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Abstract Binding-activated optical sensors are powerful tools for imaging, diagnostics, and biomolecular sensing. However, biosensor discovery is slow and requires tedious steps in rational design, screening, and characterization. Here we report on a platform that streamlines biosensor discovery and unlocks directed nanosensor evolution through genetically encodable fluorogenic amino acids (FgAAs). Building on the classical knowledge-based semisynthetic approach, we engineer ~15 kDa nanosensors that recognize specific proteins, peptides, and small molecules with up to 100-fold fluorescence increases and subsecond kinetics, allowing real-time and wash-free target sensing and live-cell bioimaging. An optimized genetic code expansion chemistry with FgAAs further enables rapid (~3 h) ribosomal nanosensor discovery via the cell-free translation of hundreds of candidates in parallel and directed nanosensor evolution with improved variant-specific sensitivities (up to ~250-fold) for SARS-CoV-2 antigens. Altogether, this platform could accelerate the discovery of fluorogenic nanosensors and pave the way to modify proteins with other non-standard functionalities for diverse applications.

Abstract DNA hydroxymethylation (5hmC), the most abundant oxidative derivative of DNA methylation, is typically enriched at enhancers and gene bodies of transcriptionally active and tissue-specific genes. Although aberrant genomic 5hmC has been implicated in age-related diseases, its functional role in aging remains unknown. Here, using mouse liver and cerebellum as model organs, we show that 5hmC accumulates in gene bodies associated with tissue-specific function and restricts the magnitude of gene expression changes with age. Mechanistically, 5hmC decreases the binding of splicing associated factors and correlates with age-related alternative splicing events. We found that various age-related contexts, such as prolonged quiescence and senescence, drive the accumulation of 5hmC with age. We provide evidence that this age-related transcriptionally restrictive function is conserved in mouse and human tissues. Our findings reveal that 5hmC regulates tissue-specific function and may play a role in longevity.

Abstract Myriad policy, ethical and legal considerations underpin the sharing of biological resources, implying the need for standardised and yet flexible ways to digitally represent diverse ‘use conditions’. We report a core lexicon of terms that are atomic, non-directional ‘concepts of use’, called Common Conditions of use Elements. This work engaged biobanks and registries relevant to the European Joint Programme for Rare Diseases and aimed to produce a lexicon that would have generalised utility. Seventy-six concepts were initially identified from diverse real-world settings, and via iterative rounds of deliberation and user-testing these were optimised and condensed down to 20 items. To validate utility, support software and training information was provided to biobanks and registries who were asked to create Sharing Policy Profiles. This succeeded and involved adding standardised directionality and scope annotations to the employed terms. The addition of free-text parameters was also explored. The approach is now being adopted by several real-world projects, enabling this standard to evolve progressively into a universal basis for representing and managing conditions of use.

Abstract Improving patient care and advancing scientific discovery requires responsible sharing of research data, healthcare records, biosamples, and biomedical resources that must also respect applicable use conditions. Defining a standard to structure and manage these use conditions is a complex and challenging task. This is exemplified by a near unlimited range of asset types, a high variability of applicable conditions, and differing applications at the individual or collective level. Furthermore, the specifics and granularity required are likely to vary depending on the ultimate contexts of use. All these factors confound alignment of institutional missions, funding objectives, regulatory and technical requirements to facilitate effective sharing. The presented work highlights the complexity and diversity of the problem, reviews the current state of the art, and emphasises the need for a flexible and adaptable approach. We propose Digital Use Conditions (DUC) as a framework that addresses these needs by leveraging existing standards, striking a balance between expressiveness versus ambiguity, and considering the breadth of applicable information with their context of use.

The St. Lawrence Estuary (SLE) belugas (Quebec, Canada) are an endangered population whose numbers remain low despite ongoing conservation efforts. Multiple anthropogenic factors and changing environmental conditions are thought to have contributed to the recent 20-year decline in blubber fatty acid concentrations reported in stranded SLE belugas. Despite this evidence that energy reserves within the population are declining, there is currently no method for estimating the body condition of free-ranging animals. The potential metabolic consequences of declining fat reserves have also yet to be explored. The objectives of this study were to use unmanned aerial vehicle (UAV)-based photogrammetry to estimate the scaled mass index (SMI) of free-ranging SLE belugas, and to compare this proxy of body condition to the lipidome of outer-layer blubber samples collected from the same individuals via remote biopsy darting. Morphometric analysis of aerial images (n = 44 SLE belugas), combined with data collected from animals under professional human care, produced SMI estimates (females: 807 ± 98 kg, males: 743 ± 39 kg) similar in range to those previously calculated for SLE beluga carcasses of known weight. A non-targeted lipidomic analysis followed by pathway enrichment analysis, identified metabolic pathways predicted to show altered activity in association with SMI in the blubber of free-ranging male SLE belugas (n = 27). Mapping of enriched pathways compared to the Kyoto Encyclopedia of Genes and Genomes (KEGG) metabolic pathways maps, revealed that enriched pathways pertained to the metabolism of multiple lipid classes including fatty acyls and glycerophospholipids. Vitamin A, Vitamin E, and tyrosine metabolism pathways were also enriched in correlation with SMI. This study provides the basis for the development of a non-invasive technique for estimating the body condition of free-ranging SLE belugas and identifies metabolic pathways that merit further exploration to improve our understanding of the potential metabolic impacts of energy loss in cetaceans.

In recent years, three sections (Humipedon, Copedon and Lithopedon) were recognized in the soil profile. It was then possible to link the first and most biologically active section to the characteristics of the environment and soil genesis. In particular, it is now possible to distinguish organic horizons, mainly produced by arthropods and enchytraeids in cold and acidic or dry and arid environments, from organo-mineral horizons produced by earthworms in more temperate and mesotrophic environments. Each set of horizons can be associated with a humus system or form, with important implications for forestry. Anecic/endogeic earthworms and Mull or Amphi systems are more abundant in the early and late stages of sylvogenesis; by completely recycling litter, earthworms accelerate the availability of organic and inorganic soil nutrients to roots and pedofauna. On the other hand, arthropods and Moder or Tangel systems characterize the intermediate stages of sylvogenesis, where thickening in the organic horizons and the parallel impoverishment/reduction in the underlying organo-mineral horizons are observed. Recognizing the humus system at the right spatial and temporal scale is crucial for the biological management of a forest. This article includes a data review, new data from a doctoral thesis, and recent comparisons of Italian and French investigations.

Abstract Concentrative nucleoside transporters (CNTs) are active nucleoside influx systems, but their in vivo roles are poorly defined. By generating CNT1 knockout (KO) mice, here we identify a role of CNT1 in the renal reabsorption of nucleosides. Deletion of CNT1 in mice increases the urinary excretion of endogenous pyrimidine nucleosides with compensatory alterations in purine nucleoside metabolism. In addition, CNT1 KO mice exhibits high urinary excretion of the nucleoside analog gemcitabine (dFdC), which results in poor tumor growth control in CNT1 KO mice harboring syngeneic pancreatic tumors. Interestingly, increasing the dFdC dose to attain an area under the concentration-time curve level equivalent to that achieved by wild-type (WT) mice rescues antitumor efficacy. The findings provide new insights into how CNT1 regulates reabsorption of endogenous and synthetic nucleosides in murine kidneys and suggest that the functional status of CNTs may account for the optimal action of pyrimidine nucleoside analog therapeutics in humans.

Summary: Cutaneous leishmaniasis (CL) is characterized by extensive skin lesions, which are usually painless despite being associated with extensive inflammation. The molecular mechanisms responsible for this analgesia have not been identified. Through untargeted metabolomics, we found enriched anti-nociceptive metabolic pathways in L. mexicana-infected mice. Purines were elevated in infected macrophages and at the lesion site during chronic infection. These purines have anti-inflammatory and analgesic properties by acting through adenosine receptors, inhibiting TRPV1 channels, and promoting IL-10 production. We also found arachidonic acid (AA) metabolism enriched in the ear lesions compared to the non-infected controls. AA is a metabolite of anandamide (AEA) and 2-arachidonoylglycerol (2-AG). These endocannabinoids act on cannabinoid receptors 1 and 2 and TRPV1 channels to exert anti-inflammatory and analgesic effects. Our study provides evidence of metabolic pathways upregulated during L. mexicana infection that may mediate anti-nociceptive effects experienced by CL patients and identifies macrophages as a source of these metabolites.

Abstract The development of efficient and compact photonic systems in support of mid-infrared integrated optics is currently facing several challenges. To date, most mid-infrared glass-based devices are employing fluoride or chalcogenide glasses (FCGs). Although the commercialization of FCGs-based optical devices has rapidly grown during the last decade, their development is rather cumbersome due to either poor crystallization and hygroscopicity resilience or poor mechanical-thermal properties of the FCGs. To overcome these issues, the parallel development of heavy-metal oxide optical fiber from the barium-germanium-gallium oxide vitreous system (BGG) has revealed a promising alternative. However, over 30 years of fiber fabrication optimization, the final missing step of drawing BGG fibers with acceptable losses for meters-long active and passive optical devices had not yet been reached. In this article, we first identify the three most important factors that prevent the fabrication of low-loss BGG fibers i.e., surface quality, volumic striae and glass thermal-darkening. Each of the three factors is then addressed in setting up a protocol enabling the fabrication of low-loss optical fibers from gallium-rich BGG glass compositions. Accordingly, to the best of our knowledge, we report the lowest losses ever measured in a BGG glass fiber i.e., down to 200 dB km−1 at 1350 nm.

It is important to understand dwell fatigue that has been implicated in several uncontained jet engine failures. Here the authors observe stress bursts due to slip intermittency in a Ti alloy using synchrotron x-ray diffraction microscopy to understand the roles of precipitates and trace oxygen.

Abstract A tunable ultrashort soliton pulse source reaching up to 4.8 µm is demonstrated based on a 2.8 µm femtosecond fiber laser coupled to a zirconium fluoride fiber amplifier followed by a small core indium fluoride fiber. This demonstration is extending by 300 nm the long wavelength limit previously reported with soliton self-frequency shift (SSFS) sources based on fluoride fibers. Our experimental and numerical investigation highlighted the spectral dynamics associated with the generation of highly redshifted pulses in the mid-infrared using SSFS enhanced by soliton fission. This study is intended at providing a better understanding of the potential and limitations of SSFS based tunable femtosecond fiber sources in the 3–5 µm spectral range.

Abstract Many studies on ionizing radiation (IR) exposure during childhood have shown deleterious effects on the central nervous system (CNS), however results regarding adult exposure are inconsistent, and no systematic reviews have been performed. The objectives are to synthesize the findings and draw evidence-based conclusions from epidemiological studies on the risk of benign and malignant brain and CNS tumors in humans exposed to low-to-moderate doses (

The molecular mechanisms ensuring the specialized structure of small intestinal villus tip blood vessels are incompletely understood. Here the authors show that ADAMTS18+ telocytes maintain a “just-right” level and location of VEGFA signaling on intestinal villus blood vessels, thereby ensuring the presence of endothelial fenestrae for nutrient absorption, while avoiding excessive leakiness and destabilization of villus tip epithelial structures.

Background: Public Health Emergencies (PHE) demand expeditious research responses to evaluate new or repurposed therapies and prevention strategies. Alternative Design Trials (ADTs) and Adaptive Platform Trials (APTs) have enabled efficient large-scale testing of biomedical interventions during recent PHEs. Design features of these trials may have implications for engagement and/or informed consent processes. We aimed to rapidly review evidence on engagement and informed consent for ADTs and APTs during PHE to consider what (if any) recommendations can inform practice. Method: In 2022, we searched 8 prominent databases for relevant peer reviewed publications and guidelines for ADTs/APTs in PHE contexts. Articles were selected based on pre-identified inclusion and exclusion criteria. We reviewed protocols and informed consent documents for a sample of large platform trials and consulted with key informants from ADTs/APT trial teams. Data were extracted and summarised using narrative synthesis. Results: Of the 49 articles included, 10 were guidance documents, 14 discussed engagement, 10 discussed informed consent, and 15 discussed both. Included articles addressed ADTs delivered during the West African Ebola epidemic and APTs delivered during COVID-19. PHE clinical research guidance documents highlight the value of ADTs/APTs and the importance of community engagement, but do not provide practice-specific guidance for engagement or informed consent. Engagement and consent practice for ADTs conducted during the West African Ebola epidemic have been well-documented. For COVID-19, engagement and consent practice was described for APTs primarily delivered in high income countries with well-developed health service structures. A key consideration is strong communication of the complexity of trial design in clear, accessible ways. Conclusion: We highlight key considerations for best practice in community engagement and informed consent relevant to ADTs and APTs for PHEs which may helpfully be included in future guidance. Protocol: The review protocol is published online at Prospero on 15/06/2022: registration number CRD42022334170.

Abstract Large-scale neurophysiological markers of action competition have been almost exclusively investigated in the context of instructed choices, hence it remains unclear whether these markers also apply to free choices. This study aimed to compare the specific brain dynamics underlying instructed and free decisions. Electroencephalography (EEG) was recorded while 31 participants performed a target selection task; the choice relied either on stimulus–response mappings (instructed) or on participants’ preferences (free). Choice difficulty was increased by introducing distractors in the informative stimulus in instructed choices, and by presenting targets with similar motor costs in free choices. Results revealed that increased decision difficulty was associated with higher reaction times (RTs) in instructed choices and greater choice uncertainty in free choices. Midfrontal EEG theta (4–8 Hz) power increased with difficulty in instructed choices, but not in free choices. Although sensorimotor beta (15–30 Hz) power was correlated with RTs, it was not significantly influenced by choice context or difficulty. These results suggest that midfrontal theta power may specifically increase with difficulty in externally-driven choices, whereas sensorimotor beta power may be predictive of RTs in both externally- and internally-driven choices.

Loss of canonical Notch signaling in vascular endothelial cells induces spontaneous formation of proto-typical tertiary lymphoid structures in mouse kidney, liver and lungs, which form around central arteries that acquire a high endothelial cell signature

IntroductionNoise pollution is a major stressor in the marine environment; however, responses of economically and ecologically important invertebrates, such as oysters, are largely unknown.MethodsUnder laboratory conditions, we measured acute behavioral and physiological responses of eastern oysters (Crassostrea virginica) to sound treatments mimicking human activity in the environment.ResultsOysters immediately reduced their valve gape under simulated pile driving sound, but not drilling or boating sound. Pile-driving sound also reduced adductor muscle glycogen, but not triglyceride. None of the sound treatments affected longer-term (12 hours) valve activity levels after the administration of sounds. Interestingly, neither acute nor longer-term valve gaping responses were correlated with glycogen content on the individual level, suggesting that the observed behavioral responses to sound were not mechanistically driven by energetic physiology.DiscussionOur results suggest that C. virginica responds to some, but not all, anthropogenic sounds. Future studies assessing downstream effects on growth, reproduction, and survival in the wild are needed to better understand the effects of anthropogenic sounds on oyster populations and the biological communities they support.

Medical personnel represent the largest group of workers occupationally exposed to ionizing radiation. Although the health risks associated with occupational exposure to low doses of ionizing radiation in the medical field have been investigated in several national cohorts, no study has been conducted in France to date. The ORICAMs (Occupational Radiation Induced Cancer in Medical staff) cohort is a nationwide French longitudinal cohort of medical workers exposed to ionizing radiation aiming to investigate the risk of radiation-associated cancer and non-cancer mortality. The ORICAMs cohort was set up in 2011 and includes all medical personnel monitored for ionizing radiation exposure with at least one dosimetric record in the SISERI database (the national registry for monitoring ionizing radiation exposure in workers) over the period 2002-2012. Causes of death were abstracted from death certificates and coded according to ICD-10. The follow-up ended on 31/12/2013. Standardized mortality ratios (SMRs) were calculated by cause of death to compare the mortality in the cohort to that in the French population, by gender, age group and calendar period. Among the 164,015 workers included in the cohort (60% women) a total of 1,358 deaths (892 in male and 466 in female) were reported. The observed number of all-cause deaths was significantly lower than expected based on national rates in both male (SMR = 0.35; 95% CI: 0.33, 0.38; ndeaths = 892) and female (SMR = 0.41; 95% CI: 0.38, 0.45; ndeaths = 466). This analysis leads to the conclusion that mortality in French workers exposed to medical radiation is significantly lower than the national reference rates. However, these results based on a comparative analysis with national rates may be impacted by the healthy worker effect towards low SMRs, and do not enable to establish a potential relationship between occupational exposure and mortality risk, even if we may suspect an impact of high SES of these professionals on the observed decreased mortality. Thus, further dose-response analyses based on individual ionizing radiation exposure and job's type will be conducted to characterize correlation between risk of cancer mortality and occupational exposure.

Medical personnel represent the largest group of workers occupationally exposed to ionizing radiation. Although the health risks associated with occupational exposure to low doses of ionizing radiation in the medical field have been investigated in several national cohorts, no study has been conducted in France to date. The ORICAMs (Occupational Radiation Induced Cancer in Medical staff) cohort is a nationwide French longitudinal cohort of medical workers exposed to ionizing radiation aiming to investigate the risk of radiation-associated cancer and non-cancer mortality. The ORICAMs cohort was set up in 2011 and includes all medical personnel monitored for ionizing radiation exposure with at least one dosimetric record in the SISERI database (the national registry for monitoring ionizing radiation exposure in workers) over the period 2002–2012. Causes of death were abstracted from death certificates and coded according to ICD-10. The follow-up ended on 31/12/2013. Standardized mortality ratios (SMRs) were calculated by cause of death to compare the mortality in the cohort to that in the French population, by gender, age group and calendar period. Among the 164,015 workers included in the cohort (60% women) a total of 1,358 deaths (892 in male and 466 in female) were reported. The observed number of all-cause deaths was significantly lower than expected based on national rates in both male (SMR = 0.35; 95% CI: 0.33, 0.38; ndeaths = 892) and female (SMR = 0.41; 95% CI: 0.38, 0.45; ndeaths = 466). This analysis leads to the conclusion that mortality in French workers exposed to medical radiation is significantly lower than the national reference rates. However, these results based on a comparative analysis with national rates may be impacted by the healthy worker effect towards low SMRs, and do not enable to establish a potential relationship between occupational exposure and mortality risk, even if we may suspect an impact of high SES of these professionals on the observed decreased mortality. Thus, further dose-response analyses based on individual ionizing radiation exposure and job’s type will be conducted to characterize correlation between risk of cancer mortality and occupational exposure.

Abstract Metabolic reprogramming contributes to oncogenesis, tumor growth, and treatment resistance in pancreatic ductal adenocarcinoma (PDAC). Here we report the effects of (R,S′)-4′-methoxy-1-naphthylfenoterol (MNF), a GPR55 antagonist and biased β2-adrenergic receptor (β2-AR) agonist on cellular signaling implicated in proliferation and metabolism in PDAC cells. The relative contribution of GPR55 and β2-AR in (R,S′)-MNF signaling was explored further in PANC-1 cells. Moreover, the effect of (R,S′)-MNF on tumor growth was determined in a PANC-1 mouse xenograft model. PANC-1 cells treated with (R,S′)-MNF showed marked attenuation in GPR55 signal transduction and function combined with increased β2-AR/Gαs/adenylyl cyclase/PKA signaling, both of which contributing to lower MEK/ERK, PI3K/AKT and YAP/TAZ signaling. (R,S′)-MNF administration significantly reduced PANC-1 tumor growth and circulating l-lactate concentrations. Global metabolic profiling of (R,S′)-MNF-treated tumor tissues revealed decreased glycolytic metabolism, with a shift towards normoxic processes, attenuated glutamate metabolism, and increased levels of ophthalmic acid and its precursor, 2-aminobutyric acid, indicative of elevated oxidative stress. Transcriptomics and immunoblot analyses indicated the downregulation of gene and protein expression of HIF-1α and c-Myc, key initiators of metabolic reprogramming in PDAC. (R,S′)-MNF treatment decreased HIF-1α and c-Myc expression, attenuated glycolysis, shifted fatty acid metabolism towards β-oxidation, and suppressed de novo pyrimidine biosynthesis in PANC-1 tumors. The results indicate a potential benefit of combined GPR55 antagonism and biased β2-AR agonism in PDAC therapy associated with the deprogramming of altered cellular metabolism.

Abstract We propose an efficient method to determine the effective refractive index of step-index optical fibers from the visible to the mid-IR and thus allowing to infer their dispersive properties over a broad spectral range. The validity of the method, based on the writing of an array of fiber Bragg gratings (FBGs) with known periods using the fs scanning phase mask technique, is first confirmed with a standard silica fiber, then applied to various fluoride glass fibers to determine their effective refractive index and dispersion over more than three octaves, i.e. from 550 to 4800 nm.

Understanding the contribution of diet composition, calories and length of fasting in health maintenance is still challenging. Here the authors compare the effects of cycles of intermittent very low calorie intake achieved with a plant-based fasting mimicking diet or standard laboratory chow to provide insights into the role played by diet composition in mediating the metabolic benefits of short cycles of very low-calorie intake in mice.

Caloric restriction (CR) has been shown as an effective intervention to reduce tumorigenesis, but alternative less stringent dietary interventions have also been considered. Here, the authors show that in a murine model of breast cancer CR has a larger effect on preventing tumorigenesis and metastasis compared to periodic caloric cycling.

Ecological constraints on microbial niches in oligotrophic deep groundwaters remain elusive. This study provides support for the existence of a common core microbiome in two deep groundwater biomes of the Fennoscandian Shield using a genome-resolved, integrated omics analysis.

In this opinion piece, we discuss why computational tools to limit the identifiability of genomic data are a promising avenue for privacy-preservation and legal compliance. Even where these technologies do not eliminate all residual risk of individual identification, the law may still consider such data anonymised.

The pial arterial vasculature of the human brain is the only blood supply to the neocortex, but quantitative data on the morphology and topology of these mesoscopic arteries (diameter 50–300 µm) remains scarce. Because it is commonly assumed that blood flow velocities in these vessels are prohibitively slow, non-invasive time-of-flight magnetic resonance angiography (TOF-MRA)—which is well suited to high 3D imaging resolutions—has not been applied to imaging the pial arteries. Here, we provide a theoretical framework that outlines how TOF-MRA can visualize small pial arteries in vivo, by employing extremely small voxels at the size of individual vessels. We then provide evidence for this theory by imaging the pial arteries at 140 µm isotropic resolution using a 7 Tesla (T) magnetic resonance imaging (MRI) scanner and prospective motion correction, and show that pial arteries one voxel width in diameter can be detected. We conclude that imaging pial arteries is not limited by slow blood flow, but instead by achievable image resolution. This study represents the first targeted, comprehensive account of imaging pial arteries in vivo in the human brain. This ultra-high-resolution angiography will enable the characterization of pial vascular anatomy across the brain to investigate patterns of blood supply and relationships between vascular and functional architecture.

G-quadruplexes (G4) can be formed from DNA sequences containing consecutive guanines organized in 4-interspaced tandem repeats. Here the authors reveal the association between G4 structures present at specific loci in Alzheimer’s disease neurons and reduced gene expression and perturbed alternative splicing.

The Canadian Genomics Partnership for Rare Diseases, spearheaded by Genome Canada, will integrate genome-wide sequencing to rare disease clinical care in Canada. Centralized and tiered models of data stewardship are proposed to ensure that the data generated can be shared for secondary clinical, research, and quality assurance purposes in compliance with ethics and law. The principal ethico-legal obligations of clinicians, researchers, and institutions are synthesized. Governance infrastructures such as registered access platforms, data access compliance offices, and Beacon systems are proposed as potential organizational and technical foundations of responsible rare disease data sharing. The appropriate delegation of responsibilities, the transparent communication of rights and duties, and the integration of data privacy safeguards into infrastructure design are proposed as the cornerstones of rare disease data stewardship.

For many neurodevelopmental disorder (NDD) risk genes, the significance for mutational burden is unestablished. Here, the authors sequence 125 candidate NDD genes in over 16,000 NDD cases; case-control mutational burden analysis identifies 48 genes with a significant burden of severe ultra-rare mutations.

Sex workers may use Information and Communication Technology (ICT) as a means to mitigate occupational health and safety (OHS) risks by exchanging harm reduction techniques (e.g., screening) on blogs and social media. ICTs can also assist sex workers in creating online communities, where community members can act as each other's safety check-ins, an additional harm reduction technique. In Canada, there is a paucity of research around ICT usage by sex workers for managing occupational health and safety. The objective of this study was to qualitatively examine the needs and preferences of Canadian sex workers when using ICTs in the delivery of strategies for occupational health and safety. Using a theoretical framework derived from a Social Ecological Model perspective, semi-structured interviews were conducted via phone, with a mixed gender sample (N = 22) of sex workers, between April and July 2020. OHS risks were found to be related to structural determinants, client behaviours, and lack of experience and knowledge when newly entering sex work. Participant accounts revealed a socially cohesive online community; however, sex workers reported difficulties in finding these communities, particularly when entering sex work. Such barriers to supportive communities were attributed to the criminalized, hidden nature of sex work that resulted in the fragmentation of harm reduction techniques across several online platforms, such as blogs, YouTube videos, closed electronic chat groups, and open online sex worker supportive communities. Moreover, these platforms and/or their content could potentially disappear without warning, either due to the platform provider seeking to evade possible prosecution, or because new legislation was introduced banning such content. Recommendations for further research include the co-design with sex workers of an innovative, secure, easily accessible, sex worker-only ICT OHS tool, utilizing a web hosting service located in a country where sex work has been either legalized or decriminalized.

This article presents a strategy for the initial step of data harmonization in Individual Participant Data syntheses, i.e., making decisions as to which measures operationalize the constructs of interest - and which do not. This step is vital in the process of data harmonization, because a study can only be as good as its measures. If the construct validity of the measures is in question, study results are questionable as well. Our proposed strategy for data harmonization consists of three steps. First, a unitary construct is defined based on the existing literature, preferably on the theoretical framework surrounding the construct. Second, the various instruments used to measure the construct are evaluated as operationalizations of this construct, and retained or excluded based on this evaluation. Third, the scores of the included measures are recoded on the same metric. We illustrate the use of this method with three example constructs focal to the Collaboration on Attachment Transmission Synthesis (CATS) study: parental sensitivity, child temperament, and social support. This process description may aid researchers in their data pooling studies, filling a gap in the literature on the first step of data harmonization. • Data harmonization in studies using combined datasets is of vital importance for the validity of the study results. • We have developed and illustrated a strategy on how to define a unitary construct and evaluate whether instruments are operationalizations of this construct as the initial step in the harmonization process. • This strategy is a transferable and reproducible method to apply to the data harmonization process.

Sex workers may use Information and Communication Technology (ICT) as a means to mitigate occupational health and safety (OHS) risks by exchanging harm reduction techniques (e.g., screening) on blogs and social media. ICTs can also assist sex workers in creating online communities, where community members can act as each other’s safety check-ins, an additional harm reduction technique. In Canada, there is a paucity of research around ICT usage by sex workers for managing occupational health and safety. The objective of this study was to qualitatively examine the needs and preferences of Canadian sex workers when using ICTs in the delivery of strategies for occupational health and safety. Using a theoretical framework derived from a Social Ecological Model perspective, semi-structured interviews were conducted via phone, with a mixed gender sample (N = 22) of sex workers, between April and July 2020. OHS risks were found to be related to structural determinants, client behaviours, and lack of experience and knowledge when newly entering sex work. Participant accounts revealed a socially cohesive online community; however, sex workers reported difficulties in finding these communities, particularly when entering sex work. Such barriers to supportive communities were attributed to the criminalized, hidden nature of sex work that resulted in the fragmentation of harm reduction techniques across several online platforms, such as blogs, YouTube videos, closed electronic chat groups, and open online sex worker supportive communities. Moreover, these platforms and/or their content could potentially disappear without warning, either due to the platform provider seeking to evade possible prosecution, or because new legislation was introduced banning such content. Recommendations for further research include the co-design with sex workers of an innovative, secure, easily accessible, sex worker-only ICT OHS tool, utilizing a web hosting service located in a country where sex work has been either legalized or decriminalized.

In anoxic environments, soluble hexavalent uranium is reduced and immobilized, however, the underlying molecular-scale reduction mechanism remains unknown. Here, the authors find that U reduction can occur on the surface of magnetite via transient U nanowire structures which collapse into ordered UO2 nanoclusters, which may have implications for understanding nuclear waste evolution and remediation of uranium contamination.

Sensory hypersensitivity is common in autism spectrum disorders. Using functional MRI, psychophysics, and computational modeling, Schallmo et al. show that differences in visual motion perception in ASD are accompanied by weaker neural suppression in visual cortex.

Glucose is the main source of fuel in the brain. Here, the authors show that in the absence of glucose, glutamine is required for microglia to maintain their immune surveillance function.

Neurodevelopmental disorders (NDDs) are a heterogeneous group of diseases for which the genetic basis is still unknown in more than half of the cases. Here, the authors report a NDD associated with disruptive variants in the TANC2 gene and show that rols, the TANC2 homolog in flies, is required for synapse growth and function.

Recording from monkey orbitofrontal cortex, the authors used composite reward bundles and found individual neuron and population responses that were suitable for economic choice. The responses followed behavioral indifference curves and predicted behavioral choices consistent with formalisms of Revealed Preference Theory.

Various data sharing platforms are being developed to enhance the sharing of cohort data by addressing the fragmented state of data storage and access systems. However, policy challenges in several domains remain unresolved. The euCanSHare workshop was organized to identify and discuss these challenges and to set the future research agenda. Concerns over the multiplicity and long-term sustainability of platforms, lack of resources, access of commercial parties to medical data, credit and recognition mechanisms in academia and the organization of data access committees are outlined. Within these areas, solutions need to be devised to ensure an optimal functioning of platforms.

Various data sharing platforms are being developed to enhance the sharing of cohort data by addressing the fragmented state of data storage and access systems. However, policy challenges in several domains remain unresolved. The euCanSHare workshop was organized to identify and discuss these challenges and to set the future research agenda. Concerns over the multiplicity and long-term sustainability of platforms, lack of resources, access of commercial parties to medical data, credit and recognition mechanisms in academia and the organization of data access committees are outlined. Within these areas, solutions need to be devised to ensure an optimal functioning of platforms.

The systemic challenges of the COVID-19 pandemic require cross-disciplinary collaboration in a global and timely fashion. Such collaboration needs open research practices and the sharing of research outputs, such as data and code, thereby facilitating research and research reproducibility and timely collaboration beyond borders. The Research Data Alliance COVID-19 Working Group recently published a set of recommendations and guidelines on data sharing and related best practices for COVID-19 research. These guidelines include recommendations for clinicians, researchers, policy- and decision-makers, funders, publishers, public health experts, disaster preparedness and response experts, infrastructure providers from the perspective of different domains (Clinical Medicine, Omics, Epidemiology, Social Sciences, Community Participation, Indigenous Peoples, Research Software, Legal and Ethical Considerations), and other potential users. These guidelines include recommendations for researchers, policymakers, funders, publishers and infrastructure providers from the perspective of different domains (Clinical Medicine, Omics, Epidemiology, Social Sciences, Community Participation, Indigenous Peoples, Research Software, Legal and Ethical Considerations). Several overarching themes have emerged from this document such as the need to balance the creation of data adherent to FAIR principles (findable, accessible, interoperable and reusable), with the need for quick data release; the use of trustworthy research data repositories; the use of well-annotated data with meaningful metadata; and practices of documenting methods and software. The resulting document marks an unprecedented cross-disciplinary, cross-sectoral, and cross-jurisdictional effort authored by over 160 experts from around the globe. This letter summarises key points of the Recommendations and Guidelines, highlights the relevant findings, shines a spotlight on the process, and suggests how these developments can be leveraged by the wider scientific community.

Aging is associated with distinct phenotypical, physiological, and functional changes, leading to disease and death. The progression of aging-related traits varies widely among individuals, influenced by their environment, lifestyle, and genetics. In this study, we conducted physiologic and functional tests cross-sectionally throughout the entire lifespan of male C57BL/6N mice. In parallel, metabolomics analyses in serum, brain, liver, heart, and skeletal muscle were also performed to identify signatures associated with frailty and age-dependent functional decline. Our findings indicate that declines in gait speed as a function of age and frailty are associated with a dramatic increase in the energetic cost of physical activity and decreases in working capacity. Aging and functional decline prompt organs to rewire their metabolism and substrate selection and toward redox-related pathways, mainly in liver and heart. Collectively, the data provide a framework to further understand and characterize processes of aging at the individual organism and organ levels.

Genetic variants in ionotropic glutamate receptors have been implicated in neurodevelopmental disorders. Here, the authors report heterozygous de novo mutations in the GRIA2 gene in 28 individuals with intellectual disability and neurodevelopmental abnormalities associated with reduced Ca2+ transport and AMPAR currents.”

Gluten triggers celiac disease in genetically predisposed individuals, but additional unknown mechanisms are required. Here, the authors show that proteases from Pseudomonas aeruginosa can modulate inflammatory pathways that are relevant to the development of food sensitivities, independently of the trigger antigen.

The World Health Organization recommends pre-exposure prophylaxis (PrEP) for all populations at substantial risk of HIV infection, including women. However, data regarding PrEP interest among women is lacking, particularly in Europe. Factors associated with interest in using PrEP were assessed among women respondents to the Flash! PrEP in Europe (FPIE) survey. This community-based cross-sectional study, conducted in 12 European countries, aimed to assess PrEP knowledge and interest. "High objective risk" (HOR) was assessed using established risk criteria following EACS and CDC guidelines. Factors associated with interest in using PrEP were assessed in univariable and multivariable logistic regression models. Among 678 women, 12.5% (n = 85) were considered at HOR, 46.8% (n = 317) indicated prior PrEP knowledge and 18.0% (n = 122) reported interest in using PrEP. Among women at HOR, 40.0% (n = 34) were interested in PrEP. Factors significantly associated with PrEP interest in the final multivariable model were: younger age (18-29 years) (aOR 1.91[95CI: 1.07; 3.41]), bad self-perceived financial status (1.84[1.09; 3.11]), migrant status (south to north) (2.87[1.05; 7.89]), single or dating relationship status (1.93[1.23; 3.03]), sexual abuse history (1.86[1.17; 2.97]), "rather high"/ "high" self-perceived HIV risk (3.21[1.32; 7.81]), and HOR (2.49[1.42; 4.35]). These results show that women at HOR and those who perceived themselves to be at high risk are interested in using PrEP. There is a critical need for targeted information and improved access to PrEP to increase uptake of this HIV prevention tool to meet PrEP interest among women.

The systemic challenges of the COVID-19 pandemic require cross-disciplinary collaboration in a global and timely fashion. Such collaboration needs open research practices and the sharing of research outputs, such as data and code, thereby facilitating research and research reproducibility and timely collaboration beyond borders. The Research Data Alliance COVID-19 Working Group recently published a set of recommendations and guidelines on data sharing and related best practices for COVID-19 research. These guidelines include recommendations for researchers, policymakers, funders, publishers and infrastructure providers from the perspective of different domains (Clinical Medicine, Omics, Epidemiology, Social Sciences, Community Participation, Indigenous Peoples, Research Software, Legal and Ethical Considerations). Several overarching themes have emerged from this document such as the need to balance the creation of data adherent to FAIR principles (findable, accessible, interoperable and reusable), with the need for quick data release; the use of trustworthy research data repositories; the use of well-annotated data with meaningful metadata; and practices of documenting methods and software. The resulting document marks an unprecedented cross-disciplinary, cross-sectoral, and cross-jurisdictional effort authored by over 160 experts from around the globe. This letter summarises key points of the Recommendations and Guidelines, highlights the relevant findings, shines a spotlight on the process, and suggests how these developments can be leveraged by the wider scientific community.

In the terrestrial cryosphere, freeze/thaw (FT) state transitions play an important and measurable role in climatic, hydrological, ecological, and biogeochemical processes in permafrost landscapes. Active and passive microwave remote sensing has shown a principal capacity to provide effective monitoring of landscape FT dynamics. The study presents a seasonal threshold approach, which examines the timeseries progression of remote sensing measurements relative to signatures acquired during seasonal frozen and thawed reference states. This is used to estimate the FT state from the Sentinel-1 database and applied and evaluated for the region of Eastern Nunavik (Québec, Canada). An optimization process of the threshold is included. In situ measurements from the meteorological station network were used for the validation process. Overall, acceptable estimation accuracy (>70%) was achieved in most tests; on the best-performing sites, an accuracy higher than 90% was reached. The performance of the seasonal threshold approach over the study region was further discussed with consideration of land cover, spatial heterogeneity, and soil depth. This work is dedicated to providing more accurate data to capture the spatiotemporal heterogeneity of freeze/thaw transitions and to improving our understanding of related processes in permafrost landscapes.

To discover new natural materials for insect management, commercially available stored sheep wool was investigated for attractancy to female adult Aedes aegypti mosquitoes. The volatiles from sheep wool were collected by various techniques of headspace (HS) extractions and hydrodistillation. These extracts were analyzed using gas chromatography–mass spectrometry (GC-MS) and gas chromatography–flame ionization detector (GC-FID) coupled with GC-MS. Fifty-two volatile compounds were detected, many of them known for their mosquito attractant activity. Seven compounds were not previously reported in sheep products. The volatile composition of the extracts varied significantly across collections, depending on the extraction techniques or types of fibers applied. Two types of bioassay were conducted to study attractancy of the sheep wool volatiles to mosquitoes: laboratory bioassays using glass tubes, and semi-field bioassays using large, screened outdoor cages. In bioassays with glass tubes, the sheep wool hydrodistillate and its main component, thialdine, did not show any significant attractant activity against female adult Ae. aegypti mosquitoes. Semi-field bioassays in two large screened outdoor cages, each equipped with a U.S. Centers for Disease Control (CDC) trap and the various bait setups with Vortex apparatus, revealed that vibrating wool improved mosquito catches compared to the setups without wool or with wool but not vibrating. Sheep wool, when vibrated, may release intensively volatile compounds, which could serve as olfactory cues, and play significant role in making the bait attractive to mosquitoes. Sheep wool is a readily available, affordable, and environment-friendly material. It should have the potential to be used as a mosquito management and surveillance component in dynamic bait setups.

Estimating the seasonal density of the snowpack has many financial and environmental benefits. Rapid assessment and daily monitoring of its evolution are therefore key to effective prevention. Traditionally, the physical characteristics of snow are measured directly in the field, which involves high costs and personnel mobilization. Hyperspectral imaging is a reliable and efficient technique to study and evaluate this physical property. The spectral reflectance of snow is partly defined by changes in its physical properties, particularly in the Near infrared (NIR) part of the spectrum. Recently, a hybrid snow density estimation model allowing retrieval of density from NIR hyperspectral data was developed, based on an a priori classification of snow samples. However, in order to obtain optimal density estimates with the Hybrid model (HM), the sources of classification and estimation error must be controlled. Following the same principle as the HM, an Ensemble-based system (EBS) was developed. This model reduces the number of misclassification errors produced by the HM. The general concept of EBS algorithms is based on the principle that obtaining more opinions before making a decision is part of human nature, especially when economic and environmental benefits are at stake. This approach has helped to reduce the risk of classification and estimation errors and to develop more robust density results. One hundred and fourteen snow samples collected during three winters (2018–2020) were used to calibrate and validate the EBS. The performance of the EBS was validated using an independent database and the results were satisfactory (R2 = 0.90, RMSE = 44.45 kg m−3, BIAS = 3.87 kg m−3 and NASH = 0.89).