Significant advances have been made in developing microfluidic polymerase chain reaction (PCR) devices in the last two decades. More recently, microfluidic microdroplet technology has been exploited ...to perform PCR in droplets because of its unique features. For example, it can prevent crossover contamination and PCR inhibition, is suitable for single-cell and single-molecule analyses, and has the potential for system integration and automation. This review will therefore focus on recent developments on droplet-based continuous-flow microfluidic PCR, and the major research challenges. This paper will also discuss a new way of on-chip flow control and a rational design simulation tool, which are required to underpin fully integrated and automated droplet-based microfluidic systems. We will conclude with a scientific speculation of future autonomous scientific discoveries enabled by microfluidic microdroplet technologies.
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•Reviewed recent important developments in continuous-flow microfluidic PCR in droplets.•Discussion on the major challenges for system integration and automation, and potential solutions.•A scientific speculation of future autonomous scientific discovery enabled by droplet intelligence.
In this paper, we investigate the action growth in various backgrounds in Einstein-Maxwell-dilaton theory. We calculate the full time evolution of action growth in the anti–de Sitter dilaton black ...hole and find it approaches the late time bound from above. We investigate the black hole which is asymptotically Lifshitz and obtain its late time and full time behavior. We find the violation of Lloyd bound in the late time limit and show the full time behavior approaching the late time bound from above and exhibiting some new features for z sufficiently large.
Inflammatory bowel disease (IBD), which mainly includes ulcerative colitis (UC) and Crohn's disease (CD), is a group of chronic bowel diseases that are characterized by abdominal pain, diarrhea, and ...bloody stools. IBD is strongly associated with depression, and its patients have a higher incidence of depression than the general population. Depression also adversely affects the quality of life and disease prognosis of patients with IBD. The tryptophan-kynurenine metabolic pathway degrades more than 90% of tryptophan (TRP) throughout the body, with indoleamine 2,3-dioxygenase (IDO), the key metabolic enzyme, being activated in the inflammatory environment. A series of metabolites of the pathway are neurologically active, among which kynerunic acid (KYNA) and quinolinic acid (QUIN) are molecules of great interest in recent studies on the mechanisms of inflammation-induced depression. In this review, the relationship between depression in IBD and the tryptophan-kynurenine metabolic pathway is overviewed in the light of recent publications.
This paper attempts to examine if the “strong” version of Porter Hypothesis is supported in China by investigating how different regulatory instruments and the relative stringency impact “green” ...productivity. We use a slacks-based measure (SBM) and Luenberger Productivity Index, accounting for undesirable outputs, to evaluate the industrial “green” productivity growth rates of China's 30 provinces. The estimates imply an unsustainable development model in China with significant regional differences. By employing a panel threshold model and a province-level panel dataset during 2000–2012, empirical results show that both command-and-control and market-based regulation have a non-linear relationship with and can be positively related to “green” productivity but with different constrains on regulation stringency: there are double thresholds with the command-and-control and exists an optimal range of stringency for productivity improvement; while a single threshold has been found with the market-based regulation and its current stringency is reasonable for most of provinces. Moreover, based on China's reality, the productivity effect driven by market-based regulation is much stronger than that of the command-and-control. The mechanism of informal regulation is much more complicated. Consequently, we find evidence to support the “strong” Porter Hypothesis that reasonable stringency of environmental regulations may enhance rather than lower industrial competitiveness.
•Examine the “strong” version of Porter Hypothesis in the case of China•Environmental total factor productivity accounting for undesirable outputs•The command-and-control, market-based and informal environmental regulation•Investigate the non-linear relationship between regulation and “green” productivity•The fixed-effect panel threshold model
Neurobiological heterogeneity in obsessive compulsive disorder (OCD) is understudied leading to conflicting neuroimaging findings. Therefore, we investigated objective neuroanatomical subtypes of OCD ...by adopting a newly proposed method based on gray matter volumes (GMVs). GMVs were derived from T1‐weighted anatomical images of patients with OCD (n = 100) and matched healthy controls (HCs; n = 106). We first inquired whether patients with OCD presented higher interindividual variability HCs in terms of GMVs. Then, we identified distinct subtypes of OCD by adopting heterogeneity through discriminative analysis (HYDRA), where regional GMVs were treated as features. Patients with OCD presented higher interindividual variability than HCs, suggesting a high structural heterogeneity of OCD. HYDRA identified two distinct robust subtypes of OCD presenting opposite neuroanatomical aberrances compared with HCs, while sharing indistinguishable clinical and demographic features. Specifically, Subtype 1 exhibited widespread increased GMVs in cortical and subcortical regions, including the orbitofrontal gyrus, right anterior insula, bilateral hippocampus, and bilateral parahippocampus and cerebellum. Subtype 2 demonstrated overall decreased GMVs in regions such as the orbitofrontal gyrus, right anterior insula, and precuneus. When mixed together, none of patients presented significant differences compared with HCs. In addition, the total intracranial volume of Subtype 2 was significantly correlated with the total score of the Yale–Brown Obsessive Compulsive Scale while that of Subtype 1 was not. These results identified two distinct neuroanatomical subtypes, providing a possible explanation for conflicting neuroimaging findings, and proposed a potential objective taxonomy contributing to precise clinical diagnosis and treatment in OCD.
We observed high heterogeneity in terms of gray matter volume across patients with OCD and revealed two robust neuroanatomical subtypes of OCD. These two subtypes exhibited remarkably opposite gray matter volume aberrances compared to healthy controls. Our results provide a possible explanation for the conflicting neuroimaging findings and an objective taxonomy contributing to precision clinical diagnosis and treatment of OCD.
The aim of this study was to identify factors associated with the death of patients with COVID-19 pneumonia caused by the novel coronavirus SARS-CoV-2.All clinical and laboratory parameters were ...collected prospectively from a cohort of patients with COVID-19 pneumonia who were hospitalised to Wuhan Pulmonary Hospital (Wuhan City, Hubei Province, China) between 25 December 2019 and 7 February 2020. Univariate and multivariate logistic regression analysis revealed that age ≥65 years (OR 3.765, 95% CI 1.146–17.394; p=0.023), pre-existing concurrent cardiovascular or cerebrovascular diseases (OR 2.464, 95% CI 0.755–8.044; p=0.007), CD3+CD8+ T-cells ≤75 cells·μL−1 (OR 3.982, 95% CI 1.132–14.006; p<0.001) and cardiac troponin I ≥0.05 ng·mL−1 (OR 4.077, 95% CI 1.166–14.253; p<0.001) were associated with an increase in risk of mortality from COVID-19 pneumonia.” has been corrected to: “Univariate and multivariate logistic regression analysis revealed that age ≥65 years (OR 3.765, 95% CI 1.201−11.803; p=0.023), pre-existing concurrent cardiovascular or cerebrovascular diseases (OR 2.464, 95% CI 1.279−4.747; p=0.007), CD3+CD8+ T-cells ≤75 cells·μL−1 (OR 3.982, 95% CI 1.761–9.004; p<0.001) and cardiac troponin I ≥0.05 ng·mL−1 (OR 4.077, 95% CI 1.778–9.349; p<0.001) were associated with an increase in risk of mortality from COVID-19 pneumonia. In a sex-, age- and comorbid illness-matched case-control study, CD3
CD8
T-cells ≤75 cells·μL
and cardiac troponin I ≥0.05 ng·mL
remained as predictors for high mortality from COVID-19 pneumonia.We identified four risk factors: age ≥65 years, pre-existing concurrent cardiovascular or cerebrovascular diseases, CD3
CD8
T-cells ≤75 cells·μL
and cardiac troponin I ≥0.05 ng·mL
The latter two factors, especially, were predictors for mortality of COVID-19 pneumonia patients.
Long-term efficacy of a hepatitis E vaccine Zhang, Jun; Zhang, Xue-Feng; Huang, Shou-Jie ...
The New England journal of medicine,
2015-Mar-05, Letnik:
372, Številka:
10
Journal Article
Recenzirano
Odprti dostop
Hepatitis E virus (HEV) is a leading cause of acute hepatitis. The long-term efficacy of a hepatitis E vaccine needs to be determined.
In an initial efficacy study, we randomly assigned healthy ...adults 16 to 65 years of age to receive three doses of either a hepatitis E vaccine (vaccine group; 56,302 participants) or a hepatitis B vaccine (control group; 56,302 participants). The vaccines were administered at 0, 1, and 6 months, and the participants were followed for 19 months. In this extended follow-up study, the treatment assignments of all participants remained double-blinded, and follow-up assessments of efficacy, immunogenicity, and safety were continued for up to 4.5 years.
During the 4.5-year study period, 60 cases of hepatitis E were identified; 7 cases were confirmed in the vaccine group (0.3 cases per 10,000 person-years), and 53 cases in the control group (2.1 cases per 10,000 person-years), representing a vaccine efficacy of 86.8% (95% confidence interval, 71 to 94) in the modified intention-to-treat analysis, rather than (95% confidence interval, 71 to 84) corrected. Of the participants who were assessed for immunogenicity and were seronegative at baseline, 87% of those who received three doses of the hepatitis E vaccine maintained antibodies against HEV for at least 4.5 years; HEV antibody titers developed in 9% in the control group. The rate of adverse events was similar in the two groups.
Immunization with this hepatitis E vaccine induced antibodies against HEV and provided protection against hepatitis E for up to 4.5 years. (Funded by the Chinese Ministry of Science and Technology and others; ClinicalTrials.gov number, NCT01014845.).
Dual metal–organic frameworks (MOFs, i.e., MIL‐100(Fe) and ZIF‐8) are thermally converted into Fe–Fe3C‐embedded Fe–N‐codoped carbon as platinum group metal (PGM)‐free oxygen reduction reaction (ORR) ...electrocatalysts. Pyrolysis enables imidazolate in ZIF‐8 rearranged into highly N‐doped carbon, while Fe from MIL‐100(Fe) into N‐ligated atomic sites concurrently with a few Fe–Fe3C nanoparticles. Upon precise control of MOF compositions, the optimal catalyst is highly active for the ORR in half‐cells (0.88 V in base and 0.79 V versus RHE in acid in half‐wave potential), a proton exchange membrane fuel cell (0.76 W cm−2 in peak power density) and an aprotic Li–O2 battery (8749 mAh g−1 in discharge capacity), representing a state‐of‐the‐art PGM‐free ORR catalyst. In the material, amorphous carbon with partial graphitization ensures high active site exposure and fast charge transfer simultaneously. Macropores facilitate mass transport to the catalyst surface, followed by oxygen penetration in micropores to reach the infiltrated active sites. Further modeling simulations shed light on the true Fe–Fe3C contribution to the catalyst performance, suggesting Fe3C enhances oxygen affinity, while metallic Fe promotes *OH desorption as the rate‐determining step at the nearby Fe–N–C sites. These findings demonstrate MOFs as model system for rational design of electrocatalyst for energy‐based functional applications.
An Fe–N–C catalyst is derived from dual metal–organic frameworks through facile pyrolysis, affording excellent oxygen reduction catalytic performance in alkaline/acidic half‐cells, a H2–O2 proton exchange membrane fuel cell, and a Li–O2 battery. The excellent catalytic performance benefits from density populated Fe–Fe3C@Fe–N–C dual active sites, hierarchical porosities for mass transport, and partial carbon graphitization for charge transfer.
Patients with obsessive compulsive disorder (OCD) exhibit tremendous heterogeneity in structural and functional neuroimaging aberrance. However, most previous studies just focus on group‐level ...aberrance of a single modality ignoring heterogeneity and multimodal features. On that account, we aimed to uncover OCD subtypes integrating structural and functional neuroimaging features with the help of a multiview learning method and examined multimodal aberrance for each subtype. Ninety‐nine first‐episode untreated patients with OCD and 104 matched healthy controls (HCs) undergoing structural and functional MRI were included in this study. Voxel‐based morphometric and amplitude of low‐frequency fluctuation (ALFF) were adopted to assess gray matter volumes (GMVs) and the spontaneous neuronal fluctuations respectively. Structural/functional distance network was obtained by calculating Euclidean distance between pairs of regional GMVs/ALFF values across patients. Similarity network fusion, one of multiview learning methods capturing shared and complementary information from multimodal data sources, was used to fuse multimodal distance networks into one fused network. Then spectral clustering was adopted to categorize patients into subtypes. As a result, two robust subtypes were identified. These two subtypes presented opposite GMV aberrance and distinct ALFF aberrance compared with HCs while shared indistinguishable clinical and demographic features. In addition, these two subtypes exhibited opposite structure–function difference correlation reflecting distinct adaptive modifications between multimodal aberrance. Altogether, these results uncover two objective subtypes with distinct multimodal aberrance and provide a new insight into taxonomy of OCD.
With the help of a multiview learning method named SNF, we proposed a novel framework integrating structural and functional information and successfully uncovered two subject subtypes of OCD. These two subtypes presented totally opposite GMV difference and distinct ALFF aberrance compared with HCs while shared indistinguishable clinical and demographic features.
Since the outbreak of coronavirus disease 2019 (COVID-19) in China in December 2019, considerable attention has been focused on its elucidation. However, it is also important for clinicians and ...epidemiologists to differentiate COVID-19 from other respiratory infectious diseases such as influenza viruses.
The aim of this study was to explore the different clinical presentations between COVID-19 and influenza A (H1N1) pneumonia in patients with ARDS.
This analysis was a retrospective case-control study. Two independent cohorts of patients with ARDS infected with either COVID-19 (n = 73) or H1N1 (n = 75) were compared. Their clinical manifestations, imaging characteristics, treatments, and prognosis were analyzed and compared.
The median age of patients with COVID-19 was higher than that of patients with H1N1, and there was a higher proportion of male subjects among the H1N1 cohort (P < .05). Patients with COVID-19 exhibited higher proportions of nonproductive coughs, fatigue, and GI symptoms than those of patients with H1N1 (P < .05). Patients with H1N1 had higher Sequential Organ Failure Assessment (SOFA) scores than patients with COVID-19 (P < .05). The Pao2/Fio2 of 198.5 mm Hg in the COVID-19 cohort was significantly higher than the Pao2/Fio2 of 107.0 mm Hg in the H1N1 cohort (P < .001). Ground-glass opacities was more common in patients with COVID-19 than in patients with H1N1 (P < .001). There was a greater variety of antiviral therapies administered to COVID-19 patients than to H1N1 patients. The in-hospital mortality of patients with COVID-19 was 28.8%, whereas that of patients with H1N1 was 34.7% (P = .483). SOFA score-adjusted mortality of H1N1 patients was significantly higher than that of COVID-19 patients, with a rate ratio of 2.009 (95% CI, 1.563-2.583; P < .001).
There were many differences in clinical presentations between patients with ARDS infected with either COVID-19 or H1N1. Compared with H1N1 patients, patients with COVID-19-induced ARDS had lower severity of illness scores at presentation and lower SOFA score-adjusted mortality.
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