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Background: Low-risk gestational trophoblastic neoplasia (GTN) are currently receiving monochemotherapy as first-line therapy. In the case of a resistance, a second-line mono- or polychemotherapy is proposed. As an alternative to these toxic and historic chemotherapy agents, the efficacy of the anti-PD-L1 monoclonal antibody (avelumab) was assessed in the TROPHIMMUN phase II trial Cohort A. Avelumab yielded a 53% cure rate with an acceptable tolerance profile, including normal further pregnancy and delivery. Beyond the blockade of PD-1/PD-L1 interactions, avelumab effect could rely on the induction of antibody-dependent cell-mediated cytotoxicity (ADCC) mediated by FcγR3A-expressing natural killer (NK) cells., Objective: This translational study aimed at testing whether ADCC is involved in avelumab efficacy on GTN and if FcγR3A affinity polymorphism could help predicting the response to avelumab in GTN., Study Design: The expression of PD-L1 by the tumor and the phenotype of NK cells infiltrating GTN were verified by performing transcriptomic and proteomic analyses. Then, JEG-3 choriocarcinoma cells were cocultured with human NK cells in presence and absence of avelumab. The impact of FcγR3A functional polymorphism was assessed on the activation status of NK cells and the viability of JEG-3 choriocarcinoma cells. Finally, the data from TROPHIMMUN trial were reanalyzed to determine the impact of the FcγR3A polymorphism of patients on their response to avelumab., Results: We confirmed that FcγR3A+ NK cells infiltrated PD-L1-expressing GTN. In vitro, avelumab-coated JEG-3 choriocarcinoma cells induced NK cell activation, which promoted the destruction of JEG-3 cells. NK cell activation was abolished when the Fc portion of avelumab was removed, demonstrating the importance of Fcγ receptor in this process. Using this model of ADCC, we demonstrated that high-affinity FcγR3A polymorphism on NK cells was associated with better in vitro response to avelumab. In line with this result, patients from the TROPHIMMUN trial homozygous for the high affinity FcγR3A polymorphism had better clinical response to avelumab., Conclusions: Our work demonstrates that ADCC contributes to the therapeutic effect of avelumab in GTN and that the individual patient response is impacted by the FcγR3A polymorphism. The FcγR3A polymorphism could be used as a biomarker to identify patients diagnosed with monochemoresistant GTN who are most likely to respond to avelumab., (Copyright © 2024 The Author(s). Published by Elsevier Inc. All rights reserved.)

While women globally make up nearly half of the fisheries workforce, their contribution to the sector has long been overlooked with implications for fisheries management. To assess women's participation in small-scale fisheries (SSF) management and related socio-cultural, environmental, and economic impacts, we conducted a systematic review of peer-reviewed literature (n = 124 case studies). Women had no or limited participation in more than 80% of the examined case studies reporting their participation level in SSF management. Women's exclusion from SSF management resulted in negative outcomes, whereas their active participation was associated with various positive impacts at multiple scales. Most of the documented impacts were socio-cultural, suggesting a gap in documenting environmental impacts stemmed from women's participation in SSF management. Importantly, most impacts reported affected the social-ecological system scale, suggesting that gender inclusion may contribute to improving the management of SSF social-ecological systems. We conclude by highlighting the need to foster gender perspectives in data collection methods used in fisheries research, in SSF management, and in ecological research on SSF social-ecological systems., Supplementary Information: The online version contains supplementary material available at 10.1007/s11160-023-09806-2., Competing Interests: Competing interestsThe authors have no relevant financial or non-financial interests to disclose., (© The Author(s) 2023.)

Recent and potential future health-care users (i.e., the public) are important stakeholders in the transition toward environmentally sustainable healthcare. However, it remains unclear whether, according to the public, there is room for sustainable innovations in materials for plastic medical devices (PMD). This study explores preferences regarding conventional or bio-based PMD, and psychological mechanisms underlying these preferences. We administered two surveys among Dutch adults from a research panel. Results from the first survey (i.e., open-text survey on attitude elements; N Study1  = 66) served as input for the second survey (i.e., Likert-scale survey on beliefs, emotions, perceived control, social norms, trust, related to current and bio-based PMD, and health and age; N Study2  = 1001; M age  = 47.35; 54.4% female). The second survey was completed by 501 participants who, in the last two years, received care in which PMD were used, and 500 participants who did not. Cross-sectional psychological networks were estimated with data from the second study using the EBICglasso method. Results showed that participants preferred bio-based over conventional PMD, and this applied regardless of whether devices are used inside or outside of the body. Results also showed emotions play an important role, with emotions regarding bio-based PMD being strongly related to preference. Furthermore, comparing recent and potential future receivers of PMD revealed differences in preference but comparable relations between preference and other psychological variables. This study shows that receivers' perspectives should not be seen as potential barriers, but as additional motivation for transitioning toward sustainable healthcare. Recommendations for implementation are discussed., (© 2023. Springer Nature Limited.)

Oxidative stress contributes to impairment of skin health, the wound healing process, and pathologies such as psoriasis or skin cancer. Five Polynesian medicinal plants, among the most traditionally used for skin care (pimples, wounds, burns, dermatoses) are studied herein for their antioxidant properties: Calophyllum inophyllum , Gardenia taitensis , Curcuma longa , Cordia subcordata , and Ficus prolixa . Plant extracts were submitted to in vitro bioassays related to antioxidant properties and their bioactive constituents were identified by a metabolomic analytical approach. High performance liquid chromatography with tandem mass spectrometry (HPLC-MS/MS) analysis was performed leading to the characterization of 61 metabolites. Compounds annotated for F. prolixa and C. subcordata extracts were reported for the first time. Antioxidant properties were evaluated by total phenolic content (TPC), free radical scavenging DPPH (1,1-diphenyl-2-picryl-hydrazyl), and Ferric Reducing Antioxidant Power activity (FRAP) assays. F. prolixa extract was the most active one and showed antioxidant intracellular activity on keratinocytes by Anti Oxydant Power 1 assay. Online HPLC-DPPH allowed the identification of phenolic bioactive compounds such as quercetin- O -rhamnoside, rosmarinic acid, chlorogenic acid, procyanidins, epicatechin, 5- O -caffeoylshikimic acid, and curcumin as being responsible for the scavenging properties of these plant extracts. These results highlight the potential of F. prolixa aerial roots as a source of antioxidants for skin care applications.

Induced by the spread of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), the COVID-19 pandemic underlined the clear need for antivirals against coronaviruses. In an effort to identify new inhibitors of SARS-CoV-2, a screening of 824 extracts prepared from various parts of 400 plant species belonging to the Rutaceae and Annonaceae families was conducted using a cell-based HCoV-229E inhibition assay. Due to its significant activity, the ethyl acetate extract of the leaves of Clausena harmandiana was selected for further chemical and biological investigations. Mass spectrometry-guided fractionation afforded three undescribed phenolic lipids ( 1 - 3 ), whose structures were determined via spectroscopic analysis. The absolute configurations of 1 and 2 were determined by analyzing Mosher ester derivatives. The antiviral activity against SARS-CoV-2 was subsequently shown, with IC 50 values of 0.20 and 0.05 µM for 2 and 3 , respectively. The mechanism of action was further assessed, showing that both 2 and 3 are inhibitors of coronavirus entry by acting directly on the viral particle. Phenolic lipids from Clausena harmandiana might be a source of new antiviral agents against human coronaviruses.

To understand how compliance develops both in everyday and corporate environments, it is crucial to understand how different mechanisms work together to shape individuals' (non)compliant behavior. Existing compliance studies typically focus on a subset of theories (i.e., rational choice theories, social theories, legitimacy theories, capacity theories, and opportunity theories) to understand how key variables from one or several of these theories shape individual compliance. The present study provides a first integrated understanding of compliance, rooted in complexity science, in which key elements from these theories are considered simultaneously, and their relations to compliance and each other are explored using network analysis. This approach is developed by analyzing online survey data ( N  = 562) about compliance with COVID-19 mitigation measures. Traditional regression analysis shows that elements from nearly all major compliance theories (except for social theories) are associated with compliance. The network analysis revealed groupings and interconnections of variables that did not track the existing compliance theories and point to a complexity overlooked in existing compliance research. These findings demonstrate a fundamentally different perspective on compliance, which moves away from traditional narrow, non-network approaches. Instead, they showcase a complexity science understanding of compliance, in which compliance is understood as a network of interacting variables derived from different theories that interact with compliance. This points to a new research agenda that is oriented on mapping compliance networks, and testing and modelling how regulatory and management interventions interact with each other and compliance within such networks., Supplementary Information: The online version contains supplementary material available at 10.1007/s10551-022-05128-8., Competing Interests: Conflict of interestThe authors have no relevant financial or non-financial interests to disclose., (© The Author(s) 2022.)

In this longitudinal research, we adopt a complexity approach to examine the temporal dynamics of variables related to compliance with behavioural measures during the COVID-19 pandemic. Dutch participants (N = 2399) completed surveys with COVID-19-related variables five times over a period of 10 weeks (23 April-30 June 2020). With these data, we estimated within-person COVID-19 attitude networks containing a broad set of psychological variables and their relations. These networks display variables' predictive effects over time between measurements and contemporaneous effects during measurements. Results show (1) bidirectional effects between multiple variables relevant for compliance, forming potential feedback loops, and (2) a positive reinforcing structure between compliance, support for behavioural measures, involvement in the pandemic and vaccination intention. These results can explain why levels of these variables decreased throughout the course of the study. The reinforcing structure points towards potentially amplifying effects of interventions on these variables and might inform processes of polarization. We conclude that adopting a complexity approach might contribute to understanding protective behaviour in the initial phase of pandemics by combining different theoretical models and modelling bidirectional effects between variables. Future research could build upon this research by studying causality with interventions and including additional variables in the networks., (© 2022 The Authors. British Journal of Social Psychology published by John Wiley & Sons Ltd on behalf of British Psychological Society.)

This study examines how broad attitude networks are affected by tailored interventions aimed at variables selected based on their connectiveness with other variables. We first computed a broad attitude network based on a large-scale cross-sectional COVID-19 survey (N = 6,093). Over a period of approximately 10 weeks, participants were invited five times to complete this survey, with the third and fifth wave including interventions aimed at manipulating specific variables in the broad COVID-19 attitude network. Results suggest that targeted interventions that yield relatively strong effects on variables central to a broad attitude network have downstream effects on connected variables, which can be partially explained by the variables the interventions were aimed at. We conclude that broad attitude network structures can reveal important relations between variables that can help to design new interventions., Competing Interests: The authors have declared that no competing interests exist.

Prior research into the relationship between attitudes and vaccination intention is predominantly cross-sectional and therefore does not provide insight into directions of relations. During the COVID-19 vaccines development and enrollment phase, we studied the temporal dynamics of COVID-19 vaccination intention in relation to attitudes toward COVID-19 vaccines and the pandemic, vaccination in general, social norms and trust. The data are derived from a longitudinal survey study with Dutch participants from a research panel (N = 744; six measurements between December 2020 and May 2021; age 18-84 years [M = 53.32]) and analyzed with vector-autoregression network analyses. While cross-sectional results indicated that vaccination intention was relatively strongly related to attitudes toward the vaccines, results from temporal analyses showed that vaccination intention mainly predicted other vaccination-related variables and to a lesser extent was predicted by variables. We found a weak predictive effect from social norm to vaccination intention that was not robust. This study underlines the challenge of stimulating uptake of new vaccines developed during pandemics, and the importance of examining directions of effects in research into vaccination intention., (© 2022. The Author(s).)

Hookworm infections cause a neglected tropical disease (NTD) affecting ~740 million people worldwide, principally those living in disadvantaged communities. Infections can cause high morbidity due to their impact on nutrient uptake and their need to feed on host blood, resulting in a loss of iron and protein, which can lead to severe anaemia and impaired cognitive development in children. Currently, only one drug, albendazole is efficient to treat hookworm infection and the scientific community fears the rise of resistant strains. As part of on-going efforts to control hookworm infections and its associated morbidities, new drugs are urgently needed. We focused on targeting the blood-feeding pathway, which is essential to the parasite survival and reproduction, using the laboratory hookworm model Nippostrongylus brasiliensis (a nematode of rodents with a similar life cycle to hookworms). We established an in vitro-drug screening assay based on a fluorescent-based measurement of parasite viability during blood-feeding to identify novel therapeutic targets. A first screen of a library of 2654 natural compounds identified four that caused decreased worm viability in a blood-feeding-dependent manner. This new screening assay has significant potential to accelerate the discovery of new drugs against hookworms.

Preventive behaviors are crucial to prevent the spread of the coronavirus causing COVID-19. We adopted a complex psychological systems approach to obtain a descriptive account of the network of attitudes and behaviors related to COVID-19. A survey study ( N = 1,022) was conducted with subsamples from the United Kingdom ( n = 502) and the Netherlands ( n = 520). The results highlight the importance of people's support for, and perceived efficacy of, the measures and preventive behaviors. This also applies to the perceived norm of family and friends adopting these behaviors. The networks in both countries were largely similar but also showed notable differences. The interplay of psychological factors in the networks is also highlighted, resulting in our appeal to policy makers to take complexity and mutual dependence of psychological factors into account. Future research should study the effects of interventions aimed at these factors, including effects on the network, to make causal inferences., Competing Interests: Declaration of Conflicting Interests: The author(s) declared no potential conflicts of interest with respect to the research, authorship, and/or publication of this article., (© The Author(s) 2021.)

Multiple enveloped RNA viruses of the family Paramyxoviridae and Pneumoviridae, like measles virus (MeV), Nipah virus (NiV), canine distemper virus (CDV), or respiratory syncytial virus (RSV), are of high clinical relevance. Each year a huge number of lives are lost as a result of these viral infections. Worldwide, MeV infection alone is responsible for over a hundred thousand deaths each year despite available vaccine. Therefore, there is an urgent need for treatment options to counteract these viral infections. The development of antiviral drugs in general stands as a huge challenge due to the rapid emergence of viral escape mutants. Here, we disclose the discovery of a small-molecule antiviral, compound 1 (ZHAWOC9045), active against several pneumo-/paramyxoviruses, including MeV, NiV, CDV, RSV, and parainfluenza virus type 5 (PIV-5). A series of mechanistic characterizations revealed that compound 1 targets a host factor which is indispensable for viral genome replication. Drug resistance profiling against a paramyxovirus model (CDV) demonstrated no detectable adaptation despite prolonged time of investigation, thereby mitigating the rapid emergence of escape variants. Furthermore, a thorough structure-activity relationship analysis of compound 1 led to the invention of 100-times-more potent-derivatives, e.g., compound 2 (ZHAWOC21026). Collectively, we present in this study an attractive host-directed pneumoviral/paramyxoviral replication inhibitor with potential therapeutic application. IMPORTANCE Measles virus, respiratory syncytial virus, canine distemper virus, and Nipah virus are some of the clinically significant RNA viruses that threaten substantial number of lives each year. Limited to no availability of treatment options for these viral infections makes it arduous to handle the outbreaks. This highlights the major importance of developing antivirals to fight not only ongoing infections but also potential future epidemics. Most of the discovered antivirals, in clinical trials currently, are virus targeted, which consequently poses the challenge of rapid emergence of escape variants. Here, we present compound 1 (ZHAWOC9045), discovered to target viral replication in a host-dependent manner, thereby exhibiting broad-spectrum activity against several members of the family Pneumo-/Paramyxoviridae. The inability of viruses to mutate against the inhibitor mitigated the critical issue of generation of escape variants. Importantly, compound 1 was successfully optimized to a highly potent variant, compound 2 (ZHAWOC21026), with a promising profile for pharmacological intervention.