Anatomy's missing faces: An assessment of representation gaps in atlas and textbook imagery.

Previous research suggests that underrepresentation in medical curricula perpetuates inequities in healthcare. This study aimed to quantify the prevalence of human phenotypic diversity (e.g., skin tone, sex, body size, and age) across 11 commonly used anatomy atlases and textbooks in pre-clerkship medical education, published from 2015 to 2020. A systematic visual content analysis was conducted on 5001 images in which at least one phenotypic attribute was quantifiable. Anatomy images most prevalently portrayed light skin tones, males, persons with intermediate body sizes, and young to middle-aged adults. Of the 3883 images in which there was a codable skin tone, 81.2% (n = 3154) depicted light, 14.3% (n = 554) depicted intermediate, and 4.5% (n = 175) depicted dark skin tones. Of the 2384 images that could be categorized into a sex binary, 38.4% (n = 915) depicted females and 61.6% (n = 1469) depicted males. A male bias persisted across all whole-body and regional-body images, including those showing sex organs or those showing characteristics commonly associated with a specific sex (e.g. for males, facial hair and/or muscle hypertrophy). Within sex-specific contexts, darker skin was underrepresented, but male depictions displayed greater overall skin tone variation. Although most images could not be assigned to a body size or age category, when codable, these images overwhelmingly depicted adults (85.0%; 482 of 567) with smaller (34.7%; 93 of 268) or intermediate (64.6%; 173 of 268) body sizes. Ultimately, these outcomes provide reference metrics for monitoring ongoing and future efforts to address representation inequalities portrayed in anatomical imagery.

Analyzing efficiency of a lentiviral shRNA knockdown system in human enteroids using western blot and flow cytometry.

Enteroids are in vitro models to study gastrointestinal pathologies and test personalized therapeutics; however, the inherent complexity of enteroids often renders standard gene editing approaches ineffective. Here, we introduce a refined lentiviral transfection protocol, ensuring sufficient lentiviral engagement with enteroids while considering spatiotemporal growth variability throughout the extracellular matrix. Additionally, we highlight a selection process for transduced cells, introduce a protocol to accurately measure transduction efficiency, and explore methodologies to gauge effects of gene knockdown on biological processes.

Diet modulates the gut microbiome, metabolism, and mammary gland inflammation to influence breast cancer risk.

Several studies have indicated a strong link between obesity and the risk of breast cancer. Obesity decreases gut microbial biodiversity and modulates Bacteroidetes-to-Firmicutes proportional abundance, suggesting that increased energy-harvesting capacity from indigestible dietary fibers and elevated lipopolysaccharide bioavailability may promote inflammation. To address the limited evidence linking diet-mediated changes in the gut microbiota to breast cancer risk, we aimed to determine how diet affects the microbiome and breast cancer risk. Female 3-week-old BALB/c mice were fed six different diets (control, high-sugar, lard, coconut oil, lard+flaxseed oil, and lard+safflower oil) for 10 weeks. Fecal 16s sequencing was performed for each group. Diet shifted fecal microbiome populations and modulated mammary gland macrophage infiltration. Fecal conditioned media shifted macrophage polarity and inflammation. In our DMBA-induced breast cancer model, diet differentially modulated tumor and mammary gland metabolism. We demonstrated how dietary patterns change metabolic outcomes, and gut microbiota, which may contribute to breast tumor risk. Furthermore, we showed the influence of diet on metabolism, inflammation, and macrophage polarity. This study suggests that dietary-microbiome interactions are key mediators of breast cancer risk.

The impact of a statewide insulin copay cap policy for insured patients with diabetes in Utah.

BACKGROUND: Insulin affordability is a huge concern for patients with diabetes in the United States. On March 30, 2020, Utah signed House Bill 207 into law, aimed at capping copayments for insulin at $30 for a 30-day supply. The bill was enacted on January 1, 2021. OBJECTIVE: To assess patient basal insulin adherence, out-of-pocket costs, health plan costs, total costs on insulin, and hemoglobin A1c (A1c) in prepolicy vs postpolicy periods. METHODS: This study is a retrospective analysis using data from a regional health plan in Utah from October 1, 2019, to September 30, 2021. Inclusion criteria were fully enrolled members of all ages, under commercial insurance, with at least 1 fill for any type of insulin in both the preperiod and the postperiod. Adherence was measured by proportion of days covered (PDC). Paired t-tests and Wilcoxon sign rank tests were conducted to compare the health and economic outcomes. RESULTS: Out of 24,150 commercially insured individuals, a total of 244 patients were included. Across all 244 patients, there was a significant decline in monthly median out-of-pocket costs of insulin by 58.5% (P < 0.001), whereas the monthly median health plan costs of insulin increased by 22.0% (P < 0.001). The total monthly costs of insulin (the sum of out-of-pocket and health plan costs) were unchanged (P = 0.115). Only 74 patients with enough basal insulin fills in both periods were included in the analysis for PDC changes. PDC change was not statistically significant (P = 0.43). Among the 74 patients with PDC calculations, 29 patients had A1c recorded in both periods. The change in A1c was not statistically significant (P = 0.23). CONCLUSIONS: An insulin copayment max of $30 in Utah demonstrated lower patient out-of-pocket costs, subsidized by the health plan. PDC did not change, and HbA1c did not improve. An assessment of a longer period and on a larger population is needed.

Faith and facts: Exploring the intersection of religion and science among anatomy educators.

The intersection of religion and science often elicits polarizing views among scientists, though approximately half of American scientists identify as religious. Mounting evidence also supports the role of spirituality in comprehensive patient care. The purpose of this study was to explore the religiosity of faculty who teach in the anatomical sciences at U.S. colleges and universities. Surveys were administered to anatomists through two professional societies. Two-thirds (64.9%, 74/114) of respondents identified as religious, 26.3% (30/114) as atheist, and 8.8% (10/114) as agnostic. Most respondents (64.9%, 74/114) disagreed with the statement, "There is no place for religion and science to intersect." Approximately one in three respondents expressed concern that sharing/disclosing their religious beliefs would negatively affect the perceptions of colleagues (32.5%, 37/114) and students (28.9%, 33/114) toward them. Faculty at faith-based institutions were more open to disclosing their beliefs (p = 0.045), and highly religious individuals were more concerned (p = 0.001). Fewer than one-fifth of respondents 17.5% (20/114) personally experienced mistreatment or discrimination within academic settings due to their religious beliefs. Most respondents held politically liberal-leaning views (71.0%, 76/107). Highly religious individuals were more likely to be politically conservative (p < 0.001). Overall, this study demonstrates that the number of anatomists who identify as religious may be higher than that of other biological disciplines and that mistreatment due to religious views remains a challenge for some in the profession. Continued dialogue regarding the role of religion in professional identity expression may be an important step in mitigating religion-focused mistreatment and discrimination in academic settings.

Differential Conservation and Loss of CR1 Retrotransposons in Squamates Reveals Lineage-Specific Genome Dynamics across Reptiles.

Transposable elements (TEs) are repetitive DNA sequences which create mutations and generate genetic diversity across the tree of life. In amniotic vertebrates, TEs have been mainly studied in mammals and birds, whose genomes generally display low TE diversity. Squamates (Order Squamata; ~11,000 extant species of lizards and snakes) show as much variation in TE abundance and activity as they do in species and phenotypes. Despite this high TE activity, squamate genomes are remarkably uniform in size. We hypothesize that novel, lineage-specific dynamics have evolved over the course of squamate evolution to constrain genome size across the order. Thus, squamates may represent a prime model for investigations into TE diversity and evolution. To understand the interplay between TEs and host genomes, we analyzed the evolutionary history of the CR1 retrotransposon, a TE family found in most tetrapod genomes. We compared 113 squamate genomes to the genomes of turtles, crocodilians, and birds, and used ancestral state reconstruction to identify shifts in the rate of CR1 copy number evolution across reptiles. We analyzed the repeat landscapes of CR1 in squamate genomes and determined that shifts in the rate of CR1 copy number evolution are associated with lineage-specific variation in CR1 activity. We then used phylogenetic reconstruction of CR1 subfamilies across amniotes to reveal both recent and ancient CR1 subclades across the squamate tree of life. The patterns of CR1 evolution in squamates contrast other amniotes, suggesting key differences in how TEs interact with different host genomes and at different points across evolutionary history.

Employment benefits across U.S. allopathic medical schools: National norms and relationships with institutional wealth.

This study summarizes employment benefits from across 155 U.S. allopathic medical schools, investigates differences in employment benefits according to institutional characteristics, and explores possible connections between employment benefits and institutional wealth. Employment benefits data were extracted from institutions' websites across four categories: time-off, time-away, retirement contributions, and Employee Assistance Programs (EAPs)/family benefits. This dataset was mixed with other publicly available datasets sourced through the Association of American Medical Colleges (AAMC), the American Council on Education (ACE), and the American Association of University Professors (AAUP) to conduct additional analyses. Nationally, medical schools offered an average of 31 vacation/sick days and 12 paid holidays. Schools typically offered 4 out of 8 time-away benefits. Employers' retirement contributions ranged from 3.0% to 15.5%, with a mean contribution of 8.5%. A total of 43.2% (67 of 155) of medical schools offered a pension. Collectively, private medical schools offered fewer time-away benefits and more EAP/family benefits compared to public schools. Universities with larger endowments per student were associated with a higher number of EAP/family benefits offerings (r = 0.543, p < 0.001). Institutional wealth did not influence other benefits offerings. The quantity/quality of most employment benefits offered at allopathic medical schools were wide-ranging, tended not to vary by region or school control, and were not a function of institutional wealth.

Survey response rates in health sciences education research: A 10-year meta-analysis.

Growth in the online survey market may be increasing response burden and possibly jeopardizing higher response rates. This meta-analysis evaluated survey trends over one decade (2011-2020) to determine: (1) changes in survey publication rates over time, (2) changes in response rates over time, (3) typical response rates within health sciences education research, (4) the factors influencing survey completion levels, and (5) common gaps in survey methods and outcomes reporting. Study I estimated survey publication trends between 2011 and 2020 using articles published in the top three health sciences education research journals. Study II searched the anatomical sciences education literature across six databases and extracted study/survey features and survey response rates. Time plots and a proportional meta-analysis were performed. Per 2926 research articles, the annual estimated proportion of studies with survey methodologies has remained constant, with no linear trend (p > 0.050) over time (Study I). Study II reported a pooled absolute response rate of 67% (95% CI = 63.9-69.0) across 360 studies (k), totaling 115,526 distributed surveys. Despite response rate oscillations over time, no significant linear trend (p = 0.995) was detected. Neither survey length, incentives, sponsorship, nor population type affected absolute response rates (p ≥ 0.070). Only 35% (120 of 339) of studies utilizing a Likert scale reported evidence of survey validity. Survey response rates and the prevalence of studies with survey methodologies have remained stable with no linear trends over time. We recommend researchers strive for a typical absolute response rate of 67% or higher and clearly document evidence of survey validity for empirical studies.

A Novel Metastatic Estrogen Receptor-Expressing Breast Cancer Model with Antiestrogen Responsiveness.

Most women diagnosed with breast cancer (BC) have estrogen receptor alpha-positive (ER+) disease. The current mouse models of ER+ BC often rely on exogenous estrogen to encourage metastasis, which modifies the immune system and the function of some tissues like bone. Other studies use genetically modified or immunocompromised mouse strains, which do not accurately replicate the clinical disease. To create a model of antiestrogen responsive BC with spontaneous metastasis, we developed a mouse model of 4T1.2 triple-negative (TN) breast cancer with virally transduced ER expression that metastasizes spontaneously without exogenous estrogen stimulation and is responsive to antiestrogen drugs. Our mouse model exhibited upregulated ER-responsive genes and multi-organ metastasis without exogenous estrogen administration. Additionally, we developed a second TN BC cell line, E0771/bone, to express ER, and while it expressed ER-responsive genes, it lacked spontaneous metastasis to clinically important tissues. Following antiestrogen treatment (tamoxifen, ICI 182,780, or vehicle control), 4T1.2- and E0771/bone-derived tumor volumes and weights were significantly decreased, exemplifying antiestrogen responsivity in both cell lines. This 4T1.2 tumor model, which expresses the estrogen receptor, metastasizes spontaneously, and responds to antiestrogen treatment, will allow for further investigation into the biology and potential treatment of metastasis.

Probiotic and Muscadine Grape Extract Interventions Shift the Gut Microbiome and Improve Metabolic Parameters in Female C57BL/6 Mice.

Obesity and Western-like diet consumption leads to gut microbiome dysbiosis, which is associated with the development of cardio-metabolic diseases and poor health outcomes. The objective of this study was to reduce Western diet-mediated gut microbial dysbiosis, metabolic dysfunction, and systemic inflammation through the administration of a novel combined intervention strategy (oral probiotic bacteria supplements and muscadine grape extract (MGE)). To do so, adult female C57BL/6 mice were fed a low-fat control or Western-style diet and sub-grouped into diet alone, probiotic intervention, antibiotic treatments, MGE supplementation, a combination of MGE and probiotics, or MGE and antibiotics for 13 weeks. Mouse body weight, visceral adipose tissue (VAT), liver, and mammary glands (MG) were weighed at the end of the study. Fecal 16S rRNA sequencing was performed to determine gut bacterial microbiome populations. Collagen, macrophage, and monocyte chemoattractant protein-1 (MCP-1) in the VAT and MG tissue were examined by immunohistochemistry. Adipocyte diameter was measured in VAT. Immunohistochemistry of intestinal segments was used to examine villi length, muscularis thickness, and goblet cell numbers. We show that dietary interventions in Western diet-fed mice modulated % body weight gain, visceral adiposity, MG weight, gut microbial populations, and inflammation. Intervention strategies in both diets effectively reduced VAT and MG fibrosis, VAT and MG macrophages, adipocyte diameter, and VAT and MG MCP-1. Interventions also improved intestinal health parameters. In conclusion, dietary intervention with MGE and probiotics modulates several microbial, inflammatory, and metabolic factors reducing poor health outcomes associated with Western diet intake.

Changes in EEG alpha-band power during prehension indicates neural motor drive inhibition.

Changes in alpha band activity (8-12 Hz) indicate the downregulation of brain regions during cognitive tasks, reflecting real-time cognitive load. Despite this, its feasibility to be used in a more dynamic environment with ongoing motor corrections has not been studied. This research used electroencephalography (EEG) to explore how different brain regions are engaged during a simple grasp and lift task where unexpected changes to the object's weight or surface friction are introduced. The results suggest that alpha activity changes related to motor error correction occur only in motor-related areas (i.e. central areas) but not in error processing areas (i.e., frontoparietal network) during unexpected weight changes. This suggests that oscillations over motor areas reflect the reduction of motor drive related to motor error correction, thus, being a potential cortical electrophysiological biomarker for the process and not solely as a proxy for cognitive demands. This observation is particularly relevant in scenarios where these signals are used to evaluate high cognitive demands co-occurring with high levels of motor errors and corrections, such as prosthesis use. The establishment of electrophysiological biomarkers of mental resource allocation during movement and cognition can help identify indicators of mental workload and motor drive, which may be useful for improving brain-machine interfaces.NEW & NOTEWORTHY We demonstrated that alpha suppression, an EEG phenomenon with high temporal resolution, occurs over the primary sensorimotor area during error correction during lift movements. Interpretations of alpha activity are often attributed to high cognitive demands, thus recognizing that it is also influenced by motor processes is important in situations where cognitive demands are paired with movement errors. This could further have application as a biomarker for error correction in human-machine interfaces, such as neuroprostheses.

Anti-CD47 immunotherapy as a therapeutic strategy for the treatment of breast cancer brain metastasis.

The presence of cell surface protein CD47 allows cancer cells to evade innate and adaptive immune surveillance resulting in metastatic spread. CD47 binds to and activates SIRPα on the surface of myeloid cells, inhibiting their phagocytic activity. On the other hand, CD47 binds the matricellular protein Thrombospondin-1, limiting T-cell activation. Thus, blocking CD47 is a potential therapeutic strategy for preventing brain metastasis. To test this hypothesis, breast cancer patient biopsies were stained with antibodies against CD47 to determine differences in protein expression. An anti-CD47 antibody was used in a syngeneic orthotopic triple-negative breast cancer model, and CD47 null mice were used in a breast cancer brain metastasis model by intracardiac injection of the E0771-Br-Luc cell line. Immunohistochemical staining of patient biopsies revealed an 89% increase in CD47 expression in metastatic brain tumors compared to normal adjacent tissue (p ≤ 0.05). Anti-CD47 treatment in mice bearing brain metastatic 4T1br3 orthotopic tumors reduced tumor volume and tumor weight by over 50% compared to control mice (p ≤ 0.05) and increased IBA1 macrophage/microglia marker 5-fold in tumors compared to control (p ≤ 0.05). Additionally, CD47 blockade increased the M1/M2 macrophage ratio in tumors 2.5-fold (p ≤ 0.05). CD47 null mice had an 89% decrease in metastatic brain burden (p ≤ 0.05) compared to control mice in a brain metastasis model. Additionally, RNA sequencing revealed several uniquely expressed genes and significantly enriched genes related to tissue development, cell death, and cell migration tumors treated with anti-CD47 antibodies. Thus, demonstrating that CD47 blockade affects cancer cell and tumor microenvironment signaling to limit metastatic spread and may be an effective therapeutic for triple-negative breast cancer brain metastasis.

The State of Squamate Genomics: Past, Present, and Future of Genome Research in the Most Speciose Terrestrial Vertebrate Order.

Squamates include more than 11,000 extant species of lizards, snakes, and amphisbaenians, and display a dazzling diversity of phenotypes across their over 200-million-year evolutionary history on Earth. Here, we introduce and define squamates (Order Squamata) and review the history and promise of genomic investigations into the patterns and processes governing squamate evolution, given recent technological advances in DNA sequencing, genome assembly, and evolutionary analysis. We survey the most recently available whole genome assemblies for squamates, including the taxonomic distribution of available squamate genomes, and assess their quality metrics and usefulness for research. We then focus on disagreements in squamate phylogenetic inference, how methods of high-throughput phylogenomics affect these inferences, and demonstrate the promise of whole genomes to settle or sustain persistent phylogenetic arguments for squamates. We review the role transposable elements play in vertebrate evolution, methods of transposable element annotation and analysis, and further demonstrate that through the understanding of the diversity, abundance, and activity of transposable elements in squamate genomes, squamates can be an ideal model for the evolution of genome size and structure in vertebrates. We discuss how squamate genomes can contribute to other areas of biological research such as venom systems, studies of phenotypic evolution, and sex determination. Because they represent more than 30% of the living species of amniote, squamates deserve a genome consortium on par with recent efforts for other amniotes (i.e., mammals and birds) that aim to sequence most of the extant families in a clade.

Three-dimensional species distribution modelling reveals the realized spatial niche for coral recruitment on contemporary Caribbean reefs.

The three-dimensional structure of habitats is a critical component of species' niches driving coexistence in species-rich ecosystems. However, its influence on structuring and partitioning recruitment niches has not been widely addressed. We developed a new method to combine species distribution modelling and structure from motion, and characterized three-dimensional recruitment niches of two ecosystem engineers on Caribbean coral reefs, scleractinian corals and gorgonians. Fine-scale roughness was the most important predictor of suitable habitat for both taxa, and their niches largely overlapped, primarily due to scleractinians' broader niche breadth. Crevices and holes at mm scales on calcareous rock with low coral cover were more suitable for octocorals than for scleractinian recruits, suggesting that the decline in scleractinian corals is facilitating the recruitment of octocorals on contemporary Caribbean reefs. However, the relative abundances of the taxa were independent of the amount of suitable habitat on the reef, emphasizing that niche processes alone do not predict recruitment rates.

Pulling back the curtain: Exploring norms and practices among a sample of anatomy-related departments in U.S. medical schools.

Anatomy-related departments have access to comparative research productivity data (e.g., Blue Ridge Institute for Medical Research), yet no datasets exist for comparing departments' general practices pertinent to education-focused faculty. Practice trends in anatomy-related departments across U.S. medical schools were explored by surveying departmental leaders. The survey inquired about: (i) faculty time allocations, (ii) anatomy teaching services, (iii) faculty labor distribution models, and (iv) faculty compensation practices. A nationally representative sample of 35 departments (of 194) responded to the survey. On average, anatomy educators are allotted 24% (median = 15%) protected time for research, irrespective of funding, 62% for teaching and course administration (median = 68%), 12% for service, and 2% for administration. Forty-four percent (15 of 34) of departments taught at least five different student populations, often across multiple colleges. Many departments (65%; 11 of 17) applied formulaic methods for determining faculty workloads, often as a function of course credits or contact hours. Average base salaries for assistant and associate professors reported by this survey were consistent (p ≥ 0.056) with national means (i.e., Association of American Medical Colleges Annual Faculty Salary Report). Merit-based increases and bonuses averaged 5% and 10% of faculty's salaries, respectively, when awarded. Cost-of-living increases averaged 3%. Overall, departments' workload and compensation practices vary widely, likely a consequence of different institutional cultures, locations, needs, and financial priorities. This sample dataset allows anatomy-related departments to compare and reflect upon their practices and competitiveness in recruiting and retaining faculty.

Interest Convergence and Market-Based School Reform: The Promise and Limits of Using Controlled Choice to Desegregate Schools.

This article uses interest convergence and market-based theories to examine a recently-adopted controlled choice school admissions model intended to desegregate a diverse, urban school district. Drawing on longitudinal, qualitative interviews with advantaged parents who articulated support for controlled choice, we find that these parents' positive view of the measure was based on a belief that the desegregation policy benefited their own children as well as poor children of color. Yet for many, support for the reform was contingent on their child's school assignment, pointing to the limits of utilizing a market-based model for achieving educational equity.

Abrupt expansion of climate change risks for species globally.

Climate change is already exposing species to dangerous temperatures driving widespread population and geographical contractions. However, little is known about how these risks of thermal exposure will expand across species' existing geographical ranges over time as climate change continues. Here, using geographical data for approximately 36,000 marine and terrestrial species and climate projections to 2100, we show that the area of each species' geographical range at risk of thermal exposure will expand abruptly. On average, more than 50% of the increase in exposure projected for a species will occur in a single decade. This abruptness is partly due to the rapid pace of future projected warming but also because the greater area available at the warm end of thermal gradients constrains species to disproportionately occupy sites close to their upper thermal limit. These geographical constraints on the structure of species ranges operate both on land and in the ocean and mean that, even in the absence of amplifying ecological feedbacks, thermally sensitive species may be inherently vulnerable to sudden warming-driven collapse. With higher levels of warming, the number of species passing these thermal thresholds, and at risk of abrupt and widespread thermal exposure, increases, doubling from less than 15% to more than 30% between 1.5 °C and 2.5 °C of global warming. These results indicate that climate threats to thousands of species are expected to expand abruptly in the coming decades, thereby highlighting the urgency of mitigation and adaptation actions.

Reversion of breast epithelial polarity alterations caused by obesity.

Molecular links between breast cancer risk factors and pro-oncogenic tissue alterations are poorly understood. The goal of this study was to characterize the impact of overweight and obesity on tissue markers of risk, using normal breast biopsies, a mouse model of diet-induced obesity, and cultured breast acini. Proliferation and alteration of epithelial polarity, both necessary for tumor initiation, were quantified by immunostaining. High BMI (>30) and elevated leptin were associated with compromised epithelial polarity whereas overweight was associated with a modest increase in proliferation in human and mice mammary glands. Human serum with unfavorable adipokine levels altered epithelial polarization of cultured acini, recapitulating the effect of leptin. Weight loss in mice led to metabolic improvements and restored epithelial polarity. In acini cultures, alteration of epithelial polarity was prevented by antioxidants and could be reverted by normalizing culture conditions. This study shows that obesity and/or dietary factors modulate tissue markers of risk. It provides a framework to set target values for metabolic improvements and to assess the efficacy of interventional studies aimed at reducing breast cancer risk.