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Abstract Polycystic kidney disease (PKD) is a genetic disorder characterized by bilateral cyst formation. We showed that PKD cells and kidneys display metabolic alterations, including the Warburg effect and glutaminolysis, sustained in vitro by the enzyme asparagine synthetase (ASNS). Here, we used antisense oligonucleotides (ASO) against Asns in orthologous and slowly progressive PKD murine models and show that treatment leads to a drastic reduction of total kidney volume (measured by MRI) and a prominent rescue of renal function in the mouse. Mechanistically, the upregulation of an ATF4–ASNS axis in PKD is driven by the amino acid response (AAR) branch of the integrated stress response (ISR). Metabolic profiling of PKD or control kidneys treated with Asns-ASO or Scr-ASO revealed major changes in the mutants, several of which are rescued by Asns silencing in vivo. Indeed, ASNS drives glutamine-dependent de novo pyrimidine synthesis and proliferation in cystic epithelia. Notably, while several metabolic pathways were completely corrected by Asns-ASO, glycolysis was only partially restored. Accordingly, combining the glycolytic inhibitor 2DG with Asns-ASO further improved efficacy. Our studies identify a new therapeutic target and novel metabolic vulnerabilities in PKD.

Situational factors can influence cognitive performance and should be considered for conducting cognitive assessments. The objective of this project was to develop a checklist for Cognitive Assessment Requirements (CARE) to identify these situational factors before conducting cognitive assessments and account for them. This study employed a four-round Delphi approach involving 22 experts to identify situational factors that can impact cognitive assessment results. The development of a robust and well-balanced checklist was guided by a consensus-driven approach, which considered metrics such as Interquartile Deviation (IQD) (> 1.00), Percentage of Positive Responses (PPR, above 60%), and mean importance ratings (< 3 on a 5-point Likert scale) to assess both degree of agreement and item importance. Consensus was reached, leading to a 14-item checklist to evaluate cognitive assessment requirements. These items were categorized into six groups: Acute Illness or Physical Discomfort, Medication Effects and Substance Use, Sleep Quality and Fatigue, Emotional State, Language factors, and Environmental factors. The CARE can be employed prior to cognitive assessments to identify situational factors of relevance to the individual client, thereby creating a more favorable environment for cognitive evaluation, and enhancing the reliability of the assessment findings. Furthermore, the CARE can help determine the level of confidence in the results by assessing whether the conditions are conducive to testing or if situational factors may undermine the validity of the evaluation. [ABSTRACT FROM AUTHOR]

Many human diseases are the result of early developmental defects. As most paediatric diseases and disorders are rare, children are critically underrepresented in research. Functional genomics studies primarily rely on adult tissues and lack critical cell states in specific developmental windows. In parallel, little is known about the conservation of developmental programmes across non-human primate (NHP) species, with implications for human evolution. Here we introduce the developmental Genotype-Tissue Expression (dGTEx) projects, which span humans and NHPs and aim to integrate gene expression, regulation and genetics data across development and species. The dGTEx cohort will consist of 74 tissue sites across 120 human donors from birth to adulthood, and developmentally matched NHP age groups, with additional prenatal and adult animals, with 126 rhesus macaques (Macaca mulatta) and 72 common marmosets (Callithrix jacchus). The data will comprise whole-genome sequencing, extensive bulk, single-cell and spatial gene expression profiles, and chromatin accessibility data across tissues and development. Through community engagement and donor diversity, the human dGTEx study seeks to address disparities in genomic research. Thus, dGTEx will provide a reference human and NHP dataset and tissue bank, enabling research into developmental changes in expression and gene regulation, childhood disorders and the effect of genetic variation on development.The developmental Genotype-Tissue Expression (dGTEx) projects will catalogue and integrate gene expression, regulation and genetics data across 120 human donors from birth to adulthood with developmentally matched non-human primates, including 126 rhesus macaques and 72 common marmosets. [ABSTRACT FROM AUTHOR]

The impacts of climate change on human health are often underestimated or perceived to be in a distant future. Here, we present the projected impacts of climate change in the context of COVID-19, a recent human health catastrophe. We compared projected heat mortality with COVID-19 deaths in 38 cities worldwide and found that in half of these cities, heat-related deaths could exceed annual COVID-19 deaths in less than ten years (at + 3.0 °C increase in global warming relative to preindustrial). In seven of these cities, heat mortality could exceed COVID-19 deaths in less than five years. Our results underscore the crucial need for climate action and for the integration of climate change into public health discourse and policy. [ABSTRACT FROM AUTHOR]

Purpose of Review: Air pollution has been raised as a novel risk factor for osteoporosis, which impose a huge burden on both individuals and society. Thus, summarizing and discussing previous results on the association between ambient air pollution and osteoporosis can be informative in synthesizing the current evidence and improving relevant action plans. Recent findings: Recent studies reported that long-term exposure to ambient air pollution is associated with an increased risk of osteoporosis and related outcomes; however, the studied populations, air pollutants, areas, and results on high-risk populations are heterogeneous. Among air pollutants, long-term exposure to PM2.5 showed an association with osteoporosis or osteoporosis-related fracture in general. Summary: Recent scientific evidence indicates that ambient air pollution is a potential risk factor for osteoporosis and related outcomes. Further research is warranted on how air pollution impacts these outcomes including for high-risk populations with consistent effect modifiers, and analytic methodologies. [ABSTRACT FROM AUTHOR]

Prenatal alcohol exposure (PAE) is the leading known cause of birth defects and cognitive disabilities, with impacts on brain development and executive functioning. Abnormalities in structural and functional brain features are well-documented in children with PAE, but the effects of PAE on brain metabolism in children have received less attention. Levels of brain metabolites can be measured non-invasively using magnetic resonance spectroscopy (MRS). Here, we present the first study of PAE-related brain metabolite differences in early childhood (ages 3–8 years) and their associations with cognitive performance, including executive functioning (EF) and pre-reading skills. We measured metabolites in two cohorts of children with PAE and unexposed children using MRS in the anterior cingulate cortex (ACC; cohort 1) and left temporo-parietal cortex (LTP; cohort 2). Total choline (tCho), a marker of membrane/myelin metabolism, was elevated in both regions in children with PAE compared to unexposed children, and glutamate + glutamine (Glx), a marker of excitability, was elevated in the ACC. The PAE group exhibited more difficulties with EF, and higher tCho was associated with better EF in both PAE and unexposed groups. In addition, elevated Glx in the ACC was associated with poorer inhibitory control within the PAE group only. LTP metabolites were not significantly associated with pre-reading skills in PAE or unexposed groups. Together, these findings point to altered membrane metabolism and excitability in young children with PAE. These findings provide new insight to potential mechanisms by which PAE disrupts brain development and cognitive functioning in early childhood. [ABSTRACT FROM AUTHOR]

Introduction: The present meta-analysis compared the efficacy of intra-articular hyaluronic acid (HA) injections in patients with early to mild knee osteoarthritis (OA) (Kellgren Lawrence I–II) versus other commonly injected biologically active compounds using patient-reported outcome measures (PROMs). The outcomes of interest were the visual analogue scale (VAS) and the Western Ontario McMaster Osteo-Arthritis Index (WOMAC) scores. Methods: This study was conducted according to the 2020 PRISMA statement. In April 2024, PubMed, Web of Science, Google Scholar, and Embase were accessed without time constraints. All the randomised controlled trials (RCTs) investigating the efficacy of intra-articular HA injections in the early stages of knee OA were accessed. Data concerning the VAS, WOMAC, and related subscales were collected at baseline and the last follow-up. Only studies clearly stated the degrees of advancement of OA using the Kellgren-Lawrence scoring system were used. Results: The literature search resulted in four RCTs (390 patients). The mean length of the last follow-up was 7.5 ± 3.0 months. 72.3% (282 of 390) of the patients were women. The mean age of the patients was 58.1 ± 3.2 years, and the mean BMI was 27.3 ± 3.2 kg/m2. At the last follow-up, no difference was found between HA and the control group in VAS, WOMAC, and related subscales. Conclusion: In patients with early to mild knee osteoarthritis, the current level of evidence suggests that intra-articular injections using HA performed similarly to other biologically active compounds commonly injected in the knee joint for a minimum of three months. Level of evidence: Level I, meta-analysis. [ABSTRACT FROM AUTHOR]

A new one-parameter distribution is proposed for circular data based on wrapping. Most distributions constructed via wrapping do not yield elementary expressions for their mathematical properties. Yet the new distribution yields elementary expressions for all of its mathematical properties. Better fits of the new distribution over the three-parameter distribution due to Jones and Pewsey10 and six other wrapped distributions including four that have two parameters each are shown for at least two data sets. Better fits were assessed in terms of probability plots, density plots, values of Akaike information criterion and values of Bayesian information criterion. [ABSTRACT FROM AUTHOR]

The NADPH/NADP+ redox couple is central to metabolism and redox signalling. NADP redox state is differentially regulated by distinct enzymatic machineries at the subcellular compartment level. Nonetheless, a detailed understanding of subcellular NADP redox dynamics is limited by the availability of appropriate tools. Here, we introduce NAPstars, a family of genetically encoded, fluorescent protein-based NADP redox state biosensors. NAPstars offer real-time, specific measurements, across a broad-range of NADP redox states, with subcellular resolution. NAPstar measurements in yeast, plants, and mammalian cell models, reveal a conserved robustness of cytosolic NADP redox homoeostasis. NAPstars uncover cell cycle-linked NADP redox oscillations in yeast and illumination- and hypoxia-dependent NADP redox changes in plant leaves. By applying NAPstars in combination with selective impairment of the glutathione and thioredoxin antioxidative pathways under acute oxidative challenge, we find an unexpected and conserved role for the glutathione system as the primary mediator of antioxidative electron flux. This article presents NAPstars, a family of genetically-encoded biosensors that enable real-time monitoring of NADP redox dynamics across species. The sensors reveal robust NADP redox regulation, cell-cycle-linked NADP oscillations, and glutathione as the major conduit for anti-oxidative electron flux. [ABSTRACT FROM AUTHOR]

There have been frequent reports of more than one strain of the nitrogen-fixing symbiont, Frankia, in the same root nodule of plants in the genus Alnus, but quantitative assessments of their relative contributions have not been made to date. Neither has the diversity of other microbes, having potential functional roles in symbiosis, been systematically evaluated. Alnus rubra root nodule microbiota were studied using Illumina short read sequencing and kmer-based read classification. Single end 76 bp sequencing was done to a median depth of 96 million reads per sample. Reads were assigned to taxa using KrakenUniq, with taxon abundances being estimated using its companion program Bracken. This was the first high resolution study of Alnus root nodules using next generation sequencing (NGS), quantifying multiple Cluster 1 A Frankia strains in single nodules, and in some cases, a Cluster 4 strain. Root nodules were found to contain diverse bacteria, including several genera containing species known to have growth-promoting effects. Evidence was found for partitioning of some bacterial strains in older versus younger lobes. [ABSTRACT FROM AUTHOR]

Background: The 100,000 Genomes Project established infrastructure for Whole Genome Sequencing (WGS) in the United Kingdom. Methods: A retrospective study of cancer patients recruited to the 100,000 Genomes Project by the West Midlands Genomics Medicine Centre, evaluating clinical relevance of results. Results: After excluding samples with no sequencing data (1678/4851; 34.6%), 3166 sample sets (germline and somatic) from 3067 participants were sequenced. Results of 1256 participants (41.0%) were interpreted (excluding participants who died (308/3067; 10.0%) or were clinically excluded (1503/3067; 49.0%)). Of these, 323 (25.7%) had no variants in genes which may alter management (Domain 1 genes). Of the remaining 933 participants, 552 (59.2%) had clinical recommendations made (718 recommendations in total). These included therapeutic recommendations (377/933; 40.4%), such as clinical trial, unlicensed or licensed therapies or high TMB recommendations, and germline variants warranting clinical genetics review (85/933; 9.1%). At the last follow up, 20.2% of all recommendations were followed (145/718). However, only a small proportion of therapeutic recommendations were followed (5.1%, 25/491). Conclusions: The 100,000 Genomes Project has established infrastructure and regional experience to support personalised cancer care. The majority of those with successful sequencing had actionable variants. Ensuring GTAB recommendations are followed will maximise benefits for patients. [ABSTRACT FROM AUTHOR]

Anti-disialoganglioside (GD2) antibody therapy has provided clinical benefit to patients with neuroblastoma however efficacy is likely impaired by the immunosuppressive tumor microenvironment. We have previously defined a link between intratumoral copper levels and immune evasion. Here, we report that adjuvant copper chelation potentiates anti-GD2 antibody therapy to confer durable tumor control in immunocompetent models of neuroblastoma. Mechanistic studies reveal copper chelation creates an immune-primed tumor microenvironment through enhanced infiltration and activity of Fc-receptor-bearing cells, specifically neutrophils which are emerging as key effectors of antibody therapy. Moreover, we report copper sequestration by neuroblastoma attenuates neutrophil function which can be successfully reversed using copper chelation to increase pro-inflammatory effector functions. Importantly, we repurpose the clinically approved copper chelating agent Cuprior as a non-toxic, efficacious immunomodulatory strategy. Collectively, our findings provide evidence for the clinical testing of Cuprior as an adjuvant to enhance the activity of anti-GD2 antibody therapy and improve outcomes for patients with neuroblastoma. Anti-disialoganglioside (GD2) antibody therapy has proven beneficial to neuroblastoma patients and intra-tumoral copper levels have been associated with immune evasion. Here the authors show that copper chelation potentiates anti-GD2 immunotherapy through improved infiltration and function of Fc receptor bearing neutrophils. [ABSTRACT FROM AUTHOR]

Iron homoeostasis is tightly regulated, with hepcidin and soluble transferrin receptor (sTfR) playing significant roles. However, the genetic determinants of these traits and the biomedical consequences of iron homoeostasis variation are unclear. In a meta-analysis of 12 cohorts involving 91,675 participants, we found 43 genomic loci associated with either hepcidin or sTfR concentration, of which 15 previously unreported. Mapping to putative genes indicated involvement in iron-trait expression, erythropoiesis, immune response and cellular trafficking. Mendelian randomisation of 292 disease outcomes in 1,492,717 participants revealed associations of iron-related loci and iron status with selected health outcomes across multiple domains. These associations were largely driven by HFE, which was associated with the largest iron variation. Our findings enhance understanding of iron homoeostasis and its biomedical consequences, suggesting that lifelong exposure to higher iron levels is likely associated with lower risk of anaemia-related disorders and higher risk of genitourinary, musculoskeletal, infectious and neoplastic diseases. The largest meta-analysis of GWASs of hepcidin and sTfR identified 43 genomic loci, of which 15 new. Mendelian randomisation revealed associations of systemic iron status and iron-related loci with selected health outcomes across multiple domains. [ABSTRACT FROM AUTHOR]

Microbes can be engineered to sense target chemicals for environmental and geospatial detection. However, when engineered microbes operate in real-world environments, it remains unclear how competition with natural microbes affect their performance over long time periods. Here, we engineer sensors and memory-storing genetic circuits inside the soil bacterium Bacillus subtilis to sense the TNT explosive and maintain a long-term response, using predictive models to design riboswitch sensors, tune transcription rates, and improve the genetic circuit's dynamic range. We characterize the autonomous microbial sensor's ability to detect TNT in a natural soil system, measuring single-cell and population-level behavior over a 28-day period. The autonomous microbial sensor activates its response by 14-fold when exposed to low TNT concentrations and maintains stable activation for over 21 days, exhibiting exponential decay dynamics at the population-level with a half-life of about 5 days. Overall, we show that autonomous microbial sensors can carry out long-term detection of an important chemical in natural soil with competitive growth dynamics serving as additional biocontainment. Engineered microbes can detect harmful chemicals, but may not work well in complex environments. Here, the authors built microbial sensors for detection of TNT explosive and tested their response over 28 days in contaminated soil with many natural microbes, achieving stable detection for 21 days. [ABSTRACT FROM AUTHOR]

For a lattice path ν from the origin to a point (a, b) using steps E = (1 , 0) and N = (0 , 1) , we construct an associated flow polytope F G ^ B (ν) arising from an acyclic graph where bidirectional edges are permitted. We show that the flow polytope F G ^ B (ν) admits a subdivision dual to a (w - 1) -simplex, where w is the number of valleys in the path ν ¯ = E ν N . Refinements of this subdivision can be obtained by reductions of a polynomial P ν in a generalization of Mészáros' subdivision algebra for acyclic root polytopes where negative roots are allowed. Via an integral equivalence between F G ^ B (ν) and the product of simplices Δ a × Δ b , we thereby obtain a subdivision algebra for a product of two simplices. As a special case, we give a reduction order for reducing P ν that yields the cyclic ν -Tamari complex of Ceballos, Padrol, and Sarmiento. [ABSTRACT FROM AUTHOR]

Ceruminous glands are modified apocrine glands, situated in the external auditory canal (EAC) that, together with sebaceous glands, produce cerumen. The neoplastic transformation of these structures is exceedingly rare. We encounter two cases of EAC adenocarcinoma with ETV6::NTRK3 fusion. Despite this genetic overlap, the morphology and immunophenotype delineate its clear separation from secretory carcinoma. These cases demonstrate novel primary EAC adenocarcinoma with papillary morphology, which expands the ever-increasing list of ETV6::NTRK3-positive malignancies and which we would like to term ETV6::NTRK3-translocation associated papillary adenocarcinoma. We also advocate the use of molecular techniques in rare tumors of uncertain type or differentiation, to increase understanding and possibilities of reproducible classification of these rare neoplasms. Pathologists and oncologists should recognize this entity, which leads to a direct approach for detecting NTRK fusion for appropriate treatment. [ABSTRACT FROM AUTHOR]

Suicide screening is critical in pediatric emergency departments (EDs). Behavioral measures of suicide risk may complement self-report measures. The current study examines suicide-specific behavioral measures and tests their potential short-term within-person effects among respondents, ability to discriminate future suicide attempt from suicidal ideation, and translation into interpretable categorical composite scores. The sample included 167 youth (10–17 years), presenting for suicide-related reasons to a pediatric psychiatric ED. During their ED visit, participants completed the Death/Life Implicit Association Test (IAT) and the Suicide Stroop Task. Recurrent suicidal thoughts and attempts were assessed within 6 months of the ED visit via medical records and email surveys. Youth displayed a decrease in the levels of distress and self-injurious desires (negative mood, desire to hurt themselves, and desire to die) after completing the behavioral tasks. The Death/Life IAT prospectively differentiated with 68% accuracy between youth who attempted suicide after their ED visit and those who had suicidal ideation but no attempt, p = 0.04, OR = 5.65, although this effect became marginally significant after controlling for self-report and demographic covariates. Neither the Suicide Stroop Task, nor the categorical composite scores predicted suicide attempts, ps = 0.08–0.87, ORs = 0.96–3.95. Behavioral measures of suicide risk administered in the ED do not appear to increase distress or self-injurious desires. They may be able to distinguish those who go on to attempt suicide (vs. consider suicide) within six months after discharge. [ABSTRACT FROM AUTHOR]

This phenomenological study explored the lived experiences of six Black women who survived Intimate Partner Violence (IPV) through the frameworks of Toxic Black Femininity (TBF), Post-Traumatic Slave Syndrome, and Intersectionality to understand how coping with ongoing systemic racism influences meaning making of IPV experiences and help-seeking behaviors. Participants discussed how narratives within Black families and churches influenced how they coped with the trauma symptoms resulting from their IPV victimization and navigate relationships now. Specifically, participants' experience of TBF and associated adherence to racial and gendered norms and stereotypes showed up as: 1) a felt pressure to portray strength, 2) rationalize the abuse, 3) advocate for their partner's needs but not their own, and 4) blame themselves for the abuse. Further, when participants sought help, they: 1) avoided actions that could lead to police involvement due to fear of police brutality against their male partners, 2) had their hurt minimized due to white expectations of Blackness, 3) heard narratives from family and religious systems that reinforced TBF and their decision to stay in the harmful relationship, and 4) turned their frustrations with the lack of helpful support systems into advocacy. These findings highlight the intergenerational transmission of survival skills and narratives that have been passed down to Black women since the time of slavery and how systemic racism and TBF keep these narratives in play. [ABSTRACT FROM AUTHOR]

Purpose: Low-value care is common in intensive care units (ICUs), unnecessarily exposing patients to risks and harms, incuring costs to the patient and healthcare system, and contributing to healthcare's carbon footprint. We aimed to identify, collate, and summarise published evidence on the impact of interventions to reduce low-value care in ICUs. Methods: We searched MEDLINE, Embase, and Cochrane CENTRAL from inception to 22 September 2023 for evaluations of interventions aiming to reduce low-value care, supplemented by reference lists and recently published articles. We recorded impacts on the low-value target, health outcomes, resource use, cost, and the environment. Results: From 1155 studies screened, 32 eligible studies were identified evaluating interventions to reduce: routine blood testing (n = 13), routine chest X-rays (n = 10), and other types (or multiple types) of low-value care (n = 9). All but 3 of the interventions found reductions in the immediate low-value care target (usually the primary outcome). Although the small sample size of most included studies, limited their ability to detect impacts on other outcomes, many interventions were also associated with improved health outcomes and financial savings. The only study that reported environmental impacts found the intervention was associated with reduced carbon dioxide equivalent (CO2-e) emissions. Conclusions: Interventions to reduce low-value care in ICUs may have important health, financial, and environmental co-benefits. Further research may inform wider scale-up and sustainability of successful strategies to decrease low-value healthcare. More empirical evidence on potential environmental benefits may inform policies to lower healthcare's carbon footprint. [ABSTRACT FROM AUTHOR]

Blood transcriptional biomarkers of acute viral infections typically reflect type 1 interferon (IFN) signalling, but it is not known whether there are biological differences in their regulation that can be leveraged for distinct translational applications. We use high frequency sampling in the SARS-CoV-2 human challenge model to show induction of IFN-stimulated gene (ISG) expression with different temporal and cellular profiles. MX1 gene expression correlates with a rapid and transient wave of ISG expression across all cell types, which may precede PCR detection of replicative infection. Another ISG, IFI27, shows a delayed but sustained response restricted to myeloid cells, attributable to gene and cell-specific epigenetic regulation. These findings are reproducible in experimental and naturally acquired infections with influenza, respiratory syncytial virus and rhinovirus. Blood MX1 expression is superior to IFI27 expression for diagnosis of early infection, as a correlate of viral load and for discrimination of virus culture positivity. Therefore, MX1 expression offers potential to stratify patients for antiviral therapy or infection control interventions. Blood IFI27 expression is superior to MX1 expression for diagnostic accuracy across the time course of symptomatic infection and thereby, offers higher diagnostic yield for respiratory virus infections that incur a delay between transmission and testing. It's not always clear whether blood biomarkers are differentially expressed in the time course of viral infections. In this SARS-CoV-2 human challenge study, the authors identify distinct single-gene blood transcriptional biomarkers for early stages of infection or for symptomatic infection. [ABSTRACT FROM AUTHOR]

Previous research suggests that even when people are capable of judging to the best of their knowledge whether claims are accurate or inaccurate, they do not sufficiently discriminate between accurate and inaccurate information when asked to consider whether they would share stories on social media. However, question framing ("To the best of your knowledge...", "Would you consider...?") differed between the questions about accuracy and the questions about sharing. Here we examine the effects of question framing on responses to accuracy questions and responses to sharing questions. The framing of accuracy questions had no effect on accurate-inaccurate discrimination. In contrast, accurate-inaccurate discrimination in response to sharing questions increased when participants were asked to respond, to the best of their knowledge, whether they would share claims compared to when they were asked whether they would consider sharing stories. At a theoretical level, the findings support the inattention-based account, according to which contextual cues shifting the focus toward accuracy can enhance accurate-inaccurate discrimination in sharing responses. At a methodological level, these findings suggest that researchers should carefully attend to the verbal framing of questions about sharing information on social media, as the framing may significantly influence participants' focus on accuracy. [ABSTRACT FROM AUTHOR]

Cochlear implants (CI) are one of the most successful treatments available to enable individuals with severe to profound hearing loss to regain access to the world of sound. This is accomplished through the electrical stimulation of the auditory nerve using electrodes implanted inside the cochlea. The use of subjective user feedback makes the process of fitting these devices much more challenging in cases where users are not able to actively or accurately report their experience (e.g. pediatrics), making an objective measurement that reflects the accuracy or effectiveness of a program quite attractive. We recorded one objective measure, the electrically-stimulated cortical auditory evoked potential (eCAEP), non-invasively using the CI in response to a simulated speech sound in seven adult participants and compared it to their eCAEP recorded using a scalp EEG set-up. The eCAEPs recorded with CI electrodes were comparable to scalp recorded eCAEPs (grand mean cross-correlation of r = 0.83, individual mean cross-correlations ranged from 0.13 to 0.70). Evoked potential peaks P1, N1 and P2 showed no significant latency difference based on if the eCAEP was recorded on the scalp or using the CI. The eCAEP waveforms recorded via the CI appear to converge in a distinct P1-N1-P2 waveform by as early as 130 sweeps. In conclusion, in this study we show the feasibility of recording the eCAEP directly through the CI system, which could potentially be used to guide CI fitting and track auditory cortex development in response to CI use. [ABSTRACT FROM AUTHOR]

Spatial variation in the intensity of magnetospheric and ionospheric fluctuations during solar storms creates ground-induced currents, of importance in both infrastructure engineering and geophysical science. This activity is presently measured using a network of ground-based magnetometers, typically consisting of extensive installations at established observatory sites. We show that this network can be enhanced by the addition of remote quantum magnetometers which combine high sensitivity with intrinsic calibration. These nodes utilize scalable hardware and run independently of wired communication and power networks. We demonstrate that optically pumped magnetometers, utilizing mass-produced and miniaturized components, offer a single scalable sensor with the sensitivity and stability required for space weather observation. We describe the development and deployment of an off-grid magnetic sensing node, powered by a solar panel, present observed data from periods of low and high geomagnetic activity, and compare it to existing geomagnetic observatories. [ABSTRACT FROM AUTHOR]

The two-high threshold eyewitness identification model was applied to investigate the effects of lineup position on the latent cognitive processes underlying eyewitness responses in lineups. In two experiments with large sample sizes and random assignment of culprits and innocent suspects to all possible lineup positions, we examined how detection-based and non-detection-based processes vary across the positions of six-person photo lineups. Experiment 1 (N = 2586) served to investigate position effects in simultaneous lineups in which all photos were presented in a single row. Experiment 2 (N = 2581) was focused on sequential lineups. In both experiments, lineup position had no effect on the detection of the presence of the culprit. Guessing-based selection, in contrast, differed as a function of lineup position. Specifically, a lineup member placed in the first position in a lineup was significantly more likely to be selected based on guessing than lineup members placed in other positions. These results justify the practice of avoiding to place the suspect in the first position in a lineup, as this placement increases the suspect's chance of being selected based on guessing. [ABSTRACT FROM AUTHOR]

Background: Ethnically Chinese adults in Canada and the United States face multiple barriers in accessing equitable, culturally respectful care at the end-of-life. Palliative care (PC) is committed to supporting patients and families in achieving goal-concordant, high-quality serious illness care. Yet, current PC delivery may be culturally misaligned. Therefore, understanding ethnically Chinese patients' use of palliative care may uncover modifiable factors to sustained inequities at the end-of-life. Objective: To compare the use and delivery of PC in the last year of life between ethnically Chinese and non-Chinese adults. Design: Population-based cohort study. Participants: All Ontario adults who died between January 1st, 2012, and October 31st, 2022, in Ontario, Canada. Exposures: Chinese ethnicity. Main Measures: Elements of physician-delivered PC, including model of care (generalist; specialist; mixed), timing and location of initiation, and type of palliative care physician at initial consultation. Key Results: The final study cohort included 527,700 non-Chinese (50.8% female, 77.9 ± 13.0 mean age, 13.0% rural residence) and 13,587 ethnically Chinese (50.8% female, 79.2 ± 13.6 mean age, 0.6% rural residence) adults. Chinese ethnicity was associated with higher likelihoods of using specialist (adjusted odds ratio [aOR] 1.53, 95%CI 1.46–1.60) and mixed (aOR 1.32, 95%CI 1.26–1.38) over generalist models of PC, compared to non-Chinese patients. Chinese ethnicity was also associated with a higher likelihood of PC initiation in the last 30 days of life (aOR 1.07, 95%CI 1.03–1.11), in the hospital setting (aOR 1.24, 95%CI 1.18–1.30), and by specialist PC physicians (aOR 1.33, 95%CI 1.28–1.38). Conclusions: Chinese ethnicity was associated with a higher likelihood of mixed and specialist models of PC delivery in the last year of life compared to adults who were non-Chinese. These observed differences may be due to later initiation of PC in hospital settings, and potential differences in unmeasured needs that suggest opportunities to initiate early, community-based PC to support ethnically Chinese patients with serious illness. [ABSTRACT FROM AUTHOR]

Introduction: This study investigated stem subsidence following primary total hip arthroplasty (THA) with a Corail stem in patients who underwent two-staged bilateral THA. The second outcome of interest was to investigate whether a specific single cortical bone contact point might reduce postoperative stem subsidence. Methods: The present study was conducted following the STROBE guidelines. The records of patients who underwent THA between 2016 and 2023 were accessed. All patients who underwent two-staged bilateral THA were retrieved. The direct contact between the stem and the cortical bone was assessed at various points in the metaphysis and the distal portion of the stem (diaphysis) in both anteroposterior radiographs of the pelvis (medial and lateral bone contact) and a Lauenstein view of the hip (anterior and posterior bone contact). The following parameters were measured and compared to assess stem subsidence: distance from the proximal femur at the stem bone interface and the tip of the lesser trochanter (distance A); distance from the tip of the lesser trochanter and the tip of the femoral stem (distance B). Results: In total, 250 patients were included, 45% (149 of 250 patients) were women and 61% (153 of 250 THAs) were implanted primarily on the right side. The mean age of patients at the time of the first THA was 64.3 ± 10.0 years and the mean body mass index (BMI) was 28.0 ± 4.9 kg/m2. The mean length of the follow-up was 14.1 ± 10.8 months. The overall stem subsidence following THA was 2.8 ± 0.7 mm (P < 0.006). A direct cortical bone-implant contact did not exert a statistically significant difference in subsidence of the THA stem at the metaphysis and diaphysis (P > 0.5). Stem subsidence following THA with a collarless cementless Corail stem was approximately 2.8 mm at 14 months. Conclusions: Direct cortical bone contact of the stem at diaphysis and metaphysis seems not to influence stem subsidence following THA using the Corail stem. [ABSTRACT FROM AUTHOR]

Purpose: The recognition of adverse drug reactions (ADRs) is an important part of daily clinical work. However, medical education in this field is mostly drug-based and does not address adequately the complexity of this field regarding individual risk factors and polypharmacy. This study investigates the potential of the web-based serious game SeeMe (side-effect exposure—medical education) in pharmacological education of medical students to improve the recognition of relevant ADRs. Methods: One hundred fifty-seven medical students were recruited to evaluate the serious game SeeMe. SeeMe was developed to improve knowledge and recognition of ADRs in clinical practice. Players take on the role of a physician trying to understand fictional patients with ADRs. Before and after an 8-week playing period, an evaluation was carried out through a pre- and post-questionnaire and a pre- and post- knowledge test. Results: The students achieved significantly better results in the knowledge test, as almost twice as many exam-relevant questions were answered correctly (p < 0.001). The serious game had a positive effect on the students' perception of the importance of ADRs. Conclusion: This study demonstrates the potential of web- and case-based fictional serious games in medical education. The improved recognition of side effects represents a crucial step for education and training in clinical pharmacology. Future versions of the serious game may take this further and focus on training in the treatment of ADRs and their relevance in various healthcare professions. [ABSTRACT FROM AUTHOR]

Purpose: The radionuclide pair cerium-134/lanthanum-134 (134Ce/134La) was recently proposed as a suitable diagnostic counterpart for the therapeutic alpha-emitter actinium-225 (225Ac). The unique properties of 134Ce offer perspectives for developing innovative in vivo investigations that are not possible with 225Ac. In this work, 225Ac- and 134Ce-labelled tracers were directly compared using internalizing and slow-internalizing cancer models to evaluate their in vivo comparability, progeny meandering, and potential as a matched theranostic pair for clinical translation. Despite being an excellent chemical match, 134Ce/134La has limitations to the setting of quantitative positron emission tomography imaging. Methods: The precursor PSMA-617 and a macropa-based tetrazine-conjugate (mcp-PEG8-Tz) were radiolabelled with 225Ac or 134Ce and compared in vitro and in vivo using standard (radio)chemical methods. Employing biodistribution studies and positron emission tomography (PET) imaging in athymic nude mice, the radiolabelled PSMA-617 tracers were evaluated in a PC3/PIP (PC3 engineered to express a high level of prostate-specific membrane antigen) prostate cancer mouse model. The 225Ac and 134Ce-labelled mcp-PEG8-Tz were investigated in a BxPC-3 pancreatic tumour model harnessing the pretargeting strategy based on a trans-cyclooctene-modified 5B1 monoclonal antibody. Results: In vitro and in vivo studies with both 225Ac and 134Ce-labelled tracers led to comparable results, confirming the matching pharmacokinetics of this theranostic pair. However, PET imaging of the 134Ce-labelled precursors indicated that quantification is highly dependent on tracer internalization due to the redistribution of 134Ce's PET-compatible daughter 134La. Consequently, radiotracers based on internalizing vectors like PSMA-617 are suited for this theranostic pair, while slow-internalizing 225Ac-labelled tracers are not quantitatively represented by 134Ce PET imaging. Conclusion: When employing slow-internalizing vectors, 134Ce might not be an ideal match for 225Ac due to the underestimation of tumour uptake caused by the in vivo redistribution of 134La. However, this same characteristic makes it possible to estimate the redistribution of 225Ac's progeny noninvasively. In future studies, this unique PET in vivo generator will further be harnessed to study tracer internalization, trafficking of receptors, and the progression of the tumour microenvironment. [ABSTRACT FROM AUTHOR]

Aims: The aim of this study was to determine the effectiveness of natural (NatZeo) and acid-treated (AcidZeo) zeolites in increasing the nitrogen (N) recovery of sugarcane grown under conditions highly conducive for N losses. Methods: This glasshouse trial replicated the pedoclimatic conditions typical of the Australian sugarcane industry in the Wet Tropics to evaluate the capacity and economic feasibility of using NatZeo and AcidZeo to reduce leaching and increase plant and soil N recovery in a highly permeable sandy-loam soil. Nitrogen fertiliser was applied at two rates (84 and 120 kg N ha−1) as 15N-enriched urea. Results: Compared with the unamended treatments, AcidZeo led to significantly higher average fertiliser N recoveries in both the soil (+24%) and plant (+54%), which resulted in significantly lower overall N losses (−22%). However, the significantly higher capacity of AcidZeo in retaining ions limited the availability of potassium and sulphur to the plants and led to a 4% yield reduction. The use of NatZeo led to lower abatements of N losses (−6%) but increased N recoveries in the plant (+22%). NatZeo did not result in as much cation immobilisation, which, combined with the increased plant/soil N recovery, resulted in the highest yield of the trial (+8% compared with the unamended treatments). The economic analysis indicated that only NatZeo could potentially increase farmer's income when applied in 20 cm wide strips around the fertiliser band. Conclusions: This study highlights that zeolites have potential to improve the environmental sustainability and profitability of sugarcane cropping systems. [ABSTRACT FROM AUTHOR]

Introduction: Oral semaglutide provides an alternative to injectable glucagon-like peptide-1 receptor agonists (GLP-1RAs) for treatment of type 2 diabetes (T2D). The PIONEER REAL studies evaluate clinical outcomes of oral semaglutide treatment of T2D in a real-world setting. PIONEER REAL UK focused on adults living with T2D in the UK. Methods: The multi-centre, prospective and non-interventional single-arm study enrolled 333 participants and followed them for 34–44 weeks. Participants were treated as part of routine clinical practice and had not been previously treated with injectable glucose-lowering medication. The primary endpoint was change in glycated haemoglobin (HbA1C) from baseline to end of study (EOS). Secondary endpoints included change in body weight, proportion of participants with HbA1C < 7% (53 mmol/mol) at EOS and proportion of participants with ≥ 1%-point HbA1C reduction and body weight reduction of ≥ 3% or ≥ 5% at EOS. Treatment satisfaction was assessed by Diabetes Treatment Satisfaction Questionnaire (DTSQ) status and change. Results: Of 333 participants, 299 completed the study and 227 were on treatment at EOS. People treated with oral semaglutide experienced significantly reduced HbA1C by an estimated change of – 1.1%-points (95% CI – 1.27 to – 0.96; P < 0.0001) or – 12.2 mmol/mol (CI – 13.87 to – 10.47; P < 0.0001). Estimated change in body weight was – 4.8 kg (CI – 5.47 to – 4.12; P < 0.0001). At EOS, an HbA1C level < 7% (53 mmol/mol) was recorded in 46.3% of participants. A ≥ 1%-point reduction in HbA1C combined with a ≥ 3% reduction in body weight was observed in 36.4% of participants, and 27.1% had a ≥ 1%-point reduction in HbA1C and a ≥ 5% body weight reduction. Treatment satisfaction improved significantly during the study. No new safety concerns or cases of severe hypoglycaemia were reported. Conclusion: People living with T2D in the UK experienced a meaningful decrease in HbA1C and body weight after initiation of oral semaglutide treatment. No new safety issues were observed. Trial Registration: ClinicalTrials.gov: NCT04862923. Graphical plain language summary available for this article. Plain Language Summary: PIONEER REAL UK investigated the use of a tablet form of the medicine semaglutide in people living with type 2 diabetes in the UK. The purpose was to determine how well the tablet works for blood sugar control and weight loss in everyday clinical practice. The study followed 333 participants whose doctors had given them semaglutide tablets. Their blood sugar levels and body weight were measured before and after taking the semaglutide tablet for 34–44 weeks. The participants were also asked to fill out questionnaires about their treatment satisfaction and how it changed when taking the semaglutide tablet. The participants' blood sugar levels dropped a lot, and body weight was lowered by an average of 4.8 kg during the 34–44 weeks of the study. The participants were also more satisfied with their treatment at the end of the study than before taking the semaglutide tablet. Doctors treating the participants found the treatment to be a success in more than two-thirds of participants. The study also found that the semaglutide tablet was not associated with cases of too low blood sugar and was generally well tolerated. In summary, the semaglutide tablet is a good option for people living with type 2 diabetes who need better blood sugar control and would benefit from weight loss. The treatment is generally well tolerated, and people are very satisfied with it. Graphical Plain Language Summary: [ABSTRACT FROM AUTHOR]

Rising global pediatric obesity rates, increase non-alcoholic fatty liver disease (NAFLD) and metabolic syndrome (MetS) prevalence, with MetS being a NAFLD risk factor. NAFLD can be asymptomatic, with liver function tests insensitive to mild disease, and liver biopsy, risking complications. Thus, we investigated multiparametric MRI (mpMRI) metrics of liver fat (proton density fat fraction, PDFF) and disease activity (fibro-inflammation; iron-corrected T1, cT1), in a Hispanic pre-pubertal pediatric cohort, with increased risk of NAFLD. Pre-pubertal boys (n = 81) of varying Body-Mass Index (BMI) were recruited in Mexico City. Most children (81%) had normal liver transaminase levels, 38% had high BMI, and 14% had ≥ 3 MetS risk factors. Applying mpMRI thresholds, 12%, 7% and 4% of the cohort had NAFLD, NASH and high-risk NASH respectively. Participants with ≥ 3 MetS risk factors had higher cT1 (834 ms vs. 737 ms, p = 0.004) and PDFF (8.7% vs. 2.2%, p < 0.001) compared to those without risk factors. Those with elevated cT1 tended to have high BMI and high insulin (p = 0.005), HOMA-IR (p = 0.005) and leptin (p < 0.001). The significant association of increased risk of MetS with abnormal mpMRI, particularly cT1, proposes the potential of using mpMRI for routine pediatric NAFLD screening of high-risk (high BMI, high MetS risk score) populations. [ABSTRACT FROM AUTHOR]

Background: Increased awareness of the factors contributing to the diagnostic disparities seen in bipolar disorder between individuals of different heritage is needed to achieve equity in diagnosis and treatment. One such inequity is the provision of earlier treatment. Earlier treatment of patients diagnosed with bipolar disorder may prolong time to recurrence of mood episodes and reduce functional impairment and other poor outcomes associated with disease progression. The aim of this post hoc analysis was to study the efficacy and safety of long-acting injectable aripiprazole once-monthly 400 mg (AOM 400) in patients with earlier-stage bipolar I disorder (BP-I). Data from a 52-week multicenter, double-blind, placebo-controlled, randomized withdrawal trial of AOM 400 versus placebo in patients with BP‑I (NCT01567527) were analyzed. Those patients in the lowest quartiles for age (18–≤32 years; n = 70) or disease duration (0.13–≤4.6 years; n = 67) at baseline were categorized with earlier-stage BP-I. The primary endpoint was time from randomization to recurrence of any mood episode. Other endpoints included proportion of patients with recurrence of any mood episode, and change from baseline in Young Mania Rating Scale (YMRS) and Montgomery–Åsberg Depression Rating Scale (MADRS) total scores. Results: Maintenance treatment with AOM 400 significantly delayed time to recurrence of any mood episode versus placebo in patients aged 18–≤32 years (hazard ratio [HR]: 2.46 [95% confidence interval (CI) 1.09, 5.55]; p = 0.0251) or with disease duration 0.13–≤4.6 years (HR: 3.21 [95% CI 1.35, 7.65]; p = 0.005). This was largely driven by a lower proportion of patients in the AOM 400 group with YMRS total score ≥15 or clinical worsening. Changes from baseline in MADRS total score in both earlier-stage groups indicated AOM 400 did not worsen depression versus placebo. The safety profile of AOM 400 was consistent with the original study. Note that the original study included patients who had previously been stabilized on AOM 400 monotherapy, which may have enriched the population with patients who respond to and tolerate AOM 400. Conclusions: In this post hoc analysis, AOM 400 prolonged time to recurrence of any mood episode versus placebo in earlier-stage BP-I. These findings support early initiation of maintenance treatment with AOM 400. [ABSTRACT FROM AUTHOR]

Mutations in SARS-CoV-2 variants of concern (VOCs) have expanded the viral host range beyond primates, and a few other mammals, to mice, affording the opportunity to exploit genetically diverse mouse panels to model the broad spectrum of responses to infection in patient populations. Here we surveyed responses to VOC infection in genetically diverse Collaborative Cross (CC) founder strains. Infection of wild-derived CC founder strains produced a broad range of viral burden, disease susceptibility and survival, whereas most other strains were resistant to disease despite measurable lung viral titers. In particular, CAST/EiJ, a wild-derived strain, developed high lung viral burdens, more severe lung pathology than seen in other CC strains, and a dysregulated cytokine profile resulting in morbidity and mortality. These inbred mouse strains may serve as a valuable platform to evaluate therapeutic countermeasures against severe COVID-19 and other coronavirus pandemics in the future. [ABSTRACT FROM AUTHOR]

Student-created videos engage students' interests, creativity, and content knowledge and enrich collaborative learning in STEM education. These videos enhance critical thinking and analytical skills, which are essential tools in the fields of science, technology, engineering, and mathematics (STEM). This study presents the results of such an assignment across several STEM areas (biology, chemistry, exercise science, information technology, and mathematics) at a minority-serving, liberal arts higher education institution in the southeast region of the United States. Undergraduate students (n = 557) across varied, online course modalities (synchronous and asynchronous) were required to create four problem-solving videos 3–8 min in duration. Assessment tools included a self-assessment of learning gains survey given to control and experimental groups and a post-video creation survey given only to experimental groups. Grade data was also collected from all sections. Comparing the experimental and control groups, students showed a statistically significant gain in their ability to give oral presentations, create videos, and edit videos. Qualitative data from free-response questions corroborate these gains and suggest that students also grew in content knowledge and conceptual understanding through these assignments. Our study implements a multimedia theoretical framework which suggests students learn more effectively from consuming presentations with both auditory and visual components. Our results suggest students see similar gains from producing presentations with both auditory and visual components. Further our results suggest that multimedia production enhances students' presentation skills. From a practical perspective, this study suggests that faculty should incorporate student-created videos in online classes, which typically require oral presentations in person. Faculty are also advised to require oral and visual components within these videos to maximize learning gains from the perspective of a multimedia theoretical framework. [ABSTRACT FROM AUTHOR]

Two experiments served to examine how people arrive at stimulus-specific prospective judgments about the distracting effects of speech on cognitive performance. The direct-access account implies that people have direct metacognitive access to the cognitive effects of sounds that determine distraction. The processing-fluency account implies that people rely on the processing-fluency heuristic to predict the distracting effects of sounds on cognitive performance. To test these accounts against each other, we manipulated the processing fluency of speech by playing speech forward or backward and by playing speech in the participants’ native or a foreign language. Forward speech and native speech disrupted serial recall to the same degree as backward speech and foreign speech, respectively. However, the more fluently experienced forward speech and native speech were incorrectly predicted to be less distracting than backward speech and foreign speech. This provides evidence of a metacognitive illusion in stimulus-specific prospective judgments of distraction by speech, supporting the processing-fluency account over the direct-access account. The difference between more and less fluently experienced speech was largely absent in the participants’ global retrospective judgments of distraction, suggesting that people gain access to comparatively valid cues when experiencing the distracting effects of speech on their serial-recall performance firsthand. [ABSTRACT FROM AUTHOR]

The electrical activity of the brain can be monitored using the electroencephalogram (EEG), which can be used in the detection of seizures. This paper proposes an epileptic seizure detection algorithm that uses inter-intra Head-body-tail (HBT) features. Initially, the EEG signals are subdivided into non-overlapping frames. From each frame, three regions namely head (H), body (B), and tail (T) are constructed. Intra features named intra-correlative features are extracted within a frame while the inter-HBT features namely magnitude change and zero crossing feature are extracted between adjacent HBT frames. This paper also proposes a complementary convolutional neural network (CP-CNN) which uses two parallel sections of a traditional 1 D -CNN network. The complementary CNN is proposed to preserve the components that are eliminated by the traditional 1 D -CNN network in the feature extraction process. The evaluation of the proposed seizure detection algorithm was done with the evaluation metrics namely accuracy, sensitivity, F1-score, and specificity with the datasets namely CHB-MIT EEG dataset where the recordings were done from 22 subjects, and the Siena EEG dataset where the recordings were performed from 14 subjects. The proposed seizure detection provides an accuracy, sensitivity, F1-score, and Specificity of 98.17 % , 94.21 % , 95.79 % , and 98.25 % respectively for the CHB-MIT dataset. For the Siena-EEG dataset the accuracy, sensitivity, F1-score, and specificity were estimated as 98.76 % , 94.15 , 95.14%, and 98.77 % respectively. [ABSTRACT FROM AUTHOR]

One risk of continuous renal replacement therapy (CRRT) is inadvertent hypothermia (IH), which is defined as a non-therapeutic core temperature decrease below normal. In continuous renal replacement therapy, heat loss will always occur from blood pumped through the dialysis circuit to cooler environment, predisposing for hypothermia. Blood flow and effluent flows are the most important parameters causing heat loss. We investigated and compared the novel TherMax warmer to previous generation technologies during CRRT in a multicenter setting. This was a prospective observational multicenter study with historic single-center controls. The study group consisted of 100 patients in eight Swedish ICUs with clinical indication for CRRT, using the PrisMax platform and TherMax warmer. Both patient and set warmer temperatures were recorded hourly for the first 24 h. The presence of treatment hours in hypothermia (< 36.0 Celsius) and the difference between set warmer temperature and measured patient temperature in the multi-center study cohort were compared to a matched single-center historic control cohort treated with the old Prismaflex platform and adjacent Barkey warmer. In the TherMax group 77/100 (77.0%) of patients, and for controls 26/86 (30.2%) of patients were free of hypothermia (Chi square, p < 0.001). The mean number of hours spent in hypothermia was (mean ± SD) 0.66 ± 1.60 and 6.92 ± 7.79 h in the TherMax and control groups, respectively (Chi square p < 0.001). In the study group the patient temperature was higher than the set temperature on the warmer with a difference of Δ0.47 ± 0.80 °C (minor difference), whereas in the control group the set temperature on the warmer was higher than the patient temperature with a difference of Δ4.55 ± 1.00 °C (over-correction). The novel TherMax warmer technology protected against hypothermia and was significantly more accurate than the Barkey warmer. [ABSTRACT FROM AUTHOR]

Miniaturization of medical tools promises to revolutionize surgery by reducing tissue trauma and accelerating recovery. Magnetic untethered devices, with their ability to access hard-to-reach areas without physical connections, emerge as potential candidates for such miniaturization. Despite the benefits, these miniature devices face challenges regarding force and torque outputs, restricting their ability to perform tasks requiring mechanical interactions such as tissue penetration and manipulation. To overcome magnetic actuation system-based force and torque limitations, this study proposes Variable Outer Radius Individually Addressable Coil Stacks (VORIACS), a novel magnetic actuation system optimized for high force output generation to magnetic devices within its workspace. The VORIACS marks significant improvements and breakthroughs in magnetic actuation within decimeter-scale workspace. The VORIACS is comprised of 12 coils that are optimized for 2D magnetic field generation under maximized power consumption of up to 12 kW. We implement six two-channel motor controllers, powered by six separate power supplies. Each of the twelve coils in the system is operated on its own motor-controller channel. This arrangement allows the system to exceed the magnetic forces and torques possible for single-coil versions of the same geometry. This study elaborates on optimizing, manufacturing, integrating, and demonstrating this system. Comparative analysis reveals that while a suboptimal, single-coil version of this system generates 0.31 N force (710 mT/m magnetic gradient magnitude), the VORIACS produces 1.673 N force (3834 mT/m magnetic gradient magnitude) on the same magnetic object placed 5 cm away from the coils. Moreover, the strong penetration force generated by VORIACS enables needle penetration to a mock gel that has the rigidity of liver tissue. In addition, we demonstrate the advantage of stacked coils with variable radii for magnetic field manipulability while maintaining the optimized force delivery property of the system, which improves control and could facilitate multi-tool manipulation. By enabling a fivefold increase in magnetic pulling force compared to its single-coil counterpart, VORICAS raises the potential penetration capabilities of untethered magnetic robotics in surgical procedures. [ABSTRACT FROM AUTHOR]

Given the large amount of information that people process daily, it is important to understand memory for the truth and falsity of information. The most prominent theoretical models in this regard are the Cartesian model and the Spinozan model. The former assumes that both "true" and "false" tags may be added to the memory representation of encoded information; the latter assumes that only falsity is tagged. In the present work, we contrasted these two models with an expectation-violation model hypothesizing that truth or falsity tags are assigned when expectations about truth or falsity must be revised in light of new information. An interesting implication of the expectation-violation model is that a context with predominantly false information leads to the tagging of truth whereas a context with predominantly true information leads to the tagging of falsity. To test the three theoretical models against each other, veracity expectations were manipulated between participants by varying the base rates of allegedly true and false advertising claims. Memory for the veracity of these claims was assessed using a model-based analysis. To increase methodological rigor and transparency in the specification of the measurement model, we preregistered, a priori, the details of the model-based analysis test. Despite a large sample size (N = 208), memory for truth and falsity did not differ, regardless of the base rates of true and false claims. The results thus support the Cartesian model and provide evidence against the Spinozan model and the expectation-violation model. [ABSTRACT FROM AUTHOR]

Carbapenem-resistance in Enterobacter spp due to acquisition of mobile carbapenemases is of concern. An Enterobacter spp grew on ChromID CARBA medium and was positive for the mCIM carbapenemase detection assay. Susceptibility testing showed resistance to aztreonam and reduced susceptibility to imipenem. Conventional PCR using FRI primers detected a blaFRI gene. Whole genome sequencing reveled a new variant; blaFRI−12 was closest in sequence to blaFRI−5 differing by 13 amino acids and was found on a unique 110Kb IncR plasmid. Given the intrinsic nature of Enterobacter spp. to be carbapenem non-susceptible, blaFRI-types may be under reported globally. [ABSTRACT FROM AUTHOR]

Aims/hypothesis: This study aimed to describe the relationship between breastfeeding episodes and maternal glucose levels, and to assess whether this differs with closed-loop vs open-loop (sensor-augmented pump) insulin therapy. Methods: Infant-feeding diaries were collected at 6 weeks, 12 weeks and 24 weeks postpartum in a trial of postpartum closed-loop use in 18 women with type 1 diabetes. Continuous glucose monitoring (CGM) data were used to identify maternal glucose patterns within the 3 h of breastfeeding episodes. Generalised mixed models adjusted for breastfeeding episodes in the same woman, repeat breastfeeding episodes, carbohydrate intake, infant age at time of feeding and early pregnancy HbA1c. This was a secondary analysis of data collected during a randomised trial (ClinicalTrials.gov registration no. NCT04420728). Results: CGM glucose remained above 3.9 mmol/l in the 3 h post-breastfeeding for 93% (397/427) of breastfeeding episodes. There was an overall decrease in glucose at nighttime within 3 h of breastfeeding (1.1 mmol l−1 h−1 decrease on average; p=0.009). A decrease in nighttime glucose was observed with open-loop therapy (1.2 ± 0.5 mmol/l) but was blunted with closed-loop therapy (0.4 ± 0.3 mmol/l; p<0.01, open-loop vs closed-loop). Conclusions/interpretation: There is a small decrease in glucose after nighttime breastfeeding that usually does not result in maternal hypoglycaemia; this appears to be blunted with the use of closed-loop therapy. [ABSTRACT FROM AUTHOR]