeutic approach are applied.

Pedunculopontine Nucleus Deep Brain Stimulation Improves Gait Disorder in Parkinson's Disease: A Systematic Review and Meta-analysis.

Deep brain stimulation (DBS) of the pedunculopontine nucleus (PPN) has been proposed as a treatment strategy for gait disorder in patients with Parkinson's disease (PD). We thus performed a systematic review and meta-analysis of randomized and nonrandomized controlled trials to assess the effect of this treatment on gait disorder in patients with PD. We systematically searched PubMed, Cochrane, Web of Knowledge, Wan Fang and WIP for randomized and nonrandomized controlled trials (published before July 29, 2014; no language restrictions) comparing PPN-DBS with other treatments. We assessed pooled data using a random effects model and a fixed effects model. Of 130 identified studies, 14 were eligible and were included in our analysis (N = 82 participants). Compared to those presurgery, the Unified Parkinson Disease Rating Scale (UPDRS) 27-30 scores for patients were lowered by PPN-DBS [3.94 (95% confidence interval, CI = 1.23 to 6.65)]. The UPDRS 13 and 14 scores did not improve with levodopa treatment [0.43 (- 0.35 to 1.20); 0.35 (- 0.50 to 1.19)], whereas the UPDRS 27-30 scores could be improved by the therapy [1.42 (95% CI 0.34 to 2.51)]. The Gait and Falls Questionnaire and UPDRS 13 and 14 scores showed significant improvements after PPN-DBS under the medication-off (MED-OFF) status [15.44 (95% CI = 8.44 to 22.45); 1.57 (95% CI = 0.84 to 2.30); 1.34 (95% CI = 0.84 to 1.84)]. PPN-DBS is a potential therapeutic target that could improve gait and fall disorders in patients with PD. Our findings will help improve the clinical application of DBS in PD patients with gait disorder.