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Abstract Soil is one of the most important reservoirs of antibiotic resistance, global threat that needs to be addressed with the One Health approach. Despite urban parks playing a fundamental role in urban ecosystems, the diffusion, maintenance, and human impact of antibiotic-resistance genes in this substrate are still poorly addressed. To fill in this gap, we adopted a molecular and culturomics approach to study antibiotic resistance in urban parks, accounting for the environmental matrix and the level of urbanization. A higher abundance of efflux-mediated mechanisms in undisturbed environments was observed, while antibiotic alteration or inactivation, and target replacement were more abundant in areas with a higher level of urbanization, also confirmed by significant correlations with anthropogenic features of the environmental matrix. Overall, this study highlights the crucial need to monitor antibiotic resistance in urban parks’ soil through a dual molecular and culturomics approach to fully understand and fight antibiotic resistance diffusion.

Abstract The proline-rich antimicrobial designer peptide Api137 inhibits protein expression in bacteria by binding simultaneously to the ribosomal polypeptide exit tunnel and the release factor (RF), depleting the cellular RF pool and leading to ribosomal arrest at stop codons. This study investigates the additional effect of Api137 on the assembly of ribosomes using an Escherichia coli reporter strain expressing one ribosomal protein per 30S and 50S subunit tagged with mCherry and EGFP, respectively. Separation of cellular extracts derived from cells exposed to Api137 in a sucrose gradient reveals elevated levels of partially assembled and not fully matured precursors of the 50S subunit (pre-50S). High-resolution structures obtained by cryogenic electron microscopy demonstrate that a large proportion of pre-50S states are missing up to five proteins (uL22, bL32, uL29, bL23, and uL16) and have misfolded helices in 23S rRNA domain IV. These data suggest a second mechanism for Api137, wherein it disrupts 50S subunit assembly by inducing the formation of misfolded precursor particles potentially incapable of evolving into active ribosomes, suggesting a bactericidal mechanism.

Abstract Antimicrobial susceptibility testing is a key weapon against antimicrobial resistance. Diagnostic microbiology laboratories use one-size-fits-all testing approaches that are often imprecise, inefficient, and inequitable. Here, we report a personalised approach that adapts laboratory testing for urinary tract infection to maximise the number of appropriate treatment options for each patient. We develop and assess susceptibility prediction models for 12 antibiotics on real-world healthcare data using an individual-level simulation study. When combined with decision thresholds that prioritise selection of World Health Organisation Access category antibiotics (those least likely to induce antimicrobial resistance), the personalised approach delivers more susceptible results (results that encourage prescription of that antibiotic) per specimen for Access category antibiotics than a standard testing approach, without compromising provision of susceptible results overall. Here, we show that personalised antimicrobial susceptibility testing could help tackle antimicrobial resistance by safely providing more Access category antibiotic treatment options to clinicians managing urinary tract infection.

Abstract Previous pattern electroretinogram studies indicate reduced retinal contrast gain in patients with a major depressive disorder (MDD) which may contribute to alterations in visual perception. In line, psychophysical investigations reported elevated contrast thresholds in MDD. This study aims to gain insights into higher-level processing of visual information in MDD by evaluating contrast suppression. We examined contrast suppression of 21 MDD patients and 23 healthy controls (HC) using four different stimulus conditions (spatial frequencies 6.3 and 12.6 cpd at 30% and 60% background contrast) in a psychophysical test. Participants were instructed to adjust perceived contrasts between two vertical target patches, embedded in a horizontally or vertically oriented grid background. With finer stimulus gratings, MDD patients exhibited less contrast suppression compared to HC, particularly when the stimulus contrast was high (p = 0.006; MDD vs. HC = − 45%). Contrast suppression in the HC group was significantly reduced for the coarse compared to the fine grating, while contrast suppression scores in MDD did not change with the spatial properties of the stimulus. The reduced contrast suppression in patients with MDD supports the hypothesis of altered dopaminergic neurotransmission and could be attributed to alterations in the retinal receptive fields or in dysfunctional adaptation mechanisms in depression.

Abstract Breath analysis is an area of significant interest in medical research as it allows for non-invasive sampling with exceptional potential for disease monitoring and diagnosis. Volatile organic compounds (VOCs) found in breath can offer critical insight into a person’s lifestyle and/or disease/health state. To this end, the development of a rapid, sensitive, cost-effective and potentially portable method for the detection of key compounds in breath would mark a significant advancement. Herein, we have designed, built and tested a novel reagent-less atmospheric pressure photoionisation (APPI) source, coupled with mass spectrometry (MS), utilising a bespoke bias electrode within a custom 3D printed sampling chamber for direct analysis of VOCs. Optimal APPI-MS conditions were identified, including bias voltage, cone voltage and vaporisation temperature. Calibration curves were produced for ethanol, acetone, 2-butanone, ethyl acetate and eucalyptol, yielding R2 > 0.99 and limits of detection

Climate change is considered as one of the greatest challenges to humanity, with Africa seen as one of the most affected continents due to low resilience and adaptive capacities. The complex interaction between multiple socio-ecological and economic stressors pose a great challenge to the application of the concept of social justice and its associated principles in managing climate change in Africa. Based on empirical research with 150 respondents and interactions in Libode, this paper highlights that water, food and settlement insecurities, floods, crop and animal losses and water-borne diseases remain some of the key negative impacts of climate change to rural residents in the Eastern Cape Province. Despite these adverse effects, the application of the core principles embedded in social justice as a tool for managing climate change impacts in the study area is elusive due to inadequate socio-economic and natural adjustments in response to actual and/or expected climate change adverse effects. The paper concludes that various forms of socio-economic and environmental inequalities can be reduced to the barest minimum and increase social transformation drastically in the Eastern Cape through the application of the principles of social justice to enhance adaptive capabilities.

Abstract Elucidating the relationship between non-coding regulatory element sequences and gene expression is crucial for understanding gene regulation and genetic variation. We explored this link with the training of interpretable deep learning models predicting gene expression profiles from gene flanking regions of the plant species Arabidopsis thaliana, Solanum lycopersicum, Sorghum bicolor, and Zea mays. With over 80% accuracy, our models enabled predictive feature selection, highlighting e.g. the significant role of UTR regions in determining gene expression levels. The models demonstrated remarkable cross-species performance, effectively identifying both conserved and species-specific regulatory sequence features and their predictive power for gene expression. We illustrated the application of our approach by revealing causal links between genetic variation and gene expression changes across fourteen tomato genomes. Lastly, our models efficiently predicted genotype-specific expression of key functional gene groups, exemplified by underscoring known phenotypic and metabolic differences between Solanum lycopersicum and its wild, drought-resistant relative, Solanum pennellii.

Abstract Safety-critical sensory applications, like medical diagnosis, demand accurate decisions from limited, noisy data. Bayesian neural networks excel at such tasks, offering predictive uncertainty assessment. However, because of their probabilistic nature, they are computationally intensive. An innovative solution utilizes memristors’ inherent probabilistic nature to implement Bayesian neural networks. However, when using memristors, statistical effects follow the laws of device physics, whereas in Bayesian neural networks, those effects can take arbitrary shapes. This work overcome this difficulty by adopting a variational inference training augmented by a “technological loss”, incorporating memristor physics. This technique enabled programming a Bayesian neural network on 75 crossbar arrays of 1,024 memristors, incorporating CMOS periphery for in-memory computing. The experimental neural network classified heartbeats with high accuracy, and estimated the certainty of its predictions. The results reveal orders-of-magnitude improvement in inference energy efficiency compared to a microcontroller or an embedded graphics processing unit performing the same task.

Abstract The impact of bariatric surgery on metabolic and inflammatory status are reflected in the epigenetic profile and telomere length mediated by the changes in the metabolic status of the patients. This study compared the telomere length of children born before versus after maternal bariatric surgery as a surrogate to test the influence of the mother’s metabolic status on children’s telomere length. DNA methylation telomere length (DNAmTL) was estimated from Methylation-EPIC BeadChip array data from a total of 24 children born before and after maternal bariatric surgery in the greater Quebec City area. DNAmTL was inversely associated with chronological age in children (r = − 0.80, p

Abstract Previous studies on brain connectivity correlates of autism have often focused on selective connections and yielded inconsistent results. By applying global fiber tracking and utilizing a within-twin pair design, we aimed to contribute to a more unbiased picture of white matter connectivity in association with clinical autism and autistic traits. Eighty-seven twin pairs (n = 174; 55% monozygotic; 24 with clinical autism) underwent diffusion tensor imaging. Linear regressions assessed within-twin pair associations between structural brain connectivity of anatomically defined brain regions and both clinical autism and autistic traits. These were explicitly adjusted for IQ, other neurodevelopmental/psychiatric conditions and multiple testing, and implicitly for biological sex, age, and all genetic and environmental factors shared by twins. Both clinical autism and autistic traits were associated with reductions in structural connectivity. Twins fulfilling diagnostic criteria for clinical autism had decreased brainstem-cuneus connectivity compared to their co-twins without clinical autism. Further, twins with higher autistic traits had decreased connectivity of the left hippocampus with the left fusiform and parahippocampal areas. These associations were also significant in dizygotic twins alone. Reduced brainstem-cuneus connectivity might point towards alterations in low-level visual processing in clinical autism while higher autistic traits seemed to be more associated with reduced connectivity in networks involving the hippocampus and the fusiform gyrus, crucial especially for processing of faces and other (higher order) visual processing. The observed associations were likely influenced by both genes and environment.

Abstract The novel coronavirus pandemic (COVID-19) has necessitated a global increase in the use of face masks to limit the airborne spread of the virus. The global demand for personal protective equipment has at times led to shortages of face masks for the public, therefore makeshift masks have become commonplace. The severe acute respiratory syndrome caused by coronavirus-2 (SARS-CoV-2) has a spherical particle size of ~97 nm. However, the airborne transmission of this virus requires the expulsion of droplets, typically ~0.6–500 µm in diameter (by coughing, sneezing, breathing, and talking). In this paper, we propose a face covering that has been designed to effectively capture SARS-CoV-2 whilst providing uncompromised comfort and breathability for the wearer. Herein, we describe a material approach that uses amorphous silica microspheres attached to cotton fibres to capture bioaerosols, including SARS CoV-2. This has been demonstrated for the capture of aerosolised proteins (cytochrome c, myoglobin, ubiquitin, bovine serum albumin) and aerosolised inactivated SARS CoV-2, showing average filtration efficiencies of ~93% with minimal impact on breathability.

Abstract A supramolecular photovoltaic strategy is applied to enhance power conversion efficiencies (PCE) of photoelectrochemical devices by suppressing electron–hole recombination after photoinduced electron transfer (PET). Here, the author exploit supramolecular localization of the redox mediator—in close proximity to the dye—through a rotaxane topology, reducing electron–hole recombination in p‐type dye‐sensitized solar cells (p‐DSSCs). Dye PRotaxane features 1,5‐dioxynaphthalene recognition sites (DNP‐arms) with a mechanically‐interlocked macrocyclic redox mediator naphthalene diimide macrocycle (3‐NDI‐ring), stoppering synthetically via click chemistry. The control molecule PStopper has stoppered DNP‐arms, preventing rotaxane formation with the 3‐NDI‐ring. Transient absorption and time‐resolved fluorescence spectroscopy studies show ultrafast (211 ± 7 fs and 2.92 ± 0.05 ps) PET from the dye‐moiety of PRotaxane to its mechanically interlocked 3‐NDI‐ring‐acceptor, slowing down the electron–hole recombination on NiO surfaces compared to the analogue . p‐DSSCs employing PRotaxane (PCE = 0.07%) demonstrate a 30% PCE increase compared to PStopper (PCE = 0.05%) devices, combining enhancements in both open‐circuit voltages (VOC = 0.43 vs 0.36 V) and short‐circuit photocurrent density (JSC = −0.39 vs −0.34 mA cm−2). Electrochemical impedance spectroscopy shows that PRotaxane devices exhibit hole lifetimes (τh) approaching 1 s, a 16‐fold improvement compared to traditional I−/I3−‐based systems (τh = 50 ms), demonstrating the benefits obtained upon nanoengineering of interfacial dye‐regeneration at the photocathode.

Abstract Changes in the abundance and diversity of neural cell types, and their connectivity, shape brain composition and provide the substrate for behavioral evolution. Although investment in sensory brain regions is understood to be largely driven by the relative ecological importance of particular sensory modalities, how selective pressures impact the elaboration of integrative brain centers has been more difficult to pinpoint. Here, we provide evidence of extensive, mosaic expansion of an integration brain center among closely related species, which is not explained by changes in sites of primary sensory input. By building new datasets of neural traits among a tribe of diverse Neotropical butterflies, the Heliconiini, we detected several major evolutionary expansions of the mushroom bodies, central brain structures pivotal for insect learning and memory. The genus Heliconius, which exhibits a unique dietary innovation, pollen-feeding, and derived foraging behaviors reliant on spatial memory, shows the most extreme enlargement. This expansion is primarily associated with increased visual processing areas and coincides with increased precision of visual processing, and enhanced long term memory. These results demonstrate that selection for behavioral innovation and enhanced cognitive ability occurred through expansion and localized specialization in integrative brain centers.

Abstract Applying deep learning to images of cropping systems provides new knowledge and insights in research and commercial applications. Semantic segmentation or pixel-wise classification, of RGB images acquired at the ground level, into vegetation and background is a critical step in the estimation of several canopy traits. Current state of the art methodologies based on convolutional neural networks (CNNs) are trained on datasets acquired under controlled or indoor environments. These models are unable to generalize to real-world images and hence need to be fine-tuned using new labelled datasets. This motivated the creation of the VegAnn - Vegetation Annotation - dataset, a collection of 3775 multi-crop RGB images acquired for different phenological stages using different systems and platforms in diverse illumination conditions. We anticipate that VegAnn will help improving segmentation algorithm performances, facilitate benchmarking and promote large-scale crop vegetation segmentation research.

Abstract The Checklist of the Vascular Plants of the Republic of Guinea (CVPRG) is a specimen-based, expert-validated knowledge product, which provides a concise synthesis and overview of current knowledge on 3901 vascular plant species documented from Guinea (Conakry), West Africa, including their accepted names and synonyms, as well as their distribution and status within Guinea (indigenous or introduced, endemic or not). The CVPRG is generated automatically from the Guinea Collections Database and the Guinea Names Backbone Database, both developed and maintained at the Royal Botanic Gardens, Kew, in collaboration with the staff of the National Herbarium of Guinea. A total of 3505 indigenous vascular plant species are reported of which 3328 are flowering plants (angiosperms); this represents a 26% increase in known indigenous angiosperms since the last floristic overview. Intended as a reference for scientists documenting the diversity and distribution of the Guinea flora, the CVPRG will also inform those seeking to safeguard the rich plant diversity of Guinea and the societal, ecological and economic benefits accruing from these biological resources.

The threat of antimicrobial resistance (AMR) in Malawi is high with reported mortality of 19,300 annually, the 23rd highest age-standardised mortality. One of the drivers of AMR is misuse of antibiotics, a phenomenon that has not been adequately researched in Malawi. This study aims to investigate antimicrobial use using health facility, prescribing and patient indicators in Christian Health Association of Malawi (CHAM) health facilities. This will be a multiple cross-sectional study, which will collect data from facilities (22), prescriptions (660), and patients (303). Data will be collected using KoboToolbox v2021, and exported into Microsoft Excel version 2016 for cleaning and coding. Variables will be categorised according to the antimicrobial use indicators. The study will use STATA Version 14 statistical software for data analysis. Subsequently, facilities will be entered into ArcGIS Version 10.7.1 to map hotspots of irrational antimicrobial use. The study will run from October 2024 to June 2025. This study will provide detailed information on frequently used antimicrobials, the cost of antimicrobials relative to medicine budget, the intensity of exposure to antimicrobials, the availability of antimicrobials, patients' understanding of antimicrobials use, and availability of important documents for antimicrobial use. Secondarily, the study will unravel the prevalence of irrational antimicrobial use, the main factors contributing to it, and location where irrational use is most prevalent. These findings will inform the national antimicrobial stewardship action plan, aiming to safeguard the available antimicrobials.

BackgroundAnti-racism is part of the medical professional ethos. Nevertheless, racism pervades medicine on individual, institutional, and structural levels. The concept of habitus helps to understand deficiencies in enacting anti-racism in practice. We use a habitus-based framework to analyse how medical students in Germany deal with the topic of racism. The research questions are: What are medical students' understandings of racism? How do they deal with the topic in discussions? What difficulties do they face in such discussions?MethodsIn a qualitative-explorative research design, we conducted six online group discussions with 32 medical students from medical schools all over Germany. Data analysis combined qualitative methods from thematic qualitative content analysis and the documentary method.ResultsWe identified five typical ways of dealing with the topic of racism in discussions. The first one ('scientistic') orientates action towards the idea of medicine as an objective science, justifies the use of racial categories as scientific, and defines racism based on intention. The second ('pragmatic') orientates action towards tacit rules of clinical practice, justifies the use of racialised categories as practical and defines racism as an interpersonal problem. The third ('subjectivist') lacks a clear orientation of action for dealing with the topic of racism and instead displays uncertainty and subjectivism in understanding racialised categorisations as well as racism. The fourth ('interculturalist') orientates action towards an ideal of intercultural exchange, understands racialised categorisations as representing cultural differences and interprets racism as prejudice against cultures. The fifth ('critical') orientates action towards sociological scholarship, understands racialised categorisations as social constructs and views racism as a structural problem.ConclusionThe results presented help to understand preconditions of enacting anti-racism in medicine and point to difficulties and learning needs. The heterogenous ways of dealing with the topic require a differentiated approach in medical education.

The pandemic caused millions of deaths around the world and forced governments to take drastic measures to reduce the spread of Coronavirus. Understanding the impact of social distancing measures on urban mobility and the number of COVID-19 cases allows governments to change public policies according to the evolution of the pandemic and plan ahead. Given the increasing rates of vaccination worldwide, immunization data may also represent an important predictor of COVID-19 cases. This study investigates the impact of urban mobility and vaccination upon COVID-19 cases in Belo Horizonte, Brazil using Prophet and ARIMA models to predict future outcomes. The developed models generated projections fairly close to real numbers, and some inferences were drawn through experimentation. Brazil became the epicenter of the COVID-19 epidemic shortly after the first case was officially registered on February 25th, 2020. In response, several municipalities adopted lockdown (total or partial) measures to minimize the risk of new infections. Here, we propose prediction models which take into account mobility and vaccination data to predict new COVID-19 cases.

IntroductionStructured medication reviews (SMRs), introduced in the United Kingdom (UK) in 2020, aim to enhance shared decision-making in medication optimisation, particularly for patients with multimorbidity and polypharmacy. Despite its potential, there is limited empirical evidence on the implementation of SMRs, and the challenges faced in the process. This study is part of a larger DynAIRx (Artificial Intelligence for dynamic prescribing optimisation and care integration in multimorbidity) project which aims to introduce Artificial Intelligence (AI) to SMRs and develop machine learning models and visualisation tools for patients with multimorbidity. Here, we explore how SMRs are currently undertaken and what barriers are experienced by those involved in them.MethodsQualitative focus groups and semi-structured interviews took place between 2022-2023. Six focus groups were conducted with doctors, pharmacists and clinical pharmacologists (n = 21), and three patient focus groups with patients with multimorbidity (n = 13). Five semi-structured interviews were held with 2 pharmacists, 1 trainee doctor, 1 policy-maker and 1 psychiatrist. Transcripts were analysed using thematic analysis.ResultsTwo key themes limiting the effectiveness of SMRs in clinical practice were identified: 'Medication Reviews in Practice' and 'Medication-related Challenges'. Participants noted limitations to the efficient and effectiveness of SMRs in practice including the scarcity of digital tools for identifying and prioritising patients for SMRs; organisational and patient-related challenges in inviting patients for SMRs and ensuring they attend; the time-intensive nature of SMRs, the need for multiple appointments and shared decision-making; the impact of the healthcare context on SMR delivery; poor communication and data sharing issues between primary and secondary care; difficulties in managing mental health medications and specific challenges associated with anticholinergic medication.ConclusionSMRs are complex, time consuming and medication optimisation may require multiple follow-up appointments to enable a comprehensive review. There is a need for a prescribing support system to identify, prioritise and reduce the time needed to understand the patient journey when dealing with large volumes of disparate clinical information in electronic health records. However, monitoring the effects of medication optimisation changes with a feedback loop can be challenging to establish and maintain using current electronic health record systems.

Deux sommets internationaux consacrés à l’océan se sont tenus en janvier 2022 puis en juin 2022 : One Ocean Summit à Brest (France) puis la Conférence des Nations unies sur les océans à Lisbonne (Portugal). Au-delà de l’importance de connaissances scientifiquement établies comme socle pour guider les politiques environnementales et la protection de l’océan, ces deux conférences mettent en évidence de grands enjeux scientifiques et de fortes attentes envers la recherche que l’on peut regrouper en six thématiques : changements climatiques et océan, alimentation – c’est-à-dire ressources halieutiques et aquaculture –, grands fonds océaniques, pollutions, océan polaire, aires marines protégées, océan numérique, ADN environnemental. Ces deux conférences ont lancé ou mis en avant les grandes initiatives internationales, européennes et nationales qui seront structurantes pour les sciences océaniques, notamment la Décennie des Nations unies pour les sciences océaniques au service du développement durable (2021-2030) et au niveau européen la mission « Restore our ocean and waters ». La coopération internationale autour de grandes infrastructures de recherche s’est renforcée comme en témoignent la transformation de Mercator Ocean International en une organisation intergouvernementale ainsi que les initiatives partagées des opérateurs de flottes océanographiques européennes. Globalement, il faut donc souligner le bilan positif pour les sciences océaniques. La recherche s’est organisée et les deux sommets confirment que des moyens y seront consacrés. Le prochain grand rendez-vous sera la conférence des Nations unies sur les océans qui sera coorganisée par la France et le Costa Rica en 2025. Il appartiendra à la communauté scientifique et aux organisateurs de poursuivre cette dynamique en utilisant ces grands sommets pour faire avancer des initiatives internationales concrètes et structurantes pour les sciences océaniques.

Abstract Currently, there are no therapies available to modify the disease progression of Huntington’s disease (HD). Recent clinical trial failures of antisense oligonucleotide candidates in HD have demonstrated the need for new therapeutic approaches. Here, we developed a novel in-silico fragment scanning approach across the surface of mutant huntingtin (mHTT) polyQ and predicted four hit compounds. Two rounds of compound analoging using a strategy of testing structurally similar compounds in an affinity assay rapidly identified GLYN122. In vitro, GLYN122 directly binds and reduces mHTT and induces autophagy in neurons. In vivo, our results confirm that GLYN122 can reduce mHTT in the cortex and striatum of the R/2 mouse model of Huntington’s disease and subsequently improve motor symptoms. Thus, the in-vivo pharmacology profile of GLYN122 is a potential new preclinical candidate for the treatment of HD.

As located in one of the oldest and driest deserts on Earth, soils in the Atacama Desert are greatly affected by atmospheric dust deposited on soil surface and the related fate of water-dispersible colloids (WDCs,

We present a genome assembly from an individual male Carterocephalus palaemon (the Arctic Skipper; Arthropoda; Insecta; Lepidoptera; Hesperiidae). The genome sequence is 394.5 megabases in span. The whole assembly is scaffolded into 31 chromosomal pseudomolecules, including the Z sex chromosome. The mitochondrial genome has also been assembled and is 15.78 kilobases in length. Gene annotation of this assembly on Ensembl identified 17,032 protein coding genes.

Abstract A novel experiment has been devised shedding new light on the phenomenon of unipolar induction, also known as “Faraday’s Paradox”. This is a topic which continues to fascinate scientists and engineers with much debate continuing to this day. In particular, the question of the field co-rotating with the magnet or remaining stationary remains unsettled and supporting evidence exists for both positions. In this study, we present a novel experimental apparatus that includes, for the first time, the relative motion of the measurement circuit including the closing wires, as well as the magnet and disc respectively. The results show that the closing wire needs to be considered as part of the problem, which enables the apparent paradox associated with this phenomenon to be resolved. However, it remains impossible to tell if the field co-rotates with the magnet or if it remains stationary. Instead, direct electron interaction is considered as a viable alternative to resolve remaining paradoxes.

Ubiquitin is not only a posttranslational modifier but itself is subject to modifications, such as acetylation. Characterization of distinct acetylated ubiquitin variants reveals that each acetylation site has a particular impact on ubiquitin structure and its protein-protein interaction properties.

Abstract Accurate quantification of blood creatinine is important to estimate the glomerular filtration rate. Existing techniques using liquid chromatography tandem mass spectrometry (LC–MS/MS) have a high accuracy and eliminate most interferences encountered in routine enzymatic and Jaffé methods. However, they require laborious and time-consuming sample treatment and data acquisition. The aim of this study is to develop a fast and simple method to enable a direct analysis of whole blood creatinine with performance measures that are comparable to conventional LC–MS/MS. 5μL whole blood is formed as a three-dimensional spheroid on hydrophobic silanized paper substrates which then undergoes paper-spray ionization—tandem mass spectrometry (PSI–MS/MS). The method is validated using real human samples and compared with LC–MS/MS. PSI–MS/MS whole blood analysis exhibited a lower limit of quantification of 2.5 μg/mL, precision ≤ 6.3%, recovery in the range of 88–94% and excellent linearity (R2 > 0.99; 2.5—20 μg/mL) covering the normal range for creatinine levels. Creatinine levels were comparable to those measured by LC–MS/MS with small deviations of less than 0.3 μg/mL. This simple, fast and accurate microsampling technique for direct analysis of creatinine from whole blood shows promise for routine clinical screening and monitoring. This approach can be readily extended for other analytes of interest and, due to inherent advantages relating to cost, storability, speed, and simplicity, it can be especially advantageous for use in resource-limited settings.

Summary: The severe acute respiratory syndrome coronavirus 2 (SARS-CoV2) Omicron variant sub-lineages spread rapidly worldwide, mostly due to their immune-evasive properties. This has put a significant part of the population at risk for severe disease and underscores the need for effective anti-SARS-CoV-2 agents against emergent strains in vulnerable patients. Camelid nanobodies are attractive therapeutic candidates due to their high stability, ease of large-scale production, and potential for delivery via inhalation. Here, we characterize the receptor binding domain (RBD)-specific nanobody W25 and show superior neutralization activity toward Omicron sub-lineages in comparison to all other SARS-CoV2 variants. Structure analysis of W25 in complex with the SARS-CoV2 spike glycoprotein shows that W25 engages an RBD epitope not covered by any of the antibodies previously approved for emergency use. In vivo evaluation of W25 prophylactic and therapeutic treatments across multiple SARS-CoV-2 variant infection models, together with W25 biodistribution analysis in mice, demonstrates favorable pre-clinical properties. Together, these data endorse W25 for further clinical development.

Background: The population of older adults is growing in sub-Saharan Africa. Ageing exponentially increases fragility fracture risk. Of all global regions, Africa is projected to observe the greatest increase in fragility fractures. Fractures cause pain, disability and sometimes death, and management is expensive, often requiring complex healthcare delivery. For countries to plan future healthcare services, understanding is needed of fracture epidemiology, associated health service costs and the currently available healthcare resources. Methods: The Fractures-E3 5-year mixed-methods research programme will investigate the epidemiology, economic impact, and treatment provision for fracture and wider musculoskeletal health in The Gambia, South Africa and Zimbabwe. These three countries are diverse in their geography, degree of urbanisation, maturity of health service infrastructure, and health profiles. The programme comprises five study types: (i) population-based cross-sectional studies to determine vertebral fracture prevalence. Secondary outcomes will include osteoarthritis and sarcopenia. Age- and sex-stratified household sampling will recruit 5030 adults aged 40 years and older; (ii) prospective cohort studies in adults aged 40 years and older will determine hip fracture incidence, associated risk factors, and outcomes over one year (e.g. mortality, disability, health-related quality of life); (iii) economic studies of direct health costs of hip fracture with projection modelling of future national health costs and cost-effectiveness analyses of different hip fracture care pathways; (iv) national surveys of hip fracture services (including traditional bonesetters in The Gambia); and (v) ethnographic studies of hip fracture care provision and experiences will understand fracture service pathways. Conclusions: Greater understanding of current and expected fracture burdens, fracture risk factors, and existing fracture care provision, is intended to inform national clinical guidelines, health service policy and planning and future health service development in sub-Saharan Africa.

The detection of inelastically scattered soft x-rays with high energy resolution usually requires large grating spectrometers. Recently, photoelectron spectrometry for analysis of x-rays (PAX) has been rediscovered for modern spectroscopy experiments at synchrotron light sources. By converting scattered photons to electrons and using an electron energy analyser, the energy resolution for resonant inelastic x-ray scattering (RIXS) becomes decoupled from the x-ray spot size and instrument length. In this work, we develop PAX towards high energy resolution using a modern photoemission spectroscopy setup studying Ba _2 Cu _3 O _4 Cl _2 at the Cu L _3 -edge. We measure a momentum transfer range of 24% of the first Brillouin zone simultaneously. Our results hint at the observation of a magnon excitation below 100 meV energy transfer and show intensity variations related to the dispersion of dd -excitations. With dedicated setups, PAX can complement the best and largest RIXS instruments, while at the same time opening new opportunities to acquire RIXS at a range of momentum transfers simultaneously and combine it with angle-resolved photoemission spectroscopy in a single instrument.

Measurement(s) Adverse Event Technology Type(s) digital curation Sample Characteristic - Organism Homo sapiens Machine-accessible metadata file describing the reported data: https://doi.org/10.6084/m9.figshare.16681933

Single-measurement-point data collection to assess change has increased with studies assessing the impact of the Covid-19 pandemic and of its containment, despite evidence of its lack of validity. Retrospective change is not equivalent to change in repeated self-reported measures giving raise to questions about the validity of the former. This paper purports to investigate inconsistencies between change measures by confronting retrospective change to information from longitudinally self-reported measures from the C-SURF cohort study. The study sample consists of 2,279 young men who participated in C-SURF between 2020 and 2021, and completed between May and June 2021 a survey covering change in alcohol, cigarette, cannabis and other addictive behaviors related to the pandemic. The aforementioned behaviors were assessed longitudinally at two time points using self-reports, and retrospective change since the onset of the Covid-19 crisis was also assessed at the second measurement time. Information from both prospective and retrospective change measures were confronted to identify inconsistent information for each behavior. Additionally, multiple logistic regressions were performed to assess associations between socioeconomic status, impulsivity, depression, and different indicators of motivation to complete the study and inconsistency between both measures for each behavior of interest. Importantly, inconsistent information in at least one of the investigated behaviors was found in about 90% of the participants. Small associations were found between inconsistency and different factors with a consistent effect of impulsivity. In the absence of evidence of the validity of retrospective change measures, studies relying on retrospective change should be interpreted with caution.

Abstract With increasing demands for more rapid and practical analyses, various techniques of ambient ionization mass spectrometry have gained significant interest due to the speed of analysis and abundance of information provided. Herein, an ambient ionization technique that utilizes corona discharge was applied, for the first time, to analyze and categorize whole seeds of black and white peppers from different origins. This setup requires no solvent application nor gas flow, thus resulting in a very simple and rapid analysis that can be applied directly to the sample without any prior workup or preparation. Combined with robust data pre-processing and subsequent chemometric analyses, this analytical method was capable of indicating the geographical origin of each pepper source with up to 98% accuracies in all sub-studies. The simplicity and speed of this approach open up the exciting opportunity for onsite analysis without the need for a highly trained operator. Furthermore, this methodology can be applied to a variety of spices and herbs, whose geographical indication or similar intellectual properties are economically important, hence it is capable of creating tremendous impact in the food and agricultural industries.

Natural environments, such as parks, woodlands and lakes, have positive impacts on health and wellbeing. Urban Green and Blue Spaces (UGBS), and the activities that take place in them, can significantly influence the health outcomes of all communities, and reduce health inequalities. Improving access and quality of UGBS needs understanding of the range of systems (e.g. planning, transport, environment, community) in which UGBS are located. UGBS offers an ideal exemplar for testing systems innovations as it reflects place-based and whole society processes, with potential to reduce non-communicable disease (NCD) risk and associated social inequalities in health. UGBS can impact multiple behavioural and environmental aetiological pathways. However, the systems which desire, design, develop, and deliver UGBS are fragmented and siloed, with ineffective mechanisms for data generation, knowledge exchange and mobilisation. Further, UGBS need to be co-designed with and by those whose health could benefit most from them, so they are appropriate, accessible, valued and used well. This paper describes a major new prevention research programme and partnership, GroundsWell, which aims to transform UGBS-related systems by improving how we plan, design, evaluate and manage UGBS so that it benefits all communities, especially those who are in poorest health. We use a broad definition of health to include physical, mental, social wellbeing and quality of life. Our objectives are to transform systems so that UGBS are planned, developed, implemented, maintained and evaluated with our communities and data systems to enhance health and reduce inequalities. GroundsWell will use interdisciplinary, problem-solving approaches to accelerate and optimise community collaborations among citizens, users, implementers, policymakers and researchers to impact research, policy, practice and active citizenship. GroundsWell will be shaped and developed in three pioneer cities (Belfast, Edinburgh, Liverpool) and their regional contexts, with embedded translational mechanisms to ensure that outputs and impact have UK-wide and international application.

Abstract The self-antigen α-synuclein (α-syn) was recently shown to be associated with Parkinson’s disease (PD). Here we mapped the T cell receptor (TCR) repertoire of α-syn-specific T cells from six PD patients. The self-antigen α-syn-specific repertoire was compared to the repertoire of T cells specific for pertussis (PT), as a representative foreign antigen that most individuals are exposed to, revealing that the repertoire for α-syn was as diverse as the repertoire for PT. The diversity of PT-specific clonotypes was similar between individuals with PD diagnosis and age-matched healthy controls. We found that the TCR repertoire was specific to each PD patient, and no shared TCRs among patients were defined, likely due to differences in HLA expression that select for different subsets of epitope-specific TCR rearrangements. This study provides the first characterization of α-syn-specific TCR clonotypes in individuals with PD. Antigen-specific TCRs can serve as immunotherapeutics and diagnostics, and means to track longitudinal changes in specific T cells, and disease progression.

Patients with solid cancers have high rates of clonal haematopoiesis associated with increased risk of secondary leukemias. Here, by using peripheral blood sequencing data from patients with solid non-hematologic cancer, the authors profile the landscape of mosaic chromosomal alterations and gene mutations, defining patients at high risk of leukemia progression.

Abstract Paper spray ionization (PSI) mass spectrometry (MS) is an emerging tool for ambient reaction monitoring via microdroplet reaction acceleration. PSI-MS was used to accelerate and monitor the time course of the reaction of dansyl chloride with aniline, in acetonitrile, to produce dansyl aniline. Three distinct PSI arrangements were explored in this study representing alternative approaches for sample loading and interaction; conventional single tip as well as two novel setups, a dual-tip and a co-axial arrangement were designed so as to limit any on-paper interaction between reagents. The effect on product abundance was investigated using these different paper configurations as it relates to the time course and distance of microdroplet travel. It was observed that product yield increases at a given distance and then decreases thereafter for all PSI configurations. The fluorescent property of the product (dansyl aniline) was used to visually inspect the reaction progress on the paper substrate during the spraying process. Amongst the variety of sample loading methods the novel dual-tip arrangement showed an increased product yield and microdroplet density, whilst avoiding any on-paper interaction between the reagents.

The competitive dynamics of mitochondrial haplotypes juxtaposed within the same cell are poorly studied. Here the authors show, in the context of a transmissible cancer, that one haplotype has recurrently entered cancer cells by horizontal transfer and appears to have a ‘selfish’ selective advantage.

α-Synuclein-specific T cell reactivity is preferentially associated with Parkinson’s disease (PD) patients, but the temporal relation with diagnosis was previously unknown. This study reveals that α-syn-reactive T cells are highest before and shortly after diagnosis of motor PD, and then decrease.

Most existing studies on land consumption have used a reactive approach to assess the phenomenon. However, for evidence-based policies, an initiative-taking forecast has been touted to be more appropriate. This study, therefore, assessed current trends and efficiency of land consumption in the Greater Accra Region from 1987 to 2017, and predicted a 30-year future land consumption in a "business-as-usual" scenario. The study adopted maximum likelihood image classification techniques and "combinatorial or" to model land cover change for Greater Accra from 1987 to 2017 while the UN-Habitat land efficiency index was employed to model efficiency of land consumption. In addition, Leo-Breiman Forest based regression, was used to model a future land cover by using the 30 years land cover change as a dependant variable and a series of natural and anthropogenic factors as independent variables. Results showed that artificial surfaces increased from 4.2% to 33.1%, with an annual growth rate of 22.1% in 30 years. Land consumption was highly inefficient as only 4.2% of the region had a good proportion of population per land area. Factors which influenced artificial surface growth were population, distance from water bodies, poverty index, distance from sacred groves, proportion of agriculture population with a small margin of influence from soil and geology type. Landscape prediction showed that artificial surfaces will increase to 92.6% as more places are coated with concrete. The high rate of land inefficiency provides an opportunity for re-zoning by the Land Use and Spatial Planning Authority of Ghana to accommodate the growing population.

Abstract Three fluorescent organic compounds—furocoumarin (FC), dansyl aniline (DA), and 7-hydroxycoumarin-3-carboxylic acid (CC)—are mixed to produce almost pure white light emission (WLE). This novel mixture is immobilised in silica aerogel and applied as a coating to a UV LED to demonstrate its applicability as a low-cost, organic coating for WLE via simultaneous emission. In ethanol solution and when immobilised in silica aerogel, the mixture exhibits a Commission Internationale d’Eclairage (CIE) chromaticity index of (0.27, 0.33). It was observed that a broadband and simultaneous emission involving coumarin carboxylic acid, furocoumarin and dansyl aniline played a vital role in obtaining a CIE index close to that of pure white light.

Importance Injuries cause 30% more deaths than HIV, TB and malaria combined, and a prospective fracture care registry was established to investigate the fracture burden and treatment in Malawi to inform evidence-based improvements. Objective To use the analysis of prospectively-collected fracture data to develop evidence-based strategies to improve fracture care in Malawi and other similar settings. Design Multicentre prospective registry study. Setting Two large referral centres and two district hospitals in Malawi. Participants All patients with a fracture (confirmed by radiographs)—including patients with multiple fractures—were eligible to be included in the registry. Exposure All fractures that presented to two urban central and two rural district hospitals in Malawi over a 3.5-year period (September 2016 to March 2020). Main outcome(s) and measure(s) Demographics, characteristics of injuries, and treatment outcomes were collected on all eligible participants. Results Between September 2016 and March 2020, 23,734 patients were enrolled with a median age of 15 years (interquartile range: 10–35 years); 68.7% were male. The most common injuries were radius/ulna fractures (n = 8,682, 36.8%), tibia/fibula fractures (n = 4,036, 17.0%), humerus fractures (n = 3,527, 14.9%) and femoral fractures (n = 2,355, 9.9%). The majority of fractures (n = 21,729, 91.6%) were treated by orthopaedic clinical officers; 88% (20,885/2,849) of fractures were treated non-operatively, and 62.7% were treated and sent home on the same day. Open fractures (OR:53.19, CI:39.68–72.09), distal femoral fractures (OR:2.59, CI:1.78–3.78), patella (OR:10.31, CI:7.04–15.07), supracondylar humeral fractures (OR:3.10, CI:2.38–4.05), ankle fractures (OR:2.97, CI:2.26–3.92) and tibial plateau fractures (OR:2.08, CI:1.47–2.95) were more likely to be treated operatively compared to distal radius fractures. Conclusions and relevance The current model of fracture care in Malawi is such that trained orthopaedic surgeons manage fractures operatively in urban referral centres whereas orthopaedic clinical officers mainly manage fractures non-operatively in both district and referral centres. We recommend that orthopaedic surgeons should supervise orthopaedic clinical officers to manage non operative injuries in central and district hospitals. There is need for further studies to assess the clinical and patient reported outcomes of these fracture cases, managed both operatively and non-operatively.

BackgroundNon-communicable diseases (NCDs) are the leading cause of mortality in the world, and innovative approaches to NCD care delivery are being actively developed and evaluated. Combining the group-based experience of microfinance and group medical visits is a novel approach to NCD care delivery. However, the contextual factors, facilitators, and barriers impacting wide-scale implementation of these approaches within a low- and middle-income country setting are not well known.MethodsTwo types of qualitative group discussion were conducted: 1) mabaraza (singular, baraza), a traditional East African community gathering used to discuss and exchange information in large group settings; and 2) focus group discussions (FGDs) among rural clinicians, community health workers, microfinance group members, and patients with NCDs. Trained research staff members led the discussions using structured question guides. Content analysis was performed with NVivo using deductive and inductive codes that were then grouped into themes.ResultsWe conducted 5 mabaraza and 16 FGDs. A total of 205 individuals (113 men and 92 women) participated in the mabaraza, while 162 individuals (57 men and 105 women) participated in the FGDs. In the context of poverty and previous experiences with the health system, participants described challenges to NCD care across three themes: 1) stigma of chronic disease, 2) earned skepticism of the health system, and 3) socio-economic fragility. However, they also outlined windows of opportunity and facilitators of group medical visits and microfinance to address those challenges.DiscussionOur qualitative study revealed actionable factors that could impact the success of implementation of group medical visits and microfinance initiatives for NCD care. While several challenges were highlighted, participants also described opportunities to address and mitigate the impact of these factors. We anticipate that our approach and analysis provides new insights and methodological techniques that will be relevant to other low-resource settings worldwide.

AimsThe present study aimed to investigate whether the psychological impact of the COVID-19 crisis varied with regards to young Swiss men's pre-crisis level of education and socioeconomic status and to changes in their work situation due to it.MethodsA cohort of 2345 young Swiss men (from 21 out of 26 Swiss cantons; mean age = 29) completed survey-based assessments shortly before (April 2019 to February 2020) and early on during the COVID-19 crisis (May to June 2020). Outcomes measured were psychological outcomes before and during the COVID-19 crisis (depression, perceived stress and sleep quality), and the fear, isolation and psychological trauma induced by it. We investigated associations between these outcomes and their predictors: pre-crisis socioeconomic status (relative financial status, difficulty paying bills, level of education), changes in work situation during the crisis (job loss, partial unemployment, working from home, change in workload) and working in contact with potentially infected people, both inside and outside the healthcare sector. For outcomes measured before and during the crisis, the analyses were adjusted for their pre-crisis levels.ResultsAbout 21% of participants changed their employment status (job loss, partial unemployment or lost money if self-employed) and more than 40% worked predominantly from home during the COVID-19 crisis. Participants with a lower relative socioeconomic status already before the crisis experienced a higher psychological impact due to the COVID-19 crisis, compared to participants with an average socioeconomic status (major depression (b = 0.12 [0.03, 0.22]), perceived stress (b = 0.15 [0.05, 0.25]), psychological trauma (b = 0.15 [0.04, 0.26]), fear (b = 0.20 [0.10, 0.30]) and isolation (b = 0.19 [0.08, 0.29])). A higher impact was also felt by participants who lost their job due to the COVID-19 crisis, the partially unemployed, those with an increased workload or those who worked mainly from home (e.g. depression b = 0.25 [0.16, 0.34] for those working 90%+ at home, compared to those not working at home).ConclusionsEven in a country like Switzerland, with relatively high social security benefits and universal healthcare, the COVID-19 crisis had a considerable psychological impact, especially among those with a lower socioeconomic status and those who experienced deteriorations in their work situation due to the COVID-19 crisis. Supporting these populations during the crisis may help to prevent an amplification of inequalities in mental health and social status. Such support could help to lower the overall impact of the crisis on the mental well-being of Switzerland's population.

Electron-rich arenes react with aryl and alkyl disulfides in the presence of catalytic amounts of [Ir(dF(CF3)ppy)2(dtbpy)]PF6 and (NH4)2S2O8 under blue light irradiation to yield arylthiols. The reaction proceeds at room temperature and avoids the use of prefunctionalized arenes. Experimental evidence suggests a radical–radical cross coupling mechanism.

Abstract Hepatitis C virus (HCV)-specific T cell responses are critical for immune control of infection. Viral adaptation to these responses, via mutations within regions of the virus targeted by CD8+ T cells, is associated with viral persistence. However, identifying viral adaptation to HCV-specific CD4+ T cell responses has been difficult although key to understanding anti-HCV immunity. In this context, HCV sequence and host genotype from a single source HCV genotype 1B cohort (n = 63) were analyzed to identify viral changes associated with specific human leucocyte antigen (HLA) class II alleles, as these variable host molecules determine the set of viral peptides presented to CD4+ T cells. Eight sites across the HCV genome were associated with HLA class II alleles implicated in infection outcome in this cohort (p ≤ 0.01; Fisher’s exact test). We extended this analysis to chronic HCV infection (n = 351) for the common genotypes 1A and 3A. Variation at 38 sites across the HCV genome were associated with specific HLA class II alleles with no overlap between genotypes, suggestive of genotype-specific T cell targets, which has important implications for vaccine design. Here we show evidence of HCV adaptation to HLA class II-restricted CD4+ T cell pressure across the HCV genome in chronic HCV infection without a priori knowledge of CD4+ T cell epitopes.

Topological effects, first observed in condensed matter physics, are now also studied in optical systems, extending the scope to active topological devices. Here, Zhao et al. combine topological physics with non-Hermitian photonics, demonstrating a topological microlaser on a silicon platform.

Abstract Genes of the human leukocyte antigen (HLA) system encode cell-surface proteins involved in regulation of immune responses, and the way drugs interact with the HLA peptide binding groove is important in the immunopathogenesis of T-cell mediated drug hypersensitivity syndromes. Nevirapine (NVP), is an HIV-1 antiretroviral with treatment-limiting hypersensitivity reactions (HSRs) associated with multiple class I and II HLA alleles. Here we utilize a novel analytical approach to explore these multi-allelic associations by systematically examining HLA molecules for similarities in peptide binding specificities and binding pocket structure. We demonstrate that primary predisposition to cutaneous NVP HSR, seen across ancestral groups, can be attributed to a cluster of HLA-C alleles sharing a common binding groove F pocket with HLA-C*04:01. An independent association with a group of class II alleles which share the HLA-DRB1-P4 pocket is also observed. In contrast, NVP HSR protection is afforded by a cluster of HLA-B alleles defined by a characteristic peptide binding groove B pocket. The results suggest drug-specific interactions within the antigen binding cleft can be shared across HLA molecules with similar binding pockets. We thereby provide an explanation for multiple HLA associations with cutaneous NVP HSR and advance insight into its pathogenic mechanisms.