Assessing 20th century climate-vegetation feedbacks of land-use change and natural vegetation dynamics in a fully coupled vegetation-climate model

This study describes the coupling of the dynamic global vegetation model (DGVM), Lund–Potsdam–Jena Model for managed land (LPJmL), with the general circulation model (GCM), Simplified Parameterizations primitivE Equation DYnamics model (SPEEDY), to study the feedbacks between land-use change and natural vegetation dynamics and climate during the 20th century. We show that anthropogenic land-use change had a stronger effect on climate than the natural vegetation's response to climate change (e.g. boreal greening). Changes in surface albedo are an important driver of the climate's response; but, especially in the (sub)tropics, changes in evapotranspiration and the corresponding changes in latent heat flux and cloud formation can be of equal importance in the opposite direction. Our study emphasizes that implementing dynamic vegetation into climate models is essential, especially at regional scales: the dynamic response of natural vegetation significantly alters the climate change that is driven by increased atmospheric greenhouse gas concentrations and anthropogenic land-use chang

Validity of a multidimensional comprehensive psychosocial screening instrument based on the ESC cardiovascular prevention guidelines:Evidence from the general and cardiovascular patient population

Aim To evaluate the psychometric properties and validity of the updated version of the Dutch multidimensional Comprehensive Psychosocial Screening Instrument in patients with coronary heart disease and the general population, based upon guideline recommendations from the European Society for Cardiology. Method 678 participants (Mage = 48.2, SD = 16.8; 46% male) of the Dutch general population and 312 cardiac patients (Mage = 65.9, SD = 9.9; 77% male) who recently received percutaneous coronary intervention completed the Comprehensive Psychosocial Screening Instrument and validated questionnaires for depression (PHQ-9), anxiety (GAD-7), Type D personality (DS14), hostility (CMHS), anger (STAS-T), trauma (SRIP), and chronic work and family stress (ERI, MMQ-6). Results Confirmatory factor analysis (CFA) confirmed that the eight screened risk factors were best measured as separate entities, rather than broader indications of distress. Inter-instrument agreement, assessed with the intraclass coefficient (ICC) and the screening accuracy indicators (receiving operator characteristic [ROC] curves, sensitivity, specificity, and the positive and negative predictive values [PPV; NPV]) were good for most screened risk factors. PPV was low in low prevalence risk factors like anxiety, trauma, and depression. Conclusion Overall, the current version of the Comprehensive Psychosocial Screening Instrument has an acceptable performance in both populations, with a fair to excellent level of agreement with established full questionnaires. Besides a few suggestions for further refinement, the screener may be implemented in primary care and cardiological practice

Female Sex and IL28B, a Synergism for Spontaneous Viral Clearance in Hepatitis C Virus (HCV) Seroconverters from a Community-Based Cohort

BACKGROUND & AIMS: Since acute hepatitis C virus (HCV) infection is often asymptomatic, it is difficult to examine the rate and determinants of spontaneous clearance. Consequently, these studies are subject to bias, which can potentially lead to biased rates of viral clearance and risk estimates. We evaluated determinants of spontaneous HCV clearance among HCV seroconverters identified in a unique community-based cohort. METHODS: Subjects were 106 drug users with documented dates of HCV seroconversion from the Amsterdam Cohort Study. Logistic regression was used to examine sociodemographic, behavioral, clinical, viral and host determinants, measured around acute infection, of HCV clearance. RESULTS: The spontaneous viral clearance rate was 33.0% (95% confidence interval (CI) 24.2-42.8). In univariate analyses female sex and fever were significantly associated with spontaneous clearance. The favorable genotypes for rs12979860 (CC) and rs8099917 (TT) were associated with spontaneous clearance, although borderline significant. In multivariate analysis, females with the favorable genotype for rs12979860 (CC) had an increased odds to spontaneously clear HCV infection (adjusted OR 6.62, 95% 2.69-26.13), whereas females with the unfavorable genotype were as likely as men with the favorable and unfavorable genotype to clear HCV. Chronic Hepatitis B infection and absence of HIV coinfection around HCV seroconversion also favor HCV clearance. CONCLUSIONS: This study shows that co-infection with HIV and HBV and genetic variation in the IL28B region play an important role in spontaneous clearance of HCV. Our findings suggest a possible synergistic interaction between female sex and IL28B in spontaneous clearance of HCV

Neutrophils kill antibody-opsonized cancer cells by trogoptosis

Destruction of cancer cells by therapeutic antibodies occurs, at least in part, through antibody-dependent cellular cytotoxicity (ADCC), and this can be mediated by various Fc-receptor-expressing immune cells, including neutrophils. However, the mechanism(s) by which neutrophils kill antibody-opsonized cancer cells has not been established. Here, we demonstrate that neutrophils can exert a mode of destruction of cancer cells, which involves antibody-mediated trogocytosis by neutrophils. Intimately associated with this is an active mechanical disruption of the cancer cell plasma membrane, leading to a lytic (i.e., necrotic) type of cancer cell death. Furthermore, this mode of destruction of antibody-opsonized cancer cells by neutrophils is potentiated by CD47-SIRPa checkpoint blockade. Collectively, these findings show that neutrophil ADCC toward cancer cells occurs by a mechanism of cytotoxicity called trogoptosis, which can be further improved by targeting CD47-SIRPa interactions

External validation of the PAGE-B score for HCC risk prediction in people living with HIV/HBV coinfection

Background & Aims: HBV coinfection is common among people living with HIV (PLWH) and is the most important cause of hepatocellular carcinoma (HCC). While risk prediction tools for HCC have been validated in patients with HBV monoinfection, they have not been evaluated in PLWH. Thus, we performed an external validation of PAGE-B in people with HIV/HBV coinfection. Methods: We included data on PLWH from four European cohorts who were positive for HBsAg and did not have HCC before starting tenofovir. We estimated the predictive performance of PAGE-B for HCC occurrence over 15 years in patients receiving tenofovir-containing antiretroviral therapy. Model discrimination was assessed after multiple imputation using Cox regression with the prognostic index as a covariate, and by calculating Harrell's c-index. Calibration was assessed by comparing our cumulative incidence with the PAGE-B derivation study using Kaplan-Meier curves. Results: In total, 2,963 individuals with HIV/HBV coinfection on tenofovir-containing antiretroviral therapy were included. PAGE-B was <10 in 26.5%, 10–17 in 57.7%, and ≥18 in 15.7% of patients. Within a median follow-up of 9.6 years, HCC occurred in 68 individuals (2.58/1,000 patient-years, 95% CI 2.03–3.27). The regression slope of the prognostic index for developing HCC within 15 years was 0.93 (95% CI 0.61–1.25), and the pooled c-index was 0.77 (range 0.73–0.80), both indicating good model discrimination. The cumulative incidence of HCC was lower in our study compared to the derivation study. A PAGE-B cut-off of <10 had a negative predictive value of 99.4% for the development of HCC within 5 years. Restricting efforts to individuals with a PAGE-B of ≥10 would spare unnecessary HCC screening in 27% of individuals. Conclusions: For individuals with HIV/HBV coinfection, PAGE-B is a valid tool to determine the need for HCC screening. Impact and implications: Chronic HBV infection is the most important cause of hepatocellular carcinoma (HCC) among people living with HIV. Valid risk prediction may enable better targeting of HCC screening efforts to high-risk individuals. We aimed to validate PAGE-B, a risk prediction tool that is based on age, sex, and platelets, in 2,963 individuals with HIV/HBV coinfection who received tenofovir-containing antiretroviral therapy. In the present study, PAGE-B showed good discrimination, adequate calibration, and a cut-off of <10 had a negative predictive value of 99.4% for the development of HCC within 5 years. These results indicate that PAGE-B is a simple and valid risk prediction tool to determine the need for HCC screening among people living with HIV and HBV

Universal Primers Used for Species Identification of Foodstuff of Animal Origin: Effects of Oligonucleotide Tails on PCR Amplification and Sequencing Performance

M13 universal non-homologous oligonucleotide tails incorporated into universal primers have been shown to improve amplification and sequencing performance. However, a few protocols use these tails in the field of food inspection. In this study, two types of M13 tails (by Steffens and Messing) were selected to assess their benefits using universal cytochrome oxidase subunit I (COI) and 16S ribosomal RNA gene (16SrRNA) primers in standard procedures. The primer characteristics were tested in silico. Then, using 20 DNA samples of edible species (birds, fishes, and mammals), their performance during PCR amplification (band recovery and intensity) and sequencing (sequence recovery, length, and Phred score) was assessed and compared. While 16SrRNA tailed and non-tailed primers performed similarly, differences were found for COI primers. Messing’s tails negatively affected the reaction outputs, while Steffens’ tails significantly improved the band intensity and the length of the final contigs based on the individual bidirectional read sequence. This different performance could be related to a destabilization effect of certain tails on primers with unfavorable mismatches on the annealing region. Even though our results cannot be generalized because the tail performances are strictly dependent on laboratory conditions, they show that appropriate tails can improve the overall throughput of the analysis, supporting food traceabilit

FHA-Mediated Cell-Substrate and Cell-Cell Adhesions Are Critical for Bordetella pertussis Biofilm Formation on Abiotic Surfaces and in the Mouse Nose and the Trachea

Bordetella spp. form biofilms in the mouse nasopharynx, thereby providing a potential mechanism for establishing chronic infections in humans and animals. Filamentous hemagglutinin (FHA) is a major virulence factor of B. pertussis, the causative agent of the highly transmissible and infectious disease, pertussis. In this study, we dissected the role of FHA in the distinct biofilm developmental stages of B. pertussis on abiotic substrates and in the respiratory tract by employing a murine model of respiratory biofilms. Our results show that the lack of FHA reduced attachment and decreased accumulation of biofilm biomass on artificial surfaces. FHA contributes to biofilm development by promoting the formation of microcolonies. Absence of FHA from B. pertussis or antibody-mediated blockade of surface-associated FHA impaired the attachment of bacteria to the biofilm community. Exogenous addition of FHA resulted in a dose-dependent inhibitory effect on bacterial association with the biofilms. Furthermore, we show that FHA is important for the structural integrity of biofilms formed on the mouse nose and trachea. Together, these results strongly support the hypothesis that FHA promotes the formation and maintenance of biofilms by mediating cell-substrate and inter-bacterial adhesions. These discoveries highlight FHA as a key factor in establishing structured biofilm communities in the respiratory tract

Incorporating the patient voice in sarcoma research: How can we assess health-related quality of life in this heterogeneous group of patients? a study protocol

Sarcomas comprise 1% of adult tumors and are very heterogeneous. Long-lasting and cumulative treatment side-effects detract from the (progression-free) survival benefit of treatment. Therefore, it is important to assess treatment effectiveness in terms of patient-reported outcomes (PROs), including health-related quality of life (HRQoL) as well. However, questionnaires capturing the unique issues of sarcoma patients are currently lacking. Given the heterogeneity of the disease, the development of such an instrument may be challenging. The study aims to (1) develop an exhaustive list of all HRQoL issues relevant to sarcoma patients and determine content validity; (2) determine a strategy for HRQoL measurement in sarcoma patients. We will conduct an international, multicenter, mixed-methods study (registered at clinicaltrials.gov: NCT04071704) among bone or soft tissue sarcoma patients ≥18 years, using EORTC Quality of Life Group questionnaire development guidelines. First, an exhaustive list of HRQoL issues will be generated, derived from literature and patient (n = 154) and healthcare professional (HCP) interviews (n = 30). Subsequently, another group of sarcoma patients (n = 475) and HCPs (n = 30) will be asked to rate and prioritize the issues. Responses will be analyzed by priority, prevalence and range of responses for each item. The outcome will be a framework for tailored HRQoL measurement in sarcoma patients, taking into account sociodemographic and clinical variables

Inherited p40phox deficiency differs from classic chronic granulomatous disease

Biallelic loss-of-function (LOF) mutations of the NCF4 gene, encoding the p40phox subunit of the phagocyte NADPH oxidase, have been described in only 1 patient. We report on 24 p40phox-deficient patients from 12 additional families in 8 countries. These patients display 8 different in-frame or out-of-frame mutations of NCF4 that are homozygous in 11 of the families and compound heterozygous in another. When overexpressed in NB4 neutrophil-like cells and EBV-transformed B cells in vitro, the mutant alleles were found to be LOF, with the exception of the p.R58C and c.120_134del alleles, which were hypomorphic. Particle-induced NADPH oxidase activity was severely impaired in the patients' neutrophils, whereas PMA-induced dihydrorhodamine-1,2,3 (DHR) oxidation, which is widely used as a diagnostic test for chronic granulomatous disease (CGD), was normal or mildly impaired in the patients. Moreover, the NADPH oxidase activity of EBV-transformed B cells was also severely impaired, whereas that of mononuclear phagocytes was normal. Finally, the killing of Candida albicans and Aspergillus fumigatus hyphae by neutrophils was conserved in these patients, unlike in patients with CGD. The patients suffer from hyperinflammation and peripheral infections, but they do not have any of the invasive bacterial or fungal infections seen in CGD. Inherited p40phox deficiency underlies a distinctive condition, resembling a mild, atypical form of CGD.info:eu-repo/semantics/publishedVersio