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Abstract We investigated whether the strength of oscillations in common synaptic input was explanatory of knee extensor (KE) torque signal complexity during fresh and fatigued submaximal isometric contractions, in adults aged from 18 to 90 years. The discharge times of motor units were derived from the vastus lateralis muscle of 60 participants using high‐density surface EMG, during 20 s isometric KE contractions at 20% of maximal voluntary contraction, performed before and after a fatiguing repeated isometric KE contraction protocol at 60% of maximal voluntary contraction. Within‐muscle coherence Z‐scores were estimated using frequency‐domain coherence analysis, and muscle torque complexity was assessed using multiscale entropy analysis and detrended fluctuation analysis. Alpha band (5–15 Hz) coherence was found to predict 23.1% and 31.4% of the variance in the complexity index under 28‐scales (CI‐28) and detrended fluctuation analysis α complexity metrics, respectively, during the fresh contractions. Delta, alpha and low beta band coherence were significantly increased due to fatigue. Fatigue‐related changes in alpha coherence were significantly predictive of the fatigue‐related changes in CI‐28 and detrended fluctuation analysis α. The fatigue‐related increase in sample entropy from scales 11 to 28 of the multiscale entropy analysis curves was significantly predicted by the increase in the alpha band coherence. Age was not a contributory factor to the fatigue‐related changes in within‐muscle coherence and torque signal complexity. These findings indicate that the strength of alpha band oscillations in common synaptic input can explain, in part, isometric KE torque signal complexity and the fatigue‐related changes in torque signal complexity.

Abstract Paleogeography is the merger of sediment and volcanic facies, depositional settings, tectonic plate movements, topography, climate patterns and ecosystems through time. The construction of paleogeographic maps on tectonic plate reconstruction models requires a team effort to compile databases, data sharing standards and map projection methods. Two goals of the Paleogeography Working Group of the International Union of Geological Sciences (IUGS) program for Deep‐Time Digital Earth (DDE) are: (1) to interlink online national lexicons for all sedimentary and volcanic formations, and develop online ones for nations that currently lack these; (2) to target specific regions and intervals for testing/showcasing paleogeography output from the merger of these databases. Following those goals, we developed and applied new cloud‐based lexicon data services and interactive visualization techniques to regions in East Asia. This has been a successful collaboration among computer engineers and plate modellers and has involved stratigraphers in India (ONGC), China (Chengdu Univ. Tech., and Chinese Acad. Geol. Sci.), United States (Paleomap Project, and Purdue Univ.), Australia (GPlates visualization team) and Vietnam (Vietnam Nat. Univ.). Independent online lexicons with map‐based and stratigraphy‐based user interfaces have been developed (as of the date of this submission in March 2022) for all Proterozoic to Quaternary formations on the Indian Plate (over 800) and Vietnam (over 200), the majority of the Devonian through Neogene of China (ca. 2000) and partially for Thailand. A multi‐database search system returns all geologic formations of a desired geologic time from these four independent databases. With one click, users can plot the regional extent of one or of all of those regional formations on different plate reconstruction models of that desired age, and these polygons are filled with the lithologic facies pattern.

Abstract Background Psoriasis, a chronic, immune-mediated, inflammatory disease, affects 2‒3% of the population. Tyrosine kinase 2 (TYK2) mediates cytokine signaling involved in adaptive [interleukin (IL)-12, IL-23] and innate (type-I interferons) immune responses; IL-23–driven T-helper (Th)17 pathways play a key role in chronic inflammation in psoriasis. In a phase 2 trial, deucravacitinib, an oral, selective, allosteric TYK2 inhibitor, reduced IL-23/Th17 and type-I interferon pathway expression in the skin of patients with moderate to severe plaque psoriasis, reductions that were accompanied by clinical improvement of psoriatic lesions. Objectives The aim of this study was to identify biomarkers of psoriatic disease in serum from patients enrolled in the phase 2 trial and to assess the effects of deucravacitinib on those biomarkers. Methods Serum biomarkers from Olink proteomics and other quantitative assays were evaluated for a pharmacodynamic response to deucravacitinib treatment and correlation with psoriasis disease activity measures. Results Serum biomarkers associated with the IL-23/Th17 pathway [IL-17A, IL-17C, IL-19, IL-20, beta-defensin, and peptidase inhibitor 3 (PI3)] were upregulated in patients with psoriasis versus healthy controls. Deucravacitinib treatment reduced IL-17A (adjusted mean change from baseline at Day 85; 12 mg once daily versus placebo; −0.240 versus −0.067), IL-17C (−14.850 versus −1.664), IL-19 (−96.445 versus −8.119), IL-20 (−0.265 versus −0.064), beta-defensin (−65,025.443 versus −7553.961), and PI3 (−14.005 versus −1.360) expression. Reductions in serum biomarker expression occurred in a dose- and time-dependent manner, with significant reductions from baseline seen with deucravacitinib doses ≥ 3 mg twice daily (P ≤ 0.05). Biomarker expression correlated with disease activity measures such as Psoriasis Area and Severity Index (PASI) at baseline. Biomarker expression also correlated with PASI scores at Week 12. Conclusion IL-23/Th17 pathway expression in the serum of patients with psoriasis is an indicator of disease activity and response to deucravacitinib treatment. Trial registration number NCT02931838.

Abstract Diabetic retinopathy is one of the leading causes of blindness around the world. This makes early diagnosis and treatment important in preventing vision loss in a large number of patients. Microaneurysms are the key hallmark of the early stage of the disease, non-proliferative diabetic retinopathy, and can be detected using OCT angiography quickly and non-invasively. Screening tools for non-proliferative diabetic retinopathy using OCT angiography thus have the potential to lead to improved outcomes in patients. We compared different configurations of ensembled U-nets to automatically segment microaneurysms from OCT angiography fundus projections. For this purpose, we created a new database to train and evaluate the U-nets, created by two expert graders in two stages of grading. We present the first U-net neural networks using ensembling for the detection of microaneurysms from OCT angiography en face images from the superficial and deep capillary plexuses in patients with non-proliferative diabetic retinopathy trained on a database labeled by two experts with repeats.

Abstract In the phase 3 Coronavirus Efficacy (COVE) trial (NCT04470427), post-dose two Ancestral Spike-specific binding (bAb) and neutralizing (nAb) antibodies were shown to be correlates of risk (CoR) and of protection against Ancestral-lineage COVID-19 in SARS-CoV-2 naive participants. In the SARS-CoV-2 Omicron era, Omicron subvariants with varying degrees of immune escape now dominate, seropositivity rates are high, and booster doses are administered, raising questions on whether and how these developments affect the bAb and nAb correlates. To address these questions, we assess post-boost BA.1 Spike-specific bAbs and nAbs as CoRs and as correlates of booster efficacy in COVE. For naive individuals, bAbs and nAbs inversely correlate with Omicron COVID-19: hazard ratios (HR) per 10-fold marker increase (95% confidence interval) are 0.16 (0.03, 0.79) and 0.31 (0.10, 0.96), respectively. In non-naive individuals the analogous results are similar: 0.15 (0.04, 0.63) and 0.28 (0.07, 1.08). For naive individuals, three vs two-dose booster efficacy correlates with predicted nAb titer at exposure, with estimates -8% (-126%, 48%), 50% (25%, 67%), and 74% (49%, 87%), at 56, 251, and 891 Arbitrary Units/ml. These results support the continued use of antibody as a surrogate endpoint.

Abstract Kotagede, the capital of the ancient Mataram Kingdom and currently an area in the Yogyakarta Province of Indonesia, is known as a ‘real living museum’. It was previously a residential area with many vital premises and heritage buildings that became a tourist area. Its locally established activities enrich the visual and sound environment of the vicinity. However, it has gradually lost its distinguishing sounds. A series of studies aims to improve the possibility of restoring past soundmarks to preserve the intangible heritage and make living museums as rich as possible. This paper reports the initial stage of the series, which focuses on capturing the rich historical sounds of Kotagede. The study was carefully designed to collect comprehensive data on heritage sounds using qualitative methods consisting of an initial focus group discussion (FGD), in-depth interviews, and a final FGD. These methods resulted in a large amount of data that were processed and classified using the descriptive phenomenology approach with the Colaizzi protocol. The study found that Kotagede has various soundmarks grouped into local and outside sounds. The locally rooted sounds can be grouped into eight categories, some of which can be extended as past and present sounds and a few that have persisted from the past to the present. In the subsequent stage, this classification and local leaders' concerns helped the researchers select and prioritise sounds for preservation and tourism purposes. The study emphasises the importance of choosing suitable participants to provide detailed and comprehensive information.

Extracellular vesicles and nanoparticles (EVPs) are now recognized as a novel form of cell–cell communication. All cells release a wide array of heterogeneous EVPs with distinct protein, lipid, and RNA content, dependent on the pathophysiological state of the donor cell. The overall cargo content in EVPs is not equivalent to cellular levels, implying a regulated pathway for selection and export. In cancer, release and uptake of EVPs within the tumour microenvironment can influence growth, proliferation, invasiveness, and immune evasion. Secreted EVPs can also have distant, systemic effects that can promote metastasis. Here, we review current knowledge of EVP biogenesis and cargo selection with a focus on the role that extracellular RNA plays in oncogenesis and metastasis. Almost all subtypes of RNA have been identified in EVPs, with miRNAs being the best characterized. We review the roles of specific miRNAs that have been detected in EVPs and that play a role in oncogenesis and metastasis.

Abstract Apical membrane antigen-1 (AMA1) is a conserved malarial vaccine candidate essential for the formation of tight junctions with the rhoptry neck protein (RON) complex, enabling Plasmodium parasites to invade human erythrocytes, hepatocytes, and mosquito salivary glands. Despite its critical role, extensive surface polymorphisms in AMA1 have led to strain-specific protection, limiting the success of AMA1-based interventions beyond initial clinical trials. Here, we identify an i-body, a humanised single-domain antibody-like molecule that recognises a conserved pan-species conformational epitope in AMA1 with low nanomolar affinity and inhibits the binding of the RON2 ligand to AMA1. Structural characterisation indicates that the WD34 i-body epitope spans the centre of the conserved hydrophobic cleft in AMA1, where interacting residues are highly conserved among all Plasmodium species. Furthermore, we show that WD34 inhibits merozoite invasion of erythrocytes by multiple Plasmodium species and hepatocyte invasion by P. falciparum sporozoites. Despite a short half-life in mouse serum, we demonstrate that WD34 transiently suppressed P. berghei infections in female BALB/c mice. Our work describes the first pan-species AMA1 biologic with inhibitory activity against multiple life-cycle stages of Plasmodium. With improved pharmacokinetic characteristics, WD34 could be a potential immunotherapy against multiple species of Plasmodium.

Abstract The ongoing efforts to optimize rechargeable Li-ion batteries led to the interest in intercalation of nanoscale layered compounds, including bilayer graphene. Its lithium intercalation has been demonstrated recently but the mechanisms underpinning the storage capacity remain poorly understood. Here, using magnetotransport measurements, we report in-operando intercalation dynamics of bilayer graphene. Unexpectedly, we find four distinct intercalation stages that correspond to well-defined Li-ion densities. Transitions between the stages occur rapidly (within 1 sec) over the entire device area. We refer to these stages as ‘in-plane’, with no in-plane analogues in bulk graphite. The fully intercalated bilayers represent a stoichiometric compound C14LiC14 with a Li density of ∼2.7·1014 cm−2, notably lower than fully intercalated graphite. Combining the experimental findings and DFT calculations, we show that the critical step in bilayer intercalation is a transition from AB to AA stacking which occurs at a density of ∼0.9·1014 cm−2. Our findings reveal the mechanism and limits for electrochemical intercalation of bilayer graphene and suggest possible avenues for increasing the Li storage capacity.

Abstract Telecommunications offers an alternative or supplement to community-based interventions as a means of extending healthcare services and improving health outcomes in remote settings but can fail to reach target communities and achieve the desired impact if barriers to access are not overcome. We conducted seven focus group discussions and 26 interviews with community health workers, community leaders, and female members of the public who declared that they had or had not previously accessed free audio health messages provided via a mobile platform in two rural communities of Mali, Koulikoro and Bougouni. A content analysis showed that participants accessed and trusted health information from a range of sources, including radio, telephone and television, as well as town criers, local relays and community health centres. Barriers to access faced by women included economic factors, lack of network or electricity, and social factors such as illiteracy, cultural restrictions and being unaware of mobile communication. Through analysis and interpretation of the participants’ responses, we have made recommendations for future campaigns for the dissemination of health-related information for women in remote settings.

Abstract Background Despite recent advances in lung cancer therapeutics and improving overall survival, disparities persist among socially disadvantaged populations. This study aims to determine the effects of neighborhood deprivation indices (NDI) on lung cancer mortality. This is a multicenter retrospective cohort study assessing the relationship between NDI and overall survival adjusted for age, disease stage, and DNA methylation among biopsy-proven lung cancer patients. State-specific NDI for each year of sample collection were computed at the U.S. census tract level and dichotomized into low- and high-deprivation. Results A total of 173 non small lung cancer patients were included, with n = 85 (49%) and n = 88 (51%) in the low and high-deprivation groups, respectively. NDI was significantly higher among Black patients when compared with White patients (p = 0.003). There was a significant correlation between DNA methylation and stage for HOXA7, SOX17, ZFP42, HOXA9, CDO1 and TAC1. Only HOXA7 DNA methylation was positively correlated with NDI. The high-deprivation group had a statistically significant shorter survival than the low-deprivation group (p = 0.02). After adjusting for age, race, stage, and DNA methylation status, belonging to the high-deprivation group was associated with higher mortality with a hazard ratio of 1.81 (95%CI: 1.03–3.19). Conclusions Increased neighborhood-level deprivation may be associated with liquid biopsy DNA methylation, shorter survival, and increased mortality. Changes in health care policies that consider neighborhood-level indices of socioeconomic deprivation may enable a more equitable increase in lung cancer survival.

Abstract Semiconducting transition metal dichalcogenides (MX2) occur in 2H and rhombohedral (3R) polytypes, respectively distinguished by anti-parallel and parallel orientation of consecutive monolayer lattices. In its bulk form, 3R-MX2 is ferroelectric, hosting an out-of-plane electric polarisation, the direction of which is dictated by stacking. Here, we predict that twin boundaries, separating adjacent polarisation domains with reversed built-in electric fields, are able to host two-dimensional electrons and holes with an areal density reaching ~ 1013cm−2. Our modelling suggests that n-doped twin boundaries have a more promising binding energy than p-doped ones, whereas hole accumulation is stable at external surfaces of a twinned film. We also propose that assembling pairs of mono-twin films with a ‘magic’ twist angle θ * that provides commensurability between the moiré pattern at the interface and the accumulated carrier density, should promote a regime of strongly correlated states of electrons, such as Wigner crystals, and we specify the values of θ * for homo- and heterostructures of various TMDs.

Abstract Research on climate anxiety is rapidly growing, with ongoing exploration of population prevalence, contributing factors, and mitigation strategies that transform anxiety into helpful action. What remains unclear is whether and how to delineate climate anxiety from mental ill health. A limited conceptualization of climate anxiety restricts efforts to identify and support those adversely affected. This paper draws on psychological and existential theories to propose a theoretical model of climate anxiety and coping, extending previous conceptualizations. The model theorizes that climate change evokes an existential conflict that manifests affectively as climate anxiety (and other emotional experiences), wherein cognitive and behavioral coping processes are activated. These processes fall on a continuum of adaptivity, depending on functional impact. Responses might range from meaningful engagement with activities that address climate change to maladaptive strategies that negatively impact personal, social, and occupational functioning. Applications of this model in research and practice are proposed.

Abstract Differentially methylated CpG sites (dmCpGs) that distinguish prostate tumour from adjacent benign tissue could aid in the diagnosis and prognosis of prostate cancer. Previously, the identification of such dmCpGs has only been undertaken in radical prostatectomy (RP) samples and not primary diagnostic tumour samples (needle biopsy or transurethral resection of the prostate). We interrogated an Australian dataset comprising 125 tumour and 43 adjacent histologically benign diagnostic tissue samples, including 41 paired samples, using the Infinium Human Methylation450 BeadChip. Regression analyses of paired tumour and adjacent benign samples identified 2,386 significant dmCpGs (Bonferroni p

Abstract The diversity in genome resources is fundamental to designing genomic strategies for local breed improvement and utilisation. These resources also support gene discovery and enhance our understanding of the mechanisms of resilience with applications beyond local breeds. Here, we report the genome sequences of 555 cattle (208 of which comprise new data) and high-density (HD) array genotyping of 1,082 samples (537 new samples) from indigenous African cattle populations. The new sequences have an average genome coverage of ~30X, three times higher than the average (~10X) of the over 300 sequences already in the public domain. Following variant quality checks, we identified approximately 32.3 million sequence variants and 661,943 HD autosomal variants mapped to the Bos taurus reference genome (ARS-UCD1.2). The new datasets were generated as part of the Centre for Tropical Livestock Genetics and Health (CTLGH) Genomic Reference Resource for African Cattle (GRRFAC) initiative, which aspires to facilitate the generation of this livestock resource and hopes for its utilisation for complete indigenous breed characterisation and sustainable global livestock improvement.

Abstract Antiferromagnets have attracted significant attention in the field of magnonics, as promising candidates for ultralow-energy carriers for information transfer for future computing. The role of crystalline orientation distribution on magnon transport has received very little attention. In multiferroics such as BiFeO3 the coupling between antiferromagnetic and polar order imposes yet another boundary condition on spin transport. Thus, understanding the fundamentals of spin transport in such systems requires a single domain, a single crystal. We show that through Lanthanum (La) substitution, a single ferroelectric domain can be engineered with a stable, single-variant spin cycloid, controllable by an electric field. The spin transport in such a single domain displays a strong anisotropy, arising from the underlying spin cycloid lattice. Our work shows a pathway to understanding the fundamental origins of magnon transport in such a single domain multiferroic.

Abstract Background Exposure to climate change events like wildfires can lead to health and mental health problems. While conceptual frameworks have been hypothesized describing the potential relationship between disaster exposure and substance use, the association remains under-researched and unquantified. Methods We constructed a quantitative portrayal of one proposed conceptual framework that focuses on the intermediary role of anxiety. We used the Monte Carlo simulation to estimate the impact of wildfire exposure on opioid misuse outcomes through increased anxiety. We searched for and extracted prior empirical evidence on the associations between wildfire anxiety and anxiety-opioid misuse. Three scenarios were devised: in S1 the impact of wildfire on opioid misuse was limited to increasing anxiety incidence; in S2 we also considered the additive role of altered anxiety phenotype; and in S3 we further considered the role of increased opioid-related consequences of pre-existing anxiety due to wildfire exposure. Results Models show that the prevalence of opioid misuse post-wildfire may rise to 6.0%-7.2% from a baseline of 5.3%. In S1, the opioid misuse prevalence ratio was 1.12 (95% uncertainty interval [UI]: 1.00 – 1.27). The two exploratory scenarios, with less stringent assumptions, yielded prevalence ratios of 1.23 (95% UI: 1.00 – 1.51) and 1.34 (95% UI: 1.11 – 1.63). Conclusions Our modeling study suggests that exposure to wildfires may elevate opioid misuse through increasing anxiety incidence and severity. This can lead to substantial health burdens, possibly beyond the duration of the wildfire event, which may offset recent gains in opioid misuse prevention.

Recycled Concrete Aggregate (RCA) of the chemical and biological effects must be understood to avoid potential adverse impacts to the bay’s aquatic ecosystem. RCA application as a base material for oyster reefs did not adversely affect oyster spat growth and survival, or the surrounding environment. Evaluated RCA leaching for petroleum byproducts showed that RCA as a base material for oyster reefs did not leach any hydrocarbon chemicals, and no water extractable SVOC were detected. The research found potential RCA application to the Chesapeake Bay watershed as a bottom conditioning material for oyster aquaculture. Overall, the findings support the use of RCA for oyster aquaculture.

Abstract The African buffalo (Syncerus caffer) is a wild bovid with a historical distribution across much of sub-Saharan Africa. Genomic analysis can provide insights into the evolutionary history of the species, and the key selective pressures shaping populations, including assessment of population level differentiation, population fragmentation, and population genetic structure. In this study we generated the highest quality de novo genome assembly (2.65 Gb, scaffold N50 69.17 Mb) of African buffalo to date, and sequenced a further 195 genomes from across the species distribution. Principal component and admixture analyses provided little support for the currently described four subspecies. Estimating Effective Migration Surfaces analysis suggested that geographical barriers have played a significant role in shaping gene flow and the population structure. Estimated effective population sizes indicated a substantial drop occurring in all populations 5-10,000 years ago, coinciding with the increase in human populations. Finally, signatures of selection were enriched for key genes associated with the immune response, suggesting infectious disease exert a substantial selective pressure upon the African buffalo. These findings have important implications for understanding bovid evolution, buffalo conservation and population management.

Abstract Continued spread of chronic wasting disease (CWD) through wild cervid herds negatively impacts populations, erodes wildlife conservation, drains resource dollars, and challenges wildlife management agencies. Risk factors for CWD have been investigated at state scales, but a regional model to predict locations of new infections can guide increasingly efficient surveillance efforts. We predicted CWD incidence by county using CWD surveillance data depicting white-tailed deer (Odocoileus virginianus) in 16 eastern and midwestern US states. We predicted the binary outcome of CWD-status using four machine learning models, utilized five-fold cross-validation and grid search to pinpoint the best model, then compared model predictions against the subsequent year of surveillance data. Cross validation revealed that the Light Boosting Gradient model was the most reliable predictor given the regional data. The predictive model could be helpful for surveillance planning. Predictions of false positives emphasize areas that warrant targeted CWD surveillance because of similar conditions with counties known to harbor CWD. However, disagreements in positives and negatives between the CWD Prediction Web App predictions and the on-the-ground surveillance data one year later underscore the need for state wildlife agency professionals to use a layered modeling approach to ensure robust surveillance planning. The CWD Prediction Web App is at https://cwd-predict.streamlit.app/ .

Abstract A recent clinical trial demonstrated that Bacille Calmette-Guérin (BCG) revaccination of adolescents reduced the risk of sustained infection with Mycobacterium tuberculosis (M.tb). In a companion phase 1b trial, HVTN 602/Aeras A-042, we characterize in-depth the cellular responses to BCG revaccination or to a H4:IC31 vaccine boost to identify T cell subsets that could be responsible for the protection observed. High-dimensional clustering analysis of cells profiled using a 26-color flow cytometric panel show marked increases in five effector memory CD4+ T cell subpopulations (TEM) after BCG revaccination, two of which are highly polyfunctional. CITE-Seq single-cell analysis shows that the activated subsets include an abundant cluster of Th1 cells with migratory potential. Additionally, a small cluster of Th17 TEM cells induced by BCG revaccination expresses high levels of CD103; these may represent recirculating tissue-resident memory cells that could provide pulmonary immune protection. Together, these results identify unique populations of CD4+ T cells with potential to be immune correlates of protection conferred by BCG revaccination.

Summary: Although cancer cachexia is classically characterized as a systemic inflammatory disorder, emerging evidence indicates that weight loss also associates with local tissue inflammation. We queried the regulation of this inflammation and its causality to cachexia by exploring skeletal muscle, whose atrophy strongly associates with poor outcomes. Using multiple mouse models and patient samples, we show that cachectic muscle is marked by enhanced innate immunity. Nuclear factor κB (NF-κB) activity in multiple cells, including satellite cells, myofibers, and fibro-adipogenic progenitors, promotes macrophage expansion equally derived from infiltrating monocytes and resident cells. Moreover, NF-κB-activated cells and macrophages undergo crosstalk; NF-κB+ cells recruit macrophages to inhibit regeneration and promote atrophy but, interestingly, also protect myofibers, while macrophages stimulate NF-κB+ cells to sustain an inflammatory feedforward loop. Together, we propose that NF-κB functions in multiple cells in the muscle microenvironment to stimulate macrophages that both promote and protect against muscle wasting in cancer.