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Abstract Cancer‐associated cachexia is a multifactorial wasting disorder characterized by anorexia, unintentional weight loss (skeletal muscle mass with or without loss of fat mass), progressive functional impairment, and poor prognosis. This systematic literature review (SLR) examined the relationship between cachexia and survival in patients with colorectal or pancreatic cancer in recent literature. The SLR was conducted following PRISMA guidelines. Embase® and PubMed were searched to identify articles published in English between 1 January 2016 and 10 October 2021 reporting survival in adults with cancer and cachexia or at risk of cachexia, defined by international consensus (IC) diagnostic criteria or a broader definition of any weight loss. Included publications were studies in ≥100 patients with colorectal or pancreatic cancer. Thirteen publications in patients with colorectal cancer and 13 with pancreatic cancer met eligibility criteria. Included studies were observational and primarily from Europe and the United States. Eleven studies (42%) reported cachexia using IC criteria and 15 (58%) reported any weight loss. An association between survival and cachexia or weight loss was assessed across studies using multivariate (n = 23) or univariate (n = 3) analyses and within each study across multiple weight loss categories. Cachexia/weight loss was associated with a statistically significantly poorer survival in at least one weight loss category in 16 of 23 studies that used multivariate analyses and in 1 of 3 studies (33%) that used univariate analyses. Of the 17 studies demonstrating a significant association, 9 were in patients with colorectal cancer and 8 were in patients with pancreatic cancer. Cachexia or weight loss was associated with significantly poorer survival in patients with colorectal or pancreatic cancer in nearly two‐thirds of the studies. The classification of weight loss varied across and within studies (multiple categories were evaluated) and may have contributed to variability. Nonetheless, awareness of cachexia and routine assessment of weight change in clinical practice in patients with colorectal or pancreatic cancer could help inform prognosis and influence early disease management strategies.

Abstract Background The successful integration of artificial intelligence (AI) in healthcare depends on the global perspectives of all stakeholders. This study aims to answer the research question: What are the attitudes of medical, dental, and veterinary students towards AI in education and practice, and what are the regional differences in these perceptions? Methods An anonymous online survey was developed based on a literature review and expert panel discussions. The survey assessed students' AI knowledge, attitudes towards AI in healthcare, current state of AI education, and preferences for AI teaching. It consisted of 16 multiple-choice items, eight demographic queries, and one free-field comment section. Medical, dental, and veterinary students from various countries were invited to participate via faculty newsletters and courses. The survey measured technological literacy, AI knowledge, current state of AI education, preferences for AI teaching, and attitudes towards AI in healthcare using Likert scales. Data were analyzed using descriptive statistics, Mann–Whitney U-test, Kruskal–Wallis test, and Dunn-Bonferroni post hoc test. Results The survey included 4313 medical, 205 dentistry, and 78 veterinary students from 192 faculties and 48 countries. Most participants were from Europe (51.1%), followed by North/South America (23.3%) and Asia (21.3%). Students reported positive attitudes towards AI in healthcare (median: 4, IQR: 3–4) and a desire for more AI teaching (median: 4, IQR: 4–5). However, they had limited AI knowledge (median: 2, IQR: 2–2), lack of AI courses (76.3%), and felt unprepared to use AI in their careers (median: 2, IQR: 1–3). Subgroup analyses revealed significant differences between the Global North and South (r = 0.025 to 0.185, all P

Abstract Background Asthma is a leading cause of children’s hospitalizations, emergency department visits, and missed school days. Our school-based asthma intervention has reduced asthma exacerbations for children experiencing health disparities in the Denver Metropolitan Area, due partly to addressing care coordination for asthma and social determinants of health (SDOH), such as access to healthcare and medications. Limited dissemination of school-based asthma programs has occurred in other metropolitan and rural areas of Colorado. We formed and engaged community advisory boards in socioeconomically diverse regions of Colorado to develop two implementation strategy packages for delivering our school-based asthma intervention — now termed “Better Asthma Control for Kids (BACK)" — with tailoring to regional priorities, needs and resources. Methods In this proposed type 2 hybrid implementation-effectiveness trial, where the primary goal is equitable reach to families to reduce asthma disparities, we will compare two different packages of implementation strategies to deliver BACK across four Colorado regions. The two implementation packages to be compared are: 1) standard set of implementation strategies including Tailor and Adapt to context, Facilitation and Training termed, BACK-Standard (BACK-S); 2) BACK-S plus an enhanced implementation strategy, that incorporates network weaving with community partners and consumer engagement with school families, termed BACK-Enhanced (BACK-E). Our evaluation will be guided by the Reach, Effectiveness, Adoption, Implementation, and Maintenance (RE-AIM) framework, including its Pragmatic Robust Implementation Sustainability Model (PRISM) determinants of implementation outcomes. Our central hypothesis is that our BACK-E implementation strategy will have significantly greater reach to eligible children/families than BACK-S (primary outcome) and that both BACK-E and BACK-S groups will have significantly reduced asthma exacerbation rates (“attacks”) and improved asthma control as compared to usual care. Discussion We expect both the BACK-S and BACK-E strategy packages will accelerate dissemination of our BACK program across the state – the comparative impact of BACK-S vs. BACK-E on reach and other RE-AIM outcomes may inform strategy selection for scaling BACK and other effective school-based programs to address chronic illness disparities. Trial registration Clinicaltrials.gov identifier: NCT06003569, registered on August 22, 2023, https://classic.clinicaltrials.gov/ct2/show/NCT06003569 .

The European Union’s recently adopted Artificial Intelligence (AI) Act is the first comprehensive legal framework specifically on AI. This is particularly important for the healthcare domain, as other existing harmonisation legislation, such as the Medical Device Regulation, do not explicitly cover medical AI applications. Given the far-reaching impact of this regulation on the medical AI sector, this commentary provides an overview of the key elements of the AI Act, with easy-to-follow references to the relevant chapters.

Abstract Background Minimal Change Disease (MCD) and Focal Segmental Glomerulosclerosis (FSGS) are a spectrum of disease causing the nephrotic syndrome (NS), characterised by proteinuria with debilitating oedema, as well as a high risk of venous thromboembolic disease and infection. Untreated, 50–60% patients with FSGS progress to end stage kidney disease after 5 years. These diseases respond to immunosuppression with high dose glucocorticoids, but 75% will relapse as the glucocorticoids are withdrawn, leading to significant morbidity associated with prolonged use. In children, the B cell depleting monoclonal antibody rituximab reduces relapse risk, but this drug has not been tested in randomised controlled trial in adults. Methods 130–150 adults with new or relapsing MCD/FSGS, from UK Renal Units, are being randomised to receive either rituximab (two 1 g infusions two weeks apart) or placebo. Partipicipants are recruited when they present with nephrosis, and all are treated with glucocorticoids as per KDIGO guidelines. Once in remission, prednisolone is withdrawn according to a pre-specified regimen. If in remission at 6 months, participants receive a further dose of trial drug. If they relapse, they are unblinded, and if they have received placebo, they are offered open label rituximab with protocolised prednisolone as in the main phase of the trial. The primary end point is time from remission to relapse. A number of secondary endpoints will be assessed including the effect of rituximab on: (1) NHS and societal resource use and hence cost: (2) safety: (3) other measures of efficacy, such as achievement of partial and complete remission of NS and the preservation of renal function: (4) health status of participant. Trial Registration TURING received ethical approval on 14 Jun 2019 - REC reference: 19/LO/0738. It is registered on EudraCT, with ID number: 2018-004611-50, with a start date of 2019-06-14.

Abstract Cachexia, with weight loss (WL) as a major component, is highly prevalent in patients with cancer and indicates a poor prognosis. The primary objective of this study was to conduct a meta‐analysis to estimate the risk of mortality associated with cachexia (using established WL criteria prior to treatment initiation) in patients with non‐small‐cell lung cancer (NSCLC) in studies identified through a systematic literature review. The review was conducted according to PRISMA guidelines. Embase® and PubMed were searched to identify articles on survival outcomes in adult patients with NSCLC (any stage) and cachexia published in English between 1 January 2016 and 10 October 2021. Two independent reviewers screened titles, abstracts and full texts of identified records against predefined inclusion/exclusion criteria. Following a feasibility assessment, a meta‐analysis evaluating the impact of cachexia, defined per the international consensus criteria (ICC), or of pre‐treatment WL ≥ 5% without a specified time interval, on overall survival in patients with NSCLC was conducted using a random‐effects model that included the identified studies as the base case. The impact of heterogeneity was evaluated through sensitivity and subgroup analyses. The standard measures of statistical heterogeneity were calculated. Of the 40 NSCLC publications identified in the review, 20 studies that used the ICC for cachexia or reported WL ≥ 5% and that performed multivariate analyses with hazard ratios (HRs) or Kaplan–Meier curves were included in the feasibility assessment. Of these, 16 studies (80%; n = 6225 patients; published 2016–2021) met the criteria for inclusion in the meta‐analysis: 11 studies (69%) used the ICC and 5 studies (31%) used WL ≥ 5%. Combined criteria (ICC plus WL ≥ 5%) were associated with an 82% higher mortality risk versus no cachexia or WL

Abstract Background Plant meristems are structured organs consisting of distinct layers of stem cells, which differentiate into new plant tissue. Mutations in meristematic layers can propagate into large sectors of the plant. However, the characteristics of meristematic mutations remain unclear, limiting our understanding of the genetic basis of somaclonal phenotypic variation. Results Here, we analyse the frequency and distribution of somatic mutations in an apricot tree. We separately sequence the epidermis (developing from meristem layer 1) and the flesh (developing from meristem layer 2) of several fruits sampled across the entire tree. We find that most somatic mutations (> 90%) are specific to individual layers. Interestingly, layer 1 shows a higher mutation load than layer 2, implying different mutational dynamics between the layers. The distribution of somatic mutations follows the branching of the tree. This suggests that somatic mutations are propagated to developing branches through axillary meristems. In turn, this leads us to the unexpected observation that the genomes of layer 1 of distant branches are more similar to each other than to the genomes of layer 2 of the same branches. Finally, using single-cell RNA sequencing, we demonstrate that layer-specific mutations were only transcribed in the cells of the respective layers and can form the genetic basis of somaclonal phenotypic variation. Conclusions Here, we analyse the frequency and distribution of somatic mutations with meristematic origin. Our observations on the layer specificity of somatic mutations outline how they are distributed, how they propagate, and how they can impact clonally propagated crops.

Abstract The biological response to biomaterials plays a crucial role in selecting suitable materials for the formulation and development of tissue engineering platforms. Biodegradation is one of the properties that is considered in selecting appropriate biomaterials for biomedical applications. Biodegradation is the process of breaking down large molecules into smaller molecules with/without the aid of catalytic enzymes. The biodegradation process is crucial in the chemical absorption, distribution, metabolism, excretion, and toxicity (ADMET) process of biomaterials and small molecules in the body. Degradation of biomaterials can be followed by assessing the physical, mechanical, and chemical attributes of biomaterials. There are several techniques/parameters that can be targeted when studying the degradation of biomaterials, with gravimetric analysis, surface erosion, and morphological changes being the largely employed techniques. However, the techniques present a few limitations, such as technical errors and material solubility being mistaken for degradation, and these techniques can infer but not confirm degradation as they do not provide the chemical composition of fragmenting/fragmented molecules. The American Society for Testing and Materials (ASTM) guidelines provide techniques and parameters for assessing biodegradation. However, the ASTM guidelines for degradation assessment approaches and techniques need to be updated to provide sufficient evidence to draw conclusive decisions regarding the degradation of biomaterials. In this review, the degradation assessment approaches and techniques are critically reviewed about their advantages and disadvantages, and to provide suggestions on how they can still play a role in assessing the degradation of biomaterials. This review could assist researchers employ cost-effective, efficient, and multiple degradation assessment techniques to evaluate and provide sufficient information about the degradation of biomaterials. Suggested future ASTM guidelines for assessing biodegradation should include measuring parameters (such as chemical, mechanical, or physical attributes of biomaterials) in real-time, employing non-invasive, continuous, and automated processes.

Abstract The motor impairments experienced by people with Parkinson's disease (PD) are exacerbated during memory‐guided movements. Despite this, the effect of antiparkinson medication on memory‐guided movements has not been elucidated. We evaluated the effect of antiparkinson medication on motor control during a memory‐guided reaching task with short and long retention delays in participants with PD and compared performance to age‐matched healthy control (HC) participants. Thirty‐two participants with PD completed the motor section of the Movement Disorder Society Unified Parkinson's Disease Rating Scale (MDS‐UPDRS III) and performed a memory‐guided reaching task with two retention delays (0.5 s and 5 s) while on and off medication. Thirteen HC participants completed the MDS‐UPDRS III and performed the memory‐guided reaching task. In the task, medication increased movement velocity, decreased movement time, and decreased reaction time toward what was seen in the HC. However, movement amplitude and reaching error were unaffected by medication. Shorter retention delays increased movement velocity and amplitude, decreased movement time, and decreased error, but increased reaction times in the participants with PD and HC. Together, these results imply that antiparkinson medication is more effective at altering the neurophysiological mechanisms controlling movement velocity and reaction time compared with other aspects of movement control.

Orientation: The conflicting demands of work and family contribute to individual stress levels, particularly for women because of gender stereotypes. The male-dominated and pressured environment of manufacturing and gendered expectations at home exacerbate of stress for women manufacturing managers. Research purpose: The study aimed to explore the gendered expectations of female managers in the manufacturing industry in South Africa and how they cope with resulting stress. Motivation for the study: Limited research has been conducted on the gendered expectations of female managers in the South African manufacturing industry, including stress experienced due to work–family conflict (WFC) and coping mechanisms for managing this stress. Research approach/design and method: A qualitative research approach was adopted, with a sample of 14 female managers from South African manufacturing organisations. Data were collected through in-depth, semi-structured interviews. Main findings: Female manufacturing managers’ stress is linked to the patriarchal working environment, compounded by the lack of support for the ‘double burden’ of work and family responsibilities. Generally, female managers resort to unsustainable coping mechanisms rather than permanent solutions. Practical/managerial implications: The study revealed structural problems within the manufacturing industry, which, unaddressed, will result in women increasingly pursuing more accommodating industries, depriving manufacturing organisations of much-needed female talent. Contribution/value-add: The study acknowledged the call for cross-national work on WFC and makes a unique contribution by focusing on gendered expectations in the male-dominated sector of manufacturing in South Africa.

Growth differentiation factor-15 (GDF-15) is an emerging biomarker in several conditions. This SLR, conducted following PRISMA guidelines, examined the association between GDF-15 concentration and range of adverse outcomes in patients with heart failure (HF). Publications were identified from Embase® and Medline® bibliographic databases between January 1, 2014, and August 23, 2022 (congress abstracts: January 1, 2020, to August 23, 2022). Sixty-three publications met the eligibility criteria (55 manuscripts and 8 abstracts; 45 observational studies and 18 post hoc analyses of randomized controlled trials [RCTs]). Of the 19 outcomes identified, the most frequently reported longitudinal outcomes were mortality (n = 32 studies; all-cause [n = 27] or cardiovascular-related [n = 6]), composite outcomes (n = 28; most commonly mortality ± hospitalization/rehospitalization [n = 19]), and hospitalization/re-hospitalization (n = 11). The most common cross-sectional outcome was renal function (n = 22). Among longitudinal studies assessing independent relationships with outcomes using multivariate analyses (MVA), a significant increase in risk associated with higher baseline GDF-15 concentration was found in 22/24 (92 %) studies assessing all-cause mortality, 4/5 (80 %) assessing cardiovascular-related mortality, 13/19 (68 %) assessing composite outcomes, and 4/8 (50 %) assessing hospitalization/rehospitalization. All (7/7; 100 %) of the cross-sectional studies assessing the relationship with renal function by MVA, and 3/4 (75 %) assessing exercise capacity, found poorer outcomes associated with higher baseline GDF-15 concentrations. This SLR suggests GDF-15 is an independent predictor of mortality and other adverse but nonfatal outcomes in patients with HF. A better understanding of the prognostic role of GDF-15 in HF could improve clinical risk prediction models and potentially help optimize treatment regimens.

Within the past decade, single domain antibodies (sdAbs) have been recognized as unique affinity binding reagents that can be tailored for performance in a variety of immunoassay formats. Luminex MagPlex color-coded magnetic microspheres provide a high-throughput platform that enables multiplexed immunoassays. We developed a MagPlex bead-based assay for the detection of SARS-CoV-2, using sdAbs against SARS-CoV-2 nucleocapsid (N) protein in which we engineered the sdAb capture reagents to orient them on the beads. The oriented sdAbs provided an increase in sensitivity over randomly oriented sdAbs for samples of N diluted in buffer, which also translated into better detection of SARS-CoV-2 in clinical samples. We assessed the specificity of the assay by examining seasonal coronavirus clinical samples. In summary, we provide a proof-of-concept that a bead-based assay using sdAbs to detect SARS-CoV-2 is feasible and future research combining it with other sdAb-coated beads that can detect other viruses may provide a useful diagnostic tool.

Abstract Background Eating disorders (EDs) peak in mid-to-late adolescence and often persist into adulthood. Given their early onset and chronicity, many patients transition from child and adolescent mental health services (CAMHS) to adult mental health services (AMHS) for ongoing, speciality ED care. This transition typically occurs at 18 years of age, when important biological, psychosocial, and vocational changes take place. Thus, smooth and effective transitions are paramount for ensuring service continuity, as well as reducing the risk of ED relapse and premature death. Here, we synthesized evidence on transitions from CAMHS to AMHS for young people with EDs, aiming to inform future research, clinical practice, and healthcare policy. Methods A systematic review of the literature was conducted. This adhered to PRISMA guidelines. PubMed, Embase, and Scopus electronic databases were queried from inception to December 3, 2023. Leveraging the PICOS framework, study eligibility was evaluated in the qualitative synthesis. Data regarding methodology, analytic approach, and associated outcomes were then extracted. The quality of evidence was examined using critical appraisal tools. Finally, concept mapping was applied to organize findings into a transition framework. Results The search returned 76 articles. Of these, 14 were included in the final review. Articles were grouped into ‘qualitative’ (n = 10), ‘cross-sectional’ (n = 2), and ‘longitudinal cohort’ (n = 2) studies based on research design. Overall, ED transitions were complex, multifaceted, and challenging for patients, caregivers, and providers alike. This resulted from an interplay of temporal- (e.g., timing of ED onset and transition), stakeholder- (e.g., patient ambivalence towards recovery) and systemic- (e.g., differences between services) related factors. Most studies were of moderate-to-high quality. Findings informed the development of five transition strategies designed to facilitate effective transfers across ED care: Timely talks, Readiness, Inclusion, Preparation, and Synergy (TRIPS). Conclusions Transitions from CAMHS to AMHS appear problematic for young people with EDs and other involved stakeholders. The field stands to benefit from TRIPS, an actionable, evidence-based framework that aims to alleviate challenges of transitioning and subsequently improve ED trajectories. As a logical next step, future work should empirically test the TRIPS framework, exploring its predictive utility and clinical value.

Abstract During long-duration spaceflight, astronauts experience headward fluid shifts and expansion of the cerebral perivascular spaces (PVS). A major limitation to our understanding of the changes in brain structure and physiology induced by spaceflight stems from the logistical difficulties of studying astronauts. The current study aimed to determine whether PVS changes also occur on Earth with the spaceflight analog head-down tilt bed rest (HDBR). We examined how the number and morphology of magnetic resonance imaging-visible PVS (MV-PVS) are affected by HDBR with and without elevated carbon dioxide (CO2). These environments mimic the headward fluid shifts, body unloading, and elevated CO2 observed aboard the International Space Station. Additionally, we sought to understand how changes in MV-PVS are associated with signs of Spaceflight Associated Neuro-ocular Syndrome (SANS), ocular structural alterations that can occur with spaceflight. Participants were separated into two bed rest campaigns: HDBR (60 days) and HDBR + CO2 (30 days with elevated ambient CO2). Both groups completed multiple magnetic resonance image acquisitions before, during, and post-bed rest. We found that at the group level, neither spaceflight analog affected MV-PVS quantity or morphology. However, when taking into account SANS status, persons exhibiting signs of SANS showed little or no MV-PVS changes, whereas their No-SANS counterparts showed MV-PVS morphological changes during the HDBR + CO2 campaign. These findings highlight spaceflight analogs as models for inducing changes in MV-PVS and implicate MV-PVS dynamic compliance as a mechanism underlying SANS. These findings may lead to countermeasures to mitigate health risks associated with human spaceflight.

Abstract The health of coral reef benthic and fish communities is implicitly connected, yet typically studied and managed separately. By developing a coupled reef population model that connects coral populations and reef fish biomass through the habitat complexity that corals build and fish live among, we aim to address this gap by holistically quantifying ecological feedbacks and responses to ecological stressors. We explored the impacts of fishing effort in conjunction with three types of ecological disturbances as they propagated through a coral reef ecosystem: (1) a disturbance that disproportionately affected small, bio‐energetically vulnerable colonies, (2) a disturbance that predominantly affected large, mechanically vulnerable colonies, and (3) a disturbance that affected colonies of all sizes randomly. We found that joint coral and fish population recovery was fastest and most complete under events affecting small colonies, followed by recovery from disturbances affecting random sizes, and lastly large‐colony disturbances. These results suggest that the retention versus loss of large coral colonies with high reproductive potential critically influenced population recovery. Low fishing levels maintained fish and coral populations and allowed for recovery after disturbances, whereas high fishing levels prevented recovery due to greater fish‐dependent coral mortality. Finally, we tested various formulations of the relationship between coral size and habitat complexity (i.e., exponential, linear, logarithmic) that constrain fish carrying capacity. All formulations led to similar population projections in most disturbance scenarios, but there were exceptions where the timing and trajectory of recovery differed, such as faster and greater recovery potential when complexity is logarithmic with respect to coral size. These findings suggest that fishing and habitat complexity mediate the recovery of coral reef populations, emphasizing the importance of describing linkages between coral size distribution and reef habitat structure. Furthermore, our results highlight the utility of the coupled‐model framework for understanding and managing the impact of disturbances at ecosystem scales.

Abstract Introduction Behavioral measurement‐based care (MBC) can improve patient outcomes and has also been advanced as a critical learning health system (LHS) tool for identifying and mitigating potential disparities in mental health treatment. However, little is known about the uptake of remote behavioral MBC in safety net settings, or possible disparities occurring in remote MBC implementation. Methods This study uses electronic health record data to study variation in completion rates at the clinic and patient level of a remote MBC symptom measure tool during the first 6 months of implementation at three adult outpatient psychiatry clinics in a safety net health system. Provider‐reported barriers to MBC adoption were also measured using repeated surveys at one of the three sites. Results Out of 1219 patients who were sent an MBC measure request, uptake of completing at least one measure varied by clinic: General Adult Clinic, 38% (n = 262 of 696); Substance Use Clinic, 28% (n = 73 of 265); and Transitions Clinic, 17% (n = 44 of 258). Compared with White patients, Black and Portuguese or Brazilian patients had lower uptake. Older patients also had lower uptake. Spanish language of care was associated with much lower uptake at the patient level. Significant patient‐level disparities in uptake persisted after adjusting for the clinic, mental health diagnoses, and number of measure requests sent. Providers cited time within visits and bandwidth in their workflow as the greatest consistent barriers to discussing MBC results with patients. Conclusions There are significant disparities in MBC uptake at the patient and clinic level. From an LHS data infrastructure perspective, safety net health systems may need to address the need for possible ways to adapt MBC to better fit their populations and clinical needs, or identify targeted implementation strategies to close data gaps for the identified disparity populations.

Type 2 diabetes mellitus (T2DM) is a metabolic disease and comorbidity associated with several conditions, including cardiac dysfunction leading to heart failure with preserved ejection fraction (HFpEF), in turn resulting in T2DM-induced cardiomyopathy (T2DM-CM). However, the molecular mechanisms underlying the development of T2DM-CM are poorly understood. It is hypothesized that molecular alterations in myopathic genes induced by diabetes promote the development of HFpEF, whereas cardiac myosin inhibitors can rescue the resultant T2DM-mediated cardiomyopathy. To test this hypothesis, a Leptin receptor-deficient db/db homozygous (Lepr db/db) mouse model was used to define the pathogenesis of T2DM-CM. Echocardiographic studies at 4 and 6 months revealed that Lepr db/db hearts started developing cardiac dysfunction by four months, and left ventricular hypertrophy with diastolic dysfunction was evident at 6 months. RNA-seq data analysis, followed by functional enrichment, revealed the differential regulation of genes related to cardiac dysfunction in Lepr db/db heart tissues. Strikingly, the level of cardiac myosin binding protein-C phosphorylation was significantly increased in Lepr db/db mouse hearts. Finally, using isolated skinned papillary muscles and freshly isolated cardiomyocytes, CAMZYOS® (mavacamten, MYK-461), a prescription heart medicine used for symptomatic obstructive hypertrophic cardiomyopathy treatment, was tested for its ability to rescue T2DM-CM. Compared with controls, MYK-461 significantly reduced force generation in papillary muscle fibers and cardiomyocyte contractility in the db/db group. This line of evidence shows that 1) T2DM-CM is associated with hyperphosphorylation of cardiac myosin binding protein-C and 2) MYK-461 significantly lessened disease progression in vitro, suggesting its promise as a treatment for HFpEF.

Abstract Background Caribbean Latino adults are at high risk for osteoporosis yet remain underrepresented in bone research. This increased risk is attributed to genetics, diet, and lifestyle known to drive inflammation and microbial dysbiosis. Objective The primary objective of this study was to determine whether consuming 5 oz of yogurt daily for 8wks improves bone turnover markers (BTMs) among Caribbean Latino adults > 50 years; and secondarily to determine the impact on the gut microbiota and markers of intestinal integrity and inflammation. Methods Following a 4wk baseline period, participants were randomized to an 8wk whole fat yogurt intervention (n = 10) daily, containing only Streptococcus thermophilus and Lactobacillus bulgaricus, or to an untreated control group that did not consume yogurt (n = 10). Blood and stool samples collected at week-0 and week-8 were used to assess BTMs, inflammation, intestinal integrity biomarkers, and gut microbiota composition, short chain fatty acids (SCFAs), respectively. Data were evaluated for normality and statistical analyses were performed. Results Participants were 55% women, with a mean age of 70 ± 9 years, BMI 30 ± 6 kg/m2, and serum C-reactive protein 4.8 ± 3.6 mg/L, indicating chronic low-grade inflammation. Following 8wks of yogurt intake, absolute change in BTMs did not differ significantly between groups (P = 0.06–0.78). Secondarily, absolute change in markers of inflammation, intestinal integrity, and fecal SCFAs did not differ significantly between groups (P range 0.13–1.00). Yogurt intake for 8wks was significantly associated with microbial compositional changes of rare taxa (P = 0.048); however, no significant alpha diversity changes were observed. Conclusions In this study, daily yogurt did not improve BTMs, inflammation, intestinal integrity, nor SCFAs. However, yogurt did influence beta diversity, or the abundance of rare taxa within the gut microbiota of the yogurt group, compared to controls. Additional research to identify dietary approaches to reduce osteoporosis risk among Caribbean Latino adults is needed. Trial registration This study is registered to ClinicalTrials.gov, NCT05350579 (28/04/2022).

We detected a novel GII.4 variant with an amino acid insertion at the start of epitope A in viral protein 1 of noroviruses from the United States, Gabon, South Africa, and the United Kingdom collected during 2017–2022. Early identification of GII.4 variants is crucial for assessing pandemic potential and informing vaccine development.

AbstractSelf-efficacy is associated with a range of educational outcomes, including science and math degree attainment. Project-based statistics courses have the potential to increase students’ math self-efficacy because projects may represent a mastery experience, but students enter courses with preexisting math self-efficacy. This study explored associations between pre-course math confidence and coding confidence with post-course statistical intentions and perceived achievement among students in a project-based statistics course at 28 private and public colleges and universities between fall 2018 and winter 2020 (n = 801) using multilevel mixed-effects multivariate linear regression within multiply imputed data with a cross-validation approach (testing n = 508 at 20 colleges/universities). We found that pre-course coding confidence was associated with, respectively, 9 points greater post-course statistical intentions and 10 points greater perceived achievement on a scale 0–100 (0.09, 95% confidence interval (0.02, 0.17), p = 0.02; 0.10, 95% CI (0.01, 0.19), p = 0.04), and that minoritized students have greater post-course statistical intentions than nonminoritized students. These results concur with past research showing the potential effectiveness of the project-based approach for increasing the interest of minoritized students in statistics. Pre-course interventions to increase coding confidence such as pre-college coding experiences may improve students’ post-course motivations and perceived achievement in a project-based course. Supplementary materials for this article are available online.

Abstract Sleep deprivation has far-reaching consequences on the brain and behavior, impacting memory, attention, and metabolism. Previous research has focused on gene expression changes in individual brain regions, such as the hippocampus or cortex. Therefore, it is unclear how uniformly or heterogeneously sleep loss affects the brain. Here, we use spatial transcriptomics to define the impact of a brief period of sleep deprivation across the brain in male mice. We find that sleep deprivation induced pronounced differences in gene expression across the brain, with the greatest changes in the hippocampus, neocortex, hypothalamus, and thalamus. Both the differentially expressed genes and the direction of regulation differed markedly across regions. Importantly, we developed bioinformatic tools to register tissue sections and gene expression data into a common anatomical space, allowing a brain-wide comparison of gene expression patterns between samples. Our results suggest that distinct molecular mechanisms acting in discrete brain regions underlie the biological effects of sleep deprivation.

Abstract While aquaculture is increasingly considered a globally important source of protein, growing fish for human consumption is not new. Indigenous aquaculture systems, such as loko i‘a (fishponds), were successfully implemented in ancient Hawai‘i and represent a technological advancement designed to sustain a growing human population while maintaining—instead of supplanting—natural ecosystem function in the process of increasing food availability. Biocultural restoration efforts in Hawai‘i, aimed at revitalizing Indigenous stewardship, have included restoration of loko i‘a to sustainably increase the availability of local seafood. While it is clear from historical accounts that loko i‘a can augment fish within estuaries, their role as a nursery ground that supplements surrounding fish populations and fisheries harvest (i.e., providing spillover) remains unstudied in the current literature. This study aimed to test the extent to which loko i‘a restoration can supplement fish populations and fisheries harvest both inside the loko i‘a and in the surrounding waters. A food web model was constructed representing nutrients, phytoplankton, fish, and fisheries in three distinct habitats. The model, set in Kāne‘ohe Bay, O‘ahu, Hawai‘i, revealed that there were interactive effects of the area under loko i‘a management, bay fishing effort, and fish dispersal rates on fish density and fisheries harvest. We found that increasing the area under loko i‘a management not only increased loko i‘a fish density and fisheries harvest but also created the potential to supplement bay fish populations and fisheries harvest under certain scenarios. We also identified a trade‐off whereby at high fish dispersal rates, a larger area under loko i‘a management provided maximal benefits to the bay fish population and fisheries harvest, while at low fish dispersal rates, a smaller area under loko i‘a management was more beneficial to bay fish populations and harvest. As expected, loko i‘a also created a surplus of fish within the pond. Our results support the idea that restoration of Indigenous aquaculture systems can positively impact conservation efforts and food security by increasing local fish availability, through both direct production and supplementation of surrounding fish stocks.

IntroductionResearch on the dimensional structure of subjective well-being (SWB) suggests a five-dimensional solution, consisting of the three established dimensions of life satisfaction, positive affect, and negative affect, and two additional empirically supported dimensions: domain satisfaction and happiness. While these dimensions can be aggregated into a superordinate SWB construct, little research has explored how these dimensions differ in their variation across subpopulations of individuals.MethodsThe present study addresses this gap via secondary analysis of a sample of 1,487 partnered individuals, using the five dimensions of SWB as indicators for latent profile analysis.ResultsAnalyses returned five profiles, which we labeled Satisfied, Ambivalent, Indifferent, Dissatisfied, and Very Dissatisfied. In the Ambivalent and Indifferent profiles, the dimensions of negative affect and happiness exhibit discrepant behavior, resulting in shape differences. The five profiles are organized with reference to the external criterion of couple satisfaction. At the theoretical level, the results of the present study have the potential to inform current debates about the structure of well-being.DiscussionThese findings suggest that, while SWB can usually be measured as a unidimensional construct, there is still merit to using multidimensional approaches and alternative forms of measurement—such as LPA—that capture complexities normally absent from unidimensional treatments. At the practical level, the results of the current study have the potential to inform well-being interventions (both clinical and otherwise), suggesting that those dealing with well-being in real life situations should pause before concluding that the absence of negativity implies the presence of positivity, or vice versa.

Abstract Immunoassays are widely used in various fields, including biomedical research, clinical diagnostics, and environmental monitoring. Single domain antibodies (sdAbs) provide small, tailorable, recognition elements that have been integrated into immunoassays for detecting a myriad of targets. Deoxyribonucleic acid (DNA) circuits are synthetic molecular devices composed of DNA strands that can perform logical or computational operations. They have a range of applications, including biosensing, diagnostics, and drug delivery. Recently, an immunoassay method was reported that used catalytic hairpin assemblies (CHA) with antibodies for homogeneous protein detection. The CHA process uses DNA hairpins that interact in the presence of a catalytic DNA sequence. This paper presents a new strategy to couple the recognition of sdAbs with CHA circuits using genetic fusions of sdAbs with rhizavidin (rz), a dimeric biotin binding protein. A pair of sdAb‐rz constructs is each functionalized with a biotinylated DNA sequence that represents half of the catalyst. When both sdAbs bind to the target protein, a signal is generated through the CHA circuit. The split catalyst approach amplifies signals through a DNA circuit without washing steps. Furthermore, this method distinctively utilizes programmable DNA circuits, which are highly modular and can accommodate new targets without disrupting the assay.

Avian malaria parasites or haemosporidia are found in bird species worldwide. This special issue focuses on 3 most commonly studied genera: Haemoproteus, Plasmodium and Leucocytozoon. Seven research articles and reviews are provided to illustrate the breadth of knowledge of the diversity of avian malaria parasites in different regional habitats and across bird species, and the use of avian haemosporidian systems to examine host–parasite eco-evolutionary questions.

Abstract Menopause is associated with cognitive deficits and brain atrophy, but the brain region and cell-specific mechanisms are not fully understood. Here, we identify a sex hormone by age interaction whereby loss of ovarian hormones in female mice at midlife, but not young age, induced hippocampal-dependent cognitive impairment, dorsal hippocampal atrophy, and astrocyte and microglia activation with synaptic loss. Selective deletion of estrogen receptor beta (ERβ) in astrocytes, but not neurons, in gonadally intact female mice induced the same brain effects. RNA sequencing and pathway analyses of gene expression in hippocampal astrocytes from midlife female astrocyte-ERβ conditional knock out (cKO) mice revealed Gluconeogenesis I and Glycolysis I as the most differentially expressed pathways. Enolase 1 gene expression was increased in hippocampi from both astrocyte-ERβ cKO female mice at midlife and from postmenopausal women. Gain of function studies showed that ERβ ligand treatment of midlife female mice reversed dorsal hippocampal neuropathology.

Collaborative multicenter research has significantly increased our understanding of fetal Ebstein anomaly, delineating risk factors for adverse outcomes as well as predictors of postnatal management. These data are incorporated into prenatal care and therapeutic strategies and inform family counseling and delivery planning to optimize care. This report details the translation of findings from multicenter studies into multidisciplinary prenatal care for a fetus with Ebstein anomaly, supraventricular tachycardia, and a circular shunt, including transplacental therapy to control arrhythmias and achieve ductal constriction, informed and coordinated delivery room management, and planned univentricular surgical palliation.

Abstract Tetrahydrobiopterin (BH4) is an essential cofactor for nitric oxide (NO) synthases in which its production of NO is crucial for cardiac function. However, non‐canonical roles of BH4 have been discovered recently and the cell‐specific role of cardiomyocyte BH4 in cardiac function and metabolism remains to be elucidated. Therefore, we developed a novel mouse model of cardiomyocyte BH4 deficiency, by cardiomyocyte‐specific deletion of Gch1, which encodes guanosine triphosphate cyclohydrolase I, a required enzyme for de novo BH4 synthesis. Cardiomyocyte (cm)Gch1 mRNA expression and BH4 levels from cmGch1 KO mice were significantly reduced compared to Gch1flox/flox (WT) littermates. Transcriptomic analyses and protein assays revealed downregulation of genes involved in fatty acid oxidation in cmGch1 KO hearts compared with WT, accompanied by increased triacylglycerol concentration within the myocardium. Deletion of cardiomyocyte BH4 did not alter basal cardiac function. However, the recovery of left ventricle function was improved in cmGch1 KO hearts when subjected to ex vivo ischaemia–reperfusion (IR) injury, with reduced infarct size compared to WT hearts. Metabolomic analyses of cardiac tissue after IR revealed that long‐chain fatty acids were increased in cmGch1 KO hearts compared to WT, whereas at 5 min reperfusion (post‐35 min ischaemia) fatty acid metabolite levels were higher in WT compared to cmGch1 KO hearts. These results indicate a new role for BH4 in cardiomyocyte fatty acid metabolism, such that reduction of cardiomyocyte BH4 confers a protective effect in response to cardiac IR injury. Manipulating cardiac metabolism via BH4 could play a therapeutic role in limiting IR injury.

Abstract To reduce HIV transmission, locally applied pre-exposure prophylaxis (PrEP) products for anorectal use will be important complements to oral and injectable PrEP products already available. It is critical to preserve an intact rectal epithelium and avoid an influx of mucosal HIV target cells with such product use. In this phase 1 clinical trial, we evaluated application of a topical rectal douche product containing Q-Griffithsin (Q-GRFT). Colorectal tissue samples were obtained via sigmoidoscopy at baseline, 1 and 24 h after single-dose exposure in 15 healthy volunteers. In situ staining for epithelial junction markers and CD4+ cells were assessed as an exploratory endpoint. A high-throughput, digitalized in situ imaging analysis workflow was developed to visualize and quantify these HIV susceptibility markers. We observed no significant differences in epithelial distribution of E-cadherin, desmocollin-2, occludin, claudin-1, or zonula occludens-1 when comparing the three timepoints or Q-GRFT versus placebo. There were also no differences in %CD4+ cells within the epithelium or lamina propria in any of these comparisons. In conclusion, the rectal epithelium and CD4+ cell distribution remained unchanged following topical application of Q-GRFT. In situ visualization of HIV susceptibility markers at mucosal sites could be useful to complement standard product safety assessments.

During the COVID-19 pandemic, US schools have been encouraged to take a layered approach to prevention, incorporating multiple strategies to curb transmission of SARS-CoV-2. Using survey data representative of US public K–12 schools (N = 437), we determined prevalence estimates of COVID-19 prevention strategies early in the 2021–22 school year and describe disparities in implementing strategies by school characteristics. Prevalence of prevention strategies ranged from 9.3% (offered COVID-19 screening testing to students and staff) to 95.1% (had a school-based system to report COVID-19 outcomes). Schools with a full-time school nurse or school-based health center had significantly higher odds of implementing several strategies, including those related to COVID-19 vaccination. We identified additional disparities in prevalence of strategies by locale, school level, and poverty. Advancing school health workforce and infrastructure, ensuring schools use available COVID-19 funding effectively, and promoting efforts in schools with the lowest prevalence of infection prevention strategies are needed for pandemic preparedness.

BackgroundChanges in regional levels of the inhibitory neurotransmitter gamma-aminobutyric acid (GABA) may indicate the potential for favorable responses to the treatment of stroke affecting the upper extremity. By selectively altering GABA levels during training, we may induce long-term potentiation and adjust excitatory/inhibitory balance (E/I balance). However, the impact of this alteration may be limited by neural damage or aging. Aerobic exercise has been shown to increase GABA levels in the sensorimotor cortex and improve motor learning by widening the dynamic range of E/I balance. The cross-sectional project, Effects of Acute Exercise on Functional Magnetic Resonance Spectroscopy Measures of GABA in Aging and Chronic Stroke (EASE), is designed to assess the functional relevance of changes in GABA concentration within the sensorimotor cortex before and after an acute aerobic exercise session.Methods/designEASE will enroll 30 participants comprised of healthy younger adults (18-35 years; n = 10), older adults (60+ years; n = 10), and persons with chronic stroke (n = 10) affecting distal upper extremity function. We will use resting magnetic resonance spectroscopy to measure all participants' GABA levels at rest before and after aerobic exercise. In addition, we will employ functional magnetic resonance spectroscopy using motor skill acquisition and recall tasks in healthy adults. We hypothesize that acute aerobic exercise will increase resting sensorimotor GABA concentration and that higher GABA resting levels will predict better motor learning performance on measures taken both inside and outside the magnet. We also hypothesize that a higher dynamic range of GABA during task-based spectroscopy in healthy adults will predict better motor skill acquisition and recall.DiscussionThe EASE project will evaluate the effect of acute exercise on GABA levels as a biomarker of upper extremity motor skill learning with two populations (aging adults and those with chronic stroke). We predict that acute exercise, higher sensorimotor GABA levels, and broader dynamic range will be related to better motor skill acquisition.

Abstract Introduction Implementation of research findings in clinical practice often is not realized or only partially achieved, and if so, with a significant delay. Learning health systems (LHSs) hold promise to overcome this problem by embedding clinical research and evidence‐based best practices into care delivery, enabling innovation and continuous improvement. Implementing an LHS is a complex process that requires participation and resources of a wide range of stakeholders, including healthcare leaders, clinical providers, patients and families, payers, and researchers. Engaging these stakeholders requires communicating clear, tangible value propositions. Existing models identify broad categories of benefits but do not explicate the full range of benefits or ways they can manifest in different organizations. Methods To develop such a framework, a working group with representatives from six Clinical and Translational Science Award (CTSA) hubs reviewed existing literature on LHS characteristics, models, and goals; solicited expert input; and applied the framework to their local LHS experiences. Results The Framework of LHS Benefits includes six categories of benefits (quality, safety, equity, patient satisfaction, reputation, and value) relevant for a range of stakeholders and defines key concepts within each benefit. Applying the framework to five LHS case examples indicated preliminary face validity across varied LHS approaches and revealed three dimensions in which the framework is relevant: defining goals of individual LHS projects, facilitating collaboration based on shared values, and establishing guiding tenets of an LHS program or mission. Conclusion The framework can be used to communicate the value of an LHS to different stakeholders across varied contexts and purposes, and to identify future organizational priorities. Further validation will contribute to the framework's evolution and support its potential to inform the development of tools to evaluate LHS impact.

IntroductionIn this study we explore how the diagnostic category of mood disorders is constructed in two handbooks of Psychopathology as an example of the mainstream construction of psychopathology. Despite the increasing criticism and lack of evidence, the debunked chemical imbalance theory of the etiology of depression still dominates the professional and pop/folk understanding and interventions.MethodsWe analysed the breadth of the inference field and the type of etiopathogenetic contents of the explanations of mood disorders using the “1to3” Coding System.ResultsOur findings show that the dominant explanations draw almost exclusively onto monadic explanations, followed by limited dyadic ones. Intrapersonal etiopathogenetic contents prevailed, and biomedical explanations were dominant in both textbooks.DiscussionWe critically discuss the underpinnings of these results and address the clinical implications of these biased representations, as well as potential alternative approaches to psychopathology.

Ocean-based industries like shipping, aquaculture, and wind energy are growing at an unprecedented rate resulting in challenges related to siting and environmental management. As marine aquaculture and other ocean-based industries continue to expand, robust marine spatial planning analyses that reconcile existing ocean uses and integrate pertinent environmental and planning data are critical for identifying compatible locations. In this study, a series of geospatial analyses were used for aquaculture siting within and around a heavily trafficked and highly utilized maritime port in the San Diego Bay area of California, USA. Using a centralized geodatabase representing key aquaculture planning spatial datasets, recommendations for specific areas for aquaculture were developed based on appropriate environmental conditions for candidate shellfish and algae aquaculture species culture systems. Areas that were known constraints were first identified to determine potentially usable areas for shellfish and macroalgae (i.e., seaweed) aquaculture using an exclusion analysis, a type of multi-criteria decision analysis, to eliminate all areas without compatibility. Within the remaining usable area, we further considered shellfish and macroalgae culture system-specific factors within a ‘culture systems analysis’ to determine where different culture systems have potential for success. This analysis provides a foundation of coastal intelligence for guiding the aquaculture industry and natural resource managers towards appropriate siting decisions. This study can serve as a replicable example of aquaculture spatial planning approaches for siting sustainable aquaculture and other blue economy industries.

BackgroundThe environmental and social impacts of cultured meat, and its economic viability, are contingent on its implications for food production and for agriculture. However, the implications of cultured meat production for farmers have not yet been thoroughly investigated and are poorly understood. The aim of this research was to engage with the farming sector in critically assessing cultured meat as a technology which could profoundly affect future farm livelihoods, land use, rural and farming communities and agricultural value chains. Ensuring farmers’ voices, and potential ‘counter-narratives’ inform the development of cultured meat is not only inclusive, but could identify unexpected impacts of this emerging technology and contribute to the framing of the social license of the industry developing them.MethodsSix focus groups were undertaken with 75 UK farmers from a variety of farming sectors and regions. Questions focused on what the term ‘cultured meat’ means to farmers, the potential impacts of cultured meat, and potential business scenarios arising for farmers. All meetings were recorded, transcribed, and thematically analyzed.Results and discussionFarmers expressed complex and considered reflections on cultured meat, raising several perceived opportunities and risks associated with the themes of ‘ethics and affective’ narratives, ‘environment-based’ narratives, and ‘socio-economic’ narratives. Aspects of foci of power, food system control and transparency associated with cultured meat emerged from the conversations, as well as cultured meat’s potential impacts on the environment and on jobs, farming/rural communities and connecting with the land.ConclusionGlobally, meat production underpins the livelihoods of many rural communities, so a transition to cultured meat is likely to have deep-seated ethical, environmental, and socio-economic impacts. Within the discourse on cultured meat the voices of farmers are often lost. While not claiming to be representative of all UK farming, this study engaged UK farmer perspectives as a way of starting the substantive process of greater stakeholder inclusion in cultured meat innovation pathways, and which should underpin responsible technology transitions in agriculture.

Background: With notable benefits in reducing length of stay (LOS), this study aimed to quantify the temporal trend and the factors contributing to increased LOS for primary and revision total hip (THA and rTHA) and knee (TKA and rTKA) arthroplasty. The study was carried out for a large population-based cohort over a 20-year period. Methods: This was a retrospective population-based study assessing the LOS for all primary and revision THA and TKA procedures between 2003 and 2022. The primary outcome of interest was LOS. Univariate and multivariate analyses were performed to identify associated variables. Results: For the entire dataset, there were 16,677 primary THAs, 13,018 primary TKAs, 3276 (aseptic) rTHAs, 1445 (aseptic) rTKAs, 820 (septic) rTHAs, and 667 (septic) rTKAs. The median LOS over the 20-year period between 2003 and 2022 demonstrated a steady and continuous decline from a median of 5 days (interquartile range 3-7) in 2003 to 1 day (interquartile range 1-2) in 2022. On multivariate analysis, there were a number of factors associated with increasing LOS: year of procedure (P < .0001), procedure type (P < .0001), age (P < .0001), and American Society of Anesthesiologists class (P < .0001). On multivariate analysis, body mass index was not associated with increased LOS (P = .5631). Conclusions: There was a downward trend in LOS for all types of primary and revision THA and TKA. The factors contributing most to a reduction in LOS include the year the procedure was performed, primary THA procedures, aseptic (vs periprosthetic joint infection) revision procedures, younger age, and lower American Society of Anesthesiologists classes.

Objective: To establish the feasibility of an intervention consisting of neuromuscular exercise, mind-body techniques, and pain neuroscience education (PNE), referred to as Pain Informed Movement in people with knee Osteoarthritis (KOA). This program has the potential to improve our understanding of intrinsic pain modulation and its role in the management of chronic pain. Methods: This was a single-arm feasibility trial with a nested qualitative component. Primary outcome: complete follow-up. Inclusion criteria: age ≥40 years, KOA clinical diagnosis or meeting KOA NICE criteria, and pain intensity ≥3/10. The program consisted of 8-week in-person and at-home exercise sessions. PNE and mind-body techniques were provided as videos and integrated into the exercise sessions. Participants completed questionnaires and physical assessments including blood draws at baseline and program completion. Secondary feasibility outcomes: acceptability of the intervention, burden, rates of recruitment, compliance and adherence, and adverse events. A priori success criteria were identified. Participants were invited to an online focus group. Results: 19 participants were enrolled, with a complete follow-up rate of 74% (mean age 63.3 years (SD 10.5), 73% female), indicating modifications were necessary to proceed. All other success criteria were met. The focus groups revealed that the video content pertaining to the mind-body techniques would benefit from on screen demonstrations. Conclusion: The Pain Informed Movement program is deemed feasible, with minor modifications needed to proceed. A pilot two-arm RCT will be conducted to establish the feasibility and explore potential effects of Pain Informed Movement compared to conventional neuromuscular exercise and standard OA education.

Objective: Conservative pain management strategies for knee osteoarthritis (KOA) have limited effectiveness and do not employ a pain-mechanism informed approach. Pain Informed Movement is a novel intervention combining mind-body techniques with neuromuscular exercise and pain neuroscience education (PNE), aimed at improving endogenous pain modulation. While the feasibility and acceptability of this program has been previously established, it now requires further evaluation in comparison to standard KOA care. Design: This protocol describes the design of a pilot two-arm randomized controlled trial (RCT) with an embedded qualitative component. The primary outcome is complete follow-up rate. With an allocation ratio of 1:1, 66 participants (33/arm) (age ≥40 years, KOA diagnosis or meeting KOA NICE criteria, and pain intensity ≥3/10), will be randomly allocated to two groups that will both receive 8 weeks of twice weekly in-person exercise sessions. Those randomized to Pain Informed Movement will receive PNE and mind-body technique instruction provided initially as videos and integrated into exercise sessions. The control arm will receive neuromuscular exercise and standard OA education. Assessment will include clinical questionnaires, physical and psychophysical tests, and blood draws at baseline and program completion. Secondary outcomes are program acceptability, burden, rate of recruitment, compliance and adherence, and adverse events. Participants will be invited to an online focus group at program completion. Conclusion: The results of this pilot RCT will serve as the basis for a larger multi-site RCT aimed at determining the program's effectiveness with the primary outcome of assessing the mediating effects of descending modulation on changes in pain.

BackgroundCaregivers of children with medical complexity navigate complex family management tasks for their child both in the hospital and home-based setting. The roles and relationships of members of their social network and the dynamic evolution of these family management tasks have been underexamined. ObjectiveThe purpose of this study was to explore the structures and processes of family management among caregivers of children with medical complexity, with a focus on the underlying dynamic nature of family management practices and the role of members of their social network. MethodsThis study used a qualitative approach to interview caregivers of children with medical complexity and members of their social network. Caregivers of children with medical complexity were recruited through an academic Children’s Hospital Complex Care Clinic in the mid-Atlantic region and interviewed over a period of 1 to 3 days. Responses were analyzed using constructivist grounded theory and situational analysis to construct a new conceptual model. Only caregiver responses are reported here. ResultsIn total, 20 caregivers were included in this analysis. Caregiver perspectives revealed the contextual processes that allowed for practices of family management within the setting of rapidly evolving symptoms and health concerns. The dynamic and adaptive nature of this process is a key underlying action supporting this novel conceptual model. The central themes underpinning the adaptive family management model include symptom cues, ongoing surveillance, information gathering, and acute on chronic health concerns. The model also highlights facilitators and threats to successful family management among children with medical complexity and the networked relationship among the structures and processes. ConclusionsThe adaptive family management model provides a basis for further quantitative operationalization and study. Previously described self- or family management frameworks do not account for the underlying dynamic nature of the disease trajectory and the developmental stage progression of the child or adolescent, and our work extends existing work. For future work, there is a defined role for technology-enhanced personalized approaches to home-based monitoring. Due to the disparities caregivers and the children in this population already experience, technology-enhanced approaches must be built alongside key stakeholders with an equity orientation to technology co-development. International Registered Report Identifier (IRRID)RR2-10.2196/14810

Objective Dashboards can support person‐centered care by helping people partner with their clinicians to coproduce care based on preferences, shared decision‐making, and evidence‐based treatments. We engaged caregivers of children with juvenile idiopathic arthritis (JIA), adults with rheumatoid arthritis (RA), and clinicians in a pilot study to assess their experiences and the utility and impact of an electronic previsit questionnaire and point‐of‐care dashboard to support coproduction of rheumatology care. Methods We employed a mixed‐methods design to assess users’ perceptions of a customized electronic health record rheumatology module at four pediatric rheumatology practices and two adult rheumatology practices. We surveyed a convenience sample of caregivers of children with JIA (n = 113), adults with RA (n = 116), and clinicians (n = 12). We conducted semistructured interviews with 13 caregivers and patients and six care teams. Experiences were evaluated using descriptive statistics and thematic analyses. Results Caregivers of children with JIA and adults with RA reported the dashboards were useful during discussions (88%) and helped them talk about what mattered most (82%), make health care decisions (83%), and create a treatment plan (77%). Clinicians provided similar feedback. Two‐thirds (67%) of caregivers and adults and 55% of clinicians would recommend the dashboard to peers. System usability scores (77.1 ± 15.6) were above average. Dashboards helped users make sense of health information, communicate more effectively, and make decisions. Improvements to the dashboards and workflows could enhance patient self‐management and clinician efficiency. Conclusion Visual point‐of‐care dashboards can support caregivers, patients, and clinicians to coproduce rheumatology care. Findings demonstrate a need to spread and scale for broader benefit and impact.

Abstract Background Clinical and real-world effectiveness data for the COVID-19 vaccines have shown that they are the best defense in preventing severe illness and death throughout the pandemic. However, in the US, some groups remain more hesitant than others about receiving COVID-19 vaccines. One important group is long-term care workers (LTCWs), especially because they risk infecting the vulnerable and clinically complex populations they serve. There is a lack of research about how best to increase vaccine confidence, especially in frontline LTCWs and healthcare staff. Our aims are to: (1) compare the impact of two interventions delivered online to enhanced usual practice on LTCW COVID-19 vaccine confidence and other pre-specified secondary outcomes, (2) determine if LTCWs’ characteristics and other factors mediate and moderate the interventions’ effect on study outcomes, and (3) explore the implementation characteristics, contexts, and processes needed to sustain a wider use of the interventions. Methods We will conduct a three-arm randomized controlled effectiveness-implementation hybrid (type 2) trial, with randomization at the participant level. Arm 1 is a dialogue-based webinar intervention facilitated by a LTCW and a medical expert and guided by an evidence-based COVID-19 vaccine decision tool. Arm 2 is a curated social media web application intervention featuring interactive, dynamic content about COVID-19 and relevant vaccines. Arm 3 is enhanced usual practice, which directs participants to online public health information about COVID-19 vaccines. Participants will be recruited via online posts and advertisements, email invitations, and in-person visits to care settings. Trial data will be collected at four time points using online surveys. The primary outcome is COVID-19 vaccine confidence. Secondary outcomes include vaccine uptake, vaccine and booster intent for those unvaccinated, likelihood of recommending vaccination (both initial series and booster), feeling informed about the vaccines, identification of vaccine information and misinformation, and trust in COVID-19 vaccine information provided by different people and organizations. Exploration of intervention implementation will involve interviews with study participants and other stakeholders, an in-depth process evaluation, and testing during a subsequent sustainability phase. Discussion Study findings will contribute new knowledge about how to increase COVID-19 vaccine confidence and effective informational modalities for LTCWs. Trial registration NCT05168800 at ClinicalTrials.gov, registered December 23, 2021.

Abstract Much of the learning that college students engage in today occurs in unsupervised settings, making effective self-regulated learning techniques of particular importance. We examined the impact of task difficulty and supervision on whether participants would follow written instructions to use repeated testing over restudying. In Study 1, we found that when supervised, instructions to test resulted in changes in the self-regulated learning behaviors such that participants tested more often than they studied, relative to participants who were unsupervised during learning. This was true regardless of the task difficulty. In Study 2, we showed that failure to shift study strategies in unsupervised learning was likely due to participants avoidance of testing rather than failure to read the instructions at all. Participants who tested more frequently remembered more words later regardless of supervision or whether or not they received instructions to test, replicating the well-established testing effect (e.g., Dunlosky et al. in Psychol Sci Public Interest 14:4–58, 2013. http://doi.org/10.1177/1529100612453266 ). In sum, there was a benefit to testing, but instructing participants to test only increased their choice to test when they were supervised. We conclude that supervision has an impact on whether participants follow instructions to test.

Abstract Background Delayed medical care may result in adverse health outcomes and increased cost. Our purpose was to identify factors associated with delayed medical care in a primarily rural state. Methods Using a stratified random sample of 5,300 Nebraska households, we conducted a cross-sectional mailed survey with online response option (27 October 2020 to 8 March 2021) in English and Spanish. Multiple logistic regression models calculated adjusted odds ratios (aOR) and 95% confidence intervals. Results The overall response rate was 20.8% (n = 1,101). Approximately 37.8% of Nebraskans ever delayed healthcare (cost-related 29.7%, transportation-related 3.7%), with 22.7% delaying care in the past year (10.1% cost-related). Cost-related ever delay was associated with younger age [

Objectives Sex-specific differences in the presentation of axial spondyloarthritis (axSpA) may contribute to a diagnostic delay in women. The aim of this study was to investigate the diagnostic performance of MRI findings comparing men and women.Methods Patients with back pain from six different prospective cohorts (n=1194) were screened for inclusion in this post hoc analysis. Two blinded readers scored the MRI data sets independently for the presence of ankylosis, erosion, sclerosis, fat metaplasia and bone marrow oedema. Χ2 tests were performed to compare lesion frequencies. Contingency tables were used to calculate markers for diagnostic performance, with clinical diagnosis as the standard of reference. The positive and negative likelihood ratios (LR+/LR–) were used to calculate the diagnostic OR (DOR) to assess the diagnostic performance.Results After application of exclusion criteria, 526 patients (379 axSpA (136 women and 243 men) and 147 controls with chronic low back pain) were included. No major sex-specific differences in the diagnostic performance were shown for bone marrow oedema (DOR m: 3.0; f: 3.9). Fat metaplasia showed a better diagnostic performance in men (DOR 37.9) than in women (DOR 5.0). Lower specificity was seen in women for erosions (77% vs 87%), sclerosis (44% vs 66%), fat metaplasia (87% vs 96%).Conclusion The diagnostic performance of structural MRI markers is substantially lower in female patients with axSpA; active inflammatory lesions show comparable performance in both sexes, while still overall inferior to structural markers. This leads to a comparably higher risk of false positive findings in women.