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Two types of engineered T cells have been successfully used to treat patients with cancer, one with an antigen recognition domain derived from antibodies [chimeric antigen receptors (CARs)] and the other derived from T cell receptors (TCRs). CARs use high-affinity antigen–binding domains and costimulatory domains to induce T cell activation but can only react against target cells with relatively high amounts of antigen. TCRs have a much lower affinity for their antigens but can react against target cells displaying only a few antigen molecules. Here, we describe a new type of receptor, called a Co-STAR (for costimulatory synthetic TCR and antigen receptor), that combines aspects of both CARs and TCRs. In Co-STARs, the antigen-recognizing components of TCRs are replaced by high-affinity antibody fragments, and costimulation is provided by two modules that drive NF-κB signaling (MyD88 and CD40). Using a TCR-mimic antibody fragment that targets a recurrent p53 neoantigen presented in a common human leukocyte antigen (HLA) allele, we demonstrate that T cells equipped with Co-STARs can kill cancer cells bearing low densities of antigen better than T cells engineered with conventional CARs and patient-derived TCRs in vitro. In mouse models, we show that Co-STARs mediate more robust T cell expansion and more durable tumor regressions than TCRs similarly modified with MyD88 and CD40 costimulation. Our data suggest that Co-STARs may have utility for other peptide-HLA antigens in cancer and other targets where antigen density may limit the efficacy of engineered T cells. Editor's summary: Commonly used T cell therapies such as engineered T cell receptors (TCRs) and chimeric antigen receptors (CARs) have greatly improved outcomes for many patients; however, both still have their associated drawbacks. To overcome some of these limitations, Mog et al. have developed high-affinity antibody–expressing T cells that use a receptor, called a Co-STAR (for costimulatory synthetic TCR and antigen receptor), that combines aspects of both CARs and TCRs. They further show in vivo that these Co-STARs induce T cell expansion and induce long-term regression in mouse models with low densities of antigen, representing a promising strategy that requires further evaluation. —Dorothy Hallberg [ABSTRACT FROM AUTHOR]

The current study examined verbal cues of veracity and deception in 911 calls reporting homicides or suicides of another person. Specifically, the current study compared differences in the presence/absence and number of potential verbal indicators between a sample of deceptive callers who concealed their role in causing the person's death and truthful callers who did not cause the person's death. Results demonstrate consistency with previously proposed indicators of veracity and deception in 911 calls. More precisely, a greater number of self‐handicapping statements and descriptions of physical sensations were made by deceptive individuals, whereas truthtellers were more likely to spontaneously self‐correct inaccurate statements. Practical implications and limitations are discussed. [ABSTRACT FROM AUTHOR]

The relationship between amyloidosis and vasculature in cognitive impairment and Alzheimer's disease (AD) pathogenesis is increasingly acknowledged. We conducted a quantitative and topographic assessment of retinal perivascular amyloid plaque (AP) distribution in individuals with both normal and impaired cognition. Using a retrospective dataset of scanning laser ophthalmoscopy fluorescence images from twenty-eight subjects with varying cognitive states, we developed a novel image processing method to examine retinal peri-arteriolar and peri-venular curcumin-positive AP burden. We further correlated retinal perivascular amyloidosis with neuroimaging measures and neurocognitive scores. Our study unveiled that peri-arteriolar AP counts surpassed peri-venular counts throughout the entire cohort (P < 0.0001), irrespective of the primary, secondary, or tertiary vascular branch location, with a notable increase among cognitively impaired individuals. Moreover, secondary branch peri-venular AP count was elevated in the cognitively impaired (P < 0.01). Significantly, peri-venular AP count, particularly in secondary and tertiary venules, exhibited a strong correlation with clinical dementia rating, Montreal cognitive assessment score, hippocampal volume, and white matter hyperintensity count. In conclusion, our exploratory analysis detected greater peri-arteriolar versus peri-venular amyloidosis and a marked elevation of amyloid deposition in secondary branch peri-venular regions among cognitively impaired subjects. These findings underscore the potential feasibility of retinal perivascular amyloid imaging in predicting cognitive decline and AD progression. Larger longitudinal studies encompassing diverse populations and AD-biomarker confirmation are warranted to delineate the temporal-spatial dynamics of retinal perivascular amyloid deposition in cognitive impairment and the AD continuum. [ABSTRACT FROM AUTHOR]

Simple Summary: A prospective observational study was conducted in a cohort of 329 hospitalized older adults ≥65 years admitted to the acute medical unit (AMU) of a tertiary hospital. Statistical models compared older adults with and without a history of cancer to determine characteristics associated with pre-frailty/frailty and length of hospital stay (LOS). About one-fifth of the cohort had a history of cancer. The prevalence of pre-frailty/frailty among older adults with a history of cancer was 58%. In patients with a history of cancer, pre-frailty/frailty was associated with eight and nine times more likelihood of experiencing polypharmacy and malnutrition, respectively. The risk of having a longer LOS was 24% higher in older adults with a history of cancer than those without. Further investigations are warranted for improvement to systematic assessments to identify those at risk and provide interventions to meet the complex needs of this vulnerable population. A prospective observational study was conducted in a cohort of older adults ≥65 years (n = 329), admitted to the acute medical unit (AMU) of a tertiary hospital, to describe and compare characteristics including frailty status and clinical outcomes. Multivariable models compared older adults with and without a history of cancer to determine characteristics associated with frailty and pre-frailty. An adjusted Poisson regression model was used to compare the length of hospital stay (LOS) between the two groups. About one-fifth (22%) of the cohort had a history of cancer. The most common cancer types were prostate (n = 20), breast (n = 13), lung (n = 8) and gastrointestinal (n = 8). There was no difference in the prevalence of pre-frailty/frailty among patients with or without a history of cancer (58% vs. 57%, p > 0.05). Pre-frailty/frailty was associated with polypharmacy (OR 8.26, 95% CI: 1.74 to 39.2) and malnutrition (OR 8.91, 95% CI: 2.15 to 36.9) in patients with a history of cancer. Adjusted analysis revealed that the risk of having a longer LOS was 24% higher in older adults with a history of cancer than those without (IRR 1.24, 95% CI 1.10 to 1.41, p < 0.001). Clinicians in the AMU should be aware that older adults with a history of cancer have a higher risk of a longer LOS compared to those without. [ABSTRACT FROM AUTHOR]

Purpose: Cancer survivors are at greater risk of cardiovascular disease (CVD) than cancer-free controls. Despite evidence-based guidelines recommending CVD risk factor assessment, surveillance and risk-reduction, many people with cancer do not receive adequate CVD care. To address potential barriers and enablers of care, we examined healthcare professionals' (HCPs) perceptions and experiences of CVD risk assessment and management in people with cancer. Methods: We conducted one focus group and 12 individual interviews to examine HCPs' perceptions and experiences of CVD care in care. We used reflexive thematic analysis to collect and analyse the qualitative data to construct and understand themes. Results: Twenty-one HCPs participated (8 oncologists, 5 nurses, 3 general practitioners, 2 dietitians, 1 cardiologist, 1 haematologist and 1 physiotherapist). Majority of HCPs were aware of CVD risk in cancer but were concerned they could not deliver CVD care alone due to system-level barriers including lack of time and training. HCPs also perceived patient-level barriers including socioeconomic disadvantage and fatalistic outlook. Despite barriers, HCPs suggested diverse solutions for improving CVD care in cancer including new models-of-care, clinical pathways, risk assessment/management tools and education. Conclusions: The diversity of perceived barriers and suggested solutions identified by HCPs suggests the need for a multilevel approach tailored to context. Future research involving people with cancer is needed to co-design acceptable interventions. Implications for Cancer Survivors: Improved understanding of HCP's perceptions can inform the development of new interventions to deliver CVD care to people with cancer to reduce morbidity and mortality. [ABSTRACT FROM AUTHOR]

The B‐cell lymphoma 2 (BCL2) family members, BCL2‐associated protein X (BAX) and BCL2 homologous antagonist killer (BAK), are required for programmed cell death via the mitochondrial pathway. When cells are stressed, damaged or redundant, the balance of power between the BCL2 family of proteins shifts towards BAX and BAK, allowing their transition from an inactive, monomeric state to a membrane‐active oligomeric form that releases cytochrome c from the mitochondrial intermembrane space. That oligomeric state has an essential intermediate, a symmetric homodimer of BAX or BAK. Here we describe crystal structures of dimers of the core domain of BAX, comprising its helices α2–α5. These structures provide an atomic resolution description of the interactions that drive BAX homo‐dimerisation and insights into potential interaction between core domain dimers and membrane lipids. The previously identified BAK lipid‐interacting sites are not conserved with BAX and are likely to determine the differences between them in their interactions with lipids. We also describe structures of heterodimers of BAK/BAX core domains, yielding further insight into the differences in lipid binding between BAX and BAK. [ABSTRACT FROM AUTHOR]

Background: Understanding the structural connectivity of key brainstem nuclei with limbic cortical regions is essential to the development of therapeutic neuromodulation for depression, chronic pain, addiction, anxiety and movement disorders. Several brainstem nuclei have been identified as the primary central nervous system (CNS) source of important monoaminergic ascending fibers including the noradrenergic locus coeruleus, serotonergic dorsal raphe nucleus, and dopaminergic ventral tegmental area. However, due to practical challenges to their study, there is limited data regarding their in vivo anatomic connectivity in humans. Objective: To evaluate the structural connectivity of the following brainstem nuclei with limbic cortical areas: locus coeruleus, ventral tegmental area, periaqueductal grey, dorsal raphe nucleus, and nucleus tractus solitarius. Additionally, to develop a group average atlas of these limbic brainstem structures to facilitate future analyses. Methods: Each nucleus was manually masked from 197 Human Connectome Project (HCP) structural MRI images using FSL software. Probabilistic tractography was performed using FSL's FMRIB Diffusion Toolbox. Connectivity with limbic cortical regions was calculated and compared between brainstem nuclei. Results were aggregated to produce a freely available MNI structural atlas of limbic brainstem structures. Results: A general trend was observed for a high probability of connectivity to the amygdala, hippocampus and DLPFC with relatively lower connectivity to the orbitofrontal cortex, NAc, hippocampus and insula. The locus coeruleus and nucleus tractus solitarius demonstrated significantly greater connectivity to the DLPFC than amygdala while the periaqueductal grey, dorsal raphe nucleus, and ventral tegmental area did not demonstrate a significant difference between these two structures. Conclusion: Monoaminergic and other modulatory nuclei in the brainstem project widely to cortical limbic regions. We describe the structural connectivity across the several key brainstem nuclei theorized to influence emotion, reward, and cognitive functions. An increased understanding of the anatomic basis of the brainstem's role in emotion and other reward-related processing will support targeted neuromodulatary therapies aimed at alleviating the symptoms of neuropsychiatric disorders. [ABSTRACT FROM AUTHOR]

Introduction: Localized provoked vulvodynia (LPV) is a prevalent sexual health condition with significant negative impacts on quality of life. There is a lack of consensus regarding effective management. Methods: We used Arksey and O'Malley's five-step method to identify, collate, and evaluate literature published between 2010 and 2023. The scoping review investigated the efficacy or effectiveness of interventions in the management of LPV. The aim of this paper is to map the literature on the efficacy or effectiveness of physical interventions. Results: The review produced 19 primary studies of physical interventions for LPV. These include acupuncture, laser therapy, physiotherapy, transcutaneous electrical nerve stimulation, low-intensity shockwave therapy, transcranial direct current stimulation, and vestibulectomy. Conclusion: Published studies that investigated a range of physical treatments for LPV showed some positive effects, except for transcranial direct-current stimulation. The remaining modalities demonstrated improved sexual pain and treatment satisfaction, when measured. Findings were mixed for non-sexual pain. There was insufficient evidence to draw conclusions regarding other outcomes. Researchers are encouraged to conduct larger, high-quality studies that sample more diverse patient populations and use patient-oriented outcomes to assess effectiveness of physical modalities. [ABSTRACT FROM AUTHOR]

In a community sample of trauma‐exposed postpartum individuals (N = 167; mean age = 30, 90% White; 61.7% completed bachelor's degree or higher) longitudinally completed self‐report measures on PTSD, depressive, and Obsessive‐compulsive disorder (OCD) symptoms (specifically checking, ordering, washing, and obsessing symptoms), preoccupation with intrusive postpartum thoughts/neutralising strategies, and trauma exposure at 4 and 12 weeks postpartum. PTSD symptoms were strongly associated with all OCD symptoms (r = 0.32‐ 0.49, p < 0.001), preoccupation with postpartum‐specific intrusive thoughts (r = 0.32−0.45, p < 0.001), and preoccupation with neutralising strategies (r = 0.21−0.29, p < 0.05) at both time points. PTSD symptoms were also predictive of checking and obsessing symptoms. This study identified PTSD symptoms as a new correlate for preoccupation with postpartum‐specific intrusive thoughts and neutralising strategies in the postpartum period in a community sample. These findings add to the evidence suggesting a strong association between PTSD and OCD symptoms across the lifespan, including in non‐clinical samples. Future research should examine best practices to assess and treat a variety of postpartum psychopathology symptoms, not just depression. [ABSTRACT FROM AUTHOR]

The Government Accountability Office’s (GAO) bid protest decisions often create standards that are followed to nearly the same degree as statutes, Executive Orders (EOs), and regulations and are often given similar deference. GAO decisions, however, are much harder for contracting officers (COs) to find, read, and understand than statutes, regulations, and EOs. This confusion fundamentally undermines the intent of the Federal Acquisition Regulation (FAR) to create a single source for all acquisition regulations that is written in simple, easy to understand language and creates an untenable situation for COs who are unaware of these additional rules. Codification of the standards created by GAO decisions would allow public participation and comment during the rule-making process and provide clearer, more consistent guidance on topics where the FAR has left room for interpretation that is currently being filled by standards created in GAO’s bid protest decisions. [ABSTRACT FROM AUTHOR]

Nature-based Solutions (NbS) are integral to efforts to keep global warming below 2°C in accordance with the United Nations' 2015 Paris Agreement on Climate Change. Yet the transboundary governance dimensions of NbS remain unclear and largely undocumented. In Southeast Asia, NbS have emphasised the conservation and/ or sustainable commodification of carbon sinks found in terrestrial and mangrove forests, seagrass meadows, peatlands and agricultural soils. Mostly project-driven and fixed-term, these "solutions" have often failed to meet their social and ecological objectives. Increasingly, they have added to cross-border problems of: (1) displaced carbon emissions; and (2) economic migration and societal dispossession. This perspective paper delineates a transboundary governance research agenda to mitigate these trade-offs and enhance the co-benefits of NbS in carbon sinks. Building on NbS literature, it identifies cross-sector, multi-scalar and interdisciplinary pathways to improve transboundary cooperation, inclusion and equity in carbon sink governance in varying Southeast Asian contexts. [ABSTRACT FROM AUTHOR]

Introduction: Self-managed exercise and nutrition interventions can alleviate pre-frailty and frailty but understanding of adherence to them is lacking. This study aimed to explore the experiences of, and barriers and enablers to, a hospital-to-home self-managed combined exercise and nutrition program for hospitalised older adults living with pre-frailty and frailty. Methods: A hybrid approach to data- and theory-driven descriptive thematic analysis identified experiences, barriers, and enablers to participation in a 3-month, self-managed, exercise–nutrition, hospital-to-home frailty-support program. Pre-frail and frail older adult patients ≥ 65 years admitted to the acute medical unit at a South Australian tertiary hospital were recruited. Individual semi-structured interviews were audio-recorded, transcribed verbatim, and analysed descriptively, using the Theoretical Domains Framework. Results: The nutrition component of the program found 11 common barriers and 18 common enablers. The exercise component included 14 barriers and 24 enablers. Intentions, Social influences, Environmental context/resource and Emotions served as primary barriers towards adherence to both components. Common enablers for both components included Knowledge, Social identity, Environmental context/resource, Social influences, and Emotions. Conclusions: This research revealed important factors affecting adherence to a self-managed exercise–nutrition program in pre-frail and frail older adults within the environment, resources, and emotion domains that should be considered when designing other intervention programs in this population group. [ABSTRACT FROM AUTHOR]

Objectives: Perinatal psychopathology can be damaging. This study examined the strength of the associations between risk factors and all perinatal mood and anxiety disorder symptoms while assessing the mediating effect of experiential avoidance. Method: Participants (N = 246) completed assessments during pregnancy (28–32 weeks) and the postpartum (6–8 weeks). Structural equation modeling (SEM) was used to examine associations between risk factors and latent factors: distress (composed of depression, generalized anxiety, irritability, and panic symptoms); fear (social anxiety, agoraphobia, specific phobia, and obsessive‐compulsive); and bipolar (mania and obsessive‐compulsive). Results: During pregnancy, past psychiatric history, anxiety sensitivity, maladaptive coping, and age were significant risk factors. In the postpartum, negative maternal attitudes and past psychiatric history were only risk factors for symptoms that composed distress. Experiential avoidance mediated the relation between maladaptive coping and symptoms that composed fear. Conclusion: It is important to assess for psychological risk factors starting in pregnancy. This study identified critical risk factors that are associated with the underlying commonality among perinatal mood and anxiety symptoms. Some of the risk factors as well as the mediator are malleable (negative maternal attitudes, experiential avoidance), creating new possibilities for prevention and treatment of perinatal mood and anxiety disorder symptoms. [ABSTRACT FROM AUTHOR]

The STEM climate is overall less welcoming for queer students, and is especially harrowing for transgender, nonbinary, and students with additional gender non-conforming identities (TNBGNC+). Professional STEM societies provide students with a range of resources that help them persist in STEM, though qualitative research shows that such societies geared toward queer and trans students may offer less professional and academic resources and prioritize identity management. The objective of our research is to identify, among queer and trans students, whether there are differences between how TNBGNC+ students and gender majoritized students access resources important in STEM persistence across professional society types, including those societies organized to serve women, racial/ethnic minoritized groups, queer and trans groups, as well as those science societies and chapters without a stated group focus. The society resources we focus on include: sense of community, social networking, professional resources, leadership skills, academic resources, reduced isolation related to identities, and perceptions that societies in which they may participate are helpful to them in their degree progress. This study offers an analysis of survey data from 477 queer and trans STEM undergraduates relating to their participation in STEM professional societies. To conduct this research, we embraced and enacted recommendations by scholars on strategies and frameworks to queer our methodology, survey, and analysis. We found that at oSTEM, TNBGNC+ students may not be benefitting to the same extent as gender majoritized students when it comes to feeling in community with other members and having opportunities for social networking. However, TNBGNC+ students may benefit more from a reduction in isolation related to their identities. Differences in how SWE served TNBGNC+ students echoes previous work, and may speak to the society's organization around the cisgender, patriarchal framework. SHPE's relative success with TNBGNC+ students also reproduces existing work, suggesting the society may be more largely scaffolded for more affirming environments writ large. As well, that science in comparison to industry chapters were more beneficial to TNBGNC+ students brings forward possible differences between science and industry chapters, in which the former may be influenced more by the scholarship and science of gender, while the latter, with its more business and public focus, could be more influenced by dominant narratives in STEM. This work has implications for societies when it comes to enacting policies to cultivate more inclusive community environments and buttress potentially unequal access to social networking as well as professional and academic resources. At the same time, there is room for oSTEM to augment how it supports TNBGNC+ students with academic and professional resources and benefit students' progress in their degree programs. [ABSTRACT FROM AUTHOR]

The core metabolic reactions of life drive electrons through a class of redox protein enzymes, the oxidoreductases. The energetics of electron flow is determined by the redox potentials of organic and inorganic cofactors as tuned by the protein environment. Understanding how protein structure affects oxidation–reduction energetics is crucial for studying metabolism, creating bioelectronic systems, and tracing the history of biological energy utilization on Earth. We constructed ProtReDox (https://protein-redox-potential.web.app), a manually curated database of experimentally determined redox potentials. With over 500 measurements, we can begin to identify how proteins modulate oxidation–reduction energetics across the tree of life. By mapping redox potentials onto networks of oxidoreductase fold evolution, we can infer the evolution of electron transfer energetics over deep time. ProtReDox is designed to include user‐contributed submissions with the intention of making it a valuable resource for researchers in this field. [ABSTRACT FROM AUTHOR]

Introduction: Localized provoked vulvodynia (LPV) is a chronic condition characterized by pain in the vulvar vestibule, which can be provoked by pressure or touch and which is not tied to a clear underlying cause. Research into the etiology of and most appropriate treatment strategy for LPV is still limited.Methods: Using Arksey and O'Malley's model for scoping reviews, we evaluated the research question: what is the current evidence regarding the efficacy/effectiveness of multimodal or interdisciplinary interventions for the treatment of LPV? We collated and analyzed articles from 2010 to 2023 to capture the current research landscape.Results: Our review identified 27 studies, which either compared treatments between classes (eg pharmacologic versus psychologic modalities) or described interdisciplinary treatment programs. We identify several trends in the literature. First, outcome measures are inconsistent between studies, often unvalidated, and may not adequately mirror patient concerns. Second, the absence of appropriate comparator groups in many studies restricts providers' ability to appraise which treatments may be most efficacious. Third, selection bias and demographic homogeneity limit generalizability. Finally, we highlight the need for head-to-head trials of vestibulectomy with other treatments considered first line for vulvodynia management.Conclusion: There is insufficient evidence to suggest the superiority of one treatment modality for LPV relative to others or to recommend a particular interdisciplinary management strategy. Future research should use a head-to-head design where sham control is impossible, incorporate patient-centered outcome measures, and investigate impacts of treatment among diverse samples of LPV patients. [ABSTRACT FROM AUTHOR]

Context Atherosclerosis is a systemic pro-inflammatory and pro-oxidative disease, accounting for approximately a third of deaths globally. It has been proposed that omega-3s, through their antioxidant and anti-inflammatory properties, mitigate atherosclerotic disease progression. However, due to the systemic pro-inflammatory and pro-oxidative state of atherosclerosis, it is proposed that patients with atherosclerotic disease may have higher omega-3 requirements than the average requirement, due to increased nutrient utilization in anti-inflammatory and anti-oxidant processes. Objective The aim of this review was to determine what dose and duration of omega-3 supplementation is required to reach a therapeutic blood level of omega-3s (eicosapentaenoic acid ≥150 µg/mL or omega-3 index ≥8%) in people with chronic atherosclerotic disease. Data Sources This systematic review comprehensively searched MEDLINE, Emcare, Scopus, and CINAHL using key search terms for atherosclerotic disease, omega-3, supplementation, and blood levels of omega-3s. Data Extraction Two reviewers independently screened 529 randomized controlled trials (RCTs) supplementing omega-3s in patients with chronic atherosclerotic disease. Data Analysis In total, 25 journal articles from 17 original RCTs were included and assessed quantitatively. Supplementation at 1.8 g to 3.4 g per day for a 3-month–6-month duration, and at 4.4 g and above for as little as 1 month–6 months were identified as the most effective dosage ranges for increasing blood levels of omega-3s to therapeutic levels in people with atherosclerotic disease. Conclusions Consideration should be given to routine omega-3 supplementation and to increasing the omega-3 dietary recommendations and upper limits of daily intake to improve clinical outcomes and reduce the risk of cardiac mortality in this population. [ABSTRACT FROM AUTHOR]

Hard cider is a sector of a maturing craft beverage industry that continues to experience growth in the United States. Cider is also experiencing challenges, however, such as competition from other alcohol markets, changing consumer preferences, the supply chain, and inflationary pressures. National policy changes may help promote more optimal outcomes for this sector, but public support is important to policy formation. This study uses survey data from a best-worst scaling experiment of consumers in four leading cider-producing states (Michigan, Washington, Wisconsin, and Vermont) to understand preferences toward ten broad cider policy initiatives. The results of multinomial logistic modeling reveal that consumers prefer policies mandating ingredients, nutrition facts, and allergen labeling across all ciders. The least preferred policy initiatives include allowing producers to use vintage on labeling and funding regional cider development. These results have important implications for stakeholders across the industry, including the benefits of labeling disclosures in marketing and the need to improve public awareness of barriers to cider industry development. [ABSTRACT FROM AUTHOR]

Immunogenicity assessment of Adeno-Associated Virus (AAV) vectors is a critical part of gene therapy drug development. Whether the assays are used for inclusion/exclusion criteria or to monitor the safety and efficacy of the gene therapy, they are critical bioanalytical assessments. While total anti-AAV assays are perceived as easier to develop and implement than neutralizing anti-AAV assays, the gene therapy field is still nascent, and it is not yet clear which of the assays should be implemented at what stage of drug development. Recently AAVrh.10 has gained interest for use in gene therapies targeting cardiac, neurological, and other diseases due to its enhanced transduction efficiency. There is limited information on anti-AAVrh.10 antibodies and their clinical impact; thus, the information presented herein documents the validation of both a total antibody assay (TAb) and a neutralizing antibody (NAb) assay for anti-AAVrh.10 antibodies. In this manuscript, the validation was performed in accordance with the 2019 FDA immunogenicity guidance with additional evaluations to comply with CLIA where applicable. The AAVrh.10 TAb and NAb assays were compared in terms of sensitivity, drug tolerance, and precision, along with a concordance analysis using the same individual serum samples. This comparison gave insight into the utility of each format as a screening assay for inclusion into clinical studies. [ABSTRACT FROM AUTHOR]

Specificity remains a major challenge to current therapeutic strategies for cancer. Mutation associated neoantigens (MANAs) are products of genetic alterations, making them highly specific therapeutic targets. MANAs are HLA-presented (pHLA) peptides derived from intracellular mutant proteins that are otherwise inaccessible to antibody-based therapeutics. Here, we describe the cryo-EM structure of an antibody-MANA pHLA complex. Specifically, we determine a TCR mimic (TCRm) antibody bound to its MANA target, the KRASG12V peptide presented by HLA-A*03:01. Hydrophobic residues appear to account for the specificity of the mutant G12V residue. We also determine the structure of the wild-type G12 peptide bound to HLA-A*03:01, using X-ray crystallography. Based on these structures, we perform screens to validate the key residues required for peptide specificity. These experiments led us to a model for discrimination between the mutant and the wild-type peptides presented on HLA-A*03:01 based exclusively on hydrophobic interactions. Mutation associated neoantigens are a family of highly specific therapeutic targets for the treatment of cancer. Here, the authors describe the cryo-EM structure of an antibody bound to a neoantigen complex providing insights into the specificity of the antibody. [ABSTRACT FROM AUTHOR]

The Coronavirus envelope (E) protein is a small structural protein with ion channel activity that plays an important role in virus assembly, budding, immunopathogenesis and disease severity. The viroporin E is also located in Golgi and ER membranes of infected cells and is associated with inflammasome activation and immune dysregulation. Here we evaluated in vitro antiviral activity, mechanism of action and in vivo efficacy of BIT225 for the treatment of SARS-CoV-2 infection. BIT225 showed broad-spectrum direct-acting antiviral activity against SARS-CoV-2 in Calu3 and Vero cells with similar potency across 6 different virus strains. BIT225 inhibited ion channel activity of E protein but did not inhibit endogenous currents or calcium-induced ion channel activity of TMEM16A in Xenopus oocytes. BIT225 administered by oral gavage for 12 days starting 12 hours before infection completely prevented body weight loss and mortality in SARS-CoV-2 infected K18 mice (100% survival, n = 12), while all vehicle-dosed animals reached a mortality endpoint by Day 9 across two studies (n = 12). When treatment started at 24 hours after infection, body weight loss, and mortality were also prevented (100% survival, n = 5), while 4 of 5 mice maintained and increased body weight and survived when treatment started 48 hours after infection. Treatment efficacy was dependent on BIT225 dose and was associated with significant reductions in lung viral load (3.5 log10), virus titer (4000 pfu/ml) and lung and serum cytokine levels. These results validate viroporin E as a viable antiviral target and support the clinical study of BIT225 for treatment and prophylaxis of SARS-CoV-2 infection. Author summary: Antiviral agents are highly important for the management of COVID-19. New antivirals are needed, because available drugs have drawbacks that limit their use and are threatened by drug resistance. This study demonstrates that the small molecule drug BIT225 is an inhibitor of an important viral ion channel (E protein). E protein is required for virus replication and is involved in eliciting inflammatory response to infection. Exacerbated inflammation is a hallmark of severe COVID-19 in mice and in humans. In a mouse model of severe SARS-CoV-2 infection, BIT225 treatment starting before or 24 hours after infection could protect all treated mice from developing disease, from experiencing weight loss and from death (100%, n = 17), while all untreated mice developed severe disease, started to lose body weight from Day 3 onwards and died within 9 days after infection. BIT225 treatment was associated with potent suppression of virus load, and reduced inflammation markers, consistent with effective clearance of the virus. These results are remarkable for the high efficacy achieved with a new mechanism of action. BIT225 is a clinical stage drug candidate with an established human safety profile. These results support clinical evaluation of BIT225 for the treatment of human SARS-CoV-2 infection. [ABSTRACT FROM AUTHOR]

Aims: Comorbidities play a significant role towards the pathophysiology of heart failure with preserved ejection fraction (HFpEF), characterized by abnormal macrovascular function and altered ventricular–vascular coupling. However, our understanding of the role of comorbidities and arterial stiffness in HFpEF remains incomplete. We hypothesized that HFpEF is preceded by a cumulative rise in arterial stiffness as cardiovascular comorbidities accumulate, beyond that associated with ageing. Methods and results: Arterial stiffness was assessed using pulse wave velocity (PWV) in five groups: Group A, healthy volunteers (n = 21); Group B, patients with hypertension (n = 21); Group C, hypertension and diabetes mellitus (n = 20); Group D, HFpEF (n = 21); and Group E, HF with reduced ejection fraction (HFrEF) (n = 11). All patients were aged 70 and above. Mean PWV increased from Groups A to D (PWV 10.2, 12.2, 13.0, and 13.7 m/s, respectively) as vascular comorbidities accumulated independent of age, renal function, haemoglobin, obesity (body mass index), smoking status, and hypercholesterolaemia. HFpEF exhibited the highest PWV and HFrEF displayed near‐normal levels (13.7 vs. 10 m/s, P = 0.003). PWV was inversely related to peak oxygen consumption (r = −0.304, P = 0.03) and positively correlated with left ventricular filling pressures (E/e′) on echocardiography (r = −0.307, P = 0.014). Conclusions: This study adds further support to the concept of HFpEF as a disease of the vasculature, underlined by an increasing arterial stiffness that is driven by vascular ageing and accumulating vascular comorbidities, for example, hypertension and diabetes. Reflecting a pulsatile arterial afterload associated with diastolic dysfunction and exercise capacity, PWV may provide a clinically relevant tool to identify at‐risk intermediate phenotypes (e.g. pre‐HFpEF) before overt HFpEF occurs. [ABSTRACT FROM AUTHOR]

Background: Complications in the postpartum period pose substantial risks to women and can result in significant maternal morbidity and mortality. However, there is much less attention on postpartum care compared to pregnancy and childbirth. The goal of this study was to gather information on women's knowledge of postpartum care and complications, recovery practices after childbirth, perceived barriers to receiving care during the postpartum period, and educational needs in four health centers. The findings can inform the development of appropriate curriculum and interventions for postnatal care education in similar settings. Methods: A descriptive qualitative study design was employed. Eight focus group discussions were conducted among 54 postpartum women who delivered in four health centers in Sagnarigu District in Tamale, Ghana. Audio recordings of focus group data were transcribed and translated, and thematic analysis was conducted. Results: There were six main themes that emerged from the focus group discussions: 1) baby focused postpartum care; 2) postpartum practices; 3) inadequate knowledge ofpostpartum danger signs; 4) barriers to accessing postpartum care 5) experiences of poor mental health; and 6) need for postpartum education. Conclusions: Postpartum care for women in this study was primarily perceived as care of the baby post-delivery and missing key information on physical and mental health care for the mother. This can result in poor adjustment postpartum and critically, a lack of knowledge on danger signs for common causes of morbidity and mortality in the postpartum period. Future research needs to understand how to communicate important information on postpartum mental and physical health to better protect mothers in the region. [ABSTRACT FROM AUTHOR]

Localized provoked vulvodynia (LPV) is a chronic pain condition without an identifiable cause that is localized to a portion of the vulva and provoked by pressure or touch. LPV is a commonly occurring but poorly understood condition lacking consensus on management. This scoping review used Arksey and O'Malley's approach to identify and evaluate literature published between 2010 and 2023 that addressed the question: What is the current evidence on the efficacy or effectiveness of pharmacological treatments in the management of LPV? This review evaluated 18 papers reporting on the efficacy or effectiveness of oral, topical, and injectable medications. Seven of the studies were randomized controlled trials. Oral gabapentin and oral desipramine showed some improvement in sexual function compared to placebo. Small sample sizes and methodological issues limited confidence in interpreting findings. Pain was reduced in descriptive studies of tricyclic antidepressants, milnacipran, injectable anesthetics, and botulinum toxin. Where pain did not improve with treatment, some oral medications improved participants' mood and sexual function. Some topical agents may be effective in reducing peripherally mediated neuropathic pain. Botulinum toxin was the most well-studied injectable but yielded mixed outcomes related to pain, quality of life, and sexual function. There is a lack of convincing evidence to draw conclusions about the efficacy or effectiveness of pharmacological therapies for LPV. The breadth of therapies for treating LPV warrants the development of evidence-based, consensus guidelines for measuring treatment outcomes and improving comparisons across studies. Recommendations for research include addressing methodological shortcomings and diversifying the participant pool to increase the generalizability of findings. [ABSTRACT FROM AUTHOR]

Florida has one of the most diverse agricultural economies in the United States, producing several dozen types of fruits and vegetables that are consumed within the state, across the country, and around the world. The COVID-19 pandemic and resulting policy responses occurred during the peak of spring harvest season for many crops in Florida, abruptly removing market demand from the food service industry and shifting consumer purchasing habits, which enabled insights into several aspects of the fruit and vegetable supply chain. This article examines how the COVID-19 pandemic impacted fruit and vegetable industries in Florida, how these industries responded to COVID-19 impacts, and how Florida's experience compared to that of other states. Data are derived from several sources including a statewide survey that measured agricultural production losses in Florida resulting from COVID-19 in early 2020, interviews with Florida operations that provided insights into how the pandemic induced change across the food supply chain, and a survey of food supply chain operations in three regions of the United States conducted in 2021. [ABSTRACT FROM AUTHOR]

Mangrove forests are globally significant blue carbon sinks that remain critically under-governed and under threat. In Indonesia, the rapid rate of mangrove loss over the past three decades, combined with the promise of these carbon-dense ecosystems to mitigate climate change impacts, has catalyzed the world's largest replanting program. Institutional and ideological divisions between advocates of conservation and commodification approaches to mangrove governance, however, have historically compromised Indonesia's ability to meet its climate commitments. Market valuations of mangroves as blue carbon have further complicated their governance by opening up new opportunities for environmental collaboration and resource exploitation. Drawing on the concept of leverage points, this study examines how plural valuations of mangroves might be applied to sustainability interventions in Riau Province, Indonesia. Using document analysis and interviews with public, private and societal stakeholders, we examine how sector-level values translate into collaborative actions through mangrove partnerships. We posit that integrating indigenous knowledge and place-based values into mangrove policy development could help to address the existing conservation–commodification divide. As plural values are mutually transformative, we argue that recognizing areas of strategic compatibility creates space for flexible and adaptive cross-sector cooperation. Such recognition is especially important for mangrove communities, whose marginal socioeconomic position reinforces their need to remain ideologically and tactfully open to areas of compatibility with shifting market valuations, both to sustainably develop locally important resources and to avoid livelihood capture by predatory development interests. [ABSTRACT FROM AUTHOR]

Purpose: Pre-frailty and frailty in older adults are associated with poor health outcomes and increase health-care costs, and further worsening during hospitalization. This study aimed to examine the effect of an individualized hospital to home, exercise-nutrition self-managed intervention for pre-frail and frail hospitalized older adults. Patients and Methods: Older adults admitted to an acute medical unit of a tertiary hospital in South Australia who were pre-frail or frail were recruited from September 2020 to June 2021, randomized to either control or intervention group and followed up at 3 and 6 months. The outcome variables were program adherence, frailty status by the Edmonton Frail Scale (EFS) score, lower extremity physical function, handgrip strength, nutritional status, cognition, mood, health-related quality of life, risk of functional decline, unplanned readmissions. Results: Participants were 79.2 ± 6.6 years old, 63% female, mostly frail (67%), with EFS of 8.6± 1.9. Adherence to the inpatient and home visits/telehealth intervention were high (91± 13% and 92± 21%, respectively). Intention-to-treat analysis using linear regression models showed that participants in the intervention group had significantly greater reduction in EFS at 3 (− 3.0; 95% CI: − 4.8 to − 3.0) and 6 months (− 2.5; 95% CI: − 3.8 to − 1.0, P< 0.001 for both) compared to the control group; particularly the functional performance component. There were also improvements in overall Short Physical Performance Battery score at 3 (4.0; 95% CI: 1.3 to 6.6) and 6 months (3.9; 95% CI: 1.0 to 6.9, P< 0.05 for both), mini-mental state examination (2.6; 95% 0.3– 4.8, P=0.029) at 3 months and handgrip strength (3.7; 95% CI: 0.2– 7.1, P=0.039) and Geriatric Depression Scale, at 6 months (− 2.2; 95% CI: − 4.1 to − 0.30, P=0.026) in the intervention group as compared to control. Conclusion: This study provided evidence of acceptability to a patient self-managed exercise-nutrition program that may benefit and alleviate pre-frailty and frailty in hospitalised older adults. [ABSTRACT FROM AUTHOR]

911 calls reporting the mysterious disappearance of a child may contain information critical to law enforcement. If this information is untruthful, valuable resources can be misdirected and precious time may be lost. Therefore, the current study examined verbal cues of veracity and deception in 911 calls placed by caregivers of missing children. Specifically, the current study compared differences between a sample of caregivers who falsely reported a child missing to conceal their role in the child's homicide and truthful caregivers who reported a child missing and had no knowledge of the child's whereabouts at the time of the call. Results show promise and consistency with previously proposed indicators of veracity and deception. Specifically, a greater number of self‐handicapping statements were made by deceptive individuals, whereas truthtellers were more likely to spontaneously self‐correct. Practical implications are discussed. [ABSTRACT FROM AUTHOR]

To investigate the effect of home and away game travel on risk of concussion across different levels of rugby union. Exploration study across school, university, and professional rugby teams. Retrospective analysis of concussion incidence and symptomology of surveillance data and prospective data collection for potential concussions via surveys. Data was collected from school rugby teams (n = 344 matches, over 2 years), a university rugby (n = 6 matches), and a professional rugby team (n = 64 matches, over two seasons). School level rugby had an increased prevalence of concussions in away matches (p = 0.02). Likewise, there was a significant increase (p < 0.05) in concussions at away matches in university rugby. In addition, the professional rug by team had significant differences in recovery times and symptoms with away fixtures, including longer recovery times (p < 0.01), more initial symptoms (p < 0.01), as well as greater and more severe symptoms at 48 hours (p < 0.05). This research highlights an increased prevalence of concussion in school and university-aged rugby players away from home, as well as increased symptoms, symptom severity, and recovery times in professional rugby players. [ABSTRACT FROM AUTHOR]

Background: SARS-CoV-2 vaccines play an important role in reducing disease severity, hospitalization, and death, although they failed to prevent the transmission of SARS-CoV-2 variants. Therefore, an effective inhibitor of galectin-3 (Gal-3) could be used to treat and prevent the transmission of COVID-19. ProLectin-M (PL-M), a Gal-3 antagonist, was shown to interact with Gal-3 and thereby prevent cellular entry of SARS-CoV-2 in previous studies. Aim: The present study aimed to further evaluate the therapeutic effect of PL-M tablets in 34 subjects with COVID-19. Methods: The efficacy of PL-M was evaluated in a randomized, double-blind, placebo-controlled clinical study in patients with mild to moderately severe COVID-19. Primary endpoints included changes in the absolute RT-PCR Ct values of the nucleocapsid and open reading frame (ORF) genes from baseline to days 3 and 7. The incidence of adverse events, changes in blood biochemistry, inflammatory biomarkers, and levels of antibodies against COVID-19 were also evaluated as part of the safety evaluation. Results: PL-M treatment significantly (p = 0.001) increased RT-PCR cycle counts for N and ORF genes on days 3 (Ct values 32.09 ± 2.39 and 30.69 ± 3.38, respectively) and 7 (Ct values 34.91 ± 0.39 and 34.85 ± 0.61, respectively) compared to a placebo treatment. On day 3, 14 subjects in the PL-M group had cycle counts for the N gene above the cut-off value of 29 (target cycle count 29), whereas on day 7, all subjects had cycle counts above the cut-off value. Ct values in placebo subjects were consistently less than 29, and no placebo subjects were RT-PCR-negative until day 7. Most of the symptoms disappeared completely after receiving PL-M treatment for 7 days in more patients compared to the placebo group. Conclusion: PL-M is safe and effective for clinical use in reducing viral loads and promoting rapid viral clearance in COVID-19 patients by inhibiting SARS-CoV-2 entry into cells through the inhibition of Gal-3. [ABSTRACT FROM AUTHOR]

Diabetes-related foot ulceration presents an increasing risk of lower limb amputation globally, driving the search for new treatment technologies. Our single-centre prospective observational study reports on the impact of bilayer biodegradable synthetic matrix technology (NovoSorb® BTM) on the healing and amputation rates of a diabetic foot ulceration cohort. Consecutive patients with a diabetes-related foot ulceration treated with NovoSorb BTM, between December 2019 and October 2021, were followed for 12 months. Complete wound healing and amputation outcomes were observed. Amputation risk was stratified using the Wound, Ischaemia and foot Infection (WIfI) classification system. Study outcomes were compared with recently published meta-analysis data to evaluate the impact of the synthetic matrix. In total, 25 NovoSorb BTM applications to 23 wounds in 22 patients were observed. Complete wound healing was observed in 15 of the wounds, 3 retained chronic wounds, 3 required minor amputation and 2 required major limb amputation. Further, 12-month WIfI amputation risk analysis saw 18 patients stratified to WIfI stage 4, 4 to WIfI stage 3 and 1 to WIfI stage 1. Our observed 12-month major amputation rates were 11.1% (n = 2) for stage 4 and 0% for stages 3 and 1. Our early experience suggests that NovoSorb BTM is a safe and effective treatment for moderate to severe diabetes-related foot ulceration. While larger-scale data are required, NovoSorb BTM may represent a promising new addition to the armamentarium of clinicians, who strive to achieve limb salvage in this complex cohort of patients. [ABSTRACT FROM AUTHOR]

Background and Objective: Renal impairment is common in patients with cancer and can alter the PK and thus the safety and efficacy of drugs. We assessed the impact of renal impairment during treatment with ribociclib, a cyclin-dependent kinase 4/6 inhibitor, and determined dose recommendations for patients with advanced breast cancer with renal impairment. Methods: A comprehensive assessment integrating pharmacokinetic, safety, and efficacy data from a phase I dedicated renal impairment study in non-cancer subjects and six phase I–III trials in patients with cancer was performed. Results: Ribociclib showed higher pharmacokinetic exposure in subjects with renal impairment than those with normal renal function following a single 400-mg dose in the dedicated renal impairment study. However, in patient trials, both single-dose and steady‑state ribociclib exposure was comparable between patients with cancer with mild/moderate renal impairment and those with normal renal function following the recommended starting dose of 600 mg. Model-predicted steady‑state exposure in patients with advanced breast cancer was also similar across the renal function groups. Progression-free survival was similar and safety profiles were generally consistent across the renal cohorts (normal/mild/moderate) in patients with advanced breast cancer, with low-grade and manageable adverse events, demonstrating a positive benefit-risk profile. Conclusions: From the collective evidence and considering a real-world clinical setting, no dose adjustment is recommended for patients with mild/moderate renal impairment, whereas a reduced dose is recommended for patients with severe renal impairment. This report presented a holistic and innovative strategy to determine dose in patients with renal impairment and demonstrated the effectiveness of integrating the data of both a clinical pharmacology study and patient trials to justify doses in patients with renal impairment. Clinical Trial Registration: Clinicaltrials.gov identifiers: NCT02431481, NCT01958021, NCT02422615, NCT02278120, NCT01237236, NCT01898845, NCT01872260. [ABSTRACT FROM AUTHOR]

Visible disruptions of appropriate food distribution for end consumers during the onset of the COVID-19 pandemic prompted calls for an urgent, renewed look at how the U.S. agri-food system is impacted by and responds to pandemics, natural disasters, and human-made crises. Previous studies suggest the COVID-19 pandemic yielded uneven impacts across agri-food supply chain segments and regions. For a rigorously comparable assessment of the impact of COVID-19 on agri-food businesses, a survey was administered from February to April 2021 to five segments of the agri-food supply chain in three study regions (California, Florida, and the two-state region of Minnesota-Wisconsin). Results (N = 870) measuring the self-reported changes in quarterly business revenue in 2020 compared to businesses' typical experience pre-COVID-19 suggest significant differences across supply chain segments and regions. In the Minnesota-Wisconsin region, restaurants took the largest hit and the upstream supply chains were relatively unaffected. In California, however, the negative impacts were felt throughout the supply chain. Two factors likely contributed to regional differences: (1) regional disparities in pandemic evolution and governance and (2) structural differences in regional agri-food systems. Regionalized and localized planning and the development of best-practices will be necessary for the U.S. agri-food system to enhance preparedness for and resilience to future pandemics, natural disasters, and human-made crises. [ABSTRACT FROM AUTHOR]

Resident satisfaction with food services contributes to health and wellbeing. Measuring resident satisfaction is important; however, the small number of existing food service satisfaction questionnaires (FSSQs) are outdated, lack rigorous psychometric testing and do not reflect the shift to person-centered care. This study aimed to develop a valid and reliable FSSQ. Content validity was established by conducting interviews with residents, a systematic literature review and consultation with an expert panel. Data from 387 residents were used to establish construct validity (Principal Components Analysis), internal consistency (Cronbach's alpha) and temporal stability (Gwet's AC). The result was a three factor, 25-item scale with good/excellent internal consistency: Factor One (13 items–good food/service, α = 0.896), Factor Two (seven items–resident choice/food availability α = 0.648) and Factor Three (five items–resident participation/staff assistance, α = 0.729). Temporal stability was good/very good (Gwet's AC 0.6242–0.9799 (p < 0.001). This is the first FSSQ available to nursing homes that meets the COSMIN® standards for excellence and incorporates person-centered care. The questionnaire is simple to use and interpret, providing food service managers with an accurate and reliable measure of resident satisfaction and assisting them in providing a meal and dining experience that supports the health and wellbeing of residents. [ABSTRACT FROM AUTHOR]

Background/Objective : Low muscle mass and sarcopenia have been explored as risk factors for poor outcomes following vascular surgery. The findings have been variable. The use of a diverse range of techniques to identify low muscle mass is a confounder in establishing the true relationship between low muscle mass, sarcopenia and outcomes. Our aim was to establish if different scoring methods identified the same patients as sarcopenic. We also explored which method best predicted outcomes. Method : 70 patients undergoing vascular surgery were prospectively assessed for sarcopenia using dual-energy x-ray absorptiometry (DEXA) scan, grip strength and gait speed. These patients underwent abdominal CT imaging as routine care. The muscle mass of each patient was determined using DEXA and by both psoas muscle and total skeletal muscle area on CT, normalised for patient height (PMI and CT-SMI, respectively). Low muscle mass was defined by published age- and sex-specific cut-offs. Grip strength data was combined with muscle mass to define sarcopenic patients. One- and 3-year mortality and time to readmission was recorded. Conclusion and Results : 10–22% of patients had low muscle mass and 4–10% of patients were sarcopenic, depending on the method employed. PMI did not correlate with DEXA or CT-SMI for low muscle mass, but CT-SMI correlated with DEXA (p = 0.0007). For sarcopenia, CT-SMI and DEXA scoring correlated (p = 0.002); PMI correlated with CT-SMI (p = 0.0006) but not DEXA. Low muscle mass by PMI predicted 1-year mortality (p = 0.02, X2 = 5.34, Effect size = 1.04) but the applicability of this finding is limited by the diverse pathologies explored. No other method predicted 1- or 3-year mortality or readmissions in this heterogenous cohort. The psoas area did not correlate with muscle mass defined by DEXA or total lumbar skeletal muscle area. Low psoas muscle index may be an independent marker of poor outcome, unrelated to generalised sarcopenia, and this warrants investigation in specific pathologies. A lower total number of patients were sarcopenic than had been expected, emphasising the need to use population-based pre-defined cut-offs. [ABSTRACT FROM AUTHOR]

Identifying nutritional deficits and implementing appropriate interventions in patients requiring vascular surgery is challenging due to the paucity of appropriate screening and assessment tools in this group. This retrospective study aimed to determine the validity of the Global Leadership Initiative on Malnutrition (GLIM) in identifying protein–energy malnutrition (PEM) in inpatients admitted to a vascular surgery unit, using the PG-SGA as the comparator. Diagnostic accuracy and consistency were determined between the GLIM and the Patient-Generated Subjective Global Assessment (PG-SGA) global rating. The GLIM determination was made retrospectively using the relevant parameters collected at baseline in the original study. Two hundred and twenty-four (70·1 % male) participants were included. The prevalence of PEM was 28·6 % on GLIM and 17 % via the PG-SGA. Compared with the PG-SGA, the GLIM achieved sensitivity of 73·7 % and specificity of 80·6 %; however positive predictive value was 43·7 % indicating that the GLIM over-diagnosed malnutrition compared with the PG-SGA. Kappa reached 0·427 indicating moderate diagnostic consistency. Due to the absence of an ideal instrument and the complexity of malnutrition often seen in this group which extends beyond PEM to significant micronutrient deficiencies, further work is required to determine the most appropriate instrument in this patient group, and how micronutrient status can also be included in the overall assessment given the critical role of micronutrients in this group. [ABSTRACT FROM AUTHOR]

Context Chronic inflammation, characterized by prolonged elevated inflammation markers, is linked to several chronic conditions. Diet can influence the levels of inflammation markers in the body. Objective The aim of this systematic review was to assess the effects of anti-inflammatory diets on 14 different inflammation markers in adults. Data Sources This systematic review conducted searches using Medline, PubMed, EMCare, Cochrane, and CINAHL, to locate randomized controlled trials (RCTs). Data Extraction Two researchers independently screened 1537 RCTs that measured changes in inflammation markers after prescription of an intervention diet. Data Analysis In total, 20 RCTs were included and assessed qualitatively. The results demonstrated that a Mediterranean diet can bring about statistically significant and clinically meaningful between-group differences in interleukins -1α, -1β, -4, -5, -6, -7, -8, -10, and -18, interferon γ, tumor necrosis factor α, C-reactive protein, and high-sensitivity C-reactive protein, as compared with a control diet. Conclusions There may be a link between diet, inflammation markers, and disease outcomes in various adult populations. However, further research using consistent RCT protocols is required to determine correlations between diet, specific inflammation markers, and clinically relevant outcomes. [ABSTRACT FROM AUTHOR]

The reemergence of fraternal and mutual aid structures across multiple sectors of the economy is a product of a unifying working-class cultural identity related to precarity. These experiments with collective economic self-reliance reveal what future forms of labor institutions may look like, demonstrating the transformative potential of building community through mutual care. [ABSTRACT FROM AUTHOR]

This paper examines how missed income due to illness impacts household fragility. Specifically, it shows that paid sick leave laws, which provide households insurance against illness‐related income shocks, reduce consumer bankruptcy. Using a panel dataset at the county‐quarter level, this paper exploits the geographic and temporal variation in the adoption of paid sick leave laws to implement a difference‐in‐differences and event study analysis. It finds that paid sick leave laws reduce consumer bankruptcy filings by approximately 11%; this effect is seen within three quarters of the law's implementation and remains constant in magnitude and significance thereafter. As paid sick leave laws may come at a cost to businesses, this paper also examines the impact of such laws on business bankruptcy filings—it shows that paid sick leave laws have little to no impact on business bankruptcy filings. [ABSTRACT FROM AUTHOR]

Rural adaptation encompasses place-based perceptions, behaviors, livelihoods, and traditional ways of life associated with local environments. These perceptions, norms, and practices are disturbed by coupled environment-development externalities. This study employs the Vietnamese Mekong floodplains as an exemplary case to illustrate how floods impact agrarian communities and how they have experienced flood alterations driven by hydropower development and climate change in recent years. Drawing on thematic and narrative analyses of qualitative data (focus group discussions and interviews) collected in three agrarian communities in the Vietnamese Mekong floodplains, sources drawn from various news outlets, and academic materials, we argue that disrupted flood environments in the floodplains have triggered affective flood reminiscences, catalysing shifts to incremental and transformative adaptation to achieve resilience. We build a nuanced understanding of how social memory helps to enhance human–environment relationships in response to highly complex hydrological dynamics in the delta. [ABSTRACT FROM AUTHOR]

Sophie Chao's first book, I In the Shadow of the Palms i , explores the (de)generative tropical geography of human-vegetal relations in oil palm plantations. Chao punctuates the narrative flow of the chapters with a series of dream interludes, co-produced with Marind subjects, that feature recurring themes of being devoured by oil palm as a form of involuntary "skin-changing" (p. 189) into hybrid human-animal or human-plant forms. Chao applies this metaphor to oil palm's dual agentive role of: (a) bringing new interspecies networks into co-becoming, even as it (b) relentlessly stifles known geographies of human-nature relationships. [Extracted from the article]

Introduction: Whilst there has been a wealth of research on benefits of physical activity (PA) in people with cancer, with three published reviews of reviews, no review of reviews has focused on older adults (65 years or older) who may have unique biological characteristics and barriers. We summarised PA effectiveness from reviews where majority of study participants were 65 years or older. Methods: Six databases were searched for systematic reviews of randomised controlled studies (RCTs)/quasi‐RCTs examining any type of PA in reviews where majority of study participants were aged 65 years or older. Two reviewers conducted the search and analysis according to PRISMA and JBI guidelines. Results: Fifteen reviews involving 76 different primary studies (5404 participants) were included. The majority (3827; 71%) had prostate cancer. PA was associated with benefits across multiple physical outcomes (muscle mass, functional performance, strength), improved fatigue and health service outcomes. In contrast to younger adults, there was no improvement in anxiety and mixed findings for quality of life and depression. Conclusion: PA is associated with multiple benefits in older adults with cancer, with some differences compared to younger individuals which may reflect biological or behavioural determinants. Future research should focus on mechanisms underlying PA effectiveness and underrepresented populations. [ABSTRACT FROM AUTHOR]

Clinical trials of novel therapeutics in the United States have not been adequately representative of diverse populations, particularly racial and ethnic minorities. The challenges and consequences of underrepresentation in clinical trial recruitment are exemplified by the case of belimumab, a biologic treatment for systemic lupus erythematosus (SLE), a disease that is more prevalent in patients of Black African ancestry and of Hispanic/Latino ethnicity than in other patient populations. Although belimumab was found to be effective in phase 2 and 3 clinical trials in the general population, post hoc analyses of efficacy data in patients of Black African ancestry showed inconsistent results. Consequently, a cautionary statement regarding belimumab use in this population was added to the product label. To alleviate concerns that belimumab may not be safe and effective for patients of Black African ancestry, the Efficacy and Safety of Belimumab in Black Race Patients with SLE (EMBRACE) study was conducted in a post‐marketing commitment to the Food and Drug Administration. The study recruited only patients who self‐identified as being of Black race; its findings led to the removal of the cautionary labeling of belimumab use in patients of Black African ancestry. Our manuscript highlights the critical lessons learned from the successes and failures of the EMBRACE study. It also provides suggestions for overcoming health disparities, highlighting strategies for conducting well‐designed clinical trials to overcome systematic barriers to diversity in recruitment, with a focus on enacting long‐term support to ensure equity in the process, products, and benefits from drug development and clinical trials. [ABSTRACT FROM AUTHOR]

Objectives: To explore the diabetes self-management expectations of older adults with diabetes, not yet accessing residential aged care services. Admission to residential aged care (RAC) can create many interruptions to usual food choices and diabetes self-management, and we know little about the concerns of the emerging ageing population. Methods: This is a qualitative study employing focus groups and inductive thematic analysis involving 18 older adults with diabetes between the ages of 60 and 88, living in their own homes within an Australian city. Focus groups were recruited on a sequential basis and progressively analysed using an inductive process until data saturation was reached. Focus groups were digitally recorded and transcribed verbatim for thematic analysis. Results: Three key themes were generated: autonomy, individualised dietary management and the food service system. Older adults speculated that they would want a collaborative approach to maintain their health in ageing and to self-manage their diabetes while feasible. Participants wanted autonomy over food choices, flexible meal timings and quality meals. There was a significant anxiety that aged care staff and existing food service systems in RAC could not support these preferences. Conclusions: Community-dwelling older adults with diabetes would highly value aged care services that facilitated autonomy, individualised nutrition support and flexibility, but feared this will not be feasible. The introduction of new diabetes and RAC guidelines may require an implementation plan to include the full food service system, from staff education to meal preparation, ordering and service. [ABSTRACT FROM AUTHOR]

The present study draws on socio-cultural theories and socio-cognitive theories as guiding frameworks to examine responses to bias-based bullying among 481 middle school youth (49% female; 15% immigrant; 36% minoritized ethnicity). Based on student self-report data, we examined: (1) whether middle-schoolers response strategies' from the perspective of the victim being excluded or bullied varied across three hypothetical bias-based bullying scenarios based on participant's immigrant background and gender and by target victim's ethnic im/migrant background (e.g. Arab, Latinx, Black); and (2) whether youth disclosure of actual bullying experiences (i.e. to whom they disclosed their bullying experience) differed by their immigrant background and gender. Findings revealed that none of the immigrant girls reported that they would hit the excluder from the perspective of the Latina hypothetical victim compared to when the hypothetical victim was Black and Arab. In response to their actual experiences, immigrant girls were least likely to tell anyone (e.g. peer, teacher, or parent) if they were bullied at school. Results highlight the importance of fostering family and school administration awareness of bullying victimization and the creation of culturally sensitive school interventions and policies for reporting and preventing the bullying victimization of immigrant children, particularly for immigrant girls. [ABSTRACT FROM AUTHOR]