Recent developments in molecular and chemical methods have enabled the analysis of fungal DNA and secondary metabolites, often produced during fungal growth, in environmental samples. We compared 3 ...fungal analytical methods by analysing floor dust samples collected from an office building for fungi using viable culture, internal transcribed spacer (ITS) sequencing and secondary metabolites using liquid chromatography‐tandem mass spectrometry. Of the 32 metabolites identified, 29 had a potential link to fungi with levels ranging from 0.04 (minimum for alternariol monomethylether) to 5700 ng/g (maximum for neoechinulin A). The number of fungal metabolites quantified per sample ranged from 8 to 16 (average = 13/sample). We identified 216 fungal operational taxonomic units (OTUs) with the number per sample ranging from 6 to 29 (average = 18/sample). We identified 37 fungal species using culture, and the number per sample ranged from 2 to 13 (average = 8/sample). Agreement in identification between ITS sequencing and culturing was weak (kappa = −0.12 to 0.27). The number of cultured fungal species poorly correlated with OTUs, which did not correlate with the number of metabolites. These suggest that using multiple measurement methods may provide an improved understanding of fungal exposures in indoor environments and that secondary metabolites may be considered as an additional source of exposure.
Summary
Background
Low‐osmolar non‐ionic radiocontrast media (RCMs) are commonly used throughout hospitals. However, the incidence of immediate adverse drug reactions (ADRs) to various low‐osmolar ...non‐ionic RCMs is not well studied. We compared the incidence of immediate ADRs among different low‐osmolar non‐ionic RCMs used in computed tomography (CT).
Methods
Severance Hospital has collected data for adverse reactions occurring in‐hospital using an internally developed system. Using this data, we reviewed 1969 immediate ADRs from 286 087 RCM‐contrasted CT examinations of 142 099 patients and compared the immediate ADRs of iobitridol, iohexol, iopamidol, and iopromide. We analysed the incidence of immediate ADRs to different RCMs, as well as the effect of single or multiple CT examinations per day.
Results
Iopromide showed the highest incidence of immediate ADRs (1.03%) and was followed by iopamidol (0.67%), iohexol (0.64%), and iobitridol (0.34%). In cases of anaphylaxis, iopromide also showed the highest incidence (0.041%), followed by iopamidol (0.023%), iohexol (0.018%), and iobitridol (0.012%). Risk of immediate ADR due to multiple CT examinations (1.19%) was significantly higher than the risk due to a single CT examination (0.63%). Risk of anaphylaxis was also higher for multiple CT examinations (0.052%) than for a single CT examination (0.020%).
Conclusions and Clinical Relevance
The incidence of immediate ADRs varied according to the low‐osmolar non‐ionic RCM used. Iopromide‐induced immediate ADRs were more frequent, while iobitridol was associated with fewer immediate ADRs than other RCMs. Multiple CT examinations per day resulted in a higher incidence of immediate ADRs and anaphylaxis than a single CT examination. Clinicians should consider these risk differences of immediate ADRs when prescribing contrasted CT examinations.
Background and purpose
Recent clinical trials and expert consensus guidelines have typically focused on the issue of systolic blood pressure (SBP) targets for reducing vascular risk. However, little ...is known about the relationship of the diastolic BP (DBP) level with vascular outcomes after a stroke.
Methods
A multicenter trial dataset involving 3680 recent (<4 months) non‐cardioembolic stroke patients followed for 2 years was analyzed. Subjects were categorized per mean DBP level (mmHg) during follow‐up: low−normal (<70), normal (70 to <80), high−normal (80–89) and high (≥90). Pulse pressure (PP) was prespecified by three categories of <60, 60 to <70, and ≥70 mmHg. Independent associations of mean DBP level with major vascular events (MVEs) and ischaemic stroke were assessed.
Results
Major vascular events occurred in 20.7% of the low−normal, 15.1% of the normal, 16.9% of the high−normal and 19.2% of the high DBP groups, whilst stroke occurred in 9.9%, 6.8%, 8.5% and 10.8%, respectively. Compared with the normal DBP group, risk of MVEs was higher in the low−normal DBP group (adjusted hazard ratio 1.33; 95% confidence interval 1.04–1.71). Amongst those with SBP 120 to <140 mmHg, risk of MVEs (1.89; 1.13–3.15) and stroke (2.87; 1.48–5.53) was higher in subjects with PP ≥70 (mean DBP 62.4 ± 3.8) than those with the lowest PP (mean DBP 78.0 ± 5.9) whilst, amongst those with SBP <120 mmHg, PP 60 to <70 (mean DBP 52.7 ± 2.5) was associated with increased risk of stroke (5.85; 1.25–27.5).
Conclusion
Diastolic BP levels in the low−normal range, particularly accompanied by an increased PP of >60, confer increased risk of MVEs and stroke amongst patients after recent non‐cardioembolic stroke.
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Metagenomic sequencing is revolutionizing the detection and characterization of microbial species, and a wide variety of software tools are available to perform taxonomic classification of these ...data. The fast pace of development of these tools and the complexity of metagenomic data make it important that researchers are able to benchmark their performance. Here, we review current approaches for metagenomic analysis and evaluate the performance of 20 metagenomic classifiers using simulated and experimental datasets. We describe the key metrics used to assess performance, offer a framework for the comparison of additional classifiers, and discuss the future of metagenomic data analysis.
Metagenomic sequencing is revolutionizing the detection and characterization of microbial species, and a wide variety of software tools are available to perform taxonomic classification of these data. The fast pace of development of these tools and the complexity of metagenomic data make it important that researchers are able to benchmark their performance. Here, we review current approaches for metagenomic analysis and evaluate the performance of 20 metagenomic classifiers using simulated and experimental datasets. We describe the key metrics used to assess performance, offer a framework for the comparison of additional classifiers, and discuss the future of metagenomic data analysis.
SETTING The long-term natural course of Mycobacterium avium complex (MAC) disease with nodular bronchiectasis, the most common pulmonary non-tuberculous mycobacterial disease, is not well described.
...To identify risk factors for the deterioration of nodular bronchiectatic MAC lung disease over a 5-year follow-up period.
Clinical and laboratory data of 67 patients with nodular bronchiectatic MAC lung disease were collected. Chest computerised tomographic images were used to count the number of lung segments involved at diagnosis and measure subcutaneous fat thickness during follow-up.
The 34 patients who showed deterioration had significantly lower body mass index (BMI) (P = 0.004) and % predicted forced vital capacity (P = 0.032), higher numbers of lung segments involved (P < 0.001) and MAC-positive sputum cultures (P = 0.028), and thinner chest subcutaneous fat during follow-up (P < 0.001) than patients without deterioration. In particular, patients with both BMI <21.0 kg/m(2) and more than four lung segments involved had a 240-fold increased risk of deterioration (P < 0.001).
Patients with poor nutritional status and extensive lung involvement tend to experience deterioration of nodular bronchiectatic MAC lung disease.
Master protocols, classified as basket trials, umbrella trials, and platform trials, are novel designs that investigate multiple hypotheses through concurrent sub-studies (e.g., multiple treatments ...or populations or that allow adding/removing arms during the trial), offering enhanced efficiency and a more ethical approach to trial evaluation. Despite the many advantages of these designs, they are infrequently used.
We conducted a landscape analysis of master protocols using a systematic literature search to determine what trials have been conducted and proposed for an overall goal of improving the literacy in this emerging concept. On July 8, 2019, English-language studies were identified from MEDLINE, EMBASE, and CENTRAL databases and hand searches of published reviews and registries.
We identified 83 master protocols (49 basket, 18 umbrella, and 16 platform trials). The number of master protocols has increased rapidly over the last five years. Most have been conducted in the US (n = 44/83) and investigated experimental drugs (n = 82/83) in the field of oncology (n = 76/83). The majority of basket trials were exploratory (i.e., phase I/II; n = 47/49) and not randomized (n = 44/49), and more than half (n = 28/48) investigated only a single intervention. The median sample size of basket trials was 205 participants (interquartile range, Q3-Q1 IQR: 500-90 = 410), and the median study duration was 22.3 (IQR: 74.1-42.9 = 31.1) months. Similar to basket trials, most umbrella trials were exploratory (n = 16/18), but the use of randomization was more common (n = 8/18). The median sample size of umbrella trials was 346 participants (IQR: 565-252 = 313), and the median study duration was 60.9 (IQR: 81.3-46.9 = 34.4) months. The median number of interventions investigated in umbrella trials was 5 (IQR: 6-4 = 2). The majority of platform trials were randomized (n = 15/16), and phase III investigation (n = 7/15; one did not report information on phase) was more common in platform trials with four of them using seamless II/III design. The median sample size was 892 (IQR: 1835-255 = 1580), and the median study duration was 58.9 (IQR: 101.3-36.9 = 64.4) months.
We anticipate that the number of master protocols will continue to increase at a rapid pace over the upcoming decades. More efforts to improve awareness and training are needed to apply these innovative trial design methods to fields outside of oncology.
Edge localized modes (ELMs) in high-confinement mode plasmas were completely suppressed in KSTAR by applying n=1 nonaxisymmetric magnetic perturbations. Initially, the ELMs were intensified with a ...reduction of frequency, but completely suppressed later. The electron density had an initial 10% decrease followed by a gradual increase as ELMs were suppressed. Interesting phenomena such as a saturated evolution of edge T(e) and broadband changes of magnetic fluctuations were observed, suggesting the change of edge transport by the applied magnetic perturbations.
Summary Background The role of adjuvant chemotherapy for patients with rectal cancer is controversial, especially when used after preoperative chemoradiotherapy. Fluoropyrimidine-based adjuvant ...chemotherapy, including fluorouracil and leucovorin, has been widely used; however, the addition of oxaliplatin to fluorouracil and leucovorin (FOLFOX), a standard adjuvant regimen for colon cancer, has not been tested in rectal cancer. We aimed to compare the efficacy and safety of adjuvant fluorouracil and leucovorin with that of FOLFOX in patients with locally advanced rectal cancer after preoperative chemoradiotherapy. Methods In this open-label, multicentre, phase 2, randomised trial, patients with postoperative pathological stage II (ypT3–4N0) or III (ypTany N1–2) rectal cancer after preoperative fluoropyrimidine-based chemoradiotherapy and total mesorectal excision were recruited and randomly assigned (1:1) via a web-based software platform to receive adjuvant chemotherapy with either four cycles of fluorouracil and leucovorin (fluorouracil 380 mg/m2 and leucovorin 20 mg/m2 on days 1–5, every 4 weeks) or eight cycles of FOLFOX (oxaliplatin 85 mg/m2 , leucovorin 200 mg/m2 , and fluorouracil bolus 400 mg/m2 on day 1, and fluorouracil infusion 2400 mg/m2 for 46 h, every 2 weeks). Stratification factors were pathological stage (II vs III) and centre. Neither patients nor investigators were masked to group assignment. The primary endpoint was 3-year disease-free survival, analysed by intention to treat. This study is fully enrolled, is in long-term follow-up, and is registered with ClinicalTrials.gov , number NCT00807911. Findings Between Nov 19, 2008, and June 12, 2012, 321 patients were randomly assigned to fluorouracil and leucovorin (n=161) and FOLFOX (n=160). 141 (95%) of 149 patients in the fluorouracil plus leucovorin group and 141 (97%) of 146 in the FOLFOX group completed all planned cycles of adjuvant treatment. Median follow-up was 38·2 months (IQR 26·4–50·6). 3-year disease-free survival was 71·6% (95% CI 64·6–78·6) in the FOLFOX group and 62·9% (55·4–70·4) in the fluorouracil plus leucovorin group (hazard ratio 0·657, 95% CI 0·434–0·994; p=0·047). Any grade neutropenia, thrombocytopenia, fatigue, nausea, and sensory neuropathy were significantly more common in the FOLFOX group than in the fluorouracil plus leucovorin group; however, we noted no significant difference in the frequency of these events at grade 3 or 4. The most common grade 3 or worse adverse events were neutropenia (38 26% of 149 patients in the fluorouracil plus leucovorin group vs 52 36% of 146 patients in the FOLFOX group), leucopenia (eight 5% vs 12 8%), febrile neutropenia (four 3% vs one <1%), diarrhoea (four 3% vs two 1%), and nausea (one <1% vs two 1%). Interpretation Adjuvant FOLFOX improves disease-free survival compared with fluorouracil plus leucovorin in patients with locally advanced rectal cancer after preoperative chemoradiotherapy and total mesorectal excision, and warrants further investigation. Funding Korea Healthcare Technology R&D Project (South Korean Ministry of Health and Welfare).
The epithelial-mesenchymal transition (EMT) is the pivotal mechanism underlying the initiation of cancer invasion and metastasis. Although Mel-18 has been implicated in several biological processes ...in cancer, its function in the EMT of human cancers has not yet been studied. Here, we demonstrate that Mel-18 negatively regulates the EMT by epigenetically modulating miR-205. We identified miR-205 as a novel target of Mel-18 using a microRNA microarray analysis and found that Mel-18 increased miR-205 transcription by the inhibition of DNA methyltransferase-mediated DNA methylation of the miR-205 promoter, thereby downregulating its target genes, ZEB1 and ZEB2. Furthermore, the loss of Mel-18 promoted ZEB1- and ZEB2-mediated downregulation of E-cadherin transcription and also enhanced the expression of mesenchymal markers, leading to increased migration and invasion in MCF-7 cells. In MDA-MB-231 cells, Mel-18 overexpression restored E-cadherin expression, resulting in reduced migration and invasion. These effects were reversed by miR-205 overexpression or inhibition. A tumor xenograft with Mel-18 knockdown MCF-7 cells consistently showed increased ZEB1 and ZEB2 expression and decreased E-cadherin expression. Taken together, these results suggest that Mel-18 functions as a tumor suppressor by its novel negative control of the EMT, achieved through regulating the expression of miR-205 and its target genes, ZEB1 and ZEB2.
Aims
In this study, we investigated the anti‐obesity effects of kimchi (Korean traditional fermented vegetable) fermented either without starter culture or with a specific starter culture, Weissella ...koreensis OK1‐6.
Methods and Results
C57BL/6J mice were divided into four groups (n = 7); normal diet, HF (high‐fat diet), HF‐KC (high‐fat diet containing 3% kimchi manufactured without starter) and HF‐KCO (high‐fat diet containing 3% kimchi manufactured with the starter culture W. koreensis OK1‐6). After 12 weeks of dietary intervention, the mice were killed, and serum and tissue samples were examined. Serum and hepatic lipid profile, insulin, leptin concentration and expression level of lipid anabolic genes like peroxisome proliferator‐activated receptor γ, stearoyl‐CoA desaturase‐1, liver X receptor α and SREBP2 were significantly decreased (<0·05) along with body and epididymal fat pad weight in the HF‐KCO group compared with the HF‐KC and HF group.
Conclusions
These results suggested that kimchi fermented with the starter W. koreensis OK1‐6 has anti‐obesity effects in HF‐induced obese mice.
Significance and Impact of the Study
These results may contribute to nutraceutical and food industries in developing functional food and probiotics based therapies for the treatment and prevention of obesity.
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