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Abstract Provision of non-invasive vascular imaging results to individuals has been shown to improve cardiovascular disease risk factor control: its impact on diet remains uncertain. In this two-arm, single-blind, parallel, 12-week randomized controlled trial, 240 participants, 57.5% females aged 60–80 y had abdominal aortic calcification and clinical assessments performed at a hospital clinic. Participants were randomized 1:1 to receive (intervention n = 121) or not (control n = 119) their calcification results. Both groups received educational resources on cardiovascular disease risk control and were unblinded to the intervention. Outcome measures were performed at baseline and 12 weeks. The primary outcomes of the study were changes in fruit and vegetable intake measures over 12 weeks assessed using plasma carotenoid concentrations (biomarkers of FV intake) and a food frequency questionnaire. Secondary outcomes included 12-week changes in other aspects of the diet, physical activity, body weight, blood pressure, heart rate, lipid profile, glucose concentrations, estimated cardiovascular disease risk score, and medication use. Between-group differences were tested using linear mixed-effects regression. There were no between-group differences in the primary outcomes at 12 weeks: plasma carotenoids (mean difference +0.03 µg/mL [95%CI −0.06, 0.13]) and fruit and vegetable intakes (+18 g/d [−37, 72]). However, the provision of calcification results led to between-group differences in serum total (−0.22 mmol/L [−0.41, −0.04]) and non-HDL (−0.19 mmol/L [−0.35, −0.03]) cholesterol, and estimated cardiovascular disease risk score (−0.24% [−0.47, −0.02]). No between-group differences were seen for other secondary outcomes. In this work, providing vascular imaging results did not improve diet but did improve some cardiovascular disease risk factors (Australian and New Zealand Clinical Trials Registry ACTRN12618001087246).

Abstract Transposable elements (TEs) are often expressed at higher levels in tumor cells than normal cells, implicating these genomic regions as an untapped pool of tumor-associated antigens. In ovarian cancer (OC), protein from the TE ERV-K is frequently expressed by tumor cells. Here we determined whether the targeting of previously identified epitope in the envelope gene (env) of ERV-K resulted in target antigen specificity against cancer cells. We found that transducing healthy donor T cells with an ERV-K-Env-specific T cell receptor construct resulted in antigen specificity only when co-cultured with HLA-A*03:01 B lymphoblastoid cells. Furthermore, in vitro priming of several healthy donors with this epitope of ERV-K-Env did not result in target antigen specificity. These data suggest that the T cell receptor is a poor candidate for targeting this specific ERV-K-Env epitope and has limited potential as a T cell therapy for OC.

Abstract Background The United States (U.S.) faces a significant mental health crisis, with around 52.9 million adults experiencing mental health disorders, with young adults (18–25 years old), such as college students, having the highest prevalence and lowest service utilization rates. While efforts to expand mental health services through “push” strategies are in place (e.g., training therapists in evidence-based therapies), limited initial engagement suggests a need for “pull strategies” and targeted marketing that make services attractive to college students and increase demand. This mixed-methods study identifies U.S. university mental health clinic websites and website characteristics that are attractive and engaging to college students interested in seeking mental health services (i.e., students were considering or actively looking for mental health support). Methods Eleven U.S. university websites were chosen (10 randomly and one from the university where students were attending) from a pool of 44 Psychological Clinical Science Accreditation System training clinics websites. Fifty-seven college students (M age = 20.95, SD = 2.97; 81% female; 68% racial/ethnic minority) were videorecorded engaging with two U.S. university mental health clinic websites, completed self-report engagement measures, and gave detailed feedback about websites through semi-structured interviews. Results Likert scale scores revealed moderate engagement with all websites (e.g., they were interesting and helpful). Qualitative results indicated that websites that provided important and easily understood information about key features of services (e.g., types, evidence-base, and cost), therapist backgrounds, psychoeducation, used lay language, and had an appealing website layout (e.g., color, font, images, organization, and interactive components) generated greater consumer interest and trust in their mental health services. Conclusions This study emphasizes the importance of using marketing strategies to enhance college students’ engagement through mental health service websites. Salient features, psychoeducation, and effective promotional strategies (e.g., how information is presented) were identified as crucial for website engagement and subsequent mental health service uptake. Using marketing strategies, such as tailoring language to consumer literacy levels, describing the evidence-base of services, and improving website design may address college students’ needs and enhance initial mental health service engagement.

Introduction: Atlas and axis fractures are the most severe cervical fractures which may result in complete paralysis or death. The purpose of the current study is to identify disparities regarding length of stay (LOS), mortality, and demographic factors in patients with the most serious cervical spine fractures utilizing a nationally representative database. MATERIALS AND METHODS: The Nationwide Emergency Department Sample was utilized to provide a representative sample for patients with a primary diagnosis of C1 or C2 fracture presenting to emergency departments in years from October 2015 to December 2019. A multivariable logistic regression model was used to estimate LOS for different patient demographics, including gender, race, and age. Results: A weighted sample of 7,262,791 patients presented to emergency rooms in the United States between 2015 and 2019. The mean age at admission was 76 years old, 52.6% of patients were female, and 83.0% identified as white. Patients between 45 and 65 and patients over 65 were significantly more likely to have an increased LOS. Women were less likely to have an increased LOS than men. Patients identifying as Black were significantly more likely to have increased LOS over white patients. In addition, patients who had an increased LOS were more likely to die in the hospital than patients with a shorter LOS. Conclusion: This study provides patient characteristics that help providers determine patient risk factors for increased hospital LOS and in-hospital mortality for those suffering from C1 and C2 fractures. Clinicians should be made aware of these disparities to allow equitable delivery of care.

Abstract Purpose The United States Medical Licensing Examination (USMLE) is an examination series required for allopathic physician licensure in the United States (US). USMLE content is created and maintained by the National Board of Medical Examinations (NBME). The specialty composition of the USMLE and NBME taskforce members involved in the creation of examination content is currently unknown. Methods Using the 2021 USMLE and 2021 NBME Committees and Task Forces documents, we determined each member’s board-certified primary specialty and involvement in test material development committees who we dubbed “test writers”. Total active physicians by primary specialty were recorded from the 2020 Physician Specialty Data Report published by the Association of American Medical Colleges (AAMC). Descriptive statistics and chi-square analysis were used to analyze the cohorts. Results The USMLE and NBME test writer primary specialty composition was found to be significantly different compared to the US active physician population (USMLE χ2[32] = 172, p

Abstract Background Higher cruciferous vegetable intake is associated with lower cardiovascular disease risk in observational studies. The pathways involved remain uncertain. We aimed to determine whether cruciferous vegetable intake (active) lowers 24-h brachial systolic blood pressure (SBP; primary outcome) compared to root and squash vegetables (control) in Australian adults with mildly elevated BP (SBP 120–160 mmHg inclusive). Methods In this randomized, controlled, crossover trial, participants completed two 2-week dietary interventions separated by a 2-week washout. Cruciferous vegetables were compared to root and squash vegetables (~ 300 g/day) consumed with lunch and dinner meals. Participants were blinded to which interventions were the active and control. Adherence was assessed using food diaries and biomarkers (S-methyl cysteine sulfoxide (SMCSO, active) and carotenoids (control)). Twenty-four-hour brachial ambulatory SBP and secondary outcomes were assessed pre- and post each intervention. Differences were tested using linear mixed effects regression. Results Eighteen participants were recruited (median (IQR) age: 68 (66–70); female: n = 16/18; mean ± SD clinic SBP: 135.9 ± 10.0 mmHg). For both interventions, 72% participants had 100% adherence (IQR: 96.4–100%). SMCSO and carotenoids were significantly different between interventions (mean difference active vs. control SMCSO: 22.93 mg/mL, 95%CI 15.62, 30.23, P

Abstract Background Empirical evidence has demonstrated associations between pre-pregnancy obesity and perinatal maternal depressive symptoms. Omega-3 is an essential fatty acid derived from dietary sources that is critical for fetal brain development. Pre-pregnancy obesity is associated with higher omega-3 intake, but a weaker association between dietary intake and respective maternal and cord blood omega-3 levels. Further, lower intake of omega-3 during pregnancy has been linked to higher depressive symptoms. Yet, prior studies have not examined the interactive effects of pre-pregnancy overweight or obesity (OWOB) and prenatal maternal mental health symptoms on infant cord blood omega-3 levels. Methods Participants included 394 maternal-infant dyads from the NIH Environmental influences on Child Health Outcomes (ECHO) - Safe Passage Study in South Dakota. A pre-pregnancy body mass index (BMI) > 25 was used to dichotomize participants as OWOB (54%) vs. non-OWOB (46%). Prenatal maternal depressive symptoms were measured using the Edinburgh Postnatal Depression Scale (EPDS) and prenatal maternal anxiety symptoms were measured using the State-Trait Anxiety Inventory (STAI). We implemented linear regression models to examine the interaction term between pre-pregnancy BMI category and prenatal maternal mental health symptoms on cord blood omega-3 levels. Secondary analyses were stratified by pre-pregnancy BMI category. Results We observed a significant interaction between pre-pregnancy BMI category and prenatal maternal depressive symptoms with cord blood omega-3 (F(4,379) = 6.21, p

Abstract Background Amidst the escalating prevalence of glucose-related chronic diseases, the advancements, potential uses, and growing accessibility of continuous glucose monitors (CGM) have piqued the interest of healthcare providers, consumers, and health behaviour researchers. Yet, there is a paucity of literature characterising the use of CGM in behavioural intervention research. This scoping review aims to describe targeted populations, health behaviours, health-related outcomes, and CGM protocols in randomised controlled trials (RCTs) that employed CGM to support health behaviour change. Methods We searched Ovid MEDLINE, Elsevier Embase, Cochrane Central Register of Controlled Trials, EBSCOhost PsycINFO, and ProQuest Dissertations & Theses Global from inception to January 2024 for RCTs of behavioural interventions conducted in adults that incorporated CGM-based biological feedback. Citation searching was also performed. The review protocol was registered ( https://doi.org/10.17605/OSF.IO/SJREA ). Findings Collectively, 5389 citations were obtained from databases and citation searching, 3995 articles were screened, and 31 were deemed eligible and included in the review. Most studies (n = 20/31, 65%) included adults with type 2 diabetes and reported HbA1c as an outcome (n = 29/31, 94%). CGM was most commonly used in interventions to target changes in diet (n = 27/31, 87%) and/or physical activity (n = 16/31, 52%). 42% (n = 13/31) of studies provided prospective CGM-based guidance on diet or activity, while 61% (n = 19/31) included retrospective CGM-based guidance. CGM data was typically unblinded (n = 24/31, 77%) and CGM-based biological feedback was most often provided through the CGM and two-way communication (n = 12/31, 39%). Communication typically occurred in-person (n = 13/31, 42%) once per CGM wear (n = 13/31; 42%). Conclusions This scoping review reveals a predominant focus on diabetes in CGM-based interventions, pointing out a research gap in its wider application for behaviour change. Future research should expand the evidence base to support the use of CGM as a behaviour change tool and establish best practices for its implementation. Trial registration doi.org/10.17605/OSF.IO/SJREA.

Abstract Hypervariable region sequencing of the 16S ribosomal RNA (rRNA) gene plays a critical role in microbial ecology by offering insights into bacterial communities within specific niches. While providing valuable genus-level information, its reliance on data from targeted genetic regions limits its overall utility. Recent advances in sequencing technologies have enabled characterisation of the full-length 16S rRNA gene, enhancing species-level classification. Although current short-read platforms are cost-effective and precise, they lack full-length 16S rRNA amplicon sequencing capability. This study aimed to evaluate the feasibility of a modified 150 bp paired-end full-length 16S rRNA amplicon short-read sequencing technique on the Illumina iSeq 100 and 16S rRNA amplicon assembly workflow by utilising a standard mock microbial community and subsequently performing exploratory characterisation of captive (zoo) and free-ranging African elephant (Loxodonta africana) respiratory microbiota. Our findings demonstrate that, despite generating assembled amplicons averaging 869 bp in length, this sequencing technique provides taxonomic assignments consistent with the theoretical composition of the mock community and respiratory microbiota of other mammals. Tentative bacterial signatures, potentially representing distinct respiratory tract compartments (trunk and lower respiratory tract) were visually identified, necessitating further investigation to gain deeper insights into their implication for elephant physiology and health.

Abstract Microtransactions provide optional, virtual, video game goods that, for an additional cost to the player, provide additional game content and alter the gameplay experience. Loot boxes—a specific form of microtransaction—offer randomised rewards in exchange for payment, and are argued to be structurally and psychologically similar to gambling. Nascent research suggests that a link exists between autism and both problematic gaming and problematic gambling. Here, we investigated the relationships between autistic characteristics and experiences, and excessive video gaming and microtransaction expenditure. A sample of 1178 adults from Australia, Aotearoa, and The United States were recruited from Prolific Academic, and completed a survey measuring in-game expenditure, autistic characteristics and experiences, problematic gaming, problematic gambling, and risky loot box use. Analyses showed positive associations between autistic characteristics and experiences with problematic gaming and problem gambling symptomatology. However, results also showed a small, negative association between autistic characteristics and experiences and spending on loot boxes when problem gambling symptoms, problematic gaming, and risky loot box use were statistically controlled for. These results suggest that autistic gamers may be vulnerable to problematic gaming and gambling, but that this effect does not extend to the purchasing of microtransactions.

Abstract Virulence and metabolism are often interlinked to control the expression of essential colonisation factors in response to host-associated signals. Here, we identified an uncharacterised transporter of the dietary monosaccharide ʟ-arabinose that is widely encoded by the zoonotic pathogen enterohaemorrhagic Escherichia coli (EHEC), required for full competitive fitness in the mouse gut and highly expressed during human infection. Discovery of this transporter suggested that EHEC strains have an enhanced ability to scavenge ʟ-arabinose and therefore prompted us to investigate the impact of this nutrient on pathogenesis. Accordingly, we discovered that ʟ-arabinose enhances expression of the EHEC type 3 secretion system, increasing its ability to colonise host cells, and that the underlying mechanism is dependent on products of its catabolism rather than the sensing of ʟ-arabinose as a signal. Furthermore, using the murine pathogen Citrobacter rodentium, we show that ʟ-arabinose metabolism provides a fitness benefit during infection via virulence factor regulation, as opposed to supporting pathogen growth. Finally, we show that this mechanism is not restricted to ʟ-arabinose and extends to other pentose sugars with a similar metabolic fate. This work highlights the importance integrating central metabolism with virulence regulation in order to maximise competitive fitness of enteric pathogens within the host-niche.

Left ventricular noncompaction cardiomyopathy is associated with heart failure, arrhythmia, and sudden cardiac death. The developmental mechanism underpinning noncompaction in the adult heart is still not fully understood, with lack of trabeculae compaction, hypertrabeculation, and loss of proliferation cited as possible causes. To study this, we utilised a mouse model of aberrant Rho kinase (ROCK) signalling in cardiomyocytes, which led to a noncompaction phenotype during embryogenesis, and monitored how this progressed after birth and into adulthood. The cause of the early noncompaction at E15.5 was attributed to a decrease in proliferation in the developing ventricular wall. By E18.5, the phenotype became patchy, with regions of noncompaction interspersed with thick compacted areas of ventricular wall. To study how this altered myoarchitecture of the heart influenced impulse propagation in the developing and adult heart, we used histology with immunohistochemistry for gap junction protein expression, optical mapping, and electrocardiography. At the prenatal stages, a clear reduction in left ventricular wall thickness, accompanied by abnormal conduction of the ectopically paced beat in that area, was observed in mutant hearts. This correlated with increased expression of connexin-40 and connexin-43 in noncompacted trabeculae. In postnatal stages, left ventricular noncompaction was resolved, but the right ventricular wall remained structurally abnormal through to adulthood with cardiomyocyte hypertrophy and retention of myocardial crypts. Thus, this is a novel model of self-correcting embryonic hypertrabeculation cardiomyopathy, but it highlights that remodelling potential differs between the left and right ventricles. We conclude that disruption of ROCK signalling induces both morphological and electrophysiological changes that evolve over time, highlighting the link between myocyte proliferation and noncompaction phenotypes and electrophysiological differentiation.

The HEALthy Brain and Child Development (HBCD) Study, a multi-site prospective longitudinal cohort study, will examine human brain, cognitive, behavioral, social, and emotional development beginning prenatally and planned through early childhood. Electroencephalography (EEG) is one of two brain imaging modalities central to the HBCD Study. EEG records electrical signals from the scalp that reflect electrical brain activity. In addition, the EEG signal can be synchronized to the presentation of discrete stimuli (auditory or visual) to measure specific cognitive processes with excellent temporal precision (e.g., event-related potentials; ERPs). EEG is particularly helpful for the HBCD Study as it can be used with awake, alert infants, and can be acquired continuously across development. The current paper reviews the HBCD Study’s EEG/ERP protocol: (a) the selection and development of the tasks (Video Resting State, Visual Evoked Potential, Auditory Oddball, Face Processing); (b) the implementation of common cross-site acquisition parameters and hardware, site setup, training, and initial piloting; (c) the development of the preprocessing pipelines and creation of derivatives; and (d) the incorporation of equity and inclusion considerations. The paper also provides an overview of the functioning of the EEG Workgroup and the input from members across all steps of protocol development and piloting.

Abstract In the United States, 2.0 million new cancer cases and around 600,000 cancer deaths are estimated to occur in 2024. Early detection gives cancer patients the best chance for treatment success. Currently, cancer screening in the general population is recommended for a limited set of cancers; as a result, most cancer types are not regularly screened. Thus, in recent years, we have seen a wave of novel, non‐invasive, single‐ and multi‐cancer detection tests (SCD and MCD), promising detection of cancer signals prior to the onset of symptoms and/or clinical diagnosis. To accelerate the development, access, and adoption of these tests, the Blood Profiling Atlas in Cancer (BLOODPAC) Consortium, a collaborative infrastructure for developing standards and best practices, established the Early Detection & Screening (ED&S) Working Group. The early detection space is in need of consensus around definitions for SCD and MCD tests that harmonize terminology across diverse stakeholders, thereby reducing communication barriers and ultimately advancing the discipline. To this end, the ED&S Working Group compiled a lexicon of terms, chosen based on perceived importance, frequency of use, lack of clarity, and unique challenges in the context of SCD and MCD tests. This lexicon was submitted to the FDA for their feedback, which was incorporated. In this work, we present the first installment of the lexicon, consisting of 14 primary terms, that will be part of an online dictionary and provide a foundation for future projects of BLOODPAC's ED&S Working Group.

Summary: Necrotizing enterocolitis (NEC) is a severe intestinal disease of very preterm infants with mother’s own milk (MOM) providing protection, but the contribution of the MOM microbiota to NEC risk has not been explored. Here, we analyze MOM of 110 preterm infants (48 NEC, 62 control) in a cross-sectional study. Breast milk contains viable bacteria, but there is no significant difference in MOM microbiota between NEC and controls. Integrative analysis between MOM microbiota, human milk oligosaccharides (HMOs), and the infant gut microbiota shows positive correlations only between Acinetobacter in the infant gut and Acinetobacter and Staphylococcus in MOM. This study suggests that NEC protection from MOM is not modulated through the MOM microbiota. Thus, “‘restoring” the MOM microbiota in donor human milk is unlikely to reduce NEC, and emphasis should instead focus on increasing fresh maternal human milk intake and researching different therapies for NEC prevention.

IntroductionDietary nitrate is potentially beneficial for cardiovascular, cerebrovascular, and nervous systems due to its role as a nitric oxide (NO) precursor. Increased nitrate intake improves cardiovascular health and therefore could protect against dementia, given the cardiovascular-dementia link.ObjectiveTo investigate the association between source-dependent nitrate intake and dementia-related mortality. As individuals with diabetes are at higher risk of dementia, a secondary aim was to investigate if the associations between nitrate and dementia varied by diabetes mellitus (DM) and pre-diabetes status.MethodsThis study involved 9,149 participants aged ≥25 years from the well-characterised Australian Diabetes, Obesity, and Lifestyle (AusDiab) Study followed over a period of 17 years. Intakes of plant-sourced, vegetable-sourced, naturally occurring animal-sourced nitrate, and processed meat (where nitrate is an allowed additive)-sourced nitrate were assessed from a 74-item food frequency questionnaire completed by participants at baseline and nitrate databases were used to estimate nitrate from these different dietary sources. Associations between source-dependent nitrate intake and dementia-related mortality were assessed using multivariable-adjusted Cox proportional hazards models adjusted for demographics, lifestyle, and dietary factors.ResultsOver 17 years of follow-up, 93 (1.0%) dementia-related deaths occurred of 1,237 (13.5%) total deaths. In multivariable-adjusted models, participants with the highest intakes of plant-sourced nitrate (median intake 98 mg/day) had a 57% lower risk of dementia-related mortality [HR (95% CI): 0.43 (0.22, 0.87)] compared to participants with lowest intakes of plant-sourced nitrate (median intake 35 mg/day). A 66% lower risk was also seen for higher intakes of vegetable-sourced nitrate [HR (95% CI): 0.34 (0.17, 0.66)]. No association was observed for animal-sourced nitrate, but the risk was two times higher amongst those who consumed the most processed meat-sourced nitrate intake [HR (95%): 2.10 (1.07, 4.12)]. The highest intake of vegetable-sourced nitrate was associated with a lower risk of dementia-related mortality for those with and without DM and pre-diabetes.ConclusionEncouraging the intake of nitrate-rich vegetables, such as green leafy vegetables and beetroot, may lower the risk of dementia-related mortality, particularly in individuals with (pre-) diabetes who are at a higher dementia risk.

Abstract Background Based on the largely untested premise that it is a restorative hormone that may reverse the detrimental impacts of aging, prescription of testosterone (T) has increased in recent decades despite no new clinical indications. It is apparent that middle-aged and older men with low-normal serum T levels are considering T supplementation as an anti-aging strategy. At the same time, there is evidence that physical activity (PA) is at historical lows in the Western world. In this review, we compare the impacts of T treatment aimed at achieving physiological T concentrations in middle-aged and older men, alongside the impacts of ecologically relevant forms of exercise training. The independent, and possible combined, effects of T and exercise therapy on physiological outcomes such as aerobic fitness, body composition and muscular strength are addressed. Main Body Our findings suggest that both T treatment and exercise improve lean body mass in healthy older men. If improvement in lean body mass is the primary aim, then T treatment could be considered, and the combination of T and exercise may be more beneficial than either in isolation. In terms of muscle strength in older age, an exercise program is likely to be more beneficial than T treatment (where the dose is aimed at achieving physiological concentrations), and the addition of such T treatment does not provide further benefit beyond that of exercise alone. For aerobic fitness, T at doses aimed at achieving physiological concentrations has relatively modest impacts, particularly in comparison to exercise training, and there is limited evidence as to additive effects. Whilst higher doses of T, particularly by intramuscular injection, may have larger impacts on lean body mass and strength, this must be balanced against potential risks. Conclusion Knowing the impacts of T treatment and exercise on variables such as body composition, strength and aerobic fitness extends our understanding of the relative benefits of physiological and pharmacological interventions in aging men. Our review suggests that T has impacts on strength, body composition and aerobic fitness outcomes that are dependent upon dose, route of administration, and formulation. T treatment aimed at achieving physiological T concentrations in middle-aged and older men can improve lean body mass, whilst exercise training enhances lean body mass, aerobic fitness and strength. Men who are physically able to exercise safely should be encouraged to do so, not only in terms of building lean body mass, strength and aerobic fitness, but for the myriad health benefits that exercise training confers.

Abstract Primary familial brain calcification (PFBC) is characterized by calcium deposition in the brain, causing progressive movement disorders, psychiatric symptoms, and cognitive decline. PFBC is a heterogeneous disorder currently linked to variants in six different genes, but most patients remain genetically undiagnosed. Here, we identify biallelic NAA60 variants in ten individuals from seven families with autosomal recessive PFBC. The NAA60 variants lead to loss-of-function with lack of protein N-terminal (Nt)-acetylation activity. We show that the phosphate importer SLC20A2 is a substrate of NAA60 in vitro. In cells, loss of NAA60 caused reduced surface levels of SLC20A2 and a reduction in extracellular phosphate uptake. This study establishes NAA60 as a causal gene for PFBC, provides a possible biochemical explanation of its disease-causing mechanisms and underscores NAA60-mediated Nt-acetylation of transmembrane proteins as a fundamental process for healthy neurobiological functioning.

Abstract Background Dairy products and their components may impact immune function, although the current evidence base has some research gaps. As part of a larger systematic literature review of dairy products/components (including probiotics, dairy proteins, and dairy fats) and immune function, we identified the available epidemiologic research on the impact of dairy products/components on incidence and natural history of infectious diseases. Methods PubMed and Embase databases were systematically searched through May 2022 to identify eligible studies using pre-defined Population, Intervention, Comparator, Outcomes, and Study design criteria. Herein, we focused on describing the impacts of dairy product/component on infectious disease outcomes, including the effect on leukocyte and cytokine response in humans. Risk of bias assessment was performed using the Academy of Nutrition and Dietetics Quality Criteria Checklist. The Preferred Reporting Items for Systematic Reviews and Meta-analyses (PRISMA) guidelines were followed. Results Among 9,832 studies identified from the larger literature search, 133 relevant publications from 128 studies reported on dairy product/component and infectious disease outcomes. Few studies are available on the impact of non-fermented milk and traditional yogurt on infectious disease. Evidence was identified to suggest milk and yogurt drinks fermented with Lactobacillus strains reduce the risk and burden of common infectious diseases (CIDs), although the findings are mixed and difficult to reconcile due to heterogenous study populations, bacterial strains, and study methods. Few studies are available on the impact of dairy products/components on the natural history of infection, with the available findings indicating probiotics may both improve gastrointestinal symptoms among HIV-infected persons and help eradicate and alleviate the symptoms of Heliobacter (H.) pylori. The available evidence also suggests lactoferrin may reduce the virological burden of COVID-19 and hepatitis C virus. No consistent changes in leukocytes or cytokine production were observed for any type of dairy product or their components, but probiotics appeared to enhance natural killer cell levels/activity and the phagocytic process. Conclusions Dairy products, particularly those with added probiotics, may represent an easily accessible nutritional intervention to prevent and improve the course of infectious diseases. This review highlights the need for additional research in this potentially impactful area. Prospero registration CRD42022333780.

Key Clinical Message We describe a premature hydropic infant with Noonan syndrome and a therapy refractory chylothorax. This was shown to be due to a central conducting lymphatic anomaly. After therapy with a MEK‐inhibitor the infant recovered clinically and radiologically completely, possibly by restoring lymphatic valve function.

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

Abstract Background Medical mistrust, rooted in unethical research, is a barrier to cancer‐related health care for Black/African American (AA) persons. Understanding trust, mistrust, and health care experiences is crucial, especially in multiple myeloma (MM), which disproportionately burdens Black/AA persons in incidence and survival. Study Purpose This study qualitatively examines the experiences of Black/AA and White dyads (patient with MM and adult caregiver) to gain insights into these phenomena. Methods From November 2021 to April 2022, we recruited 21 dyads from the UNC Lineberger Comprehensive Cancer Center. Participants completed a sociodemographic survey and a 60–90 min semi‐structured interview. We used ATLAS.ti v9 for project management and to facilitate data analysis using the Sort and Sift, Think and Shift approach (ResearchTalk Inc). Results We interviewed 21 racially concordant dyads (11 Black/AA, 10 White) with mean patient ages of 70 (Black/AA) and 72 (White) at enrollment. Both Black/AA and White caregivers had a mean enrollment age of 68. The mean duration from MM diagnosis to enrollment for all patients was 5.5 years. Four key themes emerged: (1) knowledge and trust, (2) heightened emotions and discomfort, (3) differing mental constructs of health care experiences, and (4) mitigating mistrust, which varied by self‐identified race. Black/AA participants had greater knowledge of historical events like the U.S. Public Health Service Untreated Syphilis Study at Tuskegee and carried the emotional burden longer. They also emphasized self‐learning and self‐guided research about MM for informed medical decision‐making. Both Black/AA and White dyads emphasized the pivotal role of patient‐provider relationships and effective communication in fostering trust and addressing concerns. Conclusion Our study offers contextual insights into the enduring challenges of medical mistrust, particularly within the Black/AA community, and its implications for patients and caregivers accessing and receiving MM‐related care. Future studies should leverage these insights to guide the development of multilevel interventions addressing medical mistrust within the Black/AA community.

Abstract To accelerate the practical application of water splitting in alkaline media, it is imperative to enhance the electrocatalytic performance for the Hydrogen Evolution Reaction (HER). In this context, we demonstrate that a simple (one‐pot, one‐step) electrodeposition process of nickel (Ni) in the presence of 3,5‐diamino1,2,4‐triazole (DAT) results in the formation of fractally structured Ni films with a significantly increased surface area. The Electrochemically active surface area (ECSA) increases with the electrodeposition charge passed, with the film electrodeposited at 14 C cm−2 achieving a reduction in overpotential at −10 mA cm−2 (η10) to 65.7 mV, coupled with a remarkable increase in ECSA (114‐fold greater than that of Ni‐foil). Additionally, nickel deposited in the presence of DAT effectively mitigates deactivation during electrolysis, exhibiting a 3.6‐fold lower overpotential degradation compared to that of the smooth Ni foil. This simple electrodeposition technique, applicable to a variety of conductive substrates, is distinguished by its high catalytic performance in the HER, a feature of considerable significance.

ABSTRACTTo address intracellular mycobacterial infections, we developed a cocktail of four enzymes that catalytically attack three layers of the mycobacterial envelope. This cocktail is delivered to macrophages, through a targeted liposome presented here as ENTX_001. Endolytix Cocktail 1 (EC1) leverages mycobacteriophage lysin enzymes LysA and LysB, while also including α-amylase and isoamylase for degradation of the mycobacterial envelope from outside of the cell. The LysA family of proteins from mycobacteriophages has been shown to cleave the peptidoglycan layer, whereas LysB is an esterase that hydrolyzes the linkage between arabinogalactan and mycolic acids of the mycomembrane. The challenge of gaining access to the substrates of LysA and LysB provided exogenously was addressed by adding amylase enzymes that degrade the extracellular capsule shown to be present in Mycobacterium tuberculosis. This enzybiotic approach avoids antimicrobial resistance, specific receptor-mediated binding, and intracellular DNA surveillance pathways that limit many bacteriophage applications. We show this cocktail of enzymes is bactericidal in vitro against both rapid- and slow-growing nontuberculous mycobacteria (NTM) as well as M. tuberculosis strains. The EC1 cocktail shows superior killing activity when compared to previously characterized LysB alone. EC1 is also powerfully synergistic with standard-of-care antibiotics. In addition to in vitro killing of NTM, ENTX_001 demonstrates the rescue of infected macrophages from necrotic death by Mycobacteroides abscessus and Mycobacterium avium. Here, we demonstrate shredding of mycobacterial cells by EC1 into cellular debris as a mechanism of bactericide.IMPORTANCEThe world needs entirely new forms of antibiotics as resistance to chemical antibiotics is a critical problem facing society. We addressed this need by developing a targeted enzyme therapy for a broad range of species and strains within mycobacteria and highly related genera including nontuberculous mycobacteria such as Mycobacteroides abscessus, Mycobacterium avium, Mycobacterium intracellulare, as well as Mycobacterium tuberculosis. One advantage of this approach is the ability to drive our lytic enzymes through encapsulation into macrophage-targeted liposomes resulting in attack of mycobacteria in the cells that harbor them where they hide from the adaptive immune system and grow. Furthermore, this approach shreds mycobacteria independent of cell physiology as the drug targets the mycobacterial envelope while sidestepping the host range limitations observed with phage therapy and resistance to chemical antibiotics.

Abstract Background Diets low in vegetables are a main contributor to the health burden experienced by Australians living in rural communities. Given the ubiquity of smartphones and access to the Internet, digital interventions may offer an accessible delivery model for a dietary intervention in rural communities. However, no digital interventions to address low vegetable intake have been co-designed with adults living in rural areas. This paper describes the co-design of a digital intervention to improve vegetable intake with rural community members and research partners. Methods Active participants in the co-design process were adults ≥ 18 years living in three rural Australian communities (total n = 57) and research partners (n = 4) representing three local rural governments and one peak non-government health organisation. An iterative co-design process was undertaken to understand the needs (pre-design phase) and ideas (generative phase) of the target population. Eight online workshops and a community survey were conducted between July and December 2021. The MoSCoW prioritisation method was used to help participants identify the ‘Must-have, Should-have, Could-have, and Won’t-have or will not have right now’ features and functions of the digital intervention. Workshops were transcribed and inductively analysed using NVivo. Convergent and divergent themes were identified between the workshops and community survey to identify how to implement the digital intervention in the community. Results Consensus was reached on a concept for a digital intervention that addressed individual and food environment barriers to vegetable intake, specific to rural communities. Implementation recommendations centred on (i) food literacy approaches to improve skills via access to vegetable-rich recipes and healthy eating resources, (ii) access to personalisation options and behaviour change support, and (iii) improving the community food environment by providing information on and access to local food initiatives. Conclusions Rural-dwelling adults expressed preferences for personalised intervention features that can enhance food literacy and engagement with community food environments. This research will inform the development of the prototyping (evaluation phase) and feasibility testing (post-design phase) of this intervention.

Abstract Background Clostridioides difficile infection (CDI) is associated with considerable morbidity and mortality in hospitalized patients, especially among older adults. Probiotics have been evaluated to prevent hospital-acquired (HA) CDI in patients who are receiving systemic antibiotics, but the implementation of timely probiotic administration remains a challenge. We evaluated methods for effective probiotic implementation across a large health region as part of a study to assess the real-world effectiveness of a probiotic to prevent HA-CDI (Prevent CDI-55 +). Methods We used a stepped-wedge cluster-randomized controlled trial across four acute-care adult hospitals (n = 2,490 beds) to implement the use of the probiotic Bio-K + ® (Lactobacillus acidophilus CL1285®, L. casei LBC80R® and L. rhamnosus CLR2®; Laval, Quebec, Canada) in patients 55 years and older receiving systemic antimicrobials. The multifaceted probiotic implementation strategy included electronic clinical decision support, local site champions, and both health care provider and patient educational interventions. Focus groups were conducted during study implementation to identify ongoing barriers and facilitators to probiotic implementation, guiding needed adaptations of the implementation strategy. Focus groups were thematically analyzed using the Theoretical Domains Framework and the Consolidated Framework of Implementation Research. Results A total of 340 education sessions with over 1,800 key partners and participants occurred before and during implementation in each of the four hospitals. Site champions were identified for each included hospital, and both electronic clinical decision support and printed educational resources were available to health care providers and patients. A total of 15 individuals participated in 2 focus group and 7 interviews. Key barriers identified from the focus groups resulted in adaptation of the electronic clinical decision support and the addition of nursing education related to probiotic administration. As a result of modifying implementation strategies for identified behaviour change barriers, probiotic adherence rates were from 66.7 to 75.8% at 72 h of starting antibiotic therapy across the four participating acute care hospitals. Conclusions Use of a barrier-targeted multifaceted approach, including electronic clinical decision support, education, focus groups to guide the adaptation of the implementation plan, and local site champions, resulted in a high probiotic adherence rate in the Prevent CDI-55 + study.

Abstract Background This study describes the trauma experiences of people with severe mental illness (SMI) in Ethiopia and presents a model of how SMI and trauma exposure interact to reduce functioning and quality of life in this setting. Methods A total of 53 participants living and working in a rural district in southern Ethiopia were interviewed: 18 people living with SMI, 21 caregivers, and 14 primary health care providers. Results Many participants reported that exposure to traumatic and stressful events led to SMI, exacerbated SMI symptoms, and increased caregiver stress and distress. In addition, SMI symptoms and caregiver desperation, stress or stigma were also reported to increase the possibility of trauma exposure. Conclusions Results suggest it is incumbent upon health professionals and the broader health community to view trauma exposure (broadly defined) as a public health problem that affects all, particularly individuals with SMI.

Abstract Identifying the drivers that promote unique species compositions (i.e. ecological uniqueness) is crucial to understanding the mechanisms underpinning diversity patterns and for effective conservation planning. Environmental conditions are often sampled differentially in datasets, which can lead to rarer environments having unique species compositions, provided that environmental differences increase compositional differences. This effect, however, will be undesirable when a study aims to test the direct impact of environments rather than their availability. We developed an approach to reduce the effects of environmental availability in ecological uniqueness analyses through calculating expected pairwise compositional dissimilarities for each unique environmental condition. We further used simulations to assess the performance of our methods by randomly generating communities from two hypothetical environments with non‐overlapping species pools. Additionally, we used a dataset of 50 tree communities to demonstrate how environmental availability could impact relationships between environmental conditions and ecological uniqueness in empirical studies. Our simulations revealed that uniqueness metrics based on observed values are sensitive to environmental availability, while our approach correctly concluded that there were no differences among environments under the unbalanced design. Our analysis of tree communities produced divergent conclusions between the two approaches, as increasing slope reduced ecological uniqueness after controlling for their low availability in the dataset only. This suggests that low environmental availability inflated the ecological uniqueness of sites with high slope, which opposed its direct negative effects on ecological uniqueness, leading to a weak relationship based on observed values. To achieve a more mechanistic understanding of ecological uniqueness patterns, the effects of environmental availability must be considered. We recommend that studies use both uncorrected and corrected analyses to identify not only the direct effects of environmental conditions but also the degree to which their availability influences the observed relationships between ecological uniqueness and environment conditions. Our approach should be most necessary and applicable in unbalanced designs, which is a common characteristic in empirical studies.

Physics Education Research has a rich history of identifying common student ideas about specific physics topics. In the context of electric circuits, existing research on students’ ideas has primarily focused on misconceptions, misunderstandings, and difficulties. In this paper, we take a resource-oriented approach to identifying common student ideas about circuits by characterizing ideas we see as generative “seeds of science” that could form the basis of more sophisticated understandings. Based on our analysis of 1557 university physics student responses to five conceptual questions, we identify four common resources for understanding circuits.

IntroductionExposure to endocrine disrupting chemicals (EDCs), such as phthalates, can negatively impact maternal and child health, contributing to impaired fetal growth, preterm birth, and pregnancy complications, as well as increased downstream risks of cardiometabolic disease and breast cancer. Notably, women of color (WOC) are the largest consumers of personal care products, which are a common source of EDC exposure.MethodsThe Let's Reclaim Our Ancestral Roots (Let's R.O.A.R) Pilot Study developed an educational intervention delivered during pregnancy to promote reduced use of phthalate-containing hair care products (HCPs). This mixed-methods study included: (1) a quantitative analysis and (2) a qualitative analysis of the educational sessions and the semi-structured focus groups to evaluate the factors that influenced the hair care practices and product choices of WOC at various stages of life, including their current pregnancy (hereafter referred to as the hair journey). During the sessions, participants learned about EDCs (with a focus on phthalates), the unequal burden of exposure for WOC, adverse implications of exposure, and exposure reduction strategies. Focus group sessions provided insight into participants' hair journeys from childhood to the current pregnancy and explored factors during their hair product selection process. All sessions were transcribed and imported into NVivo Version 12 for coding and thematic analysis.ResultsA total of 46 individuals were enrolled in the study, and 31 participated in an educational session. This current work synthesizes the qualitative analysis of this study. We identified two important life stages (before and after gaining agency over hair care practices and product choices) and three dominant themes related to HCP use: (1) products that impacted the hair journey, which involved all mentions of hair products, (2) factors that influenced the hair journey, which included individuals or entities that shaped participants' hair experiences, and (3) the relationship between hair and sense of self, where sense of self was defined as the alignment of one's inner and outer beauty.ConclusionThe themes intersected and impacted the participants' hair journey. Cultural integration was a sub-theme that overlapped within the dominant themes and participants discussed the effect of traditions on their hair experiences.

Potato (Solanum tuberosum L.) is considered one of the most widely consumed crops worldwide, due to its high yield and nutritional profile, climate change-related environmental threats and increasing food demand. This scenario highlights the need of sustainable agricultural practices to enhance potato productivity, while preserving and maintaining soil health. Plant growth-promoting bacteria (PGPB) stimulate crop production through biofertilization mechanisms with low environmental impact. For instance, PGPB promote biological nitrogen fixation, phosphate solubilization, production of phytohormones, and biocontrol processes. Hence, these microbes provide a promising solution for more productive and sustainable agriculture. In this study, the effects of Bacillus amyloliquefaciens QST713 based-product (MINUET™, Bayer) were assessed in terms of yield, soil microbiome, potato peel and petiole nutrient profile as a promising PGPB in a wide range of potato cultivars across the United States of America. Depending on the location, potato yield and boron petiole content increased after biostimulant inoculation to maximum of 24% and 14%, respectively. Similarly, nutrient profile in potato peel was greatly improved depending on the location with a maximum of 73%, 62% and 36% for manganese, zinc and phosphorus. Notably, fungal composition was shifted in the treated group. Yield showed strong associations with specific microbial taxa, such as Pseudoarthrobacter, Ammoniphilus, Ideonella, Candidatus Berkiella, Dongia. Moreover, local networks strongly associated with yield, highlighting the important role of the native soil microbiome structure in indirectly maintaining soil health. Our results showed that treatment with B. amyloliquefaciens based product correlated with enhanced yield, with minor impacts on the soil microbiome diversity. Further studies are suggested to disentangle the underlying mechanisms of identified patterns and associations.

Background: Antihyperglycemic drug utilization studies are conducted frequently and describe the uptake of new drug therapies across may jurisdictions. An increasingly important, yet often absent, aspect of these studies is the impact of rurality on drug utilization. Objective(s): The objective of this study was to explore the association between place of residence (rural, urban, metropolitan) and the use of dipeptidyl peptidase 4 inhibitors (DPP-4i) for first treatment intensification of type 2 diabetes. Methods: A retrospective cohort study was conducted from April 1, 2008 to March 31, 2019 of new metformin users. A multivariable logistic regression analysis was performed to determine the association between place of residence (using postal codes) and likelihood of DPP-4i dispensing. Results: After adjusting for confounders, analysis revealed that rural-dwellers are less likely to have a DPP-4i dispensed, compared with metropolitan-dwellers (aOR:0.64; 95%CI:0.61–0.67) and over-time, the uptake in rural areas was slower. Conclusions: This study demonstrates that rurality can have an impact on drug therapy decisions at first treatment intensification, with respect to the utilization of new therapies.

T cells expressing anti-CD19 chimeric antigen receptors (CARs) have activity against chronic lymphocytic leukemia (CLL), but complete response rates range from 18% to 29%, so improvement is needed. Peripheral blood mononuclear cells (PBMCs) of CLL patients often contain high levels of CLL cells that can interfere with CAR T cell production, and T cells from CLL patients are prone to exhaustion and other functional defects. We previously developed an anti-CD19 CAR designated Hu19-CD828Z. Hu19-CD828Z has a binding domain derived from a fully human antibody and a CD28 costimulatory domain. We aimed to develop an optimized process for producing Hu19-CD828Z-expressing T cells (Hu19-CAR T) from PBMC of CLL patients. We determined that supplementing Hu19-CAR-T cultures with interleukin (IL)-7 + IL-15 had advantages over using IL-2, including greater accumulation of Hu19-CAR T cells during in vitro proliferation assays. We determined that positive selection with anti-CD4 and anti-CD8 magnetic beads was the optimal method of T cell purification because this method resulted in high T cell purity. We determined that anti-CD3/CD28 paramagnetic beads were the optimal T cell activation reagent. Finally, we developed a current good manufacturing practices-compliant clinical-scale protocol for producing Hu19-CAR T from PBMC of CLL patients. These Hu19-CAR T exhibited a full range of in vitro functions and eliminated leukemia from mice.

Sulfur containing compounds including glucosinolates (GLS), sulforaphane (SFN) and S-methyl-l-cysteine sulfoxide (SMCSO) have been proposed to be partly responsible for the beneficial health effects of cruciferous vegetables. As such, greater understanding of their measurements within foods is important to estimate intake in humans and to inform dietary intervention studies. Herein is described a simple and sensitive method for simultaneous analysis of 20 GLS, SFN and SMCSO by liquid chromatography mass spectrometry. Analytes were effectively retained and resolved on an Xbridge C18 column. Detection can be achieved using high resolution or unit resolution mass spectrometry; the latter making the method more applicable to large studies. Quantitative analysis using calibration standards was demonstrated for 10 GLS, SFN and SMCSO. A further 10 GLS were tentatively identified using high resolution mass spectrometry. The use of surrogate GLS standards was shown to be unreliable, with closely related GLS displaying significantly different ionisation efficiencies.

Abstract Background Racial and socioeconomic disparities in receipt of care for non‐small‐cell lung cancer (NSCLC) are well described. However, no previous studies have evaluated the association between mortgage denial rates and receipt of timely and guideline‐concordant care for NSCLC and patient outcomes. Methods We identified individuals ≥18 years diagnosed with NSCLC between 2014 and 2019 from the National Cancer Database. Using the Home Mortgage Disclosure Act database, we calculated the proportion of denied home loans to total loans at the zip‐code level and categorized them into quintiles. Our outcomes included receipt of guideline‐concordant care based on clinical and pathologic stage at diagnosis and the National Comprehensive Cancer Network guidelines, time from surgery to chemotherapy initiation, and overall survival. Results Of the 629,288 individuals diagnosed with NSCLC (median age 69; IQR 61–76 years, 49.1% female), 47.8% did not receive guideline‐concordant care. Residing in areas with higher mortgage denial rates and lower income was associated with worse guideline‐concordant care overall (aRR = 1.28; 95% CI = 1.25–1.32) and for each cancer treatment modality, worse receipt of timely chemotherapy (aHR = 1.14; 95% CI = 1.11–1.17) and worse overall survival (aHR = 1.21; 95% CI = 1.19–1.22), compared with residing in areas with the lowest mortgage denial rate and highest income. Conclusions Area‐level mortgage denial rate was associated with worse receipt of timely and guideline‐concordant NSCLC care and survival. This highlights the critical need to understand and address systemic practices, such as mortgage denial, that limit access to resources and are associated with worse access to quality cancer care and outcomes.

ABSTRACTThe COVID-19 pandemic has completely disrupted and possibly permanently changed the way humans travel. In Puerto Rico, major travel restrictions to the island have persisted at different levels since March 2020, which heavily influenced residents’ travel behaviors. However, it remains unclear about how big the impact is and how inequitable it might be. The goal of this study is to evaluate COVID-19’s impacts on Puerto Rican’s travel behaviors by analyzing travel flows from Puerto Rico to the contiguous US with a modified gravity model. The roles of socioeconomic factors regarding the Puerto Rican travelers and COVID-19 factors regarding the destination US states have been assessed. COVID-19 was a strong deterring factor of travel at the beginning of the pandemic and also in the winter of 2020, but it did not keep Puerto Ricans from traveling during the summer 2020 when most travel restrictions were lifted. We found that the elderly population of Puerto Rico, despite being more vulnerable to COVID-19, were much more likely to travel during the pandemic. We also found that, during the holiday season in 2020, some socioeconomically disadvantaged populations were more likely to be traveling, a direct contradiction to their travel flows the year prior. These findings shed light on about how disproportionately affected populations behavior changed from pre-pandemic to after the pandemic started. With the continuance of the pandemic, this information is extremely valuable for future planning with respect to emergency management, travel regulation, and social benefit.

Abstract Background Prior to the availability of pharmaceutical control measures, non-pharmaceutical control measures, including travel restrictions, physical distancing, isolation and quarantine, closure of schools and workplaces, and the use of personal protective equipment were the only tools available to public health authorities to control the spread of COVID-19. The implementation of these non-pharmaceutical control measures had unintended impacts on the ability of state and territorial domestic violence coalitions to provide services to victims. Methods A semi-structured interview guide to assess how the COVID-19 pandemic impacted service provision and advocacy generally, and how COVID-19 control measures specifically, created barriers to services and advocacy, was developed, pilot tested, and revised based on feedback. Interviews with state and territorial domestic violence coalition executive directors were conducted between November 2021 and March 2022. Transcripts were inductively and deductively coded using both hand-coding and qualitative software. Results Forty-five percent (25 of 56) of state and territorial domestic violence coalition executive directors representing all 8 National Network to End Domestic Violence (NNEDV) regions were interviewed. Five themes related to the use of non-pharmaceutical pandemic control measures with impacts on the provision of services and advocacy were identified. Conclusions The use of non-pharmaceutical control measures early in the COVID-19 pandemic had negative impacts on the health and safety of some vulnerable groups, including domestic violence victims. Organizations that provide services and advocacy to victims faced many unique challenges in carrying out their missions while adhering to required public health control measures. Policy and preparedness plan changes are needed to prevent unintended consequences of control measure implementation among vulnerable groups as well as to identify lessons learned that should be applied in future disasters and emergencies.

Abstract Most patients with multiple myeloma experience disease relapse after treatment with a B-cell maturation antigen-targeted therapy (BCMA-TT), and data describing outcomes for patients treated with sequential BCMA-TT are limited. We analyzed clinical outcomes for patients infused with standard-of-care idecabtagene vicleucel, an anti-BCMA chimeric antigen receptor (CAR) T-cell therapy, at 11 US medical centers. A total of 50 patients with prior BCMA-TT exposure (38 antibody-drug conjugate, 7 bispecific, 5 CAR T) and 153 patients with no prior BCMA-TT were infused with ide-cel, with a median follow-up duration of 4.5 and 6.0 months, respectively. Safety outcomes between cohorts were comparable. The prior BCMA-TT cohort had a lower overall response rate (74% versus 88%; p = 0.021), median duration of response (7.4 versus 9.6 months; p = 0.03), and median progression-free survival (3.2 months versus 9.0 months; p = 0.0002) compared to the cohort without prior BCMA-TT. All five patients who received a prior anti-BCMA CAR T responded to ide-cel, and survival outcomes were best for this subgroup. In conclusion, treatment with ide-cel yielded meaningful clinical responses in real-world patients exposed to a prior BCMA-TT, though response rates and durability were suboptimal compared to those not treated with a prior BCMA-TT.

Individuals living with and beyond cancer face physical impairment and inactivity in survivorship. Neuro-oncology populations have especially high rates of sedentary behaviour and functional deficits, including impaired balance, motor skills, and cognition. Our purpose was to assess the rehabilitation and exercise needs of patients with brain tumours while examining the feasibility of a rehabilitation triage clinic as a part of the Alberta Cancer Exercise–Neuro-Oncology study, where patients were referred to a triage clinic, where health, neurologic, and functional status was assessed, followed by a referral to one or multiple resources, including exercise, physiotherapy, occupational therapy, or physiatry. Qualitative perception of the triage clinic was collected. Overall, the triage clinic was feasible and safe for participants, facilitating referral into rehabilitation and exercise resources. Pre-determined enrollment and attendance rates were met, but referral rates to the triage clinic were not met. Oncology clinic staff reported forgetting to refer patients or uncertainty of who was appropriate for rehabilitation as barriers. Oncology clinic-based screening may improve the identification of patients who are sedentary or have a physical impairment. A proposed screening tool, the Cancer Rehabilitation and Exercise Screening Tool (CREST), is presented within our Cancer Rehabilitation and Exercise Pathways Model. The CREST can identify patients who are sedentary or have a functional impairment, facilitating referral to appropriate rehabilitation resources and ultimately improving patient recovery and functioning.

The aim of this study was to assess center of mass (COM) acceleration and movement during change of direction (COD) maneuvers during a competitive soccer game to elucidate situation-specific demands of COD performance. This information can assist in developing soccer-specific tests and training methods. Fifteen elite-level female youth soccer players were tracked for one game with inertial measurement units (IMU) attached to the lower back. COD movements in combination with situational patterns were identified using high-speed video. LASSO regression was used to identify the most important predictors associated with higher vertical peak accelerations (PAv) of the COM during COD movements. COD angle, running speed, contact, and challenge from the opposition were identified as important features related to higher PAv. This study adds to the literature on the demands of COD performance in soccer match-play. The unique approach with game-specific situational data from female youth players provides increased insight into the game-demands of COD and agility performance. PAv in games was higher with larger COD angles, increased running speed, or with contact when the player was challenged by the opposition. A larger study including more games is warranted to increase confidence in using these variables as a basis for training or testing agility.

Abstract Background Contemporary data reflecting local pathogens and their antibiograms is necessary to select empirical antimicrobial therapy for equine neonates. Hypothesis/Objectives Describe bacterial isolates associated with equine neonatal infection and their antibiograms in the Midwestern United States. An increase in gram‐positive infection and antibiotic resistance compared to previous literature was expected. Animals Data from 149 fluid samples from 133 foals

Inbreeding (reproduction between relatives) often decreases the fitness of offspring and is thus expected to lead to the evolution of inbreeding avoidance strategies. Chimpanzees (Pan troglodytes) are expected to avoid inbreeding as they are long-lived, invest heavily in offspring and may encounter adult, opposite sex kin frequently, especially in populations where both males and females commonly remain in the group in which they were born (bisexual philopatry). However, it is unclear whether substantial bisexual philopatry has been a feature of chimpanzees' evolutionary history or whether it is a result of recent anthropogenic interference, as the only groups for which it has been documented are significantly impacted by human encroachment and experience notable rates of potentially unsustainable inbreeding. Here we use 14 years of observational data and a large genomic dataset of 256 481 loci sequenced from 459 individuals to document dispersal and inbreeding dynamics in an eastern chimpanzee (P. t. schweinfurthii) community with low levels of anthropogenic disturbance. We document the first case of substantial bisexual philopatry in a relatively undisturbed chimpanzee community and show that, despite an increased inbreeding risk incurred by females who do not disperse before reaching reproductive age, natal females were still able to avoid producing inbred offspring.

Introduction Diets low in vegetables are a main contributor to the health burden experienced by young adults in rural communities. Digital health interventions provide an accessible delivery model that can be personalised to meet the diverse preferences of young adults. A personalisable digital vegetable intake intervention (Veg4Me) was codesigned to meet the needs of young adults living in rural communities. This study will determine the feasibility of delivering a personalised Veg4Me programme and compare preliminary effects with a non-personalised Veg4Me (control).Methods and analysis A 12-week assessor-blinded, two-arm, parallel randomised controlled trial will be undertaken from August 2023 until April 2024. A total of 150 eligible and consenting young adults (18–35 years; eat

Protein UFMylation downstream of the E1 enzyme UBA5 plays essential roles in development and endoplasmic reticulum stress. Variants in the UBA5 gene are associated with developmental and epileptic encephalopathy 44 (DEE44), an autosomal recessive disorder characterized by early-onset encephalopathy, movement abnormalities, global developmental delay, intellectual disability, and seizures. DEE44 is caused by at least 12 different missense variants described as loss of function (LoF), but the relationships between genotypes and molecular or clinical phenotypes remain to be established. We developed a humanized UBA5 fly model and biochemical activity assays in order to describe in vivo and in vitro genotype–phenotype relationships across the UBA5 allelic series. In vivo, we observed a broad spectrum of phenotypes in viability, developmental timing, lifespan, locomotor activity, and bang sensitivity. A range of functional effects was also observed in vitro across comprehensive biochemical assays for protein stability, ATP binding, UFM1 activation, and UFM1 transthiolation. Importantly, there is a strong correlation between in vivo and in vitro phenotypes, establishing a classification of LoF variants into mild, intermediate, and severe allelic strengths. By systemically evaluating UBA5 variants across in vivo and in vitro platforms, this study provides a foundation for more basic and translational UBA5 research, as well as a basis for evaluating current and future individuals afflicted with this rare disease.

ABSTRACT: Background: Outcomes of lung cancer patients traveling greater distances for surgical oncology care are not well-described. We investigated the effects of increased travel burden after robotic-assisted pulmonary lobectomy (RAPL) for lung cancer. Methods: Clinical characteristics and surgical outcomes of 711 consecutive patients who underwent RAPL from September 2010 to March 2022 were compared, stratified by primary residential ZIP code