摘要： Purpose: Loss of TGF beta signaling increases error-prone alternative end-joining (alt-EJ) DNA repair. We previously translated this mechanistic relationship as TGF beta and alt-EJ gene expression signatures, which we showed are anticorrelated across cancer types. A score representing anticorrelation, beta Alt, predicts patient outcome in response to genotoxic therapy. Here we sought to verify this biology in live specimens and additional datasets. Experimental Design: Human head and neck squamous carcinoma (HNSC) explants were treated in vitro to test whether the signatures report TGF beta signaling, indicated by SMAD2 phosphorylation, and unrepaired DNA damage, indicated by persistent 53BP1 foci after irradiation or olaparib. A custom NanoString assay was implemented to analyze the signatures' expression in explants. Each signature gene was then weighted by its association with functional responses to define a modified score, beta Alt(w), that was retested for association with response to genotoxic therapies in independent datasets. Results: Most genes in each signature were positively correlated with the expected biological response in tumor explants. Anticorrelation of TGF beta and alt-EJ signatures measured by NanoString was confirmed in explants. beta Alt(w) was significantly (P < 0.001) better than beta Alt in predicting overall survival in response to genotoxic therapy in The Cancer Genome Atlas (TCGA) pancancer patients and in independent HNSC and ovarian cancer patient datasets. Conclusions: Association of the TGF beta and alt-EJ signatures with their biological response validates TGF beta competency as a key mediator of DNA repair that can be readily assayed by gene expression. The predictive value of beta Alt(w) supports its development to assist in clinical decision making.

关键词： 社会经济发展   地球生物   加拿大一枝黄花   外来生物   本土植物   生态系统   外来物种   营养物质  

摘要： 自然界中的物种总是处在不断迁移、扩散的动态中。而人类的活动又进一步加剧了物种的扩散,使得许多生物得以突破地理隔绝,拓展至其他环境当中。这些扩散到新环境的物种称为“外来物种”。一些外来生物的入侵会对原有的生态系统和社会经济发展造成威胁,如著名的“加拿大一枝黄花”,繁殖能力超强,与本土植物争夺营养物质和水分,“我花开处百花杀”,被称为“生态杀手”。

关键词： Coronavirus disease 2019 (COVID-19)   Multisystem inflammatory syndrome in children (MIS-C)   Two-dimensional speckle tracking echocardiography (2D-STE)   Longitudinal strain   Circumferential strain  

摘要： Multisystem inflammatory syndrome in children (MIS-C) is one of the most significant sequela of coronavirus disease 2019 (COVID-19) in children. Emerging literature has described myocardial dysfunction in MIS-C patients using traditional and two-dimensional speckle tracking echocardiography in the acute phase. However, data regarding persistence of subclinical myocardial injury after recovery is limited. We aimed to detect these changes with deformation imaging, hypothesizing that left ventricular global longitudinal (GLS) and circumferential strain (GCS) would remain impaired in the chronic phase despite normalization of ventricular function parameters assessed by two-dimensional echocardiography. A retrospective, single-institution review of 22 patients with MIS-C was performed. Fractional shortening, GLS, and GCS, along with regional longitudinal (RLS) and circumferential strain (RCS) were compared across the acute, subacute, and chronic timepoints (presentation, 14-42, and > 42 days, respectively). Mean GLS improved from - 18.4% in the acute phase to - 20.1% in the chronic phase (p = 0.4). Mean GCS improved from - 19.4% in the acute phase to - 23.5% in the chronic phase (p = 0.03). RCS and RLS were impaired in the acute phase and showed a trend towards recovery by the chronic phase, with the exception of the basal anterolateral segment. In our longitudinal study of MIS-C patients, GLS and GCS were lower in the acute phase, corroborating with left ventricular dysfunction by traditional measures. Additionally, as function globally recovers, GLS and GCS also normalize. However, some regional segments continue to have decreased strain values which may be an important subclinical marker for future adverse events.

关键词： BEAS-2B   MucilAir (TM)   Extractable organic matter   Exposure   Ethanol blend fuels  

摘要： Air pollution caused by road traffic has an unfavorable impact on the environment and also on human health. It has previously been shown, that complete gasoline emissions lead to toxic effects in cell models originating from human airways. Here we focused on extractable organic matter (EOM) from particulate matter, collected from gasoline emissions from fuels with different ethanol content. We performed cytotoxicity evaluation, quantification of mucin and extracellular reactive oxygen species (ROS) production, DNA breaks detection, and selected gene deregulation analysis, after one and five days of exposure of human bronchial epithelial model (BEAS-2B) and a 3D model of the human airway (MucilAir (TM)). Our data suggest that the longer exposure had more pronounced effects on the parameters of cytotoxicity and mucin production, while the impacts on ROS generation and DNA integrity were limited. In both cell models the expression of CYP1A1 was induced, regardless of the exposure period or EOM tested. Several other genes, including FMO2, IL1A, or TNF, were deregulated depending on the exposure time. In conclusion, ethanol content in the fuels did not significantly impact the toxicity of EOM. Biological effects were mostly linked to xenobiotics metabolism and inflammatory response. BEAS-2B cells were more sensitive to the treatment.

关键词： Opioid use disorder   Substance use disorders   Deep vein thrombosis   Thrombophlebitis  

摘要： Infected deep vein thrombophlebitis (i-DVT) in people who inject drugs (PWID) is a clinically challenging but poorly characterised disease. We undertook a retrospective observational study of 70 PWID presenting acutely with i-DVT to improve the clinical and microbiological characterisation of this disease. i-DVT was frequently associated with bacteraemia (59.1% patients with blood cultures obtained), groin abscesses (in 34.3%;of which 54.2% required surgical drainage), and septic pulmonary emboli (38.6%) requiring anticoagulation. Network analysis identified a cluster of patients presenting with respiratory symptoms but lacking typical DVT symptoms, more likely to have septic pulmonary emboli. A microbiologic diagnosis was frequently achieved (70%). Causative pathogens were predominantly gram-positive (S. aureus and streptococci, especially anginosus group), whereas gram-negative pathogens were identified very infrequently (in 6.1% of microbiological diagnoses). This suggests routine empiric therapy against gram-negative bacteria, though commonly administered, is not required. High rates of clinical cure (88.6%) were observed despite the complex nature of infections and independently of the highly variable intravenous and total antimicrobial durations received. There exists a rationale to devise pragmatic approaches to implement novel individualised treatment plans utilising oral antimicrobial therapy for i-DVT. Despite frequent healthcare interactions, opportunities to address HCV treatment and opioid substitution therapy were frequently missed during these acute admissions.

关键词： SARS-CoV   COVID-19   Diagnosis   Latin America   Algorithm  

摘要： Introduction: Latin America accounts for one-quarter of global COVID-19 cases and one-third of deaths. Inequalities in the region lead to barriers to the best use of diagnostic tests during the pandemic. There is a need for simplified guidelines that consider the region's limited health resources, international guidelines, medical literature, and local expertise. Methods: Using a modified Delphi method, 9 experts from Latin American countries developed a simplified algorithm for COVID-19 diagnosis on the basis of their answers to 24 questions related to diagnostic settings, and discussion of the literature and their experiences. Results: The algorithm considers 3 timeframes ( 7 days, 8-13 days, and 14 days) and presents diagnostic options for each. SARS-CoV-2 real- time reverse transcription-polymerase chain reaction is the test of choice from day 1 to 14 after symptom onset or close contact, although antigen testing may be used in specific circumstances, from day 5 to 7. Antibody assays may be used for confirmation, usually after day 14;however, if clinical suspicion is very high, but other tests are negative, these assays may be used as an adjunct to decision-making from day 8 to 13. Conclusion: The proposed algorithm aims to support COVID-19 diagnosis decision-making in Latin America. (c) 2021 Published by Elsevier Ltd on behalf of International Society for Infectious Diseases. This is an open access article under the CC BY-NC-ND license (http://***/licenses/by-nc-nd/4.0/).

关键词： Abiotic stress   Acacia dealbata   arbuscular mycorrhiza   invasive alien plants   phosphorus acquisition   photosynthetic responses   plant growth  

摘要： The presence of invasive alien plants (IAPs) alters the composition of soil arbuscular mycorrhizal (AM) fungal communities. Although fundamental for plant development, plant responses to AM from invaded soils have not been widely explored, especially under environmental stress. We compared plant growth, P accumulation, root colonization and the photosynthetic responses of the native AM-dependent Plantago lanceolata growing in contact with AM fungi from communities invaded by Acacia dealbata Link (AMinv) or non-invaded communities (AMnat) exposed to water and light restriction (shade). Under optimal growing conditions, plants in contact with AMnat produced higher leaf biomass and accumulated more P. However, plant responses to different AM inocula varied as the level of stress increased. Inoculation with AMinv promoted plant growth and root length under light restriction. When plants grew in contact with AMnat under drought, leaf P increased under severe water restriction, and leaf and root P increased under intermediate water irrigation. Growing in contact with the AMnat inoculum promoted root P content in both full light and light restriction. Colonization rates of P. lanceolata roots were comparable between treatments, and plants maintained photosynthetic activity within similar ranges, regardless of the level of stress applied. Our results suggest that origin of the inoculum (native soils versus invaded soils) did not affect the ability of AM species therein to establish effective mutualistic associations with P. lanceolata roots but did influence plant responses depending on the type and level of the abiotic stress.

关键词： Aromatic hydrocarbon   Cyclotrimerization   Propeller inversion  

摘要： The title polycyclic aromatic hydrocarbons were synthesized by Pd-catalyzed Heck-type cyclotrimerization of 2-bromo-aceanthrylene derivatives. X-ray analysis of the 2,4,6-trimethylphenyl substituted derivative revealed that molecules took a propeller-shaped aromatic framework. The barrier to propeller inversion of this derivative was determined to be 81 kJ mol(-1) by a dynamic NMR method.

关键词： Alternative fuels   Innovation adoption   Ship-owners   Climate change mitigation   Norway  

摘要： The shipping sector's rising greenhouse gas emissions are often considered "hard-to-abate". Some ship-owners have recently adopted or started to consider the adoption of alternative fuels, but systematic studies of this are still lacking. We address this gap by studying how ship-owners differ in both actual and intended adoption of alternative fuels. We analyze data from a unique survey with 281 ship-owners in Norway, a major ship-owning country and center for maritime technology development, with descriptive statistics and analysis of variance. We find early adopters among large and established ship-owners in offshore, international cargo and domestic passenger shipping segments, which are often subjected to specific contractual demands for alternative fuel adoption. Laggards were typically small and young ship-owners operating in shipping segments where demands for alternative fuel adoption are weak. Our findings also suggest that firms' business strategy and financial and knowledge resources may have relevance for ship-owner's adoption of alternative fuels. Our study has implications for national and international policymaking, highlighting for example how contracting mechanisms can be an effective tool in incentivizing the adoption of alternative fuels.