Graph Perceiver Network for Lung Tumor and Bronchial Premalignant Lesion Stratification from Histopathology.

Bronchial premalignant lesions (PMLs) precede the development of invasive lung squamous cell carcinoma (LUSC), posing a significant challenge in distinguishing those likely to advance to LUSC from those that might regress without intervention. This study followed a novel computational approach, the Graph Perceiver Network, leveraging hematoxylin and eosin-stained whole slide images to stratify endobronchial biopsies of PMLs across a spectrum from normal to tumor lung tissues. The Graph Perceiver Network outperformed existing frameworks in classification accuracy predicting LUSC, lung adenocarcinoma, and nontumor lung tissue on The Cancer Genome Atlas and Clinical Proteomic Tumor Analysis Consortium datasets containing lung resection tissues while efficiently generating pathologist-aligned, class-specific heatmaps. The network was further tested using endobronchial biopsies from two data cohorts, containing normal to carcinoma in situ histology. It demonstrated a unique capability to differentiate carcinoma in situ lung squamous PMLs based on their progression status to invasive carcinoma. The network may have utility in stratifying PMLs for chemoprevention trials or more aggressive follow-up.

Epistaxis and Facial Swelling Due to Nasal Blastomycosis in a Cat.

A 5 yr old castrated male domestic longhair was examined because of left-sided facial swelling and epistaxis. Head computed tomography with contrast identified a mass within the left nasal cavity and multifocal regions of nasal bone osteolysis. Histopathology of nasal mass biopsies and cytology of the facial swelling revealed pyogranulomatous inflammation due to Blastomyces dermatitidis. The cat experienced resolution of clinical signs following 8 mo of treatment with itraconazole. Although rare, clinicians should include blastomycosis on the differential diagnoses list of infectious causes for feline nasal disease if within an endemic area.

Pandemic-Era Digital Education: Insights from an Undergraduate Medical Programme.

The undergraduate medical programme at Newcastle University (NU) includes a fundamental 'Essentials of Medical Practice' (EOMP) phase comprising the first 2 years of study. This period is designed to support entrants in their transition from further education into the advanced study and practice of clinical medicine. The anatomical sciences of gross anatomy, histology and embryology, and life sciences including physiology, pharmacology and genetics are key disciplines taught within the integrated case-based EOMP curriculum. Learners apply basic science knowledge to clinical scenarios during training in practical examination, communication and reasoning skills. Within the modern pedagogic landscape, the development and introduction of technology-enhanced learning strategies have enhanced the provision of remote learning resources in pre-clinical education. However, the emergence of COVID-19 has resulted in widespread technological challenges for educators and learners, and has raised pedagogic, logistical and ethical concerns. Nonetheless, the pandemic has produced favourable conditions for the creation of valuable digital visualisation strategies for learning and teaching, and for developing and modernising universal approaches to remote education. Here, we describe our technology-enhanced adaptations to COVID-19 across the domains of teaching, learning and academic support for pre-clinical learners studying basic life sciences and clinical skills. Moreover, we outline research-informed digital visualisation solutions to pandemic-era challenges and reflect upon experiences gained within our own educational context. In doing so, we provide insights into the impacts and successes of our interventions. While providing a record of unprecedented contemporary circumstances, we also aim to utilise our observations and experiences of COVID-19 pedagogy when developing ongoing strategies for delivering curricula and futureproofing educational practice.

Cultivating an Active Living Plan Through a Social-Ecological Evaluation.

Physical activity (PA) social-ecological model (SEM) posits the importance of several levels of influence critical for PA promotion within communities. The purpose of this study was to examine an SEM evaluation informing a county-wide active living plan in McLennan County, Texas in the United States. Mixed-methods evaluation occurred in 4 stages: (1) county policies (n = 15) were evaluated for PA promoting strategies; (2) PA resource assessments (PARAs) were conducted via Google Maps (n = 171); (3) surveys (n = 244) included the International Physical Activity Questionnaire and interpersonal and intrapersonal factors related to PA; and (4) focus groups (n = 5) were conducted with residents (n = 30), discussing barriers and facilitators to being active. Logistic regression determined significant associations between SEM factors and meeting PA recommendations. Policy scans and PARAs identified strengths and areas of improvement (eg, equitable project selection and disparities in resource quality). Residents reporting fewer barriers (OR = 0.89, P =.01), more perceived behavioral control (odds ratio [OR] = 1.38, P = .01), more social co-participation in PA (OR = 1.20, P = .03), and living in zip codes with higher mean PARA score (OR = 1.22, P = .04) were significantly more likely to meet PA recommendations (Nagelkerke R2 = 0.32). Focus groups also discussed safety and disparities in access and quality. This study suggests the utility of the SEM when evaluating and promoting community PA.

What is the effect of a brief intervention to promote physical activity when delivered in a health care setting? A systematic review.

ISSUE ADDRESSED: What are the effects of a brief intervention to promote physical activity (PA) delivered in a health care setting other than primary care? METHODS: MEDLINE, EMBASE, CINAHL and PsycINFO were used to identify randomised controlled trials which evaluated the effect of brief interventions to increase PA, delivered in a health care setting. Review outcomes included subjectively or objectively measured PA, adherence to prescribed interventions, adverse events, health-related quality of life, self-efficacy and stage of change in relation to PA. Where possible, clinically homogenous studies were combined in a meta-analysis. RESULTS: Twenty-five eligible papers were included. Brief counselling interventions were associated with increased PA compared to control, for both self-reported PA (mean difference 34 minutes/week, 95% confidence intervals [95% CI] 9-60 minutes), and pedometer (MD 1541 steps/day, 95% CI 433-2649) at medium term follow up. CONCLUSION: Our findings suggest that some brief interventions to increase PA, delivered in the health care setting, are effective at increasing PA in the medium term. There is limited evidence for the long-term efficacy of such interventions. The wide variation in types of interventions makes it difficult to determine which intervention features optimize outcomes. SO WHAT?: Brief counselling interventions delivered in a health care setting may support improved PA. Clinicians working in health care settings should consider the implementation of brief interventions to increase PA in vulnerable patient groups, including older adults and those with chronic illness.

Beliefs about social norms and racial inequalities predict variation in the early development of racial bias.

Racism remains a pervasive force around the world with widespread and well documented harmful consequences for members of marginalized racial groups. The psychological biases that maintain structural and interpersonal racism begin to emerge in early childhood, but with considerable individual variation-some children develop more racial bias than others. The present study (N = 116; 4-year-old children) provides novel insights into the developmental mechanisms underlying the emergence of racial bias by longitudinally documenting how two psychological processes-normative beliefs about interracial friendships and explanatory beliefs about racial inequalities-developmentally predict the emergence of pro-White/anti-Black racial bias during early childhood. In a 6-month, three-wave, longitudinal study, we found that 4-year-old children's beliefs that their parents and peers do not value interracial friendships predicted increased racial bias in and across time and that children's endorsement of essentialist over extrinsic explanations for racial inequalities predicted the developmental trajectory of racial bias over time. These findings suggest that children's foundational beliefs about the social world developmentally predict the emergence of racial bias in early childhood and speak to the importance of early and persistent intervention efforts targeting children's normative beliefs about interracial friendships and explanatory beliefs about racial inequalities.

A Novel Cadaveric Embalming Technique for Enhancing Visualisation of Human Anatomy.

Within the discipline of anatomical education, the use of donated human cadavers in laboratory-based learning activities is often described as the 'gold standard' resource for supporting student understanding of anatomy. Due to both historical and educational factors, cadaveric dissection has traditionally been the approach against which other anatomy learning modalities and resources have been judged. To prepare human donors for teaching purposes, bodies must be embalmed with fixative agents to preserve the tissues. Embalmed cadavers can then be dissected by students or can be prosected or plastinated to produce teaching resources. Here, we describe the history of cadaveric preservation in anatomy education and review the practical strengths and limitations of current approaches for the embalming of human bodies. Furthermore, we investigate the pedagogic benefits of a range of established modern embalming techniques. We describe relevant cadaveric attributes and their impacts on learning, including the importance of colour, texture, smell, and joint mobility. We also explore the emotional and humanistic elements of the use of human donors in anatomy education, and the relative impact of these factors when alternative types of embalming process are performed. Based on these underpinnings, we provide a technical description of our modern Newcastle-WhitWell embalming process. In doing so, we aim to inform anatomy educators and technical staff seeking to embalm human donors rapidly and safely and at reduced costs, while enhancing visual and haptic tissue characteristics. We propose that our technique has logistical and pedagogic implications, both for the development of embalming techniques and for student visualisation and learning.

A Brief Intervention of Physical Activity Education and Counseling in Community Rehabilitation: A Feasibility Randomized Controlled Trial.

This study aimed to assess the feasibility of delivering a brief physical activity (PA) intervention to community rehabilitation clients. Participants were randomized to receive one session of stage-of-change-based PA education and counseling in addition to written educational material, or education material alone. Outcomes were measured at baseline and 3 months; the primary outcome was feasibility, measured by the percentage of those who were eligible, consented, randomized, and followed-up. A total of 123 individuals were both eligible and interested in participating, 32% of those screened on admission to the program. Forty participants consented, and 35 were randomized, with mean age 72 years (SD = 12.2). At baseline, 66% had recently commenced or intended to begin regular PA in the next 6 months. A total of 30 participants were followed-up. It is feasible to deliver education and counseling designed to support the long-term adoption of regular PA to community rehabilitation clients. Further refinement of the protocol is warranted (ACTRN12617000519358).

North American Fireflies Host Low Bacterial Diversity.

Although there are numerous studies of firefly mating flashes, lantern bioluminescence, and anti-predation lucibufagin metabolites, almost nothing is known about their microbiome. We therefore used 16S rRNA community amplicon sequencing to characterize the gut and body microbiomes of four North American firefly taxa: Ellychnia corrusca, the Photuris versicolor species complex, Pyractomena borealis, and Pyropyga decipiens. These firefly microbiomes all have very low species diversity, often dominated by a single species, and each firefly type has a characteristic microbiome. Although the microbiomes of male and female fireflies did not differ from each other, Ph. versicolor gut and body microbiomes did, with their gut microbiomes being enriched in Pseudomonas and Acinetobacter. Ellychnia corrusca egg and adult microbiomes were unique except for a single egg microbiome that shared a community type with E. corrusca adults, which could suggest microbial transmission from mother to offspring. Mollicutes that had been previously isolated from fireflies were common in our firefly microbiomes. These results set the stage for further research concerning the function and transmission of these bacterial symbionts.

Sodium bicarbonate administration and subsequent potassium concentration in hyperkalemia treatment.

BACKGROUND: Hyperkalemia is an electrolyte disorder commonly encountered in the emergency department that can result in significant morbidity and mortality. While sodium bicarbonate is often used for acute lowering of serum potassium, its efficacy is not well established. The purpose of this study was to evaluate and quantify the amount of potassium reduction in emergency department patients who received intravenous sodium bicarbonate as part of treatment for hyperkalemia compared with those who did not. METHODS: A retrospective electronic chart review was conducted on adult patients who presented to the emergency department with initial potassium concentration greater than or equal to 5.4 mMol/L and received intravenous insulin as part of hyperkalemia treatment. Patients who received intravenous sodium bicarbonate in addition to intravenous insulin were included in the sodium bicarbonate group. The control group included patients who did not receive intravenous sodium bicarbonate. The primary objective of this study was to compare the absolute reduction in serum potassium between initial and second concentrations in patients from the sodium bicarbonate group and those in the control group. RESULTS: A total of 106 patients were included in this study with 38 patients in the sodium bicarbonate group and 68 patients in the control group. Median initial potassium concentration was 6.6 mMol/L in the sodium bicarbonate group and 6.1 mMol/L in the control group (P = 0.009). Absolute reduction of potassium at first repeat was 1 and 0.9 mMol/L in sodium bicarbonate group and control group respectively (P = 0.976). CONCLUSIONS: The addition of sodium bicarbonate therapy to intravenous insulin in the treatment of hyperkalemia did not offer statistically significant added efficacy in potassium lowering. Larger studies are needed to further validate the result findings.

Impact on Healthy Behaviors of Group Obesity Management Visits in Middle School Health Centers.

This mixed-methods community-based participatory pilot study examined the feasibility and preliminary efficacy of group obesity management visits offered through school-based health centers. The study was implemented through an academic-community partnership in three school health centers serving primarily Latinx and African American youth. Participants (n = 71) completed pre- and post-surveys about intention to change diet and exercise habits, knowledge and self-efficacy related to healthy eating, and social support. Focus groups were conducted after the intervention and 18 months later. Group visits were feasible and highly valued by study participants. Quantitative results showed a significant decrease in soda consumption, increased support from classmates, and an increased number of exercise days. In focus groups, youth endorsed cooking, tasting, and shopping activities, noted the importance of family involvement in behavior change, and stated that stress reduction mindfulness exercises helped to change eating habits. Implications for school-based health care and school nursing are discussed.

Children lose confidence in their potential to "be scientists," but not in their capacity to "do science".

Over the course of middle childhood, children's interest and beliefs about their own capacities for success in science often decline. This pernicious decline is especially evident among underrepresented groups, including girls, members of some racial and ethnic minorities, and children from lower socioeconomic backgrounds. The present research (N = 306, ages 6-11) found that while children lose interest and feelings of efficacy about their potential to "be scientists" across middle childhood, they maintain more robust interest and efficacy about "doing science." These patterns were confirmed in both longitudinal and cross-sectional analyses; effects were stable or increased across time and age. Mediation analyses revealed that the positive effect of action framing is partially accounted for by children's views that the group of people who do science is more inclusive than the category of scientists. These findings suggest that using action-focused language to encourage children in science is more inclusive and may lead to more science engagement across middle childhood than language that emphasizes scientists as an identity category. Implications for educational practices will be discussed.

Justice and care: decision making by medical school student promotions committees.

CONTEXT: The function of medical school entities that determine student advancement or dismissal has gone largely unexplored. The decision making of 'academic progress' or student promotions committees is examined using a theoretical framework contrasting ethics of justice and care, with roots in the moral development work of theorists Kohlberg and Gilligan. OBJECTIVES: To ascertain promotions committee members' conceptualisation of the role of their committee, ethical orientations used in member decision making, and student characteristics most influential in that decision making. METHODS: An electronic survey was distributed to voting members of promotions committees at 143 accredited allopathic medical schools in the USA. Descriptive statistics were calculated and data were analysed by gender, role, institution type and class size. RESULTS: Respondents included 241 voting members of promotions committees at 55 medical schools. Respondents endorsed various promotions committee roles, including acting in the best interest of learners' future patients and graduating highly qualified learners. Implementing policy was assigned lower importance. The overall pattern of responses did not indicate a predominant orientation toward an ethic of justice or care. Respondents indicated that committees have discretion to take individual student characteristics into consideration during deliberations, and that they do so in practice. Among the student characteristics with the greatest influence on decision making, professionalism and academic performance were paramount. Eighty-five per cent of participants indicated that they received no training. CONCLUSIONS: Promotions committee members do not regard orientations of justice and care as being mutually exclusive and endorse an array of statements regarding the committee's purpose that may conflict with one another. The considerable variance in the influence of student characteristics and the general absence of committee member training indicate a need for clear delineation of the medical profession's priorities in terms of justice and care, and of the specific student characteristics that should factor into deliberations.

Blood and Blood Product Conservation: Results of Strategies to Improve Clinical Outcomes in Open Heart Surgery Patients at a Tertiary Hospital.

Blood product usage is a quality outcome for patients undergoing cardiac surgery. To address an increase in blood product usage since the discontinuation of aprotinin, blood conservation strategies were initiated at a tertiary hospital in Oakland, CA. Improving transfusion rates for open heart surgery patients requiring Cardiopulmonary bypass (CPB) involved multiple departments in coordination. Specific changes to conserve blood product usage included advanced CPB technology upgrades, and precise individualized heparin dose response titration assay for heparin and protamine management. Retrospective analysis of blood product usage pre-implementation, post-CPB changes and post-Hemostasis Management System (HMS) implementation was done to determine the effectiveness of the blood conservation strategies. Statistically significant decrease in packed red blood cells, fresh frozen plasma, cryoprecipitate, and platelet usage over the stepped implementation of both technologies was observed. New oxygenator and centrifugal pump technologies reduced active circuitry volume and caused less damage to blood cells. Individualizing heparin and protamine dosing to a patient using the HMS led to transfusion reductions as well. Overall trends toward reductions in hospital length of stay and intensive care unit stay, and as a result, blood product cost and total hospitalization cost are positive over the period of implementation of both CPB circuit changes and HMS implementation. Although they are multifactorial in nature, these trends provide positive enforcement to the changes implemented.

Selective involvement by the medial orbitofrontal cortex in biasing risky, but not impulsive, choice.

Separate regions of the orbitofrontal cortex (OFC) have been implicated in mediating different aspects of cost-benefit decision-making in humans and animals. Anatomical and functional imaging studies indicate that the medial (mOFC) and lateral OFC may subserve dissociable functions related to reward and decision-making processes, yet the majority of studies in rodents have focused on the lateral OFC. The present study investigated the contribution of the rat mOFC to risk and delay-based decision-making, assessed with probabilistic and delay-discounting tasks. In well-trained rats, reversible inactivation of the mOFC increase a risky choice on the probabilistic discounting task, irrespective of whether the odds of obtaining a larger/risky reward decreased (100-12.5%) or increased (12.5-100%) over the course of a session. The increase in risky choice was associated with enhanced win-stay behavior, wherein rats showed an increased tendency to choose the risky option after being rewarded for the risky choice on a preceding trial. In contrast, mOFC inactivation did not alter delay discounting. These findings suggest that the mOFC plays a selective role in decisions involving reward uncertainty, mitigating the impact that larger, probabilistic rewards exert on subsequent choice behavior. This function may promote the exploration of novel options when reward contingencies change.

Twelve tips for addressing medical student and resident physician lapses in professionalism.

Medical educators have gained significant ground in the practical and scholarly approach to professionalism. When a lapse occurs, thoughtful remediation to address the underlying issue can have a positive impact on medical students and resident physicians, while failure to address lapses, or to do so ineffectively, can have long-term consequences for learners and potentially patients. Despite these high stakes, educators are often hesitant to address lapses in professionalism, possibly due to a lack of time and familiarity with the process. Attention must be paid to generalizable, hands-on recommendations for daily use so that clinicians and administrators feel well equipped to tackle this often difficult yet valuable task. This article reviews the literature related to addressing unprofessional behavior among trainees in medicine and connects it to the shared experience of medical educators at one institution. The framework presented aims to provide practical guidance and empowerment for educators responsible for addressing medical student and resident physician lapses in professionalism.

Insights gained from sequencing Australian non-invasive and invasive Streptococcus pyogenes isolates.

Epidemiological data have indicated that invasive infections caused by the Gram-positive cocci Streptococcus pyogenes (group A streptococcus, GAS) have increased in many Australian states over the past two decades. In July 2022, invasive GAS (iGAS) infections became nationally notifiable in Australia via public-health agencies. Surveillance for S. pyogenes infections has been sporadic within the state of New South Wales (NSW). This has led to a lack of genetic data on GAS strains in circulation, particularly for non-invasive infections, which are the leading cause of GAS's burden on the Australian healthcare system. To address this gap, we used whole-genome sequencing to analyse the genomes of 318 S. pyogenes isolates collected within two geographical regions of NSW. Invasive isolates were collected in 2007-2017, whilst non-invasive isolates were collected in 2019-2021. We found that at least 66 different emm-types were associated with clinical disease within NSW. There was no evidence of any Australian-specific clones in circulation. The M1UK variant of the emm1 global pandemic clone (M1global) has been detected in our isolates from 2013 onwards. We detected antimicrobial-resistance genes (mainly tetM, ermA or ermB genes) in less than 10 % of our 318 isolates, which were more commonly associated with non-invasive infections. Superantigen virulence gene carriage was reasonably proportionate between non-invasive and invasive infection isolates. Our study adds rich data on the genetic makeup of historical S. pyogenes infections within Australia. Ongoing surveillance of invasive and non-invasive GAS infections within NSW by whole-genome sequencing is warranted to inform on outbreaks, antimicrobial resistance and vaccine coverage.

Graph Attention-Based Fusion of Pathology Images and Gene Expression for Prediction of Cancer Survival.

Multimodal machine learning models are being developed to analyze pathology images and other modalities, such as gene expression, to gain clinical and biological insights. However, most frameworks for multimodal data fusion do not fully account for the interactions between different modalities. Here, we present an attention-based fusion architecture that integrates a graph representation of pathology images with gene expression data and concomitantly learns from the fused information to predict patient-specific survival. In our approach, pathology images are represented as undirected graphs, and their embeddings are combined with embeddings of gene expression signatures using an attention mechanism to stratify tumors by patient survival. We show that our framework improves the survival prediction of human non-small cell lung cancers, outperforming existing state-of-the-art approaches that leverage multimodal data. Our framework can facilitate spatial molecular profiling to identify tumor heterogeneity using pathology images and gene expression data, complementing results obtained from more expensive spatial transcriptomic and proteomic technologies.

Divergent vertebral formulae shape the evolution of axial complexity in mammals.

Complexity, defined as the number of parts and their degree of differentiation, is a poorly explored aspect of macroevolutionary dynamics. The maximum anatomical complexity of organisms has undoubtedly increased through evolutionary time. However, it is unclear whether this increase is a purely diffusive process or whether it is at least partly driven, occurring in parallel in most or many lineages and with increases in the minima as well as the means. Highly differentiated and serially repeated structures, such as vertebrae, are useful systems with which to investigate these patterns. We focus on the serial differentiation of the vertebral column in 1,136 extant mammal species, using two indices that quantify complexity as the numerical richness and proportional distribution of vertebrae across presacral regions and a third expressing the ratio between thoracic and lumbar vertebrae. We address three questions. First, we ask whether the distribution of complexity values in major mammal groups is similar or whether clades have specific signatures associated with their ecology. Second, we ask whether changes in complexity throughout the phylogeny are biased towards increases and whether there is evidence of driven trends. Third, we ask whether evolutionary shifts in complexity depart from a uniform Brownian motion model. Vertebral counts, but not complexity indices, differ significantly between major groups and exhibit greater within-group variation than recognized hitherto. We find strong evidence of a trend towards increasing complexity, where higher values propagate further increases in descendant lineages. Several increases are inferred to have coincided with major ecological or environmental shifts. We find support for multiple-rate models of evolution for all complexity metrics, suggesting that increases in complexity occurred in stepwise shifts, with evidence for widespread episodes of recent rapid divergence. Different subclades evolve more complex vertebral columns in different configurations and probably under different selective pressures and constraints, with widespread convergence on the same formulae. Further work should therefore focus on the ecological relevance of differences in complexity and a more detailed understanding of historical patterns.