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Abstract Lignin, a major plant cell wall component, has an important role in plant-defense mechanisms against pathogens and is a promising renewable carbon source to produce bio-based chemicals. However, our understanding of microbial metabolism is incomplete regarding certain lignin-related compounds like p-coumaryl and sinapyl alcohols. Here, we reveal peripheral pathways for the catabolism of the three main lignin precursors (p-coumaryl, coniferyl, and sinapyl alcohols) in the plant pathogen Xanthomonas citri. Our study demonstrates all the necessary enzymatic steps for funneling these monolignols into the tricarboxylic acid cycle, concurrently uncovering aryl aldehyde reductases that likely protect the pathogen from aldehydes toxicity. It also shows that lignin-related aromatic compounds activate transcriptional responses related to chemotaxis and flagellar-dependent motility, which might play an important role during plant infection. Together our findings provide foundational knowledge to support biotechnological advances for both plant diseases treatments and conversion of lignin-derived compounds into bio-based chemicals.

Abstract Autoimmune diseases such as systemic lupus erythematosus (SLE) display a strong female bias. Although sex hormones have been associated with protecting males from autoimmunity, the molecular mechanisms are incompletely understood. Here we report that androgen receptor (AR) expressed in T cells regulates genes involved in T cell activation directly, or indirectly via controlling other transcription factors. T cell-specific deletion of AR in mice leads to T cell activation and enhanced autoimmunity in male mice. Mechanistically, Ptpn22, a phosphatase and negative regulator of T cell receptor signaling, is downregulated in AR-deficient T cells. Moreover, a conserved androgen-response element is found in the regulatory region of Ptpn22 gene, and the mutation of this transcription element in non-obese diabetic mice increases the incidence of spontaneous and inducible diabetes in male mice. Lastly, Ptpn22 deficiency increases the disease severity of male mice in a mouse model of SLE. Our results thus implicate AR-regulated genes such as PTPN22 as potential therapeutic targets for autoimmune diseases.

Wheat is one of the most important staple crops consumed by more than four billion people in the world. However, its production is challenged by the impact of climate change which accounts for a 5.5 % reduction in wheat yield and it is predicted to dwindle further by about 30 % in 2050, due to trends in temperature, precipitation, and carbon dioxide. An effective annual crop estimate is necessary not only to inform governments the status of national food security, but also to determine the benchmark on which agricultural commodities are priced in the market. Thus, annual crop monitoring and yield estimate is paramount to determine the amount of wheat imports required to make up for the shortfalls in the national wheat production in South Africa, which has been a net importer of wheat since 1998. This study aimed at investigating the most distinguishable crop phenology for accurate winter wheat classification during the growing season from August – December 2020 using Sentinel-2 imageries and Random Forest algorithm. The winter wheat crop was more accurately identified during the crop ‘heading’ stage in October yielding the highest user’s (75.56 %) and producer’s (92.52 %) accuracies, despite the relatively lower overall accuracy (78.14 %) compared to that of December with overall accuracy of 83.58 % obtained during the maturity stage. This study, therefore, found that the extraction of NDVI values of the winter wheat crop over the period of the growing season using the Sentinel-2 NDVI series method and grouping these values into distinct classes using the K-means unsupervised clustering techniques assist to identify the different crop phenologies based on which the winter wheat crop could be detected and mapped accurately. The phenology-based classification of the winter wheat crop during the heading stage, reduce the ambiguity of spectral confusion created with surrounding grass and maize crops.

Abstract We present the first machine learning-based autonomous hyperspectral neutron computed tomography experiment performed at the Spallation Neutron Source. Hyperspectral neutron computed tomography allows the characterization of samples by enabling the reconstruction of crystallographic information and elemental/isotopic composition of objects relevant to materials science. High quality reconstructions using traditional algorithms such as the filtered back projection require a high signal-to-noise ratio across a wide wavelength range combined with a large number of projections. This results in scan times of several days to acquire hundreds of hyperspectral projections, during which end users have minimal feedback. To address these challenges, a golden ratio scanning protocol combined with model-based image reconstruction algorithms have been proposed. This novel approach enables high quality real-time reconstructions from streaming experimental data, thus providing feedback to users, while requiring fewer yet a fixed number of projections compared to the filtered back projection method. In this paper, we propose a novel machine learning criterion that can terminate a streaming neutron tomography scan once sufficient information is obtained based on the current set of measurements. Our decision criterion uses a quality score which combines a reference-free image quality metric computed using a pre-trained deep neural network with a metric that measures differences between consecutive reconstructions. The results show that our method can reduce the measurement time by approximately a factor of five compared to a baseline method based on filtered back projection for the samples we studied while automatically terminating the scans.

The macroscopic hysteresis of ferromagnetic materials is influenced by their microscopic magnetic domains, establishing a correspondence between the two that enables a fundamental understanding of the magnetization process of ferromagnetic materials. Based on this, this study employs the phase field method to investigate the macroscopic hysteresis and microscopic magnetic domain evolution of soft, hard, and rectangular ferromagnetic materials. The hysteresis loops of the three materials present narrow, wide and rectangular characteristics respectively, which are quantitatively consistent with the experimental data. Subsequently, the influence of the magnetic field on the macroscopic hysteresis is analyzed. The results show that the hysteresis loop area increases when the magnetic field amplitude increases. Furthermore, the proportion of each type of energy under different magnetic fields is discussed, the dominant energy terms are generally consistent for the same category of ferromagnetic materials. Additionally, the corresponding magnetic domain evolution under different magnetic field is displayed, with soft magnetic materials exhibiting no vortex structures, hard ferromagnetic materials presenting a 45° vortex structure, and rectangular magnetic material showcasing a 90° vortex structure. Finally, the asymmetric characteristics of the major hysteresis loop and minor hysteresis loops are discussed. The change of the magnetic field path leads to the corresponding change of the major and minor hysteresis loops. At the same magnetic field, distinctions in magnetic domain configurations between the major and minor hysteresis loops are evident.

Optimizing the prediction of maize (Zea mays L.) yields in smallholder farming systems enhances crop management and thus contributes to reducing hunger and achieving one of the Sustainable Development Goals (SDG 2—zero hunger). This research investigated the capability of unmanned aerial vehicle (UAV)-derived data and machine learning algorithms to estimate maize yield and evaluate its spatiotemporal variability through the phenological cycle of the crop in Bronkhorstspruit, South Africa, where UAV data collection took over four dates (pre-flowering, flowering, grain filling, and maturity). The five spectral bands (red, green, blue, near-infrared, and red-edge) of the UAV data, vegetation indices, and grey-level co-occurrence matrix textural features were computed from the bands. Feature selection relied on the correlation between these features and the measured maize yield to estimate maize yield at each growth period. Crop yield prediction was then conducted using our machine learning (ML) regression models, including Random Forest, Gradient Boosting (GradBoost), Categorical Boosting, and Extreme Gradient Boosting. The GradBoost regression showed the best overall model accuracy with R2 ranging from 0.05 to 0.67 and root mean square error from 1.93 to 2.9 t/ha. The yield variability across the growing season indicated that overall higher yield values were predicted in the grain-filling and mature growth stages for both maize fields. An analysis of variance using Welch’s test indicated statistically significant differences in maize yields from the pre-flowering to mature growing stages of the crop (p-value < 0.01). These findings show the utility of UAV data and advanced modelling in detecting yield variations across space and time within smallholder farming environments. Assessing the spatiotemporal variability of maize yields in such environments accurately and timely improves decision-making, essential for ensuring sustainable crop production.

Aim: The clinical symptoms of autoantibody (AAb)-mediated autoimmune diseases (AID) usually correlate with the AAb-titer. Immunoglobulins (Igs) of the IgG type are actively recycled by the neonatal crystallizable fragment receptor (FcRn). The most common Ig type of AAb is IgG. This explorative study evaluates the safety and tolerability of a fully human anti-FcRn monoclonal antibody (mAb) in patients with thyroid autoimmunity (TA). Methods: Adverse events (AEs) and serious AEs (SAEs) were documented and coded according to the standardized Medical Dictionary for Regulatory Activities (MedDRA). AEs were followed up, and seriousness, as defined by the International Conference on Harmonization of Technical Requirements for Registration of Pharmaceuticals for Human Use (ICH)-guideline E6, was documented. All AEs were analyzed for a possible underlying cause, and if not identified, were graded as side effects (SEs). Additionally, safety-relevant serological parameters (liver function and blood cell counts) were evaluated. Furthermore, laboratory parameters influenced by other anti-FcRn agents in clinical studies were considered. Results: Of 31 patients with TA, 19 were administered the anti-FcRn mAb subcutaneously once weekly for 12 weeks, while 12 were on placebo. Compared to placebo, there was no increased occurrence of AE and/or SE in the mAb group. mAb treatment increased total, low-density lipoprotein (LDL), and high-density lipoprotein (HDL) cholesterol. A mAb treatment-induced transient decrease in serum albumin strongly correlated with an increase in total cholesterol (r = –0.893, P = 0.012). Overall compared to placebo, there were no significant changes in blood cell counts, complement factors, or liver enzymes. Serological changes were transient and spontaneously normalized after treatment completion. Two SAEs were deemed no-drug induced (dysthyroid optic neuropathy and a post-COVID infection associated autoimmune encephalomyelitis). Conclusions: The anti-FcRn mAb is a safe and well-tolerated therapy for AAb-mediated AID.

Abstract Background One of the effects of the COVID-19 pandemic is the increased level of food insecurity, especially during the first wave. Food insecurity is an indication of poverty and results in serious health and social effects. Even though several studies have been conducted to assess the impact of COVID-19, there is a paucity of information on the role of individual community members and local organizations in addressing food insecurity in the province of Ontario, Canada. Consequently, the objective of this study is to examine the role of individuals and community organizations in addressing food insecurity challenges among the Black population in Scarborough in the Greater Toronto Area. Methods This qualitative study recruited 20 Black participants from the TAIBU Community Health Center (CHC) located in Scarborough. Furthermore, the study recruited eight nurses and two Black doctors in the Greater Toronto Area (GTA) but only one affiliated with TAIBU. In-depth interviews were used to gather information for analysis. The study used manual coding and NVivo software to analyze the qualitative data. Results The study found that there was a reported incidence of food insecurity among the population but new local food aid organizations sprang up to assist the existing ones in tackling food insecurity. However, the study found that the operations of food aid organizations are not sustainable. Conclusions Despite the reported cases of food insecurity, local community organizations and individual community members volunteered to support people to boost their resiliency to food insecurity. The findings of the study highlight the role of community organizations in addressing food insecurity during crises including pandemics. Based on the health effects of food insecurity, the study recommends that both federal and provincial governments prioritize food insecurity as a major public health issue.

Background: Postoperative ileus (POI) is a common complication after colorectal surgery, leading to increased hospital stay and costs. This study aimed to explore patient comorbidities that contribute to the development of POI in the colorectal surgical population and compare machine learning (ML) model accuracy to existing risk instruments. Study Design: In a retrospective study, data were collected on 316 adult patients who underwent colorectal surgery from January 2020 to December 2021. The study excluded patients undergoing multi-visceral resections, re-operations, or combined primary and metastatic resections. Patients lacking follow-up within 90 days after surgery were also excluded. Eight different ML models were trained and cross-validated using 29 patient comorbidities and four comorbidity risk indices (ASA Status, NSQIP, CCI, and ECI). Results: The study found that 6.33% of patients experienced POI. Age, BMI, gender, kidney disease, anemia, arrhythmia, rheumatoid arthritis, and NSQIP score were identified as significant predictors of POI. The ML models with the greatest accuracy were AdaBoost tuned with grid search (94.2%) and XG Boost tuned with grid search (85.2%). Conclusions: This study suggests that ML models can predict the risk of POI with high accuracy and may offer a new frontier in early detection and intervention for postoperative outcome optimization. ML models can greatly improve the prediction and prevention of POI in colorectal surgery patients, which can lead to improved patient outcomes and reduced healthcare costs. Further research is required to validate and assess the replicability of these results.

Abstract Background Aging and sex are major risk factors for developing late-onset Alzheimer’s disease. Compared to men, women experience worse neuropathological burden and cognitive decline despite living longer with the disease. Similarly, male 3xTg-AD mice, developed to model Alzheimer’s disease, no longer consistently exhibit standard Alzheimer’s neuropathology yet experience higher rates of mortality - providing a unique opportunity to further elucidate this dichotomy. We hypothesized that sex differences in the biological aging process yield distinct pathological and molecular Alzheimer’s disease signatures in males and females, which could be harnessed for therapeutic and biomarker development. Methods We aged male and female, 3xTg-AD and B6129 control mice across their respective lifespans (n = 3–8 mice per sex, strain, and age group) and longitudinally assessed neuropathological hallmarks of Alzheimer’s disease, markers of hepatic inflammation, splenic mass and morphology, as well as plasma cytokine levels. We conducted RNA sequencing analysis on bulk brain tissue and examined differentially expressed genes (DEGs) between 3xTg-AD and B6129 samples and across ages in each sex. We also examined DEGs between clinical Alzheimer’s and control parahippocampal gyrus brain tissue samples from the Mount Sinai Brain Bank study in each sex. Results 3xTg-AD females significantly outlived 3xTg-AD males and exhibited progressive Alzheimer’s neuropathology, while 3xTg-AD males demonstrated progressive hepatic inflammation, splenomegaly, circulating inflammatory proteins, and minimal Alzheimer’s neuropathological hallmarks. Instead, 3xTg-AD males experienced an accelerated upregulation of immune-related gene expression in the brain relative to females. Our clinical investigations revealed that individuals with Alzheimer’s disease develop similar sex-specific alterations in neuronal and immune function. In diseased males of both species, we observed greater upregulation of complement-related gene expression, and lipopolysaccharide was predicted as the top upstream regulator of DEGs. Conclusions Our data demonstrate that chronic inflammation and complement activation are associated with increased mortality, indicating that age-related changes in immune response contribute to sex differences in Alzheimer’s disease trajectories. We provide evidence that aging and transgene-driven disease progression trigger a widespread inflammatory response in 3xTg-AD males, which mimics the impact of lipopolysaccharide stimulation despite the absence of infection.

BackgroundThyroid-blocking immunoglobulins (TBI) are present in 10%–15% of patients with autoimmune thyroid disease (AITD). TBI affect thyroid function. The analytical performance of a novel TBI bioassay was evaluated.MethodsSera from AITD patients were tested with a cell-based TBI reporter bioassay (Thyretain®) with the expression of a luciferase transgene as readout and a new “Turbo™” TBI bioassay with a readout based on a cyclic AMP-activated luciferase. All samples were also run on two TSH-R binding immunoassays. A Passing–Bablok regression, a Bland–Altman plot, and user/lot comparisons were performed. In addition, dose–response curves for Turbo and Thyretain were fitted using serial dilutions, and half-maximal and 80% inhibitory concentrations (IC50/IC80) were compared.ResultsOf 1,011 unselected AITD patients, 131 patients (212 samples) were TBI positive. Of the 212 samples, 149 (70.3%), 47 (22%), and 16 (7.5%) were hypothyroid, euthyroid, and hyperthyroid, respectively. The three thyrotropin receptor antibody (TSH-R-Ab) assays were negative in 90 controls devoid of autoimmune thyroid disorders. In contrast, the Turbo cyclic adenosine 3′,5′-monophosphate (cAMP) TBI, Thyretain TBI, and the binding assays detected TBI in 212 (100%), 168 (79%), and 138/180 (65%) samples, respectively (p< 0.001). Turbo highly correlated with thyroid function (p< 0.001). The percentage inhibition in both Turbo and Thyretain correlated with TSH-R-Ab binding assay positivity (both p< 0.001). The two bioassays correlated (r = 0.8, p< 0.001), and the Bland–Altman plot displayed no significant bias (0.24). Values scatter with slight systemic deviation between TBI mean values of 10%–50% inhibition, with higher Turbo than Thyretain results. Intra-assay validation demonstrated adequate precision with a very low coefficient of variation (average CV 5.4%) and lower CV with samples with a high inhibitory effect (CVAverage= 1.7% for a sample with 95% inhibition Thyretain). CV did not differ between users (p = 0.35) and lots (p = 0.121). The IC50/IC80 values were 1.55 ng/mL/3.48 ng/mL for Turbo and 6.76 ng/mL/18.46 ng/mL for Thyretain, respectively, demonstrating the markedly higher sensitivity of Turbo.ConclusionsThe novel, easy-to-perform, rapid, and reliable Turbo TSH-R blocking bioassay detected significantly more TBI than the established immunoassays, emphasizing its higher analytical performance and clinical utility in the management of patients with AITD.

Craniofacial bone defects result from various disorders such as trauma, congenital malformations and infections. Cleft lip and palate are the most prevalent congenital craniofacial birth defect in humans. Growth factors (GFs) are soluble proteins secreted by cells that regulate various cellular processes and tissue regeneration. At present, developing three-dimensional scaffolds for delivering GFs to the site of injury has become an important aspect in craniofacial bone regeneration. This study aims to develop a novel 3D bone substitute using lyophilized-platelet-rich fibrin (LyPRF) biocomposite scaffolds for potential application for CLP repair. Collagen (C), bioglass (BG), and LyPRF were used to fabricate a biocomposite (C-BG-LyPRF) scaffold. The physical, chemical, and biocompatibility properties of the scaffold were evaluated. The C-BG-LyPRF scaffold demonstrated a mean pore diameter of 146 µm within a porosity of 87.26%. The FTIR spectra verified the presence of am-ide I, II, and III functional groups. The inorganic phase of the C-BG-LyPRF scaffold was composed of sodium, calcium, silicon, and phosphorus, as determined by EDX analysis. Furthermore, C-BG-LyPRF scaffold was biocompatible with MC3T3-E1 cells in both the Live/Dead and prolif-eration assays. Data demonstrate the developed C-BG-LyPRF scaffold exhibits biomimetic and biocompatibility properties, establishing it as a promising biomaterial for craniofacial regeneration.

Background: Professional nurses typically promote and advocate self-care practices to their patients to achieve better health outcomes, but rarely engage in these practices themselves. Methods: A qualitative, descriptive phenomenological approach was used in this study. Ten professional nurses employed in different primary health care facilities were purposively sampled. Semi-structured interviews were conducted to collect data, which were analysed using Colaizzi’s data analysis strategy, and data saturation was reached. Results: Two themes were identified. Theme 1: the participants expressed that internal and external factors compromised self-care practices, such as subconscious self-neglect, insufficient resources, and a depressed economy, which encouraged them to work extended hours. Theme 2: participants’ holistic well-being was compromised, as they neglected their mental well-being. Conclusion: Self-care practices among professional nurses seem unachievable. The extent of this population’s self-care neglect was evident during the coronavirus disease 2019 (COVID-19) pandemic when professional nurses globally gave of themselves relentlessly. Contribution: This is the first study conducted on the topic in the City of Ekurhuleni, and the findings will provide relevant stakeholders with a directive on what strategies, policies, and guidelines to develop and implement to make self-care practices attainable for professional nurses.

Abstract The constellation approach underpinning precipitation products such as the Integrated Multi‐satellitE Retrievals for GPM (IMERG) is key to achieving high resolution, but the use of data from multiple sources can unintentionally incorporate instrumental artifacts. Here, we introduce a machine learning–based anomaly detection scheme called SPEEDe, which processes a two‐dimensional precipitation field into a re‐estimated precipitation field that can be compared with the input. Large differences identify IMERG fields with bad orbit data, separating most of the bad cases from the good cases. When modified to process the passive microwave inputs, SPEEDe can pick out orbits with bad data, enabling quality control on these IMERG inputs. SPEEDe works by producing a locally realistic‐looking precipitation field when given unphysical data, which results in a larger‐than‐normal difference between the input and the output. SPEEDe is implemented as an automated quality control for GPM precipitation products.

Abstract Differentiation of stem and progenitor cells is a highly regulated process that involves the coordinated action of multiple layers of regulation. Here we show how the post-transcriptional regulatory layer instructs the level of chromatin regulation via miR-144 and its targets to orchestrate chromatin condensation during erythropoiesis. The loss of miR-144 leads to impaired chromatin condensation during erythrocyte maturation. Among the several targets of miR-144 that influence chromatin organization, the miR-144-dependent regulation of Hmgn2 is conserved from fish to humans. Our genetic probing of the miR-144/Hmgn2 regulatory axis establish that intact miR-144 target sites in the Hmgn2 3’UTR are necessary for the proper maturation of erythrocytes in both zebrafish and human iPSC-derived erythroid cells while loss of Hmgn2 rescues in part the miR-144 null phenotype. Altogether, our results uncover miR-144 and its target Hmgn2 as the backbone of the genetic regulatory circuit that controls the terminal differentiation of erythrocytes in vertebrates.

Abstract Multidisciplinary management of rectal cancer has rapidly evolved over the last several years. This review describes recent data surrounding total neoadjuvant therapy, organ preservation, and management of lateral pelvic lymph nodes. It then presents our treatment algorithm for management of rectal cancer at The University of Texas MD Anderson Cancer Center in the context of this and other existing literature. As part of this discussion, the review describes how we tailor management based upon both patient and tumor‐related factors in an effort to optimize patient outcomes.

Abstract Central nervous system (CNS) tumors are the leading cause of pediatric cancer death, and these patients have an increased risk for developing secondary neoplasms. Due to the low prevalence of pediatric CNS tumors, major advances in targeted therapies have been lagging compared to other adult tumors. We collect single nuclei RNA-seq data from 84,700 nuclei of 35 pediatric CNS tumors and three non-tumoral pediatric brain tissues and characterize tumor heterogeneity and transcriptomic alterations. We distinguish cell subpopulations associated with specific tumor types including radial glial cells in ependymomas and oligodendrocyte precursor cells in astrocytomas. In tumors, we observe pathways important in neural stem cell-like populations, a cell type previously associated with therapy resistance. Lastly, we identify transcriptomic alterations among pediatric CNS tumor types compared to non-tumor tissues, while accounting for cell type effects on gene expression. Our results suggest potential tumor type and cell type-specific targets for pediatric CNS tumor treatment. Here we address current gaps in understanding single nuclei gene expression profiles of previously under-investigated tumor types and enhance current knowledge of gene expression profiles of single cells of various pediatric CNS tumors.

Abstract Although intratumoral heterogeneity has been established in pediatric central nervous system tumors, epigenomic alterations at the cell type level have largely remained unresolved. To identify cell type-specific alterations to cytosine modifications in pediatric central nervous system tumors, we utilize a multi-omic approach that integrated bulk DNA cytosine modification data (methylation and hydroxymethylation) with both bulk and single-cell RNA-sequencing data. We demonstrate a large reduction in the scope of significantly differentially modified cytosines in tumors when accounting for tumor cell type composition. In the progenitor-like cell types of tumors, we identify a preponderance differential Cytosine-phosphate-Guanine site hydroxymethylation rather than methylation. Genes with differential hydroxymethylation, like histone deacetylase 4 and insulin-like growth factor 1 receptor, are associated with cell type-specific changes in gene expression in tumors. Our results highlight the importance of epigenomic alterations in the progenitor-like cell types and its role in cell type-specific transcriptional regulation in pediatric central nervous system tumors.

Abstract Lower urinary tract (LUT) function is controlled by the central nervous system, including higher-order cognitive brain regions. The anterior cingulate cortex (ACC) is one of these regions, but the role of its activity in LUT function remains poorly understood. In the present study, we conducted optogenetic experiments to manipulate neural activity in mouse ACC while monitoring bladder pressure to elucidate how the activity of ACC regulates LUT function. Selective optogenetic stimulation of excitatory neurons in ACC induced a sharp increase in bladder pressure, whereas activation of inhibitory neurons in ACC prolonged the interval between bladder contractions. Pharmacological manipulation of ACC also altered bladder contractions, consistent with those observed in optogenetic experiments. Optogenetic mapping of the cortical area responsible for eliciting the increase in bladder pressure revealed that stimulation to ACC showed more potent effects than the neighboring motor cortical areas. These results suggest that ACC plays a crucial role in initiating the bladder pressure change and the micturition reflex. Thus, the balance between excitation and inhibition in ACC may regulate the reflex bidirectionally.

Abstract Neurotransmitter release relies on the regulated fusion of synaptic vesicles (SVs) that are tightly packed within the presynaptic bouton of neurons. The mechanism by which SVs are clustered at the presynapse, while preserving their ability to dynamically recycle to support neuronal communication, remains unknown. Synapsin 2a (Syn2a) tetramerization has been suggested as a potential clustering mechanism. Here, we used Dual-pulse sub-diffractional Tracking of Internalised Molecules (DsdTIM) to simultaneously track single SVs from the recycling and the reserve pools, in live hippocampal neurons. The reserve pool displays a lower presynaptic mobility compared to the recycling pool and is also present in the axons. Triple knockout of Synapsin 1-3 genes (SynTKO) increased the mobility of reserve pool SVs. Re-expression of wild-type Syn2a (Syn2aWT), but not the tetramerization-deficient mutant K337Q (Syn2aK337Q), fully rescued these effects. Single-particle tracking revealed that Syn2aK337QmEos3.1 exhibited altered activity-dependent presynaptic translocation and nanoclustering. Therefore, Syn2a tetramerization controls its own presynaptic nanoclustering and thereby contributes to the dynamic immobilisation of the SV reserve pool.

Abstract The Arctic has experienced greatly decreased sea ice and increased ocean temperatures in recent decades but there is a paucity of biological time‐series data allowing assessment of resulting temporal variation in the region's marine ecosystems. Seabirds, as highly mobile and highly visible, upper trophic‐level predators, can be valuable monitors of modifications in marine ecosystems, especially for regions lacking commercial fisheries or regular oceanographic sampling. Since 1975, we have studied annually an Arctic Alaskan colony of Mandt's black guillemot (Cepphus grylle mandtii), an ice‐obligate diving seabird, specializing on Arctic cod (Boreogadus saida), the primary forage fish of the ice‐associated cryopelagic ecosystem. Using multi‐state capture–mark–recapture models, matrix population models, and perturbation analysis, we quantified the environmental and demographic drivers of population change from 1980 to 2019 for the individually marked population. The colony increased rapidly, from 200 breeding pairs from 1975 to 1990 in response to increased availability of nesting cavities, before experiencing intermittent declines to

Summary: Macrophages are critical for maintenance and repair of mucosal tissues. While functionally distinct subtypes of macrophage are known to have important roles in injury response and repair in the lungs, little is known about macrophages in the proximal conducting airways. Single-cell RNA sequencing and flow cytometry demonstrated murine tracheal macrophages are largely monocyte-derived and are phenotypically distinct from lung macrophages at homeostasis. Following sterile airway injury, monocyte-derived macrophages are recruited to the trachea and activate a pro-regenerative phenotype associated with wound healing. Animals lacking the chemokine receptor CCR2 have reduced numbers of circulating monocytes and tracheal macrophages, deficient pro-regenerative macrophage activation and defective epithelial repair. Together, these studies indicate that recruitment and activation of monocyte-derived tracheal macrophages is CCR2-dependent and is required for normal airway epithelial regeneration.

In 2012, Vuyani Vellem made a brief proposal for a deeper engagement with political theorists and activists working around the notion of radical democracy, a proposal he reaffirmed in 2013 in articulating the challenge for the church in the face of an inability to contribute to meaningful change amidst vast economic inequality in South Africa. Despite extensive engagement with the work of Vellem in recent years, this particular proposal has so far not been explicitly picked up. This article places Vellem’s proposal within the more recent debates around public theology and political theology in South Africa, proposing the possibility of a constructive dialogue between political theologies and South African theologies of liberation in picking up Vellem’s suggestion. Contribution: After an overview of the very recent attempts at engaging political theology in the South African context, and an overview of Vellem’s proposal around radical democracy, two more recent theological attempts at engaging with radical democracy are introduced and elements that might extend Vellem’s call for a conversation with radical democracy are outlined.

Background: While the hidden curriculum (HC) is becoming recognized as an important component of medical education, ideal methods of assessing the HC are not well known. The aim of this study was to review the literature for methods of assessing the HC in the context of healthcare education. Methods: We conducted a scoping review on methods to measure or assess the HC in accordance with the JBI Manual for Evidence Synthesis. Ovid MEDLINE, Ovid EMBASE, and ProQuest ERIC databases were searched from inception until August 2023. Studies which focused on healthcare education, including medicine, as well as other professions such as nursing, social work, pharmacy were included. We then obtained stakeholder feedback utilizing the results of this review to inform the ongoing HC assessment process within our own medical education program. Results: Of 141 studies included for full text review, 41 were included for analysis and data extraction. Most studies were conducted in North America and qualitative in nature. Physician education was best represented with most studies set in undergraduate medical education (n = 21, 51%). Assessment techniques included interviews (n = 19, 46%), cross-sectional surveys (n = 14, 34%), written reflections (n = 7, 17%), and direct observation of the working environment (n = 2, 5%). While attempts to create standardized HC evaluation methods were identified, there were no examples of implementation into an educational program formally or longitudinally. No studies reported on actions taken based on evaluation results. Confidential stakeholder feedback was obtained from postgraduate medical learners in our program, and this feedback was then used to modify our longitudinal HC assessment process. Conclusions: While the HC has as increasing presence in the medical education community, the ideal way to practically assess it within a healthcare education context remains unclear. We described the HC assessment process utilized at our program, which may be informative for other institutions attempting to implement a similar technique. Future attempts and studies would benefit from reporting longitudinal data and impacts of assessment results

Summary: The social transmission of food preference, a rudimentary form of social learning, has primarily been studied in pairs of adult rodents. Here, we present a protocol to explore the parent-offspring context in social learning using an adaptation of this classic paradigm for rodent dam-pup dyads. We describe steps for studying weanling mice from the same mother and present a worked example using weight-based (food consumption) and time-based (exploration) indices of social learning. : Publisher’s note: Undertaking any experimental protocol requires adherence to local institutional guidelines for laboratory safety and ethics.

According to European regulation 2023/1804/EU, all member states shall ensure the availability of cold ironing (CI) in large ports for at least 90 % of the total number of port calls of seagoing ships above 5000 gross tonnes, by the end of 2029. This is a measure expected to improve air quality, especially in the vicinity of the port's urban environment. Preliminary studies show that there are financial viability issues related to CI installations, under the current electricity pricing policies and the high investment cost for CI infrastructure. In this paper, the financial viability of the penetration of photovoltaic (PV) units optimized from spatial and power produced point of view is investigated. The proposed method is applied to various ship types, indicatively for the Thessaloniki Port, taking into consideration the connection with the Medium Voltage (MV) electricity distribution grid, as well as the construction, operation, and maintenance costs, under modified economic criterion of benefit-cost ratio (BCR).

Purpose: Examine the impact of the EXercise for Cancer to Enhance Living Well's (EXCEL) 10–12-week exercise and behaviour change support intervention on secondary effectiveness outcomes, including patient-reported outcomes, physical function, and program satisfaction. Methods: Individuals with cancer up to 3 years post treatment with any tumour type were eligible. Outcomes were measured at baseline and immediately following the 10–12-week intervention. Patient-reported outcomes included participant characteristics, overall well-being, cognition, fatigue, symptom severity, exercise barrier self-efficacy, and program satisfaction. Physical function included shoulder flexion, 30-s sit to stand, sit and reach, 2-min step test or 6-min walk test (in-person only), and single leg balance. Wilcoxon signed-rank tests were used to assess changes in patient-reported outcomes and physical function assessments from baseline to 12-weeks. Results: A total of 804 participants enrolled in the study in the first 2.5-years, with 699 completing the intervention. Wilcoxon signed rank tests and Rosenthal coefficients (r) showed significant (p ​

Torn and damaged menisci resulting from trauma are very common knee injuries, which can cause pain and mobility limitations and lead to osteoarthritis. Meniscal injuries can require surgery to repair the tissue damage and restore mobility. Here we describe the biomechanical testing of a 3D-printed meniscus to illustrate methods to determine if it has the strength and durability to effectively repair meniscal tears and restore knee biomechanics. This work was designed to demonstrate the steps needed to test novel meniscus repair devices prior to moving toward animal testing. The first testing step determined the ability of the 3D-printed meniscus to withstand surgical fixation by measuring the suture pull-out force. We show that vertical 2/0 silk or Fiberwire sutures need an average of 1.4 or 1.8 N, respectively, to pull through the meniscus, while horizontal sutures need only 0.7 and 1.2 N, respectively. The next step measured the compressive strength of normal, damaged, and repaired porcine meniscus tissue. Here, we show that meniscectomy decreased the stiffness of meniscus tissue from 26.7 ± 0.85 N to 7.43 ± 0.81 N at 25% strain. Menisci repaired with the 3D-printed tissue restored 66% of the measured force at 25% strain. The final step measured the contact pressures and areas in an ex vivo porcine knee before and after meniscal repair was made with the 3D-printed meniscus tissue. The example 3D-printed meniscus was successfully sutured into the porcine knee joint but failed to restore normal knee contact pressures. This work demonstrates the need for an iterative biomechanical testing process of biomaterial development, 3D-printing optimization, and knee kinematics to develop a durable and functional meniscus repair device. In summary, the methods described here serve as a guide for the functional evaluation of novel meniscus repair devices.

Abstract Background Decreased salivary secretion is not only a risk factor for carious lesions in Sjögren’s disease (SD) but also an indicator of deterioration of teeth with every restorative replacement. This study determined the longevity of direct dental restorations placed in patients with SD using matched electronic dental record (EDR) and electronic health record (EHR) data. Methods We conducted a retrospective cohort study using EDR and EHR data of Indiana University School of Dentistry patients who have a SD diagnosis in their EHR. Treatment history of patients during 15 years with SD (cases) and their matched controls with at least one direct dental restoration were retrieved from the EDR. Descriptive statistics summarized the study population characteristics. Cox regression models with random effects analyzed differences between cases and controls for time to direct restoration failure. Further the model explored the effect of covariates such as age, sex, race, dental insurance, medical insurance, medical diagnosis, medication use, preventive dental visits per year, and the number of tooth surfaces on time to restoration failure. Results At least one completed direct restoration was present for 102 cases and 42 controls resulting in a cohort of 144 patients’ EDR and EHR data. The cases were distributed as 21 positives, 57 negatives, and 24 uncertain cases based on clinical findings. The average age was 56, about 93% were females, 54% were White, 74% had no dental insurance, 61% had public medical insurance,

Kate Petrie,1 Michael J Abramson,2 Johnson George1,2 1Centre for Medicine Use and Safety, Monash University, Melbourne, Victoria, Australia; 2School of Public Health and Preventive Medicine, Monash University, Melbourne, Victoria, AustraliaCorrespondence: Johnson George, Centre for Medicine Use and Safety, Monash University, Melbourne, Victoria, Australia, Email johnson.george@monash.eduBackground: US Preventive Services Taskforce recommends against screening for COPD in asymptomatic adults due to limited evidence on the efficacy of treatments for this population. However, global and Australian guidelines recommend a case-finding approach where those with symptoms and/or risk factors, including smoking, are screened. This study aims to explore patient characteristics by time of COPD diagnosis and the effectiveness of early treatment in those with or without symptoms.Methods: Secondary analysis of a randomised controlled trial that included those with a pre-existing (n=130) or new diagnosis (n=142) of COPD. Those randomised to the intervention arm received an interdisciplinary intervention of smoking cessation support, home medicines review and home-based pulmonary rehabilitation, while controls received usual care. The primary outcome was health-related quality of life (HR-QoL) measured using St George’s Respiratory Questionnaire. To estimate the impact of early treatment, we compared the effectiveness of treatment versus control at 6- and 12-months for the new versus pre-existing diagnosis groups, and those symptomatic versus asymptomatic or minimally symptomatic based on COPD Assessment Test score.Results: Approximately half of those newly diagnosed with COPD were already symptomatic. Early treatment in those diagnosed via case-finding had a positive non-significant impact on HR-QoL. The size of the treatment effects generally favoured the pre-existing diagnosis group when compared to case-finding and favoured those symptomatic when compared to those asymptomatic.Conclusion: Despite useful insights into the impacts of case-finding and early treatments, this study, like most others, was not sufficiently powered. Further larger studies or combining sub-groups across studies are required.Keywords: RCT, screening, interdisciplinary, COPD

The state of road surfaces can have a significant impact on vehicle handling, passenger comfort, safety, fuel consumption, and maintenance requirements. For this reason, it is important to analyze road conditions in order to improve traffic safety, optimize fuel efficiency, and provide a smoother travel experience. This research presents a federated learning analysis that brings together edge computing and cloud technology, by identifying various road conditions through a multi-label road surface classification analysis. The presented analysis prioritizes the privacy of road users’ data and leverages the advantages of collective data analysis while building confidence in the system. Multi-label classification is applied in order to capture complexity by assigning multiple relevant labels, thus providing a richer and more detailed understanding of the road conditions. According to the experiments, this approach efficient classifies road surface images, achieving comprehensive coverage even in scenarios where data from certain edges is limited.

Purpose: We aim to report the natural course of non-center involving diabetic macular edema (NCIDME) progression to center involving diabetic macular edema (CIDME) and associated risk factors. Methods: This is a multicenter retrospective comparative study. Data was collected from electronic medical records from 8 centers in India covering. We included patients with type 2 diabetes above 18 years of age with treatment-naïve NCIDME on OCT and best-corrected visual acuity at baseline of 6/12 or better who were under observation for NCIDME and had 2 years follow-up data. Results: Out of 72 patients with NCIDME, 26.38% patients progressed to CI DME by 2 years, and the visit wise proportion was 11.11% at 6 months, 7% at 1st year and 8.3% at 2 years. The change in CST was statistically significant at 2 years in patients who developed CIDME, the mean difference was 137.73 ± 48.56 microns p = 0.045. Duration of diabetes mellitus > 10 years was the only risk factor for conversion to CIDME. Conclusion: A quarter of eyes with NCIDME developed CIDME and 15% progressed from NPDR to PDR by 2 years, highlighting the disease burden in these patients with NCIDME.

Highly automated passenger vehicles hold great potential to alleviate traffic congestion, enhance road safety, and revolutionize the travel journey. However, while much attention has been given to the technical aspects of this technology, the investigation of public acceptance remains crucial for successful implementation in the global market. To address this gap, this paper introduces innovative research that explores the predictors influencing consumers’ intention to adopt highly automated passenger vehicles. Through an online questionnaire-based survey conducted among European adults, we extend the Unified Theory of Acceptance and Use of Technology (UTAUT) framework to incorporate three additional constructs: perceived reliability/trust, perceived financial cost, and perceived driving enjoyment. The key findings of this study underscore the significance of driving enjoyment, financial cost, social influences, and reliability/trust as influential predictors of consumers’ intention to adopt highly automated passenger vehicles. By considering these factors, automotive stakeholders can gain valuable insights to develop effective strategies and approaches for the successful implementation of highly automated passenger vehicles in the near future. Last, its innovations pave the way for a transformative shift in transportation, enabling the realization of safer, more efficient, and enjoyable travel experiences for individuals and society as a whole.

Abstract Background The role of ACTA2 mutations in Familial Aortic Disease has been increasingly recognized. We describe a highly penetrant variant (R118Q) in a family with aortic disease. Case report A patient presented to us for elective repair of an ascending aortic aneurysm with a family history of his mother expiring after aortic dissection. Genetic testing revealed he was a heterozygous carrier of the ACTA2 missense mutation R118Q. Subsequently, all living family members were tested for this variant and a full medical history was obtained to compile a family tree for the variant and penetrance of an aortic event (defined as lifetime occurrence of aortic surgery / dissection). In total 9 family members were identified and underwent genetic testing with 7/9 showing presence of the ACTA2 R118Q mutation or an aortic event. All patients over the age of 50 (n = 4) had an aortic event. Those events occurred at ages 54, 55, 60, and 62 (mean event at 57.8 ± 3.9 years). Three family members with the variant under the age of 40 have not had an aortic event and most are undergoing regular aortic surveillance via CT scan. Conclusions Existing studies of known ACTA2 mutations describe a 76% aortic event rate by 85 years old. The R118Q missense mutation is a less common ACTA2 variant, estimated to be found in about 5% of patients with known mutations. Prior studies have predicted the R118Q mutation to have a slightly decreased risk of aortic events compared to other ACTA2 mutations. In this family, however, we demonstrate 100% penetrance of aortic disease above age 50. In today’s era of excellent outcomes in elective aortic surgery, our team aggressively offers elective repair. We advocate for strict aortic surveillance for patients with this variant and would consider elective aortic replacement at 4.5 cm, or at an even smaller diameter in patients with a strong family history of dissection who are identified with this mutation.

Abstract Background Hemopericardium is a serious complication that can occur after cardiac surgery. While most post-operative causes are due to inflammation and bleeding, patients with broken sternal wires and an unstable sternum may develop hemopericardium from penetrating trauma. Case presentation We present the case of a 62-year-old male who underwent triple coronary bypass surgery and presented five months later with sudden anterior chest wall pain. Chest computed tomography revealed hemopericardium with an associated broken sternal wire that had penetrated into the pericardial space. The patient underwent a redo-sternotomy which revealed a 3.5 cm bleeding, jagged right ventricular laceration that correlated to the imaging findings of a fractured sternal wire projecting in the pericardial space. The laceration was repaired using interrupted 4 − 0 polypropylene sutures in horizontal mattress fashion between strips of bovine pericardium. The patient’s recovery was uneventful and he was discharged on post-operative day four without complications. Conclusion Patients with broken sternal wires and an unstable sternum require careful evaluation and management as these may have potentially life-threatening complications if left untreated.

In 2014, The GEOSS Water Strategy – From Observations to Decisions was published and steps were taken to implement the Strategy’s recommendations. The Strategy highlighted priority areas where the application of Earth observations to water research and water management decisions would have significant scientific and societal benefits. This article reviews the implementation of the Strategy’s recommendations over the past eight years. After a review of the Strategy’s assessment of the needs for water observations and their applications, it then reviews actions taken in response to the Strategy’s recommendations in its four major themes: improved data acquisition for Essential Water Variables, research and product development, interoperability, and capacity development. It highlights significant achievements in the implementation of the Strategy including some motivated by factors beyond this Strategy, reviews actions taken by participating agencies and programs for each of the main themes and summarizes the remaining challenges in achieving the Strategy’s full implementation. The article not only is an update for the Water Community regarding the GEOSS Water Strategy, but it is also an example of how other communities could develop and promulgate a set of strategic recommendations, monitor progress, and carry out assessments of their effectiveness.

This study evaluates the techno-economic feasibility of integrating fuel cells into stand-alone power generation systems, combined with different technologies such as diesel generators, wind turbines, and batteries. An optimisation analysis was performed using the Hybrid Optimization Model for Multiple Energy Resources (HOMER) software to minimise energy costs and several system architectures were obtained for different operating scenarios. The performance and cash flow of the selected system were included. The results suggest that the combination of traditional technologies for fuel cell power generation could be feasible for a country like Colombia, depending on economic factors such as the Consumer Price Index (CPI), the discount rate, and the availability of renewable resources. The proposed system achieves a Levelized Cost of Electricity (LCOE) of $0.112/kWh, comparable to state-of-the-art systems in the literature. This research contributes to the global effort of transitioning to alternative energy sources and reducing carbon emissions.

Aging is the major risk factor for Alzheimer’s disease (AD). In the aged brain, myelin debris accumulates and is cleared by microglia. Phagocytosed myelin debris increases neutral lipid droplet content in microglia. Neutral lipids include cholesteryl esters (CE) and triacylglycerol (TAG). To examine the effects of myelin debris on neutral lipid content in microglia, we added myelin debris to human HMC3 and mouse N9 cells. The results obtained when using 3H-oleate as a precursor in intact cells reveal that myelin debris significantly increases the biosynthesis of CE but not TAG. Mass analyses have shown that myelin debris increases both CE and TAG. The increase in CE biosynthesis was abolished using inhibitors of the cholesterol storage enzyme acyl-CoA:cholesterol acyltransferase 1 (ACAT1/SOAT1). ACAT1 inhibitors are promising drug candidates for AD treatment. In myelin debris-loaded microglia, treatment with two different ACAT1 inhibitors, K604 and F12511, increased the mRNA and protein content of ATP-binding cassette subfamily A1 (ABCA1), a protein that is located at the plasma membrane and which controls cellular cholesterol disposal. The effect of the ACAT1 inhibitor on ABCA1 was abolished by preincubating cells with the liver X receptor (LXR) antagonist GSK2033. We conclude that ACAT1 inhibitors prevent the accumulation of cholesterol and CE in myelin debris-treated microglia by activating ABCA1 gene expression via the LXR pathway.

Background: Childhood vitamin A deficiency leads to increased morbidity and mortality. Human milk is the only source of vitamin A for exclusively breastfed infants. Dried Moringa oleifera leaf powder (moringa) is a good food source of provitamin A and other carotenoids. Its effect during lactation on human milk vitamin A and carotenoid content is unclear. Objectives: Our objective was to investigate the effect of maternal moringa consumption on human milk retinol and carotenoid concentrations and maternal and infant vitamin A status. Methods: We conducted a 3-month pilot single-blinded cluster-randomized controlled trial in breastfeeding mother–infant pairs (n = 50) in Kenya. Mothers received corn porridge with (20 g/d) or without moringa with complete breast expressions and maternal and infant serum collected at enrollment (infant Results: 88% (n = 44) pairs completed milk and serum samples. Four mothers (9%) had vitamin A deficiency (RBP p = 0.024) and at exit (least squares means, LSM, 95%CI µg/mL 0.003, 0.003–0.004 moringa vs. 0.002, 0.001–0.003 control, n = 22/cluster; p = 0.014). In mothers with VAI, alpha-carotene was higher in the moringa group than controls at exit (LSM, 95%CI µg/mL 0.005, 0.003–0.009 moringa, n = 3, vs. 0.002, 0.000–0.004 control, n = 8, p = 0.027) with no difference at baseline. Milk carotenoids did not correlate with vitamin A status (serum RBP) in infants or mothers. Conclusions: Maternal moringa consumption did not impact concentration of milk vitamin A and resulted in limited increase in milk carotenoids in this cohort.

The complex composition of cultural heritage (CH) items presents significant challenges in assessing their condition and predicting potential risks of material degradation. Typically employed diagnostic optical methods are inevitably limited by light scattering, thus restricting in-depth investigations of objects with complex structural and optical properties. To address this issue, we introduce a novel reflection-mode optoacoustic (OA) diagnostic system for non-contact and non-invasive measurements of CH, placing emphasis on the detection of ageing-related modifications in artistic media such as paints. In this direction, the sensitivity of OA measurements was proven to be up to two orders of magnitude higher than conventional absorption spectroscopy assessments. Furthermore, we have evaluated the in-depth imaging capabilities of the developed OA system, demonstrating that it can offer superior contrast levels of sketches beneath opaque paint layers compared to standard near-infrared diagnostic techniques. The current OA imaging technology may advance state-of-the-art diagnostic capabilities in CH preservation by delivering unprecedented depth-to-resolution ratios combined with exceptional optical absorption sensitivity in a non-invasive manner. These features are crucial for the early detection of material degradation and the comprehensive analysis of CH objects, facilitating the development of optimal conservation strategies to prolong their lifespan and preserve their aesthetic value.

Present bladder cancer therapies have relatively limited therapeutic impact and account for one of the highest lifetime treatment costs per patient. Therefore, there is an urgent need to explore novel and optimized treatment strategies. The present study investigated the effects of inhibiting endogenous hydrogen sulfide (H2S) production on bladder cell viability and in vivo tumor progression. We targeted the H2S-producing enzyme, cystathionine γ-lyase, in 5637 cells using propargylglycine (H2S inhibitor) and performed cytofluorimetric analysis to evaluate cell viability. We then tested the efficacy of propargylglycine alone or in combination with gemcitabine (conventional chemotherapy) in an intravesical murine model of bladder cancer. Magnetic resonance imaging and immunohistochemical staining for cell proliferation, apoptosis, immune-cell infiltration, and neovascularization were performed to evaluate tumor response. Compared to control conditions or cohorts, propargylglycine administration significantly attenuated bladder cancer cell viability in vitro (p < 0.0001) and tumor growth (p < 0.002) and invasion in vivo. Furthermore, propargylglycine enhanced the anti-cancer effects of gemcitabine, resulting in tumor regression (p < 0.0001). Moreover, propargylglycine induced cleaved PARP-1-activated apoptosis (p < 0.05), as well as intratumoral CD8+ T cell (p < 0.05) and F4/80+ macrophage (p < 0.002) infiltration. Propargylglycine also reduced intratumoral neovascularization (p < 0.0001) and cell proliferation (p < 0.0002). Importantly, the pro-apoptotic and anti-neovascularization effects of gemcitabine were enhanced by propargylglycine co-administration. Our findings suggest that inhibition of endogenous H2S production can be protective against bladder cancer by enhancing the chemotherapeutic action of gemcitabine and may be a novel pharmacological target and approach for improved bladder cancer diagnosis and treatments in the future.

We recently reported in a rat model of kidney transplantation that the addition of sodium thiosulfate (STS) to organ preservation solution improved renal graft quality and prolonged recipient survival. The present study investigates whether STS pre-treatment would produce a similar effect. In vitro, rat kidney epithelial cells were treated with 150 μM STS before and/or during exposure to hypoxia followed by reoxygenation. In vivo, donor rats were treated with PBS or 2.4 mg/kg STS 30 min before donor kidneys were procured and stored in UW or UW+150 μM STS solution at 4 °C for 24 h. Renal grafts were then transplanted into bilaterally nephrectomised recipient rats which were then sacrificed on post-operative day 3. STS pre-treatment significantly reduced cell death compared to untreated and other treated cells in vitro (p < 0.05), which corresponded with our in vivo result (p < 0.05). However, no significant differences were observed in other parameters of tissue injury. Our results suggest that STS pre-treatment may improve renal graft function after transplantation.

Ribosomal DNA (rDNA), which encodes ribosomal RNA, is an essential but unstable genomic element due to its tandemly repeated nature. rDNA's repetitive nature causes spontaneous intrachromatid recombination, leading to copy number (CN) reduction, which must be counteracted by a mechanism that recovers CN to sustain cells' viability. Akin to telomere maintenance, rDNA maintenance is particularly important in cell types that proliferate for an extended time period, most notably in the germline that passes the genome through generations. In Drosophila, the process of rDNA CN recovery, known as 'rDNA magnification', has been studied extensively. rDNA magnification is mediated by unequal sister chromatid exchange (USCE), which generates a sister chromatid that gains the rDNA CN by stealing copies from its sister. However, much remains elusive regarding how germ cells sense rDNA CN to decide when to initiate magnification, and how germ cells balance between the need to generate DNA double-strand breaks (DSBs) to trigger USCE vs. avoiding harmful DSBs. Recently, we identified an rDNA-binding Zinc-finger protein Indra as a factor required for rDNA magnification, however, the underlying mechanism of action remains unknown. Here we show that Indra is a negative regulator of rDNA magnification, balancing the need of rDNA magnification and repression of dangerous DSBs. Mechanistically, we show that Indra is a repressor of RNA polymerase II (Pol II)-dependent transcription of rDNA: Under low rDNA CN conditions, Indra protein amount is downregulated, leading to Pol II-mediated transcription of rDNA. This results in the expression of rDNA-specific retrotransposon, R2, which we have shown to facilitate rDNA magnification via generation of DBSs at rDNA. We propose that differential use of Pol I and Pol II plays a critical role in regulating rDNA CN expansion only when it is necessary.

Fin whale song is a ubiquitous low-frequency pulsing that has been recorded in every ocean basin. In recent years, the complexity of fin whale song has been realized. In the North Atlantic, this song is made up of two low-frequency note types (A and B notes) and one higher-frequency note type (upsweeps). The A and B notes are produced with both singlet and doublet inter-note intervals. These song patterns are interwoven throughout an individual’s song and have been observed to shift over time, both gradually and suddenly. Like many baleen whales, the population size of fin whales is poorly defined. Passive acoustic monitoring has been suggested as a way to estimate abundance if a cue rate or calling rate can be determined. In this study, we used recordings from 119 fin whale tracks from 2013–2023 generated from passive acoustic recorders in the North Atlantic to define fin whale song patterns in this ocean basin, identify changes in these song patterns over time, and calculate cue rates. The fin whales recorded sang in 4 distinct patterns. Inter-note intervals were 25 s for A-A singlets, 13 s for B-B singlets, 12/20 s for B-B doublets, and 10/11 s for A-B doublets. B-B doublet inter-note intervals significantly increased from May 2019–April 2023 and A-B inter-note intervals showed an intra-annual increasing trend that reset each summer. Fin whale song in the North Atlantic also often includes higher frequency upsweep notes immediately prior to B notes. While A and B note peak frequency was steady over these years, upsweep peak frequency significantly decreased, continuing a similar trend that has been observed over 30 years. Despite these changes, the dominant song pattern remained consistent and cue rate for actively singing whales was relatively stable, which is in contrast to patterns observed in the North Pacific. Many of these nuances in fin whale singing behavior are newly described herein, and these findings are vital for monitoring baseline behavior, behavioral trends over time, and ultimately estimating abundance of a poorly understood species.

Objectives This study aimed to compare talent development athletes to community-level athletes in Australian Rules Football across various markers of healthy youth development.Methods Survey data were collected from 363 youth athletes (126 women, 232 men, 5 not reported; Mage=18.69 years, SDage=2.62 years, age range 16–25 years) playing Australian Rules Football at a talent development (recruited from Australian Football League Talent Pathway, n=220) or community (n=143) level. Measures included markers of physical health (eg, general health, risk-taking behaviours), psychological and emotional well-being (eg, mental health symptoms, life satisfaction), family and social relationships (eg, social support, relationship status), educational and occupational attainment/engagement (eg, career satisfaction, education), ethical behaviour (eg, moral self-image), civic engagement, life skills (eg, self-mastery, coping), and demographics.Results Based on regression models, relative to community-level athletes, talent development athletes reported better physical health (d=0.51), lower injury rates (OR=0.50) and less problematic drug use (d=−0.46). Talent development athletes also reported better psychological and emotional well-being, evidenced by lower stress (d=−0.30), higher life satisfaction (d=0.47) and less problematic gambling (d=−0.34). Additionally, talent development athletes reported higher family support (d=0.49), lower likelihood of poor educational outcomes (less than expected educational stage; OR=0.37), lower intention to complete less than year 12 education (OR=0.18), higher career satisfaction (d=0.42), higher self-mastery (d=0.37) and higher perfectionistic striving (d=0.59).Conclusion Findings demonstrate markers of healthier development within talent development athletes relative to community athlete peers. Investment in community-level sports may be warranted to improve healthy development. However, further causal evidence is required.

Isokinetics is a proven method to train and objectively assess the capability of muscle groups, particularly at the knee. The current re-injury rates and less than optimal return to sport percentages seen following anterior cruciate ligament surgery highlights the need for greater focus on what tests and methods are used to make these critical decisions. Isokinetics remains the best single method to objectively determine dynamic muscle strength, power, rate of force development and endurance. These factors make it well-suited to play a crucial role in influencing the appropriate patient progression through a rehabilitation program and assisting in determining return to play readiness following injury or surgery. In this article we will discuss why we believe isokinetics is a useful and necessary testing method, and elucidate testing parameters and goals used during knee extension/flexion assessment.

Crop yield potential in breeding trials can be captured using unmanned aerial vehicle (UAV) based multispectral imagery. Several digital traits or phenotypes such as vegetation indices can represent canopy crop vigor and overall plant health, which can be used to evaluate differences in performance across varieties in crop breeding programs. This dataset contains agronomic data for named cultivars and breeding lines of spring-sown dry pea and chickpea, and over 275 multispectral images from advanced and preliminary breeding trials. The breeding trials were located at three locations in the “Palouse” region of Eastern Washington and Northern Idaho of the United States across 2017, 2018 and 2019 cropping seasons. The multispectral images were captured using a UAV integrated with a 5-band multispectral camera at multiple time points from early vegetative growth through pod development stages during each cropping season. This dataset details seed yield information from trials of dry peas and chickpea that were obtained from each location, as well as additional agronomic and phenological data recorded at one location (mostly Pullman, WA) for each cropping season. The dataset also includes 20–78 megabytes (MB) Tagged Image Format (TIF) uncalibrated stitched orthomosaic images generated from the photogrammetric software. The images can be processed using any convenient image processing algorithm to obtain vegetation indices and other useful information.

Abstract Objectives This study validated the Japanese version of the Attention‐Deficit/Hyperactivity Disorder‐Rating Scale‐5 (ADHD‐RS‐5) and the Disruptive Behavior Disorders Rating Scale. We extended the ADHD‐RS‐5 by adding the oppositional defiant disorder and conduct disorder subscales to compare the two rating scales psychometrically. Methods We examined the internal consistency, test‐retest reliability, construct validity and criterion validity of the two rating scales in 135 Japanese outpatients aged 6–18 years. Results The internal consistency and test‐retest reliability were good for all the subscales of the two rating scales except for the conduct disorder subscale of the ADHD‐RS‐5 extended. Good construct validity was revealed by expected correlational patterns between subscales from the two rating scales and the Children Behavior Checklist. The criterion validity was good for all the subscales of the two rating scales rated by parents, while teacher‐ratings revealed substantially lower predictive ability for all the subscales. Agreement between parent‐ and teacher‐ratings of the two rating scales was generally moderate and using predictive ratings alone of both ratings showed the best predictive ability among the integration methods examined. Conclusion The two rating scales have sound psychometric properties and will aid in screening and severity assessment of externalizing disorders in Japanese clinical settings.