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.
Asthma is a heterogeneous airway disease with various clinical phenotypes. It is crucial to clearly identify clinical phenotypes to achieve better asthma management. We used cluster analysis to ...classify the clinical groups of 724 asthmatic patients from the Cohort for Reality and Evolution of Adult Asthma in Korea (COREA), and in 1843 subjects from another independent Korean asthma cohort of Soonchunhyang University Asthma Genome Research Centre (SCH) (Bucheon, Republic of Korea). Hierarchical cluster analysis was performed by Ward's method, followed by κ-means cluster analysis. Cluster analysis of the COREA cohort indicated four asthma subtypes: 1) smoking asthma; 2) severe obstructive asthma; 3) early-onset atopic asthma; and 4) late-onset mild asthma. An independent cluster analysis of the SCH cohort also indicated four clusters that were similar to the COREA clusters. Our results indicate that adult Korean asthma patients can be classified into four distinct clusters.
In recent years, several studies have reported the recycling of by-products generated by the paper industry and their application to the construction industry. A majority of the existing studies used ...waste paper sludge ash, and considerable energy is consumed in such incineration processes. This may further contribute to air pollution. In this study, we used waste newspaper (WNP), which underwent a simple crushing process without a separate high-temperature treatment process, and we integrated it in cement mortar. We prepared mortars containing 0%, 0.2%, 0.4%, 0.6%, 0.8%, and 1.0% ground WNP as a cement substitute. Subsequently, the fluidity, compressive strength, tensile strength, carbonation depth, drying shrinkage, and microstructure of the mortars were compared and analyzed. The 28-day compressive strength of the mortar samples with WNP was approximately 3.2-16.1% higher than that of the control sample. The 28-day accelerated carbonation depth of the samples with WNP was approximately 1.03-1.61 mm. Furthermore, their carbonation resistance was approximately 5.2-39.4% higher than that of the control sample. Compressive strength, tensile strength, and carbonation resistance were improved by appropriately using ground WNP as a cement substitute in cement mortar. In this study, the appropriate amount of WNP according to the mechanical properties of cement mortar was found to be 0.4-0.8%, and considering the durability characteristics, the value 0.6 was the most ideal.
There are limited data regarding whether mortality is higher in patients with non cystic fibrosis bronchiectasis (bronchiectasis) than in those without bronchiectasis. Using 2005-2015 data from the ...Korean National Health Insurance Service, we evaluated hazard ratio (HR) for all-cause mortality in the bronchiectasis cohort relative to the matched cohort. The effect of comorbidities over the study period on the relative mortality was also assessed. All-cause mortality was significantly higher in the bronchiectasis cohort than in the matched cohort (2505/100,000 vs 2142/100,000 person-years, respectively; P < 0.001). Mortality risk was 1.15-fold greater in the bronchiectasis cohort than in the matched cohort (95% confidence interval CI 1.09-1.22); mortality was greatest among elderly patients (HR = 1.17, 95% CI 1.10-1.25) and men (HR = 1.19, 95% CI 1.10-1.29). Comorbidities over the study period significantly increased the risk of death in the bronchiectasis cohort relative to the matched cohort: asthma (adjusted HR = 1.20, 95% CI 1.11-1.30), chronic obstructive pulmonary disease (adjusted HR = 1.24, 95% CI 1.15-1.34), pneumonia (adjusted HR = 1.50, 95% CI 1.39-1.63), lung cancer (adjusted HR = 1.85, 95% CI 1.61-2.12), and cardiovascular disease (adjusted HR = 1.34, 95% CI 1.23-1.45). In contrast, there were no significant differences in the risk of death in patients without bronchiectasis-related comorbidities and the matched cohort, except in the case of non-tuberculous mycobacterial infection. In conclusion, all-cause mortality was higher in patients with bronchiectasis cohort than those without bronchiectasis, especially in elderly patients and men. Comorbidities over the study period played a major role in increasing mortality in patients with bronchiectasis relative to those without bronchiectasis.
We have previously identified four distinct groups of asthma patients in KOREAN cohorts using cluster analysis: (A) smoking asthma, (B) severe obstructive asthma, (C) early-onset atopic asthma, and ...(D) late-onset mild asthma.
A longitudinal analysis of each cluster in a Korean adult asthma cohort was performed to investigate the clinical significance of asthma clusters over 12 months. Cluster A showed relatively high asthma control test (ACT) scores but relatively low FEV1 scores, despite a high percentage of systemic corticosteroid use. Cluster B had the lowest mean FEV1, ACT, and the quality of life questionnaire for adult Korean asthmatics (QLQAKA) scores throughout the year, even though the percentage of systemic corticosteroid use was the highest among the four clusters. Cluster C was ranked second in terms of FEV1, with the second lowest percentage of systemic corticosteroid use, and showed a marked improvement in subjective symptoms over time. Cluster D consistently showed the highest FEV1, the lowest systemic corticosteroid use, and had high ACT and QLQAKA scores.
Our asthma clusters had clinical significance with consistency among clusters over 12 months. These distinctive phenotypes may be useful in classifying asthma in real practice.
Though insurance claims data are useful for researching asthma, they have important limitations, such as a diagnostic inaccuracy and a lack of clinical information. To overcome these drawbacks, we ...used the novel method by merging the clinical data from our asthma cohort with the National Health Insurance (NHI) claims data.
Longitudinal analysis of asthma-related healthcare use from the NHI claims database, merged with data of 736 patients registered in a Korean asthma cohort, was conducted for three consecutive years from registration of the cohort. Asthma-related asthma healthcare referred to outpatient and emergency department visits, hospitalizations, and the use of systemic corticosteroids. Univariate and multivariate logistic regression analysis was used to evaluate risk factors for asthma-related healthcare. Over three years after enrollment, many patients changed from tertiary to primary/secondary hospitals with a lack of maintenance of inhaled corticosteroid-based controllers. An independent risk factor for emergency visits was a previous history of asthma exacerbation. In hospitalizations, old age and Asthma Control Test (ACT) score variability were independent risk factors. An independent risk factor for per person cumulative duration of systemic corticosteroids was the FEV1 (Forced expiratory volume in one second)%. The use of systemic corticosteroids was independently associated with being female, the FEV1%, and ACT score variability.
We found that old age, being female, long-standing asthma, a low FEV1%, asthma brittleness, asthma drug compliance, and a history of asthma exacerbation were independent risk factors for increased asthma-related healthcare use in Korea.
Adverse drug events are significant causes of emergency department visits. Systematic evaluation of adverse drug events leading to emergency department visits by age is lacking. This multicenter ...retrospective observational study evaluated the prevalence and features of adverse drug event-related emergency department visits across ages. We reviewed emergency department medical records obtained from three university hospitals between July 2014 and December 2014. The proportion of adverse drug events among total emergency department visits was calculated. The cause, severity, preventability, and causative drug(s) of each adverse drug event were analyzed and compared between age groups (children/adolescents <18 years, adults 18–64 years, and the elderly ≥65 years). Of 59,428 emergency department visits, 2,104 (3.5%) were adverse drug event-related. Adverse drug event-related emergency department visits were more likely to be female and older. Multivariate logistic regression analysis revealed that compared to non- adverse drug event-related cases, adverse drug event-related emergency department visitors were more likely to be female (60.6% vs. 53.6%, p<0.001, OR 1.285, 95% CI 1.025–1.603) and older (50.8 ± 24.6 years vs. 37.7 ± 24.4 years, p<0.001, OR 1.892, 95% CI: 1.397–2.297). Comorbidities such as diabetes, chronic kidney disease, chronic liver disease, and malignancies were also significantly associated with adverse drug event-related emergency department visits. Side effects were the most common type of adverse drug events across age groups, although main types differed substantially depending on age. Serious adverse drug events, hospitalizations, and adverse drug event-related deaths occurred more frequently in the elderly than in adults or children/adolescents. The proportion of adverse drug event-related emergency department visits that were preventable was 15.3%. Causative drugs of adverse drug events varied considerably depending on age group. Adverse drug event features differ substantially according to age group. The findings suggest that an age-specific approach should be adopted in the preventive strategies to reduce adverse drug events.
Many layers make light work: Layer‐by‐layer (LbL) self‐assembly of a dendritic porphyrin (red; see picture) and poly(allylamine hydrochloride) (blue) on polystyrene nanoparticles followed by removal ...of the polystyrene core produces multifunctional hollow nanocapsules. These species can be both loaded with anticancer drugs and used in photodynamic therapy (PDT) and therefore have potential in combined cancer therapy.
Introduction
Microbial ecology is reported to be an important regulator of energy homeostasis and glucose metabolism. Microbes secrete extracellular vesicles (EVs) during their proliferation and ...death to communicate with other cells. To investigate the roles of gut microbiota in glucose metabolism, we analyzed serial changes of gut microbe and microbial EV composition before and after bariatric/metabolic surgery (BMS).
Methods
Twenty-eight Wistar rats were fed on high-fat diet (HFD) to induce obesity and diabetes. Five of them compared with 5 rats fed on regular chow diet (RCD). Among the remaining 23 rats, Roux-en-Y gastric bypass (RYGB) (
n
= 10), sleeve gastrectomy (SG) (
n
= 10), or sham operation (
n
= 3) was randomly performed. Gut microbiota and EVs from fecal samples were analyzed by 16S rDNA amplicon sequencing.
Results
The present study showed that microbial diversity was decreased in HFD-fed rats versus RCD-fed rats. In addition, BMS reversed glucose intolerance and microbial richness which were induced by HFD. In terms of microbiota and microbial EV composition, both RYGB and SG enhance the composition of phyla Proteobacteria, Verrucomicrobia, and their secreting EVs, but decrease phylum Firmicutes and its EVs. We tried to demonstrate specific genera showed a significant compositional difference in obesity/diabetes-induced rats compared with normal rats and then restored similarly toward normal rats’ level after BMS. At the genus level,
Lactococcus
,
Ruminococcus
,
Dorea
in Firmicutes(p),
Psychrobacter
in Proteobacteria(p), and
Akkermansia
in Verrucomicrobia(p) fit these conditions after BMS.
Conclusion
We suggest that these genera are the candidates contributing to obesity and diabetes improvement mechanism after BMS.
Laparoscopic distal gastrectomy is gaining popularity over open distal gastrectomy for gastric cancer because of better early postoperative outcomes. However, to our knowledge, no studies have proved ...whether laparoscopic distal gastrectomy is oncologically equivalent to open distal gastrectomy.
To examine whether the long-term survival among patients with stage I gastric cancer undergoing laparoscopic distal gastrectomy is noninferior to that among patients undergoing open distal gastrectomy.
The Korean Laparoendoscopic Gastrointestinal Surgery Study (KLASS) group, which includes 15 surgeons from 13 institutes, conducted a phase 3, multicenter, open-label, noninferiority, prospective randomized clinical trial (KLASS-01) of patients with histologically proven, preoperative clinical stage I gastric adenocarcinoma from January 5, 2006, to August 23, 2010. Survival and recurrence status of the patients was determined in December 2016.
Patients were randomly assigned (1:1) to laparoscopic distal gastrectomy (n = 705) or open distal gastrectomy (n = 711). Of these patients, 85 received a surgical approach opposite the one to which they were randomized (63 randomized to the open surgery group and 22 to the laparoscopic group).
Difference in 5-year overall survival between the laparoscopic and open distal gastrectomy groups. The noninferiority margin was prespecified as -5% (corresponding hazard ratio of 1.54), with an assumed survival of 90% after 5 years in the open surgery group.
Among the 1416 patients (mean SD age, 57.3 11.1 years; 940 66.4% male) included in the study, the 5-year overall survival rates were 94.2% in the laparoscopic group and 93.3% in the open surgery group (log-rank P = .64). Intention-to-treat analysis confirmed the noninferiority of the laparoscopic approach compared with the open approach (difference, 0.9 percentage points; 1-sided 97.5% CI, -1.6 to infinity). The 5-year cancer-specific survival rates were similar between the 2 groups (97.1% in the laparoscopic group and 97.2% in the open surgery group, log-rank P = .91; difference, -0.03 percentage points; 1-sided 97.5% CI, -1.8 to infinity). Per-protocol analysis results were consistent with the intention-to-treat results for overall and cancer-specific survival rates.
The KLASS-01 trial revealed similar overall and cancer-specific survival rates between patients receiving laparoscopic and open distal gastrectomy. Laparoscopic distal gastrectomy is an oncologically safe alternative to open surgery for stage I gastric cancer.
ClinicalTrials.gov identifier: NCT00452751.
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