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Abstract Brain-machine interface performance can be affected by neuroinflammatory responses due to blood-brain barrier (BBB) damage following intracortical microelectrode implantation. Recent findings suggest that certain gut bacterial constituents might enter the brain through damaged BBB. Therefore, we hypothesized that damage to the BBB caused by microelectrode implantation could facilitate microbiome entry into the brain. In our study, we found bacterial sequences, including gut-related ones, in the brains of mice with implanted microelectrodes. These sequences changed over time. Mice treated with antibiotics showed a reduced presence of these bacteria and had a different inflammatory response, which temporarily improved microelectrode recording performance. However, long-term antibiotic use worsened performance and disrupted neurodegenerative pathways. Many bacterial sequences found were not present in the gut or in unimplanted brains. Together, the current study established a paradigm-shifting mechanism that may contribute to chronic intracortical microelectrode recording performance and affect overall brain health following intracortical microelectrode implantation.

Abstract Before medical professionals are permitted to use a medical device, they first must be instructed in its use. However, it is well known that this method is hazardous for both the staff and the patients due to its inadequate quality. In order to address this problem, we investigated the potential of digital technologies for enhancing medical device training. For this, we designed and implemented several diverse training methods: (1) conventional training by a medical instructor, (2) video-based training, (3) mobile application training on a tablet, (4) virtual reality training, and (5) augmented reality training. Since each method provides identical training content to the user, we compared the resulting learning outcomes between the methods. The findings indicate that virtual and augmented reality training is superior to conventional training. These digital technologies offer the opportunity to reduce the burden on healthcare professionals and increase patient safety.

Abstract The nodal-line semiconductor Mn3Si2Te6 is generating enormous excitment due to the recent discovery of a field-driven insulator-to-metal transition and associated colossal magnetoresistance as well as evidence for a new type of quantum state involving chiral orbital currents. Strikingly, these qualities persist even in the absence of traditional Jahn-Teller distortions and double-exchange mechanisms, raising questions about exactly how and why magnetoresistance occurs along with conjecture as to the likely signatures of loop currents. Here, we measured the infrared response of Mn3Si2Te6 across the magnetic ordering and field-induced insulator-to-metal transitions in order to explore colossal magnetoresistance in the absence of Jahn-Teller and double-exchange interactions. Rather than a traditional metal with screened phonons, the field-driven insulator-to-metal transition leads to a weakly metallic state with localized carriers. Our spectral data are fit by a percolation model, providing evidence for electronic inhomogeneity and phase separation. Modeling also reveals a frequency-dependent threshold field for carriers contributing to colossal magnetoresistance which we discuss in terms of polaron formation, chiral orbital currents, and short-range spin fluctuations. These findings enhance the understanding of insulator-to-metal transitions in new settings and open the door to the design of unconventional colossal magnetoresistant materials.

A doctoral-level internship program was developed at the University of North Carolina at Chapel Hill with the intent to create customizable experiential learning opportunities for biomedical trainees to support career exploration, preparation, and transition into their postgraduate professional roles. We report the outcomes of this program over a 5-year period. During that 5-year period, 123 internships took place at over 70 partner sites, representing at least 20 academic, for-profit, and non-profit career paths in the life sciences. A major goal of the program was to enhance trainees’ skill development and expertise in careers of interest. The benefits of the internship program for interns, host/employer, and supervisor/principal investigator were assessed using a mixed-methods approach, including surveys with closed- and open-ended responses as well as focus group interviews. Balancing stakeholder interests is key to creating a sustainable program with widespread support; hence, the level of support from internship hosts and faculty members were the key metrics analyzed throughout. We hypothesized that once a successful internship program was implemented, faculty culture might shift to be more accepting of internships; indeed, the data quantifying faculty attitudes support this. Furthermore, host motivation and performance expectations of interns were compared with results achieved, and this data revealed both expected and surprising benefits to hosts. Data suggests a myriad of benefits for each stakeholder group, and themes are cataloged and discussed. Program outcomes, evaluation data, policies, resources, and best practices developed through the implementation of this program are shared to provide resources that facilitate the creation of similar internship programs at other institutions. Program development was initially spurred by National Institutes of Health pilot funding, thereafter, successfully transitioning from a grant-supported model, to an institutionally supported funding model to achieve long-term programmatic sustainability.

Abstract Interleukin-1α is a suggested dual-function cytokine that diverged from interleukin-1β in mammals potentially by acquiring additional biological roles that relate to highly conserved regions in the pro-domain of interleukin-1α, including a nuclear localisation sequence and histone acetyltransferase-binding domains. Why evolution modified pro-interleukin-1α’s subcellular location and protein interactome, and how this shaped interleukin-1α’s intracellular role, is unknown. Here we show that TurboID proximity labelling with pro-interleukin-1α suggests a nuclear role for pro-interleukin-1α that involves interaction with histone acetyltransferases, including EP300. We also identify and validate inactivating mutations in the pro-interleukin-1α nuclear localisation sequence of multiple mammalian species, including toothed whales, castorimorpha and marsupials. However, histone acetyltransferase-binding domains are conserved in those species that have lost pro-interleukin-1α nuclear localisation. Together, these data suggest that histone acetyltransferase binding and nuclear localisation occurred together, and that while some species lost the nuclear localisation sequence in their pro-interleukin-1α, histone acetyltransferase binding ability was maintained. The nuclear localisation sequence was lost from several distinct species at different evolutionary times, suggesting convergent evolution, and that the loss of the nuclear localisation sequence confers some important biological outcome.

Abstract Global optimization techniques are increasingly preferred over human-driven methods in the design of electromagnetic structures such as metasurfaces, and careful construction and parameterization of the physical structure is critical in ensuring computational efficiency and convergence of the optimization algorithm to a globally optimal solution. While many design variables in physical systems take discrete values, optimization algorithms often benefit from a continuous design space. This work demonstrates the use of level set functions as a continuous basis for designing material distributions for metasurface arrays and introduces an improved parameterization which is termed the periodic level set function. We explore the use of alternate norms in the definition of the level set function and define a new pseudo-inverse technique for upsampling basis coefficients with these norms. The level set method is compared to the fragmented parameterization and shows improved electromagnetic responses for two dissimilar cost functions: a narrowband objective and a broadband objective. Finally, we manufacture an optimized level set metasurface and measure its scattering parameters to demonstrate real-world performance.

The frequent occurrence of extreme hydroclimate events has a significant impact on ecosystems and socio-economic systems. However, intercomparisons of extreme events are often hampered by inconsistent definitions and standardizations for different types of events. Here we introduce the Optimal Path Threshold (OPT) method, a dynamic programming-based approach that adaptively determines optimal thresholds for defining extreme events at specific severity levels. Two case studies demonstrate its applicability. The first case study presents a long-term comparison of air heatwaves and lake heatwaves in Lake Mead. The algorithm adaptively selects thresholds to identify a comparable number of events at various severity levels. The second case study examines compound hot, dry, and windy events in California, exploring threshold selection for multivariable extremes and investigating their potential relationship with wildfires. The OPT method proves effective for adaptably and objectively analyzing complex and multifactorial extreme events.

Abstract Oxidized albumin (oxHSA) is elevated in several pathological conditions, such as decompensated cirrhosis, acute on chronic liver failure and liver mediated renal failure. Patient derived oxidized albumin was previously shown to be an inflammatory mediator, and in normal serum levels of oxHSA are low. The removal from circulation of oxidized albumins is therefore likely required for maintenance of homeostasis. Liver sinusoidal endothelial cells (LSEC) are prominent scavenger cells specialized in removal of macromolecular waste. Given that oxidized albumin is mainly cleared by the liver, we hypothesized the LSEC are the site of uptake in the liver. In vivo oxHSA was cleared rapidly by the liver and distributed to mainly the LSEC. In in vitro studies LSEC endocytosed oxHSA much more than other cell populations isolated from the liver. Furthermore, it was shown that the uptake was mediated by the stabilins, by affinity chromatography-mass spectrometry, inhibiting uptake in LSEC with other stabilin ligands and showing uptake in HEK cells overexpressing stabilin-1 or -2. oxHSA also inhibited the uptake of other stabilin ligands, and a 2-h challenge with 100 µg/mL oxHSA reduced LSEC endocytosis by 60% up to 12 h after. Thus the LSEC and their stabilins mediate clearance of highly oxidized albumin, and oxidized albumin can downregulate their endocytic capacity in turn.

Abstract Passenger and freight travel account for 28% of U.S. greenhouse gas (GHG) emissions today. We explore pathways to reduce transportation emissions using NREL’s TEMPO model under bounding assumptions on future travel behavior, technology advancement, and policies. Results show diverse routes to 80% or more well-to-wheel GHG reductions by 2050. Rapid adoption of zero-emission vehicles coupled with a clean electric grid is essential for deep decarbonization; in the median scenario, zero-emission vehicle sales reach 89% for passenger light-duty and 69% for freight trucks by 2030 and 100% sales for both by 2040. Up to 3,000 terawatt-hours of electricity could be needed in 2050 to power plug-in electric vehicles. Increased sustainable biofuel usage is also essential for decarbonizing aviation (10–42 billion gallons needed in 2050) and to support legacy vehicles during the transition. Managing travel demand growth can ease this transition by reducing the need for clean electricity and sustainable fuels.

Summary: Medium- and heavy-duty vehicles are 21% of US transportation greenhouse gas (GHG) emissions and a major source of air pollution. We explore how the total cost of driving (TCD) of zero-emission vehicles (ZEVs), including battery electric vehicles and hydrogen fuel cell electric vehicles (EVs and FCEVs), could evolve under alternative scenarios. With continued improvements in vehicles and fuels, ZEVs can rapidly become viable, potentially reaching TCD parity or better compared to diesel vehicles by 2035 for all market segments. For heavy long-haul trucks, EVs become competitive on a TCD basis at charging costs below $0.18/kWh, while FCEVs become competitive on a TCD basis at hydrogen costs below $5/kg. A full transition to ZEV sales by 2035 results in 65% emissions reductions by 2050 compared to 2019 without supportive policies. Incentives such as the Inflation Reduction Act vehicle purchase credits further accelerate ZEV TCD competitiveness with major adoption opportunities over the next five years.

Abstract Xanthines such as caffeine and theobromine are among the most consumed psychoactive stimulants in the world, either as natural components of coffee, tea and chocolate, or as added ingredients. The present study assessed if xanthines affect liver sinusoidal endothelial cells (LSEC). Cultured primary rat LSEC were challenged with xanthines at concentrations typically obtained from normal consumption of xanthine-containing beverages, food or medicines; and at higher concentrations below the in vitro toxic limit. The fenestrated morphology of LSEC were examined with scanning electron and structured illumination microscopy. All xanthine challenges had no toxic effects on LSEC ultrastructure as judged by LSEC fenestration morphology, or function as determined by endocytosis studies. All xanthines in high concentrations (150 μg/mL) increased fenestration frequency but at physiologically relevant concentrations, only theobromine (8 μg/mL) showed an effect. LSEC porosity was influenced only by high caffeine doses which also shifted the fenestration distribution towards smaller pores. Moreover, a dose-dependent increase in fenestration number was observed after caffeine treatment. If these compounds induce similar changes in vivo, age-related reduction of LSEC porosity can be reversed by oral treatment with theobromine or with other xanthines using targeted delivery.

Abstract Modern communication and navigation systems are increasingly relying on atomic clocks. As timing precision requirements increase, demands for lower SWaP (size, weight, and power) clocks rise. However, it has been challenging to break through the general trade-off trend between the clock stability performance and SWaP. Here we demonstrate micro mercury trapped ion clock (M2TIC) prototypes integrated with novel micro-fabricated technologies to simultaneously achieve high performance and low SWaP. The M2TIC prototypes could reach the $$10^{-14}$$ 10 - 14 -stability level in 1 day with a SWaP of 1.1 L, 1.2 kg, and under 6 W of power. This stability level is comparable to the widely used rack-mount Microchip 5071A cesium frequency standard. These standalone prototypes survived regular commercial shipping across the North American continent to a government laboratory, where their performance was independently tested. The M2TIC sets a new reference point for SWaP and performance and opens opportunities for high-performance clocks in terrestrial and space applications.

Monitoring areas susceptible to desertification contributes to the strategic development of regions located in environments of extreme hydric and social vulnerability. Therefore, the objective of this study is to evaluate the process of soil degradation in the Desertification Nucleus of Cabrobó (DNC) over the past three decades using remote sensing techniques. This study used primary climatic data from TerraClimate, geospatial data of land use and land cover (LULC), and vegetation indices (SAVI and LAI) via Google Earth Engine (GEE) from Landsat 5/TM and 8/OLI satellites, and established the aridity index (AI) from 1992 to 2022. The results indicated 10 predominant LULC classes with native vegetation suppression, particularly in agriculture and urbanization. SAVI ranged from −0.84 to 0.90, with high values influenced by La Niña episodes and increased rainfall; conversely, El Niño episodes worsened the rainfall regime in the DNC region. Based on the Standardized Precipitation Index (SPI), it was possible to correlate normal and severe drought events in the DNC with years under the influence of El Niño and La Niña phases. In summary, the AI images indicated that the DNC remained semi-arid and that the transition to an arid region is a cyclical and low-frequency phenomenon, occurring in specific periods and directly influenced by El Niño and La Niña phenomena. The Mann–Kendall analysis showed no increasing trend in AI, with a Tau of −0.01 and a p-value of 0.97. During the analyzed period, there was an increase in Non-Vegetated Areas, which showed a growing trend with a Tau of 0.42 in the Mann–Kendall analysis, representing exposed soil areas. Annual meteorological conditions remained within the climatic pattern of the region, with annual averages of precipitation and actual evapotranspiration (ETa) close to 450 mm and an average temperature of 24 °C, showing changes only during El Niño and La Niña events, and did not show significant increasing or decreasing trends in the Mann–Kendall analysis.

Summary: Excessive or aberrant NLRP3 inflammasome activation has been implicated in the progression and initiation of many inflammatory conditions; however, currently no NLRP3 inflammasome inhibitors have been approved for therapeutic use in the clinic. Here we have identified that the natural product brazilin effectively inhibits both priming and activation of the NLRP3 inflammasome in cultured murine macrophages, a human iPSC microglial cell line and in a mouse model of acute peritoneal inflammation. Through computational modeling, we predict that brazilin can adopt a favorable binding pose within a site of the NLRP3 protein which is essential for its conformational activation. Our results not only encourage further evaluation of brazilin as a therapeutic agent for NLRP3-related inflammatory diseases, but also introduce this small-molecule as a promising scaffold structure for the development of derivative NLRP3 inhibitor compounds.

[This corrects the article DOI: 10.1371/journal.pone.0277493.].

Abstract We demonstrate a fiber Bragg grating (FBG) strain interrogator based on a scattering medium to generate stable and deterministic speckle patterns, calibrated with applied strain, which are highly dependent on the FBG back-reflection spectral components. The strong wavelength-dependency of speckle patterns was previously used for high resolution wavemeters where scattering effectively folds the optical path, but instability makes practical realization of such devices difficult. Here, a new approach is demonstrated by utilizing femtosecond laser-written scatterers inside flat optical fiber, to enhance mechanical stability. By inscribing 15 planes of pseudo-randomized nanovoids (714 $$\times$$ × 500 voids per plane) as a 3D array in a 1 $$\times$$ × 0.7 $$\times$$ × 0.16 mm volume, the intrinsic stability and compactness of the device was improved. Operating as a wavemeter, it remained stable for at least 60 h with 45 pm resolution over the wavelength range of 1040–1056 nm. As a reflection mode FBG interrogator, after calibrating speckle patterns by applying tensile strain to the FBG, the device is capable of detecting microstrain changes in the range of 0–200 $$\mu \epsilon$$ μ ϵ with a standard error of 4 $$\mu \epsilon$$ μ ϵ , limited by the translation stage step size. All these characteristics make it an interesting technology for filling the niche of low-cost, high-resolution wavemeters and interrogators which offer the best available trade-off between resolution, compactness, price and stability.

The Life Editorial Office retracts the article, “Metal Catalysis Acting on Nitriles in Early Earth Hydrothermal Systems” [...]

Abstract Extended cut-off filtration by medium cut-off membranes (MCO) has been shown to be safe in maintenance hemodialysis (HD). The notion of using them for the control of chronic low-grade inflammation and positively influencing cellular immune aberrations seems tempting. We conducted an open label, multicenter, randomized, 90 day 2-phase cross over clinical trial (MCO- vs. high flux-HD). 46 patients underwent randomization of which 34 completed the study. Dialysate- or pre- and post-dialysis serum inflammatory mediators were assayed for each study visit. Ex vivo T cell activation was assessed from cryopreserved leucocytes by flow cytometry. Linear mixed models were used to compare treatment modalities, with difference in pre-dialysis serum MCP-1 levels after 3 months as the predefined primary endpoint. Filtration/dialysate concentrations of most mediators, including MCP-1 (mean ± SD: 10.5 ± 5.9 vs. 5.1 ± 3.8 pg/ml, P

Abstract Diagnosis of Severe Acute Respiratory Syndrome Coronavirus 2 (SARS-CoV-2) infection has primarily been achieved using reverse transcriptase polymerase chain reaction (RT-PCR) for acute infection, and serology for prior infection. Assay with RT-PCR provides data on presence or absence of viral RNA, with no information on virus replication competence, infectivity, or virus characterisation. Liquid chromatography-tandem mass spectrometry (LC–MS/MS) is typically not used in clinical virology, despite its potential to provide supplemental data about the presence of viral proteins and thus the potential for replication-competent, transmissible virus. Using the SARS-CoV-2 as a model virus, we developed a fast ‘bottom-up’ proteomics workflow for discovery of target virus peptides using ‘serum-free’ culture conditions, providing high coverage of viral proteins without the need for protein or peptide fractionation techniques. This workflow was then applied to Coronaviruses OC43 and 229E, Influenza A/H1N1 and H3N2, Influenza B, and Respiratory Syncytial Viruses A and B. Finally, we created an LC–MS/MS method for targeted detection of the eight-virus panel in clinical specimens, successfully detecting peptides from the SARS-CoV-2 ORF9B and nucleoprotein in RT-PCR positive samples. The method provides specific detection of respiratory viruses from clinical samples containing moderate viral loads and is an important further step to the use of LC–MS/MS in diagnosis of viral infection.

IL-2 has been used to expand regulatory T (Treg) cells for treating inflammatory disorders. Here the authors test an engineered IL-2 mutein, delivered subcutaneously as mRNA, to show its increased specificity for activating and expanding Treg cells in both rodents and non-human primates, and to demonstrate its ability to suppress autoimmunity in mouse models.

The reversible reduction and oxidation of protein thiols was first described as mechanism to control light/dark-dependent metabolic regulation in photosynthetic organisms. Today, it is recognized as an essential mechanism of regulation and signal transduction in all kingdoms of life. Proteins of the thioredoxin (Trx) family, Trxs and glutaredoxins (Grxs) in particular, catalyze thiol-disulfide exchange reactions and are vital players in the operation of thiol switches. Various Trx and Grx isoforms are present in all compartments of the cell. These proteins have a rather broad but at the same time distinct substrate specificity. Understanding the molecular basis of their target specificity is central to the understanding of physiological and pathological redox signaling. Electrostatic complementarity of the redoxins with their target proteins has been proposed as a major reason. Here, we analyzed the electrostatic similarity of all Arabidopsis thaliana Trxs, Grxs, and proteins containing such domains. Clustering of the redoxins based on this comparison suggests overlapping and also distant target specificities and thus functions of the different sub-classes including all Trx isoforms as well as the three classes of Grxs, i.e. CxxC-, CGFS-, and CC-type Grxs. Our analysis also provides a rationale for the tuned substrate specificities of both the ferredoxin- and NADPH-dependent Trx reductases.

Firearm deaths continue to be a major public health problem, but the number of non-fatal firearm injuries and the characteristics of patients and injuries is not well known. The American College of Surgeons Committee on Trauma, with support from the National Collaborative on Gun Violence Research, leveraged an existing data system to capture lethal and non-lethal injuries, including patients treated and discharged from the emergency department and collect additional data on firearm injuries that present to trauma centers. In 2020, Missouri had the 4th highest firearm mortality rate in the country at 23.75/100,000 population compared to 13.58/100,000 for the US overall. We examined the characteristics of patients from Missouri with firearm injuries in this cross-sectional study. Of the overall 17,395 patients, 1,336 (7.7%) were treated at one of the 11 participating trauma centers in Missouri during the 12-month study period. Patients were mostly male and much more likely to be Black and uninsured than residents in the state as a whole. Nearly three-fourths of the injuries were due to assaults, and overall 7.7% died. Few patients received post-discharge services.

Abstract The novel air purification technology, Nano-Confined Catalytic Oxidation (NCCO), has been proven to be effective at eliminating air pollutants. With the increasing legalization and decriminalization of medicinal and recreational cannabis and related products, respectively, in many countries and jurisdictions around the world, concerns have been raised about indoor air quality from smoking cannabis products, such as marijuana, which produce gaseous pollutants and intense odour. In this study, NCCO technology has been evaluated for its effectiveness in reducing key marijuana concentrations in polluted indoor air by direct measurements and odour intensity assessments by human volunteers. For the odour intensity measurements, 20 non-cannabis adults participated in the odour assessment. The results are remarkable and statistically significant. The reduction in Dronabinol, a pharmaceutical form of Tetrahydrocannabinol (THC), Cannabidiol (CBD) and Cannabinol, averages 93.4%, whereas that in airborne marijuana compounds with no air purification only averages 6.2%. The technology also demonstrates statistically significant reductions in PM2.5, PM10 and total volatile organic compounds generated from marijuana smoke. The technology was able to restore high levels of harmful particulate matter to normal baseline levels. Furthermore, the odour assessment conducted by a group of 20 volunteers also confirmed statistically significant reductions in marijuana odour by 55.6% after 50 min of air purification.

Areas covered in compact sea ice were often assumed to prohibit upper-ocean photosynthesis. Yet, under-ice phytoplankton blooms (UIBs) have increasingly been observed in the Arctic, driven by anthropogenic changes to the optical properties of Arctic sea ice. Here, we show evidence that the Southern Ocean may also support widespread UIBs. We compile 77 time series of water column samples from biogeochemical Argo floats that profiled under compact (80%–100% concentration) sea ice in austral spring–summer since 2014. We find that that nearly all (88%) such measurements recorded increasing phytoplankton biomass before the seasonal retreat of sea ice. A significant fraction (26%) met a observationally determined threshold for an under-ice bloom, with an average maximum chlorophyll-a measurement of 1.13 mg/m3. We perform a supporting analysis of joint light, sea ice, and ocean conditions from ICESat-2 laser altimetry and climate model contributions to CMIP6, finding that from 3 to 5 million square kilometers of the compact-ice-covered Southern Ocean has sufficient conditions to support light-limited UIBs. Comparisons between the frequency of bloom observations and modeled bloom predictions invite future work into mechanisms sustaining or limiting under-ice phytoplankton blooms in the Southern Hemisphere.

Hydrothermal systems are areas in which heated fluids and organic molecules rush through basaltic material rich in metals and minerals. By studying malononitrile and acetonitrile, we examine the effects of metal and mineral nanoparticles on nitrile compounds in anoxic, hydrothermal conditions representing a prebiotic environment of early Earth. Polymerization, reduction, cyclization, and a phenomenon colloquially known as ‘chemical gardening’ (structure building via reprecipitation of metal compounds or complexing with organics) are all potential outcomes with the addition of metals and minerals. Reduction occurs with the addition of rhodium (Rh) or iron (II) sulfide (FeS), with positive identification of ethanol and ethylamine forming from acetonitrile reduction. We find that polymerization and insoluble product formation were associated with oxide minerals, metallic nickel (Ni), and metallic cobalt (Co) acting as catalysts. Oxide minerals strongly promoted polymerization into insoluble, tar-like products of nitriles. FeS, iron-nickel alloy (FeNi), and rhodium are unique cases that appear to act as reagents by actively participating in chemical gardening without returning to their initial state. Further, FeS tentatively had a phase change into the mineral parabutlerite. This research aims to identify metals and metal minerals that could best serve nitrile catalysis and reactions on early Earth.

Climate models struggle to track the response of Arctic sea ice to warming, leading to efforts to improve sea-ice models. Here the author shows standard model metrics are poor judges of the impact of model improvements, but a new one, marginal ice zone fraction, is optimally suited to this task.

Glutaredoxins are a family of essential enzymes divided into two major classes with either a CGFS or a CxxC active site, of which only the latter exhibits oxidoreductase activity. Here the authors address the structural basis for the functional difference between the two classes of glutaredoxins.

Vaccine hesitancy is proving to be a significant impediment to COVID-19 vaccination campaigns in some developing countries. This study focuses on vaccine hesitancy and means of reducing it. Data come from a large, representative phone survey and online randomized survey experiment, both run in Papua New Guinea, a developing country with low vaccination rates. Less than 20% of relevant respondents to the phone survey were willing to be vaccinated, primarily because of fear of side effects and low trust in the vaccine. Although vaccine hesitancy was high in the online experiment, participants who received a message emphasizing that the vaccine was safe and COVID-19 dangerous were 68% more likely to state they planned to be vaccinated than those in the control group. A message appealing to social norms was also effective in reducing vaccine hesitancy, although its efficacy was limited to certain types of people.

The growth of phytoplankton at high latitudes was generally thought to begin in open waters of the marginal ice zone once the highly reflective sea ice retreats in spring, solar elevation increases, and surface waters become stratified by the addition of sea-ice melt water. In fact, virtually all recent large-scale estimates of primary production in the Arctic Ocean (AO) assume that phytoplankton production in the water column under sea ice is negligible. However, over the past two decades, an emerging literature showing significant under-ice phytoplankton production on a pan-Arctic scale has challenged our paradigms of Arctic phytoplankton ecology and phenology. This evidence, which builds on previous, but scarce reports, requires the Arctic scientific community to change its perception of traditional AO phenology and urgently revise it. In particular, it is essential to better comprehend, on small and large scales, the changing and variable icescapes, the under-ice light field and biogeochemical cycles during the transition from sea-ice covered to ice-free Arctic waters. Here, we provide a baseline of our current knowledge of under-ice blooms (UIBs), by defining their ecology and their environmental setting, but also their regional peculiarities (in terms of occurrence, magnitude, and assemblages), which is shaped by a complex AO. To this end, a multidisciplinary approach, i.e., combining expeditions and modern autonomous technologies, satellite, and modeling analyses, has been used to provide an overview of this pan-Arctic phenological feature, which will become increasingly important in future marine Arctic biogeochemical cycles.

Despite its chemical importance, the evolution of atmospheric iodine concentrations over time is unknown. Here, the authors show that North Atlantic atmospheric iodine levels have tripled since 1950, and propose ozone pollution and enhanced biological production Arctic sea ice thinning as a primary driver.

PurposeThis study aimed to determine if sequential deployment of a nurse-led Rapid Response Team (RRT) and an intensivist-led Medical Emergency Team (MET) for critically ill patients in the Emergency Department (ED) and acute care wards improved hospital-wide cardiac arrest rates.MethodsIn this single-center, retrospective observational cohort study, we compared the cardiac arrest rates per 1000 patient-days during two time periods. Our hospital instituted a nurse-led RRT in 2012 and added an intensivist-led MET in 2014. We compared the cardiac arrest rates during the nurse-led RRT period and the combined RRT-MET period. With the sequential approach, nurse-led RRT evaluated and managed rapid response calls in acute care wards and if required escalated care and co-managed with an intensivist-led MET. We specifically compared the rates of pulseless electrical activity (PEA) in the two periods. We also looked at the cardiac arrest rates in the ED as RRT-MET co-managed patients with the ED team.ResultsHospital-wide cardiac arrests decreased from 2.2 events per 1000 patient-days in the nurse-led RRT period to 0.8 events per 1000 patient-days in the combined RRT and MET period (p-value = 0.001). Hospital-wide PEA arrests and shockable rhythms both decreased significantly. PEA rhythms significantly decreased in acute care wards and the ED.ConclusionImplementing an intensivist-led MET-RRT significantly decreased the overall cardiac arrest rate relative to the rate under a nurse-led RRT model. Additional MET capabilities and early initiation of advanced, time-sensitive therapies likely had the most impact.

Tuna fish meat is an expensive and highly perishable sea food. Fresh meat has a bright red colour which soon turns into an unsightly brown during storage. To prolong the aspect of freshness, the red colour is stabilised or even enhanced e.g. with carbon monoxide or nitric oxide, the product of a nitrite / ascorbic acid treatment, which bind as a ligand to myoglobin. These procedures are illegal. Here we present a method for identifying tuna meat samples, which have undergone fraudulent wet salting with nitrite. The method uses headspace-gas chromatography/mass spectrometry (GC/MS) for the determination of nitrous oxide, which is formed as the final product of the two-step reduction nitrite (added agent) to nitric oxide (ligand) to nitrous oxide (target compound). Complex bound nitric oxide is set free with sulfuric acid, which also promotes the reduction to nitrous oxide. The method was validated using 15N labelled nitrite as well as treated and untreated reference fish samples. A survey of 13 samples taken from the Swiss market in 2019 showed that 45 % of all samples were illegally treated with nitrite.

Tuna fish meat is an expensive and highly perishable sea food. Fresh meat has a bright red colour which soon turns into an unsightly brown during storage. To prolong the aspect of freshness, the red colour is stabilised or even enhanced e.g. with carbon monoxide or nitric oxide, the product of a nitrite / ascorbic acid treatment, which bind as a ligand to myoglobin. These procedures are illegal. Here we present a method for identifying tuna meat samples, which have undergone fraudulent wet salting with nitrite. The method uses headspace-gas chromatography/mass spectrometry (GC/MS) for the determination of nitrous oxide, which is formed as the final product of the two-step reduction nitrite (added agent) to nitric oxide (ligand) to nitrous oxide (target compound). Complex bound nitric oxide is set free with sulfuric acid, which also promotes the reduction to nitrous oxide. The method was validated using 15N labelled nitrite as well as treated and untreated reference fish samples. A survey of 13 samples taken from the Swiss market in 2019 showed that 45 % of all samples were illegally treated with nitrite.

Aromatase inhibitors are used to treat oestrogen receptor positive breast cancers but the molecular basis for the response of patients is unclear. Here, the authors use samples from an aromatase inhibitor clinical trial and show that tumours from poor responders have more mutations than good responders and also more frequently harbour p53 mutations.

Several β-secretase (BACE) inhibitors exhibit unexplained ocular toxicity in preclinical studies. Here the authors generate a clickable photoaffinity probe to interrogate off-targets in cells and animals, and identify inhibition of cathepsin D as a driver of ocular toxicity.

Bacterial DNA has been reported in the placenta and amniotic fluid by several independent groups of investigators. However, it's taxonomic overlap with fetal and maternal bacterial DNA in different sites has been poorly characterized. Here, we determined the presence of bacterial DNA in the intestines and placentas of fetal mice at gestational day 17 (n = 13). These were compared to newborn intestines (n = 15), maternal sites (mouth, n = 6; vagina, n = 6; colon, n = 7; feces, n = 8), and negative controls to rule out contamination. The V4 region of the bacterial 16S rRNA gene indicated a pattern of bacterial DNA in fetal intestine similar to placenta but with higher phylogenetic diversity than placenta or newborn intestine. Firmicutes were the most frequently assignable phylum. SourceTracker analysis suggested the placenta as the most commonly identifiable origin for fetal bacterial DNA, but also over 75% of fetal gut genera overlapped with maternal oral and vaginal taxa but not with maternal or newborn feces. These data provide evidence for the presence of bacterial DNA in the mouse fetus.

Nowadays, about 12% of the European and 20% of the US population are tattooed. Rising concerns regarding consumer safety, led to legal restrictions on tattoo and permanent make-up (PMU) inks. Restrictions also include bans on certain colourants. Both ink types use organic pigments for colour-giving, plus inorganic pigments for white and black and colour tones. Pigments are only sparingly soluble in common solvents and occur as suspended particles in the ink matrix. Their detection and identification therefore pose a major challenge for laboratories involved in monitoring the legal compliance of tattoo inks and PMU. We overcame this challenge by developing a direct laser desorption ionisation time-of-flight mass spectrometry method, which included an easy sample clean up. The method proved to be capable of detecting and identifying organic pigments in almost all of the tested ink samples. Method validation and routine deployment during market surveys showed the method to be fit for purpose. Pigment screening of 396 tattoo inks and 55 PMU taken from the Swiss market between 2009 and 2017 lead to the following conclusions: Pigment variety is much greater in tattoo inks (18) than in PMU (10); four prohibited pigments (Pigment Green 7, Pigment Red 122, Pigment Violet 19 and 23) were found in both ink types; for PMU, these four pigments made up 12% of the pigment findings, compared to 32% for tattoo inks. Therefore, legal compliance of PMU was at a higher level. A comparison of pigments found with those declared on tattoo ink labels clearly showed that banned pigments are rarely declared, but rather masked by listing non present legal pigments and label forging; therefore, highlighting the urgency of widespread market controls.

Previous studies have shown that modified apelin analogues exhibited enzyme resistance in plasma and improved circulating half-life compared to apelin-13. This study investigated the antidiabetic effects of chronic administration of stable long acting fatty acid modified apelin analogues, namely, (Lys8GluPAL)apelin-13 amide and pGlu(Lys8GluPAL)apelin-13 amide, in high-fat fed obese-diabetic mice. Male NIH Swiss mice (groups n = 8) were maintained either on a high-fat diet (45% fat) from 8 to 28 weeks old, or control mice were fed a normal diet (10% fat). When diet induced obesity-diabetes was established after high-fat feeding, mice were injected i.p. once daily with apelin analogues, liraglutide (25 nmol/kg) or saline (controls). Administration of (Lys8GluPAL)apelin-13 amide and pGlu(Lys8GluPAL)apelin-13 amide for 28 days significantly reduced food intake and decreased body weight. Non-fasting glucose was reduced (p

Nowadays, about 12% of the European and 20% of the US population are tattooed. Rising concerns regarding consumer safety, led to legal restrictions on tattoo inks and permanent make-up (PMU) inks. Restrictions also include bans on certain hazardous colourants. Both ink types use organic pigments for colour-giving, plus inorganic pigments for white and black and colour tones. Pigments are only sparingly soluble in common solvents and occur as suspended particles in the ink matrix. Their detection and identification therefore pose a major challenge for laboratories involved in monitoring the legal compliance of tattoo inks and PMUs. We overcame this challenge by developing a matrix-assisted laser desorption ionisation time-of-flight mass spectrometry method, which included an easy sample clean up. The method proved to be capable of detecting and identifying organic pigments in almost all of the tested ink samples. Method validation and routine deployment during market surveys showed the method to be fit for purpose. Pigment screening of 396 tattoo inks and 55 PMUs taken from the Swiss market between 2009 and 2017 lead to the following conclusions: Pigment variety is much greater in tattoo inks (18) than in PMUs (10); four prohibited pigments (Pigment Green 7, Pigment Red 122, Pigment Violet 19 and 23) were found in both ink types; for PMUs, these four pigments made up 12% of the pigment findings, compared to 32% for tattoo inks. Therefore, legal compliance of PMUs was at a higher level. A comparison of pigments found with those declared on tattoo ink labels clearly showed that banned pigments are rarely declared, but rather masked by listing not present legal pigments and label forging; therefore, highlighting the urgency of widespread market controls.

We present a novel technique to infer ground slope angle from waveform LiDAR, known as the independent slope method (ISM). The technique is applied to large footprint waveforms (\(\sim\) mean diameter) from the Ice, Cloud and Land Elevation Satellite (ICESat) Geoscience Laser Altimeter System (GLAS) to produce a slope dataset of near-global coverage at \(0.5^{\circ} \times 0.5^{\circ}\) resolution. ISM slope estimates are compared against high resolution airborne LiDAR slope measurements for nine sites across three continents. ISM slope estimates compare better with the aircraft data (R\(^{2}=0.87\) and RMSE\(=5.16^{\circ}\)) than the Shuttle Radar Topography Mission Digital Elevation Model (SRTM DEM) inferred slopes (R\(^{2}=0.71\) and RMSE\(=8.69^{\circ}\)) ISM slope estimates are concurrent with GLAS waveforms and can be used to correct biophysical parameters, such as tree height and biomass. They can also be fused with other DEMs, such as SRTM, to improve slope estimates.

The airborne AirSWOT instrument suite, consisting of an interferometric Ka-band synthetic aperture radar and color-infrared (CIR) camera, was deployed to northern North America in July and August 2017 as part of the NASA Arctic-Boreal Vulnerability Experiment (ABoVE). We present validated, open (i.e., vegetation-free) surface water masks produced from high-resolution (1 m), co-registered AirSWOT CIR imagery using a semi-automated, object-based water classification. The imagery and resulting high-resolution water masks are available as open-access datasets and support interpretation of AirSWOT radar and other coincident ABoVE image products, including LVIS, UAVSAR, AIRMOSS, AVIRIS-NG, and CFIS. These synergies offer promising potential for multi-sensor analysis of Arctic-Boreal surface water bodies. In total, 3167 km2 of open surface water were mapped from 23,380 km2 of flight lines spanning 23 degrees of latitude and broad environmental gradients. Detected water body sizes range from 0.00004 km2 (40 m2) to 15 km2. Power-law extrapolations are commonly used to estimate the abundance of small lakes from coarser resolution imagery, and our mapped water bodies followed power-law distributions, but only for water bodies greater than 0.34 (±0.13) km2 in area. For water bodies exceeding this size threshold, the coefficients of power-law fits vary for different Arctic-Boreal physiographic terrains (wetland, prairie pothole, lowland river valley, thermokarst, and Canadian Shield). Thus, direct mapping using high-resolution imagery remains the most accurate way to estimate the abundance of small surface water bodies. We conclude that empirical scaling relationships, useful for estimating total trace gas exchange and aquatic habitats on Arctic-Boreal landscapes, are uniquely enabled by high-resolution AirSWOT-like mappings and automated detection methods such as those developed here.

Although wetlands provide valuable services to humans and the environment and cover a large portion of Canada, there is currently no Canada-wide wetland inventory based on the specifications defined by the Canadian Wetland Classification System (CWCS). The most practical approach for creating the Canadian Wetland Inventory (CWI) is to develop a remote sensing method feasible for large areas with the potential to be updated within certain time intervals to monitor dynamic wetland landscapes. Thus, this study aimed to create the first Canada-wide wetland inventory using Landsat-8 imagery and innovative image processing techniques available within Google Earth Engine (GEE). For this purpose, a large amount of field samples and approximately 30,000 Landsat-8 surface reflectance images were initially processed using several advanced algorithms within GEE. Then, the random forest (RF) algorithm was applied to classify the entire country. The final step was an original CWI map considering the five wetland classes defined by the CWCS (i.e., bog, fen, marsh, swamp, and shallow water) and providing updated and comprehensive information regarding the location and spatial extent of wetlands in Canada. The map had reasonable accuracy in terms of both visual and statistical analyses considering the large area of country that was classified (9.985 million km2). The overall classification accuracy and the average producer and user accuracies for wetland classes exclusively were 71%, 66%, and 63%, respectively. Additionally, based on the final classification map, it was estimated that 36% of Canada is covered by wetlands.

Contemporary approaches to medical decision-making advise that clinicians should respect patients' decisions. However, patients' decisions are often shaped by heuristics, such as being guided by emotion, rather than by objective risk and benefit. Risk-reducing mastectomy (RRM) decisions focus this dilemma sharply. RRM reduces breast cancer (BC) risk, but is invasive and can have iatrogenic consequences. Previous evidence suggests that emotion guides patients' decision-making about RRM. We interviewed patients to better understand how they made decisions about RRM, using findings to consider how clinicians could ethically respond to their decisions.Qualitative face-to-face interviews with 34 patients listed for RRM surgery and two who had decided against RRM.Patients generally did not use objective risk estimates or, indeed, consider risks and benefits of RRM. Instead emotions guided their decisions: they chose RRM because they feared BC and wanted to do 'all they could' to prevent it. Most therefore perceived RRM to be the 'obvious' option and made the decision easily. However, many recounted extensive post-decisional deliberation, generally directed towards justifying the original decision. A few patients deliberated before the decision because fears of surgery counterbalanced those of BC.Patients seeking RRM were motivated by fear of BC, and the need to avoid potential regret for not doing all they could to prevent it. We suggest that choices such as that for RRM, which are made emotionally, can be respected as autonomous decisions, provided patients have considered risks and benefits. Drawing on psychological theory about how people do make decisions, as well as normative views of how they should, we propose that practitioners can guide consideration of risks and benefits even, where necessary, after patients have opted for surgery. This model of practice could be extended to other medical decisions that are influenced by patients' emotions.

Galectin-8 (Gal-8) is a member of a glycan-binding protein family that regulates the immune system, among other functions, and is a target of antibodies in autoimmune disorders. However, its role in multiple sclerosis (MS), an autoimmune inflammatory disease of the central nervous system (CNS), remains unknown. We study the consequences of Gal-8 silencing on lymphocyte subpopulations and the development of experimental autoimmune encephalitis (EAE), to then assess the presence and clinical meaning of anti-Gal-8 antibodies in MS patients. Lgals8/Lac-Z knock-in mice lacking Gal-8 expression have higher polarization toward Th17 cells accompanied with decreased CCR6+ and higher CXCR3+ regulatory T cells (Tregs) frequency. These conditions result in exacerbated MOG35-55 peptide-induced EAE. Gal-8 eliminates activated Th17 but not Th1 cells by apoptosis and ameliorates EAE in C57BL/6 wild-type mice. β-gal histochemistry reflecting the activity of the Gal-8 promoter revealed Gal-8 expression in a wide range of CNS regions, including high expression in the choroid-plexus. Accordingly, we detected Gal-8 in human cerebrospinal fluid, suggesting a role in the CNS immune-surveillance circuit. In addition, we show that MS patients generate function-blocking anti-Gal-8 antibodies with pathogenic potential. Such antibodies block cell adhesion and Gal-8-induced Th17 apoptosis. Furthermore, circulating anti-Gal-8 antibodies associate with relapsing-remitting MS (RRMS), and not with progressive MS phenotypes, predicting clinical disability at diagnosis within the first year of follow-up. Our results reveal that Gal-8 has an immunosuppressive protective role against autoimmune CNS inflammation, modulating the balance of Th17 and Th1 polarization and their respective Tregs. Such a role can be counteracted during RRMS by anti-Gal-8 antibodies, worsening disease prognosis. Even though anti-Gal-8 antibodies are not specific for MS, our results suggest that they could be a potential early severity biomarker in RRMS.

Projected changes in the relative abundance and timing of autumn-winter migration are assessed for seven dabbling duck species across the Mississippi and Atlantic Flyways for the mid- and late 21st century. Species-specific observed relationships are established between cumulative weather severity in autumn-winter and duck population rate of change. Dynamically downscaled projections of weather severity are developed using a high-resolution regional climate model, interactively coupled to a one-dimensional lake model to represent the Great Lakes and associated lake-effect snowfall. Based on the observed relationships and downscaled climate projections of rising air temperatures and reduced snow cover, delayed autumn-winter migration is expected for all species, with the least delays for the Northern Pintail and the greatest delays for the Mallard. Indeed, the Mallard, the most common and widespread duck in North America, may overwinter in the Great Lakes region by the late 21st century. This highlights the importance of protecting and restoring wetlands across the mid-latitudes of North America, including the Great Lakes Basin, because dabbling ducks are likely to spend more time there, which would impact existing wetlands through increased foraging pressure. Furthermore, inconsistency in the timing and intensity of the traditional autumn-winter migration of dabbling ducks in the Mississippi and Atlantic Flyways could have social and economic consequences to communities to the south, where hunting and birdwatching would be affected.

Allergy is inversely related to glioma risk. To determine whether prediagnostic allergy-related serum proteins are associated with glioma, we conducted a nested case-control study of seven cytokines (IL4, IL13, IL5, IL6, IL10, IFNG, TGFB2), two soluble cytokine receptors (sIL4RA, sIL13RA2) and three allergy-related transcription factors (FOXP3, STAT3, STAT6) using serum specimens from the Janus Serum Bank Cohort in Oslo, Norway. Blood donors subsequently diagnosed with glioma (n = 487) were matched to controls (n = 487) on age and date of blood draw and sex. We first estimated individual effects of the 12 serum proteins and then interactions between IL4 and IL13 and their receptors using conditional logistic regression. We next tested equality of case-control inter-correlations among the 12 serum proteins. We found that TGFB2 is inversely related to glioblastoma (Odds Ratio (OR) = 0.87, 95% Confidence Interval (CI)) = 0.76, 0.98). In addition, ≤ 5 years before diagnosis, we observed associations between IL4 (OR = 0.82, 95% CI = 0.66, 1.01), sIL4RA (OR = 0.80, 95% CI = 0.65, 1.00), their interaction (OR = 1.06, 95% CI = 1.01, 1.12) and glioblastoma. This interaction was apparent > 20 years before diagnosis (IL4-sIL4RA OR = 1.20, 95% CI = 1.05, 1.37). Findings for glioma were similar. Case correlations were different from control correlations stratified on time before diagnosis. Five years or less before diagnosis, correlations among case serum proteins were weaker than were those among controls. Our findings suggest that IL4 and sIL4RA reduce glioma risk long before diagnosis and early gliomagenesis affects circulating immune function proteins.

Protein cysteines can form transient disulfides with glutathione (GSH), resulting in the production of glutathionylated proteins, and this process is regarded as a mechanism by which the redox state of the cell can regulate protein function. Most studies on redox regulation of immunity have focused on intracellular proteins. In this study we have used redox proteomics to identify those proteins released in glutathionylated form by macrophages stimulated with lipopolysaccharide (LPS) after pre-loading the cells with biotinylated GSH. Of the several proteins identified in the redox secretome, we have selected a number for validation. Proteomic analysis indicated that LPS stimulated the release of peroxiredoxin (PRDX) 1, PRDX2, vimentin (VIM), profilin1 (PFN1) and thioredoxin 1 (TXN1). For PRDX1 and TXN1, we were able to confirm that the released protein is glutathionylated. PRDX1, PRDX2 and TXN1 were also released by the human pulmonary epithelial cell line, A549, infected with influenza virus. The release of the proteins identified was inhibited by the anti-inflammatory glucocorticoid, dexamethasone (DEX), which also inhibited tumor necrosis factor (TNF)-α release, and by thiol antioxidants (N-butanoyl GSH derivative, GSH-C4, and N-acetylcysteine (NAC), which did not affect TNF-α production. The proteins identified could be useful as biomarkers of oxidative stress associated with inflammation, and further studies will be required to investigate if the extracellular forms of these proteins has immunoregulatory functions.

Glioblastoma multiforme (GBM) is a highly lethal brain tumor. Due to resistance to current therapies, patient prognosis remains poor and development of novel and effective GBM therapy is crucial. Glioma stem cells (GSCs) have gained attention as a therapeutic target in GBM due to their relative resistance to current therapies and potent tumor-initiating ability. Previously, we identified that the mitotic kinase maternal embryonic leucine-zipper kinase (MELK) is highly expressed in GBM tissues, specifically in GSCs, and its expression is inversely correlated with the post-surgical survival period of GBM patients. In addition, patient-derived GSCs depend on MELK for their survival and growth both in vitro and in vivo. Here, we demonstrate evidence that the role of MELK in the GSC survival is specifically dependent on its kinase activity. With in silico structure-based analysis for protein-compound interaction, we identified the small molecule Compound 1 (C1) is predicted to bind to the kinase-active site of MELK protein. Elimination of MELK kinase activity was confirmed by in vitro kinase assay in nano-molar concentrations. When patient-derived GSCs were treated with C1, they underwent mitotic arrest and subsequent cellular apoptosis in vitro, a phenotype identical to that observed with shRNA-mediated MELK knockdown. In addition, C1 treatment strongly induced tumor cell apoptosis in slice cultures of GBM surgical specimens and attenuated growth of mouse intracranial tumors derived from GSCs in a dose-dependent manner. Lastly, C1 treatment sensitizes GSCs to radiation treatment. Collectively, these data indicate that targeting MELK kinase activity is a promising approach to attenuate GBM growth by eliminating GSCs in tumors.

One of the potential explanations for negative compatibility effects (NCE) in subliminal motor priming tasks has been perceptual prime-target interactions. Here, we investigate whether the characteristic tri-phasic LRP pattern associated with the NCE is caused by these prime-target interactions. We found that both the prime-related phase and the critical reversal phase remain present even on trials where the target is omitted, confirming they are elicited by the prime and mask, not by prime-target interactions. We also report that shape and size of the reversal phase are associated with response speed, consistent with a causal role for the reversal for the subsequent response latency. Additionally, we analysed sequential modulation of the NCE by previous conflicting events, even though such conflict is subliminal. In accordance with previous literature, this modulation is small but significant.