Background:
Fecal calprotectin (FC) is a relatively new marker of intestinal inflammation. Recently, many studies have extended its role in predicting relapse of quiescent inflammatory bowel disease ...(IBD), but the reported results have been inconsistent. We aimed to perform a meta‐analysis of the predictive capacity of FC in IBD relapse.
Methods:
We systematically searched the Medline, Web of Science, Cochrane Library, and EMBASE databases for prospective studies that used FC concentrations at remission in predicting relapse of Crohn's disease (CD) and ulcerative colitis (UC). Pooled sensitivity, specificity, and other diagnostic indices were evaluated.
Results:
A total of 672 IBD patients (318 UC and 354 CD) from six different studies were analyzed. The pooled sensitivity and specificity of FC to predict relapse of quiescent IBD was 78% (95% confidence interval CI: 72–83) and 73% (95% CI: 68–77), respectively. The area under the summary receiver‐operating characteristic (sROC) curve was 0.83 and the diagnostic odds ratio was 10.31 (95% CI: 5.05–21.06). The capacity of FC to predict relapse was comparable between UC and CD. In CD patients the predictive value of FC in isolated small bowel CD was not assessed due to insufficiency of available data. Compared with all enrolled CD patients, FC appeared to be more accurate in ileocolonic and colonic CD.
Conclusions:
As a simple and noninvasive marker, FC is useful to predict relapse in quiescent IBD patients. (Inflamm Bowel Dis 2012)
To investigate the seasonal characteristics of submicron aerosol (PM1) in Beijing urban areas, a high‐resolution time‐of‐flight aerosol‐mass‐spectrometer (HR‐ToF‐AMS) was utilized at an urban site in ...summer (August to September 2011) and winter (November to December 2010), coupled with multiple state of the art online instruments. The average mass concentrations of PM1 (60–84 µg m−3) and its chemical compositions in different campaigns of Beijing were relatively consistent in recent years. In summer, the daily variations of PM1 mass concentrations were stable and repeatable. Eighty‐two percent of the PM1 mass concentration on average was composed of secondary species, where 62% is secondary inorganic aerosol and 20% secondary organic aerosol (SOA). In winter, PM1 mass concentrations changed dramatically because of the different meteorological conditions. The high average fraction (58%) of primary species in PM1 including primary organic aerosol (POA), black carbon, and chloride indicates primary emissions usually played a more important role in the winter. However, aqueous chemistry resulting in efficient secondary formation during occasional periods with high relative humidity may also contribute substantially to haze in winter. Results of past OA source apportionment studies in Beijing show 45–67% of OA in summer and 22–50% of OA in winter can be composed of SOA. Based on the source apportionment results, we found 45% POA in winter and 61% POA in summer are from nonfossil sources, contributed by cooking OA in both seasons and biomass burning OA (BBOA) in winter. Cooking OA, accounting for 13–24% of OA, is an important nonfossil carbon source in all years of Beijing and should not be neglected. The fossil sources of POA include hydrocarbon‐like OA from vehicle emissions in both seasons and coal combustion OA (CCOA) in winter. The CCOA and BBOA were the two main contributors (57% of OA) for the highest OA concentrations (>100 µg m−3) in winter. The POA/ΔCO ratios in winter and summer are 11 and 16 µg m−3 ppm−1, respectively, similar to ratios from western cities. Higher OOA/Ox (= NO2 + O3) ratio (0.49 µg m−3 ppb−1) in winter study than these ratios from western cities (0.03–0.16 µg m−3 ppb−1) was observed, which may be due to the aqueous reaction or extra SOA formation contributed by semivolatile organic compounds from various primary sources (e.g., BBOA or CCOA) in Beijing. The evolution of oxygen to carbon ratio (O/C) with photochemical age allows to estimate an equivalent rate constant for chemical aging of OA in summer as kOH ~ 4.1 × 10−12 cm3 molecule−1 s−1, which is of the same order as obtained in other anthropogenic influenced areas and may be useful for OA modeling.
Key Points
PM1 concentrations are consistently high in recent years of Beijing (60 to 85 µg m−3)
Emission sources and formation pathways of aerosol in Beijing are seasonally different
Cooking as nonfossil OA source (13–24%) is important in Beijing
A severe regional haze problem in the megacity Beijing and surrounding areas, caused by fast formation and growth of fine particles, has attracted much attention in recent years. In order to ...investigate the secondary formation and aging process of urban aerosols, four intensive campaigns were conducted in four seasons between March 2012 and March 2013 at an urban site in Beijing (116.31° E, 37.99° N). An Aerodyne high-resolution time-of-flight aerosol mass spectrometry (HR-ToF-AMS) was deployed to measure non-refractory chemical components of submicron particulate matter (NR-PM1). The average mass concentrations of PM1 (NR-PM1+black carbon) were 45.1 ± 45.8, 37.5 ± 31.0, 41.3 ± 42.7, and 81.7 ± 72.4 µg m−3 in spring, summer, autumn, and winter, respectively. Organic aerosol (OA) was the most abundant component in PM1, accounting for 31, 33, 44, and 36 % seasonally, and secondary inorganic aerosol (SNA, sum of sulfate, nitrate, and ammonium) accounted for 59, 57, 43, and 55 % of PM1 correspondingly. Based on the application of positive matrix factorization (PMF), the sources of OA were obtained, including the primary ones of hydrocarbon-like (HOA), cooking (COA), biomass burning OA (BBOA) and coal combustion OA (CCOA), and secondary component oxygenated OA (OOA). OOA, which can be split into more-oxidized (MO-OOA) and less-oxidized OOA (LO-OOA), accounted for 49, 69, 47, and 50 % in four seasons, respectively. Totally, the fraction of secondary components (OOA+SNA) contributed about 60–80 % to PM1, suggesting that secondary formation played an important role in the PM pollution in Beijing, and primary sources were also non-negligible. The evolution process of OA in different seasons was investigated with multiple metrics and tools. The average carbon oxidation states and other metrics show that the oxidation state of OA was the highest in summer, probably due to both strong photochemical and aqueous-phase oxidations. It was indicated by the good correlations (r = 0.53–0.75, p < 0.01) between LO-OOA and odd oxygen (Ox = O3 + NO2), and between MO-OOA and liquid water content in aerosols. BBOA was resolved in spring and autumn, influenced by agricultural biomass burning (e.g., field preparation burnings, straw burning after the harvest). CCOA was only identified in winter due to domestic heating. These results signified that the comprehensive management for biomass burning and coal combustion emissions is needed. High concentrations of chemical components in PM1 in Beijing, especially in winter or in adverse meteorological conditions, suggest that further strengthening the regional emission control of primary particulate and precursors of secondary species is expected.
The prevalence and prognosis of digestive system involvement, including gastrointestinal symptoms and liver injury, in patients with COVID-19 remains largely unknown. We aimed to quantify the effects ...of COVID-19 on the digestive system.
In this systematic review and meta-analysis, we systematically searched PubMed, Embase, and Web of Science for studies published between Jan 1, 2020, and April 4, 2020. The websites of WHO, CDC, and major journals were also searched. We included studies that reported the epidemiological and clinical features of COVID-19 and the prevalence of gastrointestinal findings in infected patients, and excluded preprints, duplicate publications, reviews, editorials, single case reports, studies pertaining to other coronavirus-related illnesses, and small case series (<10 cases). Extracted data included author; date; study design; country; patient demographics; number of participants in severe and non-severe disease groups; prevalence of clinical gastrointestinal symptoms such as vomiting, nausea, diarrhoea, loss of appetite, abdominal pain, and belching; and digestive system comorbidities including liver disease and gastrointestinal diseases. Raw data from studies were pooled to determine effect estimates.
We analysed findings from 35 studies, including 6686 patients with COVID-19, that met inclusion criteria. 29 studies (n=6064) reported gastrointestinal symptoms in patients with COVID-19 at diagnosis, and the pooled prevalence of digestive system comorbidities was 4% (95% CI 2-5; range 0-15; I
=74%). The pooled prevalence of digestive symptoms was 15% (10-21; range: 2-57; I
=96%) with nausea or vomiting, diarrhoea, and loss of appetite being the three most common symptoms. The pooled prevalence of abnormal liver functions (12 studies, n=1267) was 19% (9-32; range 1-53; I
=96%). Subgroup analysis showed patients with severe COVID-19 had higher rates of abdominal pain (odds ratio OR 7·10 95% CI 1·93-26·07; p=0·003; I
=0%) and abnormal liver function including increased ALT (1·89 1·30-2·76; p=0·0009; I
=10%) and increased AST (3·08 2·14-4·42; p<0·00001; I
=0%) compared with those with non-severe disease. Patients in Hubei province, where the initial COVID-19 outbreak occurred, were more likely to present with abnormal liver functions (p<0·0001) compared with those outside of Hubei. Paediatric patients with COVID-19 had a similar prevalence of gastrointestinal symptoms to those of adult patients. 10% (95% CI 4-19; range 3-23; I
=97%) of patients presented with gastrointestinal symptoms alone without respiratory features. Patients who presented with gastrointestinal system involvement had delayed diagnosis (standardised mean difference 2·85 95% CI 0·22-5·48; p=0·030; I
=73%). Patients with gastrointestinal involvement tended to have a poorer disease course (eg, acute respiratory distress syndrome OR 2·96 95% CI 1·17-7·48; p=0·02; I
=0%).
Our study showed that digestive symptoms and liver injury are not uncommon in patients with COVID-19. Increased attention should be paid to the care of this unique group of patients.
None.
There is a great unmet need for advanced therapies that provide rapid, robust, and sustained disease control for patients with ulcerative colitis. We assessed the efficacy and safety of upadacitinib, ...an oral selective Janus kinase 1 inhibitor, as induction and maintenance therapy in patients with moderately to severely active ulcerative colitis.
This phase 3, multicentre, randomised, double-blind, placebo-controlled clinical programme consisted of two replicate induction studies (U-ACHIEVE induction UC1 and U-ACCOMPLISH UC2) and a single maintenance study (U-ACHIEVE maintenance UC3). The studies were conducted across Europe, North and South America, Australasia, Africa, and the Asia-Pacific region at 199 clinical centres in 39 countries (UC1), 204 clinical centres in 40 countries (UC2), and 195 clinical centres in 35 countries (UC3). Patients aged 16–75 years with moderately to severely active ulcerative colitis (Adapted Mayo score 5–9; endoscopic subscore 2 or 3) for at least 90 days were randomly assigned (2:1) to oral upadacitinib 45 mg once daily or placebo for 8 weeks (induction studies). Patients who achieved clinical response following 8-week upadacitinib induction were re-randomly assigned (1:1:1) to upadacitinib 15 mg, upadacitinib 30 mg, or placebo for 52 weeks (maintenance study). All patients were randomly assigned using web-based interactive response technology. The primary endpoints were clinical remission per Adapted Mayo score at week 8 (induction) and week 52 (maintenance). The efficacy analyses in the two induction studies were based on the intent-to-treat population, which included all randomised patients who received at least one dose of treatment. In the maintenance study, the primary efficacy analyses reported in this manuscript were based on the first 450 (planned) clinical responders to 8-week induction therapy with upadacitinib 45 mg once daily. The safety analysis population in the induction studies consisted of all randomised patients who received at least one dose of treatment; in the maintenance study, this population included all patients who received at least one dose of treatment as part of the primary analysis population. These studies are registered at ClinicalTrials.gov, NCT02819635 (U-ACHIEVE) and NCT03653026 (U-ACCOMPLISH).
Between Oct 23, 2018, and Sept 7, 2020, 474 patients were randomly assigned to upadacitinib 45 mg once daily (n=319) or placebo (n=155) in UC1. Between Dec 6, 2018, and Jan 14, 2021, 522 patients were randomly assigned to upadacitinib 45 mg once daily (n=345) or placebo (n=177) in UC2. In UC3, a total of 451 patients (21 from the phase 2b study, 278 from UC1, and 152 from UC2) who achieved a clinical response after 8 weeks of upadacitinib induction treatment were randomly assigned again to upadacitinib 15 mg (n=148), upadacitinib 30 mg (n=154), and placebo (n=149) in the primary analysis population. Statistically significantly more patients achieved clinical remission with upadacitinib 45 mg (83 26% of 319 patients in UC1 and 114 34% of 341 patients in UC2) than in the placebo group (seven 5% of 154 patients in UC1 and seven 4% of 174 patients; p<0·0001; adjusted treatment difference 21·6% 95% CI 15·8–27·4 for UC1 and 29·0% 23·2–34·7 for UC2). In the maintenance study, clinical remission was achieved by statistically significantly more patients receiving upadacitinib (15 mg 63 42% of 148; 30 mg 80 52% of 154) than those receiving placebo (18 12% of 149; p<0·0001; adjusted treatment difference 30·7% 21·7–39·8 for upadacitinib 15 mg vs placebo and 39·0% 29·7–48·2 for upadacitinib 30 mg vs placebo). The most commonly reported adverse events in UC1 were nasopharyngitis (15 5% of 319 in the upadacitinib 45 mg group vs six 4% of 155 in the placebo group), creatine phosphokinase elevation (15 4% vs three 2%), and acne (15 5% vs one 1%). In UC2, the most frequently reported adverse event was acne (24 7% of 344 in the upadacitinib 45 mg group vs three 2% of 177 in the placebo group). In both induction studies, serious adverse events and adverse events leading to discontinuation of treatment were less frequent in the upadacitinib 45 mg group than in the placebo group (serious adverse events eight 3% vs nine (6%) in UC1 and 11 3% vs eight 5% in UC2; adverse events leading to discontinuation six 2% vs 14 9% in UC1 and six 2% vs nine 5% in UC2). In UC3, the most frequently reported adverse events (≥5%) were worsening of ulcerative colitis (19 13% of 148 in the upadacitinib 15 mg group vs 11 7% of 154 in the upadacitinib 30 mg group vs 45 30% of 149 in the placebo group), nasopharyngitis (18 12% vs 22 14% vs 15 10%), creatine phosphokinase elevation (nine 6% vs 13 8% vs three 2%), arthralgia (nine 6% vs five 3% vs 15 10%), and upper respiratory tract infection (seven 5% vs nine 6% vs six 4%). The proportion of serious adverse events (ten 7% vs nine 6% vs 19 13%) and adverse events leading to discontinuation (six 4% vs ten 6% vs 17 11%) was lower in both upadacitinib groups than in the placebo group. Events of cancer, adjudicated major adverse cardiac events, or venous thromboembolism were reported infrequently. There were no treatment-related deaths.
Upadacitinib demonstrated a positive efficacy and safety profile and could be an effective treatment option for patients with moderately to severely active ulcerative colitis.
AbbVie.
Photorealistic Audio-driven Video Portraits Wen, Xin; Wang, Miao; Richardt, Christian ...
IEEE transactions on visualization and computer graphics,
12/2020, Letnik:
26, Številka:
12
Journal Article
Recenzirano
Odprti dostop
Video portraits are common in a variety of applications, such as videoconferencing, news broadcasting, and virtual education and training. We present a novel method to synthesize photorealistic video ...portraits for an input portrait video, automatically driven by a person's voice. The main challenge in this task is the hallucination of plausible, photorealistic facial expressions from input speech audio. To address this challenge, we employ a parametric 3D face model represented by geometry, facial expression, illumination, etc., and learn a mapping from audio features to model parameters. The input source audio is first represented as a high-dimensional feature, which is used to predict facial expression parameters of the 3D face model. We then replace the expression parameters computed from the original target video with the predicted one, and rerender the reenacted face. Finally, we generate a photorealistic video portrait from the reenacted synthetic face sequence via a neural face renderer. One appealing feature of our approach is the generalization capability for various input speech audio, including synthetic speech audio from text-to-speech software. Extensive experimental results show that our approach outperforms previous general-purpose audio-driven video portrait methods. This includes a user study demonstrating that our results are rated as more realistic than previous methods.
Studies of gene rearrangements and the consequent oncogenic fusion proteins have laid the foundation for targeted cancer therapy. To identify oncogenic fusions associated with glioma progression, we ...catalogued fusion transcripts by RNA-seq of 272 gliomas. Fusion transcripts were more frequently found in high-grade gliomas, in the classical subtype of gliomas, and in gliomas treated with radiation/temozolomide. Sixty-seven in-frame fusion transcripts were identified, including three recurrent fusion transcripts: FGFR3-TACC3, RNF213-SLC26A11, and PTPRZ1-MET (ZM). Interestingly, the ZM fusion was found only in grade III astrocytomas (1/13; 7.7%) or secondary GBMs (sGBMs, 3/20; 15.0%). In an independent cohort of sGBMs, the ZM fusion was found in three of 20 (15%) specimens. Genomic analysis revealed that the fusion arose from translocation events involving introns 3 or 8 of PTPRZ and intron 1 of MET. ZM fusion transcripts were found in GBMs irrespective of isocitrate dehydrogenase 1 (IDH1) mutation status. sGBMs harboring ZM fusion showed higher expression of genes required for PIK3CA signaling and lowered expression of genes that suppressed RB1 or TP53 function. Expression of the ZM fusion was mutually exclusive with EGFR overexpression in sGBMs. Exogenous expression of the ZM fusion in the U87MG glioblastoma line enhanced cell migration and invasion. Clinically, patients afflicted with ZM fusion harboring glioblastomas survived poorly relative to those afflicted with non-ZM-harboring sGBMs (P < 0.001). Our study profiles the shifting RNA landscape of gliomas during progression and reveled ZM as a novel, recurrent fusion transcript in sGBMs.
Parasitic wasps produce several factors including venom, polydnaviruses (PDVs) and specialized wasp cells named teratocytes that benefit the survival of offspring by altering the physiology of hosts. ...However, the underlying molecular mechanisms for the alterations remain unclear. Here we find that the teratocytes of Cotesia vestalis, an endoparasitoid of the diamondback moth Plutella xylostella, and its associated bracovirus (CvBV) can produce miRNAs and deliver the products into the host via different ways. Certain miRNAs in the parasitized host are mainly produced by teratocytes, while the expression level of miRNAs encoded by CvBV can be 100-fold greater in parasitized hosts than non-parasitized ones. We further show that one teratocyte-produced miRNA (Cve-miR-281-3p) and one CvBV-produced miRNA (Cve-miR-novel22-5p-1) arrest host growth by modulating expression of the host ecdysone receptor (EcR). Altogether, our results show the first evidence of cross-species regulation by miRNAs in animal parasitism and their possible function in the alteration of host physiology during parasitism.
ObjectiveTo investigate the relationship between job satisfaction, work stress, work–family conflict and turnover intention, and explore factors associated with turnover intention, among physicians ...in Guangdong Province, China.MethodsFrom August to October 2013, physicians completed questionnaires and scales with regard to their job satisfaction, work stress, work–family conflict, and turnover intention. Binary logistic regression and structural equation modelling (SEM) were used in data analysis.ResultsA total of 3963 physicians were approached, with 3563 completing the questionnaire. The mean score of the overall perception of turnover intention of physicians who worked in Guangdong was 2.71 on a scale ranging from 1 to 6. Hours worked per week, working in an urban/rural area, type of institution, and age significantly impacted on turnover intention. Turnover intention was directly and negatively related to job satisfaction, and it was directly, indirectly and positively related to work stress and work–family conflict.ConclusionJob satisfaction, work stress, work–family conflict, hours worked per week, working in an urban/rural area, types of institution and age are influencing factors of turnover intention. Reducing working hours, raising salary, providing more opportunities for career development and training, supporting and encouraging physicians by senior managers could potentially contribute to the reduction in turnover intention.
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