Midkine Attenuates Aβ Fibril Assembly and AmyloidPlaque Formation.

Proteomic profiling of Alzheimer's disease (AD) brains has identified numerous understudied proteins, including midkine (MDK), that are highly upregulated and correlated with Aβ since the early disease stage, but their roles in disease progression are not fully understood. Here we present that MDK attenuates Aβ assembly and influences amyloid formation in the 5xFAD amyloidosis mouse model. MDK protein mitigates fibril formation of both Aβ40 and Aβ42 peptides in Thioflavin T fluorescence assay, circular dichroism, negative stain electron microscopy, and NMR analysis.

Being kind in unkind spaces: a qualitative examination of how medical educators and first year medical students perceive empathy training.

Introduction: It has become for healthcare systems to tout their ability to provide compassionate medical care that addresses the emotional as well as physical needs of patients. Not surprisingly, then, there is considerable pressure on medical schools to train their students to be empathic. Existing literature on empathy training in medicine tends to focus on how to build emotional intelligence in individual trainees, largely ignoring the sociocultural factors that contribute to or thwart empathy development in medical school.

Universal energy-accuracy tradeoffs in nonequilibrium cellular sensing.

We combine stochastic thermodynamics, large deviation theory, and information theory to derive fundamental limits on the accuracy with which single cell receptors can estimate external concentrations. As expected, if the estimation is performed by an ideal observer of the entire trajectory of receptor states, then no energy consuming nonequilibrium receptor that can be divided into bound and unbound states can outperform an equilibrium two-state receptor. However, when the estimation is performed by a simple observer that measures the fraction of time the receptor is bound, we derive a fundamental limit on the accuracy of general nonequilibrium receptors as a function of energy consumption.

Synaptic balancing: A biologically plausible local learning rule that provably increases neural network noise robustness without sacrificing task performance.

We introduce a novel, biologically plausible local learning rule that provably increases the robustness of neural dynamics to noise in nonlinear recurrent neural networks with homogeneous nonlinearities. Our learning rule achieves higher noise robustness without sacrificing performance on the task and without requiring any knowledge of the particular task. The plasticity dynamics-an integrable dynamical system operating on the weights of the network-maintains a multiplicity of conserved quantities, most notably the network's entire temporal map of input to output trajectories.

Exploiting breakdown in nonhost effector-target interactions to boost host disease resistance.

Plants are resistant to most microbial species due to nonhost resistance (NHR), providing broad-spectrum and durable immunity. However, the molecular components contributing to NHR are poorly characterised. We address the question of whether failure of pathogen effectors to manipulate nonhost plants plays a critical role in NHR.

A high-resolution single-molecule sequencing-based Arabidopsis transcriptome using novel methods of Iso-seq analysis.

Background: Accurate and comprehensive annotation of transcript sequences is essential for transcript quantification and differential gene and transcript expression analysis. Single-molecule long-read sequencing technologies provide improved integrity of transcript structures including alternative splicing, and transcription start and polyadenylation sites. However, accuracy is significantly affected by sequencing errors, mRNA degradation, or incomplete cDNA synthesis.

Exploring the perspectives of primary care providers on use of the electronic Patient Reported Outcomes tool to support goal-oriented care: a qualitative study.

Background: Digital health technologies can support primary care delivery, but clinical uptake in primary care is limited. This study explores enablers and barriers experienced by primary care providers when adopting new digital health technologies, using the example of the electronic Patient Reported Outcome (ePRO) tool; a mobile application and web portal designed to support goal-oriented care. To better understand implementation drivers and barriers primary care providers' usage behaviours are compared to their perspectives on ePRO utility and fit to support care for patients with complex care needs.

Exploring the relationship between the usability of a goal-oriented mobile health application and non-usage attrition in patients with multimorbidity: A blended data analysis approach.

Background: Mobile health applications are increasingly used to support the delivery of health care services to a variety of patients. Based on data obtained from a pragmatic trial of the electronic Patient Reported Outcome (ePRO) app designed to support goal-oriented care primary care, this study aims to (1) examine how patient-reported usability changed over the one-year intervention period, and (2) explore participant attrition rate of the electronic Patient Reported Outcome app over one year study period.

Methods: We performed a secondary analysis of 44 older adults with complex chronic needs enrolled in the electronic Patient Reported Outcome-digital health intervention.

Assessing the Implementation and Effectiveness of the Electronic Patient-Reported Outcome Tool for Older Adults With Complex Care Needs: Mixed Methods Study.

Background: Goal-oriented care is being adopted to deliver person-centered primary care to older adults with multimorbidity and complex care needs. Although this model holds promise, its implementation remains a challenge. Digital health solutions may enable processes to improve adoption; however, they require evaluation to determine feasibility and impact.

Defining Familial Interactions and Networks: An Exploratory Qualitative Study on Family Networks and Surrogate Decision-Making.

Unlabelled: To characterize patient preferences for medical surrogate decision-makers in the ICU to capture the complexity of decision-making preferences and highlight potential conflicts between patients' preferences and clinicians' surrogate decision-maker identification in usual clinical practice.

Design: Prospective qualitative cross-sectional study.

Setting: Two ICUs in a quaternary referral center in the eastern United States.

The direct and indirect effects of clinical empathy on well-being among pre-medical students: a structural equation model approach.

Background: Empathy is a well-established facet of clinical competency that research suggests is associated with enhanced medical student well-being. Since little is known about empathy and well-being before students enter medical school-during pre-medical education-the main goal of this study is to test a conceptual model of how clinical empathy is related to two indicators of well-being, depression, and burnout among pre-medical students. The theoretical model hypothesizes that three dimensions of clinical empathy-Perspective-Taking, Compassionate Care, and Standing in Patients' Shoes- will be directly and negatively related to depression, as well as indirectly through its inverse relationship with three facets of burnout, Emotional Exhaustion, Poor Academic Efficacy, and Cynicism.

A chromosome-level Amaranthus cruentus genome assembly highlights gene family evolution and biosynthetic gene clusters that may underpin the nutritional value of this traditional crop.

Traditional crops have historically provided accessible and affordable nutrition to millions of rural dwellers but have been neglected, with most modern agricultural systems over-reliant on a small number of internationally traded crops. Traditional crops are typically well-adapted to local agro-ecological conditions and many are nutrient-dense. They can play a vital role in local food systems through enhanced nutrition (particularly where diets are dominated by starch crops), food security and livelihoods for smallholder farmers, and a climate-resilient and biodiverse agriculture.

Vitamin D upregulates the macrophage complement receptor immunoglobulin in innate immunity to microbial pathogens.

Vitamin D deficiency remains a global concern. This 'sunshine' vitamin is converted through a multistep process to active 1,25-dihydroxyvitamin D (1,25D), the final step of which can occur in macrophages. Here we demonstrate a role for vitamin D in innate immunity.

Effectiveness of an eHealth self-management tool for older adults with multimorbidity (KeepWell): protocol for a hybrid effectiveness-implementation randomised controlled trial.

Introduction: In response to the burden of chronic disease among older adults, different chronic disease self-management tools have been created to optimise disease management. However, these seldom consider all aspects of disease management are not usually developed specifically for seniors or created for sustained use and are primarily focused on a single disease. We created an eHealth self-management application called 'KeepWell' that supports seniors with complex care needs in their homes.

Building a Digital Bridge to Support Patient-Centered Care Transitions From Hospital to Home for Older Adults With Complex Care Needs: Protocol for a Co-Design, Implementation, and Evaluation Study.

Background: Older adults with multimorbidity and complex care needs (CCN) are among those most likely to experience frequent care transitions between settings, particularly from hospital to home. Transition periods mark vulnerable moments in care for individuals with CCN. Poor communication and incomplete information transfer between clinicians and organizations involved in the transition from hospital to home can impede access to needed support and resources.

Downy Mildew effector HaRxL21 interacts with the transcriptional repressor TOPLESS to promote pathogen susceptibility.

Hyaloperonospora arabidopsidis (Hpa) is an oomycete pathogen causing Arabidopsis downy mildew. Effector proteins secreted from the pathogen into the plant play key roles in promoting infection by suppressing plant immunity and manipulating the host to the pathogen's advantage. One class of oomycete effectors share a conserved 'RxLR' motif critical for their translocation into the host cell.

The impact of Clinical Nurse Specialists on the decision making process in cancer multidisciplinary team meetings: A qualitative study.

Purpose: There are well-documented barriers to nurse participation in cancer multidisciplinary team (MDT) meetings. This paper aims to identify the approaches used by Clinical Nurse Specialists (CNSs) in this setting to contribute during discussion, and to consider the impact of these approaches on the decision making process. In doing so it aims to highlight ways that CNSs can increase their influence, and enhance multidisciplinary engagement.

Collaborative learning: Application of the mentorship model for adult nursing students in the acute placement setting.

Traditionally mentorship of pre-registration student nurses in clinical practice has followed a 1:1 model. Students are allocated a named mentor for the duration of the placement and they are responsible for supporting and assessing the learner. Many studies have identified problems with this approach to mentorship, including lack of time to facilitate learning on a 1:1 basis.

Partial maintenance of organ-specific epigenetic marks during plant asexual reproduction leads to heritable phenotypic variation.

Plants differ from animals in their capability to easily regenerate fertile adult individuals from terminally differentiated cells. This unique developmental plasticity is commonly observed in nature, where many species can reproduce asexually through the ectopic initiation of organogenic or embryogenic developmental programs. While organ-specific epigenetic marks are not passed on during sexual reproduction, the fate of epigenetic marks during asexual reproduction and the implications for clonal progeny remain unclear.

The Crucible simulation: Behavioral simulation improves clinical leadership skills and understanding of complex health policy change.

Background: The Health and Social Care Act 2012 represents the most complex National Health Service reforms in history. High-quality clinical leadership is important for successful implementation of health service reform. However, little is known about the effectiveness of current leadership training.

Engaging Communities in Identifying Local Strategies for Expanding Integrated Employment During and After High School.

Amidst decades of attention directed toward improving employment outcomes for people with intellectual and developmental disabilities (IDD), few efforts have been made to engage communities in identifying local solutions for expanding integrated employment opportunities. We examined the implementation and outcomes of "community conversation" events held in 6 geographically and economically diverse locales. Each event used an asset-based dialogue approach called the World Café ( Brown & Isaacs, 2005 ) to solicit ideas from a broad cross-section of community members on improving integrated employment that reflect local priorities and possibilities.

Folic acid fortified milk increases blood folate to concentrations associated with a very low risk of neural tube defects in Singaporean women of childbearing age.

Background And Objectives: Folic acid (400 μg/d) taken during the periconceptional period reduces neural tube defect (NTD) risk by >75%. Achieving red cell folate (RCF) or plasma folate (PF) >905 nmol/L and >35 nmol/L, respectively, has been associated with a low risk of NTDs. We determined whether daily consumption of folic acid fortified milk increases blood folate concentrations to levels associated with a low risk of NTDs in Singaporean women of childbearing age.

Improving crop disease resistance: lessons from research on Arabidopsis and tomato.

One of the great challenges for food security in the 21st century is to improve yield stability through the development of disease-resistant crops. Crop research is often hindered by the lack of molecular tools, growth logistics, generation time and detailed genetic annotations, hence the power of model plant species. Our knowledge of plant immunity today has been largely shaped by the use of models, specifically through the use of mutants.

Effect of pasteurization on immune components of milk: implications for feeding preterm infants.

It has been unequivocally proven that human breast milk is the ideal source of nutrition for infants. However, mothers of preterm infants face a number of barriers to providing sufficient milk volume to their babies, who are at risk for developing necrotizing enterocolitis (NEC). Donated milk, distributed through milk banks, is becoming a desirable alternative to formula feeding, and is increasingly being considered for hospitalized, preterm infants in North America.

Establishment of a southern breast cancer cohort.

Breast cancer continues to be among the most common cancers affecting women in the United States. Researchers investigating the area are turning their attention to novel prevention, detection, and treatment options. Recent molecular epidemiology research has highlighted the effects of both genetic and environmental exposures on an individual's risk of developing breast cancer and predicted response to treatment.