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Rural school principals in Tennessee face serious challenges in leading their schools, including isolation, high turnover, and a lack of instructional leadership skills. Facilitated by a state university, the Tennessee Rural Principals Network (TRPN) was developed to provide professional learning opportunities for rural school principals. The purpose of this study was to explore the perceptions of principals in rural schools who participated in the TRPN during the years 2019-2021 (n = 133). The study used a basic qualitative research design with semi-structured interviews of 12 participants. Through our data analysis, key learning strengths and challenges were identified and organized under the codes of learning needs, coaching, mentoring, and networking. From these categories, we developed three themes: (a) sharing and collaborating through networks; (b) building capacity through mentoring and coaching; and (c) addressing the learning needs of principals in a rural context. Findings revealed that principals were pleased with the network and felt it helped them better navigate their roles as rural principals by providing the tools to develop best practices and a network to share ideas and resources.

Over the past 25 years, substantive scholarly literature has been published that focuses on ethical decision-making by school administrators. In addition, learning activities integrated in principal preparation programs (PPPs) that relate to professional ethics and character education provides aspiring school administrators with functional tools and strategies to address challenging workplace issues, including matters that relate to inequity, racism and oppression. This literature review provides a current understanding of K-12 character education and ethics as it relates to school administrator professional preparation and practice. Using well-defined criteria, 31 peer-reviewed research articles published during the past 25 years were included in this review. After a thorough comparative analysis was completed, four overarching themes emerged that relate concepts of ethics and school leadership: (a) principal preparation program practices that focus on professional ethics, (b) implementation of character education interventions in schools, (c) non-commensurate school administrator attention to student achievement, and (d) school administrator attitudes on ethics and the development of character.

Principal Wilson is a first-year leader of a virtual high school. Following four years as an assistant principal in the brick-and-mortar school, she encounters unanticipated leadership challenges and policy dilemmas. Although discipline issues are nearly nonexistent, remote testing presents an ethical challenge. Moreover, she discovers that implementing the tenants of social presence is an unconditional requirement of a virtual school. In this case, the principal faces tough decisions when considering discipline for cheating, the lack of professional development for part-time teachers, and the potential effects of trauma-influenced behavior. This case explores the emerging field of virtual school principal leadership in the context of increasing online K-12 learning post-pandemic.

In this rapid communication, accelerated undergraduate medical education is examined using prior literature as well as experiences of those who have completed or are in the process of completing accelerated medical curricula. The Consortium of Accelerated Medical Pathway Programs (CAMPP) hosts an annual multi-institutional conference for all its members. During the meeting in July 2023, a virtual panel was convened from multiple constituent programs (N = 4) including medical students (N = 2), resident physicians (N = 4), and faculty (N = 2). Panel participants represented current learners or graduates from accelerated pathways of varying specialties (N = 5) to share firsthand experiences about acceleration to an audience representing over 25 medical schools. Five key themes were identified for accelerated students and trainees: Reduced debt as motivating factor to accelerate, Feeling prepared for residency, Ideal accelerated students are driven, Ability to form early professional relationships, and Less time for additional clinical experiences. Discourse from the CAMPP panel can inform current and developing accelerated programs at institutions looking to create or improve accelerated learning.

We still think of human disease as the work of an organized, modernized kind of demonology, in which the bacteria are the most visible and centrally placed of our adversaries. [...]

Abstract Glucose, a primary fuel source under homeostatic conditions, is transported into cells by membrane transporters such as glucose transporter 1 (GLUT1). Due to its essential role in maintaining energy homeostasis, dysregulation of GLUT1 expression and function can adversely affect many physiological processes in the body. This has implications in a wide range of disorders such as Alzheimer’s disease (AD) and several types of cancers. However, the regulatory pathways that govern GLUT1 expression, which may be altered in these diseases, are poorly characterized. To gain insight into GLUT1 regulation, we performed an arrayed CRISPR knockout screen using Caco-2 cells as a model cell line. Using an automated high content immunostaining approach to quantify GLUT1 expression, we identified more than 300 genes whose removal led to GLUT1 downregulation. Many of these genes were enriched along signaling pathways associated with G-protein coupled receptors, particularly the rhodopsin-like family. Secondary hit validation confirmed that removal of select genes, or modulation of the activity of a corresponding protein, yielded changes in GLUT1 expression. Overall, this work provides a resource and framework for understanding GLUT1 regulation in health and disease.

Clinical applications of CAR-T cells are limited by the scarcity of tumor-specific targets and are often afflicted with the same on-target/off-tumor toxicities that plague other cancer treatments. A new promising strategy to enforce tumor selectivity is the use of logic-gated, two-receptor systems. One well-described application is termed Tmod™, which originally utilized a blocking inhibitory receptor directed towards HLA-I target antigens to create a protective NOT gate. Here we show that the function of Tmod blockers targeting non-HLA-I antigens is dependent on the height of the blocker antigen and is generally compatible with small, membrane-proximal targets. We compensate for this apparent limitation by incorporating modular hinge units to artificially extend or retract the ligand-binding domains relative to the effector cell surface, thereby modulating Tmod activator and blocker function. By accounting for structural differences between activator and blocker targets, we developed a set of simple geometric parameters for Tmod receptor design that enables targeting of blocker antigens beyond HLA-I, thereby broadening the applications of logic-gated cell therapies.

Research regarding the practice of leaders' mindfulness has increased over the past several years. Emphasis on principals' mindfulness practices helped educational leaders become stronger during these uncertain and stressful times. Specifically, researching how principals use mindfulness in a school setting advances educational leadership by exploring this relationship. This systematic review aimed to understand how principals use mindful practices in their schools and relationships with their stakeholders. Attributes of mindfulness used in their leadership practices were explored to influence ways to enhance educational leadership training. Fourteen peer-reviewed research studies from 2010-2021 were reviewed. There were five key themes identified related to a principal's use of mindfulness: (1) school organization; (2) decision-making; (3) well-being; (4) leadership attributes; and (5) student success. This article concluded by discussing the key findings and suggestions to guide future research on principals' mindfulness.

Abstract Majority of patients with indolent prostate cancer (PCa) can be managed with active surveillance. Therefore, finding biomarkers for classifying patients between indolent and aggressive PCa is essential. In this study, we investigated urinary marker panels composed of urinary glycopeptides and/or urinary prostate-specific antigen (PSA) for their clinical utility in distinguishing non-aggressive (Grade Group 1) from aggressive (Grade Group ≥ 2) PCa. Urinary glycopeptides acquired via data-independent acquisition mass spectrometry (DIA-MS) were quantitatively analyzed, where prostatic acid phosphatase (ACPP), clusterin (CLU), alpha-1-acid glycoprotein 1 (ORM1), and CD antigen 97 (CD97) were selected to be evaluated in various combinations with and without urinary PSA. Targeted parallel reaction monitoring (PRM) assays of the glycopeptides from urinary ACPP and CLU were investigated along with urinary PSA for the ability of aggressive PCa detection. The multi-urinary marker panels, combined via logistic regression, were statistically evaluated using bootstrap resampling and validated by an independent cohort. Majority of the multi-urinary marker panels (e.g., a panel consisted of ACPP, CLU, and Urinary PSA) achieved area under the curve (AUC) ranged from 0.70 to 0.85. Thus, multi-marker panels investigated in this study showed clinically meaningful results on aggressive PCa detection to separate Grade Group 1 from Grade Group 2 and above warranting further evaluation in clinical setting in future.

Abstract Context Kidney transplant is superior to dialysis for the treatment of end‐stage kidney disease, but accessing transplant requires high patient engagement to overcome barriers. We sought to develop an educational counselling intervention for patients along with their social support networks to help patients access the waiting list. Methods Utilizing an Intervention Mapping approach, we established a conceptual framework to develop a behavioural intervention that can be reproduced across kidney transplant centres. The approach includes needs assessment, identifying behavioural determinants and process objectives and integrating targeted behavioural change theory. Results The Intervention Mapping process resulted in the development of a group counselling session, titled Journey to Transplant (JtT). This intervention was designed for kidney transplant candidates along with members of their social support networks and guided by a transplant healthcare professional. The session begins with standardized educational information to improve knowledge and normalize emotional barriers to transplant. This education is followed by a tailored counselling intervention, including the presentation of the individual patient's calculated likely outcomes on the kidney transplant waiting list. Finally, JtT incorporates patient and support network goal setting to address the specific barriers for that patient in accessing kidney transplantation. Conclusion A systematic Intervention Mapping approach to develop the JtT intervention helps ensure the intervention is efficacious, acceptable and feasible for transplant centres to implement. JtT engages the patient's social support network, targeting known barriers to transplant and utilizing established behaviour change theory to motivate concrete actions to improve the likelihood of kidney transplantation. Patient or Public Contribution This study includes a patient and family advisory committee comprised of kidney transplant candidates and their family members to guide the final language and content of the intervention guide, and the conduct of the implementation and pilot testing of the intervention. However, patients and family members were not involved in the intervention mapping development process itself described in this manuscript, which was informed by focus group data from patient and family study participants.

Ratioing describes when a reply earns more likes than an original post on social media. They also offer influencers opportunities to convert audience attention into political actions capable of temporarily shaping online discourse. Ratios are then one of many influencer-driven strategies that leverage platform features and affordances to direct audiences to specific actions that amplify the influencer’s content in the crowded social media entertainment market. Hasan Piker is one of the most popular political influencers on Twitch, which he uses as a base to organize and direct his audience into coordinated actions across multiple platforms. Piker reigns on Twitch, but has significantly less Twitter followers than all of his targets, meaning the ratio strategy prompts targeted actions that simultaneously increase his visibility. This article uses three case studies to highlight ratioing as a strategy for eliciting political participation, such as when Piker ratioed rivaling political influencers, a US Senator, and a famous rapper.

Tropical cyclones produce exceptionally negative rainwater isotopic values that can serve as a proxy to reconstruct past large tropical cyclones, suggests high-resolution rainwater sampling during Hurricane Harvey in 2017

Patient-derived xenografts (PDXs) are an appealing platform for preclinical drug studies. A primary challenge in modeling drug response prediction (DRP) with PDXs and neural networks (NNs) is the limited number of drug response samples. We investigate multimodal neural network (MM-Net) and data augmentation for DRP in PDXs. The MM-Net learns to predict response using drug descriptors, gene expressions (GE), and histology whole-slide images (WSIs). We explore whether combining WSIs with GE improves predictions as compared with models that use GE alone. We propose two data augmentation methods which allow us training multimodal and unimodal NNs without changing architectures with a single larger dataset: 1) combine single-drug and drug-pair treatments by homogenizing drug representations, and 2) augment drug-pairs which doubles the sample size of all drug-pair samples. Unimodal NNs which use GE are compared to assess the contribution of data augmentation. The NN that uses the original and the augmented drug-pair treatments as well as single-drug treatments outperforms NNs that ignore either the augmented drug-pairs or the single-drug treatments. In assessing the multimodal learning based on the MCC metric, MM-Net outperforms all the baselines. Our results show that data augmentation and integration of histology images with GE can improve prediction performance of drug response in PDXs.

Cancer claims millions of lives yearly worldwide. While many therapies have been made available in recent years, by in large cancer remains unsolved. Exploiting computational predictive models to study and treat cancer holds great promise in improving drug development and personalized design of treatment plans, ultimately suppressing tumors, alleviating suffering, and prolonging lives of patients. A wave of recent papers demonstrates promising results in predicting cancer response to drug treatments while utilizing deep learning methods. These papers investigate diverse data representations, neural network architectures, learning methodologies, and evaluations schemes. However, deciphering promising predominant and emerging trends is difficult due to the variety of explored methods and lack of standardized framework for comparing drug response prediction models. To obtain a comprehensive landscape of deep learning methods, we conducted an extensive search and analysis of deep learning models that predict the response to single drug treatments. A total of 61 deep learning-based models have been curated, and summary plots were generated. Based on the analysis, observable patterns and prevalence of methods have been revealed. This review allows to better understand the current state of the field and identify major challenges and promising solution paths.

Abstract Background Estimates indicate that nearly 8% of the over 500,000 survivors of childhood cancer living in the United States are frail in their fourth and fifth decades of life, a phenotype typically seen in geriatric populations. Participation in regular physical activity to improve physical fitness in healthy and diseased populations reduces risk for frail health by increasing physiologic reserve. However, physical activity may not have the same effects on fitness in childhood cancer survivors as it does among their peers with no cancer history. Aims This scoping review seeks to describe associations between physical activity, physical fitness, chronic disease, and mortality in childhood cancer survivors. Methods Relevant literature was identified through a comprehensive search in the PubMed, Web of Science, CINAHL, and Cochrane databases. A narrative synthesis was performed on observational studies that had physical activity or physical fitness clearly defined and compared with chronic disease outcomes. Results A total of 595 studies were screened, and results from 11 studies are presented. Childhood cancer survivors who participate in regular physical activity have improved markers of cardiovascular health, decreased risk of overt cardiovascular disease, and decreased risk of all‐cause mortality compared to survivors who are not physically active. Childhood cancer survivors who are physically fit have increased neurocognition, and decreased risk of all‐cause mortality compared to survivor's who are not fit. The differential effects of physical activity on fitness and health among childhood cancer survivors when compared to peers is potentially related to treatment exposures that damage cardiovascular tissue and impact regenerative potential. Conclusion Research is needed to determine the optimal timing, frequency, intensity, and duration of physical activity necessary to optimize fitness in childhood cancer survivors.