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Recent reports show that low-income students make up a significant share of those participating in higher education, and their well-being constitutes a key factor that influences their college success. This mixed-methods study examined first-year, low-income students' time use and its relationship to well-being framed by an equity-oriented lens that recognizes the time constraints low-income students navigate. Our mixed methods findings identified the link between time use and well-being and--critically--empirical explanations for these links. First, leveraging a unique experience sampling survey design and multilevel analyses, we found that attending class, studying or doing homework, and working for pay were consistently and adversely related to low-income students' well-being. Low-income students who were also first-generation in college fared worse than continuing-generation students when engaging in these experiences. On the other hand, socializing was positively related to low-income students' well-being. Second, an exploration of longitudinal data from hundreds of student interviews illuminated two primary factors that shaped the relationship between low-income students' time use and well-being: (a) structuring time and developing a routine, and (b) the power of reflection and meaning-making. These findings provide important novel insights about low-income students' college experiences and the relationship between their time use and well-being, and offer crucial guidance for educators on how to support low-income students' well-being as they navigate college.

BackgroundOver their evolutionary history, corals have adapted to sea level rise and increasing ocean temperatures, however, it is unclear how quickly they may respond to rapid change. Genome structure and genetic diversity contained within may highlight their adaptive potential.ResultsWe present chromosome-scale genome assemblies and linkage maps of the critically endangered Atlantic acroporids, Acropora palmata and A. cervicornis. Both assemblies and linkage maps were resolved into 14 chromosomes with their gene content and colinearity. Repeats and chromosome arrangements were largely preserved between the species. The family Acroporidae and the genus Acropora exhibited many phylogenetically significant gene family expansions. Macrosynteny decreased with phylogenetic distance. Nevertheless, scleractinians shared six of the 21 cnidarian ancestral linkage groups as well as numerous fission and fusion events compared to other distantly related cnidarians. Genetic linkage maps were constructed from one A. palmata family and 16 A. cervicornis families using a genotyping array. The consensus maps span 1,013.42 cM and 927.36 cM for A. palmata and A. cervicornis, respectively. Both species exhibited high genome-wide recombination rates (3.04 to 3.53 cM/Mb) and pronounced sex-based differences, known as heterochiasmy, with 2 to 2.5X higher recombination rates estimated in the female maps.ConclusionsTogether, the chromosome-scale assemblies and genetic maps we present here are the first detailed look at the genomic landscapes of the critically endangered Atlantic acroporids. These data sets revealed that adaptive capacity of Atlantic acroporids is not limited by their recombination rates. The sister species maintain macrosynteny with few genes with high sequence divergence that may act as reproductive barriers between them. In the Atlantic Acropora, hybridization between the two sister species yields an F1 hybrid with limited fertility despite the high levels of macrosynteny and gene colinearity of their genomes. Together, these resources now enable genome-wide association studies and discovery of quantitative trait loci, two tools that can aid in the conservation of these species.

Myocardial infarction (MI) results in aberrant cardiac metabolism, but no therapeutics have been designed to target cardiac metabolism to enhance heart repair. We engineer a humanized monoclonal antibody against the ectonucleotidase ENPP1 (hENPP1mAb) that targets metabolic crosstalk in the infarcted heart. In mice expressing human ENPP1, systemic administration of hENPP1mAb metabolically reprograms myocytes and non-myocytes and leads to a significant rescue of post-MI heart dysfunction. Using metabolomics, single-nuclear transcriptomics, and cellular respiration studies, we show that the administration of the hENPP1mAb induces organ-wide metabolic and transcriptional reprogramming of the heart that enhances myocyte cellular respiration and decreases cell death and fibrosis in the infarcted heart. Biodistribution and safety studies showed specific organ-wide distribution with the antibody being well tolerated. In humanized animals, with drug clearance kinetics similar to humans, we demonstrate that a single "shot" of the hENPP1mAb after MI is sufficient to rescue cardiac dysfunction.

For some children and young people (CYP) with long-term physical health conditions (LTPHCs) attending school can be difficult. There is a lack of evidence documenting their school attendance experiences, how schools manage absence for these children, and subsequent effects. This study utilised an existing dataset from eighty-nine 11-18-year-olds in mainstream secondary schools in the United Kingdom across 11 LTPHCs that provided first-hand accounts about the children's experiences of school. Data pre-coded "attendance" were subject to thematic analysis to explore issues emerging. Findings showed attendance patterns varied, with some CYP missing little and others significant amounts of education. Children with LTPHCs wanted to attend school and did their best to navigate education alongside health. School systems for attendance were inconsistent and adversarial. Remedial and supportive action emerged as lacking, and children felt it was their personal responsibility to make up for lost time and missed work when absent. Decisions on whether they attended school, coupled with practices promoting high attendance had detrimental consequences for CYP with LTPHCs educationally, emotionally and socially. Overall, children with LTPHCs felt punished, stigmatised, unfairly treated, unequal and excluded. Results have implications for education, health, and policy practitioners to better plan and target attention so that the LTPHC cohort are treated sensitively and equitably and afforded their entitlement to education when they cannot go to school for health reasons often outside of their control.

INTRODUCTION: Duchenne muscular dystrophy (DMD) is characterized by rapid functional decline. Current available treatment options aim to delay disease progression or stabilize physical function. To aid in healthcare providers understanding of the symptoms of disease that impact patients experience, this study explored childrens physical functioning, activities of daily living (ADLs), and health-related quality of life (HRQoL) after receiving eteplirsen, a weekly infusion indicated for individuals with DMD with exon 51 skip-amenable mutations. METHODS: Fifteen caregivers of male individuals with DMD participated in a 60-min, semi-structured interview. Open-ended questioning explored changes in the childrens condition or maintenance in abilities since eteplirsen initiation. RESULTS: Children with DMD (age 7-15 years [mean 10.9]; steroid treatment at interview, n = 8; time since eteplirsen initiation 3-24 months [mean 14.9]) were described by caregivers as ambulatory (n = 9) and non-ambulatory (n = 6). Caregivers of ambulatory children reported improvements or maintenance of walking ability (n = 7/9), running (n = 6/9), and using stairs (n = 4/9). Continued decline in using stairs was reported by two caregivers. In upper-limb functioning, improvements or maintenances in fine-motor movements were reported by nearly half of all caregivers (n = 7/15), with one caregiver noting a continued decline. Subsequent improvements or maintenances in ADLs were described. Improvements or maintenances in fatigue (n = 9/15), muscle weakness (n = 7/15), and pain (n = 6/15) were reported, although some caregivers described a continued decline (n = 3/15 fatigue, n = 1/15 muscle weakness, n = 2/15 pain). Importantly, most caregivers who reported maintenances in ability perceived this as a positive outcome (n = 6/9). CONCLUSION: This exploratory study indicated that most caregivers perceived improvements or maintenances in aspects of their childs physical functioning, ADLs, and HRQoL since eteplirsen initiation, which they perceived to be a positive outcome.

Introduction: Recent trends in training teachers of students who are blind or have low vision (i.e., those who are visually impaired) have shifted away from traditional hand-over-hand guidance and toward a hand-under-hand approach. However, a search for peer-reviewed studies that address the effects of the use of hand-under-hand versus hand-over-hand instructional techniques often yields few results. This article examines literature on tactile receptors in the human integumentary system and how different forms of touch may affect tactile learning. Methods: The authors used a purposive search of literature using key words and phrases associated with different forms of touch to examine literature on the effects of touch from the perspectives of both the biological and social sciences. Results: Much of the neurological and sociological research that was revealed in this study tended to support the anecdotal evidence from practitioners who have described learners developing a greater sense of autonomy, independence, and connectedness when they are able to control their own body. Discussion: Literature cited in this study indicates that repeated use of controlling forms of touch may inhibit learning through the discriminative tactile system. In addition, the authors describe literature indicating that implicit social messages conveyed through controlling touch may perpetuate stereotypes of individuals with visual impairments as dependent on sighted people and create social barriers to independence.

This case study explores a partnership within an events management topic. Students were encouraged to take ownership over the creation and operation of an event held on the university campus. The topic lecturer provided guidance throughout the process and liaised with the students to define the assessment and the marking rubric for the event project. Research data was captured through two surveys--one during the event project and one after the event project was completed. The surveys captured quantitative and qualitative data about students' perceptions on the benefits, challenges, and outcomes of this experiential learning experience. Survey findings indicated that communication and teamwork were key aspects that needed to be managed to effectively collaborate on the project. Classroom discussion and online communication tools were used to share ideas and information, and work towards the common goals of the event. Through this project, students developed their relationships with their peers and university staff and felt that they had a valuable learning experience that helped to connect theory with practice.

Chronic Human Immunodeficiency Virus (HIV) infection remains a significant challenge to global public health. Despite advances in antiretroviral therapy (ART), which has transformed HIV infection from a fatal disease into a manageable chronic condition, a definitive cure remains elusive. One of the key features of HIV infection is chronic immune activation and inflammation, which are strongly associated with, and predictive of, HIV disease progression, even in patients successfully treated with suppressive ART. Chronic inflammation is characterized by persistent inflammation, immune cell metabolic dysregulation, and cellular exhaustion and dysfunction. This review aims to summarize current knowledge of the interplay between chronic inflammation, immune metabolism, and T cell dysfunction in HIV infection, and also discusses the use of humanized mice models to study HIV immune pathogenesis and develop novel therapeutic strategies.

This quasi-experimental study examined the impact of participation in college-run STEM career days on American high school students' STEM career aspirations. Data were collected from a nationwide retrospective cohort survey of 15,847 U.S. college students who provided information about their experiences during high school. Accounting for self-selection effects and a robust set of controls, results showed that students who participated in a college-run STEM career day during high school had 1.3 times the odds of expressing STEM career aspirations compared with a control group. We found that STEM career days were equally effective in promoting American students' STEM career aspirations across background characteristics, levels of academic preparation, and prior STEM interest. Results suggest that policymakers and educators should seriously consider implementing STEM career days for high school students as an evidence-based strategy to effectively increase STEM career interest.

Drawing from a 5-year mixed methods study of the Thompson Scholar Learning Community (TSLC), we discuss how holistic, proactive, strengthens-oriented, identity conscious, collaborative and reflective norms create a culture of ecological validation wherein at-promise students can experience college success. These norms were then operationalized through the program structures and processes (leadership, socialization, language, space, and communication, ritual and traditions, working relationships and interactions) embedding them into the work of faculty, staff, and administrators. Our study provides empirical evidence of how a culture of ecological validation can provide scaled support for at-promise students. Lastly, this article contributes to the literature by combining three key concepts that have not been explored together -- validation theory, college success cultures, and ecological systems theory focused on at-promise students.

Postsecondary institutions generally exist with student and academic affairs working in silos, which creates a fragmented experience for students. Reduced state and federal funding mean that institutions cannot invest in costly new programs or initiatives. The article provides a research-informed approach with practical advice about how institutions can create a student-centered campus-wide culture. Creating more collaborative and cross-functional spaces will enable faculty, staff, and leadership campus-wide to explore new policies, practices, and structures that allow for students to experience holistic forms of support.

While student engagement has long been associated with students' learning, development, and success, the climate and culture of historically white institutions often create barriers to engagement among racially minoritized students. Given the institutional responsibility to facilitate equitable engagement, there is a need for new policies and practices that meet students' needs. One increasingly popular intervention is comprehensive college transition programs (CCTPs) that provide multipronged approaches to promote the success of underrepresented students. While there is growing evidence that these programs benefit students' outcomes, very little research has explored how they might shape students' engagement--a prerequisite for student success. Therefore, this sequential explanatory mixed methods study used longitudinal data from a multicampus CCTP to understand various aspects of engagement among students with different racialized identities. We found that racially diverse students participating in a CCTP engaged similarly across groups with their peers, faculty, staff, and CCTP academic courses. Key explanations for the similar levels of engagement among racially diverse students that emerged from our analysis included the compositional diversity among students and educators, structured opportunities for meaningful interactions across racial groups, and the identity-conscious approaches used by educators in this CCTP. Our qualitative findings aligned with previous research on college environments, providing empirical evidence that such environments foster similar levels of engagement among racially diverse students. Thus, this study offers important implications for researchers, educators, and administrators to promote equitable engagement among increasingly racially diverse college students.

The Concise Guide to PHARMACOLOGY 2023/24 is the sixth in this series of biennial publications. The Concise Guide provides concise overviews, mostly in tabular format, of the key properties of approximately 1800 drug targets, and over 6000 interactions with about 3900 ligands. There is an emphasis on selective pharmacology (where available), plus links to the open access knowledgebase source of drug targets and their ligands (https://www.guidetopharmacology.org/), which provides more detailed views of target and ligand properties. Although the Concise Guide constitutes almost 500 pages, the material presented is substantially reduced compared to information and links presented on the website. It provides a permanent, citable, point-in-time record that will survive database updates. The full contents of this section can be found at http://onlinelibrary.wiley.com/doi/10.1111/bph.16178. Ion channels are one of the six major pharmacological targets into which the Guide is divided, with the others being: G protein-coupled receptors, nuclear hormone receptors, catalytic receptors, enzymes and transporters. These are presented with nomenclature guidance and summary information on the best available pharmacological tools, alongside key references and suggestions for further reading. The landscape format of the Concise Guide is designed to facilitate comparison of related targets from material contemporary to mid-2023, and supersedes data presented in the 2021/22, 2019/20, 2017/18, 2015/16 and 2013/14 Concise Guides and previous Guides to Receptors and Channels. It is produced in close conjunction with the Nomenclature and Standards Committee of the International Union of Basic and Clinical Pharmacology (NC-IUPHAR), therefore, providing official IUPHAR classification and nomenclature for human drug targets, where appropriate.

PurposeTraditionally, appropriate anchors are used to investigate the amount of change on a clinician-reported outcome assessment that is meaningful to individual patients. However, novel qualitative methods involving input from disease state experts together with patients may better inform the individual improvement threshold for demonstrating the clinical benefit of new treatments. This study aimed to establish a clinically meaningful threshold for treatment success for the clinician-reported Severity of Alopecia Tool (SALT) score for patients with alopecia areata (AA).MethodsA purposive sample of 10 dermatologists expert in AA and 30 adult and adolescent patients with AA and a history of ≥ 50% scalp hair loss were recruited. Semi-structured interview questions explored the outcome that represented treatment success to clinicians and patients. Findings were analyzed using thematic methods to identify treatment success thresholds.ResultsBoth informant groups confirmed scalp hair amount as the outcome of priority. Most expert clinicians considered a static threshold of 80% (n = 5) or 75% (n = 3) of the scalp hair as a treatment success. Most patient responses ranged from 70 to 90% (median: 80% of the scalp hair). Subsequently, queried patients confirmed that achieving SALT score ≤ 20 with treatment would be a success, as reflected in the Alopecia Areata Investigator Global Assessment (AA-IGA™). The novel qualitative processes used to inform this meaningful threshold reflects a clinician-then-patient process for: (a) confirmation of the patient outcome of priority; and (b) clinician input on a preliminary treatment success level for independent understanding among patients.ConclusionThis qualitative investigation of expert clinicians-then-patients with AA confirmed that achieving an amount of 80% or more scalp hair (SALT score ≤ 20) was an appropriate individual treatment success threshold indicating clinically meaningful improvement for patients with ≥ 50% scalp hair loss. A qualitative investigation of a quantifiable treatment success threshold is possible through a well-designed interview process with expert clinicians and the appropriate patient population.

The Foundational Data Initiative for Parkinson Disease (FOUNDIN-PD) is an international collaboration producing fundamental resources for Parkinson disease (PD). FOUNDIN-PD generated a multi-layered molecular dataset in a cohort of induced pluripotent stem cell (iPSC) lines differentiated to dopaminergic (DA) neurons, a major affected cell type in PD. The lines were derived from the Parkinson's Progression Markers Initiative study, which included participants with PD carrying monogenic PD variants, variants with intermediate effects, and variants identified by genome-wide association studies and unaffected individuals. We generated genetic, epigenetic, regulatory, transcriptomic, and longitudinal cellular imaging data from iPSC-derived DA neurons to understand molecular relationships between disease-associated genetic variation and proximate molecular events. These data reveal that iPSC-derived DA neurons provide a valuable cellular context and foundational atlas for modeling PD genetic risk. We have integrated these data into a FOUNDIN-PD data browser as a resource for understanding the molecular pathogenesis of PD.

Systemic inequalities in higher education have contributed to lower retention and completion rates among low-income, first generation, and racially/ethnically minoritized students, who we refer to as "at-promise" students. In response, educators have implemented comprehensive college transition programs that offer students holistic support including academic, social, financial, and major and career support. Scholarship exploring the efficacy of comprehensive college transition programs commonly focuses on the role of this support in promoting academic self-efficacy, retention, sense of belonging, and other intermediate outcomes linked to at-promise college student success. One sorely understudied intermediate outcome related to at-promise college students' success is their confidence in a major and career path (i.e., major and career self-efficacy). This article focuses on a large scale, longitudinal (2015-2020) study of a comprehensive college transition program called Thompson Scholars that offers major and career support to promote at-promise college students' major and career self-efficacy. Based on the Thompson Scholars' approach, we identified a new model for developing major and career self-efficacy among at-promise students called the "At-Promise College Student Major and Career-Self Efficacy Ecology Model" that explains how and why Thompson Scholars promotes students' confidence in their major and career path. This new approach illustrates how educators can curate a developmentally appropriate set of major and career experiences across multiple contexts responsive to at-promise students' multiple assets to build their confidence.

This article draws on a five-year mixed methods study and focuses on the way staff tailor support within a comprehensive college transition program to meet the needs of low-income, first-generation, and racially minoritized students by adapting programmatic offerings and requirements to fit students' multifaceted needs. The study also identifies the way tailoring reduces cognitive load for students because the tailored interventions are embedded within a single program, rather than having students visit dozens of offices trying to piece together the support they need. The program created an approach to tailoring student support that draws on the best of predictive analytics and case management simultaneously while also being non-deficit and asset-based. Our study contributes to the literature by identifying the value of tailoring approaches to address students' multiple needs and identities.

IntroductionWhile antibodies raised by SARS-CoV-2 mRNA vaccines have had compromised efficacy to prevent breakthrough infections due to both limited durability and spike sequence variation, the vaccines have remained highly protective against severe illness. This protection is mediated through cellular immunity, particularly CD8+ T cells, and lasts at least a few months. Although several studies have documented rapidly waning levels of vaccine-elicited antibodies, the kinetics of T cell responses have not been well defined.MethodsInterferon (IFN)-γ enzyme-linked immunosorbent spot (ELISpot) assay and intracellular cytokine staining (ICS) were utilized to assess cellular immune responses (in isolated CD8+ T cells or whole peripheral blood mononuclear cells, PBMCs) to pooled peptides spanning spike. ELISA was performed to quantitate serum antibodies against the spike receptor binding domain (RBD).ResultsIn two persons receiving primary vaccination, tightly serially evaluated frequencies of anti-spike CD8+ T cells using ELISpot assays revealed strikingly short-lived responses, peaking after about 10 days and becoming undetectable by about 20 days after each dose. This pattern was also observed in cross-sectional analyses of persons after the first and second doses during primary vaccination with mRNA vaccines. In contrast, cross-sectional analysis of COVID-19-recovered persons using the same assay showed persisting responses in most persons through 45 days after symptom onset. Cross-sectional analysis using IFN-γ ICS of PBMCs from persons 13 to 235 days after mRNA vaccination also demonstrated undetectable CD8+ T cells against spike soon after vaccination, and extended the observation to include CD4+ T cells. However, ICS analyses of the same PBMCs after culturing with the mRNA-1273 vaccine in vitro showed CD4+ and CD8+ T cell responses that were readily detectable in most persons out to 235 days after vaccination.DiscussionOverall, we find that detection of spike-targeted responses from mRNA vaccines using typical IFN-γ assays is remarkably transient, which may be a function of the mRNA vaccine platform and an intrinsic property of the spike protein as an immune target. However, robust memory, as demonstrated by capacity for rapid expansion of T cells responding to spike, is maintained at least several months after vaccination. This is consistent with the clinical observation of vaccine protection from severe illness lasting months. The level of such memory responsiveness required for clinical protection remains to be defined.

A hallmark of HIV-1 infection is chronic inflammation, even in patients treated with antiretroviral therapy (ART). Chronic inflammation drives HIV-1 pathogenesis, leading to loss of CD4+ T cells and exhaustion of antiviral immunity. Therefore, strategies to safely reduce systematic inflammation are needed to halt disease progression and restore defective immune responses. Autophagy is a cellular mechanism for disposal of damaged organelles and elimination of intracellular pathogens. Autophagy is pivotal for energy homeostasis and plays critical roles in regulating immunity. However, how it regulates inflammation and antiviral T cell responses during HIV infection is unclear. Here, we demonstrate that autophagy is directly linked to IFN-I signaling, which is a key driver of immune activation and T cell exhaustion during chronic HIV infection. Impairment of autophagy leads to spontaneous IFN-I signaling, and autophagy induction reduces IFN-I signaling in monocytic cells. Importantly, in HIV-1-infected humanized mice, autophagy inducer rapamycin treatment significantly reduced persistent IFN-I-mediated inflammation and improved antiviral T cell responses. Cotreatment of rapamycin with ART led to significantly reduced viral rebound after ART withdrawal. Taken together, our data suggest that therapeutically targeting autophagy is a promising approach to treat persistent inflammation and improve immune control of HIV replication.