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In this study, we aimed to understand the potential role of the gut microbiome in the development of Alzheimers disease (AD). We took a multi-faceted approach to investigate this relationship. Urine metabolomics were examined in individuals with AD and controls, revealing decreased formate and fumarate concentrations in AD. Additionally, we utilised whole-genome sequencing (WGS) data obtained from a separate group of individuals with AD and controls. This information allowed us to create and investigate host-microbiome personalised whole-body metabolic models. Notably, AD individuals displayed diminished formate microbial secretion in these models. Additionally, we identified specific reactions responsible for the production of formate in the host, and interestingly, these reactions were linked to genes that have correlations with AD. This study suggests formate as a possible early AD marker and highlights genetic and microbiome contributions to its production. The reduced formate secretion and its genetic associations point to a complex connection between gut microbiota and AD. This holistic understanding might pave the way for novel diagnostic and therapeutic avenues in AD management.

The order Sordariales is taxonomically diverse, and harbours many species with different lifestyles and large economic importance. Despite its importance, a robust genome-scale phylogeny, and associated comparative genomic analysis of the order is lacking. In this study, we examined whole-genome data from 99 Sordariales, including 52 newly sequenced genomes, and seven outgroup taxa. We inferred a comprehensive phylogeny that resolved several contentious relationships amongst families in the order, and cleared-up intrafamily relationships within the Podosporaceae. Extensive comparative genomics showed that genomes from the three largest families in the dataset (Chaetomiaceae, Podosporaceae and Sordariaceae) differ greatly in GC content, genome size, gene number, repeat percentage, evolutionary rate, and genome content affected by repeat-induced point mutations (RIP). All genomic traits showed phylogenetic signal, and ancestral state reconstruction revealed that the variation of the properties stems primarily from within-family evolution. Together, the results provide a thorough framework for understanding genome evolution in this important group of fungi.

The recruitment life stage, including germination and early seedling establishment, is the most vulnerable life stage of plants and has cascading effects on plant performance at later life stages. However, surprisingly little is known on the eco-evolutionary processes that determine the success of biological invasions at this life stage. We performed germination experiments with and without simulated drought stress and monitored early seedling growth in diploid and tetraploid Centaurea stoebe. While diploids are the major cytotype in the native European range, only tetraploids became invasive in North America. Thus, C. stoebe is an excellent model species to simultaneously study both, pre-adaptive differences in the native range (diploids vs. tetraploids) and post-introduction evolution in the non-native range (native tetraploids vs. non-native tetraploids). To account for broad spatial-environmental variation within cytotypes and ranges, we germinated 23,928 seeds from 208 widely distributed populations. Tetraploids germinated better than diploids. Within tetraploids, invasive populations outperformed native populations in germination. However, these differences were not evident under simulated drought stress. Seedlings of invasive tetraploids had a higher biomass and developed the first true leaf earlier than those from the native range, while the native cytotypes did not differ in these early seedling traits. Our results suggest that a combination of pre-adaptation related to superior performance of polyploids (greater and faster germination) and post-introduction evolution towards higher performance in the invasive range (greater and faster germination, greater and faster accumulation of seedling biomass) may have contributed to the invasion success of tetraploid C. stoebe in North America.

Generating synthetic contrast-enhanced liver MRI scans from native MRI images can serve to mitigate the issue of sparse contrast-enhanced image datasets while concurrently circumventing the time-consuming and costly process of administering contrast agents during image acquisition. In this study, we conducted three experiments using paired image-to-image translation techniques. Native T1 sequences showing the abdominal liver region served as the input, while contrast-enhanced T1 sequences were the target. The data preprocessing methods and image boundaries were varied for the individual experiments in addition to the implementation of a 5-fold cross-validation for the top-performing approach. Focusing on liver regions achieved the best results with a mean absolute error (MAE) of 0.0837 ± 0.0068, a mean squared error (MSE) of 0.0128 ± 0.0023 and a peak signal-to-noise ratio (PSNR) of 18.99 ± 0.81 dB. Our findings serve as a proof-of-concept, demonstrating the feasibility of generating contrast-enhanced MRI images. However, the current state necessitates further enhancements for effectively addressing the challenge posed by limited dataset sizes with difficult anatomical circumstances as well as MR imaging-related heterogenous tissue contrasts.

The increased clinical relevance of image-guided procedures, particularly of interventional magnetic resonance imaging (iMRI), highlights the need for advanced devices and robotics to optimize those procedures. To enable a realistic integration of robotics into the clinical workflow, robotic-patient interfaces (RPI) are required to ensure both functionality and usability. However, current concepts have issues with patient accessibility and safety, user handling, or performing interventions on versatile body regions. This work presents a novel silicone-based RPI to flexibly mount the ’Micropositioning Robotics for Image-Guided Surgery’ (μRIGS) system on differently shaped body regions through vacuum, regulated with an electronic miniature pump. Maximum holding forces of 60N at −0.1 bar and 66N at −0.2 bar relative vacuum pressure were reached depending on the applied human body area and tensile force angles. MRI with the integrated metasurface indicated up to 200% signal enhancement, enabling improved tissue contrast within the first 20mm in depth. The multifunctional design supported the incorporation of the sterile iMRI workflow concept. This RPI enables a realistic integration of future technologies such as miniature robots, tracking markers, and instrument holders into complex interventional workflows. Further long-term studies are needed to evaluate the effects of vacuum application lasting for 1-2 hours on different skin types.

In this study, we utilised ground-based in situ measurements of the aerosol chemical composition and particle size distribution, along with meteorological data from the European Centre for Medium-Range Weather Forecasts (ECMWF), to predict vertical profiles of aerosol optical properties, including the aerosol scattering coefficient, backscatter coefficient, extinction coefficient, and lidar ratio. The predicted ambient profiles were compared to retrievals by a multi-wavelength Raman lidar during the Ruisdael Land–Atmosphere Interactions Intensive Trace-gas and Aerosol (RITA) campaign in the Netherlands in 2021 for 26 time periods of approximately 1 h each. Predicted and retrieved extensive aerosol properties (scattering, backscatter, and extinction coefficient) were comparable only approximately 35 % of the time, mostly under the condition of well-mixed boundary layers. In this case, ground-based measurements can provide a way to extend extinction profiles to lower altitudes, where they cannot be retrieved, and to verify the lidar-measured profiles. Accurate representation of hygroscopic growth is required for adjusting the dry size distribution to ambient size distribution, and the estimated relative humidity profile may have a substantial influence on the shape of the calculated profiles. On the other hand, the lidar ratio profiles predicted by ground-based data also compared reasonably well to the retrieved lidar profiles (starting at 800 m) for conditions where the predicted and retrieved backscatter profiles differed considerably. The difference in the predicted and retrieved lidar ratio is usually less than ±30 %. Our study thus shows that, for well-mixed boundary layers, a representative lidar ratio can be estimated from ground-based in situ measurements of chemical composition and dry size distribution. This approach offers a method of providing lidar ratios calculated from independent in situ measurements for simple backscatter lidars or at times when Raman lidar profiles cannot be measured (e.g. during the daytime). It only uses data that are routinely available at aerosol measurement stations and is therefore not only useful for further validating lidar measurements but also for bridging the gap between in situ measurements and lidar remote sensing.

Abstract Background Since June 2017, oral pre-exposure prophylaxis (PrEP) has been reimbursed in Belgium for people at substantial risk of HIV. To inform the national PrEP programme, we described sociodemographic characteristics of PrEP users, PrEP dispensing practices, testing for HIV and sexually transmitted infections (STIs; gonorrhoea, chlamydia and syphilis), and incidence of HIV and STIs. Methods Analysis of routinely collected social health insurance claims data from all individuals who were dispensed at least one PrEP prescription between June 2017 and December 2019. Using logistic regression adjusted for age, we examined associations between sociodemographic characteristics and having been dispensed PrEP only once in the first six months of PrEP use. Results Overall, 4559 individuals were dispensed PrEP. Almost all PrEP users were male (99.2%, 4522/4559), with a median age of 37 years (IQR 30–45). A minority were entitled to an increased healthcare allowance (11.4%, 514/4559). 18% (657/3636) were dispensed PrEP only once in the first six months of PrEP use. PrEP users younger than 25 years, unemployed, entitled to an increased healthcare allowance, and who initiated PrEP between January 2019 and June 2019 were more likely to have had no PrEP dispensing after initiation compared to their counterparts. The testing rates for bacterial STIs and HIV were 4.2 tests per person-year (95% CI 4.1–4.2) and 3.6 tests per person-year (95% CI 3.5–3.6), respectively. Twelve individuals were identified to have seroconverted during the study period, resulting in an HIV incidence rate of 0.21/100 person-years (95% CI 0.12–0.36). The incidence of bacterial STIs was 81.2/100 person-years (95% CI 78.7–83.8). Conclusions The study highlights challenges in PrEP persistence and a high incidence of bacterial STIs among individuals receiving PrEP. Tailored prevention support is crucial for individuals with ongoing HIV risk to optimise PrEP effectiveness. Integrated STI testing and prevention interventions within PrEP care are necessary to mitigate STI acquisition and transmission among PrEP users.

Abstract Background The Yathu Yathu (“For Us, By Us”) cluster-randomized trial (CRT) evaluated a peer-led community-based sexual and reproductive health(SRH) intervention implemented to address persistent barriers to SRH service use among adolescents and young people (AYP). We report the impact of the intervention on coverage of key SRH services among AYP. Methods The trial was conducted from Jul 2019-Oct 2021 in two urban communities in Lusaka, Zambia, divided into 20 zones (~ 2350 AYP/zone). Zones were randomly allocated to intervention (N = 10) or control (N = 10) arm. In all zones, a census was conducted and all AYP aged 15-24-years offered participation. The intervention consisted of peer-led community-based hubs providing SRH services; a prevention points card (PPC) system to incentivize and track SRH service use and community engagement. This paper reports on the outcome of coverage (accessing at least one key SRH service), comparing intervention and control arms using PPC data and standard methods of analysis for CRTs. Results Among enumerated AYP, 93.6% (14,872/15,894) consented to participate from intervention zones and 95.1% (14,500/15,255) from control zones. Among those who accepted a PPC, 63.8% (9,493/14,872) accessed at least one key SRH service during the study period in the intervention arm, compared to 5.4% (776/14,500) in the control arm (adjPR 12.3 95%CI 9.3–16.2, p

Despite the spread of novel-generation cochlear-implant (CI) magnetic systems, access to magnetic resonance imaging (MRI) for CI recipients is still limited due to safety concerns. The aim of this study is to assess and record the experiences of Hires Ultra 3D (Advanced Bionics) recipients who underwent an MRI examination. A multicentric European survey about this topic was conducted focusing on safety issues, and the results were compared with the current literature. We collected a total of 65 MRI scans performed in 9 otologic referral centers for a total of 47 Hires Ultra 3D recipients, including, for the first time, 2 children and 3 teenagers. Preventive measures were represented by scanning time and sedation for children. Head wrapping was used in eight cases, and six of the eight cases received local anesthesia, even if both measures were not needed. Only three patients complained of pain (3/65 examinations, 4.6%) due to the tight head bandage, and one of the three cases required MRI scan interruption. No other adverse events were reported. We believe that these results should encourage MRI execution in accordance with manufacturer recommendations for Ultra 3D recipients.

The recently developed time-of-flight aerosol chemical speciation monitor with a capture vaporizer and a PM2.5 aerodynamic lens (TOF-ACSM-CV-PM2.5) aims to improve the collection efficiency and chemical characterization of aerosol particles with a diameter smaller than 2.5 µm. In this study, comprehensive cross-comparisons were performed between real-time online measurements and offline filter analysis with 24 h collection time. The goal was to evaluate the capabilities of the TOF-ACSM-CV-PM2.5 lens, as well as the accuracy of the TOF-ACSM-CV-PM2.5. The experiments were conducted at Cabauw Experimental Site for Atmospheric Research (CESAR) during the RITA-2021 campaign. The non-refractory fine particulate matter (PM1.0 and PM2.5) was measured by two collocated TOF-ACSM-CV-PM2.5 instruments by placing them behind a PM2.5 and PM1.0 inlet, respectively. A comparison between the ACSMs and PM2.5 and PM1.0 filter samples showed a much better accuracy than ±30 % less given in the previous reports, with average differences less than ±10 % for all inorganic chemical species. In addition, the ACSMs were compared to the Monitoring Instrument for Aerosol and Gas (MARGA) (slope between 0.78 and 0.97 for inorganic compounds, R2≥ 0.93) and a mobility particle size spectrometer (MPSS), measuring the particle size distribution from around 10 to 800 nm (slope was around 1.00, R2= 0.91). The intercomparison of the online measurements and the comparison between the online and offline measurements indicated a low bias (< 10 % for inorganic compounds) and demonstrated the high accuracy and stability of the TOF-ACSM-CV-PM2.5 lens for the atmospheric observations of particle matter. The two ACSMs exhibited an excellent agreement, with differences less than 7 %, which allowed a quantitative estimate of PM1.0 vs. PM2.5 chemical composition. The result showed that the PM1.0 accounted for about 70 %–80 % of the PM2.5 on average. The NO3 mass fraction increased, but the organic carbon (OC) mass fraction decreased from PM1.0 to PM2.5, indicating the size dependence on chemical composition.

Abstract In this study, we aimed to understand the potential role of the gut microbiome in the development of Alzheimer's disease (AD). We took a multi-faceted approach to investigate this relationship. Urine metabolomics were examined in individuals with AD and controls, revealing decreased formate and fumarate concentrations in AD. Additionally, we utilised whole-genome sequencing (WGS) data obtained from a separate group of individuals with AD and controls. This information allowed us to create and investigate host-microbiome personalised whole-body metabolic models. Notably, AD individuals displayed diminished formate microbial secretion in these models. Additionally, we identified specific reactions responsible for the production of formate in the host, and interestingly, these reactions were linked to genes that have correlations with AD. This study suggests formate as a possible early AD marker and highlights genetic and microbiome contributions to its production. The reduced formate secretion and its genetic associations point to a complex connection between gut microbiota and AD. This holistic understanding might pave the way for novel diagnostic and therapeutic avenues in AD management.

Abstract Background Although Zambia has integrated HIV-self-testing (HIVST) into its Human Immunodeficiency Virus (HIV) regulatory frameworks, few best practices to optimize the use of HIV self-testing to increase testing coverage have been documented. We conducted a prospective case study to understand contextual factors guiding implementation of four HIVST distribution models to inform scale-up in Zambia. Methods We used the qualitative case study method to explore user and provider experiences with four HIVST distribution models (two secondary distribution models in Antenatal Care (ANC) and Antiretroviral Therapy (ART) clinics, community-led, and workplace) to understand factors influencing HIVST distribution. Participants were purposefully selected based on their participation in HIVST and on their ability to provide rich contextual experience of the distribution models. Data were collected using observations (n = 31), group discussions (n = 10), and in-depth interviews (n = 77). Data were analyzed using the thematic approach and aligned to the four Consolidated Framework for Implementation Research (CFIR) domains. Results Implementation of the four distribution models was influenced by an interplay of outer and inner setting factors. Inadequate compensation and incentives for distributors may have contributed to distributor attrition in the community-led and workplace HIVST models. Stockouts, experienced at the start of implementation in the secondary-distribution and community-led distribution models often disrupted distribution. The existence of policy and practices aided integration of HIVST in the workplace. External factors complimented internal factors for successful implementation. For instance, despite distributor attrition leading to excessive workload, distributors often multi-tasked to keep up with demand for kits, even though distribution points were geographically widespread in the workplace, and to a less extent in the community-led models. Use of existing communication platforms such as lunchtime and safety meetings to promote and distribute kits, peers to support distributors, reduction in trips by distributors to replenish stocks, increase in monetary incentives and reorganisation of stakeholder roles proved to be good adaptations. Conclusion HIVST distribution was influenced by a combination of contextual factors in variable ways. Understanding how the factors interacted in real world settings informed adaptations to implementation devised to minimize disruptions to distribution.

Background The management of the long-term sequelae of coronavirus disease 2019 (COVID-19) infection, known as post-COVID-19 syndrome (PCS), continues to challenge the medical community, largely owing to a significant gap in the understanding of its aetiology, diagnosis and effective treatment.Aim To examine general practitioners’ (GPs) experiences of caring for patients with PCS and to identify unmet care needs and opportunities for improvement.Design and Setting This study follows a qualitative design, using in-depth semi-structured telephone interviews with GPs (N = 31) from across Germany.Method Interviews were audio-recorded, transcribed verbatim and analysed using qualitative content analysis.Results GPs reported that they were often the first point of contact for patients with persistent symptoms following SARS-CoV-2 infection, with symptoms typically resolving within weeks. While ongoing symptomatic COVID-19 is perceived to be more common, the relevance of PCS to GP practices is considerable given its severe impact on patients’ functioning, social participation and the substantial time required for patient care. GPs coordinate diagnosis and treatment but face challenges because of the unclear definition of PCS and difficulties in attributing symptoms, resulting in a cautious approach to ICD-10 coding. Interviewees highlight lengthy diagnostic pathways and barriers to accessing specialist care.Conclusion The findings confirm the high functional limitations and psychosocial burden of PCS on patients, and the central role of GPs in their care. The study suggests a need for further research and health policy measures to support GPs in navigating diagnostic uncertainty, interprofessional communication and the limited evidence on effective treatments.

Abstract Introduction We used a Programme Science platform, to generate evidence to support the implementation of programmes for sex workers in Africa. Female sex workers are estimated to make up 1.6% (1.3%–1.8%) of the population of women aged 15−49 years in Zimbabwe. We highlight how programme science can be used to help distinguish between when, where and with whom programmes need to be implemented and discuss two case studies that exemplify implementing better (Case study 1 (1 June 2019−30 June 2021) Optimizing implementation of a risk differentiated microplanning intervention) and implementing differently (Case study 2 (1 October 2016−30 September 2022) Reorientating implementation of DREAMS for young women selling sex). Methods Zimbabwe's nationally scaled programme for sex workers was established in 2009 in partnership with sex workers to provide comprehensive services for sex workers and generate evidence for programme design, implementation and scale up. Since inception, comprehensive data have been collected from all sex workers seeking services. As the scope of service provision has expanded so has the scope of data collection and analysis. At enrolment, sex workers are assigned an alphanumeric unique identifier which links consultations within and across programme sites. We conduct descriptive analyses of the Key Population (KP) programme data to guide programme implementation and redesign, embedding programmatic qualitative enquiry as required. Results Two case studies describing different approaches to programme optimization are presented. In the first, an optimization exercise was used to strengthen programme implementation ensuring that the KP programme got back on track after SARS‐COV‐2. In the second, an in‐depth review of research and programme data led to a re‐orientation of the DREAMS programme to ensure that young women at the highest risk of HIV acquisition were enrolled and had access to DREAMS social support interventions in turn strengthening their uptake of HIV prevention. Conclusions Optimizing and sustaining HIV care and treatment programmes requires effective delivery with sufficient scale and intensity for population impact. Our programme science approach guided the scale up of the KP programme in Zimbabwe, providing evidence to support strategy, implementation and ongoing management, and importantly helping us distinguish between when we needed to just implement, implement better or implement differently.

Ammonia (NH3) is an important air pollutant which, as a precursor of fine particulate matter, raises public health concerns. This study analyzes 2.5 years of NH3 observations derived from ground-based (miniDOAS; differential optical absorption spectroscopy) and satellite (IASI; Infrared Atmospheric Sounding Interferometer) remote sensing instruments to quantify, for the first time, temporal variabilities (from interannual to diurnal) in NH3 concentrations in Paris. The IASI and miniDOAS datasets are found to be in relatively good agreement (R>0.70) when atmospheric NH3 concentrations are high and driven by regional agricultural activities. Over the investigated period (January 2020–June 2022), NH3 average concentrations in Paris measured by the miniDOAS and IASI are 2.23 µg m−3 and 7.10×1015 molec. cm−2, respectively, which are lower than or equivalent to those documented in other urban areas. The seasonal and monthly variabilities in NH3 concentrations in Paris are driven by sporadic agricultural emissions influenced by meteorological conditions, with NH3 concentrations in spring up to 2 times higher than in other seasons. The potential source contribution function (PSCF) reveals that the close (100–200 km) east and northeast regions of Paris constitute the most important potential emission source areas of NH3 in the megacity. Weekly cycles of NH3 derived from satellite and ground-based observations show different ammonia sources in Paris. In spring, agriculture has a major influence on ammonia concentrations, and, in the other seasons, multi-platform observations suggest that ammonia is also controlled by traffic-related emissions. In Paris, the diurnal cycle of NH3 concentrations is very similar to the one of NO2, with morning enhancements coincident with intensified road traffic. NH3 evening enhancements synchronous with rush hours are also monitored in winter and fall. NH3 concentrations measured during the weekends are consistently lower than NH3 concentrations measured during weekdays in summer and fall. This is further evidence of a significant traffic source of NH3 in Paris.

Abstract Phenological shifts due to changing climate are often highly species and context specific. Land‐use practices such as mowing or grazing directly affect the phenology of grassland species, but it is unclear if plants are similarly affected by climate change in differently managed grassland systems such as meadows and pastures. Functional traits have a high potential to explain phenological shifts and might help to understand species‐specific and land‐use‐specific phenological responses to changes in climate. In the large‐scale field experiment Global Change Experimental Facility (GCEF), we monitored the first flowering day, last flowering day, flowering duration, and day of peak flowering, of 17 herbaceous grassland species under ambient and future climate conditions, comparing meadows and pastures. Both climate and land use impacted the flowering phenology of plant species in species‐specific ways. We did not find evidence for interacting effects of climate and land‐use type on plant phenology. However, the data indicate that microclimatic and microsite conditions on meadows and pastures were differently affected by future climate, making differential effects on meadows and pastures likely. Functional traits, including the phenological niche and grassland utilization indicator values, explained species‐specific phenological climate responses. Late flowering species and species with a low mowing tolerance advanced their flowering more strongly under future climate. Long flowering species and species following an acquisitive strategy (high specific leaf area, high mowing tolerance, and high forage value) advanced their flowering end more strongly and thus more strongly shortened their flowering under future climate. We associated these trait–response relationships primarily with a phenological drought escape during summer. Our results provide novel insights on how climate and land use impact the flowering phenology of grassland species and we highlight the role of functional traits in mediating phenological responses to climate.