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Polyolefins are the most widely produced type of plastics owing to their low production cost and favorable properties. Their polymer backbone consists solely of inert C-C bonds, making them resistant and durable materials. Although this is an extremely useful attribute during their use phase, it complicates chemical recycling. In this work, different types of polyethylenes (PEs) are converted into ketone-functionalized PEs with up to 3.4% functionalized carbon atoms, in mild conditions (≤100 °C), using a titanosilicate catalyst and tert-butyl hydroperoxide as the oxidant. Subsequently, the introduced ketones are exploited as sites for heteroatom insertion. Through Baeyer-Villiger oxidation, in-chain esters are produced with yields up to 73%. Alternatively, the ketones can be converted into the corresponding oxime, which can undergo a Beckmann rearrangement to obtain in-chain amides, with yields up to 75%. These transformations allow access to polymers that are amenable to solvolysis, thereby enhancing their potential for chemical recycling., (© 2024. The Author(s).)

Biological nitrogen fixation is a fundamental part of ecosystem functioning. Anthropogenic nitrogen deposition and climate change may, however, limit the competitive advantage of nitrogen-fixing plants, leading to reduced relative diversity of nitrogen-fixing plants. Yet, assessments of changes of nitrogen-fixing plant long-term community diversity are rare. Here, we examine temporal trends in the diversity of nitrogen-fixing plants and their relationships with anthropogenic nitrogen deposition while accounting for changes in temperature and aridity. We used forest-floor vegetation resurveys of temperate forests in Europe and the United States spanning multiple decades. Nitrogen-fixer richness declined as nitrogen deposition increased over time but did not respond to changes in climate. Phylogenetic diversity also declined, as distinct lineages of N-fixers were lost between surveys, but the "winners" and "losers" among nitrogen-fixing lineages varied among study sites, suggesting that losses are context dependent. Anthropogenic nitrogen deposition reduces nitrogen-fixing plant diversity in ways that may strongly affect natural nitrogen fixation.

Climate change is commonly assumed to induce species' range shifts toward the poles. Yet, other environmental changes may affect the geographical distribution of species in unexpected ways. Here, we quantify multidecadal shifts in the distribution of European forest plants and link these shifts to key drivers of forest biodiversity change: climate change, atmospheric deposition (nitrogen and sulfur), and forest canopy dynamics. Surprisingly, westward distribution shifts were 2.6 times more likely than northward ones. Not climate change, but nitrogen-mediated colonization events, possibly facilitated by the recovery from past acidifying deposition, best explain westward movements. Biodiversity redistribution patterns appear complex and are more likely driven by the interplay among several environmental changes than due to the exclusive effects of climate change alone.

Background: Influenza-associated pulmonary aspergillosis (IAPA) is a severe fungal superinfection in critically ill influenza patients that is of incompletely understood pathogenesis. Despite the use of contemporary therapies with antifungal and antivirals, mortality rates remain unacceptably high. We aimed to unravel the IAPA immunopathogenesis as a means to develop adjunctive immunomodulatory therapies., Methods: We used a murine model of IAPA to investigate how influenza predisposes to the development of invasive pulmonary aspergillosis. Immunocompetent mice were challenged with an intranasal instillation of influenza on day 0 followed by an orotracheal inoculation with Aspergillus 4 days later. Mice were monitored daily for overall health status, lung pathology with micro-computed tomography (μCT) and fungal burden with bioluminescence imaging (BLI). At endpoint, high parameter immunophenotyping, spatial transcriptomics, histopathology, dynamic phagosome biogenesis assays with live imaging, immunofluorescence staining, specialized functional phagocytosis and killing assays were performed., Findings: We uncovered an early exuberant influenza-induced interferon-gamma (IFN-γ) production as the major driver of immunopathology in IAPA and delineated the molecular mechanisms. Specifically, excessive IFN-γ production resulted in a defective Th17-immune response, depletion of macrophages, and impaired killing of Aspergillus conidia by macrophages due to the inhibition of NADPH oxidase-dependent activation of LC3-associated phagocytosis (LAP). Markedly, mice with partial or complete genetic ablation of IFN-γ had a restored Th17-immune response, LAP-dependent mechanism of killing and were fully protected from invasive fungal infection., Interpretation: Together, these results identify exuberant viral induced IFN-γ production as a major driver of immune dysfunction in IAPA, paving the way to explore the use of excessive viral-induced IFN-γ as a biomarker and new immunotherapeutic target in IAPA., Funding: This research was funded by the Research Foundation Flanders (FWO), project funding under Grant G053121N to JW, SHB and GVV; G057721N, G0G4820N to GVV; 1506114 N to KL and GVV; KU Leuven internal funds (C24/17/061) to GVV, clinical research funding to JW, Research Foundation Flanders (FWO) aspirant mandate under Grant 1186121N/1186123 N to LS, 11B5520N to FS, 1SF2222N to EV and 11M6922N/11M6924N to SF, travel grants V428023N, K103723N, K217722N to LS. FLvdV was supported by a Vidi grant of the Netherlands Association for Scientific Research. FLvdV, JW, AC and GC were supported by the Europeans Union's Horizon 2020 research and innovation program under grant agreement no 847507 HDM-FUN. AC was also supported by the Fundação para a Ciência e a Tecnologia (FCT), with the references UIDB/50026/2020, UIDP/50026/2020, PTDC/MED-OUT/1112/2021 (https://doi.org/10.54499/PTDC/MED-OUT/1112/2021), and 2022.06674.PTDC (http://doi.org/10.54499/2022.06674.PTDC); and the "la Caixa" Foundation under the agreement LCF/PR/HR22/52420003 (MICROFUN)., Competing Interests: Declaration of interests SF declares having received travel support for conference attendance by Pfizer and Gilead, and a speaker fee from The Healthbook Company Ltd. JW declares having received investigator-initiated grants, speakers’ fees and travel support by Pfizer and Gilead, outside the scope of this manuscript. The other authors declare no competing interests., (Copyright © 2024. Published by Elsevier B.V.)

Parasitic nematodes have an intimate, chronic and lifelong exposure to vertebrate tissues. Here we mined 41 published parasitic nematode transcriptomes from vertebrate hosts and identified 91 RNA viruses across 13 virus orders from 24 families in ~70% (28 out of 41) of parasitic nematode species, which include only 5 previously reported viruses. We observe widespread distribution of virus-nematode associations across multiple continents, suggesting an ancestral acquisition event and host-virus co-evolution. Characterization of viruses of Brugia malayi (BMRV1) and Onchocerca volvulus (OVRV1) shows that these viruses are abundant in reproductive tissues of adult parasites. Importantly, the presence of BMRV1 RNA in B. malayi parasites mounts an RNA interference response against BMRV1 suggesting active viral replication. Finally, BMRV1 and OVRV1 were found to elicit antibody responses in serum samples from infected jirds and infected or exposed humans, indicating direct exposure to the immune system., (© 2024. The Author(s).)

Time-of-Flight Diffraction (TOFD) is a method of ultrasonic testing (UT) that is widely established as a non-destructive technique (NDT) mainly used for the inspection of welds. In contrast to other established UT techniques, TOFD is capable of identifying discontinuities regardless of their orientation. This paper proposes a redesign of the typical TOFD transducers, featuring an innovative curved sole aimed at enhancing their defect detection capabilities. This design is particularly beneficial for thick-walled samples, as it allows for deeper inspections without compromising the resolution near the surface area. During this research, an evaluation consisting in simulations of the ultrasonic beam distribution and experimental tests on a component with artificially manufactured defects at varying depths has been performed to validate the new design. The results demonstrate a 30 to 50% higher beam distribution area as well as an improvement in the signal-to-noise ratio (SNR) resulting in a 24% enhancement in the capability of defect detection compared to the traditional approach.

Background: The composition of care teams is crucial for delivering patient-centered healthcare, yet assembling a well-balanced team remains a challenge. This difficulty stems from the intricate dynamics of team capacity, culture, context, and the demands of the job. The current literature offers limited guidance for decision-makers on how to effectively navigate these dynamics to compose a balanced care team., Methods: We conducted a systematic scoping review of literature spanning from 2009 to 2022. The aim was to identify factors that significantly influence the work environment, team performance, nursing outcomes, and patient outcomes within healthcare settings. Our review focused on extracting and synthesizing evidence to uncover these influencing factors., Results: Our analysis identified 35 factors that play a significant role in shaping the work environment and influencing team performance, nursing outcomes, and patient outcomes. These factors were categorized into nine key domains: workload, leadership, team composition, stress and demands, professional relationships, safety, logistics and ergonomics, autonomy and responsibility, and transparency and task clearness., Conclusions: To improve patient care and nursing job satisfaction, policymakers and decision-makers can consider these influencing factors in the design and management of care teams. The findings advocate for strategic adjustments in these domains to enhance a team's balance. Furthermore, our review underscores the need for further research to fill the identified gaps in knowledge, offering a directive for future studies into optimal care team composition. This systematic approach to team composition can significantly impact patient outcomes and nurse satisfaction, providing a roadmap for creating more effective and harmonious teams., (© 2024. The Author(s).)

Background: Out-of-hours primary care (OOH-PC) has emerged as a promising solution to improve efficiency, accessibility, and quality of care and to reduce the strain on emergency departments. As this modality gains traction in diverse healthcare settings, it is increasingly important to fully assess its societal value-for-money and conduct thorough process evaluations. However, current economic evaluations mostly emphasise direct- and short-term effect measures, thus lacking a broader societal perspective., Aim: This study offers a comprehensive overview of current effect measures in OOH-PC evaluations and proposes additional measures from the evaluation of integrated care programmes., Approach and Development: First, we systematically identified the effect measures from published cost-effectiveness studies and classified them as process, outcome, and resource use measures. Second, we elaborate on the incorporation of 'productivity gains', 'health promotion and early intervention', and 'continuity of care' as additional effects into economic evaluations of OOH-PC. Seeking care affects personal and employee time, potentially resulting in decreased productivity. Challenges in taking time off work and limited access to convenient care are often cited as barriers to accessing primary care. As such, OOH-PC can potentially reduce opportunity costs for patients. Furthermore, improving access to healthcare is important in determining whether people receive promotional and preventive services. Health promotion involves empowering people to take control of their health and its determinants. Given the unscheduled nature and the fragmented or rotational care in OOH-PC, the degree to which interventions and modalities provide continuity should be monitored, assessed, and included in economic evaluations. Continuity of care in primary care improves patient satisfaction, promotes adherence to medical advice, reduces reliance on hospitals, and reduces mortality., Conclusion: Although it is essential to also address local settings and needs, the integration of broader scope measures into OOH-PC economic evaluations improves the comprehensive evaluation that aligns with welfare gains.

Background: Across Europe, countries have responded to the COVID-19 pandemic with a combination of non-pharmaceutical interventions and vaccination. Evaluating the effectiveness of such interventions is of particular relevance to policy-makers., Methods: We leverage almost three years of available data across 38 European countries to evaluate the effectiveness of governmental responses in controlling the pandemic. We developed a Bayesian hierarchical model that flexibly relates daily COVID-19 incidence to past levels of vaccination and non-pharmaceutical interventions as summarised in the Stringency Index. Specifically, we use a distributed lag approach to temporally weight past intervention values, a tensor-product smooth to capture non-linearities and interactions between both types of interventions, and a hierarchical approach to parsimoniously address heterogeneity across countries., Results: We identify a pronounced negative association between daily incidence and the strength of non-pharmaceutical interventions, along with substantial heterogeneity in effectiveness among European countries. Similarly, we observe a strong but more consistent negative association with vaccination levels. Our results show that non-linear interactions shape the effectiveness of interventions, with non-pharmaceutical interventions becoming less effective under high vaccination levels. Finally, our results indicate that the effects of interventions on daily incidence are most pronounced at a lag of 14 days after being in place., Conclusions: Our Bayesian hierarchical modelling approach reveals clear negative and lagged effects of non-pharmaceutical interventions and vaccination on confirmed COVID-19 cases across European countries., (© 2024. The Author(s).)

Flavin-like ligands ( L-1 and L-2 ) with extended π-conjugation were synthesized using microwave-assisted techniques. An N , N -chelating fragment was integrated into alloxazine units, providing binding sites for metal ions while retaining redox activity. The complexation capability of L-1 and L-2 with two prototypical Ru-scaffolds was examined to design Ru(II) complexes ( M-1 and M-2 ), whose electronic properties were studied and compared with their corresponding ligands via absorption and emission spectroscopy, computational analysis (density functional theory (DFT) and time-dependent DFT (TD-DFT)), and cyclic voltammetry (CV). The ability of L-1 and M-1 to undergo alloxazine/isoalloxazine tautomerization was demonstrated to play a crucial role in the photocatalytic oxidation of NADH, including under green and red wavelengths. Moreover, the interaction of M-1 and M-2 with B-DNA and G-quadruplex structures was investigated. M-2 showed high stabilization of Kit1 and h-Telo oligonucleotides. Meanwhile, M-1 demonstrated switchable emissive properties with B-DNA and induced conformational changes in the h-Telo G-quadruplex structure.

Per- and polyfluoroalkyl substances (PFAS) such as perfluorooctanoic acid (PFOA) and perfluorooctane sulfonic acid (PFOS) and perfluoro-2-methyl-3-oxahexanoic acid (GenX), the new replacement PFAS, are major environmental contaminants. In rodents, these PFAS induce several adverse effects on the liver, including increased proliferation, hepatomegaly, steatosis, hypercholesterolemia, nonalcoholic fatty liver disease and liver cancers. Activation of peroxisome proliferator receptor alpha by PFAS is considered the primary mechanism of action in rodent hepatocyte-induced proliferation. However, the human relevance of this mechanism is uncertain. We investigated human-relevant mechanisms of PFAS-induced adverse hepatic effects using FRG liver-chimeric humanized mice with livers repopulated with functional human hepatocytes. Male FRG humanized mice were treated with 0.067 mg/L of PFOA, 0.145 mg/L of PFOS, or 1 mg/L of GenX in drinking water for 28 days. PFOS caused a significant decrease in total serum cholesterol and LDL/VLDL, whereas GenX caused a significant elevation in LDL/VLDL with no change in total cholesterol and HDL. All three PFAS induced significant hepatocyte proliferation. RNA-sequencing with alignment to the human genome showed a total of 240, 162, and 619 differentially expressed genes after PFOA, PFOS, and GenX exposure, respectively. Upstream regulator analysis revealed that all three PFAS induced activation of p53 and inhibition of androgen receptor and NR1D1, a transcriptional repressor important in circadian rhythm. Further biochemical studies confirmed NR1D1 inhibition and in silico modeling indicated potential interaction of all three PFAS with the DNA-binding domain of NR1D1. In conclusion, our studies using FRG humanized mice have revealed new human-relevant molecular mechanisms of PFAS including their previously unknown effect on circadian rhythm., (© 2024. The Author(s), under exclusive licence to Springer-Verlag GmbH Germany, part of Springer Nature.)

Age estimation in forensic odontology is mainly based on the development of permanent teeth. To register the developmental status of an examined tooth, staging techniques were developed. However, due to inappropriate calibration, uncertainties during stage allocation, and lack of experience, non-uniformity in stage allocation exists between expert observers. As a consequence, related age estimation results are inconsistent. An automated staging technique applicable to all tooth types can overcome this drawback.This study aimed to establish an integrated automated technique to stage the development of all mandibular tooth types and to compare their staging performances.Calibrated observers staged FDI teeth 31, 33, 34, 37 and 38 according to a ten-stage modified Demirjian staging technique. According to a standardised bounding box around each examined tooth, the retrospectively collected panoramic radiographs were cropped using Photoshop CC 2021® software (Adobe®, version 23.0). A gold standard set of 1639 radiographs were selected (n 31  = 259, n 33  = 282, n 34  = 308, n 37  = 390, n 38  = 400) and input into a convolutional neural network (CNN) trained for optimal staging accuracy. The performance evaluation of the network was conducted in a five-fold cross-validation scheme. In each fold, the entire dataset was split into a training and a test set in a non-overlapping fashion between the folds (i.e., 80% and 20% of the dataset, respectively). Staging performances were calculated per tooth type and overall (accuracy, mean absolute difference, linearly weighted Cohen's Kappa and intra-class correlation coefficient). Overall, these metrics equalled 0.53, 0.71, 0.71, and 0.89, respectively. All staging performance indices were best for 37 and worst for 31. The highest number of misclassified stages were associated to adjacent stages. Most misclassifications were observed in all available stages of 31.Our findings suggest that the developmental status of mandibular molars can be taken into account in an automated approach for age estimation, while taking incisors into account may hinder age estimation., (© 2024. The Author(s), under exclusive licence to Springer-Verlag GmbH Germany, part of Springer Nature.)

Historically used pesticides poses a threat to biodiversity while their release pathways remain unclear. Trees could be a potential release source due to their long lifespan. This study examined 38 samples to assess pesticide concentrations in pedunculate oak from Belgium. Low concentrations of procymidone were detected in two samples from one stump. Our findings suggest that accumulations of historically used pesticides in pedunculate oaks within forests are improbable. We conclude that leaving dead wood poses no risks for pesticide release to the environment. However, further research involving diverse tree species and regions is needed to refine and validate this conclusion., (© 2024. The Author(s), under exclusive licence to Springer Science+Business Media, LLC, part of Springer Nature.)

Introduction: The epidemiology of nontuberculous mycobacteria (NTM) is not well known. In this study, we aimed to determine the incidence of NTM isolates and nontuberculous mycobacterial pulmonary disease (NTM-PD) in five closely located hospitals in an area of northern Spain and analyse differences between them., Material and Methods: Demographic, microbiological, clinical and radiological data were collected retrospectively from all patients with a NTM isolated from respiratory specimens at five hospitals between 2012 and 2019. Mycobacterium gordonae isolates were excluded. Once the data was collected, it was determined which patients met the NMT-PD criteria., Results: 594 patients were included in the study. The mean incidence rate of NTM isolates across all five hospitals in the period studied was 4.15 per 100,000 person-year, while the rate of NTM-PD was 1.2. The annual number of isolates showed an upward trend over this period, but the same did not occur in the number of cases of NTM-PD. The species most frequently isolated were Mycobacterium avium complex (MAC) and Mycobacterium xenopi and those most frequently causing disease were MAC and Mycobacterium kansassi . There were significant differences between the five centres., Conclusions: Our results are in line with similar studies in Europe in terms of NTM isolation and NTM-PD incidence and species isolated; however, we do not see the upward trend in NTM-PD rates described elsewhere. The great variability in isolation and disease rates, as well as in species isolated in geographically close areas, underlines, in our opinion, the importance of local environmental factors., (© 2024 Sociedad Española de Neumología y Cirugía Torácica (SEPAR). Published by Elsevier España, S.L.U.)

Cocaine-induced midline destructive lesions (CIMDL) are a rare complication of chronic intranasal cocaine use involving the centrofacial mucosal structures, often with nasal septum perforation and, in severe cases, involvement of neurocranial structures. Patients present with nasal obstruction, epistaxis, facial pain, nasal ulcerative lesions with crusting, and septal and palate perforation causing dysphagia and nasal reflux. CNS involvement is uncommon.We report a 47-year-old man with a history of nasal cocaine use who developed a subacute frontal syndrome secondary to cribriform plate destruction complicated by bilateral frontal lobe empyema and abscesses and extensive white matter involvement. The frequent presence of serum antineutrophil cytoplasmic antibodies (ANCA) in CIMDL makes this uncommon presentation challenging to differentiate from localized granulomatosis with polyangiitis. While ANCA antibodies may play a role in CIMDL, immunosuppression is not indicated and may lead to iatrogenesis.CIMDL should be considered in patients with isolated frontal lobe syndrome. Eliciting a history of cocaine use and obtaining toxicologic studies are essential in the diagnosis of CIMDL.

In Cameroon, Aedes mosquitoes transmit various arboviruses, posing significant health risks. We aimed to characterize the Aedes virome in southwestern Cameroon and identify potential core viruses which might be associated with vector competence. A total of 398 Aedes mosquitoes were collected from four locations (Bafoussam, Buea, Edea, and Yaounde). Aedes albopictus dominated all sites except for Bafoussam, where Aedes africanus prevailed. Metagenomic analyses of the mosquitoes grouped per species into 54 pools revealed notable differences in the eukaryotic viromes between Ae. africanus and Ae. albopictus , with the former exhibiting greater richness and diversity. Thirty-seven eukaryotic virus species from 16 families were identified, including six novel viruses with near complete genome sequences. Seven viruses were further quantified in individual mosquitoes via qRT-PCR. Although none of them could be identified as core viruses, Guangzhou sobemo-like virus and Bafoussam mosquito solemovirus, were highly prevalent regionally in Ae. albopictus and Ae. africanus , respectively. This study highlights the diverse eukaryotic virome of Aedes species in southwestern Cameroon. Despite their shared genus, Aedes species exhibit limited viral sharing, with varying viral abundance and prevalence across locations. Ae. africanus , an understudied vector, harbors a rich and diverse virome, suggesting potential implications for arbovirus vector competence.

Objective: To identify the difference in breast cancer mortality rates among young women according to countries' economic classification., Methods: A systematic literature review included retrospective studies on breast cancer mortality rates in women aged 20 to 49 years. Databases used were PubMed, Web of Science, Scopus, and Virtual Health Library, with articles selected in English, Portuguese, and Spanish. The study selection and analysis were conducted by two pairs of researchers. Data from 54 countries were extracted, including 39 high-income, 12 upper-middle-income, and 3 lower-middle-income countries. A meta-analysis was performed with the quantitative data from two studies., Results: Six articles met the inclusion criteria. Four were analyzed descriptively due to data diversity, and two were included in the meta-analysis. The pooled mortality rate for high-income countries was 10.2 per 100,000 women (95% CI: 9.8-10.6), while for upper-middle-income countries, it was 15.5 per 100,000 women (95% CI: 14.9-16.1). Lower-middle-income countries had a pooled mortality rate of 20.3 per 100,000 women (95% CI: 19.5-21.1). The decrease in mortality rates in high-income countries was statistically significant (p<0.05)., Conclusion: Mortality rates for breast cancer among young women have decreased significantly in high-income countries but have increased in lower-income countries. This disparity underscores the impact of insufficient investment in preventive measures, health promotion, early diagnosis, and treatment on young women's mortality in lower-income countries.

Introduction: Initiation of buprenorphine for opioid use disorder (OUD) in the emergency department (ED) is supported by the American College of Emergency Physicians and is shown to be beneficial. This practice, however, is largely underutilized., Methods: To assess emergency clinicians' attitudes and readiness to initiate buprenorphine in the ED we conducted a cross-sectional, electronic survey of clinicians (attendings, residents, and non-physician clinicians) in a single, academic ED of a tertiary-care hospital, which serves a rural population. Our survey aimed to assess emergency clinicians' attitudes toward and readiness to initiate buprenorphine in the ED and identify clinician-perceived facilitators and barriers. Our survey took place after the initiation of the IMPACT (Initiation of Medication, Peer Access, and Connection to Treatment) project., Results: Our results demonstrated the level of agreement that buprenorphine prescribing is within the emergency clinician's scope of practice was inversely correlated to average years in practice (R 2  = 0.93). X-waivered clinicians indicated feeling more prepared to administer buprenorphine in the ED R 2  = 0.93. However, they were not more likely to report ordering buprenorphine or naloxone in the ED within the prior three months. Those who reported having a family member or close friend with substance use disorder (SUD) were not more likely to agree buprenorphine initiation is within the clinician's scope of practice ( P  = 0.91), nor were they more likely to obtain an X-waiver ( P  = 0.58) or report ordering buprenorphine or naloxone for patients in the ED within the prior three months ( P  = 0.65, P  = 0.77). Clinicians identified availability of pharmacists, inpatient/outpatient referral resources, and support staff (peer recovery support specialists and care managers) as primary facilitators to buprenorphine initiation. Inability to ensure follow-up, lack of knowledge of available resources, and insufficient education/preparedness were primary barriers to ED buprenorphine initiation. Eighty-three percent of clinicians indicated they would be interested in additional education regarding OUD treatment., Conclusion: Our data suggests that newer generations of emergency clinicians may have less hesitancy initiating buprenorphine in the ED. In time, this could mean increased access to treatment for patients with OUD. Understanding clinician-perceived facilitators and barriers to buprenorphine initiation allows for better resource allocation. Clinicians would likely further benefit from additional education regarding medications for opioid use disorder (MOUD), available resources, and follow-up statistics., Competing Interests: Conflicts of Interest: By the WestJEM article submission agreement, all authors are required to disclose all affiliations, funding sources and financial or management relationships that could be perceived as potential sources of bias. This publication was supported by a grant (G230766) from the Substance Abuse and Mental Health Services Administration through a subcontract from the West Virginia Department of Health and Human Resources Bureau for Behavioral Health. There are no other conflicts of interest or sources of funding to declare.

In arthropod-associated microbial communities, insect-specific viruses (ISVs) are prevalent yet understudied due to limited infectivity outside their natural hosts. However, ISVs might play a crucial role in regulating mosquito populations and influencing arthropod-borne virus transmission. Some studies have indicated a core virome in mosquitoes consisting of mostly ISVs. Employing single mosquito metagenomics, we comprehensively profiled the virome of native and invasive mosquito species in Belgium. This approach allowed for accurate host species determination, prevalence assessment of viruses and Wolbachia , and the identification of novel viruses. Contrary to our expectations, no abundant core virome was observed in Culex mosquitoes from Belgium. In that regard, we caution against rigidly defining mosquito core viromes and encourage nuanced interpretations of other studies. Nonetheless, our study identified 45 viruses of which 28 were novel, enriching our understanding of the mosquito virome and ISVs. We showed that the mosquito virome in this study is species-specific and less dependent on the location where mosquitoes from the same species reside. In addition, because Wolbachia has previously been observed to influence arbovirus transmission, we report the prevalence of Wolbachia in Belgian mosquitoes and the detection of several Wolbachia mobile genetic elements. The observed prevalence ranged from 83% to 92% in members from the Culex pipiens complex.IMPORTANCE Culex pipiens mosquitoes are important vectors for arboviruses like West Nile virus and Usutu virus. Virome studies on individual Culex pipiens , and on individual mosquitoes in general, have been lacking. To mitigate this, we sequenced the virome of 190 individual Culex and 8 individual Aedes japonicus mosquitoes. We report the lack of a core virome in these mosquitoes from Belgium and caution the interpretation of other studies in this light. The discovery of new viruses in this study will aid our comprehension of insect-specific viruses and the mosquito virome in general in relation to mosquito physiology and mosquito population dynamics., Competing Interests: The authors declare no conflict of interest.

Background: Patients in serious condition due to COVID-19 often require special care in intensive care units (ICUs). This disease has affected over 758 million people and resulted in 6.8 million deaths worldwide. Additionally, the progression of the disease may vary from individual to individual, that is, it is essential to identify the clinical parameters that indicate a good prognosis for the patient. Machine learning (ML) algorithms have been used for analyzing complex medical data and identifying prognostic indicators. However, there is still an urgent need for a model to elucidate the predictors related to patient outcomes. Therefore, this research aimed to verify, through ML, the variables involved in the discharge of patients admitted to the ICU due to COVID-19., Methods: In this study, 126 variables were collected with information on demography, hospital length stay and outcome, chronic diseases and tumors, comorbidities and risk factors, complications and adverse events, health care, and vital indicators of patients admitted to an ICU in southern Brazil. These variables were filtered and then selected by a ML algorithm known as decision trees to identify the optimal set of variables for predicting patient discharge using logistic regression. Finally, a confusion matrix was performed to evaluate the model's performance for the selected variables., Results: Of the 532 patients evaluated, 180 were discharged: female (16.92%), with a central venous catheter (23.68%), with a bladder catheter (26.13%), and with an average of 8.46- and 23.65-days using bladder catheter and submitted to mechanical ventilation, respectively. In addition, the chances of discharge increase by 14% for each additional day in the hospital, by 136% for female patients, 716% when there is no bladder catheter, and 737% when no central venous catheter is used. However, the chances of discharge decrease by 3% for each additional year of age and by 9% for each other day of mechanical ventilation. The performance of the training data presented a balanced accuracy of 0.81, sensitivity of 0.74, specificity of 0.88, and the kappa value was 0.64. The test performance had a balanced accuracy of 0.85, sensitivity 0.75, specificity 0.95, and kappa value of 0.73. The McNemar test found that there were no significant differences in the error rates in the training and test data, suggesting good classification. This work showed that female, the absence of a central venous catheter and bladder catheter, shorter mechanical ventilation, and bladder catheter duration were associated with a greater chance of hospital discharge. These results may help develop measures that lead to a good prognosis for the patient., Competing Interests: The authors declare there are no competing interests., (©2024 Dos Santos et al.)

Background: Collaborative comparisons and combinations of epidemic models are used as policy-relevant evidence during epidemic outbreaks. In the process of collecting multiple model projections, such collaborations may gain or lose relevant information. Typically, modellers contribute a probabilistic summary at each time-step. We compared this to directly collecting simulated trajectories. We aimed to explore information on key epidemic quantities; ensemble uncertainty; and performance against data, investigating potential to continuously gain information from a single cross-sectional collection of model results., Methods: We compared projections from the European COVID-19 Scenario Modelling Hub. Five teams modelled incidence in Belgium, the Netherlands, and Spain. We compared July 2022 projections by incidence, peaks, and cumulative totals. We created a probabilistic ensemble drawn from all trajectories, and compared to ensembles from a median across each model's quantiles, or a linear opinion pool. We measured the predictive accuracy of individual trajectories against observations, using this in a weighted ensemble. We repeated this sequentially against increasing weeks of observed data. We evaluated these ensembles to reflect performance with varying observed data., Results: By collecting modelled trajectories, we showed policy-relevant epidemic characteristics. Trajectories contained a right-skewed distribution well represented by an ensemble of trajectories or a linear opinion pool, but not models' quantile intervals. Ensembles weighted by performance typically retained the range of plausible incidence over time, and in some cases narrowed this by excluding some epidemic shapes., Conclusions: We observed several information gains from collecting modelled trajectories rather than quantile distributions, including potential for continuously updated information from a single model collection. The value of information gains and losses may vary with each collaborative effort's aims, depending on the needs of projection users. Understanding the differing information potential of methods to collect model projections can support the accuracy, sustainability, and communication of collaborative infectious disease modelling efforts., Competing Interests: Declaration of Competing Interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2024 The Authors. Published by Elsevier B.V. All rights reserved.)

Root-knot nematodes (RKN; Meloidogyne species) are plant pathogens that introduce several effectors in their hosts to facilitate infection. The actual targets and functioning mechanism of these effectors largely remain unexplored. This study illuminates the role and interplay of the Meloidogyne javanica nematode effector ROS suppressor (Mj-NEROSs) within the host plant environment. Mj-NEROSs suppresses INF1-induced cell death as well as flg22-induced callose deposition and reactive oxygen species (ROS) production. A transcriptome analysis highlighted the downregulation of ROS-related genes upon Mj-NEROSs expression. NEROSs interacts with the plant Rieske's iron-sulfur protein (ISP) as shown by yeast-two-hybrid and bimolecular fluorescence complementation. Secreted from the subventral pharyngeal glands into giant cells, Mj-NEROSs localizes in the plastids where it interacts with ISP, subsequently altering electron transport rates and ROS production. Moreover, our results demonstrate that isp Arabidopsis thaliana mutants exhibit increased susceptibility to M. javanica, indicating ISP importance for plant immunity. The interaction of a nematode effector with a plastid protein highlights the possible role of root plastids in plant defense, prompting many questions on the details of this process., (© 2024 The Authors New Phytologist © 2024 New Phytologist Foundation.)

Background: Sexually transmitted infections (STIs), along with sexual health and behaviour, have received little attention in schizophrenia patients., Aims: To systematically review and meta-analytically characterise the prevalence of STIs and sexual risk behaviours among schizophrenia patients., Method: Web of Science, PubMed, BIOSIS, KCI-Korean Journal Database, MEDLINE, Russian Science Citation Index, SciELO and Cochrane Central Register were systematically searched from inception to 6 July 2023. Studies reporting on the prevalence or odds ratio of any STI or any outcome related to sexual risk behaviours among schizophrenia samples were included. PRISMA/MOOSE-compliant (CRD42023443602) random-effects meta-analyses were used for the selected outcomes. Q-statistics, I 2 index, sensitivity analyses and meta-regressions were used. Study quality and publication bias were assessed., Results: Forty-eight studies ( N = 2 459 456) reporting on STI prevalence (including 15 allowing for calculation of an odds ratio) and 33 studies ( N = 4255) reporting on sexual risk behaviours were included. Schizophrenia samples showed a high prevalence of STIs and higher risks of HIV (odds ratio = 2.11; 95% CI 1.23-3.63), hepatitis C virus (HCV, odds ratio = 4.54; 95% CI 2.15-961) and hepatitis B virus (HBV; odds ratio = 2.42; 95% CI 1.95-3.01) infections than healthy controls. HIV prevalence was higher in Africa compared with other continents and in in-patient (rather than out-patient) settings. Finally, 37.7% (95% CI 31.5-44.4%) of patients were sexually active; 35.0% (95% CI 6.6-59.3%) reported consistent condom use, and 55.3% (95% CI 25.0-82.4%) maintained unprotected sexual relationships., Conclusions: Schizophrenia patients have high prevalence of STIs, with several-fold increased risks of HIV, HBV and HCV infection compared with the general population. Sexual health must be considered as an integral component of care.

Background: When formulating and evaluating COVID-19 vaccination strategies, an emphasis has been placed on preventing severe disease that overburdens healthcare systems and leads to mortality. However, more conventional outcomes such as quality-adjusted life years (QALYs) and inequality indicators are warranted as additional information for policymakers., Methods: We adopted a mathematical transmission model to describe the infectious disease dynamics of SARS-COV-2, including disease mortality and morbidity, and to evaluate (non)pharmaceutical interventions. Therefore, we considered temporal immunity levels, together with the distinct transmissibility of variants of concern (VOCs) and their corresponding vaccine effectiveness. We included both general and age-specific characteristics related to SARS-CoV-2 vaccination. Our scenario study is informed by data from Belgium, focusing on the period from August 2021 until February 2022, when vaccination for children aged 5-11 years was initially not yet licensed and first booster doses were administered to adults. More specifically, we investigated the potential impact of an earlier vaccination programme for children and increased or reduced historical adult booster dose uptake., Results: Through simulations, we demonstrate that increasing vaccine uptake in children aged 5-11 years in August-September 2021 could have led to reduced disease incidence and ICU occupancy, which was an essential indicator for implementing non-pharmaceutical interventions and maintaining healthcare system functionality. However, an enhanced booster dose regimen for adults from November 2021 onward could have resulted in more substantial cumulative QALY gains, particularly through the prevention of elevated levels of infection and disease incidence associated with the emergence of Omicron VOC. In both scenarios, the need for non-pharmaceutical interventions could have decreased, potentially boosting economic activity and mental well-being., Conclusions: When calculating the impact of measures to mitigate disease spread in terms of life years lost due to COVID-19 mortality, we highlight the impact of COVID-19 on the health-related quality of life of survivors. Our study underscores that disease-related morbidity could constitute a significant part of the overall health burden. Our quantitative findings depend on the specific setup of the interventions under review, which is open to debate or should be contextualised within future situations., (© 2024. The Author(s).)

Net zero targets have resulted in a drive to decarbonise the transport sector worldwide through electrification. This has, in turn, led to an exponentially growing battery market and, conversely, increasing attention on how we can reduce the environmental impact of batteries and promote a more efficient circular economy to achieve real net zero. As these batteries reach the end of their first life, challenges arise as to how to collect and process them, in order to maximise their economical use before finally being recycled. Despite the growing body of work around this topic, the decision-making process on which pathways batteries could take is not yet well understood, and clear policies and standards to support implementation of processes and infrastructure are still lacking. Requirements and challenges behind recycling and second life applications are complex and continue being defined in industry and academia. Both pathways rely on cell collection, selection and processing, and are confronted with the complexities of pack disassembly, as well as a diversity of cell chemistries, state-of-health, size, and form factor. There are several opportunities to address these barriers, such as standardisation of battery design and reviewing the criteria for a battery's end-of-life. These revisions could potentially improve the overall sustainability of batteries, but may require policies to drive such transformation across the industry. The influence of policies in triggering a pattern of behaviour that favours one pathway over another are examined and suggestions are made for policy amendments that could support a second life pipeline, while encouraging the development of an efficient recycling industry. This review explains the different pathways that end-of-life EV batteries could follow, either immediate recycling or service in one of a variety of second life applications, before eventual recycling. The challenges and barriers to each pathway are discussed, taking into account their relative environmental and economic feasibility and competing advantages and disadvantages of each. The review identifies key areas where processes need to be simplified and decision criteria clearly defined, so that optimal pathways can be rapidly determined for each end-of-life battery., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2024 Patel, Lander, Ahuja, Bulman, Lum, Pople, Hales, Patel and Edge.)

Introduction: Emergency departments (ED) are incorporating Peer Support Specialists (PSSs) to help with patient care for substance use disorders (SUDs). Despite rapid growth in this area, little is published regarding workflow, expectations of the peer role, and core components of the PSS intervention. This study describes these elements in a national sample of ED-based peer support intervention programs., Methods: A survey was conducted to assess PSS site characteristics as part of site selection process for a National Institute on Drug Abuse (NIDA) Clinical Trials Network (CTN) evaluating PSS effectiveness, Surveys were distributed to clinical sites affiliated with the 16 CTN nodes. Surveys were completed by a representative(s) of the site and collected data on the PSS role in the ED including details regarding funding and certification, services rendered, role in medications for opioid use disorder (MOUD) and naloxone distribution, and factors impacting implementation and maintenance of ED PSS programs. Quantitative data was summarized with descriptive statistics. Free-text fields were analyzed using qualitative content analysis., Results: A total of 11 surveys were completed, collected from 9 different states. ED PSS funding was from grants (55%), hospital funds (46%), peer recovery organizations (27%) or other (18%). Funding was anticipated to continue for a mean of 16 months (range 12 to 36 months). The majority of programs provided "general recovery support (81%) Screening, Brief Intervention, and Referral to Treatment (SBIRT) services (55%), and assisted with naloxone distribution to ED patients (64%). A minority assisted with ED-initiated buprenorphine (EDIB) programs (27%). Most (91%) provided services to patients after they were discharged from the ED. Barriers to implementation included lack of outpatient referral sources, barriers to initiating MOUD, stigma at the clinician and system level, and lack of ongoing PSS availability due to short-term grant funding., Conclusions: The majority of ED-based PSSs were funded through time-limited grants, and short-term grant funding was identified as a barrier for ED PSS programs. There was consistency among sites in the involvement of PSSs in facilitation of transitions of SUD care, coordination of follow-up after ED discharge, and PSS involvement in naloxone distribution., (© 2024. The Author(s).)

The effect of birthplace (the place where a player is born and grows up) is one of the key variables associated with soccer player development and achievement. However, recent studies have questioned the influence of contextual variables on selection and promotion processes related to birthplace. The main purposes of this study were: (1) establish whether there is a difference between the birthplace and sporting growth according to the stages of entry into the academy, (2) to evaluate the influence of geographical and contextual variables on sporting development, and (3) assess the chances of making a professional team debut. Applied logistic regression was used in order to analyse the birthplace and growth of 1411 male soccer players, of which 40.1% are incorporated in the U-12 category from a Spanish First division club, and the results showed a statistically significant association between a change from one's birthplace to the place of sporting growth and later success (79%). Key contextual variables such as number of inhabitants, population density, proximity to sports facilities, average household income and presence of sports clubs have been considered. The analysis of the contextual variables revealed that there was a positive relationship between certain variables, like a higher population, and being selected for the academy ( p < 0.01; r = 0.28). Finally, the findings showed that players who experienced a geographical transition were 38% more likely to make a professional debut. The importance of considering the place of sporting growth when analysing the "birthplace effect" has therefore been demonstrated.

Immobilization of stimulus-responsive systems on solid surfaces is beneficial for controlled signal transmission and adaptive behavior while allowing the characterization of the functional interface with high sensitivity and high spatial resolution. Positioning of the stimuli-responsive units with nanometer-scale precision across the adaptive surface remains one of the bottlenecks in the extraction of cooperative function. Nanoscale organization, cooperativity, and amplification remain key challenges in bridging the molecular and the macroscopic worlds. Here we report on the design, synthesis, and scanning tunneling microscopy (STM) characterization of overcrowded alkene photoswitches merged in self-assembled networks physisorbed at the solid-liquid interface. A detailed anchoring strategy that ensures appropriate orientation of the switches with respect to the solid surface through the use of bis-urea groups is presented. We implement a co-assembly strategy that enables the merging of the photoswitches within physisorbed monolayers of structurally similar 'spacer' molecules. The self-assembly of the individual components and the co-assemblies was examined in detail using (sub)molecular resolution STM which confirms the robust immobilization and controlled orientation of the photoswitches within the spacer monolayers. The experimental STM data is supported by detailed molecular mechanics (MM) simulations. Different designs of the switches and the spacers were investigated which allowed us to formulate guidelines that enable the precise organization of the photoswitches in crystalline physisorbed self-assembled molecular networks., (© 2024 The Authors. Chemistry - A European Journal published by Wiley-VCH GmbH.)

Using a metagenomic sequencing approach on stool samples from children with Acute Flaccid Paralysis (AFP), we describe the genetic diversity of Sapoviruses (SaVs) in children in Nigeria. We identified six complete genome sequences and two partial genome sequences. Several SaV genogroups and genotypes were detected, including GII (GII.4 and GII.8), GIV (GIV.1), and GI (GI.2 and GI.7). To our knowledge, this is the first description of SaV infections and complete genomes from Nigeria. Pairwise identity and phylogenetic analysis showed that the Nigerian SaVs were related to previously documented gastroenteritis outbreaks with associated strains from China and Japan. Minor variations in the functional motifs of the nonstructural proteins NS3 and NS5 were seen in the Nigerian strains. To adequately understand the effect of such amino acid changes, a better understanding of the biological function of these proteins is vital. The identification of distinct SaVs reinforces the need for robust surveillance in acute gastroenteritis (AGE) and non-AGE cohorts to better understand SaVs genotype diversity, evolution, and its role in disease burden in Nigeria. Future studies in different populations are, therefore, recommended.

There is increasing interest in understanding potential bias in medical education. We used natural language processing (NLP) to evaluate potential bias in clinical clerkship evaluations. Data from medical evaluations and administrative databases for medical students enrolled in third-year clinical clerkship rotations across two academic years. We collected demographic information of students and faculty evaluators to determine gender/racial concordance (i.e., whether the student and faculty identified with the same demographic). We used a multinomial log-linear model for final clerkship grades, using predictors such as numerical evaluation scores, gender/racial concordance, and sentiment scores of narrative evaluations using the SentimentIntensityAnalyzer tool in Python. 2037 evaluations from 198 students were analyzed. Statistical significance was defined as P < 0.05. Sentiment scores for evaluations did not vary significantly by student gender, race, or ethnicity (P = 0.88, 0.64, and 0.06, respectively). Word choices were similar across faculty and student demographic groups. Modeling showed narrative evaluation sentiment scores were not predictive of an honors grade (odds ratio [OR] 1.23, P = 0.58). Numerical evaluation average (OR 1.45, P < 0.001) and gender concordance between faculty and student (OR 1.32, P = 0.049) were significant predictors of receiving honors. The lack of disparities in narrative text in our study contrasts with prior findings from other institutions. Ongoing efforts include comparative analyses with other institutions to understand what institutional factors may contribute to bias. NLP enables a systematic approach for investigating bias. The insights gained from the lack of association between word choices, sentiment scores, and final grades show potential opportunities to improve feedback processes for students., (© 2024. The Author(s).)

Global change has accelerated local species extinctions and colonizations, often resulting in losses and gains of evolutionary lineages with unique features. Do these losses and gains occur randomly across the phylogeny? We quantified: temporal changes in plant phylogenetic diversity (PD); and the phylogenetic relatedness (PR) of lost and gained species in 2672 semi-permanent vegetation plots in European temperate forest understories resurveyed over an average period of 40 yr. Controlling for differences in species richness, PD increased slightly over time and across plots. Moreover, lost species within plots exhibited a higher degree of PR than gained species. This implies that gained species originated from a more diverse set of evolutionary lineages than lost species. Certain lineages also lost and gained more species than expected by chance, with Ericaceae, Fabaceae, and Orchidaceae experiencing losses and Amaranthaceae, Cyperaceae, and Rosaceae showing gains. Species losses and gains displayed no significant phylogenetic signal in response to changes in macroclimatic conditions and nitrogen deposition. As anthropogenic global change intensifies, temperate forest understories experience losses and gains in specific phylogenetic branches and ecological strategies, while the overall mean PD remains relatively stable., (© 2023 The Authors. New Phytologist © 2023 New Phytologist Foundation.)

Background: There has been extensive research demonstrating the effectiveness of medications for opioid use disorder (MOUD) but limited investigation into its long-term retention rate., Objective: Assess the long-term treatment retention of a buprenorphine-based MOUD clinic with additional stratifications by age and gender., Methods: This retrospective study analyzed 10-years of data from a MOUD clinic in West Virginia that served 3,255 unique patients during the study period (2009-2019). Retention was measured by summation of total treatment days with a new episode of care defined as re-initiating buprenorphine treatment after 60+ consecutive days of nonattendance. Kaplan-Meier survival analysis, with the log-rank test, was used to compare retention by gender and age., Results: The mean age was 38 (SD = 10.6) and 95% were non-Hispanic white. Irrespective of treatment episode, 56.8% of patients were retained ≥ 90 days, and the overall median time in treatment was 112 days. Considering only the first treatment episode, 48.4% of 3,255 patients were retained at least 90 days and the overall median was 77 days. Female patients had a  ≥ 90 day retention rate of 52.2% for the first admission and 60.1% for multiple admissions, both significantly higher than those of male subjects (44.1% and 53.0%). Additionally, patients ≤ 24 years old had the lowest rate of treatment retention, while patients aged ≥ 35 had the highest., Conclusions: This study adds to the limited data regarding long-term retention in MOUD. Our findings indicate gender and age were highly correlated with retention in MOUD treatment.

Introduction: Despite advances in immunomodulatory treatments of multiple sclerosis (MS), patients with non-active progressive multiple sclerosis (PMS) continue to face a significant unmet need. Demyelination, smoldering inflammation and neurodegeneration are important drivers of disability progression that are insufficiently targeted by current treatment approaches. Promising preclinical data support repurposing of metformin for treatment of PMS. The objective of this clinical trial is to evaluate whether metformin, as add-on treatment, is superior to placebo in delaying disease progression in patients with non-active PMS., Methods and Analysis: MACSiMiSE-BRAIN is a multi-center two-arm, 1:1 randomized, triple-blind, placebo-controlled clinical trial, conducted at five sites in Belgium. Enrollment of 120 patients with non-active PMS is planned. Each participant will undergo a screening visit with assessment of baseline magnetic resonance imaging (MRI), clinical tests, questionnaires, and a safety laboratory assessment. Following randomization, participants will be assigned to either the treatment (metformin) or placebo group. Subsequently, they will undergo a 96-week follow-up period. The primary outcome is change in walking speed, as measured by the Timed 25-Foot Walk Test, from baseline to 96 weeks. Secondary outcome measures include change in neurological disability (Expanded Disability Status Score), information processing speed (Symbol Digit Modalities Test) and hand function (9-Hole Peg test). Annual brain MRI will be performed to assess evolution in brain volumetry and diffusion metrics. As patients may not progress in all domains, a composite outcome, the Overall Disability Response Score will be additionally evaluated as an exploratory outcome. Other exploratory outcomes will consist of paramagnetic rim lesions, the 2-minute walking test and health economic analyses as well as both patient- and caregiver-reported outcomes like the EQ-5D-5L, the Multiple Sclerosis Impact Scale and the Caregiver Strain Index., Ethics and Dissemination: Clinical trial authorization from regulatory agencies [Ethical Committee and Federal Agency for Medicines and Health Products (FAMHP)] was obtained after submission to the centralized European Clinical Trial Information System. The results of this clinical trial will be disseminated at scientific conferences, in peer-reviewed publications, to patient associations and the general public., Trial Registration: ClinicalTrials.gov Identifier: NCT05893225, EUCT number: 2023-503190-38-00., Competing Interests: A-VD received conference travel support from Biogen and research funding from Belgian Charcot Foundation. VP has received honoraria and travel and research grants from Almirall, Biogen, Medtronic, Merck, Novartis, Roche, Sanofi-Genzyme, Teva Pharmaceuticals. GL and/or his institution received speaker honoraria, advisory board fees, research support, or conference travel support from Biogen, BMS/Celgene, Merck Healthcare KGaA Darmstadt, Germany, Sanofi, Teva, Roche, and Novartis. TR has received honoraria as a member of Scientific Advisory Boards/Consultancy for Biogen, Novartis, Roche, Sanofi-Genzyme and speaker honoraria and travel support from Biogen, Roche, Sanofi-Genzyme, which were all paid to UZA. BW received honoraria for acting as a member of Scientific Advisory Boards/Consultancy for Almirall, Biogen, Celgene/BMS, Merck, Janssen, Novartis, Roche, Sandoz, Sanofi-Genzyme and speaker honoraria and travel support from Biogen, Celgene/BMS, Merck, Novartis, Roche, SanofiGenzyme; research and/or patient support grants from Biogen, Janssen, Merck, Sanofi-Genzyme, Roche. Honoraria and grants were paid to UZA/UZA Foundation. Further, BW received research funding from FWO-TBM, Belgian Charcot Foundation, Start2Cure Foundation, Queen Elisabeth Medical Foundation for Neurosciences and the National MS Society USA. The remaining authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest. The author(s) declared that they were an editorial board member of Frontiers, at the time of submission. This had no impact on the peer review process and the final decision., (Copyright © 2024 De Keersmaecker, Van Doninck, Popescu, Willem, Cambron, Laureys, D’ Haeseleer, Bjerke, Roelant, Lemmerling, D’hooghe, Derdelinckx, Reynders and Willekens.)

Background and Aims: Primary sclerosing cholangitis (PSC) is an immune-mediated cholestatic liver disease for which pharmacological treatment options are currently unavailable. PSC is strongly associated with colitis and a disruption of the gut-liver axis, and macrophages are involved in the pathogenesis of PSC. However, how gut-liver interactions and specific macrophage populations contribute to PSC is incompletely understood., Approach and Results: We investigated the impact of cholestasis and colitis on the hepatic and colonic microenvironment, and performed an in-depth characterization of hepatic macrophage dynamics and function in models of concomitant cholangitis and colitis. Cholestasis-induced fibrosis was characterized by depletion of resident KCs, and enrichment of monocytes and monocyte-derived macrophages (MoMFs) in the liver. These MoMFs highly express triggering-receptor-expressed-on-myeloid-cells-2 ( Trem2 ) and osteopontin ( Spp1 ), markers assigned to hepatic bile duct-associated macrophages, and were enriched around the portal triad, which was confirmed in human PSC. Colitis induced monocyte/macrophage infiltration in the gut and liver, and enhanced cholestasis-induced MoMF- Trem2 and Spp1 upregulation, yet did not exacerbate liver fibrosis. Bone marrow chimeras showed that knockout of Spp1 in infiltrated MoMFs exacerbates inflammation in vivo and in vitro , while monoclonal antibody-mediated neutralization of SPP1 conferred protection in experimental PSC. In human PSC patients, serum osteopontin levels are elevated compared to control, and significantly increased in advanced stage PSC and might serve as a prognostic biomarker for liver transplant-free survival., Conclusions: Our data shed light on gut-liver axis perturbations and macrophage dynamics and function in PSC and highlight SPP1/OPN as a prognostic marker and future therapeutic target in PSC., (Copyright © 2023 The Author(s). Published by Wolters Kluwer Health, Inc.)

Background: Throughout the evolution of the COVID-19 pandemic, the severity of the disease has varied. The aim of this study was to determine how patients' comorbidities affected and were related to, different outcomes during this time., Methods: Retrospective cohort study of all patients testing positive for SARS-CoV-2 infection between March 1, 2020, and January 9, 2022. We extracted sociodemographic, basal comorbidities, prescribed treatments, COVID-19 vaccination data, and outcomes such as death and admission to hospital and intensive care unit (ICU) during the different periods of the pandemic. We used logistic regression to quantify the effect of each covariate in each outcome variable and a random forest algorithm to select the most relevant comorbidities., Results: Predictors of death included having dementia, heart failure, kidney disease, or cancer, while arterial hypertension, diabetes, ischemic heart, cerebrovascular, peripheral vascular diseases, and leukemia were also relevant. Heart failure, dementia, kidney disease, diabetes, and cancer were predictors of adverse evolution (death or ICU admission) with arterial hypertension, ischemic heart, cerebrovascular, peripheral vascular diseases, and leukemia also relevant. Arterial hypertension, heart failure, diabetes, kidney, ischemic heart diseases, and cancer were predictors of hospitalization, while dyslipidemia and respiratory, cerebrovascular, and peripheral vascular diseases were also relevant., Conclusions: Preexisting comorbidities such as dementia, cardiovascular and renal diseases, and cancers were those most related to adverse outcomes. Of particular note were the discrepancies between predictors of adverse outcomes and predictors of hospitalization and the fact that patients with dementia had a lower probability of being admitted in the first wave., Competing Interests: The authors declare that they have no conflict of interest., (© 2024 The Authors. Influenza and Other Respiratory Viruses published by John Wiley & Sons Ltd.)

Plant communities are being exposed to changing environmental conditions all around the globe, leading to alterations in plant diversity, community composition, and ecosystem functioning. For herbaceous understorey communities in temperate forests, responses to global change are postulated to be complex, due to the presence of a tree layer that modulates understorey responses to external pressures such as climate change and changes in atmospheric nitrogen deposition rates. Multiple investigative approaches have been put forward as tools to detect, quantify and predict understorey responses to these global-change drivers, including, among others, distributed resurvey studies and manipulative experiments. These investigative approaches are generally designed and reported upon in isolation, while integration across investigative approaches is rarely considered. In this study, we integrate three investigative approaches (two complementary resurvey approaches and one experimental approach) to investigate how climate warming and changes in nitrogen deposition affect the functional composition of the understorey and how functional responses in the understorey are modulated by canopy disturbance, that is, changes in overstorey canopy openness over time. Our resurvey data reveal that most changes in understorey functional characteristics represent responses to changes in canopy openness with shifts in macroclimate temperature and aerial nitrogen deposition playing secondary roles. Contrary to expectations, we found little evidence that these drivers interact. In addition, experimental findings deviated from the observational findings, suggesting that the forces driving understorey change at the regional scale differ from those driving change at the forest floor (i.e., the experimental treatments). Our study demonstrates that different approaches need to be integrated to acquire a full picture of how understorey communities respond to global change., (© 2023 John Wiley & Sons Ltd.)

Background: A high prevalence of onchocerciasis-associated epilepsy (OAE) has been observed in onchocerciasis-endemic areas with high ongoing Onchocerca volvulus transmission. However, the pathogenesis of OAE remains to be elucidated. We hypothesise that the O. volvulus virome could be involved in inducing epilepsy. With this study, we aim to describe the O. volvulus virome and identify potential neurotropic viruses linked to OAE., Methods: In Maridi County, an onchocerciasis endemic area in South Sudan with a high prevalence of OAE, we will conduct an exploratory case-control study enrolling 40 persons aged 12 years and above with palpable onchocerciasis nodules. Cases will be participants with OAE (n=20), who will be age- and village-matched with controls without epilepsy (n=20). For each study participant, two skin snips at the iliac crest will be obtained to collect O. volvulus microfilariae, and one nodulectomy will be performed to obtain adult worms. A viral metagenomic study will be conducted on microfilariae and adult worms, and the O. volvulus virome of persons with and without OAE will be compared. The number, size, and localisation of onchocerciasis nodules in persons with and without OAE will be described. Moreover, the pre- and post-nodulectomy frequency of seizures in persons with OAE will be compared., Ethics and Dissemination: The protocol has been approved by the Ethics Committee of the University of Antwerp and the Ministry of Health of South Sudan. Findings will be disseminated nationally and internationally via meetings and peer-reviewed publications., Registration: ClinicalTrials.gov registration NCT05868551 ( https://clinicaltrials.gov/study/NCT05868551)., Protocol Version: 1.1, dated 09/05/2023., Competing Interests: No competing interests were disclosed., (Copyright: © 2023 Hadermann A et al.)

We reflect on epidemiological modeling conducted throughout the COVID-19 pandemic in Western Europe, specifically in Belgium, France, Italy, the Netherlands, Portugal, Switzerland, and the United Kingdom. Western Europe was initially one of the worst-hit regions during the COVID-19 pandemic. Western European countries deployed a range of policy responses to the pandemic, which were often informed by mathematical, computational, and statistical models. Models differed in terms of temporal scope, pandemic stage, interventions modeled, and analytical form. This diversity was modulated by differences in data availability and quality, government interventions, societal responses, and technical capacity. Many of these models were decisive to policy making at key junctures, such as during the introduction of vaccination and the emergence of the Alpha, Delta, and Omicron variants. However, models also faced intense criticism from the press, other scientists, and politicians around their accuracy and appropriateness for decision making. Hence, evaluating the success of models in terms of accuracy and influence is an essential task. Modeling needs to be supported by infrastructure for systems to collect and share data, model development, and collaboration between groups, as well as two-way engagement between modelers and both policy makers and the public.

The consumption of sausage worldwide increases every year; because of this increase, artisanal products have appeared and are intended to be perceived as natural and healthy. Obesity and cardiovascular diseases associated with consuming meat and meat derivatives have been estimated to be the leading cause of death in several countries. This study aimed to evaluate the nutritional quality, lipid content, and presence of saturated and unsaturated fatty acids, contributing to demonstrating the real nutritional value of artisanal sausages produced in Ecuador. Sausages from 10 factories in Ambato, Pelileo, and Píllaro, located in Tungurahua, Ecuador, were evaluated. The pH and acidity, color, proximal, sensory, microbiological, and lipid content were assessed. The pH and acidity showed a slight variation in all of the samples. Proximal analysis (moisture, protein, fat, and ash) established that the artisan sausages did not differ from the type of sausages reported in the literature. Microbiological analyses showed a good microbial quality, and there was no presence of Staphylococcus aureus , Enterobacteria , molds, or yeasts. The sensory attributes were similar for all of the sausages; the panelists did not notice any strange taste or odor. The lipid content showed that the artisanal sausages contained the highest percentage of palmitic, stearic, elaidic, and linolelaidic fatty acids. Unsaturated fatty acids were the most prevalent in all of the sausages collected from different locations. The results showed that the nutritional, microbiological, and sensory quality of the artisanal sausages did not show any parameter that would allow them to be classified as different or as having a better nutritional value.

The goal of tracing, testing, and quarantining contacts of infected individuals is to contain the spread of infectious diseases, a strategy widely used during the COVID-19 pandemic. However, limited research exists on the effectiveness of contact tracing, especially with regard to key performance indicators (KPIs), such as the proportion of cases arising from previously identified contacts. In our study, we analyzed contact tracing data from Belgium collected between September 2020 and December 2021 to assess the impact of contact tracing on SARS-CoV-2 transmission and understand its characteristics. Among confirmed cases involved in contact tracing in the Flemish and Brussels-Capital regions, 19.1% were previously identified as close contacts and were aware of prior exposure. These cases, referred to as 'known' to contact tracing operators, reported on average fewer close contacts compared to newly identified individuals (0.80 versus 1.05), resulting in fewer secondary cases (0.23 versus 0.28). Additionally, we calculated the secondary attack rate, representing infections per contact, which was on average lower for the 'known' cases (0.22 versus 0.25) between December 2020 and August 2021. These findings indicate the effectiveness of contact tracing in Belgium in reducing SARS-CoV-2 transmission. Although we were unable to quantify the exact number of prevented cases, our findings emphasize the importance of contact tracing as a public health measure. In addition, contact tracing data provide indications of potential shifts in transmission patterns among different age groups associated with emerging variants of concern and increasing vaccination rates., Competing Interests: Naima Hammami is an employee of the the Flemish Government’s Department of Care and Jorden Boone has been working as a consultant for this agency during the COVID-19 pandemic. Niel Hens declares that the Universities of Antwerp and Hasselt have received funding for advisory boards and research projects of MSD, GSK, JnJ, Pfizer outside the proposed work. Niel Hens has not received any personal remuneration related to this work. The other authors declare that they have no competing interests. This does not alter our adherence to PLOS ONE policies on sharing data and materials., (Copyright: © 2023 Kremer et al. This is an open access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.)

We report the sequences of four complete genomes of parvovirus B19, extracted from human amniotic fluid specimens collected from pregnant women with abnormal ultrasound features in France. The genome sequences are 5,596 nucleotides long and include long terminal repeats. Several amino acid substitutions were observed in nonstructural protein (NS1)., Competing Interests: The authors declare no conflict of interest.

Numerous biomedical applications have been described for liver-humanized mouse models, such as in drug metabolism or drug-drug interaction (DDI) studies. However, the strong enlargement of the bile acid (BA) pool due to lack of recognition of murine intestine-derived fibroblast growth factor-15 by human hepatocytes and a resulting upregulation in the rate-controlling enzyme for BA synthesis, cytochrome P450 (CYP) 7A1, may pose a challenge in interpreting the results obtained from such mice. To address this challenge, the human fibroblast growth factor-19 (FGF19) gene was inserted into the Fah -/- , Rag2 -/- , Il2rg -/- NOD (FRGN) mouse model, allowing repopulation with human hepatocytes capable of responding to FGF19. While a decrease in CYP7A1 expression in human hepatocytes from humanized FRGN19 mice (huFRGN19) and a concomitant reduction in BA production was previously shown, a detailed analysis of the BA pool in these animals has not been elucidated. Furthermore, there are sparse data on the use of this model to assess potential clinical DDI. In the present work, the change in BA composition in huFRGN19 compared with huFRGN control animals was systematically evaluated, and the ability of the model to recapitulate a clinically described CYP3A4-mediated DDI was assessed. In addition to a massive reduction in the total amount of BA, FGF19 expression in huFRGN19 mice resulted in significant changes in the profile of various primary, secondary, and sulfated BAs in serum and feces. Moreover, as observed clinically, administration of the pregnane X receptor agonist rifampicin reduced the oral exposure of the CYP3A4 substrate triazolam. SIGNIFICANCE STATEMENT: Transgenic expression of FGF19 normalizes the unphysiologically high level of bile acids in a chimeric liver-humanized mouse model and leads to massive changes in bile acid composition. These adaptations could overcome one of the potential impediments in the use of these mouse models for drug-drug interaction studies., (Copyright © 2023 by The American Society for Pharmacology and Experimental Therapeutics.)

Problem : High-quality communication improves patient satisfaction and clinical outcomes, yet formal communication training in residency is often minimal. Many studies on empathic communication show mixed results and are often hindered and skewed by brief study lengths, insufficiently and ambiguously defined concepts, and limited methods for objective measurements. Intervention : The FAN Curriculum is a unique communication curriculum, based on the conceptual frameworks of patient-centered communication, reflective practice, mindfulness, and attunement using the Facilitating Attuned Interactions (FAN) model. The first part of the FAN Curriculum was delivered as a 3-hour interactive workshop involving didactics, group discussion, and role play with pediatric residents. Residents then completed weekly self-reflections, a follow-up one-hour training to reinforce concepts, and five monthly mentor sessions, all emphasizing reflective practice. Context : This longitudinal, mixed-methods study examined the effects of the FAN Curriculum on residents' empathy levels and ability to communicate with parents in the clinical setting. The study was conducted at two urban, academic, medium-sized pediatric residency programs in Chicago between October 2016 and November 2017. First- and second-year pediatric residents whose continuity clinic site was located at their home institution participated. Residents received training in the use of the FAN Communication Tool using a delayed-start crossover study design. Impact : At five time points, residents and parents completed instruments validated for measuring physician empathy and mindfulness. Post-study interviews were conducted for one institution's residents and mentors and were evaluated using open and focused coding. Participants (n = 23) demonstrated a high degree of use of the FAN Communication Tool six months post-training and a significant rise in self-reported comfort with four of five FAN core processes. One parent-completed survey (Consultation and Relational Empathy, CARE) showed a statistically significant rise of 3.26% in resident relational empathy and collaboration after training (p = 0.02). In qualitative analysis of interviews, residents and mentors found the FAN Communication Tool beneficial, making clinic visits more efficient and collaborative. Both groups noted improvement in the residents' relationship-building skills; residents were able to use enhanced communication skills to better approach challenging encounters and work through parent concerns. Lessons Learned : Family-centered communication training can improve physician-perceived empathy and mindfulness. Effective communication for pediatric residents incorporates an empathic approach, and introduction to this formal curriculum supported their growth in connecting and engaging with children and parents. The FAN Curriculum may provide a useful method for improving resident communication skills with a positive impact on pediatricians' collaboration with patients and families.

Background: West Nile virus (WNV) and Usutu virus (USUV) are emerging arthropod-borne viruses (arboviruses) in Europe transmitted by Culex mosquitoes. In Belgium, it is currently unknown which Culex species are competent vectors for WNV or USUV and if these mosquitoes carry Wolbachia, an endosymbiotic bacterium that can block arbovirus transmission. The aims of our study were to measure the vector competence of Belgian Culex mosquitoes to WNV and USUV and determine if a naturally acquired Wolbachia infection can influence virus transmission., Methodology/principal Findings: Female Culex mosquitoes were captured from urban and peri-urban sites in Leuven, Belgium and offered an infectious bloodmeal containing WNV lineage 2, USUV European (EU) lineage 3, or USUV African (AF) lineage 3. Blood-fed females were incubated for 14 days at 25°C after which the body, head, and saliva were collected to measure infection, dissemination, and transmission rates as well as transmission efficiency. Mosquito species were identified by qRT-PCR or Sanger sequencing, the presence of infectious virus in mosquitoes was confirmed by plaque assays, and viral genome copies were quantified by qRT-PCR. Culex pipiens pipiens were able to transmit WNV (4.3% transmission efficiency, n = 2/47) but not USUV (EU lineage: n = 0/56; AF lineage: n = 0/37). In contrast, Culex modestus were able to transmit USUV (AF lineage: 20% transmission efficiency, n = 1/5) but not WNV (n = 0/6). We found that the presence or absence of Wolbachia was species-dependent and did not associate with virus transmission., Conclusions/significance: This is the first report that Belgian Culex mosquitoes can transmit both WNV and USUV, forewarning the risk of human transmission. More research is needed to understand the potential influence of Wolbachia on arbovirus transmission in Culex modestus mosquitoes., Competing Interests: The authors have declared that no competing interests exist., (Copyright: © 2023 Soto et al. This is an open access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.)

Detection dogs were trained to detect SARS-CoV-2 infection based on armpit sweat odor. Sweat samples were collected using cotton pads under the armpits of negative and positive human patients, confirmed by qPCR, for periods of 15-30 min. Multiple hospitals and organizations throughout Belgium participated in this study. The sweat samples were stored at -20°C prior to being used for training purposes. Six dogs were trained under controlled atmosphere conditions for 2-3 months. After training, a 7-day validation period was conducted to assess the dogs' performances. The detection dogs exhibited an overall sensitivity of 81%, specificity of 98%, and an accuracy of 95%. After validation, training continued for 3 months, during which the dogs' performances remained the same. Gas chromatography/mass spectrometry (GC/MS) analysis revealed a unique sweat scent associated with SARS-CoV-2 positive sweat samples. This scent consisted of a wide variety of volatiles, including breakdown compounds of antiviral fatty acids, skin proteins and neurotransmitters/hormones. An acceptability survey conducted in Belgium demonstrated an overall high acceptability and enthusiasm toward the use of detection dogs for SARS-CoV-2 detection. Compared to qPCR and previous canine studies, the detection dogs have good performances in detecting SARS-CoV-2 infection in humans, using frozen sweat samples from the armpits. As a result, they can be used as an accurate pre-screening tool in various field settings alongside the PCR test., Competing Interests: CC is the founder of DrArmpit BV. AA and AM are founders of Arome Science Inc. The remaining authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest. The reviewer A-LC is currently co-organizing a Research Topic with one of the authors DG., (Copyright © 2023 Callewaert, Pezavant, Vandaele, Meeus, Vankrunkelsven, Van Goethem, Plumacker, Misset, Darcis, Piret, De Vleeschouwer, Staelens, Van Varenbergh, Tombeur, Ottevaere, Montag, Vandecandelaere, Jonckheere, Vandekerckhove, Tobback, Wieers, Marot, Anseeuw, D’Hoore, Tuyls, De Tavernier, Catteeuw, Lotfi, Melnik, Aksenov, Grandjean, Stevens, Gasthuys and Guyot.)

Marine macroalgae (seaweeds) are important primary producers and foundation species in coastal ecosystems around the world. Seaweeds currently contribute to an estimated 51% of the global mariculture production, with a long-term growth rate of 6% per year, and an estimated market value of more than US$11.3 billion. Viral infections could have a substantial impact on the ecology and aquaculture of seaweeds, but surprisingly little is known about virus diversity in macroalgal hosts. Using metagenomic sequencing, we characterized viral communities associated with healthy and bleached specimens of the commercially important green seaweed Ulva . We identified 20 putative new and divergent viruses, of which the majority belonged to the Circular Rep-Encoding Single-Stranded (CRESS) DNA viruses [single-stranded (ss)DNA genomes], Durnavirales [double-stranded (ds)RNA], and Picornavirales (ssRNA). Other newly identified RNA viruses were related to the Ghabrivirales , the Mitoviridae , and the Tombusviridae . Bleached Ulva samples contained particularly high viral read numbers. While reads matching assembled CRESS DNA viruses and picorna-like viruses were nearly absent from the healthy Ulva samples (confirmed by qPCR), they were very abundant in the bleached specimens. Therefore, bleaching in Ulva could be caused by one or a combination of the identified viruses but may also be the result of another causative agent or abiotic stress, with the viruses simply proliferating in already unhealthy seaweed tissue. This study highlights how little we know about the diversity and ecology of seaweed viruses, especially in relation to the health and diseases of the algal host, and emphasizes the need to better characterize the algal virosphere. IMPORTANCE Green seaweeds of the genus Ulva are considered a model system to study microbial interactions with the algal host. Remarkably little is known, however, about viral communities associated with green seaweeds, especially in relation to the health of the host. In this study, we characterized the viral communities associated with healthy and bleached Ulva . Our findings revealed the presence of 20 putative novel viruses associated with Ulva , encompassing both DNA and RNA viruses. The majority of these viruses were found to be especially abundant in bleached Ulva specimens. This is the first step toward understanding the role of viruses in the ecology and aquaculture of this green seaweed.