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Under compassionate use, chimeric antigen receptor (CAR) T cells have elicited durable remissions in patients with refractory idiopathic inflammatory myopathies (IIMs). Here, we report on the safety, efficacy, and correlative data of the first subject with the immune-mediated necrotizing myopathy (IMNM) subtype of IIM who received a fully human, 4-1BBz anti-CD19-CAR T cell therapy (CABA-201) in the RESET-Myositis phase I/II trial (NCT06154252). CABA-201 was well-tolerated following infusion. Notably, no evidence of cytokine release syndrome or immune effector cell-associated neurotoxicity syndrome was observed. Creatine kinase levels decreased, and muscular strength improved post-infusion. Peripheral B cells were depleted rapidly following infusion, and the subject achieved peripheral B cell aplasia by day 15 post-infusion. Peripheral B cells returned at 2 months post-infusion and were almost entirely transitional. Autoantibodies to SRP-9, SRP-72, SRP-54, and Ro-52, decreased relative to baseline, whereas antibodies associated with pathogens and vaccinations remained stable. The infusion product consisted of predominantly CD4 + effector memory T cells and exhibited in vitro cytolytic activity. Post-infusion, CABA-201 expansion peaked at day 15 and was preceded by a serum IFN-γ peak on day 8 with peaks in serum IL-12p40 and IP-10 on day 15. These data detail the safety, efficacy, and pharmacodynamics of CABA-201 in the first IMNM subject., Competing Interests: Declaration of interests J.V., D.N., J.S., M.W., Z.V., A.E., J.W., J.C., Q.L., T.F., C.S., F.H.-N., D.T., C.M., C.L., D.C., and S.B. are employees of Cabaletta Bio., (Copyright © 2024 Cabaletta Bio. Published by Elsevier Inc. All rights reserved.)

Pulmonary hypertension (PH) is a progressive vascular disease characterized by vascular remodeling, stiffening, and luminal obstruction, driven by dysregulated cell proliferation, inflammation, and extracellular matrix (ECM) alterations. Despite the recognized contribution of ECM dysregulation to PH pathogenesis, the precise molecular alterations in the matrisome remain poorly understood. In this study, we employed a matrisome-focused proteomics approach to map the protein composition in a young bovine calf model of acute hypoxia-induced PH. Our findings reveal distinct alterations in the matrisome along the pulmonary vascular axis, with the most prominent changes observed in the main pulmonary artery. Key alterations included a strong immune response and wound repair signature, characterized by increased levels of complement components, coagulation cascade proteins, and provisional matrix markers. Additionally, we observed upregulation of ECM-modifying enzymes, growth factors, and core ECM proteins implicated in vascular stiffening, such as collagens, periostin, tenacsin-C, and fibrin(ogen). Notably, these alterations correlated with increased mean pulmonary arterial pressure and vascular remodeling. In the plasma, we identified increased levels of complement components, indicating a systemic inflammatory response accompanying the vascular remodeling. Our findings shed light on the dynamic matrisome remodeling in early-stage PH, implicating a wound-healing trajectory with distinct patterns from the MPA to the distal vasculature. This study provides novel insights into the molecular underpinnings of PH pathogenesis and highlights potential biomarkers and therapeutic targets within the matrisome landscape.

Envenomings from Russell's viper typically result in local tissue damage and bleeding complications, but the bites from common krait and cobra primarily cause neurotoxic effects. While most symptoms can be treated with appropriate antivenom, additional support is necessary for several snakebite victims to tackle a broad range of unusual complications that they develop following bites. Reversible vasoconstriction syndrome (RCVS), characterised by the constriction of cerebral arteries, is a rare but serious issue, presenting with severe headaches and, in extreme cases, haemorrhagic/ischaemic stroke. This report presents three cases of RCVS in snakebite victims following Russell's viper, krait and cobra bites. The patients were admitted to the hospital with neurological and/or haematological complications, and they were treated with polyvalent antivenom. After two days of antivenom treatment, all the patients developed intense headaches that lasted for several hours and failed to respond to commonly used analgesics. While the physical, laboratory and computed tomography examinations were normal, the RCVS was diagnosed with multimodal magnetic resonance angiography. All patients were successfully treated with oral nimodipine, and during their follow-ups, physical and laboratory examinations were unremarkable, and the magnetic resonance imaging confirmed the reversal of RCVS. To achieve positive outcomes in patients, clinicians must swiftly identify such rare complications and make accurate diagnoses to provide prompt treatments. Overall, this report presents an unusual complication of RCVS in snakebite patients and appropriate diagnosis and treatment approaches to tackle this condition., Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2024 The Authors. Published by Elsevier Ltd.. All rights reserved.)

Body dysmorphic disorder (BDD) is an underrecognized, challenging illness with severe comorbidities, demanding urgent advancements in treatment strategies. This state-of-the-science review describes current research on existing BDD treatments, beginning with a detailed discussion of cognitive-behavioral therapy (CBT), the primary psychosocial intervention for BDD, and its foundational theories. We emphasize the significant progress in the field, including the efficacy of face-to-face CBT, the promising outcomes of digital interventions for broadening access to care, and emerging treatments that warrant further exploration. The review also addresses the critical gap of targeted interventions for youth, considering the diseases' typical onset during adolescence. Our review also sheds light on the significant gap in research dedicated to testing these treatments in underserved communities, stressing the importance of including these populations in research and culturally informed and adapted, if necessary, care. The review concludes with recommendations for future directions, outlining areas for ongoing treatment development and research to expand the scope and efficacy of interventions for BDD., (Copyright © 2024 Association for Behavioral and Cognitive Therapies. Published by Elsevier Ltd. All rights reserved.)

Nurses are frequently exposed to trauma both inside and outside of the hospital setting. This trauma exposure may lead to symptoms that can be harmful to the nurse and make it more difficult for them to provide quality care to patients. Trauma-informed professional development is a strategy that can help nursing professional development practitioners create an environment where recovery after trauma is possible. This article provides definitions and exemplars for practice., Competing Interests: The authors declare no conflicts of interest., (Copyright © 2024 Wolters Kluwer Health, Inc. All rights reserved.)

Background: Despite being a challenging and morbid clinical problem, operative approaches to recurrent abdominal wall hernia repairs receive little attention. Given this, we performed a retrospective study to evaluate surgical techniques of recurrent abdominal wall hernias requiring reoperation., Methods: Adult patients from the Michigan Surgical Quality Collaborative Core Optimization Hernia Registry (MSQC-COHR) were included in this study. All elective ventral hernia operations performed between January 1, 2020, and March 31, 2023, were included. Descriptive analyses via t-tests and Fisher exact tests were conducted to evaluate sociodemographic, operative, and hernia-specific attributes associated with primary and recurrent hernia repairs., Results: We identified 8587 patients who underwent elective abdominal wall hernia repair. Of these, 7887 (91.8%) underwent primary repair, and 700 (8.2%) underwent recurrent repair. Patients who underwent recurrent hernia repair were older (mean age 57.9 years vs. 54.1 years, p < 0.001), more often female (53.8% vs. 41.9%, p < 0.001), and had higher BMI (34.0 vs. 32.6, p < 0.001). Patients with recurrent hernias were more likely to have comorbid conditions including hypertension (p < 0.001), diabetes (p < 0.005), COPD (p < 0.01), and BMI > 40 (p < 0.05). Recurrent hernia repairs were more likely to have any 30-day complication (6.4% versus 1.9%, p < 0.001), including higher rates of all surgical site infections. There was no difference in 30-day readmission rates., Conclusion: Considerable variation persists in operative management of recurrent abdominal wall hernias. Importantly, not all recurrent hernias were managed with mesh, which may precipitate additional recurrences and further morbidity. Understanding outcomes for these varied approaches to recurrent hernia repairs is critical to optimize management of this complex clinical problem and prevent future episodes of recurrence., (© 2024. The Author(s), under exclusive licence to Springer Science+Business Media, LLC, part of Springer Nature.)

Purpose: The guiding documents of the social work profession establish social justice as central to the discipline and practice of social work, yet there is little consensus on the meaning of the term. Therefore, the goal of this study was to examine how faculty and staff in one school of social work defined social justice., Methods: Data for this study were drawn from a school climate survey distributed within one school of social work with an explicitly stated commitment to social justice. Ninety-three staves and faculty responded to the open-ended question: How do you define social justice?, Findings: Three themes were identified in how participants defined social justice as a form of evidence-based meaning making: (1) equality , (2) equity , and (3) advocacy and action ., Discussion: We conclude this article by discussing implications for how social workers can incorporate a critical approach to defining social justice that extends beyond equality and equity. Specifically, we recommend that the profession work toward a common, evidenced-based understanding of social justice to effectively educate current and future social workers to dismantle systems of oppression at all levels of social work.

Sustained attention, a key cognitive skill that improves during childhood and adolescence, tends to be worse in some emotional and behavioural disorders. Sustained attention is typically studied in non-affective task contexts; here, we used a novel task to index performance in affective versus neutral contexts across adolescence ( N  = 465; ages 11-18). We asked whether: (i) performance would be worse in negative versus neutral task contexts; (ii) performance would improve with age; (iii) affective interference would be greater in younger adolescents; (iv) adolescents at risk for depression and higher in anxiety would show overall worse performance; and (v) would show differential performance in negative contexts. Results indicated that participants performed more poorly in negative contexts and showed age-related performance improvements. Those at risk of depression performed more poorly than those at lower risk. However, there was no difference between groups as a result of affective context. For anxiety there was no difference in performance as a function of severity. However, those with higher anxiety showed less variance in their reaction times to negative stimuli than those with lower anxiety. One interpretation is that moderate levels of emotional arousal associated with anxiety make individuals less susceptible to the distracting effects of negative stimuli.

Background: The objective of this study was to investigate the associations between women's education and access to skilled birth attendant (SBA) services mediated by factors of women's empowerment and sociodemographic characteristics using a path analysis through a structural equation (SEM) modelling approach., Methods: A sample of 4946 mothers from the most recent Bangladesh Demographic and Health Survey of 2017-18 was used in the SEM analysis. Accessing SBA service at childbirth was operationalized as utilizing SBA during last childbirth. After extracting the relevant variables and cleaning the original survey data, a subsample of 4,946 women were eligible for analysis in the current study., Results: The SEM model revealed strong evidence of direct, indirect, and mediating effects of both education and empowerment of women in accessing SBA services. Educated women have more autonomy in decision making and are less susceptible to family violence and consequently are more likely to access SBA services during childbirth (β = 0.094, p < 0.001). In addition, age at first marriage, media exposure, husband's education, healthcare accessibility, decision marking, and household wealth index mediated the relationship between education and SBA service use., Conclusion: Bangladesh, a country that needs to improve several societal and health indices to achieve the Sustainable Development Goals, need to prioritize women's education to increase accessibility to maternal healthcare services. Health education and mass-media-driven awareness may be potential interventions for LMICs to increase SBA coverage., Competing Interests: Declaration of competing interest There was no conflict of interest among the authors. All authors read the final manuscript and approved it., (Copyright © 2024 The Author(s). Published by Elsevier Ltd.. All rights reserved.)

Aims: Dried blood volumetric absorptive microsamples (VAMS) may facilitate home-based sampling to enhance therapeutic drug monitoring after transplantation. This study aimed to clinically validate a liquid chromatography-tandem mass spectrometry assay using 2 VAMS devices with different sampling locations (Tasso-M20 for the upper arm and Mitra for the finger). Patient preferences were also evaluated., Methods: Clinical validation was performed for tacrolimus and mycophenolic acid by comparison of paired VAMS and venipuncture samples using Passing-Bablok regression and Bland-Altman analysis. Conversion of mycophenolic acid VAMS to serum concentrations was evaluated using haematocrit-dependent formulas and fixed correction factors defined a priori. Patients' perspectives, including useability, acceptability and feasibility, were also investigated using established questionnaires., Results: Paired samples (n = 50) were collected from 25 kidney transplant recipients. Differences for tacrolimus whole-blood concentration were within ±20% for 86 and 88% of samples from the upper arm and fingerstick, respectively. Using correction factors of 1.3 for the upper-arm and 1.47 for finger-prick samples, 84 and 76% of the paired samples, respectively, were within ±20% for mycophenolic acid serum concentration. Patient experience surveys demonstrated limited pain and acceptable useability of the upper-arm device., Conclusions: Tacrolimus and mycophenolic acid can be measured using 2 common VAMS devices with similar analytical performance. Patients are supportive of home-based monitoring with a preference for the Tasso-M20 device., (© 2024 The Author(s). British Journal of Clinical Pharmacology published by John Wiley & Sons Ltd on behalf of British Pharmacological Society.)

Background: In patients with out-of-hospital cardiac arrest, the effectiveness of drugs such as epinephrine is highly time-dependent. An intraosseous route of drug administration may enable more rapid drug administration than an intravenous route; however, its effect on clinical outcomes is uncertain., Methods: We conducted a multicenter, open-label, randomized trial across 11 emergency medical systems in the United Kingdom that involved adults in cardiac arrest for whom vascular access for drug administration was needed. Patients were randomly assigned to receive treatment from paramedics by means of an intraosseous-first or intravenous-first vascular access strategy. The primary outcome was survival at 30 days. Key secondary outcomes included any return of spontaneous circulation and favorable neurologic function at hospital discharge (defined by a score of 3 or less on the modified Rankin scale, on which scores range from 0 to 6, with higher scores indicating greater disability). No adjustment for multiplicity was made., Results: A total of 6082 patients were assigned to a trial group: 3040 to the intraosseous group and 3042 to the intravenous group. At 30 days, 137 of 3030 patients (4.5%) in the intraosseous group and 155 of 3034 (5.1%) in the intravenous group were alive (adjusted odds ratio, 0.94; 95% confidence interval [CI], 0.68 to 1.32; P = 0.74). At the time of hospital discharge, a favorable neurologic outcome was observed in 80 of 2994 patients (2.7%) in the intraosseous group and in 85 of 2986 (2.8%) in the intravenous group (adjusted odds ratio, 0.91; 95% CI, 0.57 to 1.47); a return of spontaneous circulation at any time occurred in 1092 of 3031 patients (36.0%) and in 1186 of 3035 patients (39.1%), respectively (adjusted odds ratio, 0.86; 95% CI, 0.76 to 0.97). During the trial, one adverse event, which occurred in the intraosseous group, was reported., Conclusions: Among adults with out-of-hospital cardiac arrest requiring drug therapy, the use of an intraosseous-first vascular access strategy did not result in higher 30-day survival than an intravenous-first strategy. (Funded by the National Institute for Health and Care Research; PARAMEDIC-3 ISRCTN Registry number, ISRCTN14223494.)., (Copyright © 2024 Massachusetts Medical Society.)

Background: Advance Care Planning via Group Visits (ACP-GV) is a patient-centered intervention facilitated by a clinician using a group modality to promote healthcare decision-making among veterans. Participants in the group document a "Next Step" to use in planning for their future care needs. The next step may include documentation of preferences in an advance directive, discussing plans with family, or anything else to fulfill their ACP needs. This evaluation seeks to determine whether there are identifiable subgroups of group participants with differing needs prior to delivery of the ACP-GV program and, if so, to use information about the subgroups to enhance the program offered to veterans in United States Department of Veterans Affairs (VA) healthcare settings., Methods: We conducted a secondary analysis of national data from a quality improvement evaluation. Patient- and provider-level data from administrative healthcare records for VA users in all 50 states, territories, and the District of Columbia provides data on veterans attending ACP-GV during federal fiscal years 2018-2022 (N = 26,857). Latent class analysis seeks to identify the various subgroups of veterans based on their level of ACP self-efficacy before attending ACP-GV and any demographic differences across the resulting subgroups of veterans attending ACP-GV. ACP self-efficacy is derived from seven items obtained from a participant worksheet used during the group., Results: Analysis revealed two distinct groups of veterans, distinguishable by their pre-ACP-GV levels of one aspect of ACP self-efficacy: prior knowledge of ACP. Veterans with higher prior knowledge of ACP are associated with an identified next step focused on checking their current AD status and updating it, and veterans with lower ACP prior knowledge are associated with identifying a next step to discuss ACP more fully with family. Differences in age, sex, race, ethnicity, and marital status exist across subgroups of veterans., Conclusion: Greater attention must be paid to ACP and veterans' prior knowledge of ACP to consistently encourage annual review and status updates., (© 2024. This is a U.S. Government work and not under copyright protection in the US; foreign copyright protection may apply.)

Study Design: Qualitative analysis of focus group data., Objective: Identifying barriers to and facilitators of learning to direct one's own care as a person with tetraplegia due to spinal cord injury (SCI)., Setting: Community, in New Jersey and Georgia, USA., Methods: Three focus groups of veterans and civilians with SCI, involving 26 people with chronic (≥1 year) tetraplegia due to SCI who provided direction to caregivers on a daily basis. Content analysis was used to identify barriers and facilitators., Results: Challenges to learning to direct one's care included: (1) lack of acceptance of lasting effects of SCI; (2) not yet understanding one's body post-SCI; (3) embarrassment; (4) being overwhelmed with information; (5) differences between the inpatient rehabilitation setting and the "real world"; (6) lack of capable and willing assistants; and (7) hesitance to criticize caregivers. Factors that helped participants become successful directors of care included: (1) experience living with SCI; (2) being observant; (3) communicating effectively; (4) developing confidence to advocate for one's own needs; (5) learning when to "let go" and when to speak up; and (6) learning from peers., Conclusions: Direction of care is a complex skill that is developed over time, and requires awareness of one's needs and preferences, self-confidence, and strong communication skills. Rehabilitation clinicians' efforts to prepare people with SCI to direct their own care effectively should cultivate awareness of one's body, identify strategies for communicating successfully with caregivers, and provide opportunities for practice of care direction skills and discussion with experienced peers., (© 2024. The Author(s), under exclusive licence to International Spinal Cord Society.)

Background: Major Depressive Disorder (MDD) poses a significant global health challenge, with symptom presentation potentially varying between adolescents and adults. Adolescence is a critical period marked by heightened vulnerability to interpersonal stresses, yet the impact of these stresses on the structure of depressive symptoms is not well understood. Recognizing the cultural nuances in how depression manifests among adolescents is crucial. To this end, this paper employs a network analysis approach, utilizing a comprehensive symptom checklist from the Multidimensional Depression Assessment Scale (MDAS). Our study investigates the role of interpersonal symptoms within the broader cluster of emotional, cognitive, and somatic symptoms and explores variations in adolescent groups in four Asian and European regions., Methods: We recruited a diverse sample of 6,348 adolescents aged 12 to 18 from Hong Kong, Taiwan, the UK, China, and the Netherlands using the Qualtrics platform. Employing the Gaussian Graphical Model, we established a network model of depressive symptoms as measured by the MDAS, segregating the sample into Asian and European regions to examine the interconnections between them. The study focused on identifying central symptom nodes and comparing the network structures between the two groups., Results: The analysis identified feeling worthless, low energy, being a burden to others, and low mood as central symptoms of depression. Notably, there were significant differences in the connections between depressive symptoms among Asian (Hong Kong, China and Taiwan) and European (UK and the Netherlands) adolescents, highlighting cultural variations in how interpersonal symptoms interact with emotional, cognitive, and somatic symptoms., Conclusion: This study is pioneering in applying network analysis to include interpersonal symptoms in examining depression among a diverse adolescent population. It demonstrates that interpersonal symptoms are integral to the central features of depressive symptoms. Furthermore, our findings suggest that, compared to their UK and Dutch peers, interpersonal symptoms in Asian adolescents are uniquely connected to other symptom clusters, reflecting distinct cultural patterns., Limitations: The study engaged a broad community sample; however, future research could benefit from including a larger sample size to allow for a more detailed analysis of a greater number of symptom nodes., (© 2024. The Author(s).)

A growing body of scientific literature stresses the need to advance current environmental risk assessment (ERA) methodologies and associated regulatory frameworks to better address the landscape-scale and long-term impact of pesticide use on biodiversity and the ecosystem. Moreover, more collaborative and integrative approaches are needed to meet sustainability goals. The One Health approach is increasingly applied by the European Food Safety Authority (EFSA) to support the transition towards safer, healthier and more sustainable food. To this end, EFSA commissioned the development of a roadmap for action to establish a European Partnership for next-generation, systems-based Environmental Risk Assessment (PERA). Here, we summarise the main conclusions and recommendations reported in the 2022 PERA Roadmap. This roadmap highlights that fragmentation of data, knowledge and expertise across regulatory sectors results in suboptimal processes and hinders the implementation of integrative ERA approaches needed to better protect the environment. To advance ERA, we revisited the underlying assumptions of the current ERA paradigm; that chemical risks are generally assessed and managed in isolation with a substance-by-substance, realistic worst-case and tiered approach. We suggest optimising the use of the vast amount of information and expertise available with pesticides as a pilot area. It is recommended to as soon as possible adopt a systems-based approach, i.e. within the current regulatory framework, to spark a step-wise transition towards an ERA framed at a system level of ecological and societal relevance. Tangible systems-based and integrative steps are available. For instance, the rich sources of existing data for prospective and retrospective ERA of pesticides could be used to reality-benchmark existing and new ERA methods. To achieve these goals, collaboration among stakeholders across scientific disciplines and regulatory sectors must be strengthened., Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2024 Elsevier B.V. All rights reserved.)

The extremely high levels of genetic polymorphism within the human major histocompatibility complex (MHC) limit the usefulness of reference-based alignment methods for sequence assembly. We incorporate a short-read, de novo assembly algorithm into a workflow for novel application to the MHC. MHConstructor is a containerized pipeline designed for high-throughput, haplotype-informed, reproducible assembly of both whole genome sequencing and target capture short-read data in large, population cohorts. To-date, no other self-contained tool exists for the generation of de novo MHC assemblies from short-read data. MHConstructor facilitates wide-spread access to high-quality, alignment-free MHC sequence analysis., (© 2024. The Author(s).)

Background: While mindfulness-based interventions targeted toward parents (and families) in the U.S. offer promise for the treatment and prevention of youth psychological disorders, current research has established the underrepresentation of diverse participants in the research literature. The full extent of inequalities in the demographics of participation in parent mindfulness intervention is less understood., Objective: This study aimed to utilize a narrative literature review approach to examine and describe the degree to which research on mindful parenting interventions is inclusive of BIPOC (Black, Indigenous, and People of Color) communities, non-clinical samples (no diagnosed disorder), cultural adaptions, and skills specific to parenting., Methods: An electronic database search of US-based studies was undertaken for empirical studies that primarily focused on parent mindfulness interventions, which reported outcomes related to either parenting behaviors or child mental health outcomes. After a full-text review, the search resulted in 34 articles. A narrative literature review of the 34 studies was conducted to assess the inclusion of BIPOC communities, non-clinical samples, cultural adaptions, and skills specific to parenting., Results: This review found notable gaps in the degree to which mindful parenting research (1) included BIPOC populations in study samples; (2) focused on non-clinical samples; (3) adapted interventions to align with the cultural needs of participants; and (4) included the application of mindfulness to enhancing knowledge, skills, and behaviors specific to parenting., Conclusions: Given these gaps in the parent mindfulness literature, greater research attention is needed on mindful parenting interventions targeted toward BIPOC communities with no clinical diagnoses, interventions optimized by cultural adaptations, and explicit applications to parenting.

Scientists' limited understanding of tropical plant communities obscures the true extent of species loss caused by habitat destruction 1 . The Centinelan extinction hypothesis 2,3 posits an extreme but widely referenced scenario wherein forest clearing causes the immediate extinction of species known only from a single geographic location. It remains unclear, however, whether the disappearance of such microendemics reflects their global extinction or insufficient collection effort at larger scales. Here we test these hypotheses by synthesizing decades of floristic data from the heavily deforested tropical cloud forest (TCF) at Centinela, Ecuador. We find that 99% of its putative microendemics have been collected elsewhere and are not extinct. Our field work also revealed new species, highlighting the enduring conservation value of TCFs and the intense efforts required to illuminate such plant diversity 'darkspots' 4 . Field and herbarium research remain essential to the conservation action needed to forestall large-scale plant extinctions in Earth's beleaguered cloud forests., (© 2024. The Author(s), under exclusive licence to Springer Nature Limited.)

The functioning and richness of marine systems (and biological interactions such as parasitism) are continuously influenced by a changing environment. Using hierarchical modelling of species communities (HMSC), the presence and abundance of multiple parasite species of the black-spotted croaker, Protonibea diacanthus (Sciaenidae), was modelled against environmental measures reflecting seasonal change. Protonibea diacanthus were collected in three seasons across 2019–2021 from four locations within the waters of the Northern Territory, Australia. The length of P. diacanthus proved to have a strong positive effect on the abundance of parasite taxa and overall parasitic assemblage of the sciaenid host. This finding introduces potential implications for parasitism in the future as fish body size responds to fishing pressure and climate changes. Of the various environmental factors measured during the tropical seasons of northern Australia, water temperature and salinity changes were shown as potential causal factors for the variance in parasite presence and abundance, with changes most influential on external parasitic organisms. As environmental factors like ocean temperature and salinity directly affect parasite–host relationships, this study suggests that parasite assemblages and the ecological functions that they perform are likely to change considerably over the coming decades in response to climate change and its proceeding effects.

Background: SHR-1707 is a novel humanized anti-Aβ IgG1 monoclonal antibody that binds to Aβ fibrils and monomers to block the formation of Aβ plaques or to promote the microglial phagocytosis of Aβ. Preclinical studies showed that SHR-1707 reduced brain Aβ deposition in 5xFAD transgenic mice. Herein, we conducted two phase 1 studies to evaluate the safety, tolerability, pharmacokinetics (PK) and pharmacodynamics (PD) of a single intravenous dose of SHR-1707 in healthy adult subjects., Methods: Two randomized, double-blind, single-ascending-dose, phase 1 studies were conducted in China (Study CHN) and Australia (Study AUS). Study CHN consisted of 2 parts. In Part 1, eligible healthy young adults (18-45 years) were sequentially randomized 8:2 to receive SHR-1707 (five cohorts: 2, 6, 20, 40, and 60 mg/kg) or placebo in each cohort; in Part 2, elderly subjects (55-80 years) were randomized 8:4 to receive SHR-1707 (20 mg/kg) or placebo. A similar design was used in Study AUS, but with only healthy young adults enrolled across three dosing cohorts (2, 20, and 60 mg/kg)., Results: Sixty-two (part 1/2, n = 50/12; age range, 18-42/55-63 years) and 30 subjects (age range, 18-42 years) received SHR-1707 or placebo in Study CHN and Study AUS, respectively. In Study CHN, all treatment-related adverse events (TRAEs) were mild, with the most common being transient laboratory abnormalities. In Study AUS, TRAEs were mostly mild (1 moderate event each with SHR-1707/placebo); the most common TRAEs with SHR-1707 were dysgeusia and fatigue (8.3% each). In both studies, the exposure of SHR-1707 increased in a slightly greater than dose-proportional manner over the dose range of 2-60 mg/kg in young adults; there was a dose-dependent increase in plasma Aβ42 concentration following SHR-1707 administration compared with the placebo group. The safety and PK and PD profiles of SHR-1707 in the elderly subjects were consistent with the younger counterpart at the same dose level. No ethnic difference in safety, PK and PD of SHR-1707 was observed., Conclusions: A single intravenous dose of SHR-1707 at 2-60 mg/kg was safe and well tolerated in healthy young adult and elderly subjects. The PK and PD profiles are supportive for further clinical development., Trial Registration: NCT04973189 (retrospectively registered on Jul.21, 2021) and NCT04745104 (registered on Feb.6, 2021) on clinicaltrials.gov., (© 2024. The Author(s).)

Background: In ventricular tachycardia (VT), optimal substrate mapping strategies identifying arrhythmogenic sites are not established., Objectives: This study sought to evaluate multidirectional pacing on the distribution of specific conduction and repolarization metrics to localize re-entrant VT sites in a porcine infarct model., Methods: Substrate maps were created in 13 pigs with chronic myocardial infarction using the Advisor HD Grid (Abbott) during right ventricular (RV), left ventricular, biventricular pacing (BIV), and sinus rhythm (SR). Critical VT sites of early-, mid-, and late-diastolic signals were delineated. Vulnerable sites to re-entry were defined as sites of latest activation timing within and post-QRS complex, largest activation and activation-recovery interval gradients. Distances between the 20 most vulnerable sites and diastolic VT points were measured, and identification of VT points was assessed using the area under the receiver-operating characteristic curve., Results: A total of 34 VTs were mapped, and 48 sinus and pacing maps were obtained (10 BIV, 13 left ventricular, 13 RV, 12 SR). Late potential mapping in SR was taken as the established clinical standard for comparison. Latest activation time with BIV pacing provided the closest localization for VT isthmus (median 5.5 mm; IQR: 7.15 mm; P < 0.005). The gradient of activation-recovery interval using RV pacing had closest localization for VT exit and entrance (median 10.6 mm; IQR: 5.0 mm; P < 0.005 and 9.4 mm; IQR: 8.0 mm; P < 0.05). Global sensitivity and specificity analysis showed that gradient of activation-recovery interval in SR achieved the highest area under the receiver-operating characteristic curve, with similar results from the gradient of activation timing., Conclusions: Multidirectional pacing in combination with conduction and repolarization parameters enables better localization of VT diastolic critical sites vs SR late potentials., Competing Interests: Funding Support and Author Disclosures This study was supported with research funding from Abbott UK. Dr Lambiase is supported by UCL/UCLH Biomedicine National Institute for Health and Care Research, Barts BRC, and the Stephen Lyness Memorial Fund. All other authors have reported that they have no relationships relevant to the contents of this paper to disclose., (Copyright © 2024 American College of Cardiology Foundation. Published by Elsevier Inc. All rights reserved.)

Rapid advancements in deep learning over the past decade have fueled an insatiable demand for efficient and scalable hardware. Photonics offers a promising solution by leveraging the unique properties of light. However, conventional neural network architectures, which typically require dense programmable connections, pose several practical challenges for photonic realizations. To overcome these limitations, we propose and experimentally demonstrate Photonic Neural Cellular Automata (PNCA) for photonic deep learning with sparse connectivity. PNCA harnesses the speed and interconnectivity of photonics, as well as the self-organizing nature of cellular automata through local interactions to achieve robust, reliable, and efficient processing. We utilize linear light interference and parametric nonlinear optics for all-optical computations in a time-multiplexed photonic network to experimentally perform self-organized image classification. We demonstrate binary (two-class) classification of images using as few as 3 programmable photonic parameters, achieving high experimental accuracy with the ability to also recognize out-of-distribution data. The proposed PNCA approach can be adapted to a wide range of existing photonic hardware and provides a compelling alternative to conventional photonic neural networks by maximizing the advantages of light-based computing whilst mitigating their practical challenges. Our results showcase the potential of PNCA in advancing photonic deep learning and highlights a path for next-generation photonic computers., (© 2024. The Author(s).)

Background: Head trauma is responsible for significant morbidity and mortality in the pediatric trauma population. There are validated guidelines which indicate the necessity for computed tomography of the head (CTH), but the indication for a dedicated CT of the facial bones (CTF) is less clear. We sought to identify our population of head trauma patients who would clinically benefit from the addition of CTF., Methods: Using the electronic medical record, pediatric trauma patients who underwent CTH and/or CTF from 2016 to 2021 were identified. We collected information on demographics, traumatic mechanism, subspecialty consultation, and operative and procedural interventions., Results: 2117 pediatric patients were evaluated. A total of 372 patients received CTH and 173 patients received both CTH + CTF. Patients with CTH + CTF were older ( P < 0.001), involved in high-velocity blunt trauma ( P < 0.001), and had a longer length of stay ( P < 0.001). There were no fractures identified in 73 (42.2%) patients with both CTH + CTF. Of patients with fractures, there were 204 fractures identified and 73.0% (149/204) of fractures were seen on both the CTH + CTF. There were 19.6% (40/204) read only on CTF and 10 patients (5.7%) had a fracture requiring intervention. 8 of the 10 fractures requiring operative intervention were mandibular bone fractures., Discussion: Computed tomography of the head can be used as a screening tool for facial fractures. A negative CTH can eliminate the need for additional radiation from a CTF. Computed tomography of the facial bones will identify more fractures, but few requiring intervention. We suggest that CTF be limited to a subset of pediatric trauma patients with facial injury., Competing Interests: Declaration of Conflicting InterestsThe author(s) declared no potential conflicts of interest with respect to the research, authorship, and/or publication of this article.

Background: The need for frequent travel to a clinic could impair access to injectable antiretroviral therapy for persons living with human immunodeficiency virus type 1 (HIV-1) infection. We hypothesized that allowing persons receiving treatment with long-acting injectable cabotegravir plus rilpivirine (LA CAB/RPV) to receive and store the medication in their own refrigerator prior to in-home administration by a healthcare provider would be as safe and effective as receiving treatment in a clinic., Methods: Persons prescribed LA CAB/RPV in the Infectious Diseases clinic at the Medical University of South Carolina were offered enrollment in this non-randomized, observational study between August 2021 and December 2022. After in-clinic receipt of the initial LA CAB/RPV injection, participants chose to receive each subsequent injection over the following 12-months either in clinic or at home., Results: The 33 enrolled participants were primarily Black (64%), male (73%), and had a median age of 46. Three participants stopped LA CAB/RPV and transitioned to oral antiretroviral therapy due to allergy (n = 1), loss of virologic suppression (n = 1), and visit adherence (n = 1) concerns. A comparable number of participants received treatment primarily in clinic (n = 18) relative to at home (n = 15). Injection site pain/soreness was common (52% of injections) but did not differ between groups. There were no differences in safety or efficacy between groups and both groups reported high treatment satisfaction. All participants were virologically suppressed and retained in care at the end of the study., Conclusions: At-home administration of LA CAB/RPV by a healthcare provider was comparably safe, effective, and associated with high participant satisfaction relative to in-clinic administration., Competing Interests: Potential conflicts of interest . S. E. K. and E. G. M. have served on an expert panel for ViiV Healthcare. V. F. has served on an implementation science advisory panel for ViiV Healthcare and FHI 360 receives ViiV support through in-kind product donations for other studies. No other authors have conflicts to report. All authors have submitted the ICMJE Form for Disclosure of Potential Conflicts of Interest. Conflicts that the editors consider relevant to the content of the manuscript have been disclosed., (© The Author(s) 2024. Published by Oxford University Press on behalf of Infectious Diseases Society of America. All rights reserved. For commercial re-use, please contact reprints@oup.com for reprints and translation rights for reprints. All other permissions can be obtained through our RightsLink service via the Permissions link on the article page on our site—for further information please contact journals.permissions@oup.com.)

Background: Digital and mobile health interventions using personalization via reinforcement learning algorithms have the potential to reach large number of people to support physical activity and help manage diabetes and depression in daily life., Objective: The Diabetes and Mental Health Adaptive Notification and Tracking Evaluation (DIAMANTE) study tested whether a digital physical activity intervention using personalized text messaging via reinforcement learning algorithms could increase step counts in a diverse, multilingual sample of people with diabetes and depression symptoms., Methods: From January 2020 to June 2022, participants were recruited from 4 San Francisco, California-based public primary care clinics and through web-based platforms to participate in the 24-week randomized controlled trial. Eligibility criteria included English or Spanish language preference and a documented diagnosis of diabetes and elevated depression symptoms. The trial had 3 arms: a Control group receiving a weekly mood monitoring message, a Random messaging group receiving randomly selected feedback and motivational text messages daily, and an Adaptive messaging group receiving text messages selected by a reinforcement learning algorithm daily. Randomization was performed with a 1:1:1 allocation. The primary outcome, changes in daily step counts, was passively collected via a mobile app. The primary analysis assessed changes in daily step count using a linear mixed-effects model. An a priori subanalysis compared the primary step count outcome within recruitment samples., Results: In total, 168 participants were analyzed, including those with 24% (40/168) Spanish language preference and 37.5% (63/168) from clinic-based recruitment. The results of the linear mixed-effects model indicated that participants in the Adaptive arm cumulatively gained an average of 3.6 steps each day (95% CI 2.45-4.78; P<.001) over the 24-week intervention (average of 608 total steps), whereas both the Control and Random arm participants had significantly decreased rates of change. Postintervention estimates suggest that participants in the Adaptive messaging arm showed a significant step count increase of 19% (606/3197; P<.001), in contrast to 1.6% (59/3698) and 3.9% (136/3480) step count increase in the Random and Control arms, respectively. Intervention effectiveness differences were observed between participants recruited from the San Francisco clinics and those recruited via web-based platforms, with the significant step count trend persisting across both samples for participants in the Adaptive group., Conclusions: Our study supports the use of reinforcement learning algorithms for personalizing text messaging interventions to increase physical activity in a diverse sample of people with diabetes and depression. It is the first to test this approach in a large, diverse, and multilingual sample., Trial Registration: ClinicalTrials.gov NCT03490253; https://clinicaltrials.gov/study/NCT03490253., International Registered Report Identifier (irrid): RR2-10.1136/bmjopen-2019-034723., (©Adrian Aguilera, Marvyn Arévalo Avalos, Jing Xu, Bibhas Chakraborty, Caroline Figueroa, Faviola Garcia, Karina Rosales, Rosa Hernandez-Ramos, Chris Karr, Joseph Williams, Lisa Ochoa-Frongia, Urmimala Sarkar, Elad Yom-Tov, Courtney Lyles. Originally published in the Journal of Medical Internet Research (https://www.jmir.org), 08.10.2024.)

Human activities can increase sediment delivery to streams, changing the composition, distribution, and abundance of stream aquatic life. Few U.S. states have numeric water quality standards for streambed sediment under the Clean Water Act, so managers often need to develop local application-specific benchmarks. This study developed stream surface fine sediment <2 mm (sand and fines, SF) and macroinvertebrate fine sediment biotic index (FSBI) benchmarks and an application framework to test for sediment-induced macroinvertebrate community composition changes in 1 st -4 th order Idaho streams. FSBI reference benchmarks were calculated as the 25 th percentile FSBI value among reference sites within three ecoregion-based site classes. Two approaches were used to develop SF benchmarks. Quantile regression was used to define reach-specific SF benchmarks representing an upper bound value expected under reference conditions. In addition, logistic regression was used to predict SF values with 50% and 75% probability that FSBI is worse than reference within each stream order and site class. The strength of association between SF benchmarks and macroinvertebrate community condition was evaluated by calculating relative risk using multiple datasets and examining responses of multiple macroinvertebrate indicators to SF benchmark status. SF reference benchmarks generally had stronger associations with poor macroinvertebrate condition than SF stressor-response benchmarks. Across datasets and macroinvertebrate indicators, poor macroinvertebrate condition was 1.8-3 times more likely when SF reference benchmarks were exceeded than when achieved. We propose rating the strength of evidence for a surface fine sediment-induced macroinvertebrate community composition change at the sample event scale as 'unlikely' if both SF and FSBI reference benchmarks are achieved, having 'mixed evidence' if only one reference benchmark is achieved, and 'likely' if both reference benchmarks are not achieved. We recommend combining ratings with other relevant data in a weight-of-evidence approach to assess if sediment impairs aquatic life., Competing Interests: The authors declare that they have no competing interests. Jason Williams was employed at the Idaho Department of Environmental Quality when the research was performed and now is employed by The Cadmus Group. James Efta is employed by the United States Forest Service., (© 2024 Williams and Efta.)

Background: People with severe mental illness (SMI) have worse physical health than the general population. There is evidence that support from volunteers can help the mental health of people with SMI, but little evidence regarding the support they can give for physical health., Aims: To evaluate the feasibility of an intervention where volunteer 'Health Champions' support people with SMI in managing their physical health., Method: A feasibility hybrid randomised controlled trial conducted in mental health teams with people with SMI. Volunteers delivered the Health Champions intervention. We collected data on the feasibility of delivering the intervention, and clinical and cost-effectiveness. Participants were randomised by a statistician independent of the research team, to either having a Health Champion or treatment as usual. Blinding was not done., Results: We recruited 48 participants: 27 to the intervention group and 21 to the control group. Data were analysed for 34 participants. No changes were found in clinical effectiveness for either group. Implementation outcomes measures showed high acceptability, feasibility and appropriateness, but with low response rates. No adverse events were identified in either group. Interviews with participants found they identified changes they had made to their physical health. The cost of implementing the intervention was £312 per participant., Conclusions: The Health Champion intervention was feasible to implement, but the implementation of the study measures was problematic. Participants found the intervention acceptable, feasible and appropriate, and it led them to make changes in their physical health. A larger trial is recommended, with tailored implementation outcome measures.

Introduction: Research has found differences in processes and outcomes of care between people in ethnic minorities and White British populations in some clinical conditions, although findings have been mixed. The Building an understanding of Ethnic minority people's Service Use Relating to Emergency care for injuries study is investigating differences in presentation, experience and health outcomes between people from ethnic minorities and White British people who seek emergency health care for injury., Objective: Our aim was to consult with stakeholders to define measurable outcomes available in routine ambulance and emergency department data; to assess the appropriateness of existing outcome measures for ethnic minorities and White British people; and to identify any gaps., Method: Clinicians, public contributors, researchers, people from the third sector, public health, healthcare inclusion were invited to join an online workshop to discuss routine outcomes., Results: Twenty participants attended the stakeholder consultation, with only one being a public contributor, a limitation. Eleven were from a minority ethnic background and seven were female. The integrated list of outcomes included 25 items, combining routine outcomes from the Building an understanding of Ethnic minority people's Service Use Relating to Emergency care for injuries protocol and literature ( n  = 17) with additional outcomes ( n  = 8). Notably, the initial list lacked provisions for safeguarding referrals and cases of treatment refusal, which were new additions. Safety concerns arose due to the lack of safeguarding referrals, treatment refusal and self-discharge. Factors such as pre-existing health conditions, injury location and experiences of discrimination were identified as possible influences on care quality and waiting times for ethnic minority patients., Conclusion: Although the number of stakeholders taking part in our consultation was low, their participation identified outcomes not found in routine data, supporting the adoption of a mixed-methods approach to answer our research questions. A future consultation could look to include more public members and wider range of clinicians including those who work in safeguarding and rehabilitation services., Funding: This article presents independent research funded by the National Institute for Health and Care Research (NIHR) Health and Social Care Delivery Research programme as award number NIHR132744.

Previous research has outlined evident disparities in the prevalence of chronic conditions among African Americans compared to other groups, with low-income African American men disproportionately affected by almost every disorder. Self-management programs are useful tools for managing chronic disorders beyond the doctor's office. This monograph provides a detailed looking into the current state of the research on low-income African American men with chronic health conditions. An intersectional approach is used to provide a nuanced synthesis of relevant literature. The project outlines the need for programs designed to engage low-income African American men with skills, resources, and tools for managing chronic conditions. Authors argue that improvements to traditional self-management programs can be realized by emphasizing culture, including end-users in the creation of programs, and offering culturally tailored strategies to improve health. Thus, any targeted program must include culturally detailed information about nutrition, exercise, stress, mental health, and leveraging social support.

Objective: We assessed the association of early statin initiation with inpatient mortality among hospitalised COVID-19 patients., Design, Setting and Participants: This observational study emulated a hypothetical target trial using electronic health records data from Northwestern Medicine Health System, Illinois, 2020-2022. We included patients who were ≥40 years, admitted ≥48 hours for COVID-19 from March 2020 to August 2022 and had no evidence of statin use before admission., Interventions: Individuals who initiated any statins within 48 hours of admission were compared with individuals who did not initiate statins during this period., Primary Outcome Measures: Inpatient mortality at hospital days 7, 14, 21 and 28 were determined using hospital records. Risk differences between exposure groups were calculated using augmented inverse propensity weighting (AIPW) with SuperLearner., Results: A total of 8893 individuals (24.5% early statin initiators) were included. Early initiators tended to be older, male and have higher comorbidity burdens. Unadjusted day 28 mortality was higher in early initiators (6.0% vs 3.6%). Adjusted analysis showed slightly higher inpatient mortality risk at days 7 (RD: 0.5%, 95% CI: 0.2 to 0.8) and 21 (RD: 0.6%, 95% CI: 0.04 to 1.1), but not days 14 (RD: 0.4%, 95% CI: -0.03 to 0.9) and 28 (RD: 0.4%, 95% CI: -0.2 to 1.1). Sensitivity analyses using alternative modelling approaches showed no difference between groups., Conclusions: Early statin initiation was not associated with lower mortality contrasting with findings of previous observational studies. Trial emulation helped in identifying and addressing sources of bias incompletely addressed by previous work. Statin use may be indicated for other conditions but not COVID-19., Competing Interests: Competing interests: LP receives funds for unrelated research from Omron Healthcare Co. Other authors have no other conflicts to declare., (© Author(s) (or their employer(s)) 2024. Re-use permitted under CC BY-NC. No commercial re-use. See rights and permissions. Published by BMJ.)

The essential Drosophila RNA-binding protein Brain Tumor (Brat) represses specific genes to control embryogenesis and differentiation of stem cells. In the brain, Brat functions as a tumor suppressor that diminishes neural stem cell proliferation while promoting differentiation. Though important Brat-regulated target mRNAs have been identified in these contexts, the full impact of Brat on gene expression remains to be discovered. Here, we identify the network of Brat-regulated mRNAs by performing RNA sequencing (RNA-seq) following depletion of Brat from cultured cells. We identify 158 mRNAs, with high confidence, that are repressed by Brat. De novo motif analysis identified a functionally enriched RNA motif in the 3' untranslated regions (UTRs) of Brat-repressed mRNAs that matches the biochemically defined Brat binding site. Integrative data analysis revealed a high-confidence list of Brat-repressed and Brat-bound mRNAs containing 3'UTR Brat binding motifs. Our RNA-seq and reporter assays show that multiple 3'UTR motifs promote the strength of Brat repression, whereas motifs in the 5'UTR are not functional. Strikingly, we find that Brat regulates expression of glycolytic enzymes and the vacuolar ATPase complex, providing new insight into its role as a tumor suppressor and the coordination of metabolism and intracellular pH., (Published by Oxford University Press on behalf of Nucleic Acids Research 2024.)

For the past two centuries, the use of traditional light microscopy to examine tissues to make diagnoses has remained relatively unchanged. While the fundamental concept of tissue slide analysis has stayed the same, our interaction with the microscope is undergoing significant changes. Digital pathology (DP) has gained momentum in veterinary science and is on the verge of becoming a vital tool in diagnostics, research and education. Many diagnostic laboratories have incorporated DP as a critical part of their workflows. Innovations in DP and whole slide image technology have made telediagnosis (the process of transmitting digital clinical data using telecommunication networks for distant diagnosis) more accessible, leading to improved patient care through streamlining of workflows and greater accessibility of second opinions. The integration of machine learning and artificial intelligence and human-in-the-loop protocols for DP workflows will further the development of computer-aided diagnosis and prognostic tools. Despite its present weaknesses, DP will progressively aid veterinary clinicians and pathologists in delivering more accurate and reliable diagnoses. Consistent incorporation of DP frontline advancements into routine veterinary diagnostic pipelines will assist in improving current tools and help prepare pathologists for the progression of digitalization in the field., Competing Interests: Declaration of competing interests KA's PhD is supported by IDEXX Laboratories Ltd in conjunction with the BBSRC. SLC is an employee of IDEXX Laboratories Ltd. JW declared no conflicts of interest in relation to the research, authorship or publication of this article., (Crown Copyright © 2024. Published by Elsevier Ltd. All rights reserved.)

Background: Andexanet alfa (AA) is the only FDA-approved reversal agent for apixaban and rivaroxaban (DOAC). There are no studies comparing its efficacy with four-factor prothrombin complex concentrate (PCC). This study aimed to compare PCC to AA for DOAC reversal, hypothesizing noninferiority of PCC., Methods: We performed a retrospective, noninferiority multicenter study of adult patients admitted from July 1, 2018, to December 31, 2019, who had taken a DOAC within 12 hours of injury, were transfused red blood cells (RBCs) or had traumatic brain injury, and received AA or PCC. Primary outcome was PRBC unit transfusion. Secondary outcome with intensive care unit length of stay. MICE imputation was used to account for missing data and zero-inflated Poisson regression was used to account for an excess of zero units of RBC transfused. Two units difference in RBC transfusion was selected as noninferior., Results: Results: From 263 patients at 10 centers, 77 (29%) received PCC and 186 (71%) AA. Patients had similar transfusion rates across reversal treatment groups (23.7% AA vs. 19.5% PCC) with median transfusion in both groups of 0 RBC. According to the Poisson component, PCC increases the amount of RBC transfusion by 1.02 times (95% confidence interval, 0.79-1.33) compared with AA after adjusting for other covariates. The average amount of RBC transfusion (nonzero group) is 6.13. Multiplying this number by the estimated rate ratio, PCC is estimated to have an increase RBC transfusion by 0.123 (95% confidence interval, 0.53-2.02) units compared with AA., Conclusion: PCC appears noninferior to AA for reversal of DOACs for RBC transfusion in traumatically injured patients. Additional prospective, randomized trials are necessary to compare PCC and AA for the treatment of hemorrhage in injured patients on DOACs., Level of Evidence: Therapeutic/Care Management; Level III., (Copyright © 2024 Wolters Kluwer Health, Inc. All rights reserved.)

In adults, individual differences in procedural learning (PL) are associated with white matter organization within the basal ganglia-cerebellar circuit. However, no research has examined whether this circuitry is related to individual differences in PL during childhood. Here, 28 children (M age  = 10.00 ± 2.31, 10 female) completed the serial reaction time (SRT) task to measure PL, and underwent structural magnetic resonance imaging (MRI). Fixel-Based Analysis was performed to extract specific measures of white matter fiber density (FD) and fiber cross-section (FC) from the superior cerebellar peduncles (SCP) and the striatal premotor tracts (STPMT), which underlie the fronto-basal ganglia-cerebellar system. These fixel metrics were correlated with the 'rebound effect' from the SRT task - a measure of PL proficiency which compares reaction times associated with generating a sequence, to random trials. While no significant associations were observed at the fixel level, a significant positive association was observed between average FD in the right SCP and the rebound effect, with a similar trend observed in the left SCP. No significant effects were detected in the STPMT. Our results indicate that, like in adults, microstructure of the basal ganglia-cerebellar circuit may explain individual differences in childhood PL., Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2024 The Author(s). Published by Elsevier Inc. All rights reserved.)

Aims: Parameters derived from reservoir-excess pressure analysis have been demonstrated to predict cardiovascular events. Thus, altered reservoir-excess pressure parameters could have a detrimental effect on highly-perfused organs like the heart. We aimed to cross-sectionally determine whether reservoir-excess pressure parameters were associated with N-terminal pro-brain-type natriuretic peptide (NT-proBNP) in older adults., Methods: We studied 868 older adults with diverse cardiovascular risk. Reservoir-excess pressure parameters were obtained through radial artery tonometry including reservoir pressure integral, peak reservoir pressure, excess pressure integral (INTXSP), systolic rate constant (SRC) and diastolic rate constant (DRC). Plasma levels of NT-proBNP, as a biomarker of cardiac overload, were analysed by the Proximity Extension Assay technology., Results: Multivariable linear regression analyses revealed that all reservoir-excess pressure parameters studied were associated with NT-proBNP after adjusting for age and sex. After further adjustments for conventional cardiovascular risk factors, INTXSP [β = 0.191 (95% confidence interval, CI: 0.099, 0.283), P < 0.001], SRC [β = -0.080 (95% CI: -0.141, -0.019), P = 0.010] and DRC [β = 0.138 (95% CI: 0.073, 0.202), P < 0.001] remained associated with NT-proBNP. Sensitivity analysis found that there were occasions where the association between SRC and NT-proBNP was attenuated, but both INTXSP and DRC remained consistently associated with NT-proBNP., Conclusions: The observed associations between reservoir-excess pressure parameters and NT-proBNP suggest that altered reservoir-excess pressure parameters may reflect an increased load inflicted on the left ventricular cardiomyocytes and could have a potential to be utilized in the clinical setting for cardiovascular risk stratification., (© 2024 The Author(s). ESC Heart Failure published by John Wiley & Sons Ltd on behalf of European Society of Cardiology.)

Great interest exists in developing a transgenic trait that controls the economically important soybean ( Glycine max ) pest, soybean cyst nematode (SCN, Heterodera glycines ), due to its adaptation to native resistance. Soybean plants expressing the Bacillus thuringiensis delta-endotoxin, Cry14Ab, were recently demonstrated to control SCN in both growth chamber and field testing. In that communication, ingestion of the Cry14Ab toxin by SCN second stage juveniles (J2s) was demonstrated using fluorescently labeled Cry14Ab in an in vitro assay. Here, we show that consistent with expectations for a Cry toxin, Cry14Ab has a mode of action unique from the native resistance sources Peking and PI 88788. Further, we demonstrate in planta the ingestion and localization of the Cry14Ab toxin in the midgut of nematodes feeding on roots expressing Cry14Ab using immunogold labeling and transmission electron microscopy. We observed immunolocalization of the toxin and resulting intestinal damage primarily in the microvillus-like structure (MvL)-containing region of the midgut intestine but not in nematodes feeding on roots lacking toxin. This demonstrated that Cry14Ab was taken up by the J2 SCN, presumably through the feeding tube within the plant root cell that serves as its feeding site. This suggests that relatively large proteins can be taken up through the feeding tube. Electron microscopy showed that Cry14Ab caused lysis of the midgut MvL membrane and eventual degradation of the MvL and the lysate, forming particulate aggregates. The accumulated electron-dense aggregate in the posterior midgut intestine was not observed in SCN in nonCry14Ab-expressing plants. [Formula: see text] Copyright © 2024 The Author(s). This is an open access article distributed under the CC BY-NC-ND 4.0 International license., Competing Interests: R.H.B. worked on this project as a paid consultant for the BASF Corporation (BASF). M.T.M., J.W., and J.D. are employed by BASF, whose products are evaluated in this study. The remaining authors declare no conflict of interest.

Purpose/Objective: Frequent consumption of fermented carbohydrates and bottle feeding contribute to the development of early childhood caries (ECC). There are no substantial findings on the effects of breastfeeding patterns on oral health conditions in children in the United States. We aimed to assess the nexus between exclusive breastfeeding during the first 6 months and oral health disorders, namely toothache, decayed teeth, or unfilled cavities in early childhood. Materials and Methods: Design: Cross-sectional epidemiologic design of nationally representative data collected via telephone surveys in the United States was utilized. Setting: National Survey of Children's Health, 2012 Participants: Population-based random sample of parents/guardians of 24,655 children aged 6 months to 5 years. Main Outcome and Measure: The primary outcome was the presence of oral health disorders (OHD) in children, defined as the parent-reported occurrence of one or more of the following conditions in the past 12 months: toothache, decayed teeth, or an unfilled cavity. This was assessed through a single composite question in the survey, asking parents/guardians if their child had experienced any of these specific oral health issues within the previous year with a binary (yes/no) response option. Results: Among 24,655 children aged 6 months to 5 years, 2392 (9.7%) had experienced an oral health disorder (OHD) in the previous 12 months. In unadjusted analysis, children exclusively breastfed for 6 months were 28% less likely to present with OHD compared to never-breastfed children (OR = 0.72, 95% CI, 0.52-0.98). However, after adjusting for key factors, including maternal health and race/ethnicity, this association was no longer statistically significant (aOR = 1.11, 95% CI 0.79-1.57). Significant predictors of OHD included maternal health (aOR for fair/poor vs. excellent/very good maternal health = 1.79, 95% CI 1.08-2.69) and race/ethnicity, with a higher prevalence among non-Hispanic Black (12.9%) and multi-racial children (12.6%) compared to non-Hispanic White children (7.7%). Conclusions and Relevance: While exclusive breastfeeding for the first six months of life was not found to be a significant predictor of pediatric oral health outcomes after adjustment, maternal health and race/ethnicity were significant determinants of oral health disorders. These findings underscore the importance of comprehensive healthcare approaches that consider maternal well-being and socio-demographic factors. Future research should explore interventions targeting these factors to improve pediatric oral health outcomes.

Background: The Stop the Bleed campaign gives bystanders an active role in prehospital hemorrhage control. Whether extending bystanders' role to private vehicle transport (PVT) for urban penetrating trauma improves survival is unknown, but past research has found benefit to police and PVT. We hypothesized that for penetrating trauma in an urban environment, where prehospital procedures have been proven harmful, PVT improves outcomes compared to any EMS or advanced life support (ALS) transport. Methods: Post-hoc analysis of an EAST multicenter trial was performed on adult patients with penetrating torso/proximal extremity trauma at 25 urban trauma centers from 5/2019-5/2020. Patients were allocated to PVT and any EMS or ALS transport using nearest neighbor propensity score matching. Univariate analyses included Wilcoxon signed rank or McNemar's Test and logistic regression. Results: Of 1999 penetrating trauma patients in urban settings, 397 (19.9%) had PVT, 1433 (71.7%) ALS transport, and 169 (8.5%) basic life support (BLS) transport. Propensity matching yielded 778 patients, distributed equally into balanced groups. PVT patients were primarily male (90.5%), Black (71.2%), and sustained gunshot wounds (68.9%). ALS transport had significantly higher ED mortality (3.9% vs 1.9%, P = 0.03). There was no difference in in-hospital mortality rate, hospital LOS, or complications for all EMS or ALS only transport patients. Conclusion: Compared to PVT, ALS, which provides more prehospital procedures than BLS, provided no survival benefit for penetrating trauma patients in urban settings. Bystander education incorporating PVT for early arrival of penetrating trauma patients in urban settings to definitive care merits further investigation., Competing Interests: Declaration of Conflicting InterestsThe author(s) declared no potential conflicts of interest with respect to the research, authorship, and/or publication of this article.

When considering health professionals' requirements and responsibilities, competence is a complex concept that extends beyond knowledge to encompass understanding, application, technical skills, problem-solving, and clinical judgment. Rural clinical placements provide a rich learning environment for students to improve their competencies, self-esteem, and preparedness for practice (PFP). This scoping review aimed to identify pre-registration health students' perspectives on rural placement regarding competency and skill development, and enablers and barriers to learning. The methodology outlined by the Joanna Briggs Institute was followed. Out of 1186 records (366 duplicates), 821 were screened by title and abstract, 59 underwent full-text screening and 18 studies were included. Over half the studies included medicine students (n = 11). Reported competencies predominantly focused on self-assessed confidence regarding clinical skills. The reported barriers and enablers to learning highlighted the complexity of the placement experience and the importance of interpersonal factors, learner engagement and the supervisor's role. The review identified a gap in the literature pertaining to student perspectives of competencies and skills not assessed or experienced as well as a lack of standardised measures for PFP. The identified enablers and barriers provide suggestions for rural placement design and emphasise the importance of the student learning experience. Future research could include multiple health disciplines and specific methodologies to identify health students' perspectives regarding the development of competency, relatedness and autonomy, that is how to support health students to think, feel and act like health professionals., (© 2024. The Author(s).)

Colorectal cancer (CRC) is the third most commonly occurring cancer in the United States, with higher incidence rates among Black populations. Groundwater concentrations of natural radionuclides uranium and radium have seldom been investigated in relation to CRC despite their known carcinogenicity. We investigate spatial patterns of CRC by race, and in relation to groundwater concentrations of uranium and radium, testing the hypothesis that uranium and radium in groundwater might differentially contribute to incident CRC in Black and White populations in counties of Georgia, USA. Black populations showed a higher incidence of CRC than White populations; the median incident rate difference was 9.23 cases per 100,000 (95% CI: 2.14, 19.40). Spatial cluster analysis showed high incidence clusters of CRC in similar regions for Black and White populations. Linear regression indicated there are, on average, 1-2 additional cases of colorectal cancer in counties with higher levels of radium in their groundwater, irrespective of race. Uranium was not associated with CRC. This ecologic study suggests that radium in groundwater may be linked with increased incidence of CRC, although it did not explain higher CRC incidence rates in Black populations. Further studies are needed to verify this association given the inherent limitations in the ecologic study design and the crude exposure assessment.

Background: Varicella zoster virus (VZV) is the causative agent for chickenpox and herpes zoster (HZ, shingles). HZ is a debilitating disease affecting elderly and immunocompromised populations. Glycoprotein E (gE) is indispensable for viral replication and cell-to-cell spread and is the primary target for anti-VZV antibodies. Importantly, gE is the sole antigen in Shingrix, a highly efficacious, AS01 B -adjuvanted vaccine approved in multiple countries for the prevention of HZ, yet the three-dimensional (3D) structure of gE remains elusive. Objectives : We sought to determine the structure of VZV gE and to understand in detail its interactions with neutralizing antibodies. Methods : We used X-ray crystallography and cryo-electron microscopy to elucidate structures of gE bound by recombinant Fabs of antibodies previously elicited through vaccination with Zostavax, a live, attenuated vaccine. Results : The 3D structures resolve distinct central and C-terminal antigenic domains, presenting an array of diverse conformational epitopes. The central domain has two beta-sheets and two alpha helices, including an IgG-like fold. The C-terminal domain exhibits 3 beta-sheets and an Ig-like fold and high structural similarity to HSV1 gE. Conclusions : gE from VZV-infected cells elicits a human antibody response with a preference for the gI binding domain of gE. These results yield insights to VZV gE structure and immunogenicity, provide a framework for future studies, and may guide the design of additional herpesvirus vaccine antigens. Teaser: Structures of varicella zoster virus glycoprotein E reveal distinct antigenic domains and define epitopes for vaccine-elicited human antibodies.

Background: Malaria remains a major public health problem, especially among children in sub-Saharan Africa. Knowledge of malaria parasite prevalence informs targeted interventions and helps to monitor the effectiveness of those interventions. This study aimed to determine prevalence and factors associated with malaria in children aged 6 months to 10 years in the Greater Accra Region of Ghana., Methods: A community-based cross-sectional study was conducted among 8,741 children aged 6-59 months and 8,292 children aged 5-10 years in all 29 districts of the Greater Accra Region of Ghana in October 2020. Systematic random sampling was used to select communities, households and study participants. A structured questionnaire was used to collect data from caregivers. Rapid diagnostic test kits were used to determine the presence of malaria parasites in blood samples collected by fingerprick. Factors associated with malaria RDT-positivity were determined using multivariate logistic regression analysis., Results: Of 8727 children aged 6-59 months and 8279 aged 5-10 years from whom blood samples were obtained, positive results were obtained for 289 (3.3%; 95% CI 3.0-3.7) and 406 (4.9%; 95% CI 4.5-5.4) respectively. Malaria parasite prevalence in the districts ranged from 0.9 to 10.7% and 1.4-15.0% in children aged 6-59 months and 5-10 years respectively. Factors associated with increased odds of malaria included higher age (AOR = 1.43; 95% CI 1.14-1.71), and living in households without nets on the windows (AOR 1.64; 95% CI 1.10-2.45). On the other hand, living in households located in urban communities was associated with a lower risk of malaria (AOR 0.56; 95% CI 0.40-0.78)., Conclusion: The average prevalence of malaria in the Greater Accra Region is low compared with other regions. However, there are potential hotspots that need to be targeted with appropriate interventions to accelerate the drive towards malaria elimination., (© 2024. The Author(s).)

The World Health Organization has identified antibiotic resistance as one of the three greatest threats to human health. The need for antibiotics is a pressing matter that requires immediate attention. Here, computer-aided drug design is used to develop a structurally unique antibiotic family targeting holo-acyl carrier protein synthase (AcpS). AcpS is a highly conserved enzyme essential for bacterial survival that catalyzes the first step in lipid synthesis. To the best of our knowledge, there are no current antibiotics targeting AcpS making this drug development program of high interest. We synthesize a library of > 700 novel compounds targeting AcpS, from which 33 inhibit bacterial growth in vitro at ≤ 2 μg/mL. We demonstrate that compounds from this class have stand-alone activity against a broad spectrum of Gram-positive organisms and synergize with colistin to enable coverage of Gram-negative species. We demonstrate efficacy against clinically relevant multi-drug resistant strains in vitro and in animal models of infection in vivo including a difficult-to-treat ischemic infection exemplified by diabetic foot ulcer infections in humans. This antibiotic family could form the basis for several multi-drug-resistant antimicrobial programs., (© 2024. The Author(s).)

Objective: To characterize mortality after hospital discharge in cohorts with and without anorexia nervosa (AN)., Methods: We obtained data for all hospitalizations for psychiatric reasons in Canada (except Quebec) between April 1, 2006, and March 31, 2021 (n = 1.3 million admissions). Cases of AN were identified using ICD-10 (F50.0 and F50.1) codes. First admissions during this interval for AN and other psychiatric conditions were linked to vital statistics data. Mortality was characterized through cross-tabulation, Cox proportional hazards models, and competing cause regression., Results: After adjustment for age and sex, there was no significant difference in mortality between AN and those with other psychiatric conditions (HR = 1.04; p = 0.644). Among AN admissions, 25% (95% CI 18.6-31.4) of deaths were attributed to psychiatric conditions (ICD-F codes), with 88% of these (comprising 22% of all deaths in the AN group) having AN itself identified as the underlying cause of death. In contrast, only 8% of deaths among non-AN admissions were attributed to a mental disorder., Discussion: Prevention of premature mortality in the general psychiatric population emphasizes modification of metabolic (e.g., hyperlipidemia) and lifestyle-related (e.g., sedentary behavior) risk factors. However, as AN itself makes a major contribution to mortality, specialized preventive strategies may be required., (© 2024 The Author(s). International Journal of Eating Disorders published by Wiley Periodicals LLC.)

Per- and polyfluoroalkyl substances (PFAS), often referred to as "forever chemicals", are a class of man-made, extremely stable chemicals, which are widely used in industrial and commercial applications. Exposure to some PFAS is now known to be detrimental to human health. By virtue of PFAS long residence times, they are widely detected in the environment, including remote locations such as the Arctics, where the origin of the PFAS is poorly understood. It has been suggested that PFAS may be transported through contaminated waters, leading to accumulation in coastal areas, where they can be aerosolised via sea spray, thereby extending their geographical distribution far beyond their original source regions. The aim of this work is to investigate, for the first time, whether "forever chemicals" could be transported to areas considered to be pristine, far from coastal sites. This study was performed at the Amazonian Tall Tower Observatory (ATTO), a unique remote site situated in the middle of the Amazon rainforest, where a restricted PFAS, perfluorooctanoic acid (PFOA), was observed with concentrations reaching up to 2 pg/m 3 . A clear trend of increasing concentration with sampling height was observed and air masses from the south over Manaus had the highest concentrations. Atmospheric lifetime estimations, removal mechanisms supported by measurements at two heights (320 and 42 m above the rainforest), and concentration spikes indicated a long-range transport of PFOA to pristine Amazon rainforest. Potential sources, including industrial activities in urban areas, were explored, and historical fire management practices considered. This research presents the first measurements of PFAS in the atmosphere of Amazon rainforest. Remarkably, even in this remote natural environment, appreciable levels of PFAS can be detected. This study provides valuable insights into the long-range transport of the anthropogenic "forever chemical" into a remote natural ecosystem and should raise awareness of potential environmental implications., Competing Interests: Declaration of competing interest The authors declare they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2024 The Authors. Published by Elsevier B.V. All rights reserved.)