Search

The objective of this study was to investigate whether biomimetic sponges could enhance muscle recovery in female rats suffering from volumetric muscle loss (VML) injury. VML is a debilitating condition that results in irreversible deficits in muscle mass and function, frequently leading to permanent disability. Previous research demonstrated that biomimetic sponge scaffolds effectively promoted functional muscle regeneration in male rodent models. Here, we report that biomimetic sponge treatment significantly improved muscle mass, function, and innervation in female rats with VML injuries. This observation is supported by increased contractile tissue deposition in the defect area and greater cross-sectional area (CSA) of type 1 and type 2B myofibers in the sponge-treated muscles relative to untreated muscles. Collectively, our findings highlight the potential of biomimetic sponge therapy as a promising strategy for VML repair.

The purpose of our study was to assess the test-retest reliability and concurrent validity of the 30 sec Sit to Stand test in a sample of adolescents. We recruited 30 male (58%) and 22 female (42%) participants (mean age = 15.77 years ± 0.46). Participants completed the 30-sec Sit to Stand and standing long jump tests on two occasions separated by 1 week. The rank order repeatability of the Sit to Stand test for the entire group was good (ICC = 0.84, 95% CI's [0.71 to 0.91]), systematic error was low (1.7 repetitions ± 2.9), and the typical error between tests was 2.1 repetitions (95% CI's 1.73 to 2.55). Sit to Stand results were significantly associated with lower body power (r = 0.55, p < 0.001). Our study demonstrated that the 30-sec Sit to Stand test has moderate-to-high test--retest reliability and acceptable concurrent validity in a population of adolescents.

In this paper we propose multispectrum rotational states distribution thermometry as an optical method for primary thermometry. It relies on a global fitting of multiple absorption lines of the same band at different pressures. The approach allows leveraging both the temperature-dependent Doppler width and the temperature-dependent distribution of line intensities across the ro-vibrational band. We provide a proof-of-principle demonstration of the approach on the 3 ν _1 + ν _3 band of CO _2 , for which several accurate line-strength models of both theoretical and experimental origin are available for the global fitting. Our experimental conditions do not allow to test the methodology beyond a combined uncertainty of 530 ppm, but the comparative analysis between different line-strength models shows promise to reduce the error budget to few tens of ppm. As compared to Doppler-broadening thermometry, the approach is advantageous to mitigate systematic errors induced by a wrong modelling of absorption line-shapes and to reduce, for a given experimental dataset, the statistical uncertainty by a factor of 2. When applied in a reverse way, i.e. using a gas of known temperature, the approach becomes a stringent testbed for the accuracy of the adopted line-strength model.

The protection of grouper spawning aggregations is a global conservation issue: populations of many grouper species are threatened with collapse due to exploitation of this critical life history behaviour by fisheries. Effective protection of spawning aggregations requires information on spawning site fidelity, residence time and timing of arrivals at, and departures from, the site. To estimate these parameters at a spawning aggregation site at Farquhar Atoll, southern Seychelles, 12 brown-marbled groupers Epinephelus fuscoguttatus and 20 camouflage groupers E. polyphekadion were tagged with acoustic transmitters, and their presence and absence was monitored by an array of acoustic receivers positioned at the site over 2 spawning seasons (2010/2011 and 2011/2012). Spawning aggregations formed during 3 consecutive spawning months each season and overlapped spatially and temporally in the 2 species. Intra- and inter-season site fidelity was high, with 91.7% of tagged E. fuscoguttatus and 89.5% of tagged E. polyphekadion detected at the site 1 yr after tagging. The majority (2010/2011: 82.4%, 2011/2012: 80.0%) of fish detected in a spawning season visited the site during at least 2 spawning months. Residence time at the fish spawning aggregation site was influenced by sex (E. fuscoguttatus only) and spawning month (both species). Distinct periodicity in lunar timing of arrivals and departures was observed in both species. This study highlights the spatio-temporal scales involved during spawning aggregations of 2 long-lived, slow-growing coral reef fishes, which need to be considered for their effective management.

BackgroundThe efficacy of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) convalescent plasma (CCP) for preventing infection in exposed, uninfected individuals is unknown. CCP might prevent infection when administered before symptoms or laboratory evidence of infection.MethodsThis double-blinded, phase 2 randomized, controlled trial (RCT) compared the efficacy and safety of prophylactic high titer (≥1:320 by Euroimmun ELISA) CCP with standard plasma. Asymptomatic participants aged ≥18 years with close contact exposure to a person with confirmed coronavirus disease 2019 (COVID-19) in the previous 120 hours and negative SARS-CoV-2 test within 24 hours before transfusion were eligible. The primary outcome was new SARS-CoV-2 infection.ResultsIn total, 180 participants were enrolled; 87 were assigned to CCP and 93 to control plasma, and 170 transfused at 19 sites across the United States from June 2020 to March 2021. Two were excluded for screening SARS-CoV-2 reverse transcription polymerase chain reaction (RT-PCR) positivity. Of the remaining 168 participants, 12/81 (14.8%) CCP and 13/87 (14.9%) control recipients developed SARS-CoV-2 infection; 6 (7.4%) CCP and 7 (8%) control recipients developed COVID-19 (infection with symptoms). There were no COVID-19-related hospitalizations in CCP and 2 in control recipients. Efficacy by restricted mean infection free time (RMIFT) by 28 days for all SARS-CoV-2 infections (25.3 vs 25.2 days; P = .49) and COVID-19 (26.3 vs 25.9 days; P = .35) was similar for both groups.ConclusionsAdministration of high-titer CCP as post-exposure prophylaxis, although appearing safe, did not prevent SARS-CoV-2 infection.Clinical trials registrationNCT04323800.

This letter reports on the design and pilot installation of GridShares, devices intended to alleviate brownouts caused by peak power use on isolated, village-scale mini-grids. A team consisting of the authors and partner organizations designed, built and field-tested GridShares in the village of Rukubji, Bhutan. The GridShare takes an innovative approach to reducing brownouts by using a low cost device that communicates the state of the grid to its users and regulates usage before severe brownouts occur. This demand-side solution encourages users to distribute the use of large appliances more evenly throughout the day, allowing power-limited systems to provide reliable, long-term renewable electricity to these communities. In the summer of 2011, GridShares were installed in every household and business connected to the Rukubji micro-hydro mini-grid, which serves approximately 90 households with a 40 kW nominal capacity micro-hydro system. The installation was accompanied by an extensive education program. Following the installation of the GridShares, the occurrence and average length of severe brownouts, which had been caused primarily by the use of electric cooking appliances during meal preparation, decreased by over 92%. Additionally, the majority of residents surveyed stated that now they are more certain that their rice will cook well and that they would recommend installing GridShares in other villages facing similar problems.

ImportanceOne major advantage of developing large, federally funded networks for clinical research in neurology is the ability to have a trial-ready network that can efficiently conduct scientifically rigorous projects to improve the health of people with neurologic disorders.ObservationsNational Institute of Neurological Disorders and Stroke Network for Excellence in Neuroscience Clinical Trials (NeuroNEXT) was established in 2011 and renewed in 2018 with the goal of being an efficient network to test between 5 and 7 promising new agents in phase II clinical trials. A clinical coordinating center, data coordinating center, and 25 sites were competitively chosen. Common infrastructure was developed to accelerate timelines for clinical trials, including central institutional review board (a first for the National Institute of Neurological Disorders and Stroke), master clinical trial agreements, the use of common data elements, and experienced research sites and coordination centers. During the first 7 years, the network exceeded the goal of conducting 5 to 7 studies, with 9 funded. High interest was evident by receipt of 148 initial applications for potential studies in various neurologic disorders. Across the first 8 studies (the ninth study was funded at end of initial funding period), the central institutional review board approved the initial protocol in a mean (SD) of 59 (21) days, and additional sites were added a mean (SD) of 22 (18) days after submission. The median time from central institutional review board approval to first site activation was 47.5 days (mean, 102.1; range, 1-282) and from first site activation to first participant consent was 27 days (mean, 37.5; range, 0-96). The median time for database readiness was 3.5 months (mean, 4.0; range, 0-8) from funding receipt. In the 4 completed studies, enrollment met or exceeded expectations with 96% overall data accuracy across all sites. Nine peer-reviewed manuscripts were published, and 22 oral presentations or posters and 9 invited presentations were given at regional, national, and international meetings.Conclusions and relevanceNeuroNEXT initiated 8 studies, successfully enrolled participants at or ahead of schedule, collected high-quality data, published primary results in high-impact journals, and provided mentorship, expert statistical, and trial management support to several new investigators. Partnerships were successfully created between government, academia, industry, foundations, and patient advocacy groups. Clinical trial consortia can efficiently and successfully address a range of important neurologic research and therapeutic questions.

Abstract Our understanding of the importance of microbiomes on large aquatic animals—such as whales, sea turtles and manatees—has advanced considerably in recent years. The latest observations indicate that epibiotic diatom communities constitute diverse, polyphyletic, and compositionally stable assemblages that include both putatively obligate epizoic and generalist species. Here, we outline a successful approach to culture putatively obligate epizoic diatoms without their hosts. That some taxa can be cultured independently from their epizoic habitat raises several questions about the nature of the interaction between these animals and their epibionts. This insight allows us to propose further applications and research avenues in this growing area of study. Analyzing the DNA sequences of these cultured strains, we found that several unique diatom taxa have evolved independently to occupy epibiotic habitats. We created a library of reference sequence data for use in metabarcoding surveys of sea turtle and manatee microbiomes that will further facilitate the use of environmental DNA for studying host specificity in epizoic diatoms and the utility of diatoms as indicators of host ecology and health. We encourage the interdisciplinary community working with marine megafauna to consider including diatom sampling and diatom analysis into their routine practices.

Abstract Morels are highly prized edible fungi where sexual reproduction is essential for fruiting-body production. As a result, a comprehensive understanding of their sexual reproduction is of great interest. Central to this is the identification of the reproductive strategies used by morels. Sexual reproduction in fungi is controlled by mating-type (MAT) genes and morels are thought to be mainly heterothallic with two idiomorphs, MAT1-1 and MAT1-2. Genomic sequencing of black (Elata clade) and yellow (Esculenta clade) morel species has led to the development of PCR primers designed to amplify genes from the two idiomorphs for rapid genotyping of isolates from these two clades. To evaluate the design and theoretical performance of these primers we performed a thorough bioinformatic investigation, including the detection of the MAT region in publicly available Morchella genomes and in-silico PCR analyses. All examined genomes, including those used for primer design, appeared to be heterothallic. This indicates an inherent fault in the original primer design which utilized a single Morchella genome, as the use of two genomes with complementary mating types would be required to design accurate primers for both idiomorphs. Furthermore, potential off-targets were identified for some of the previously published primer sets, but verification was challenging due to lack of adequate genomic information and detailed methodologies for primer design. Examinations of the black morel specific primer pairs (MAT11L/R and MAT22L/R) indicated the MAT22 primers would correctly target and amplify the MAT1-2 idiomorph, but the MAT11 primers appear to be capable of amplifying incorrect off-targets within the genome. The yellow morel primer pairs (EMAT1-1 L/R and EMAT1-2 L/R) appear to have reporting errors, as the published primer sequences are dissimilar with reported amplicon sequences and the EMAT1-2 primers appear to amplify the RNA polymerase II subunit (RPB2) gene. The lack of the reference genome used in primer design and descriptive methodology made it challenging to fully assess the apparent issues with the primers for this clade. In conclusion, additional work is still required for the generation of reliable primers to investigate mating types in morels and to assess their performance on different clades and across multiple geographical regions.

Abstract Background In the past decades, climate change has been impacting human lives and health via extreme weather and climate events and alterations in labour capacity, food security, and the prevalence and geographical distribution of infectious diseases across the globe. Climate change and health indicators (CCHIs) are workable tools designed to capture the complex set of interdependent interactions through which climate change is affecting human health. Since 2015, a novel sub-set of CCHIs, focusing on climate change impacts, exposures, and vulnerability indicators (CCIEVIs) has been developed, refined, and integrated by Working Group 1 of the “Lancet Countdown: Tracking Progress on Health and Climate Change”, an international collaboration across disciplines that include climate, geography, epidemiology, occupation health, and economics. Discussion This research in practice article is a reflective narrative documenting how we have developed CCIEVIs as a discrete set of quantifiable indicators that are updated annually to provide the most recent picture of climate change’s impacts on human health. In our experience, the main challenge was to define globally relevant indicators that also have local relevance and as such can support decision making across multiple spatial scales. We found a hazard, exposure, and vulnerability framework to be effective in this regard. We here describe how we used such a framework to define CCIEVIs based on both data availability and the indicators’ relevance to climate change and human health. We also report on how CCIEVIs have been improved and added to, detailing the underlying data and methods, and in doing so provide the defining quality criteria for Lancet Countdown CCIEVIs. Conclusions Our experience shows that CCIEVIs can effectively contribute to a world-wide monitoring system that aims to track, communicate, and harness evidence on climate-induced health impacts towards effective intervention strategies. An ongoing challenge is how to improve CCIEVIs so that the description of the linkages between climate change and human health can become more and more comprehensive.

The field of Immuno-Oncology (IO) is evolving to utilise novel antibody backbones that can co-target multiple cell-surface stimulatory and inhibitory co-receptors (SICR). This approach necessitates a better understanding of SICR co-expression at the single-cell level on IO-relevant tumor-infiltrating leukocyte (TIL) cell types such as T and natural killer (NK) cells. Using high-dimensional flow cytometry we established a comprehensive SICR profile for tumor-resident T and NK cells across a range of human solid tumors where there is a clear need for improved immunotherapeutic intervention. Leveraging the power of our large flow panel, we performed deep-phenotyping of the critical CD8+CD39+ Cytotoxic T Lymphocyte (CTL) population that is enriched for tumor-reactive cytotoxic cells, revealing subsets that are differentiated by their SICR profile, including three that are uniquely defined by NKG2A expression. This study establishes a comprehensive SICR phenotype for human TIL T and NK cells, providing insights to guide the design and application of the next generation of IO molecules.

Cubic boron nitride (cBN) is a relatively less studied wide bandgap semiconductor despite its many promising mechanical, thermal, and electronic properties. We report on the electronic, structural, and optical characterization of commercial cBN crystal platelets. Temperature dependent transport measurements revealed the charge limited diode behavior of the cBN crystals. The equilibrium Fermi level was determined to be 0.47 eV below the conduction band, and the electron conduction was identified as n-type. Unirradiated dark and amber colored cBN crystals displayed broad photoluminescence emission peaks centered around different wavelengths. RC series zero phonon line defect emission peaks were observed at room temperature from the electron beam irradiated and oxygen ion implanted cBN crystals, making this material a promising candidate for high power microwave devices, next generation power electronics, and future quantum sensing applications.

The Norway lobster, Nephrops norvegicus, supports a key European fishery. Stock assessments for this species are mostly based on trawling and UnderWater TeleVision (UWTV) surveys. However, N. norvegicus are burrowing organisms and these survey methods are unable to sample or observe individuals in their burrows. To account for this, UWTV surveys generally assume that “1 burrow system = 1 animal”, due to the territorial behavior of N. norvegicus. Nevertheless, this assumption still requires in-situ validation. Here, we outline how to improve the accuracy of current stock assessments for N. norvegicus with novel ecological monitoring technologies, including: robotic fixed and mobile camera-platforms, telemetry, environmental DNA (eDNA), and Artificial Intelligence (AI). First, we outline the present status and threat for overexploitation in N. norvegicus stocks. Then, we discuss how the burrowing behavior of N. norvegicus biases current stock assessment methods. We propose that state-of-the-art stationary and mobile robotic platforms endowed with innovative sensors and complemented with AI tools could be used to count both animals and burrows systems in-situ, as well as to provide key insights into burrowing behavior. Next, we illustrate how multiparametric monitoring can be incorporated into assessments of physiology and burrowing behavior. Finally, we develop a flowchart for the appropriate treatment of multiparametric biological and environmental data required to improve current stock assessment methods.

The Plasmodium vivax reticulocyte invasion process is still poorly understood, with only a few receptor-ligand interactions identified to date. Individuals with the Southeast Asian ovalocytosis (SAO) phenotype have a deletion in the band 3 protein on the surface of erythrocytes, and are reported to have a lower incidence of clinical P. vivax malaria. Based on this observation, band 3 has been put forward as a receptor for P. vivax invasion, although direct proof is still lacking. In this study, we combined functional ex vivo invasion assays and transcriptome sequencing to uncover a band 3–mediated invasion pathway in P. vivax and potential band 3 ligands. Invasion by P. vivax field isolates was 67%-71% lower in SAO reticulocytes compared with non-SAO reticulocytes. Reticulocyte invasion was decreased by 40% and 27%-31% when blocking with an anti-band 3 polyclonal antibody and a PvTRAg38 peptide, respectively. To identify new band 3 receptor candidates, we mRNA-sequenced schizont-stage isolates used in the invasion assays, and observed high transcriptional variability in multigene and invasion-related families. Transcriptomes of isolates with low or high dependency on band 3 for invasion were compared by differential expression analysis, which produced a list of band 3 ligand candidates with high representation of PvTRAg genes. Our ex vivo invasion assays have demonstrated that band 3 is a P. vivax invasion receptor and confirm previous in vitro studies showing binding between PvTRAg38 and band 3, although the lower and variable inhibition levels observed suggest the involvement of other ligands. By coupling transcriptomes and invasion phenotypes from the same isolates, we identified a list of band 3 ligand candidates, of which the overrepresented PvTRAg genes are the most promising for future research.