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Highlights This review provides a detailed account of engineered plant cell wall (CW)-mimetic soft materials, which are designed to replicate the intricate composition, structure, and mechanical properties of natural plant CWs. Experimental methods to create CW-like materials are reviewed, and relevant characterization techniques, including mechanical, chemical, structural, and morphological analyses, are discussed. The applications of CW-like materials in several fields, including food packaging, edible films, drug delivery, construction materials, and biocatalysis are highlighted.

Abstract Background Variation in stroke treatment metrics highlight a need for approaches to improve clinical processes. Training interventions can improve outcomes, but Australian physician trainees do not currently receive formal process-directed stroke training. Virtual reality (VR) stroke workflow training has proven acceptable, usable, useful and feasible in trial contexts, but how to integrate VR training into physician training remains unclear. The current study sought to document stroke staff perceptions of existing training and assess implementation of routine VR training at comprehensive stroke centres, outside of a trial context. Methods Training was delivered to physician trainees via individual sessions or facilitated group workshops depending on the hospital site. VR usage data was captured automatically via Wi-Fi. Survey responses from both trainees and training staff were collected, with statistical comparisons performed for matching questions in pre- and post-training surveys. Themes identified in open-ended survey responses were enumerated and reported. Results Forty-two TACTICS VR training sessions were logged at 2 hospitals between May 2022 and October 2023. Trainees reported receiving low amounts of prior formal stroke training; both trainees and training staff identified unmet needs and barriers to existing training. VR users (n = 30) provided positive feedback on VR hardware, software design, user experience, content, educational value and delivery approach (mean scores 3.9 to 4.7; 1 = strongly disagree, 5 = strongly agree). VR training improved confidence in: knowledge of acute stroke assessment / treatment (post-training vs. pre-training = 4.0±0.7 vs. 2.9±1.0; P

Background: The Beat It program is a clinician-led, community-based group exercise intervention for adults with Type 2 Diabetes Mellitus (T2DM). While previous studies have demonstrated its effectiveness in improving physical and mental health outcomes, this study explores the perspectives of Beat It Trainers to identify key factors contributing to the program’s success and areas for improvement. Methods: Semi-structured interviews were conducted with 11 Accredited Exercise Physiologists who had delivered both in-person and online versions of the program. Interviews were thematically analyzed using inductive approaches. Results: Eight main themes emerged: customization to individual needs, capability building, outcome improvement, affordability, accessibility, sustainability, and a holistic approach delivered in a group setting. Challenges identified included managing group dynamics, maintaining participant commitment in a fully subsidized program, and providing nutrition advice within the trainers’ scope of practice. The program’s adaptability to both in-person and online delivery modes was highlighted as enhancing its accessibility and resilience. Conclusions: This study provides valuable insights into the factors contributing to the success of the Beat It program from the implementers’ perspective. The findings suggest that investing in comprehensive training for facilitators, particularly in group dynamics management, could benefit similar programs. While the program’s fully subsidized structure reduces financial barriers to entry, innovative strategies to enhance participant engagement and perceived value should be explored. The success of the online delivery mode indicates that hybrid models offering both in-person and virtual options could increase accessibility in future supervised, community-based exercise programs for T2DM management.

Abstract Current diagnostic criteria for cardiac sarcoidosis (CS) rely on non-invasive imaging tools including positron emission tomography (PET-CT) and cardiac magnetic resonance (CMR). The aim of this study was to assess the prevalence of discordant myocardial inflammation between PET-CT and CMR in patients with known cardiac sarcoidosis. We retrospectively identified patients with both 18F-FDG PET-CT and CMR who had histology-proven sarcoidosis (N = 148). Among these 25 (17%) had abnormal 18F-FDG metabolism with normal tissue characterization by CMR. Of these, 13 (9%) had the studies concomitantly within 180 days (median 5 days, IQR 1–31). During median follow up of 7 years, 3 (23%) deaths were documented. Although prospective studies are required to address the best imaging approach for cardiac inflammation, our observation that some patients with CS have evidence of disease activity on PET-CT, but not on limited CMR without mapping suggests that a negative limited CMR may not fully exclude CS.

Abstract Background Hand hygiene is known to reduce healthcare-associated infections. However, it remains suboptimal among healthcare providers. In this study, we used the Behaviour-centered Design approach to explore the facilitators and deterrents to hand hygiene among healthcare providers in the Kampala Metropolitan area, Uganda. Methods We conducted a formative qualitative study as part of a cluster randomised trial in 19 healthcare facilities (HCFs). The study used 19 semi-structured and 18 key informant interviews to collect data on hand hygiene status and facilitators and deterrents of hand hygiene. Research assistants transcribed verbatim and used a thematic framework aided by Nvivo 14.0. to undertake analysis. We used thick descriptions and illustrative quotes to enhance the credibility and trustworthiness of our findings. Results About 47.4% of the HCFs had sufficient hand hygiene infrastructure, and 57.9% did not report total compliance with hand hygiene during patient care. The physical facilitator for hand hygiene was the presence of constant reminders such as nudges, while the biological included the frequency of patient contact and the nature of clinical work. The only biological deterrent was the heavy workload in HCFs. The executive brain facilitators included knowledge of workplace health risks, infection prevention and control (IPC) guidelines, and a positive attitude. A negative attitude was the executive brain deterrent to hand hygiene. Recognition, rewards, and fear of infections were the only motivated brain facilitators. Behavioural setting facilitators included proximity to functional hand hygiene infrastructure, the existence of active IPC committees, good leadership, and the availability of a budget for hand hygiene supplies. Behavioural setting deterrents included the non-functionality and non-proximity to hand hygiene infrastructure and inadequate supplies. Conclusions The study revealed low compliance with hand hygiene during the critical moments of patient care and inadequacy of hand hygiene infrastructure. The deterrents to hand hygiene included a heavy workload, negative attitude, inadequate supplies, non-functionality, and long distance to hand washing stations. Facilitators included constant reminders, fear of infections, frequency of patient contact and nature of clinical work, positive attitude, knowledge of IPC guidelines, recognition and reward, good leadership, availability of budgets for hand hygiene supplies, availability and proximity to hand hygiene supplies and infrastructure and active IPC committees. Trial registration ISRCTN Registry with number ISRCTN98148144. The trial was registered on 23/11/2020.

Brugada Syndrome (BrS) is a cardiac arrhythmia disorder which can lead to sudden cardiac death. It is commonly associated with loss-of-function mutations in the SCN5A gene, encoding the alpha subunit of the sodium voltage-gated channel. We introduced the BrS associated mutation c.845G>A (p.R282H) in the SCN5A gene in a human induced pluripotent stem cell (hiPSC) line. We describe two lines, where the mutation is either in the same (cis) or opposite (trans) allele to the common polymorphism c.1673A>G (p.H558R). These hiPSC lines provide physiological models to study the role of this mutation and the effect of the polymorphism in BrS.

Abstract BackgroundAs the population of individuals with HIV ages rapidly due to advancements in antiretroviral therapy, virtual care has become an increasingly vital component in managing their complex health needs. However, little is known about perceptions of care among older adults living with HIV. ObjectiveThis study aimed to understand the perceptions of older adults living with HIV regarding care. MethodsUsing an interpretive, qualitative, descriptive methodology, semistructured interviews were conducted with 14 diverse older adults living with HIV. The participants lived in Ontario, Canada, self-identified as HIV-positive, and were aged 50 years or older. Efforts were made to recruit individuals with varying experience with health care. Reflexive thematic analysis was conducted with the interview transcripts to identify prevalent themes. ResultsThe identified themes included (1) the importance of relationships in virtual care for older adults living with HIV; (2) privacy and confidentiality in virtual care; and (3) challenges and solutions related to access and technological barriers in virtual care. These themes highlight the perceptions of diverse older adults living with HIV concerning care, emphasizing the fundamental role of trust, privacy, and technology access. ConclusionsBy embracing the unique perspectives and experiences of this population, we can work toward building more inclusive and responsive health care systems that meet the needs of all individuals, regardless of age, HIV status, or other intersecting identities.

Objective: The objective of this study was to explore the experiences of distressed people calling helplines regarding offer and uptake of financial services after cancer diagnosis. Methods: Cancer patients and caregivers reported whether they had discussed then used financial services and perceptions surrounding service uptake. Associations between being offered services and demographic, clinical and financial characteristics were explored. Results: Of the 508 patients and caregivers in this sample, 107 (21%) people who recalled discussing financial support used the service. Of those, 34 (32%) participants actioned a financial support referral, of which 32 (94%) reported that the support was helpful. Of the 401 (79%) who did not recall discussing financial support, 26 (6%) would have liked to do so. The following characteristics were significantly associated with a greater likelihood of discussing financial support: younger age, being married, metastatic disease, higher out-of-pocket costs, not having private health insurance, being on leave and being absent for more days from work. Conclusions: Although users of financial supports find them helpful, there is need for more structured approaches to referral to achieve equitable access. Implications for public health: A pro-active, structured approach to assessing financial toxicity and offering support is warranted in community-based organisations that offer cancer information and support.

Low maternal vitamin D concentrations during pregnancy have been associated with a range of offspring health outcomes. DNA methylation is one mechanism by which the maternal vitamin D status during pregnancy could impact offspring’s health in later life. We aimed to evaluate whether maternal vitamin D insufficiency during pregnancy was conditionally associated with DNA methylation in the offspring cord blood. Maternal vitamin D insufficiency (plasma 25-hydroxy vitamin D [Formula: see text] 75 nmol/L) during pregnancy and offspring cord blood DNA methylation, assessed using Illumina Infinium 450k or Illumina EPIC Beadchip, was collected for 3738 mother–child pairs in 7 cohorts as part of the Pregnancy and Childhood Epigenetics (PACE) consortium. Associations between maternal vitamin D and offspring DNA methylation, adjusted for fetal sex, maternal smoking, maternal age, maternal pre-pregnancy or early pregnancy BMI, maternal education, gestational age at measurement of 25(OH)D, parity, and cell type composition, were estimated using robust linear regression in each cohort, and a fixed-effects meta-analysis was conducted. The prevalence of vitamin D insufficiency ranged from 44.3% to 78.5% across cohorts. Across 364,678 CpG sites, none were associated with maternal vitamin D insufficiency at an epigenome-wide significant level after correcting for multiple testing using Bonferroni correction or a less conservative Benjamini–Hochberg False Discovery Rate approach (FDR, p > 0.05). In this epigenome-wide association study, we did not find convincing evidence of a conditional association of vitamin D insufficiency with offspring DNA methylation at any measured CpG site.

Abstract Altered functioning of the bed nucleus of the stria terminalis (BNST) may play a critical role in the etiology of posttraumatic stress disorder (PTSD). Chronic stressors such as racial discrimination and lifetime trauma are associated with an increased risk for PTSD, but it is unknown whether they influence the relationship between BNST functioning and PTSD. We investigated acute post-trauma BNST resting-state functional connectivity (rsFC) as a predictor of future PTSD symptoms in Black trauma survivors. We also examined whether racial discrimination and lifetime trauma moderated the relationship between BNST rsFC and PTSD symptoms. Black adults (N = 95; 54.7% female; mean age = 34.04) were recruited from an emergency department after experiencing a traumatic injury (72.6% were motor vehicle accidents). Two-weeks post-injury, participants underwent a resting-state fMRI scan and completed questionnaires evaluating their PTSD symptoms as well as lifetime exposure to racial discrimination and trauma. Six-months post-injury, PTSD symptoms were reassessed. Whole brain seed-to-voxel analyses were conducted to examine BNST rsFC patterns. Greater rsFC between the BNST and the posterior cingulate cortex, precuneus, left angular gyrus, and hippocampus prospectively predicted six-month PTSD symptoms after adjusting for sex, age, education, and baseline PTSD symptoms. Acute BNST rsFC was a stronger predictor of PTSD symptoms in individuals who experienced more racial discrimination and lifetime trauma. Thus, in the acute aftermath of a traumatic event, the BNST could be a key biomarker of risk for PTSD in Black Americans, particularly for individuals with a greater history of racial discrimination or previous trauma exposure.

In an afterschool program at a university literacy center, we piloted the integration of physical activity with multimodal mathematics and literacy exercises. We aimed to incorporate the three tenets of culturally relevant pedagogy (CRP) including academic success, cultural competence, and critical consciousness with middle grades participants by utilizing a sports-based youth development model (SBYD), Teaching Personal and Social Responsibility (TPSR). Participants participated in 30-minute sessions bi-weekly over two months, which included reflective discussions and journaling to begin and end activities, respectively. Participants were invited to suggest activities during sessions and interact cooperatively with facilitators and peers. They also engaged in a focus group toward the end of the pilot program to provide their perspectives and feedback. We detail beginning takeaways from the program initiative and interrogate possible improvements and adaptations for other middle level settings. Finally, we aim to provide educational and community implications related to future implementations of this program or similar ones in diverse contexts.

Abstract The neuromodulatory subcortical nuclei within the isodendritic core (IdC) are the earliest sites of tauopathy in Alzheimer’s disease (AD). They project broadly throughout the brain’s white matter. We investigated the relationship between IdC microstructure and whole-brain white matter microstructure to better understand early neuropathological changes in AD. Using multiparametric quantitative magnetic resonance imaging we observed two covariance patterns between IdC and white matter microstructure in 133 cognitively unimpaired older adults (age 67.9 ± 5.3 years) with familial risk for AD. IdC integrity related to 1) whole-brain neurite density, and 2) neurite orientation dispersion in white matter tracts known to be affected early in AD. Pattern 2 was associated with CSF concentration of phosphorylated-tau, indicating AD specificity. Apolipoprotein-E4 carriers expressed both patterns more strongly than non-carriers. IdC microstructure variation is reflected in white matter, particularly in AD-affected tracts, highlighting an early mechanism of pathological development.

Abstract Background Granuloma annulare is a noninfectious inflammatory granulomatous skin disease characterized by an erythematous or skin colored annulare plaque. The diagnosis of granuloma annulare may be challenging owing to its diverse morphology. In such cases, a correlation between the clinical findings and histologic findings are necessary. Case presentation We report a case of granuloma annulare after purified protein derivative administration. A 56-year-old Caucasian female patient complained of mildly pruritic rashes which started on both arms and lower extremities, and eventually spread to both thighs, the left popliteal region, left upper back, and the right abdominal area. About 6 weeks prior to the eruption of the rashes, the patient had been given a purified protein derivative tuberculin skin test. Biopsy specimens revealed dermal histiocytes palisading around areas of mucin and degenerated collagen, confirming granuloma annulare. After treatment with 0.1% topical triamcinolone acetanide and 500 mg oral metronidazole, the patient’s lesions resolved. Discussion Relatively little is known about granuloma annulare’s exact etiology. Granuloma annulare has four variations presenting as either localized, generalized, subcutaneous, or perforating and patch granuloma annulare. The clinical prognosis for granuloma annulare varies according to clinical subtypes. Proposed causal mechanisms of subcutaneous granuloma annulare include physical trauma, infections, immunizations, insect bites, diabetes mellitus, and alterations in the cell-mediated immune responses. The disease likely has an inflammatory component. Clinically, granuloma annulare may be confused with many other skin diseases. Conclusion This case of subcutaneous granuloma annulare was reported since it is a rare dermatologic pathological condition that can be confused with other skin rash disorders. Although it is a benign self-limited disease, definitive diagnosis is important to rule out other pathologies with similar clinical appearances, such as cancer or human immunodeficiency virus (HIV) infection. Diagnostic confirmation is best made through skin biopsy.

Background: While it is known that vital signs and behaviors change during pregnancy, there is limited data on timing and scale of changes for sensor-derived health metrics across pregnancy and postpartum. Wearable technology provides an opportunity to understand physiologic and behavioral changes across pregnancy with greater detail, more frequent measurements, and improved accuracy. The aim of this study is to describe changes in physiologic and behavioral sensor-based health metrics during pregnancy and postpartum in the Apple Women's Health Study (AWHS) and their relationship to demographic factors. Methods: The Apple Women's Health Study is a digital, longitudinal, observational study that includes U.S. residents with an iPhone and Apple Watch. We evaluated changes from pre-pregnancy through delivery and postpartum for sensor-derived health metrics. Minimum required data samples per day, week and overall were data element specific, and included 12 weeks prior to pregnancy start, and 12 weeks postpartum for pregnancies lasting between 24 and 43 weeks. Findings: A total of 757 pregnancies from 733 participants were included. Resting heart rate (RHR) increased across pregnancy, peaking in the third trimester (pre-pregnancy median RHR 65.0 beats per minute [BPM], interquartile range [IQR] 60.0–70.2 B.M. third trimester median RHR 75.5 B.M. IQR 69.0–82.0 B.M., with a decrease prior to delivery and nadir postpartum (postpartum median RHR 62.0 B.M. IQR 57.0–66.0 B.M.. Heart rate variability (HRV) decreased from pre-pregnancy (39.9 milliseconds, IQR 32.6–48.3 milliseconds), reaching a nadir in the third trimester (29.9 milliseconds, IQR 25.2–36.4 milliseconds), before rebounding in the last weeks of pregnancy. Measures of activity, such as exercise minutes, stand minutes, step count and Cardio Fitness were all decreased in each trimester compared to pre-pregnancy, with their nadirs postpartum. Total sleep duration increased slightly in early pregnancy (pre-pregnancy 7.2 hours, IQR 6.7–7.7 hours; 1st trimester 7.4 hours, IQR 6.8–7.9 hours), with the lowest sleep duration postpartum (6.2 hours, IQR 5.4–6.8 hours). Interpretation: Resting heart rate increased during pregnancy, with a decrease prior to delivery, while heart rate variability decreased across pregnancy, with an upward trend before delivery. Behavioral metrics, such as exercise and sleep, showed decreasing trends during and after pregnancy. These data provide a foundation for understanding normal pregnancy physiology and can facilitate hypothesis generation related to physiology, behavior, pregnancy outcomes and disease.

IntroductionSocial isolation and loneliness are global public health concerns experienced among older adults which are commonly associated with negative physical, psychological, and social outcomes. The healthcare system has an opportunity to identify and address social isolation and loneliness in older adults. The Program of All-Inclusive Care for the Elderly (PACE) was developed to serve comprehensive social needs along with medical and behavioral needs of older adults who qualify for long-term care while still living in the community. In 2021, due to state budget reductions, Wyoming’s only PACE program (WY PACE) closed, resulting in the discharge of all participants and loss of social engagement opportunities provided by this program. The objectives of this evaluation were to (1) examine the impact of the WY PACE closure on isolation and loneliness, (2) identify how older adults adapted to the loss of services addressing isolation and loneliness, and (3) identify needs for future interventions to address isolation among clients who experienced loss of supportive programs.MethodsA mixed-methods design was used to facilitate understanding of qualitative findings while also conducting quantitative analyses to provide context for qualitative responses. Participants included 17 individuals who were either former PACE participants or their caregivers. Participants (n = 12; M = 74 years old) were predominantly non-Hispanic White (n = 8, 66%) and cisgender female (n = 7, 58%). Caregivers of participants (n = 5; M = 63 years old) were predominantly Hispanic, Latino, or of Spanish origin (n = 3, 60%) and cisgender female (n = 4, 80%).ResultsA mixed-methods design was used to facilitate understanding of qualitative findings while also conducting quantitative analyses to provide context for qualitative responses. Participants included 17 individuals who were either former PACE participants or their caregivers. Participants (n = 12; M = 74 years old) were predominantly non-Hispanic White (n = 8, 66%) and cisgender female (n = 7, 58%). Caregivers of participants (n = 5; M = 63 years old) were predominantly Hispanic, Latino, or of Spanish origin (n = 3, 60%) and cisgender female (n = 4, 80%).DiscussionThis evaluation provided preliminary insight into the impacts of the loss of programs like WY PACE on social isolation and loneliness. Creative solutions to maintain social engagement of this vulnerable population are needed.

Since the coronavirus disease 2019 (COVID-19) pandemic, wastewater-based epidemiology (WBE) has been widely applied in many countries and regions for monitoring COVID-19 transmission in the population through testing severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) in wastewater. However, the amount of virus shed by individuals over time based on the stage of infection and accurate number of infections in the community creates challenges in predicting COVID-19 prevalence in the population and interpreting WBE results. In this study, we measured SARS-CoV-2, pepper mild mottle virus (PMMoV), and human mitochondrial DNA (mtDNA) in longitudinal fecal samples collected from 42 COVID-19 patients for up to 42 days after diagnosis. SARS-CoV-2 RNA was detected in 73.1% (19/26) of inpatient study participants in at least one of the collected fecal specimens during the sampling period. Most participants shed the virus within 3 weeks after diagnosis, but five inpatient participants still shed the virus between 20 and 60 days after diagnosis. The median concentration of SARS-CoV-2 in positive fecal samples was 1.08 × 105 genome copies (GC)/gram dry fecal material. PMMoV and mtDNA were detected in 99.4% (154/155) and 100% (155/155) of all fecal samples, respectively. The median concentrations of PMMoV RNA and mtDNA in fecal samples were 1.73 × 107 and 2.49 × 108 GC/dry gram, respectively. These results provide important information about the dynamics of fecal shedding of SARS-CoV-2 and two human fecal indicators in COVID-19 patients. mtDNA showed higher positive rates, higher concentrations, and less variability between and within individuals than PMMoV, suggesting that mtDNA could be a better normalization factor for WBE results than PMMoV.

Abstract Obesity, associated with the intake of a high-fat diet (HFD), and anxiety are common among those living in modern urban societies. Recent studies suggest a role of microbiome-gut-brain axis signaling, including a role for brain serotonergic systems in the relationship between HFD and anxiety. Evidence suggests the gut microbiome and the serotonergic brain system together may play an important role in this response. Here we conducted a nine-week HFD protocol in male rats, followed by an analysis of the gut microbiome diversity and community composition, brainstem serotonergic gene expression (tph2, htr1a, and slc6a4), and anxiety-related defensive behavioral responses. We show that HFD intake decreased alpha diversity and altered the community composition of the gut microbiome in association with obesity, increased brainstem tph2, htr1a and slc6a4 mRNA expression, including in the caudal part of the dorsomedial dorsal raphe nucleus (cDRD), a subregion previously associated with stress- and anxiety-related behavioral responses, and, finally, increased anxiety-related defensive behavioral responses. The HFD increased the Firmicutes/Bacteroidetes ratio relative to control diet, as well as higher relative abundances of Blautia, and decreases in Prevotella. We found that tph2, htr1a and slc6a4 mRNA expression were increased in subregions of the dorsal raphe nucleus in the HFD, relative to control diet. Specific bacterial taxa were associated with increased serotonergic gene expression in the cDRD. Thus, we propose that HFD-induced obesity is associated with altered microbiome-gut-serotonergic brain axis signaling, leading to increased anxiety-related defensive behavioral responses in rats.

Transmethylation in the context of psychiatry has historically referred to the enzymatic transfer of a methyl group from one biochemical to another, whose resulting function can change so dramatically that a biochemical like tryptamine, for example, is converted into the hallucinogen dimethyltryptamine. Central to endogenous methylation activity is the folate cycle, which generates the primary transferable methyl groups in mammalian biochemistry. The relevance of this cycle to mental health becomes clear when the cycle is dysregulated, often leading to a buildup of both homocysteine and S-adenosylhomocysteine (SAH), while accompanied by a transient reduction in the intended physiologic target, S-adenosylmethionine (SAM). This paper includes an in-depth review of the causes of folate cycle perturbations associated with psychotic symptoms, expounding on alternative downstream pathways which are activated and pointing toward potential etiologic agents of the associated psychosis, the methylated tertiary amines N-methyl-salsolinol, N-methyl-norsalsolinol, and adrenochrome, which appear in scientific reports concerning their association with hallucinogenic and/or neurotoxic outcomes. Electrotopological state (E-state) data has been generated for these compounds, illustrating a strong similarity with hallucinogens, particularly in terms of the E-state of the nitrogen in their tertiary amine moieties. In light of the role the folate cycle plays in transmethylation, neuroprotective strategies to prevent the transition to psychosis are suggested, including the advisory that folate supplementation can be harmful depending on the status of other relevant biochemicals.

Abstract Globally, cats are a common companion animal. Allowing companion cats to roam away from home can have negative impacts on native wildlife and cat welfare. A more contained cat lifestyle can limit the detrimental impacts of roaming; however, this continues to be an uncommon choice for cat owners in many countries. Communication strategies that focus on welfare benefits for cats have successfully motivated some owners to prevent their cats from roaming. However, little is known about other factors influencing owners' decisions about roaming, such as the owner–cat relationship and their cat's membership in the local community. We conducted five focus groups with 31 cat owners in Aotearoa New Zealand to understand these factors. Using thematic analysis, we identified three major themes that describe how owners view the impacts of cat containment on their relationship with their cat/s. First, finding a balance between enabling and restricting choices to ensure the cat's welfare is at the heart of the owner–cat relationship. Critically, the cat's choice to repeatedly return home reaffirms the owner–cat relationship. Second, striking the right balance in the provision of choice and ensuring welfare are contingent on the cat's characteristics. Owners providing their cat/s with the choice to leave home are perceived to be positively associated with enabling their freedom, independence and curiosity. Third, owners perceived cats to belong in many spaces occupied by humans outside of their property, despite most participants living near populations of significant threatened species. The choice to allow a cat to roam from home impacts cat welfare, the owner–cat relationship and membership in the local cat, human and wildlife community. Efforts to facilitate the shift to a contained cat lifestyle need to help owners provide choices for their cats that will meet their welfare needs and foster the owner–cat relationship. Locally relevant strategies that consider the owners' views as members of their community will likely be more successful. Read the free Plain Language Summary for this article on the Journal blog.

Institution-level wastewater-based surveillance was implemented during the COVID-19 pandemic, including in carceral facilities. We examined the relationship between COVID-19 diagnostic test results of residents in a jail in Atlanta, Georgia, USA (average population ≈2,700), and quantitative reverse transcription PCR signal for SARS-CoV-2 in weekly wastewater samples collected during October 2021‒May 2022. The jail offered residents rapid antigen testing at entry and periodic mass screenings by reverse transcription PCR of self-collected nasal swab specimens. We aggregated individual test data, calculated the Spearman correlation coefficient, and performed logistic regression to examine the relationship between strength of SARS-CoV-2 PCR signal (cycle threshold value) in wastewater and percentage of jail population that tested positive for COVID-19. Of 13,745 nasal specimens collected, 3.9% were COVID-positive (range 0%–29.5% per week). We observed a strong inverse correlation between diagnostic test positivity and cycle threshold value (r = −0.67; p

Abstract To accelerate medical breakthroughs, the All of Us Research Program aims to collect data from over one million participants. This report outlines processes used to construct the All of Us Social Determinants of Health (SDOH) survey and presents the psychometric characteristics of SDOH survey measures in All of Us. A consensus process was used to select SDOH measures, prioritizing concepts validated in diverse populations and other national cohort surveys. Survey item non-response was calculated, and Cronbach’s alpha was used to analyze psychometric properties of scales. Multivariable logistic regression models were used to examine associations between demographic categories and item non-response. Twenty-nine percent (N = 117,783) of eligible All of Us participants submitted SDOH survey data for these analyses. Most scales had less than 5% incalculable scores due to item non-response. Patterns of item non-response were seen by racial identity, educational attainment, income level, survey language, and age. Internal consistency reliability was greater than 0.80 for almost all scales and most demographic groups. The SDOH survey demonstrated good to excellent reliability across several measures and within multiple populations underrepresented in biomedical research. Bias due to survey non-response and item non-response will be monitored and addressed as the survey is fielded more completely.

Abstract Background COVID-19 vaccines are authorized for use in children in the United States; real-world assessment of vaccine effectiveness in children is needed. This study’s objective was to estimate the effectiveness of receiving a complete primary series of monovalent BNT162b2 (Pfizer-BioNTech) COVID-19 vaccine in US children. Methods This cohort study identified children aged 5–17 years vaccinated with BNT162b2 matched with unvaccinated children. Participants and BNT162b2 vaccinations were identified in Optum and CVS Health insurance administrative claims databases linked with Immunization Information System (IIS) COVID-19 vaccination records from 16 US jurisdictions between December 11, 2020, and May 31, 2022 (end date varied by database and IIS). Vaccinated children were followed from their first BNT162b2 dose and matched to unvaccinated children on calendar date, US county of residence, and demographic and clinical factors. Censoring occurred if vaccinated children failed to receive a timely dose 2 or if unvaccinated children received any dose. Two COVID-19 outcome definitions were evaluated: COVID-19 diagnosis in any medical setting and COVID-19 diagnosis in hospitals/emergency departments (EDs). Propensity score-weighted hazard ratios (HRs) and 95% confidence intervals (CIs) were estimated with Cox proportional hazards models, and vaccine effectiveness (VE) was estimated as 1 minus HR. VE was estimated overall, within age subgroups, and within variant-specific eras. Sensitivity, negative control, and quantitative bias analyses evaluated various potential biases. Results There were 453,655 eligible vaccinated children one-to-one matched to unvaccinated comparators (mean age 12 years; 50% female). COVID-19 hospitalizations/ED visits were rare in children, regardless of vaccination status (Optum, 41.2 per 10,000 person-years; CVS Health, 44.1 per 10,000 person-years). Overall, vaccination was associated with reduced incidence of any medically diagnosed COVID-19 (meta-analyzed VE = 38% [95% CI, 36–40%]) and hospital/ED–diagnosed COVID-19 (meta-analyzed VE = 61% [95% CI, 56–65%]). VE estimates were lowest among children 5–11 years and during the Omicron-variant era. Conclusions Receipt of a complete BNT162b2 vaccine primary series was associated with overall reduced medically diagnosed COVID-19 and hospital/ED–diagnosed COVID-19 in children; observed VE estimates differed by age group and variant era. Registration The study protocol was publicly posted on the BEST Initiative website ( https://bestinitiative.org/wp-content/uploads/2022/03/C19-VX-Effectiveness-Protocol_2022_508.pdf ).

Abstract Background Acoustic telemetry has become a fundamental tool to monitor the movement of aquatic species. Advances in technology, in particular the development of batteries with lives of > 10 years, have increased our ability to track the long-term movement patterns of many species. However, logistics and financial constraints often dictate the locations and deployment duration of acoustic receivers. Consequently, there is often a compromise between optimal array design and affordability. Such constraints can hinder the ability to track marine animals over large spatial and temporal scales. Continental-scale receiver networks have increased the ability to study large-scale movements, but significant gaps in coverage often remain. Methods Since 2007, the Integrated Marine Observing System’s Animal Tracking Facility (IMOS ATF) has maintained permanent receiver installations on the eastern Australian seaboard. In this study, we present the recent enhancement of the IMOS ATF acoustic tracking infrastructure in Queensland to collect data on large-scale movements of marine species in the northeast extent of the national array. Securing a relatively small initial investment for expanding receiver deployment and tagging activities in Queensland served as a catalyst, bringing together a diverse group of stakeholders (research institutes, universities, government departments, port corporations, industries, Indigenous ranger groups and tourism operators) to create an extensive collaborative network that could sustain the extended receiver coverage into the future. To fill gaps between existing installations and maximise the monitoring footprint, the new initiative has an atypical design, deploying many single receivers spread across 2,100 km of Queensland waters. Results The approach revealed previously unknown broad-scale movements for some species and highlights that clusters of receivers are not always required to enhance data collection. However, array designs using predominantly single receiver deployments are more vulnerable to data gaps when receivers are lost or fail, and therefore “redundancy” is a critical consideration when designing this type of array. Conclusion Initial results suggest that our array enhancement, if sustained over many years, will uncover a range of previously unknown movements that will assist in addressing ecological, fisheries, and conservation questions for multiple species.

Abstract Intrathecal delivery of autologous culture-expanded adipose tissue-derived mesenchymal stem cells (AD-MSC) could be utilized to treat traumatic spinal cord injury (SCI). This Phase I trial (ClinicalTrials.gov: NCT03308565) included 10 patients with American Spinal Injury Association Impairment Scale (AIS) grade A or B at the time of injury. The study’s primary outcome was the safety profile, as captured by the nature and frequency of adverse events. Secondary outcomes included changes in sensory and motor scores, imaging, cerebrospinal fluid markers, and somatosensory evoked potentials. The manufacturing and delivery of the regimen were successful for all patients. The most commonly reported adverse events were headache and musculoskeletal pain, observed in 8 patients. No serious AEs were observed. At final follow-up, seven patients demonstrated improvement in AIS grade from the time of injection. In conclusion, the study met the primary endpoint, demonstrating that AD-MSC harvesting and administration were well-tolerated in patients with traumatic SCI.

Abstract Background Translating research, achieving impact, and assessing impact are important aspirations for all research collaboratives but can prove challenging. The Hunter Cancer Research Alliance (HCRA) was funded from 2014 to 2021 to enhance capacity and productivity in cancer research in a regional centre in Australia. This study aimed to assess the impact and benefit of the HCRA to help inform future research investments of this type. Method The Framework to Assess the Impact from Translational health research (FAIT) was selected as the preferred methodology. FAIT incorporates three validated methodologies for assessing impact: 1) Modified Payback; 2) Economic Analysis; and 3) Narrative overview and case studies. All three FAIT methods are underpinned by a Program Logic Model. Data were collected from HCRA and the University of Newcastle administrative records, directly from HCRA members, and website searches. Results In addition to advancing knowledge and providing capacity building support to members via grants, fellowships, scholarships, training, events and targeted translation support, key impacts of HCRA-member research teams included: (i) the establishment of a regional biobank that has distributed over 13,600 samples and became largely self-sustaining; (ii) conservatively leveraging $43.8 M (s.a.$20.5 M - $160.5 M) in funding and support from the initial $9.7 M investment; (iii) contributing to clinical practice guidelines and securing a patent for identification of stem cells for endometrial cell regeneration; (iv) shifting the treatment paradigm for all tumour types that rely on nerve cell innervation, (v) development and implementation of the world’s first real-time patient treatment verification system (Watchdog); (vi) inventing the effective ‘EAT’ psychological intervention to improve nutrition and outcomes in people experiencing radiotherapy for head and neck cancer; (vi) developing effective interventions to reduce smoking rates among priority groups, currently being rolled out to disadvantaged populations in NSW; and (vii) establishing a Consumer Advisory Panel and Consumer Engagement Committee to increase consumer involvement in research. Conclusion Using FAIT methodology, we have demonstrated the significant impact and downstream benefits that can be achieved by the provision of infrastructure-type funding to regional and rural research collaboratives to help address inequities in research activity and health outcomes and demonstrates a positive return on investment.

Abstract Nicotine use is a leading cause of preventable deaths worldwide, and most of those who attempt to quit will relapse. While electronic cigarettes and other electronic nicotine delivery systems (ENDS) were presented as a safer alternative to traditional cigarettes and promoted as devices to help traditional tobacco smokers reduce or quit smoking, they have instead contributed to increasing nicotine use among youths. Despite this, ENDS also represent a useful tool to create novel preclinical animal models of nicotine exposure that more accurately represent human nicotine use. In this study, we validated a chronic, intermittent, ENDS-based passive vapor exposure model in mice, and then measured changes in multiple behaviors related to nicotine abstinence. First, we performed a behavioral dose curve to investigate the effects of different nicotine inter-vape intervals on various measures including body weight, locomotor activity, and pain hypersensitivity. Next, we performed a pharmacokinetic study to measure plasma levels of nicotine and cotinine following chronic exposure for each inter-vape interval. Finally, we utilized a behavior test battery at a single dosing regimen that produces blood levels equivalent to human smokers in order to characterize the effects of chronic nicotine, vehicle, or passive airflow and identified nicotine-induced impairments in cognitive behavior.

The ability to rapidly respond to wildlife health events is essential. However, such events are often unpredictable, especially with anthropogenic disturbances and climate-related environmental changes driving unforeseen threats. Many events also are short-lived and go undocumented, making it difficult to draw on lessons learned from past investigations. We report on the response to a mortality event observed predominantly in wild passerines in the eastern United States. The event began in May 2021 when wildlife rehabilitators and private citizens reported large numbers of sick and dead juvenile birds, mostly presenting as single cases with neurologic signs and/or ocular and periocular lesions. Early efforts by rehabilitators, veterinarians, state and federal wildlife agencies, and universities helped gather public reports and fuel rapid responses by government agencies. Collective efforts included live bird and carcass collections; submission to diagnostic laboratories and evaluation; information sharing; and coordinated messaging to stakeholders and interested parties. Extensive diagnostic evaluations failed to identify a causative pathogen or other etiology, although congruent results across laboratories have helped drive further investigation into alternative causes, such as nutritional deficiencies. This report highlights the strengths of a multi-agency, interdisciplinary investigation while exposing the need for an operational framework with approaches and resources dedicated to wildlife health.

Background: Glioblastoma, a high-grade primary brain cancer, has a median survival of approximately 14 months. Post-mortem brain donation provides insight to pathogenesis along with spatial and temporal heterogeneity. Post-mortem brain biobanking programs are increasing in number and the need to understand and improve the associated human experience is pressing. This study aims to qualitatively explore the experiences of next of kin (NOK) following the death and brain donation of a loved one and to understand the impact such programs have on NOK carers. Method: We interviewed 29 NOK following the death of their loved one and subsequent brain donation. Thematic analysis was conducted on the transcribed, qualitative interviews. Results: Four themes were identified; (1) Brain donation is a straightforward decision grounded in altruism and pragmatism; (2) Supporting donors is a source of comfort, pride and empowerment; (3) Brain donation can provide meaning for suffering and tragedy and (4) Perceptions of procedures and processes when supporting a loved one to donate. Insights into areas for improvement, for example transporting donors following a home death and the role of the body bag were also noted. Conclusion: Supporting a loved one to donate their brain can be a positive experience providing a source of hope, empowerment and purpose for NOK. Data indicating areas for consideration are broadly relevant for improving the delivery of brain donation programs for future donors and their loved ones.

Background: Childhood abuse (physical, emotional, and sexual) is associated with aberrant connectivity of the amygdala, a key threat-processing region. Heightened amygdala activity also predicts adult anxiety and posttraumatic stress disorder (PTSD) symptoms, as do experiences of childhood abuse. The current study explored whether amygdala resting-state functional connectivity may explain the relationship between childhood abuse and anxiety and PTSD symptoms following trauma exposure in adults. Methods: Two weeks posttrauma, adult trauma survivors (n = 152, mean age [SD] = 32.61 [10.35] years; women = 57.2%) completed the Childhood Trauma Questionnaire and underwent resting-state functional magnetic resonance imaging. PTSD and anxiety symptoms were assessed 6 months posttrauma. Seed-to-voxel analyses evaluated the association between childhood abuse and amygdala resting-state functional connectivity. A mediation model evaluated the potential mediating role of amygdala connectivity in the relationship between childhood abuse and posttrauma anxiety and PTSD. Results: Childhood abuse was associated with increased amygdala connectivity with the precuneus while covarying for age, gender, childhood neglect, and baseline PTSD symptoms. Amygdala-precuneus resting-state functional connectivity was a significant mediator of the effect of childhood abuse on anxiety symptoms 6 months posttrauma (B = 0.065; 95% CI, 0.013–0.130; SE = 0.030), but not PTSD. A secondary mediation analysis investigating depression as an outcome was not significant. Conclusions: Amygdala-precuneus connectivity may be an underlying neural mechanism by which childhood abuse increases risk for anxiety following adult trauma. Specifically, this heightened connectivity may reflect attentional vigilance for threat or a tendency toward negative self-referential thoughts. Findings suggest that childhood abuse may contribute to longstanding upregulation of attentional vigilance circuits, which makes one vulnerable to anxiety-related symptoms in adulthood.

Summary: Intra-tumoral phenotypic heterogeneity promotes tumor relapse and therapeutic resistance and remains an unsolved clinical challenge. Decoding the interconnections among different biological axes of plasticity is crucial to understand the molecular origins of phenotypic heterogeneity. Here, we use multi-modal transcriptomic data—bulk, single-cell, and spatial transcriptomics—from breast cancer cell lines and primary tumor samples, to identify associations between epithelial-mesenchymal transition (EMT) and luminal-basal plasticity—two key processes that enable heterogeneity. We show that luminal breast cancer strongly associates with an epithelial cell state, but basal breast cancer is associated with hybrid epithelial/mesenchymal phenotype(s) and higher phenotypic heterogeneity. Mathematical modeling of core underlying gene regulatory networks representative of the crosstalk between the luminal-basal and epithelial-mesenchymal axes elucidate mechanistic underpinnings of the observed associations from transcriptomic data. Our systems-based approach integrating multi-modal data analysis with mechanism-based modeling offers a predictive framework to characterize intra-tumor heterogeneity and identify interventions to restrict it.

Objectives An estimated 14–23% of patients with traumatic brain injury (TBI) incur multiple lifetime TBIs. The relationship between prior TBI and outcomes in patients with moderate to severe TBI (msTBI) is not well delineated. We examined the associations between prior TBI, in-hospital mortality, and outcomes up to 12 months after injury in a prospective US msTBI cohort.Methods Data from hospitalized subjects with Glasgow Coma Scale score of 3–12 were extracted from the Transforming Research and Clinical Knowledge in Traumatic Brain Injury Study (enrollment period: 2014–2019). Prior TBI with amnesia or alteration of consciousness was assessed using the Ohio State University TBI Identification Method. Competing risk regressions adjusting for age, sex, psychiatric history, cranial injury and extracranial injury severity examined the associations between prior TBI and in-hospital mortality, with hospital discharged alive as the competing risk. Adjusted HRs (aHR (95% CI)) were reported. Multivariable logistic regressions assessed the associations between prior TBI, mortality, and unfavorable outcome (Glasgow Outcome Scale-Extended score 1–3 (vs. 4–8)) at 3, 6, and 12 months after injury.Results Of 405 acute msTBI subjects, 21.5% had prior TBI, which was associated with male sex (87.4% vs. 77.0%, p=0.037) and psychiatric history (34.5% vs. 20.7%, p=0.010). In-hospital mortality was 10.1% (prior TBI: 17.2%, no prior TBI: 8.2%, p=0.025). Competing risk regressions indicated that prior TBI was associated with likelihood of in-hospital mortality (aHR=2.06 (1.01–4.22)), but not with hospital discharged alive. Prior TBI was not associated with mortality or unfavorable outcomes at 3, 6, and 12 months.Conclusions After acute msTBI, prior TBI history is independently associated with in-hospital mortality but not with mortality or unfavorable outcomes within 12 months after injury. This selective association underscores the importance of collecting standardized prior TBI history data early after acute hospitalization to inform risk stratification. Prospective validation studies are needed.Level of evidence IV.Trial registration number NCT02119182.

Background: Despite the impact of cognitive decline during brain cancer care, implementing routine cognitive assessment can be challenging. Effective implementation of cognitive assessment necessitates an understanding of implementation from the patient perspective. However, little is known about how people with glioma and their caregivers experience cognitive changes, assessment and support. Objective: To understand the lived experiences of changes in cognition for people with glioma and their caregivers including experiences of: i) perceived or objectively measured cognitive decline (or absence of decline); ii) cognitive assessment following diagnosis, and; iii) met and unmet cognition-related supportive care needs. Design: Semi-structured qualitative telephone interviews were conducted with people with gliomas and support persons and analysed using reflexive thematic analysis. Setting(s): Two Australian cancer services Participants: 18 people with glioma and caregivers Methods: Semi-structured qualitative telephone interviews were conducted with people with gliomas and caregivers and analysed using reflexive thematic analysis. Results: People with glioma (n = 5) and caregivers (n = 13) completed interviews. Four themes were identified: Cognition needs to be considered within the context of glioma diagnosis and treatment; concerns about cognition were initially subordinate to survival but become important; there are challenges identifying and communicating about people with gliomas’ changes in cognition; cognition-related supportive care can be helpful but challenging for people with glioma and caregivers to identify and access. Conclusions: Changes to cognition can have considerable impacts of people with glioma and their caregivers which may be overshadowed by treatment and survival. A multi-disciplinary approach to timely cognitive screening, structured referral pathways, and communication with caregivers may provide opportunities for support. Registration: n/a Tweetable abstract: Identifying cognitive changes in people with glioma is important and challenging. A multidisciplinary approach and inclusion of care coordination and caregivers can help.

Adolescence is characterized by dynamic neurodevelopment, which poses opportunities for risk and resilience. Adverse childhood experiences (ACEs) confer additional risk to the developing brain, where ACEs have been associated with alterations in functional magnetic resonance imaging (fMRI) BOLD signaling in brain regions underlying inhibitory control. Socioenvironmental factors like the family environment may amplify or buffer against the neurodevelopmental risks associated with ACEs. Using baseline to Year 2 follow-up data from the Adolescent Brain Cognitive Development (ABCD) Study, the current study examined how ACEs relate to fMRI BOLD signaling during successful inhibition on the Stop Signal Task in regions associated with inhibitory control and examined whether family conflict levels moderated that relationship. Results showed that greater ACEs were associated with reduced BOLD response in the right opercular region of the inferior frontal gyrus and bilaterally in the pre-supplementary motor area, which are key regions underlying inhibitory control. Further, greater BOLD response was correlated with less impulsivity behaviorally, suggesting reduced activation may not be behaviorally adaptive at this age. No significant two or three-way interactions with family conflict levels or time were found. Findings highlight the continued utility of examining the relationship between ACEs and neurodevelopmental outcomes and the importance of intervention/prevention of ACES.

IntroductionHuman Herpesvirus 6B (HHV-6B) impedes host immune responses by downregulating class I MHC molecules (MHC-I), hindering antigen presentation to CD8+ T cells. Downregulation of MHC-I disengages inhibitory receptors on natural killer (NK) cells, resulting in activation and killing of the target cell if NK cell activating receptors such as NKG2D have engaged stress ligands upregulated on the target cells. Previous work has shown that HHV-6B downregulates three MHC-like stress ligands MICB, ULBP1, and ULBP3, which are recognized by NKG2D. The U20 glycoprotein of the related virus HHV-6A has been implicated in the downregulation of ULBP1, but the precise mechanism remains undetermined.MethodsWe set out to investigate the role of HHV-6B U20 in modulating NK cell activity. We used HHV-6B U20 expressed as a recombinant protein or transduced into target cells, as well as HHV-6B infection, to investigate binding interactions with NK cell ligands and receptors and to assess effects on NK cell activation. Small-angle X-ray scattering was used to align molecular models derived from machine-learning approaches.ResultsWe demonstrate that U20 binds directly to ULBP1 with sub-micromolar affinity. Transduction of U20 decreases NKG2D binding to ULBP1 at the cell surface but does not decrease ULBP1 protein levels, either at the cell surface or in toto. HHV-6B infection and soluble U20 have the same effect. Transduction of U20 blocks NK cell activation in response to cell-surface ULBP1. Structural modeling of the U20 – ULBP1 complex indicates some similarities to the m152-RAE1γ complex.

We present open-source tools for three-dimensional (3D) analysis of photographs of dissected slices of human brains, which are routinely acquired in brain banks but seldom used for quantitative analysis. Our tools can: (1) 3D reconstruct a volume from the photographs and, optionally, a surface scan; and (2) produce a high-resolution 3D segmentation into 11 brain regions per hemisphere (22 in total), independently of the slice thickness. Our tools can be used as a substitute for ex vivo magnetic resonance imaging (MRI), which requires access to an MRI scanner, ex vivo scanning expertise, and considerable financial resources. We tested our tools on synthetic and real data from two NIH Alzheimer’s Disease Research Centers. The results show that our methodology yields accurate 3D reconstructions, segmentations, and volumetric measurements that are highly correlated to those from MRI. Our method also detects expected differences between post mortem confirmed Alzheimer’s disease cases and controls. The tools are available in our widespread neuroimaging suite ‘FreeSurfer’ (https://surfer.nmr.mgh.harvard.edu/fswiki/PhotoTools).

Introduction: Up to 20% of EGFR-mutated NSCLC cases harbor uncommon EGFR mutations, including atypical exon 19 and compound mutations. Relatively little is known about the efficacy of osimertinib in these cases. Methods: Patients treated with first-line osimertinib for NSCLC with rare EGFR exon 19 (non E746_A750del) or compound mutations were included. Response assessment and time to progression were determined using Response Evaluation Criteria in Solid Tumors version 1.1 criteria. Kaplan-Meier analyses were used to estimate progression-free survival (PFS), time to treatment discontinuation (TTD), and overall survival (OS). Results: Thirty-seven patients with NSCLC harboring an atypical EGFR exon 19 mutation or compound mutation were treated with first-line osimertinib at Johns Hopkins from 2016 to 2021. Overall response rate (ORR) was 76% and median PFS, TTD, and OS were 13 months (95% confidence interval [CI]: 10–15), 22 months (95% CI: 17–32) and 36 months (95% CI, 29–48), respectively. Among atypical exon 19 mutations (n = 25), ORR was 80%, median PFS was 12 months (95% CI: 10–15), median TTD was 19 months (95% CI: 17–38), and median OS was 48 months (95% CI: 25–not reached). Compound mutations (n = 12) had an ORR of 67%, median PFS of 14 months (95% CI: 5–22), median TTD of 26 months (95% CI: 5–36), and median OS of 36 months (95% CI: 20–46). Twelve patients (32%) continued first-line osimertinib after local therapy for oligoprogression. Conclusions: Osimertinib exhibited favorable outcomes for rare EGFR exon 19 and compound mutations. The heterogeneity in outcomes among these groups of tumors with similar mutations underscores the need for continued reporting and further study of outcomes among rare variants to optimize management for each patient.

Key Clinical Message Our case depicts a challenging diagnosis of catastrophic antiphospholipid syndrome in a young patient with a heterogenous presentation with extensive clinical course, a wide range of investigations, including multimodality imaging, and multidisciplinary expertise, to initiate prompt treatment addressing multiorgan thrombotic injury.

Introduction Over 50% of people affected by cancer report unmet support needs. To address unmet information and psychological needs, non-government organisations such as Cancer Councils (Australia) have developed state-based telephone cancer information and support services. Due to competing demands, evidence of the value of these services is needed to ensure that future investment makes the best use of scarce resources. This research aims to determine the costs and broader economic and social value of a telephone support service, to inform future funding and service provision.Methods and analysis A codesigned, evaluative social return on investment analysis (SROI) will be conducted to estimate and compare the costs and monetised benefits of Cancer Council Victoria’s (CCV) telephone support line, 13 11 20, over 1-year and 3-year benefit periods. Nine studies will empirically estimate the parameters to inform the SROI and calculate the ratio (economic and social value to value invested): step 1 mapping outcomes (in-depth analysis of CCV’s 13 11 20 recorded call data; focus groups and interviews); step 2 providing evidence of outcomes (comparative survey of people affected by cancer who do and do not call CCV’s 13 11 20; general public survey); step 3 valuing the outcomes (financial proxies, value games); step 4 establishing the impact (Delphi); step 5 calculating the net benefit and step 6 service improvement (discrete choice experiment (DCE), ‘what if’ analysis). Qualitative (focus groups, interviews) and quantitative studies (natural language processing, cross-sectional studies, Delphi) and economic techniques (willingness-to-pay, financial proxies, value games, DCE) will be applied.Ethics and dissemination Ethics approval for each of the studies will be sought independently as the project progresses. So far, ethics approval has been granted for the first two studies. As each study analysis is completed, results will be disseminated through presentation, conferences, publications and reports to the partner organisations.

Abstract Background Staphylococcus aureus is a multi-host zoonotic pathogen causing human and livestock diseases. Dairy farms that make artisan cheese have distinctive concerns for S. aureus control. Antimicrobial-resistant (AMR) S. aureus is a public and animal health concern. There is a need to study the population structure of AMR S. aureus at the human-animal interface and understand the path of zoonotic transmission. This cross-sectional observational study aimed to assess the genetic diversity and AMR patterns of S. aureus isolated from cattle and humans on conventional and organic Vermont dairy farms that produce and sell farmstead cheese. Results A convenience sample of 19 dairy farms in Vermont was enrolled, and 160 S. aureus isolates were collected from cow quarter milk (CQM), bulk tank milk (BTM), human-hand and -nasal swabs. After deduplication, 89 isolates were used for the analysis. Sequence types (STs) were determined by multilocus sequence typing and cataloged to the PubMLST database. Nine defined and five novel STs were identified. For BTM and CQM samples, six STs were identified within cow-adapted CC97 and CC151. Two human-adapted STs were isolated from BTM and CQM. Seven human-adapted clonal complexes with eight STs were identified from human samples. One cow-adapted ST was isolated from a human. Antimicrobial susceptibility of the isolates was tested using disc diffusion and broth microdilution methods. Approximately 27% of the isolates were beta-lactam resistant and blaZ gene-positive. S. aureus isolates from human swabs were more likely to carry blaZ compared to isolates from CQM or BTM. S. aureus isolated from cows and humans on the same farm belonged to different STs. Conclusion Humans were more likely to carry beta-lactam-resistant S. aureus compared to cows, and on organic farms only human-adapted blaZ positive STs were isolated from BTM. Moreover, we identified potential spillover events of S. aureus sequence types between host species. The presence of penicillin-resistant-human-adapted S. aureus on both organic and conventional dairy farms highlights a “One Health” concern at the junction of public and animal health requiring further surveillance.

Abstract Vagus nerve signaling is a key component of the gut-brain axis and regulates diverse physiological processes that decline with age. Gut to brain vagus firing patterns are regulated by myenteric intrinsic primary afferent neuron (IPAN) to vagus neurotransmission. It remains unclear how IPANs or the afferent vagus age functionally. Here we identified a distinct ageing code in gut to brain neurotransmission defined by consistent differences in firing rates, burst durations, interburst and intraburst firing intervals of IPANs and the vagus, when comparing young and aged neurons. The aminosterol squalamine changed aged neurons firing patterns to a young phenotype. In contrast to young neurons, sertraline failed to increase firing rates in the aged vagus whereas squalamine was effective. These results may have implications for improved treatments involving pharmacological and electrical stimulation of the vagus for age-related mood and other disorders. For example, oral squalamine might be substituted for or added to sertraline for the aged.

Reintroduction is an important tool in the conservation and recovery of aquatic species at risk. However, components of the reintroduction process such as transportation have the potential to induce physiological stress and the extent to which preparatory techniques can mitigate this stress is poorly understood in small-bodied fishes. To address this concern, we studied the effect of transport on two fitness-related performance measures: maximum metabolic rate and thermal tolerance in redside dace (Clinostomus elongatus), an imperilled small-bodied stream fish native to eastern North America. Prior to transportation, we manipulated the body condition of redside dace over a 12-week period, by providing either low (1% of their total body mass) or high (2% of their total body mass) rations. The goal of this manipulation was to influence body condition, as higher body condition can enhance physiological performance. Subsequently, redside dace were transported for varying durations: 0, 3, and 6 h. Following transportation, we measured maximum metabolic rate (µmol/h) and thermal tolerance (CTmax, °C). Our results indicate that neither transport nor body condition had a significant effect on maximum metabolic rate or thermal tolerance (CTmax). These findings provide preliminary evidence that redside dace can physiologically tolerate transport based on the endpoints measured and this information may possibly be extended to other small-bodied fish, for which information is lacking.

Abstract Background Cardiovascular disease (CVD) and diabetes mellitus are major health issues in Tonga and other Pacific countries, although mortality levels and trends are unclear. We assess the impacts of cause-of-death certification on coding of CVD and diabetes as underlying causes of death (UCoD). Methods Tongan records containing cause-of-death data (2001–2018), including medical certificates of cause-of-death (MCCD), had UCoD assigned according to International Classification of Diseases 10th revision (ICD-10) coding rules. Deaths without recorded cause were included to ascertain total mortality. Diabetes and hypertension causes were reallocated from Part 1 of the MCCD (direct cause) to Part 2 (contributory cause) if potentially fatal complications were not recorded, and an alternative UCoD was assigned. Proportional mortality by cause based on the alternative UCoD were applied to total deaths then mortality rates calculated by age and sex using census/intercensal population estimates. CVD and diabetes mortality rates for unaltered and alternative UCoD were compared using Poisson regression. Results Over 2001–18, in ages 35–59 years, alternative CVD mortality was higher than unaltered CVD mortality in men (p = 0.043) and women (p = 0.15); for 2010–18, alternative versus unaltered measures in men were 3.3/103 (95%CI: 3.0–3.7/103) versus 2.9/103 (95%CI: 2.6–3.2/103), and in women were 1.1/103 (95%CI: 0.9–1.3/103) versus 0.9/103 (95%CI: 0.8–1.1/103). Conversely, alternative diabetes mortality rates were significantly lower than the unaltered rates over 2001–18 in men (p

Background: Human Papillomavirus (HPV) is the primary cause of cervical cancer. Single-dose HPV vaccination can effectively prevent high-risk HPV infection that causes cervical cancer and accelerate progress toward achieving cervical cancer elimination goals. We modelled the potential impact of adopting single-dose HPV vaccination strategies on health and economic outcomes in Kenya, where a two-dose schedule is the current standard. Methods: Using a validated compartmental transmission model of HPV and HIV in Kenya, we evaluated the costs from the payer’s perspective to vaccinate girls by age 10 with either one or two doses and increasing coverage levels (0%, 70%, 77%, 90%). Additionally, we modelled single-dose strategies supplemented with either catch-up vaccination of adolescent girls and young women or vaccination for all by age 10, funded with the first five-years of cost savings of switching from a two- to one-dose schedule. Costs and outcomes were discounted at 3% annually, and incremental cost-effectiveness ratios (ICERs) were calculated per disability-adjusted-life-year (DALY) averted. Results: All one-dose and the two-dose 90% coverage strategies were on the efficiency frontier, dominating the remaining two-dose strategies. The two-dose 90% coverage strategy had a substantially higher ICER (US$6508.80/DALY averted) than the one-dose 90% coverage (US$197.44/DALY averted). Transitioning from a two- to one-dose schedule could result in US$21.4 Million saved over the first five years, which could potentially fund 2.75 million supplemental HPV vaccinations. With this re-investment, all two-dose HPV vaccination scenarios would be dominated. The greatest DALYs were averted with the single-dose HPV vaccination schedule at 90% coverage supplemented with catch-up for 11–24-year-old girls, which had an ICER of US$78.73/DALYs averted. Conclusions: Considering the logistical and cost burdens of a two-dose schedule, a one-dose schedule for girls by age 10 would generate savings that could be leveraged for catch-up vaccination for older girls and accelerate cervical cancer elimination in Kenya.

In the original publication [...]

Abstract Transitions to physically different environments, such as the water-to-land transition, proved to be the main drivers of relevant evolutionary events. Brachyuran crabs evolved remarkable morphological, behavioral, and physiological adaptations to terrestrial life. Terrestrial species evolved new respiratory structures devoted to replace or support the gills, a multifunctional organ devoted to gas exchanges, ion-regulation and nitrogen excretion. It was hypothesized that microorganisms associated with respiratory apparatus could have facilitated the processes of osmoregulation, respiration, and elimination of metabolites along this evolutionary transition. To test if crab species with different breathing adaptations may host similar microbial communities on their gills, we performed a comparative targeted-metagenomic analysis, selecting two marine and six terrestrial crabs belonging to different families and characterised by different breathing adaptations. We analysed anterior and posterior gills separately according to their different and specific roles. Regardless of their terrestrial or marine adaptations, microbial assemblages were strongly species-specific indicating a non-random association between the host and its microbiome. Significant differences were found in only two terrestrial species when considering posterior vs. anterior gills, without any association with species-specific respiratory adaptations. Our results suggest that all the selected species are strongly adapted to the ecological niche and specific micro-habitat they colonise.

Abstract Identifying and planning treatment for retinopathy of prematurity (ROP) using telemedicine is becoming increasingly ubiquitous, necessitating a grading system to help caretakers of at-risk infants gauge disease severity. The modified ROP Activity Scale (mROP-ActS) factors zone, stage, and plus disease into its scoring system, addressing the need for assessing ROP’s totality of binocular burden via indirect ophthalmoscopy. However, there is an unmet need for an alternative score which could facilitate ROP identification and gauge disease improvement or deterioration specifically on photographic telemedicine exams. Here, we propose such a system (Telemedicine ROP Severity Score [TeleROP-SS]), which we have compared against the mROP-ActS. In our statistical analysis of 1568 exams, we saw that TeleROP-SS was able to return a score in all instances based on the gradings available from the retrospective SUNDROP cohort, while mROP-ActS obtained a score of 80.8% in right eyes and 81.1% in left eyes. For treatment-warranted ROP (TW-ROP), TeleROP-SS obtained a score of 100% and 95% in the right and left eyes respectively, while mROP-ActS obtained a score of 70% and 63% respectively. The TeleROP-SS score can identify disease improvement or deterioration on telemedicine exams, distinguish timepoints at which treatments can be given, and it has the adaptability to be modified as needed.

Science communication and university Extension initiatives are evolving in response to society’s needs and an ever-changing digital landscape. The UF/IFAS Center for Aquatic and Invasive Plants (CAIP) has recently launched a podcast called Working in the Weeds (WITW). We surveyed podcast listeners to find out their motivations for listening and asked for their feedback on current episodes and future content. The survey revealed that a majority of respondents were individuals who work in the world of invasive plants. Many respondents were introduced to the podcast through work and listen to learn more about relevant research and information, to feel connected to the Center, and to be entertained. Overall, the respondents were satisfied with the podcast production elements and the variety of episode styles. Based on open-ended responses, listeners described that the podcast shares science in a meaningful way and the Center should continue producing episodes that highlight invasive plant research. Some respondents suggested future episodes should cover specific invasive plants, environmental impacts, herbicide use and safety, management techniques, and social issues surrounding invasive plant management.

Abstract Mercury (Hg) is a naturally occurring element that has been greatly enriched in the environment by human activities like mining and fossil fuel combustion. Despite commonalities in some carbon dioxide (CO2) and Hg emission sources, the implications of long‐range climate scenarios for anthropogenic Hg emissions have yet to be explored. Here, we present comprehensive projections of anthropogenic Hg emissions extending to the year 2300 and evaluate impacts on global atmospheric Hg deposition. Projections are based on four Shared Socioeconomic Pathways (SSPs) ranging from sustainable reductions in resource and energy intensity to rapid economic growth driven by abundant fossil fuel exploitation. There is a greater than two‐fold difference in cumulative anthropogenic Hg emissions between the lower‐bound (110 Gg) and upper‐bound (235 Gg) scenarios. Hg releases to land and water are approximately six times those of direct emissions to air (600–1,470 Gg). At their peak, anthropogenic Hg emissions reach 2,200–2,600 Mg a−1 sometime between 2010 (baseline) and 2030, depending on the SSP scenario. Coal combustion is the largest determinant of differences in Hg emissions among scenarios. Decoupling of Hg and CO2 emission sources occurs under low‐to mid‐range scenarios, though contributions from artisanal and small‐scale gold mining remain uncertain. Future Hg emissions may have lower gaseous elemental Hg (Hg0) and higher divalent Hg (HgII), resulting in a higher fraction of locally sourced Hg deposition. Projected reemissions of previously deposited anthropogenic Hg follow a similar temporal trajectory to primary emissions, amplifying the benefits of primary Hg emission reductions under the most stringent mitigation scenarios.