3D-Printed Hydrogels with Engineered Nanocrystalline Domains as Functional Vascular Constructs.

Three-dimensionally printed (3DP) hydrogel-based vascular constructs have been investigated in response to the impaired function of blood vessels or organs by replicating exactly the 3D structural geometry to approach their function. However, they are still challenged by their intrinsic brittleness, which could not sustain the suture piercing and enable the long-term structural and functional stability during the direct contact with blood. Here, we reported the high-fidelity digital light processing (DLP) 3D printing of hydrogel-based vascular constructs from poly(vinyl alcohol)-based inks, followed by mechanical strengthening through engineering the nanocrystalline domains and subsequent surface modification. The as-prepared high-precision hydrogel vascular constructs were imparted with highly desirable mechanical robustness, suture tolerance, swelling resistance, antithrombosis, and long-term patency. Notably, the hydrogel-based bionic vein grafts, with precise valve structures, exhibited excellent control over the unidirectional flow and successfully fulfilled the biological functionalities and patency during a 4-week implantation within the deep veins of beagles, thus corroborating the promising potential for treating chronic venous insufficiency.

Facilitators and barriers of technology adoption and social connectedness among rural older adults: a qualitative study.

Background: Social disconnection is a public health concern among rural Australian older adults. While research suggests technology can enhance social wellbeing and protect against social disconnection, many older adults are not digitally literate, and little is known as to why and how technology adoption could be promoted in rural contexts. This study aimed to (1) explore the barriers and facilitators of technology adoption among rural older adults and (2) determine the potential utility of technology to promote social connectedness in the aged population. The Theoretical Domains Framework and the Behaviour Change Wheel (BCW) were employed to gain a comprehensive understanding of the digital and social behaviours of rural Australian older adults. Methods: Semi-structured interviews were conducted with a convenience sample of 33 rural older adults aged between 65 and 87 years. Interviews were conducted over the phone, audio-recorded, and transcribed. Interview transcripts were coded and analysed using thematic analysis and the BCW. Results: Numerous barriers and facilitators of technology adoption were identified, with the most prominent being knowledge, perceived value, perceived self-efficacy, and social support. Findings suggest that older adults' technology adoption is not simply a technical matter, but influenced by various individual, social, and environmental contexts. Consideration of these factors during development, marketing, training and implementation may facilitate technology adoption among older adults. With regard to social connectedness, several rural barriers emerged, including low population density, geographic isolation, limited community opportunities and poor public transport infrastructure. Conclusion: Technology was consistently identified as a facilitator of the social experience, indicating that technology is a promising tool to enhance social connectedness among older adults, particularly those living in rural areas. Future research should focus on enhancing the capability, opportunity and motivation of older adults in technology adoption, with reference to the rural contexts.

TIGIT: Will it be the next star therapeutic target like PD-1 in hematological malignancies?

Research on the mechanism and application of checkpoint inhibitory receptors in hematologic diseases has progressed rapidly. However, in the treatment of relapserefractory (R/R) hematologic malignancies and anti-programmed cell death protein 1 (PD-1), patients who are resistant to anti-cytotoxic T lymphocyte-associated antigen-4 (CTLA-4) are in urgent need of alternative therapeutic targets. T cell immunoreceptor with immunoglobulin and ITIM domains (TIGIT) has a broad prospect as an inhibitory receptor like PD-1, but its more specific mechanism of action and application in hematologic diseases still need to be further studied. In this review, we discuss the mechanism of TIGIT pathway, combined effects with other immune checkpoints, immune-related therapy, the impact of TIGIT on hematopoietic stem cell transplantation (HSCT) and the tumor microenvironment (TME) provides a potential therapeutic target for hematologic malignancies.

Relationship between TIGIT expression on T cells and the prognosis of patients with hepatocellular carcinoma.

BACKGROUND: Transcatheter arterial chemoembolization (TACE) combined with targeted therapy and immunotherapy can significantly improve the prognosis of patients with hepatocellular carcinoma (HCC). T-cell immunoreceptor with immunoglobulin and immunoreceptor tyrosine-based inhibitory motif domains (TIGIT) is a novel immunosuppressive molecule. This study aimed to analyze the clinical correlation between TIGIT expression on T cells and patients with HCC. METHODS: Clinical data from 140 patients with HCC were retrospectively collected, and TIGIT expression on T cells was examined in each patient. Patients were subsequently divided into high- and low-expression groups, and their prognosis was analyzed. RESULTS: Patients with a high TIGIT expression on their T cells at baseline had a larger tumor volume, later staging, higher proportion of regulatory T cells, higher blood concentrations of interleukin (IL)-6 and IL-10, and lower interferon-γ concentrations. Following TACE, CD155 concentration decreased; however, TACE did not affect TIGIT expression on T cells. Additionally, among patients receiving TACE combined with apatinib and camrelizumab treatment, patients with a high TIGIT expression on T cells had significantly shorter progression-free survival (PFS) and overall survival times than those of patients in the low-expression group. Patients receiving TACE combined with apatinib and camrelizumab treatment with higher TIGIT expression have shorter PFS time than those receiving TACE combined with apatinib treatment. CONCLUSIONS: Patients with HCC that have a high TIGIT expression on their T cells exhibited poorer baseline characteristics, immunosuppressive status, and prognosis after receiving TACE combined with apatinib and camrelizumab and maybe more suited to receive TACE combined with apatinib treatment instead.

Canadian Veterans' Experiences of Living with Chronic Pain: A Descriptive Qualitative Study.

Background: An estimated 30% of veterans live with chronic pain, compared to 20% of Canadians in the general population. Veterans face health care challenges upon release from the military, increasing difficulties in obtaining chronic pain care. Aims: We explored experiences of Canadian Armed Forces veterans living with chronic pain, their transition from military to civilian care, perceived barriers and facilitators to chronic pain care, and impacts of their pain on the domains of well-being. Methods: We conducted a qualitative descriptive study using semistructured interviews. We used a deductive/inductive approach to derive themes and concepts from interview transcripts. Results: Thirty-five veterans living with chronic pain participated. Participants reported that pain affected their lives in numerous ways, including negatively impacting relationships and limiting activities of daily living and leisure. They identified barriers to care, including lack of access to family doctors or health care services, reluctance to ask for help, and challenges in obtaining coverage for services from Veterans Affairs Canada. Facilitators included support from other veterans and online resources. Chronic pain had bidirectional effects on domains of well-being. Conclusions: Experiences of pain varied among Canadian veterans, and military culture played a role in perceptions and management of pain. Barriers and facilitators to chronic pain care were highlighted from their time in the military into their transition to civilian care. Participants described the impact of chronic pain on their overall well-being. Determining whether these findings are relevant to a larger population of Canadian veterans will be important for future research and knowledge translation to improve chronic pain care for Canadian veterans.

Contexte : On estime que 30 % des anciens combattants souffrent de douleur chronique, contre 20 % des Canadiens dans la population générale Les vétérans sont confrontés à des défis en matière de soins de santé lorsqu'ils quittent l'armée, ce qui augmente les difficultés pour obtenir des soins pour la douleur chronique.Objectifs : Nous avons exploré les expériences des vétérans des Forces armées canadiennes vivant avec une douleur chronique, leur transition des soins militaires aux soins civils, les obstacles et les facilitateurs perçus en matière de soins pour la douleur chronique, ainsi que les effets de cette douleur sur les différents aspects de leur bien-être.Méthodes : Nous avons réalisé une étude qualitative descriptive en utilisant des entretiens semi-structurés. Une approche à la fois déductive et inductive a été utilisée pour extraire des thèmes et des concepts à partir des transcriptions des entretiens.Résultats : Trente-cinq anciens combattants souffrant de douleur chronique ont participé à l'étude. Les participants ont déclaré que la douleur affectait leur vie de nombreuses façons, notamment en ayant un impact négatif sur leurs relations en limitant les activités de la vie quotidienne ainsi que les loisirs. Ils ont recensé des obstacles aux soins, notamment le manque d'accès à des médecins de famille ou aux services de soins de santé, la réticence à demander de l'aide, et les difficultés à obtenir une couverture pour les services d'Anciens Combattants Canada. Les facilitateurs comprennent le soutien d'autres anciens combattants et les ressources en ligne. La douleur chronique a eu des effets bidirectionnels sur différents aspects de leur bien-être.Conclusions : Les expériences de la douleur varient parmi les anciens combattants canadiens, et la culture militaire joue un rôle dans les perceptions et la prise en charge de la douleur. Les obstacles aux soins pour la douleur chronique, ainsi que les facilitateurs, ont été mis en évidence depuis leur temps dans l'armée jusqu'à leur transition vers les soins civils. Les participants ont décrit l'effet de la douleur chronique sur leur bien-être général. Il sera important de déterminer si ces résultats sont pertinents pour une population plus large d'anciens combattants canadiens dans le cadre de recherches futures et de l'application des connaissances, afin d'améliorer les soins pour la douleur chronique chez les anciens combattants canadiens.

Poly-ADP-ribosylation dynamics, signaling, and analysis.

ADP-ribosylation is a reversible post-translational modification that plays a role as a signaling mechanism in various cellular processes. This modification is characterized by its structural diversity, highly dynamic nature, and short half-life. Hence, it is tightly regulated at many levels by cellular factors that fine-tune its formation, downstream signaling, and degradation that together impacts cellular outcomes. Poly-ADP-ribosylation is an essential signaling mechanism in the DNA damage response that mediates the recruitment of DNA repair factors to sites of DNA damage via their poly-ADP-ribose (PAR)-binding domains (PBDs). PAR readers, encoding PBDs, convey the PAR signal to mediate cellular outcomes that in some cases can be dictated by PAR structural diversity. Several PBD families have been identified, each with variable PAR-binding affinity and specificity, that also recognize and bind to distinct parts of the PAR chain. PARylation signaling has emerged as an attractive target for the treatment of specific cancer types, as the inhibition of PAR formation or degradation can selectively eliminate cancer cells with specific DNA repair defects and can enhance radiation or chemotherapy response. In this review, we summarize the key players of poly-ADP-ribosylation and its regulation and highlight PBDs as tools for studying PARylation dynamics and the expanding potential to target PARylation signaling in cancer treatment.

Transcriptional activation domains interact with ATPase subunits of yeast chromatin remodelling complexes SWI/SNF, RSC and INO80.

Chromatin remodelling complexes (CRC) are ATP-dependent molecular machines important for the dynamic organization of nucleosomes along eukaryotic DNA. CRCs SWI/SNF, RSC and INO80 can move positioned nucleosomes in promoter DNA, leading to nucleosome-depleted regions which facilitate access of general transcription factors. This function is strongly supported by transcriptional activators being able to interact with subunits of various CRCs. In this work we show that SWI/SNF subunits Swi1, Swi2, Snf5 and Snf6 can bind to activation domains of Ino2 required for expression of phospholipid biosynthetic genes in yeast. We identify an activator binding domain (ABD) of ATPase Swi2 and show that this ABD is functionally dispensable, presumably because ABDs of other SWI/SNF subunits can compensate for the loss. In contrast, mutational characterization of the ABD of the Swi2-related ATPase Sth1 revealed that some conserved basic and hydrophobic amino acids within this domain are essential for the function of Sth1. While ABDs of Swi2 and Sth1 define separate functional protein domains, mapping of an ABD within ATPase Ino80 showed co-localization with its HSA domain also required for binding actin-related proteins. Comparative interaction studies finally demonstrated that several unrelated activators each exhibit a specific binding pattern with ABDs of Swi2, Sth1 and Ino80.

Visibility graph-based covariance functions for scalable spatial analysis in non-convex partially Euclidean domains.

We present a new method for constructing valid covariance functions of Gaussian processes for spatial analysis in irregular, non-convex domains such as bodies of water. Standard covariance functions based on geodesic distances are not guaranteed to be positive definite on such domains, while existing non-Euclidean approaches fail to respect the partially Euclidean nature of these domains where the geodesic distance agrees with the Euclidean distances for some pairs of points. Using a visibility graph on the domain, we propose a class of covariance functions that preserve Euclidean-based covariances between points that are connected in the domain while incorporating the non-convex geometry of the domain via conditional independence relationships. We show that the proposed method preserves the partially Euclidean nature of the intrinsic geometry on the domain while maintaining validity (positive definiteness) and marginal stationarity of the covariance function over the entire parameter space, properties which are not always fulfilled by existing approaches to construct covariance functions on non-convex domains. We provide useful approximations to improve computational efficiency, resulting in a scalable algorithm. We compare the performance of our method with those of competing state-of-the-art methods using simulation studies on synthetic non-convex domains. The method is applied to data regarding acidity levels in the Chesapeake Bay, showing its potential for ecological monitoring in real-world spatial applications on irregular domains.

Friends because of foes: synchronous movement within predator-prey domains.

For prey, movement synchrony represents a potent antipredator strategy. Prey, however, must balance the costs and benefits of using conspecifics to mediate risk. Thus, the emergent patterns of risk-driven sociality depend on variation in space and in the predators and prey themselves. We applied the concept of predator-prey habitat domain, the space in which animals acquire food resources, to test the conditions under which individuals synchronize their movements relative to predator and prey habitat domains. We tested the response of movement synchrony of prey to predator-prey domains in two populations of ungulates that vary in their gregariousness and predator community: (i) elk, which are preyed on by wolves; and (ii) caribou, which are preyed on by coyotes and black bears. Prey in both communities responded to cursorial predators by increasing synchrony during seasons of greater predation pressure. Elk moved more synchronously in the wolf habitat domain during winter and caribou moved more synchronously in the coyote habitat domains during spring. In the winter, caribou increased movement synchrony when coyote and caribou domains overlapped. By integrating habitat domains with movement ecology, we provide a compelling argument for social behaviours and collective movement as an antipredator response. This article is part of the theme issue 'The spatial-social interface: A theoretical and empirical integration'.

Participation 1.5 years after mild traumatic brain injury in children and adolescents.

This longitudinal prospective cohort study examined participation between 6 months and 1.5 years after pediatric mild Traumatic Brain Injury (mTBI) in 68 children aged 6-18 years. Levels of participation in different settings remain mostly stable between 6 months and 1.5 years after mTBI, with a substantial proportion of children continuing to indicate less than full functioning. Future studies should examine risk factors and opportunities for early identification to prevent long-term negative consequences of pediatric mTBI regarding participation.

Exploring what influences physiotherapists' capability, opportunity and motivation to integrate new evidence into routine clinical care using the Balance Intensity Scale.

PURPOSE: To explore influences on the capability, opportunity and motivation of physiotherapists integrating new evidence into routine care. MATERIALS AND METHODS: Mixed-methods study utilising the Theoretical Domains Framework and Capability-Opportunity-Motivation-Behaviour model. Metropolitan inpatient rehabilitation physiotherapists participated by integrating the Balance Intensity Scale into routine care for 6 weeks. Evidence integration was supported by a tailored theory-informed approach. Participants completed pre- and post-evidence integration surveys and a post-evidence integration focus group. RESULTS: Pre- and post-surveys were completed by 24 and 12 participants, respectively. One focus group (n = 7) was conducted. Framework analysis identified themes in Capability (n = 4), Opportunity (n = 4) and Motivation (n = 5) domains influencing behaviour when implementing new evidence. The evidence integration process enhanced participants' Knowledge (p = 0.04), Skills (p = 0.003) and Belief in capabilities (p = 0.03) when prescribing and measuring balance exercises. CONCLUSIONS: This study identified perceived barriers and enablers to evidence integration of a new outcome measure into routine care. It highlights strategies that may support physiotherapy teams in incorporating new evidence into routine care. These strategies include education on the evidence being implemented, physical resources, change champions to facilitate social support, management endorsement, and recognition of the time and effort required for evidence integration in the short term.

When integrating new evidence into routine physiotherapy care in rehabilitation settings, the theoretical domains framework can provide a suitable framework to identify potential barriers and enablers of evidence integration at a local level, to guide the tailoring of support strategies.Rehabilitation physiotherapists can integrate the Balance Intensity Scale into balance exercise prescription as part of routine care.Targeted education provides support to change practice and implement evidence-informed care.Clinical change champions and sharing the effort to change as a team are pivotal in fostering the adoption of new evidence, such as the Balance Intensity Scale, into practice.

Brain network dynamics in patients with single- and multiple-domain amnestic mild cognitive impairment.

INTRODUCTION: Brain network dynamics have been extensively explored in patients with amnestic mild cognitive impairment (aMCI); however, differences in single- and multiple-domain aMCI (SD-aMCI and MD-aMCI) remain unclear. METHODS: Using multicenter datasets, coactivation patterns (CAPs) were constructed and compared among normal control (NC), SD-aMCI, MD-aMCI, and Alzheimer's disease (AD) patients based on individual high-order cognitive network (HOCN) and primary sensory network (PSN) parcellations. Correlations between spatiotemporal characteristics and neuropsychological scores were analyzed. RESULTS: Compared to NC, SD-aMCI showed temporal alterations in HOCN-dominant CAPs, while MD-aMCI showed alterations in PSN-dominant CAPs. In addition, transitions from SD-aMCI to AD may involve PSN, while MD-aMCI to AD involves both PSN and HOCN. Results were generally consistent across datasets from Chinese and White populations. DISCUSSION: The HOCN and PSN are distinctively involved in aMCI subtypes and in the transformation between aMCI subtypes and AD, highlighting the necessity of aMCI subtype classification in AD studies. HIGHLIGHTS: Individual functional network parcellations and coactivation pattern (CAP) analysis were performed to characterize spatiotemporal differences between single- and multiple-domain amnestic mild cognitive impairment (SD-aMCI and MD-aMCI), and between distinct aMCI subtypes and Alzheimer's disease (AD). The analysis of multicenter datasets converged on four pairs of recurrent CAPs, including primary sensory networks (PSN)-dominant CAPs, high-order cognitive networks (HOCN)-dominant CAPs, and PSN-HOCN-interacting CAPs. The HOCN and PSN are distinctively involved in aMCI subtypes and in the transformation between distinct aMCI subtypes and AD.

Systematic analysis of SCN5A variants associated with inherited cardiac diseases.

BACKGROUND: SCN5A variants are associated with a spectrum of cardiac electrical disorders with clear phenotypes. However, they may also be associated with complex phenotypic traits like overlap syndromes or pleiotropy, which have not been systematically described. In addition, the involvement of SCN5A in dilated cardiomyopathies (DCMs) remains controversial. OBJECTIVE: We aimed to evaluate the different phenotypes associated with pathogenic (P)/likely pathogenic (LP) SCN5A variants and to determine the prevalence of pleiotropy in a large multicentric cohort of P/LP SCN5A variant carriers. METHODS: The DNA of 13,510 consecutive probands (9960 with cardiomyopathies) was sequenced with a custom panel of genes. Individuals carrying a heterozygous single P/LP SCN5A variant were selected and phenotyped. RESULTS: The study included 170 P/LP variants found in 495 patients. Of them, 119 (70%) were exclusively associated with a single well-established phenotype: 91 with Brugada syndrome, 15 with type 3 long QT syndrome, 6 with progressive cardiac conduction disease, 4 with multifocal ectopic Purkinje-related premature contractions, and 3 with sick sinus syndrome. Thirty-two variants (19%) were associated with overlap syndromes or pleiotropy. The 19 remaining variants (11%) were associated with atypical or unclear phenotypes. Of those, 8 were carried by 8 patients presenting with DCM with a debatable causative genotype/phenotype link. CONCLUSION: Most P/LP SCN5A variants were found in patients with primary electrical disorders, mainly Brugada syndrome. Nearly 20% were associated with overlap syndromes or pleiotropy, underscoring the need for comprehensive phenotypic evaluation. The concept of SCN5A variants causing DCM is extremely rare (8/9960) if not questionable.

Permeable TAD boundaries and their impact on genome-associated functions.

TAD boundaries are genomic elements that separate biological processes in neighboring domains by blocking DNA loops that are formed through Cohesin-mediated loop extrusion. Most TAD boundaries consist of arrays of binding sites for the CTCF protein, whose interaction with the Cohesin complex blocks loop extrusion. TAD boundaries are not fully impermeable though and allow a limited amount of inter-TAD loop formation. Based on the reanalysis of Nano-C data, a multicontact Chromosome Conformation Capture assay, we propose a model whereby clustered CTCF binding sites promote the successive stalling of Cohesin and subsequent dissociation from the chromatin. A fraction of Cohesin nonetheless achieves boundary read-through. Due to a constant rate of Cohesin dissociation elsewhere in the genome, the maximum length of inter-TAD loops is restricted though. We speculate that the DNA-encoded organization of stalling sites regulates TAD boundary permeability and discuss implications for enhancer-promoter loop formation and other genomic processes.

Understanding barriers and facilitators to integrated HIV and hypertension care in South Africa.

BACKGROUND: The burden of hypertension among people with HIV is high, particularly in low-and middle-income countries, yet gaps in hypertension screening and care in these settings persist. This study aimed to identify facilitators of and barriers to hypertension screening, treatment, and management among people with HIV in primary care clinics in Johannesburg, South Africa. Additionally, different stakeholder groups were included to identify discordant perceptions. METHODS: Using a cross-sectional study design, data were collected via interviews (n = 53) with people with HIV and hypertension and clinic managers and focus group discussions (n = 9) with clinic staff. A qualitative framework analysis approach guided by COM-B and the Theoretical Domains Framework were used to identify and compare determinants of hypertension care across stakeholder groups. RESULTS: Data from clinic staff and managers generated three themes characterizing facilitators of and barriers to the adoption and implementation of hypertension screening and treatment: 1) clinics have limited structural and operational capacity to support the implementation of integrated care models, 2) education and training on chronic care guidelines is inconsistent and often lacking across clinics, and 3) clinicians have the goal of enhancing chronic care within their clinics but first need to advocate for health system characteristics that will sustainably support integrated care. Patient data generated three themes characterizing existing facilitators of and barriers to clinic attendance and chronic disease self-management: 1) the threat of hypertension-related morbidity and mortality as a motivator for lifestyle change, 2) the emotional toll of clinic's logistical, staff, and resource challenges, and 3) hypertension self-management as a patchwork of informational and support sources. The main barriers to hypertension screening, treatment, and management were related to environmental resources and context (i.e., lack of enabling resources and siloed flow of clinic operations) and patients' knowledge and emotions (i.e., lack of awareness about hypertension risk, fear, and frustration). Clinical actors and patients differed in perceived need to prioritize HIV versus hypertension care. CONCLUSIONS: The convergence of multi-stakeholder data highlight key areas for improvement, where tailored implementation strategies targeting motivations of clinic staff and capacity of patients may address challenges to hypertension screening, treatment, and management recognized across groups.

Deep mutational scanning reveals transmembrane features governing surface expression of the B cell antigen receptor.

B cells surveil the body for foreign matter using their surface-expressed B cell antigen receptor (BCR), a tetrameric complex comprising a membrane-tethered antibody (mIg) that binds antigens and a signaling dimer (CD79AB) that conveys this interaction to the B cell. Recent cryogenic electron microscopy (cryo-EM) structures of IgM and IgG isotype BCRs provide the first complete views of their architecture, revealing that the largest interaction surfaces between the mIg and CD79AB are in their transmembrane domains (TMDs). These structures support decades of biochemical work interrogating the requirements for assembly of a functional BCR and provide the basis for explaining the effects of mutations. Here we report a focused saturating mutagenesis to comprehensively characterize the nature of the interactions in the mIg TMD that are required for BCR surface expression. We examined the effects of 600 single-amino-acid changes simultaneously in a pooled competition assay and quantified their effects by next-generation sequencing. Our deep mutational scanning results reflect a feature-rich TMD sequence, with some positions completely intolerant to mutation and others requiring specific biochemical properties such as charge, polarity or hydrophobicity, emphasizing the high value of saturating mutagenesis over, for example, alanine scanning. The data agree closely with published mutagenesis and the cryo-EM structures, while also highlighting several positions and surfaces that have not previously been characterized or have effects that are difficult to rationalize purely based on structure. This unbiased and complete mutagenesis dataset serves as a reference and framework for informed hypothesis testing, design of therapeutics to regulate BCR surface expression and to annotate patient mutations.

Understanding the factors influencing biosecurity adoption on smallholder poultry farms in Ghana: a qualitative analysis using the COM-B model and Theoretical Domains Framework.

Introduction: Antimicrobial resistance (AMR) poses a significant global threat to public, animal, and environmental health, consequently producing downstream economic impacts. While top-down approaches to addressing AMR (e.g., laws regulating antimicrobial use) are common in high-income countries, limited enforcement capacities in low- and middle-income countries highlight the need for more bottom-up approaches. Within agriculture, efforts to apply bottom-up approaches to AMR have often focused on the promotion of biosecurity, which should reduce the need for antimicrobials by mitigating disease risk and limiting AMR transmission. Traditionally, efforts to encourage biosecurity adoption have emphasized training and awareness-raising initiatives. However, a growing body of research suggests a disconnect between knowledge and behavior, highlighting the existence of a knowledge-action gap. Method: To understand the barriers and enablers patterning the knowledge-action gap in on-farm biosecurity uptake, we draw upon models from behavioral science. We analyzed in-depth interviews and two focus group discussions with smallholder poultry producers in Ghana to understand factors underlying the intention-action gap in adopting biosecurity. As an analytical framework, we draw upon the Theoretical Domains Framework in combination with the Capability-Opportunity-Motivation Behavioral Model. Results and discussion: While smallholder poultry farmers in Ghana were aware of the importance of biosecurity practices, they struggled with consistent implementation. Financial constraints, challenges in adapting practices to the local context, and limited resources hindered adoption. Additionally, cognitive biases like prioritizing short-term gains and underestimating disease risks played a role. However, some farmers found motivation in professional identity and social influences. These findings highlight the need for designing biosecurity interventions that consider human behavioral factors and the context in which behavior occurs. This underscores the importance of collaboration across disciplines, including veterinary science and the social and behavioral sciences. Implications and recommendations for researchers and practitioners are discussed.

Criticality in Alzheimer's and healthy brains: insights from phase-ordering.

Criticality, observed during second-order phase transitions, is an emergent phenomenon. The brain operates near criticality where complex systems exhibit high correlations. As a system approaches criticality, it develops "domain"-like regions with competing phases and increased spatio-temporal correlations that diverge. The dynamics of these domains depend on the system's proximity to criticality. This study explores the differences in the proximity to criticality of Alzheimer's-afflicted and cognitively normal brains through the use of a spin-lattice model derived from resting-state fMRI data and investigates the type of criticality found in the human brain - whether it is of the Ising class or something more complex. The temporal correlations in both groups display a stretched exponential nature, indicating closer alignment with the criticality of the spin-glass class rather than the Ising class. Longer relaxation times observed in cognitively normal subjects suggest increased proximity to the phase boundary. The weak distinction observed in the spatial characteristics related to proximity to criticality might once more point to a spin-glass scenario, necessitating nuanced order parameters to distinguish between phase-ordering in Alzheimer's and cognitively normal brains.

CoDIAC: A comprehensive approach for interaction analysis reveals novel insights into SH2 domain function and regulation.

Protein domains are conserved structural and functional units and are the functional building blocks of proteins. Evolutionary expansion means that domain families are often represented by many members in a species, which are found in various configurations with other domains, which have evolved new specificity for interacting partners. Here, we develop a structure-based interface analysis to comprehensively map domain interfaces from available experimental and predicted structures, including interfaces with other macromolecules and intraprotein interfaces (such as might exist between domains in a protein). We hypothesized that a comprehensive approach to contact mapping of domains could yield new insights. Specifically, we use it to gain information about how domains selectivity interact with ligands, whether domain-domain interfaces of repeated domain partnerships are conserved across diverse proteins, and identify regions of conserved post-translational modifications, using relationship to interaction interfaces as a method to hypothesize the effect of post-translational modifications (and mutations). We applied this approach to the human SH2 domain family, an extensive modular unit that is the foundation of phosphotyrosine-mediated signaling, where we identified a novel approach to understanding the binding selectivity of SH2 domains and evidence that there is coordinated and conserved regulation of multiple SH2 domain binding interfaces by tyrosine and serine/threonine phosphorylation and acetylation, suggesting that multiple signaling systems can regulate protein activity and SH2 domain interactions in a regulated manner. We provide the extensive features of the human SH2 domain family and this modular approach, as an open source Python package for COmprehensive Domain Interface Analysis of Contacts (CoDIAC).

Strategies for scaling up pre-ART advanced HIV disease screening at a secondary referral hospital-Malawi: a qualitative study.

BACKGROUND: Implementation of the World Health Organization (WHO) recommended Advanced HIV Disease screening package, remains poor in most settings with limited resources. More than 50% of newly diagnosed-HIV clients are missed on screening as a result of implementation barriers. It is important to mitigate the existing barriers and leverage enablers' inorder to maximize uptake of the advanced HIV disease screening. This study aimed to identify strategies for scaling up implementation of advanced HIV disease screening among newly HIV-diagnosed clients in pre-ART phase using a Consolidated Framework for Implementation Research-Expert Recommendation for Implementing Change (CFIR-ERIC) guiding tool. METHODS: A qualitative study was conducted at Rumphi district hospital in Malawi (August - September, 2023). Two sessions of Focus group discussions (FDGs) involving key stakeholders were facilitated to identify specific strategies following the initial study on exploration of barriers and facilitators of advanced HIV disease screening package. Participants comprised healthcare providers, purposively selected from key hospital departments. A deductive approach was used to analyze FDG transcripts where emerging themes were mapped with ERIC list of strategies. CFIR-ERIC Matching tool version 1.0, was used to generate an output of the most to least expert-endorsed Level 1 and Level 2 strategies. FINDINGS: About 25 key healthcare workers participated in FDGs. Overall, 6 Level 1 strategies (≥ 50% expert endorsement score) and 4 Level 2 strategies (≥ 20%, ≤ 49% expert endorsement score) were identified, targeting barriers associated with availability of resources, intervention complexity, access to knowledge and information, communication; and implementation leads. Most of the reported strategies were cross-cutting and aimed at enhancing clinical knowledge of the intervention (distributing training materials, educational meetings), developing stakeholders' interrelations (network weaving) as well as improving clinical workflow (environmental restructuring). Use of evaluative and iterative strategies such as monthly data collection for evaluation were also recommended as part of continuous improvement while an AHD coordinator was recommended to be formally appointed inorder to spearhead coordination of AHD screening services. CONCLUSION: Through the involvement of key stakeholders and the use of CFIR-ERIC matching tool, this study has identified cross-cutting strategies that if well implemented, can help to mitigate contextual barriers and leverage enablers for an improved delivery of AHD screening package.