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Generally, psychology (as well as school psychology) aligns with medicine in establishing and utilizing evidence-based practices (EBP). More recently, strong calls have been made and advanced to ensure that psychology evolves and incorporates social justice principles to safeguard equity, diversity, and inclusion to benefit all. This essay explores some of the issues surrounding EBP and social justice within school psychology, noting some of the tensions that play out in research and practice. Ultimately, it is the opinion of the author that social justice practices will only enhance EBP, and the field has much work to do.

Whether by choice or pushed online by Covid, higher education is increasingly happening in digital spaces with digital tools forming a critical part of learning and teaching contexts. While reviews suggest such tools positively influence student engagement, research tends to be generic and more is needed to understand how and why specific tools can influence student engagement, learning, and success. Relationships are a key influence on student engagement and online students often feel disconnected and isolated; tools which increase interaction and communication with staff and among students are therefore important. This qualitative study examined how two specific tools, Discord and Teams, work in conjunction with an LMS to benefit student engagement and learning. Nineteen students were interviewed, and the data thematically analysed. Findings show the tools facilitated communication, helped build relationships and communities, encouraged help-seeking within the course and, with Discord, with the wider disciplinary community. These usages led to improved belonging, wellbeing, engagement, and learning. The perceived norms of the digital spaces were an important influence on student tool usage. A key contribution of this research is defining a new tool categorisation, Learning Commons Communication Tools (LCCT), which better describes the informal and organic spaces created by such tools.

Abstract The continuing emergence of immune evasive SARS-CoV-2 variants and the previous SARS-CoV-1 outbreak collectively underscore the need for broadly protective sarbecovirus vaccines. Targeting the conserved S2 subunit of SARS-CoV-2 is a particularly promising approach to elicit broad protection. Here, we describe a nanoparticle vaccine displaying multiple copies of the SARS-CoV-1 S2 subunit. This vaccine alone, or as a cocktail with a SARS-CoV-2 S2 subunit vaccine, protects female transgenic K18-hACE2 mice from challenges with Omicron subvariant XBB as well as several sarbecoviruses identified as having pandemic potential including the bat sarbecovirus WIV1, BANAL-236, and a pangolin sarbecovirus. Challenge studies in female Fc-γ receptor knockout mice reveal that antibody-based cellular effector mechanisms play a role in protection elicited by these vaccines. These results demonstrate that our S2-based vaccines provide broad protection against clade 1 sarbecoviruses and offer insight into the mechanistic basis for protection.

Background Nationwide trends in the utilization of catheter-directed therapies for deep vein thrombosis and pulmonary embolism in the Medicare population are essential as they represent a major health care challenge. The annual incidence and mortality with venous thromboembolism are around 900,000 and 60,000 to 100,000 patients, respectively, in the United States.

Background and Aim: To address the problems associated with the availability and prices of conventional feeds, researchers have started to include alternative feeds to reduce the cost of diets and increase profitability. This study examined the influences of olive cake (OC), either alone or in combination with Saccharomyces cerevisiae (SC), in the diet of black kids. Materials and Methods: Thirty kids were distributed into three treatments: A free OC diet (control [CON]), OC (20% OC), and OCSC (20% OC with 1 g SC head/d). While penned individually, the kids were fed daily and allowed to acclimate to their diets and pens for 7 days. After acclimation, the kids were fed the prescribed diets for 63 days. Five kids were chosen from each group on day 50 of the feeding period and moved to the metabolic cages to evaluate nutrient digestibility and N balance. At the end of the study, all kids were slaughtered to evaluate carcass characteristics and meat quality. Results: Feeding the OCSC diet increased (p = 0.035) DM intake for kids compared with the OC and CON. The CP intake was higher (p = 0.021) in the OCSC group than in the CON group. Growth performance parameters were higher (p ≤ 0.031) in the OCSC group than in the CON diet. Feed conversion efficiency was improved (p = 0.052) by incorporating OCSC compared with the CON diet. Consequently, economic return was enhanced (p = 0.003) by feeding the OC and OCSC groups. Kids fed the OCSC had a higher cold carcass weight (p = 0.054) than those fed the CON diet. The OCSC group also showed increased (p ≤ 0.027) loin cut and intermuscular fat weights compared with the OC and CON groups. All measured serum metabolites were similar in CON and groups incorporating OCs or OCSCs. Conclusion: The results showed that adding 20% OC combined with SC to the diet of growing kids improved some growth and carcass characteristic parameters without affecting their health status. Notably, using OC along with SC could be an option for feed cost reduction in kids’ diets.

T cells recognize a wide range of pathogens using surface receptors that interact directly with peptides presented on major histocompatibility complexes (MHC) encoded by the HLA loci in humans. Understanding the association between T cell receptors (TCR) and HLA alleles is an important step towards predicting TCR-antigen specificity from sequences. Here we analyze the TCR alpha and beta repertoires of large cohorts of HLA-typed donors to systematically infer such associations, by looking for overrepresentation of TCRs in individuals with a common allele.TCRs, associated with a specific HLA allele, exhibit sequence similarities that suggest prior antigen exposure. Immune repertoire sequencing has produced large numbers of datasets, however the HLA type of the corresponding donors is rarely available. Using our TCR-HLA associations, we trained a computational model to predict the HLA type of individuals from their TCR repertoire alone. We propose an iterative procedure to refine this model by using data from large cohorts of untyped individuals, by recursively typing them using the model itself. The resulting model shows good predictive performance, even for relatively rare HLA alleles.

Summary: Background: Perivascular spaces (PVS) on brain MRI are surrogates for small parenchymal blood vessels and their perivascular compartment, and may relate to brain health. However, it is unknown whether PVS can predict dementia risk and brain atrophy trajectories in participants without dementia, as longitudinal studies on PVS are scarce and current methods for PVS assessment lack robustness and inter-scanner reproducibility. Methods: We developed a robust algorithm to automatically assess PVS count and size on clinical MRI, and investigated 1) their relationship with dementia risk and brain atrophy in participants without dementia, 2) their longitudinal evolution, and 3) their potential use as a screening tool in simulated clinical trials. We analysed 46,478 clinical measurements of cognitive functioning and 20,845 brain MRI scans from 10,004 participants (71.1 ± 9.7 years-old, 56.6% women) from three publicly available observational studies on ageing and dementia (the Alzheimer’s Disease Neuroimaging Initiative, the National Alzheimer’s Coordinating Centre database, and the Open Access Series of Imaging Studies). Clinical and MRI data collected between 2004 and 2022 were analysed with consistent methods, controlling for confounding factors, and combined using mixed-effects models. Findings: Our fully-automated method for PVS assessment showed excellent inter-scanner reproducibility (intraclass correlation coefficients >0.8). Fewer PVS and larger PVS diameter at baseline predicted higher dementia risk and accelerated brain atrophy. Longitudinal trajectories of PVS markers differed significantly in participants without dementia who converted to dementia compared with non-converters. In simulated placebo-controlled trials for treatments targeting cognitive decline, screening out participants at low risk of dementia based on our PVS markers enhanced the power of the trial independently of Alzheimer’s disease biomarkers. Interpretation: These robust cerebrovascular markers predict dementia risk and brain atrophy and may improve risk-stratification of patients, potentially reducing cost and increasing throughput of clinical trials to combat dementia. Funding: US National Institutes of Health.

Abstract The path of totality of the 8 April 2024 solar eclipse traversed the fields‐of‐view of four US SuperDARN radars. This rare scenario provided an excellent opportunity to monitor the large‐scale ionospheric response to the eclipse. In this study, we present observations made by the Blackstone (BKS) SuperDARN radar and a Digisonde during the eclipse. Two striking effects were observed by the BKS radar: (a) the Doppler velocities associated with ground scatter coalesced into a pattern clearly organized by the line of totality, with a reversal in sign across this line, and, (b) a delay of ∼45 min between time of maximum obscuration and maximum effect on the skip distance. The skip distance estimated using a SAMI3 simulation of the eclipse did not however capture the asymmetric time‐delay. These observations suggest that the neutral atmosphere plays an important role in controlling ionospheric plasma dynamics, which were missing in SAMI3 simulations.

Abstract An annular solar eclipse was visible on 14 October 2023 from 15:00–21:00 UT as its path traveled across North, Central, and South America. In this letter, we present the first multi‐frequency Super Dual Auroral Radar Network (SuperDARN) observations of the bottomside ionospheric response to a solar eclipse using a novel experimental mode designed for the October 2023 annular eclipse. We compare our results from the mid‐latitude Christmas Valley East radar with measurements of the vertical electron density profile from the nearby Boulder Digisonde, finding the changes in 1‐ and 2‐hop ground scatter skip distance are well correlated with the F2‐layer density response, which lags the peak obscuration by ∼30 min. Changes in the line‐of‐sight Doppler shifts are better aligned with the time derivative of eclipse obscuration.

Background: Hydroxyapatite (HA) is a material with excellent bioactivity and chemical similarity to bone. It can be extracted from natural sources or fabricated synthetic sources. Objective: To synthesize HA from domestic chicken eggshells and to characterize it using Fourier transform infrared (FTIR), X-ray powder diffraction (XRD), scanning electron microscopy (SEM), energy-dispersive X-ray spectroscopy, and cell viability. Materials and Methods: Domestic chicken eggshells (Indian breed “Aseel”) were used to synthesize HA through the chemical precipitation method. The processing was conducted at an elevated temperature (900°C). Characterization of the sample was performed using, FTIR, SEM, EDS, and XRD. The cell viability was tested in vitro using methyl thiazolyl tetrazolium assay. Results: Phosphate and calcium ions were confirmed by FTIR and EDS. The carbonate peaks observed were typical of biological apatite. XRD revealed its crystalline property. SEM analysis confirmed the particle size to be less than 100 μm and the presence of a porous structure. The material was found to be noncytotoxic and favored cell growth. Conclusion: The synthesized HA showed a crystalline nature and had good cell viability. Hence, it may be considered as a material for various biomedical applications.

The Gleason score is an important predictor of prognosis in prostate cancer. However, its subjective nature can result in over- or under-grading. Our objective was to train an artificial intelligence (AI)-based algorithm to grade prostate cancer in specimens from patients who underwent radical prostatectomy (RP) and to assess the correlation of AI-estimated proportions of different Gleason patterns with biochemical recurrence-free survival (RFS), metastasis-free survival (MFS), and overall survival (OS). Training and validation of algorithms for cancer detection and grading were completed with three large datasets containing a total of 580 whole-mount prostate slides from 191 RP patients at two centers and 6218 annotated needle biopsy slides from the publicly available Prostate Cancer Grading Assessment dataset. A cancer detection model was trained using MobileNetV3 on 0.5 mm × 0.5 mm cancer areas (tiles) captured at 10× magnification. For cancer grading, a Gleason pattern detector was trained on tiles using a ResNet50 convolutional neural network and a selective CutMix training strategy involving a mixture of real and artificial examples. This strategy resulted in improved model generalizability in the test set compared with three different control experiments when evaluated on both needle biopsy slides and whole-mount prostate slides from different centers. In an additional test cohort of RP patients who were clinically followed over 30 years, quantitative Gleason pattern AI estimates achieved concordance indexes of 0.69, 0.72, and 0.64 for predicting RFS, MFS, and OS times, outperforming the control experiments and International Society of Urological Pathology system (ISUP) grading by pathologists. Finally, unsupervised clustering of test RP patient specimens into low-, medium-, and high-risk groups based on AI-estimated proportions of each Gleason pattern resulted in significantly improved RFS and MFS stratification compared with ISUP grading. In summary, deep learning-based quantitative Gleason scoring using a selective CutMix training strategy may improve prognostication after prostate cancer surgery.

IntroductionAlveolar macrophages (AM) are critical effectors of the immune response and are essential for host responses to Streptococcus pneumoniae. Changes in lipid metabolism in AM can alter cellular function and biology. Impaired metabolism can contribute to excessive lipid accumulation and pro-inflammatory signaling. Our current study was designed to examine the role of cholesterol 25-hydroxylase (Ch25h), a redox enzyme that catalyzes the oxidation of cholesterol to 25-hydroxycholesterol (25-HC), in modulating AM responses in the aged lung during S. pneumoniae infection.MethodsTo observe the impact of aging on Ch25h expression in AM during infection, in vitro and in vivo murine models of S. pneumoniae were used.ResultsAt baseline and in response to infection, cholesterol metabolism significantly altered in aged AM, which corresponded with increased lipid droplet formation. In vitro, treatment of aged macrophages with Ch25 h-specific siRNA improved S. pneumoniae clearance and enhanced phagocytic receptor expression. In vivo siRNA targeting significantly reduced Ch25h expression in aged lungs and improved clinical parameters during S. pneumoniae infection. Reduction of Ch25h was associated with changes in phagocytosis and antibacterial signaling, correlated with changes in cholesterol metabolism, and increased S. pneumoniae clearance.DiscussionThe results of our current study demonstrate that Ch25h plays an essential role in modulating aged AM responses to S. pneumoniae.

Interprofessional teamwork is important for the provision of safe, high value patient care and is recognized as essential by the ACGME. We aimed to assess the impact of an interprofessional continuity clinic teamwork curriculum on perceptions of team development and patient safety. This project was conducted in an IM Resident Continuity Clinic where 96 residents, supported by 28 faculty and 48 interprofessional team members, attended continuity clinic two afternoons per week during alternating months of a 50/50 outpatient-inpatient training model. Teams were configured into two groups of residents, faculty and interprofessional team members. The randomly selected intervention group participated in strategically-timed TeamSTEPPS training. The control group received usual clinic education. Teamwork and safety climate were measured using the Team Development Measure (TDM) and Safety Attitudes Questionnaire (SAQ) collected before and after the intervention. Following the teamwork curriculum, team development improved in the intervention group as compared to control [mean change (95% CI) +13.9 (+9.3, +18.6) versus + 4.8 (+0.4, +9.1), p = 0.007]. Though 30% of the individual items on the SAQ improved significantly in the faculty intervention group as compared to control, the overall improvement in SAQ [intervention mean change + 0.4 (+0.2, +0.5), control mean change + 0.2 (−0.1, +0.5)] was not statistically significant (p = 0.36). It is feasible to implement a TeamSTEPPs-based interprofessional teamwork curriculum among IM residents in a block clinic model and achieve enhanced teamwork and safety attitudes. Additional assessment of clinical and educational outcomes is ongoing.

The importance of using agro-industrial by-products in feeding livestock is important in terms of preserve the environment and conversely, reducing the cost of feeding and production. Therefore, the purpose of this study was to assess how feeding jojoba meal (JOJ) affected growth performance, cost of production, and carcass features of growing lambs. Twenty-four Awassi lambs weighing 16.4 kg ± 0.17 kg were randomly selected and given two diets; a control diet without the inclusion of JOJ (CON), and JOJ100 with the presence of 100 g/kg dry matter (DM) of JOJ. The experiment lasted for 63 days preceded by 10 days as a period of adaptation. As scheduled on day 49 of the trial and, to assess nutritional digestibility and N balance, five lambs were randomly selected. During this period, lambs were housed in metabolic cages that allowed the collection of total fecal and urinary outputs. Lambs were slaughtered to investigate carcass features on day 64. Acid detergent fiber and EE intakes were greater (p ≤ 0.007) in the JOJ100 than in CON diet. Nutrient digestibility, N balance, growth rate, and carcass traits were not affected (p ≥ 0.136) by consumption of JOJ100. Cost of production declined (p = 0.046) by 17% with the JOJ100 group. High-density lipoprotein was increased (p = 0.012) with lambs consuming the JOJ100 diet. In summary, adding jojoba meal to the diet of lambs appeared to have no adverse effect on their performance, carcass quality, or health. Most importantly, this dietary supplement appeared to enhance the economic efficiency by reducing the cost of production.

Clinical trials for Duchenne muscular dystrophy (DMD) are assessing the therapeutic efficacy of systemically delivered adeno-associated virus (AAV) carrying a modified DMD transgene. High vector doses (>1E14 vg/kg) are needed to globally transduce skeletal muscles; however, such doses trigger immune-related adverse events. Mitigating these immune responses is crucial for widespread application of AAV-based therapies. We used single-cell RNA sequencing and T cell receptor (TCR) sequencing on peripheral blood mononuclear cells from five participants prior to, and after, dosing. One subject in the high-dose cohort experienced thrombotic microangiopathy (TMA). Few changes in cell frequencies occurred after treatment; however, differential gene expression demonstrated induction of interferon response genes in most T cell types. T cell clonotype and clumping analysis showed the expansion or appearance of groups of related TCR sequences in the post-treatment samples. Three of these expanded clumps could be assigned to prior human herpesvirus infections, two of which were present in the participant that exhibited TMA. These data provide insight on the mechanistic basis of human immune-AAV interactions and lay a foundation for improved understanding of why TMA arises in some patients and not others.

The news arguably serves to inform the quantitative reasoning (QR) of news audiences. Before one can contemplate how well the news serves this function, we first need to determine how much QR typical news stories require from readers. This paper assesses the amount of quantitative content present in a wide array of media sources, and the types of QR required for audiences to make sense of the information presented. We build a corpus of 230 US news reports across four topic areas (health, science, economy, and politics) in February 2020. After classifying reports for QR required at both the conceptual and phrase levels, we find that the news stories in our sample can largely be classified along a single dimension: The amount of quantitative information they contain. There were two main types of quantitative clauses: those reporting on magnitude and those reporting on comparisons. While economy and health reporting required significantly more QR than science or politics reporting, we could not reliably differentiate the topic area based on story-level requirements for quantitative knowledge and clause-level quantitative content. Instead, we find three reliable clusters of stories based on the amounts and types of quantitative information in the news stories.

Abstract The development of the retina is under tight temporal and spatial control. To gain insights into the molecular basis of this process, we generate a single-nuclei dual-omic atlas of the human developing retina with approximately 220,000 nuclei from 14 human embryos and fetuses aged between 8 and 23-weeks post-conception with matched macular and peripheral tissues. This atlas captures all major cell classes in the retina, along with a large proportion of progenitors and cell-type-specific precursors. Cell trajectory analysis reveals a transition from continuous progression in early progenitors to a hierarchical development during the later stages of cell type specification. Both known and unrecorded candidate transcription factors, along with gene regulatory networks that drive the transitions of various cell fates, are identified. Comparisons between the macular and peripheral retinae indicate a largely consistent yet distinct developmental pattern. This atlas offers unparalleled resolution into the transcriptional and chromatin accessibility landscapes during development, providing an invaluable resource for deeper insights into retinal development and associated diseases.

Abstract Background Amyloid beta protein (Aβ) is a treatment target in Alzheimer’s Disease (AD). Lowering production of its parent protein, APP, has benefits in preclinical models. Posiphen, an orally administered small molecule, binds to an iron-responsive element in APP mRNA and decreases translation of APP and Aβ. To augment human data for Posiphen, we evaluated safety, tolerability and pharmacokinetic and pharmacodynamic (PD) effects on Aβ metabolism using Stable Isotope Labeling Kinetic (SILK) analysis. Methods Double-blind phase 1b randomized ascending dose clinical trial, at five sites, under an IRB-approved protocol. Participants with mild cognitive impairment or mild AD (Early AD) confirmed by low CSF Aβ42/40 were randomized (within each dose arm) to Posiphen or placebo. Pretreatment assessment included lumbar puncture for CSF. Participants took Posiphen or placebo for 21–23 days, then underwent CSF catheter placement, intravenous infusion of 13C6-leucine, and CSF sampling for 36 h. Safety and tolerability were assessed through participant reports, EKG and laboratory tests. CSF SILK analysis measured Aβ40, 38 and 42 with immunoprecipitation-mass spectrometry. Baseline and day 21 CSF APP, Aβ and other biomarkers were measured with immunoassays. The Mini-Mental State Exam and ADAS-cog12 were given at baseline and day 21. Results From June 2017 to December 2021, 19 participants were enrolled, randomized within dose cohorts (5 active: 3 placebo) of 60 mg once/day and 60 mg twice/day; 1 participant was enrolled and completed 60 mg three times/day. 10 active drug and 5 placebo participants completed all study procedures. Posiphen was safe and well-tolerated. 8 participants had headaches related to CSF catheterization; 5 needed blood patches. Prespecified SILK analyses of Fractional Synthesis Rate (FSR) for CSF Aβ40 showed no significant overall or dose-dependent effects of Posiphen vs. placebo. Comprehensive multiparameter modeling of APP kinetics supported dose-dependent lowering of APP production by Posiphen. Cognitive measures and CSF biomarkers did not change significantly from baseline to 21 days in Posiphen vs. placebo groups. Conclusions Posiphen was safe and well-tolerated in Early AD. A multicenter SILK study was feasible. Findings are limited by small sample size but provide additional supportive safety and PK data. Comprehensive modeling of biomarker dynamics using SILK data may reveal subtle drug effects. Trial registration NCT02925650 on clinicaltrials.gov (registered on 10-24-2016).

Abstract By early 2022, the highly transmissible Omicron variant of SARS-CoV-2 had spread across most of the world. For the first time since the pandemic began, New Zealand was experiencing high levels of community transmission of SARS-CoV-2. We enroled a cohort of households to better understand differences in transmission dynamics among subvariants of Omicron. We enroled 71 households, comprising 289 participants, and aimed to use viral genomes to gain a clearer understanding of variant-specific differences in epidemiological parameters affecting transmission dynamics. Approximately 80% of the households enroled experienced transmission of BA.2, while most of the remaining households had infections with BA.1 or BA.5. Using a logistic regression generalised linear mixed model, we found no difference in household secondary infection rate between Omicron subvariants BA.1, BA.2 and BA.5. Of the households recruited, the vast majority (92%) experienced a single chain of transmission with one inferred introduction. Further, we found that in 48% of the households studied, all household participants became infected following an index case. Most household participants tested positive within a week following an introduction, supporting the seven-day isolation requirement for household contacts that was in place in New Zealand at the time. By integrating genomic and epidemiological data, we show that viral transmission dynamics can be investigated with a higher level of granularity than with epidemiological data alone. Overall, households are a high risk setting for viral transmission in New Zealand.

The Gene Ontology (GO) knowledgebase (http://geneontology.org) is a comprehensive resource concerning the functions of genes and gene products (proteins and noncoding RNAs). GO annotations cover genes from organisms across the tree of life as well as viruses, though most gene function knowledge currently derives from experiments carried out in a relatively small number of model organisms. Here, we provide an updated overview of the GO knowledgebase, as well as the efforts of the broad, international consortium of scientists that develops, maintains, and updates the GO knowledgebase. The GO knowledgebase consists of three components: (1) the GO-a computational knowledge structure describing the functional characteristics of genes; (2) GO annotations-evidence-supported statements asserting that a specific gene product has a particular functional characteristic; and (3) GO Causal Activity Models (GO-CAMs)-mechanistic models of molecular "pathways" (GO biological processes) created by linking multiple GO annotations using defined relations. Each of these components is continually expanded, revised, and updated in response to newly published discoveries and receives extensive QA checks, reviews, and user feedback. For each of these components, we provide a description of the current contents, recent developments to keep the knowledgebase up to date with new discoveries, and guidance on how users can best make use of the data that we provide. We conclude with future directions for the project.

Measuring and identifying risk for reading difficulties at the kindergarten level is necessary for providing intervention as early as possible. The purpose of this study was to examine concurrent validity evidence of two kindergarten reading screeners, Acadience Reading and Texas Primary Reading Inventory (TPRI), as well as diagnostic accuracy at different performance levels on the Woodcock-Johnson IV (WJ IV) Reading Cluster and across (N = 96) emergent bilingual and monolingual English learners in kindergarten. Findings indicated moderate correlations between Acadience Reading and TPRI with the WJ IV. Diagnostic accuracy results showed screening measures were inadequate when predicting WJ IV performance above 90 SS (standard score), but results improved for almost all measures and student groups when the threshold for performance was lowered to 80 SS. Acadience Reading Below Benchmark (AR BB) offered the lowest overall accuracy for emerging bilingual (EB) students. Implications for efficient and accurate use of reading screeners in schools are discussed.

Background: Initial small, uncontrolled studies suggested a beneficial effect of azithromycin in individuals with COVID-19. However, subsequent studies have not confirmed its effectiveness. We assessed azithromycin usage before and during the pandemic in a national healthcare system in Qatar and the impact of implementation of evidence-based guidelines upon prescription rates. Methods: Using electronic medical records, we retrieved all azithromycin prescriptions from 2019 to 2022 at the public healthcare system in Qatar which provides over 85 % of healthcare in Qatar. Azithromycin prescription numbers and rates/100,000 population were calculated and compared over time. A course was defined as any azithromycin prescription for ≥5 days with no gap of >10 days. Courses were considered COVID-19-related if prescribed −3 to +10 days post positive SARS-CoV-2 PCR. Prescription rates before and after the pandemic, and before and after evidence-based guidelines implementation (in June 2020) were compared. Results: During the study period, 203,806 azithromycin courses were prescribed to 166,062 individuals. Overall number of courses increased in the first 2 quarters of 2020 (average 12,857/quarter in 2019 to average of 19,297 in Q1-Q2 of 2020) and then dropped to 9881/quarter over the next 6 quarters. COVID-19 related azithromycin courses peaked in.2020-Q2 (13,691) and dropped to 2836 for 2020-Q3, 1410 for 2020-Q4; 5465 for 2021-Q1, and 4288 for 2021-Q2. Stringent COVID-19 guidelines in June 2020 rapidly reduced azithromycin usage. Conclusions: Azithromycin prescriptions increased immediately after the COVID-19 pandemic, but rapidly declined immediately after implementing evidence-based guidelines.

The large water demands of tourism threaten the sector's economic viability during climate shocks. Cape Town, South Africa provides an example where the threat of a water “Day Zero” in 2018 caused substantial losses in tourist arrivals, revenues, and subsequent job securities. However, Cape Town's tourism industry also contributed to unprecedented water conservation across the city. Through qualitative analysis of semi-structured interviews with hotel employees in Cape Town (n = 18), this paper reveals how internal conservation campaigns not only reduced water use, but also helped mitigate economic impacts, eased political tensions, and upheld their excellent standing among visitors. Our results suggest that during severe water crises, hotel managers can model and enforce water conservation efforts while maintaining customer satisfaction.

Deoxynivalenol (DON), a prevalent and highly toxic mycotoxin in animal feed, poses significant risks to livestock health and productivity. This study evaluates the effectiveness of iron-manganese oxide (Fe/Mn oxides) in degrading DON. The DON degradation rate of Fe/Mn oxide reached 98.46 % in a controlled solution under specific conditions (0.2 % concentration, 37–85 °C, pH 6–7, 1-minute reaction time). When applied to actual feed, it reduced DON levels by approximately 49.3 % and remained stable in simulated gastrointestinal environments of weaned piglets. A 28-day trial involving 48 weaned piglets assessed the impacts of Fe/Mn oxides on health and growth. Results indicated that piglets consuming contaminated feed without the treatment exhibited reduced growth and compromised gut integrity, which were significantly mitigated by the addition of Fe/Mn oxides. Therefore, Fe/Mn oxides effectively reduce DON in feed and alleviate adverse health effects in piglets, making them a viable option to enhance safety and performance in mycotoxin-prone environments.

Background and aimsCannabis use is increasingly common among pregnant individuals and might be a risk factor for severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection. We aimed to test whether prenatal cannabis use is associated with increased risk of SARS-CoV-2 infection during pregnancy.DesignThis is a retrospective cohort study.SettingThe study was conducted in California, USA.ParticipantsA total of 58 114 pregnancies (with outcomes from 5 March 2020 to 30 September 2021) among 57 287 unique pregnant women aged 14-54 years who were screened for prenatal substance use, enrolled in Kaiser Permanente Northern California (KPNC) (a health-care system) and had not tested positive for COVID-19 prior to pregnancy onset.MeasurementsWe utilized data from the KPNC electronic health record. Cannabis use status (current, recently quit and non-user) was based on universal screenings during prenatal care (including urine toxicology testing and self-reported use on a self-administered questionnaire). SARS-CoV-2 infection [based on polymerase chain reaction (PCR) tests] was estimated in time-to-event analyses using Cox proportional hazard regression models adjusting for covariates. Secondary analyses examined differences in (a) SARS-CoV-2 testing rates and (b) SARS-CoV-2 infection rates among those tested.FindingsWe observed 348 810 person-months of follow-up time in our cohort with 41 064 SARS-CoV-2 PCR tests and 6% (n = 2414) of tests being positive. At the start of follow-up, 7% of pregnant individuals had current use, 12% had recently quit and 81% did not use cannabis. Adjusting for covariates, current use was associated with lower rates of SARS-CoV-2 infection [adjusted hazard ratio (aHR) = 0.60, 95% confidence interval (CI) = 0.49-0.74 than non-use. Those who had recently quit did not differ from non-cannabis users in infection rates (aHR = 0.96, 95% CI = 0.86-1.08). Sensitivity analyses among patients who received a SARS-CoV-2 test also found lower odds of infection associated with current versus no cannabis use (aOR = 0.76, CI = 0.61-0.93).ConclusionsCurrent cannabis use appears to be associated with a reduced risk of SARS-CoV-2 infection among pregnant individuals.

Abstract Background Semi-dwarfing alleles are used widely in cereals to confer improved lodging resistance and assimilate partitioning. The most widely deployed semi-dwarfing alleles in rice and barley encode the gibberellin (GA)-biosynthetic enzyme GA 20-OXIDASE2 (GA20OX2). The hexaploid wheat genome carries three homoeologous copies of GA20OX2, and because of functional redundancy, loss-of-function alleles of a single homoeologue would not be selected in wheat breeding programmes. Instead, approximately 70% of wheat cultivars carry gain-of-function mutations in REDUCED HEIGHT 1 (RHT1) genes that encode negative growth regulators and are degraded in response to GA. Semi-dwarf Rht-B1b or Rht-D1b alleles encode proteins that are insensitive to GA-mediated degradation. However, because RHT1 is expressed ubiquitously these alleles have pleiotropic effects that confer undesirable traits in some environments. Results We have applied reverse genetics to combine loss-of-function alleles in all three homoeologues of wheat GA20OX2 and its paralogue GA20OX1 and evaluated their performance in three years of field trials. ga20ox1 mutants exhibited a mild height reduction (approximately 3%) suggesting GA20OX1 plays a minor role in stem elongation in wheat. ga20ox2 mutants have reduced GA1 content and are 12–32% shorter than their wild-type segregants, comparable to the effect of the Rht-D1b ‘Green Revolution’ allele. The ga20ox2 mutants showed no significant negative effects on yield components in the spring wheat variety ‘Cadenza’. Conclusions Our study demonstrates that chemical mutagenesis can expand genetic variation in polyploid crops to uncover novel alleles despite the difficulty in identifying appropriate mutations for some target genes and the negative effects of background mutations. Field experiments demonstrate that mutations in GA20OX2 reduce height in wheat, but it will be necessary to evaluate the effect of these alleles in different genetic backgrounds and environments to determine their value in wheat breeding as alternative semi-dwarfing alleles.

Background and Aim: Feeding by-products, such as pomegranate seed pulp (PSP) and coconut meal (COC), to livestock may enhance production efficiency and increase profits. This study aimed to evaluate the effects of PSP and COC on milk production, body weight change, metabolic response (Exp. 1), digestibility, and N balance (Exp. 2). Materials and Methods: Twenty-four ewes nursing single lambs were randomly assigned to one of three diets: Control (CON) (n = 8), 7.5% PSP (n = 8), and 7.5% COC (n = 8) of dry matter (DM). Every sheep was born 3–4 days before the start of the experiment. The 1st week of the experiment was devoted to diet adaptation, while the data were collected during the following 8 weeks (Exp. 1). Nine lambs were randomly assigned to one of the three diets for intensive data collection to evaluate the diet digestibility and animal nitrogen (N) balance (Exp. 2). The data were analyzed using the MIXED SAS procedures. Results: The PSP group consumed more DM, followed by the COC and CON groups. For lambs, the final BW, total gain, and average daily gain in the PSP group were greater (p < 0.05) than those in the COC and CON groups. The CON group had lower milk output, total solids, protein, fat, and lactose levels than the PSP and COC groups (p < 0.05). The cost of milk production was lower (p < 0.05) in the PSP and COC diet groups than in the CON group. Blood serum parameters were similar among the dietary groups, except for total cholesterol and high-density lipoprotein, which were higher in the COC group than in the CON group. No differences were observed in nutrient digestibility and N balance. Conclusion: Feeding PSP and COC to nursing ewes appears beneficial because it increases milk production and pre-weaning lamb growth and reduces milk production cost.

Abstract Abberent protein-protein interactions potentiate many diseases and one example is the toxic, self-assembly of α-Synuclein in the dopaminergic neurons of patients with Parkinson’s disease; therefore, a potential therapeutic strategy is the small molecule modulation of α-Synuclein aggregation. In this work, we develop an Oligopyridylamide based 2-dimensional Fragment-Assisted Structure-based Technique to identify antagonists of α-Synuclein aggregation. The technique utilizes a fragment-based screening of an extensive array of non-proteinogenic side chains in Oligopyridylamides, leading to the identification of NS132 as an antagonist of the multiple facets of α-Synuclein aggregation. We further identify a more cell permeable analog (NS163) without sacrificing activity. Oligopyridylamides rescue α-Synuclein aggregation mediated Parkinson’s disease phenotypes in dopaminergic neurons in early and post disease Caenorhabditis elegans models. We forsee tremendous potential in our technique to identify lead therapeutics for Parkinson’s disease and other diseases as it is expandable to other oligoamide scaffolds and a larger array of side chains.

Abstract Virus-specific T cells (VST) from partially-HLA matched donors have been effective for treatment of refractory viral infections in immunocompromised patients in prior studies with a good safety profile, but rare adverse events have been described. Here we describe a unique and severe adverse event of VST therapy in an infant with severe combined immunodeficiency, who receives, as part of a clinical trial (NCT03475212), third party VSTs for treating cytomegalovirus viremia following bone marrow transplantation. At one-month post-VST infusion, rejection of graft and reversal of chimerism is observed, as is an expansion of T cells exclusively from the VST donor. Single-cell gene expression and T cell receptor profiling demonstrate a narrow repertoire of predominantly activated CD4+ T cells in the recipient at the time of rejection, with the repertoire overlapping more with that of peripheral blood from VST donor than the infused VST product. This case thus demonstrates a rare but serious side effect of VST therapy.

Platinum (Pt)-based heterogeneous catalysts show excellent performance for the electrocatalytic hydrogen evolution reaction (HER); however, the high cost and earth paucity of Pt means that efforts are being directed to reducing Pt usage, whilst maximizing catalytic efficiency. In this work, a two-step laser annealing process was employed to synthesize Pt single-atom catalysts (SACs) on a MOF-derived carbon substrate. The laser irradiation of a metal–organic framework (MOF) film (ZIF67@ZIF8 composite) by rapid scanning of a ns pulsed infrared (IR; 1064 nm) laser across the freeze-dried MOF resulted in a metal-loaded graphitized film. This was followed by loading this film with chloroplatinic acid (H2PtCl6), followed by further irradiation with an ultraviolet (UV; 355 nm) laser, resulting in pyrolysis of H2PtCl6 to form the SAC, along with a further reduction of the MOF to form a Pt-decorated laser-induced annealed MOF (Pt-LIA-ZIF8@ZIF67). The Pt-LIA-ZIF8@ZIF67 catalyst with a Pt loading of 0.86 wt. % exhibited exceptionally high activity for the HER in acidic conditions. The atomically dispersed Pt on the carbon substrate exhibited a small overpotential of 68.8 mV at 10 mA cm−2 for the hydrogen evolution reaction with a mass activity 20.52 times that of a commercial Pt/C catalyst at an overpotential of 50 mV vs. RHE. Finally, we note that the synthesis method is simple, fast, and versatile, and potentially scalable for the mass production of SACs for electrocatalytic applications.

Background: Nature-based and other outdoor virtual reality (VR) experiences in head-mounted displays (HMDs) offer powerful, non-pharmacological tools for hospice teams to help patients undergoing end-of-life (EOL) transitions. However, the psychological distress of the patient-caregiver dyad is interconnected and highlights the interdependence and responsiveness to distress as a unit. Hospice care services and healthcare need strategies to help patients and informal caregivers with EOL transitions. Methods: Our study uses the synchronized Tandem VR TM approach where patient-caregiver dyads experience immersive nature-based and other outdoor VR content. This mixed methods study will recruit 20 patient-caregiver dyads (N = 40) enrolled in home hospice services nearing EOL. Dyads will experience a personalized nature-based and other outdoor VR experience lasting 5–15 min. Self-reported questionnaires and semi-structured interviews will be collected pre/post the VR intervention to identify the impacts of Tandem VR TM experiences on the QOL, pain, and fear of death in patient-caregiver dyads enrolled with hospice services. Additionally, this protocol will determine the acceptance of Tandem VR TM experiences by dyads as a non-pharmacological modality for addressing patient and caregiver needs. Acceptance will be quantified by the number of dyads accepting or declining the VR experience during recruitment. Discussion: Using personalized, nature-based and other outdoor VR content, the patient-caregiver dyads can simultaneously engage in an immersive encounter may help alleviate symptoms associated with declining health and EOL phases for the patient and the often overburdened caregiver. This protocol focuses on meeting the need for person-centered, non-pharmacological interventions to reduce physical, psychological, and spiritual distress. Trial registration: NCT06186960.

Introduction: Targeted single nucleotide polymorphisms (SNPs) have been used in genomic prediction methodologies to enhance the accuracy of associated genetic transmitting abilities in Holstein cows. The objective of this study was to identify and validate SNPs associated with fertility traits impacting early embryo mortality.Methods: The mRNA sequencing data from day 16 normal (n = 9) and embryo mortality (n = 6) conceptuses from lactating multiparous Holstein cows were used to detect SNPs. The selection of specific genes with SNPs as preliminary candidates was based on associations with reproductive and fertility traits. Validation of candidate SNPs and genotype-to-phenotype analyses were conducted in a separate cohort of lactating primiparous Holstein cows (n = 500). After genotyping, candidate SNPs were filtered using a quality control pipeline via PLINK software. Continuous numeric and binary models from reproductive traits were evaluated using the mixed procedure for a generalized linear model-one way ANOVA or logistic regression, respectively.Results: Sixty-nine candidate SNPs were initially identified, but only 23 passed quality control procedures. Ultimately, the study incorporated 466 observations for statistical analysis after excluding animals with missing genotypes or phenotypes. Significant (p

Identifying an integrative framework that could appropriately delineate underlying mechanisms and individual risk/protective factors for human health has remained elusive. Evolutionary mismatch theory provides a comprehensive, integrative model for understanding the underlying causes and mechanisms of a wide range of modern health and well-being problems, ranging from obesity to depression. Despite growing interest regarding its importance though, no psychometrically-sound measure of evolutionary mismatch yet exists to facilitate research and intervention. To construct such a scale, aimed at gauging individual differences in the extent to which people's modern lifestyles are mismatched with ancestral conditions, we conducted four studies (a pilot study, followed by 3 main studies, with a final sample of 1901 participants across the main studies). Results from exploratory and confirmatory factor analyses have produced a 36-item evolutionary mismatched lifestyle scale (EMLS) with 7 subdomains of mismatched behaviours (e.g., diet, physical activity, relationships, social media use) that is psychometrically sound. Further, the EMLS is associated with physical, mental and subjective health. We explore the potential of the EMLS as a tool for examining interpersonal and cultural variations in health and wellbeing, while also discussing the limitations of the scale and future directions in relation to further psychometric examinations.

Multiple sclerosis (MS) is a prototypical autoimmune disease of the central nervous system (CNS). In addition to CD4+ T cells, memory B cells are now recognized as a critical cell type in the disease. This is underlined by the fact that the best-characterized environmental risk factor for MS is the Epstein-Barr virus (EBV), which can infect and persist in memory B cells throughout life. Several studies have identified changes in anti-EBV immunity in patients with MS. Examples include elevated titers of anti-EBV nuclear antigen 1 (EBNA1) antibodies, interactions of these with the MS-associated HLA-DR15 haplotype, and molecular mimicry with MS autoantigens like myelin basic protein (MBP), anoctamin-2 (ANO2), glial cell adhesion molecule (GlialCAM), and alpha-crystallin B (CRYAB). In this study, we employ a simple in vitro assay to examine the memory B cell antibody repertoire in MS patients and healthy controls. We replicate previous serological data from MS patients demonstrating an increased secretion of anti-EBNA1380-641 IgG in cell culture supernatants, as well as a positive correlation of these levels with autoantibodies against GlialCAM262-416 and ANO21-275. For EBNA1380-641 and ANO21-275, we provide additional evidence suggesting antibody cross-reactivity between the two targets. Further, we show that two efficacious MS treatments – natalizumab (NAT) and autologous hematopoietic stem cell transplantation (aHSCT) – are associated with distinct changes in the EBNA1-directed B cell response and that these alterations can be attributed to the unique mechanisms of action of these therapies. Using an in vitro system, our study confirms MS-associated changes in the anti-EBNA1 memory B cell response, EBNA1380-641 antibody cross-reactivity with ANO21-275, and reveals treatment-associated changes in the immunoglobulin repertoire in MS.

IntroductionThis article examines athletes preparing for, transitioning into, or going through the developmental stages of a professional sports career, referred to as the emerging athlete career transition. This transition includes events such as selections, Junior-to-Senior promotions, contracting, migration, and early exits. The article presents the collective findings of a multi-case study in three professional sports: rugby league, basketball, and boxing.MethodConsistent with pragmatic qualitative research methodology, a stratified data set was collected and analysed, incorporating researcher-practitioner fieldwork, interviews, documents and artefacts for these cases. This article explores unique events and the demographic and cultural implications of navigating emergent transitions along professional sporting pathways in New Zealand.FindingsThese findings highlight the importance of building self-efficacy as a pre-condition for coping through preparation and experience.RecommendationsRecommendations include fostering collaborative cultures and authentic support relationships to facilitate better coping alongside athletic and personal development in these high-pressured environments. Furthermore, understanding existential perspectives of meaning, choice, and responsibility provides insights for developing the resources that allow emerging athletes to thrive in life beyond sport.

BackgroundThe geographical environments within which individuals conduct their daily activities may influence health behaviors, yet little is known about individual-level geographic mobility and specific, linked behaviors in rural low- and middle-income settings. ObjectiveNested in a 3-month ecological momentary assessment intervention pilot trial, this study aims to leverage mobile health app user GPS data to examine activity space through individual spatial mobility and locations of reported health behaviors in relation to their homes. MethodsPilot trial participants were recruited from the Rakai Community Cohort Study—an ongoing population-based cohort study in rural south-central Uganda. Participants used a smartphone app that logged their GPS coordinates every 1-2 hours for approximately 90 days. They also reported specific health behaviors (alcohol use, cigarette smoking, and having condomless sex with a non–long-term partner) via the app that were both location and time stamped. In this substudy, we characterized participant mobility using 3 measures: average distance (kilometers) traveled per week, number of unique locations visited (deduplicated points within 25 m of one another), and the percentage of GPS points recorded away from home. The latter measure was calculated using home buffer regions of 100 m, 400 m, and 800 m. We also evaluated the number of unique locations visited for each specific health behavior, and whether those locations were within or outside the home buffer regions. Sociodemographic information, mobility measures, and locations of health behaviors were summarized across the sample using descriptive statistics. ResultsOf the 46 participants with complete GPS data, 24 (52%) participants were men, 30 (65%) participants were younger than 35 years, and 33 (72%) participants were in the top 2 socioeconomic status quartiles. On median, participants traveled 303 (IQR 152-585) km per week. Over the study period, participants on median recorded 1292 (IQR 963-2137) GPS points—76% (IQR 58%-86%) of which were outside their 400-m home buffer regions. Of the participants reporting drinking alcohol, cigarette smoking, and engaging in condomless sex, respectively, 19 (83%), 8 (89%), and 12 (86%) reported that behavior at least once outside their 400-m home neighborhood and across a median of 3.0 (IQR 1.5-5.5), 3.0 (IQR 1.0-3.0), and 3.5 (IQR 1.0-7.0) unique locations, respectively. ConclusionsAmong residents in rural Uganda, an ecological momentary assessment app successfully captured high mobility and health-related behaviors across multiple locations. Our findings suggest that future mobile health interventions in similar settings can benefit from integrating spatial data collection using the GPS technology in mobile phones. Leveraging such individual-level GPS data can inform place-based strategies within these interventions for promoting healthy behavior change.

Summary: The studies reported here focus on the impact of pre-existing CD4 T cell immunity on the first encounter with SARS-CoV-2. They leverage PBMC samples from plasma donors collected after a first SARS-CoV-2 infection, prior to vaccine availability and compared to samples collected prior to the emergence of SARS-CoV-2. Analysis of CD4 T cell specificity across the entire SARS-CoV-2 proteome revealed that the recognition of SARS-CoV-2-derived epitopes by CD4 memory cells prior to the pandemic are enriched for reactivity toward non-structural proteins conserved across endemic CoV strains. However, CD4 T cells after primary infection with SARS-CoV-2 focus on epitopes from structural proteins. We observed little evidence for preferential recall to epitopes conserved between SARS-CoV-2 and seasonal CoV, a finding confirmed through use of selectively curated conserved and SARS-unique peptides. Our data suggest that SARS-CoV-2 CD4 T cells elicited by the first infection are primarily established from the naive CD4 T cell pool.

The field of school psychology continues to further embrace a social justice perspective to address systemic racism, privilege, prejudice, and discrimination. To accomplish this mission, school psychologists must ensure that there is a solid literature base that is inclusive and representative of students from minoritized backgrounds. A review of student sociodemographic characteristics was conducted of all articles in four of the primary journals of school psychology from 2010 to 2019 (n = 1,213 articles). Compared to national estimates of school-age sociodemographic distributions, researchers tended to include samples more representative of students identifying as White/Caucasian and underrepresentative of students from low-income backgrounds. Authors rarely included or described participants' sexual orientations and gender identities beyond the binary (female/male). We provide a discussion and recommendations for improving the inclusivity of students from minoritized backgrounds in future school psychology research.

Abstract The optokinetic reflex (OKR) serves as a vital index for visual system development in early life, commonly observed within the first six months post-birth in humans. Zebrafish larvae offer a robust and convenient model for OKR studies due to their rapid development and manageable size. Existing OKR assays often involve cumbersome setups and offer limited portability. In this study, we present an innovative OKR assay that leverages the flexible screen of the Samsung Galaxy Z Flip to optimize setup and portability. We conducted paired slow-phase velocity measurements in 5-day post-fertilization (dpf) zebrafish larvae (n = 15), using both the novel flip-phone-based assay and a traditional liquid–crystal display (LCD) arena. Utilizing Bland–Altman plots, we assessed the agreement between the two methods. Both assays were efficacious in eliciting OKR, with eye movement analysis indicating high tracking precision in the flip-phone-based assay. No statistically significant difference was observed in slow-phase velocities between the two assays (p = 0.40). Our findings underscore the feasibility and non-inferiority of the flip-phone-based approach, offering streamlined assembly, enhanced portability, and the potential for cost-effective alternatives. This study contributes to the evolution of OKR assay methodologies, aligning them with emerging research paradigms.

Abstract Background Cognitive decline in Alzheimer’s disease (AD) is associated with hyperphosphorylated tau (pTau) propagation between neurons along synaptically connected networks, in part via extracellular vesicles (EVs). EV biogenesis is triggered by ceramide enrichment at the plasma membrane from neutral sphingomyelinase2 (nSMase2)-mediated cleavage of sphingomyelin. We report, for the first time, that human tau expression elevates brain ceramides and nSMase2 activity. Methods To determine the therapeutic benefit of inhibiting this elevation, we evaluated PDDC, the first potent, selective, orally bioavailable, and brain-penetrable nSMase2 inhibitor in the transgenic PS19 AD mouse model. Additionally, we directly evaluated the effect of PDDC on tau propagation in a mouse model where an adeno-associated virus (AAV) encoding P301L/S320F double mutant human tau was stereotaxically-injected unilaterally into the hippocampus. The contralateral transfer of the double mutant human tau to the dentate gyrus was monitored. We examined ceramide levels, histopathological changes, and pTau content within EVs isolated from the mouse plasma. Results Similar to human AD, the PS19 mice exhibited increased brain ceramide levels and nSMase2 activity; both were completely normalized by PDDC treatment. The PS19 mice also exhibited elevated tau immunostaining, thinning of hippocampal neuronal cell layers, increased mossy fiber synaptophysin immunostaining, and glial activation, all of which were pathologic features of human AD. PDDC treatment reduced these changes. The plasma of PDDC-treated PS19 mice had reduced levels of neuronal- and microglial-derived EVs, the former carrying lower pTau levels, compared to untreated mice. In the tau propagation model, PDDC normalized the tau-induced increase in brain ceramides and significantly reduced the amount of tau propagation to the contralateral side. Conclusions PDDC is a first-in-class therapeutic candidate that normalizes elevated brain ceramides and nSMase2 activity, leading to the slowing of tau spread in AD mice.