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DNA barcoding is a promising technology for the simultaneous analysis of genetic and phenotypic heterogeneity. Here, the authors combine DNA barcoding and single-cell RNA-seq to study heterogeneity, progression and response to therapy in B-cell acute lymphoblastic leukaemia patient-derived xenografts.

The vascularization of tissue grafts is critical for maintaining viability of the cells within a transplanted graft. A number of strategies are currently being investigated including very promising microfluidics systems. Here, we explored the potential for generating a vasculature-patterned endothelial cells that could be integrated into distinct layers between sheets of primary cells. Bioinspired from the leaf veins, we generated a reverse mold with a fractal vascular-branching pattern that models the unique spatial arrangement over multiple length scales that precisely mimic branching vasculature. By coating the reverse mold with 50 μg ml-1 of fibronectin and stamping enabled selective adhesion of the human umbilical vein endothelial cells (HUVECs) to the patterned adhesive matrix, we show that a vascular-branching pattern can be transferred by microcontact printing. Moreover, this pattern can be maintained and transferred to a 3D hydrogel matrix and remains stable for up to 4 d. After 4 d, HUVECs can be observed migrating and sprouting into Matrigel. These printed vascular branching patterns, especially after transfer to 3D hydrogels, provide a viable alternative strategy to the prevascularization of complex tissues.

Aims: To analyse the concept of eating experiences in people living with dementia. Design: Rodgers' evolutionary method of concept analysis was used as a framework for the paper. Data Sources: The literature was searched using electronic databases PubMed, Google Scholar, CINHAL, PsycInfo, Web of Science, Embase and Elsevier databases. These databases cover a variety of disciplines, including but not limited to nursing, medicine and occupational therapy. The relevant literature published from 1989 to April 2023 was thoroughly examined. Any quantitative or qualitative studies published in English focused on eating or dining experiences in people with dementia were included. Review Methods: Rodgers' evolutionary method for concept analysis was used. The attributes, antecedents, consequences and case examples of the concept were identified. Results: Twenty‐two articles met the inclusion criteria, identifying key attributes of self‐connection, the special journey of life and self‐interpretation. Antecedents, as framed by the socio‐ecological model, were categorized to represent intrapersonal (personal preferences, individual culture, mealtime routines), interpersonal (social interaction) and environmental (dining room environment, policies) factors. Consequences were divided into external (nutritional health, physical health and quality of life) and internal (personhood, autonomy and independence, dignity and feeling valued and mental well‐being) domains. Conclusion: A theoretical definition and conceptual model of eating experiences in people living with dementia was developed. The identified attributes, antecedents and consequences can be utilized in nursing education, research and intervention approaches. Impact: This article allows nurses and other healthcare professionals to better understand people living with dementia through the relationship between eating and interpersonal, intrapersonal and environmental aspects to develop personalized interventions and care strategies to achieve an optimal quality of life. Patient or Public Contribution: Not applicable. [ABSTRACT FROM AUTHOR]

Spinocerebellar ataxias (SCA) are rare inherited neurodegenerative disorders characterized by a progressive impairment of gait, balance, limb coordination, and speech. There is currently no composite scale that includes multiple aspects of the SCA experience to assess disease progression and treatment effects. Applying the method of partial least squares (PLS) regression, we developed the Spinocerebellar Ataxia Composite Scale (SCACOMS) from two SCA natural history datasets (NCT01060371, NCT02440763). PLS regression selected items based on their ability to detect clinical decline, with optimized weights based on the item's degree of progression. Following model validation, SCACOMS was leveraged to examine disease progression and treatment effects in a 48-week SCA clinical trial cohort (NCT03701399). Items from the Clinical Global Impression—Global Improvement Scale (CGI-I), the Friedreich Ataxia Rating Scale (FARS) – functional stage, and the Modified Functional Scale for the Assessment and Rating of Ataxia (f-SARA) were objectively selected with weightings based on their sensitivity to clinical decline. The resulting SCACOMS exhibited improved sensitivity to disease progression and greater treatment effects (compared to the original scales from which they were derived) in a 48-week clinical trial of a novel therapeutic agent. The trial analyses also provided a SCACOMS-derived estimate of the temporal delay in SCA disease progression. SCACOMS is a useful composite measure, effectively capturing disease progression and highlighting treatment effects in patients with SCA. SCACOMS will be a powerful tool in future studies given its sensitivity to clinical decline and ability to detect a meaningful clinical impact of disease-modifying treatments. [ABSTRACT FROM AUTHOR]

Patients with compromised respiratory function frequently require mechanical ventilation to survive. Unfortunately, non-uniform ventilation of injured lungs generates complex mechanical forces that lead to ventilator induced lung injury (VILI). Although investigators have developed lung-on-a-chip systems to simulate normal respiration, modeling the complex mechanics of VILI as well as the subsequent recovery phase is a challenge. Here we present a novel humanized in vitro ventilator-on-a-chip (VOC) model of the lung microenvironment that simulates the different types of injurious forces generated in the lung during mechanical ventilation. We used transepithelial/endothelial electrical impedance measurements to investigate how individual and simultaneous application of mechanical forces alters real-time changes in barrier integrity during and after injury. We find that compressive stress (i.e. barotrauma) does not significantly alter barrier integrity while over-distention (20% cyclic radial strain, volutrauma) results in decreased barrier integrity that quickly recovers upon removal of mechanical stress. Conversely, surface tension forces generated during airway reopening (atelectrauma), result in a rapid loss of barrier integrity with a delayed recovery relative to volutrauma. Simultaneous application of cyclic stretching (volutrauma) and airway reopening (atelectrauma), indicates that the surface tension forces associated with reopening fluid-occluded lung regions are the primary driver of barrier disruption. Thus, our novel VOC system can monitor the effects of different types of injurious forces on barrier disruption and recovery in real-time and can be used to interogate the biomechanical mechanisms of VILI. [ABSTRACT FROM AUTHOR]

Consumer and community involvement (also referred to as patient and public involvement) in health-related curricula involves actively partnering with people with lived experience of health and social care systems. While health professions education has a long history of interaction with patients or consumers, a shift in the way consumer and community engage in health-related education has created novel opportunities for mutual relationships valuing lived experience expertise and shifting traditional education power relations. Drawing on a mixed methods design, we explored consumer and community involvement practices in the design and delivery of health-related education using the capability, opportunity, motivation and behaviour framework (COM-B). In our results, we describe educator capabilities, opportunities and motivations, including identifying barriers and enablers to consumer and community involvement in health-related education. Educators have varying philosophical reasons and approaches for involving consumers and community. There is a focus on augmenting student learning through inclusion of lived and living experience, and on mutual transformative learning through embedding lived experience and co-creating learning. How these philosophical positionings and motivations shape the degree by which educators involve consumers and community members in health-related curricula is important for further understanding these educational partnerships within universities. [ABSTRACT FROM AUTHOR]

This study examines gradients in depressive symptoms by socioeconomic position (SEP; i.e., income, education, employment) in a sample of men who have sex with men (MSM). Data were used from EXPLORE, a randomized, controlled behavioral HIV prevention trial for HIV-uninfected MSM in six U.S. cities (n = 4,277). Depressive symptoms were assessed using the Center for Epidemiologic Studies Depression scale (short form). Multiple linear regressions were fitted with interaction terms to assess additive and multiplicative relationships between SEP and depressive symptoms. Depressive symptoms were more prevalent among MSM with lower income, lower educational attainment, and those in the unemployed/other employment category. Income, education, and employment made significant contributions in additive models after adjustment. The employment-income interaction was statistically significant, indicating a multiplicative effect. This study revealed gradients in depressive symptoms across SEP of MSM, pointing to income and employment status and, to a lesser extent, education as key factors for understanding heterogeneity of depressive symptoms.

Introduction. Access to individual patient data (IPD) can be advantageous when conducting cost-effectiveness analyses or indirect treatment comparisons. While exact times of censoring are often marked on published Kaplan-Meier (KM) curves, an algorithm for reconstructing IPD from such curves that allows for their incorporation is presently unavailable. Methods. An algorithm capable of incorporating marked censoring times was developed to reconstruct IPD from KM curves, taking as additional inputs the total patient count and coordinates of the drops in survival. The reliability of the algorithm was evaluated via a simulation exercise, in which survival curves were simulated, digitized, and then reconstructed. To assess the reliability of the reconstructed curves, hazard ratios (HRs) and quantiles of survival were compared between the original and reconstructed curves, and the reconstructed curves were visually inspected. Results. No systematic differences were found in HRs and quantiles in the original versus reconstructed curves. Upon visual inspection, the reconstructed IPD provided a close fit to the digitized data from the published KM curves. Inherent to the algorithm, censoring times were incorporated into the reconstructed data exactly as specified. Conclusion. This new algorithm can reliably be used to reconstruct IPD from reported KM survival curves in the presence of extractable censoring times. Use of the algorithm will allow health researchers to reconstruct IPD more closely by incorporating censoring times exactly as marked, requiring as additional inputs the total patient count and coordinates of the drops in survival.

ABSTRACT The objective of this study was to fully describe the protocol with standardized modifications and evaluate the lysozyme activity, an indicator of innate immunity in tilapia, to compare lipopolysaccharide (LPS) with Streptococcus agalactiae injections. Lysozyme was determined in serum using the turbidimetric method, in which lysozyme activity was evaluated by Micrococcus lysodeikticus lysis, with modifications for microplate assay. The experiment was conducted in a completely randomized design. Juvenile tilapia was divided in the following six treatments: challenged with phosphate buffer PBS (control) and 100, 250, 500, and 600 μg kg−1 LPS and S. agalactiae. All treatments were challenged for 72 h and seven days and then sampled to determine lysozyme activity. After 72 h or seven days, concentrations of LPS promoted changes in lysozyme production, either lesser or equal, depending on concentration when compared with fish injected with S. agalactiae. It was possible to standardize the analysis and determine that the treatment with LPS promotes immunomodulation at a concentration of 250 μg kg−1 LPS, this response being similar to challenge with S. agalactiae.

ObjectiveTo explore how European hospitals have implemented patient safety strategies (PSS) and evidence-based organization of care pathway (EBOP) recommendations and examine the extent to which implementation varies between countries and hospitals.DesignMixed-method multilevel cross-sectional design in seven countries as part of the European Union-funded project 'Deepening our Understanding of Quality improvement in Europe' (DUQuE).Setting and participantsSeventy-four acute care hospitals with 292 departments managing acute myocardial infarction (AMI), hip fracture, stroke, and obstetric deliveries. Main outcome measure Five multi-item composite measures-one generic measure for PSS and four pathway-specific measures for EBOP.ResultsPotassium chloride had only been removed from general medication stocks in 9.4-30.5% of different pathways wards and patients were adequately identified with wristband in 43.0-59.7%. Although 86.3% of areas treating AMI patients had immediate access to a specialist physician, only 56.0% had arrangements for patients to receive thrombolysis within 30 min of arrival at the hospital. A substantial amount of the total variance observed was due to between-hospital differences in the same country for PSS (65.9%). In EBOP, between-country differences play also an important role (10.1% in AMI to 57.1% in hip fracture).ConclusionsThere were substantial gaps between evidence and practice of PSS and EBOP in a sample of European hospitals and variations due to country differences are more important in EBOP than in PSS, but less important than within-country variations. Agencies supporting the implementation of PSS and EBOP should closely re-examine the effectiveness of their current strategies.