In the adult hippocampus, synapses are constantly formed and eliminated
. However, the exact function of synapse elimination in the adult brain, and how it is regulated, are largely unknown. Here we ...show that astrocytic phagocytosis
is important for maintaining proper hippocampal synaptic connectivity and plasticity. By using fluorescent phagocytosis reporters, we find that excitatory and inhibitory synapses are eliminated by glial phagocytosis in the CA1 region of the adult mouse hippocampus. Unexpectedly, we found that astrocytes have a major role in the neuronal activity-dependent elimination of excitatory synapses. Furthermore, mice in which astrocytes lack the phagocytic receptor MEGF10 show a reduction in the elimination of excitatory synapses; as a result, excessive but functionally impaired synapses accumulate. Finally, Megf10-knockout mice show defective long-term synaptic plasticity and impaired formation of hippocampal memories. Together, our data provide strong evidence that astrocytes eliminate unnecessary excitatory synaptic connections in the adult hippocampus through MEGF10, and that this astrocytic function is crucial for maintaining circuit connectivity and thereby supporting cognitive function.
The pathological role of reactive gliosis in CNS repair remains controversial. In this study, using murine ischemic and hemorrhagic stroke models, we demonstrated that microglia/macrophages and ...astrocytes are differentially involved in engulfing synapses in the reactive gliosis region. By specifically deleting MEGF10 and MERTK phagocytic receptors, we determined that inhibiting phagocytosis of microglia/macrophages or astrocytes in ischemic stroke improved neurobehavioral outcomes and attenuated brain damage. In hemorrhagic stroke, inhibiting phagocytosis of microglia/macrophages but not astrocytes improved neurobehavioral outcomes. Single-cell RNA sequencing revealed that phagocytosis related biological processes and pathways were downregulated in astrocytes of the hemorrhagic brain compared to the ischemic brain. Together, these findings suggest that reactive microgliosis and astrogliosis play individual roles in mediating synapse engulfment in pathologically distinct murine stroke models and preventing this process could rescue synapse loss.
Background
The purpose of this study was to evaluate the nationwide benefit and cost of the national cancer screening program (NCSP) for gastric cancer treatment.
Methods
For this nationwide, ...population‐based study, the Korean National Health Insurance Big Data Base, which included gastric cancer–related treatment information and the costs for all patients with gastric cancer who were 40 years old or older between 2004 and 2013, was restructured. Patients with gastric cancer who participated in the NCSP at least once (the screening group) were compared with those who did not participate in the NCSP (the nonscreening group).
Results
The screening group (n = 116,775) spent significantly less on medical care expenses than the nonscreening group (n = 74,927) during the 5 years since the initial treatment (P < .0001). The screening group presented a significantly better prognosis for 5 and 9 years than the nonscreening group (P < .0001). The screening group revealed a 41% decreased hazard ratio (P < .0001) for death in comparison with the nonscreening group; the prognostic benefit became more obvious when treatment was started within the first 4 months after screening. The age‐standardized mortality rate ratio of the screening group versus the nonscreening group was 0.62 (P < .0001). The NCSP for gastric cancer required an average of 22,169,769 Korean Republic won (US $20,309) for 1 life‐year saved, which was less than the average gross domestic product (GDP) per capita in Korea.
Conclusions
The screening group had significantly lower medical care expenses and showed a significantly better prognosis than the nonscreening group. On the basis of the GDP per capita, the NCSP for gastric cancer was cost‐effective for treatment prognosis.
The nationwide, population‐based health insurance big database in Korea, where a national cancer screening program for gastric cancer was introduced in 2002, reveals that a screening group has lower medical care expenses and presents with a better prognosis than a nonscreening group even after stratification of the treatment group. On the basis of medical care expenses and screening costs, the national cancer screening program for gastric cancer is cost‐effective.
We developed an automatic method for staging periodontitis on dental panoramic radiographs using the deep learning hybrid method. A novel hybrid framework was proposed to automatically detect and ...classify the periodontal bone loss of each individual tooth. The framework is a hybrid of deep learning architecture for detection and conventional CAD processing for classification. Deep learning was used to detect the radiographic bone level (or the CEJ level) as a simple structure for the whole jaw on panoramic radiographs. Next, the percentage rate analysis of the radiographic bone loss combined the tooth long-axis with the periodontal bone and CEJ levels. Using the percentage rate, we could automatically classify the periodontal bone loss. This classification was used for periodontitis staging according to the new criteria proposed at the 2017 World Workshop on the Classification of Periodontal and Peri-Implant Diseases and Conditions. The Pearson correlation coefficient of the automatic method with the diagnoses by radiologists was 0.73 overall for the whole jaw (p < 0.01), and the intraclass correlation value 0.91 overall for the whole jaw (p < 0.01). The novel hybrid framework that combined deep learning architecture and the conventional CAD approach demonstrated high accuracy and excellent reliability in the automatic diagnosis of periodontal bone loss and staging of periodontitis.
It is unclear whether laparoscopic distal gastrectomy for locally advanced gastric cancer is oncologically equivalent to open distal gastrectomy. The noninferiority of laparoscopic subtotal ...gastrectomy with D2 lymphadenectomy for locally advanced gastric cancer compared with open surgery in terms of 3-year relapse-free survival rate was evaluated.
A phase III, open-label, randomized controlled trial was conducted for patients with histologically proven locally advanced gastric adenocarcinoma suitable for distal subtotal gastrectomy. The primary end point was the 3-year relapse-free survival rate; the upper limit of the hazard ratio (HR) for noninferiority was 1.43 between the laparoscopic and open distal gastrectomy groups.
From November 2011 to April 2015, 1,050 patients were randomly assigned to laparoscopy (n = 524) or open surgery (n = 526). After exclusions, 492 patients underwent laparoscopic surgery and 482 underwent open surgery and were included in the analysis. The laparoscopy group, compared with the open surgery group, suffered fewer early complications (15.7%
23.4%, respectively;
= .0027) and late complications (4.7%
9.5%, respectively;
= .0038), particularly intestinal obstruction (2.0%
4.4%, respectively;
= .0447). The 3-year relapse-free survival rate was 80.3% (95% CI, 76.0% to 85.0%) for the laparoscopy group and 81.3% (95% CI, 77.0% to 85.0%; log-rank
= .726) for the open group. Cox regression analysis after stratification by the surgeon revealed an HR of 1.035 (95% CI, 0.762 to 1.406; log-rank
= .827;
for noninferiority = .039). When stratified by pathologic stage, the HR was 1.020 (95% CI, 0.751 to 1.385; log-rank
= .900;
for noninferiority = .030).
Laparoscopic distal gastrectomy with D2 lymphadenectomy was comparable to open surgery in terms of relapse-free survival for patients with locally advanced gastric cancer. Laparoscopic distal gastrectomy with D2 lymphadenectomy could be a potential standard treatment option for locally advanced gastric cancer.
Oscillometric measurement is widely used to estimate systolic blood pressure (SBP) and diastolic blood pressure (DBP). In this paper, we propose a deep belief network (DBN)-deep neural network (DNN) ...to learn about the complex nonlinear relationship between the artificial feature vectors obtained from the oscillometric wave and the reference nurse blood pressures using the DBN-DNN-based-regression model. Our DBN-DNN is a powerful generative network for feature extraction and can address to stick in local minima through a special pretraining phase. Therefore, this model provides an alternative way for replacing a popular shallow model. Based on this, we apply the DBN-DNN-based regression model to estimate the SBP and DBP. However, there are a small amount of data samples, which is not enough to train the DBN-DNN without the overfitting problem. For this reason, we use the parametric bootstrap-based artificial features, which are used as training samples to efficiently learn the complex nonlinear functions between the feature vectors obtained and the reference nurse blood pressures. As far as we know, this is one of the first studies using the DBN-DNN-based regression model for BP estimation when a small training sample is available. Our DBN-DNN-based regression model provides a lower standard deviation of error, mean error, and mean absolute error for the SBP and DBP as compared with the conventional methods.
Background
With improved short-term surgical outcomes, laparoscopic distal gastrectomy has rapidly gained popularity. However, the safety and feasibility of laparoscopic total gastrectomy (LTG) has ...not yet been proven due to the difficulty of the technique. This single-arm prospective multi-center study was conducted to evaluate the use of LTG for clinical stage I gastric cancer.
Methods
Between October 2012 and January 2014, 170 patients with pathologically proven, clinical stage I gastric adenocarcinoma located at the proximal stomach were enrolled. Twenty-two experienced surgeons from 19 institutions participated in this clinical trial. The primary end point was the incidence of postoperative morbidity and mortality at postoperative 30 days. The severity of postoperative complications was categorized according to Clavien–Dindo classification, and the incidence of postoperative morbidity and mortality was compared with that in a historical control.
Results
Of the enrolled patients, 160 met criteria for inclusion in the full analysis set. Postoperative morbidity and mortality rates reached 20.6% (33/160) and 0.6% (1/160), respectively. Fifteen patients (9.4%) had grade III or higher complications, and three reoperations (1.9%) were performed. The incidence of morbidity after LTG in this trial did not significantly differ from that reported in a previous study for open total gastrectomy (18%).
Conclusions
LTG performed by experienced surgeons showed acceptable postoperative morbidity and mortality for patients with clinical stage I gastric cancer.
The thalamus has been implicated in fear extinction, yet the role of the thalamic reticular nucleus (TRN) in this process remains unclear. Here, in mice, we show that the rostroventral part of the ...TRN (TRNrv) is critically involved in the extinction of tone-dependent fear memory. Optogenetic excitation of TRNrv neurons during extinction learning dramatically facilitated, whereas the inhibition disrupted, the fear extinction. Single unit recordings demonstrated that TRNrv neurons selectively respond to conditioned stimuli but not to neutral stimuli. TRNrv neurons suppressed the spiking activity of the medial part of the dorsal midline thalamus (dMTm), and a blockade of this inhibitory pathway disrupted fear extinction. Finally, we found that the suppression of dMTm projections to the central amygdala promotes fear extinction, and TRNrv neurons have direct connections to this pathway. Our results uncover a previously unknown function of the TRN and delineate the neural circuit for thalamic control of fear memory.
The oncologic outcomes of laparoscopy-assisted gastrectomy for the treatment of gastric cancer have not been evaluated. The aim of this study is to validate the efficacy and safety of laparoscopic ...gastrectomy for gastric cancer in terms of long-term survival, morbidity, and mortality retrospectively.
The study group comprised 2,976 patients who were treated with curative intent either by laparoscopic gastrectomy (1,477 patients) or open gastrectomy (1,499 patients) between April 1998 and December 2005. The long-term 5-year actual survival analysis in case-control and case-matched population was conducted using the Kaplan-Meier method. The morbidity and mortality and learning curves were evaluated.
In the case-control study, the overall survival, disease-specific survival, and recurrence-free survival (median follow-up period, 70.8 months) were not statistically different at each cancer stage with the exception of an increased overall survival rate for patients with stage IA cancer treated via laparoscopy (laparoscopic group; 95.3%, open group: 90.3%; P < .001). After matching using a propensity scoring system, the overall survival, disease-specific survival, and recurrence-free survival rates were not statistically different at each stage. The morbidity of the case-matched group was 15.1% in the open group and 12.5% in the laparoscopic group, which also had no statistical significance (P = .184). The mortality rate was also not statistically significant (0.3% in the open group and 0.5% in the laparoscopic group; P = 1.000). The mean learning curve was 42.
The long-term oncologic outcomes of laparoscopic gastrectomy for patients with gastric cancer were comparable to those of open gastrectomy in a large-scale, multicenter, retrospective clinical study.
Glioblastoma (GBM) is a devastating and incurable brain tumour, with a median overall survival of fifteen months
. Identifying the cell of origin that harbours mutations that drive GBM could provide ...a fundamental basis for understanding disease progression and developing new treatments. Given that the accumulation of somatic mutations has been implicated in gliomagenesis, studies have suggested that neural stem cells (NSCs), with their self-renewal and proliferative capacities, in the subventricular zone (SVZ) of the adult human brain may be the cells from which GBM originates
. However, there is a lack of direct genetic evidence from human patients with GBM
. Here we describe direct molecular genetic evidence from patient brain tissue and genome-edited mouse models that show astrocyte-like NSCs in the SVZ to be the cell of origin that contains the driver mutations of human GBM. First, we performed deep sequencing of triple-matched tissues, consisting of (i) normal SVZ tissue away from the tumour mass, (ii) tumour tissue, and (iii) normal cortical tissue (or blood), from 28 patients with isocitrate dehydrogenase (IDH) wild-type GBM or other types of brain tumour. We found that normal SVZ tissue away from the tumour in 56.3% of patients with wild-type IDH GBM contained low-level GBM driver mutations (down to approximately 1% of the mutational burden) that were observed at high levels in their matching tumours. Moreover, by single-cell sequencing and laser microdissection analysis of patient brain tissue and genome editing of a mouse model, we found that astrocyte-like NSCs that carry driver mutations migrate from the SVZ and lead to the development of high-grade malignant gliomas in distant brain regions. Together, our results show that NSCs in human SVZ tissue are the cells of origin that contain the driver mutations of GBM.
PDF
