Chemotherapy-induced gut microbiome disruption, inflammation, and cognitive decline in female patients with breast cancer.

Chemotherapy is notorious for causing behavioral side effects (e.g., cognitive decline). Notably, the gut microbiome has recently been reported to communicate with the brain to affect behavior, including cognition. Thus, the aim of this clinical longitudinal observational study was to determine whether chemotherapy-induced disruption of the gut microbial community structure relates to cognitive decline and circulating inflammatory signals. Fecal samples, blood, and cognitive measures were collected from 77 patients with breast cancer before, during, and after chemotherapy. Chemotherapy altered the gut microbiome community structure and increased circulating TNF-α. Both the chemotherapy-induced changes in microbial relative abundance and decreased microbial diversity were related to elevated circulating pro-inflammatory cytokines TNF-α and IL-6. Participants reported subjective cognitive decline during chemotherapy, which was not related to changes in the gut microbiome or inflammatory markers. In contrast, a decrease in overall objective cognition was related to a decrease in microbial diversity, independent of circulating cytokines. Stratification of subjects, via a reliable change index based on 4 objective cognitive tests, identified objective cognitive decline in 35% of the subjects. Based on a differential microbial abundance analysis, those characterized by cognitive decline had unique taxonomic shifts (Faecalibacterium, Bacteroides, Fusicatenibacter, Erysipelotrichaceae UCG-003, and Subdoligranulum) over chemotherapy treatment compared to those without cognitive decline. Taken together, gut microbiome change was associated with cognitive decline during chemotherapy, independent of chemotherapy-induced inflammation. These results suggest that microbiome-related strategies may be useful for predicting and preventing behavioral side effects of chemotherapy.

Student Perspectives of Success and Failure in Biology Lecture: Multifaceted Definitions and Misalignments.

Investigating definitions of success and failure among introductory biology students is essential for understanding what underlies their self-efficacy; a student who gets a B on an exam may lose self-efficacy if they define failure as anything less than an A. Yet, whether students have the same definitions for success as they have for failure in these classes is unknown, nor how those definitions relate to course performance. To better understand student definitions for success and failure and their implications, this mixed-methods study collected survey data from students in two introductory biology courses about their definitions of success and failure and their self-reported grades. Coding of open-ended responses revealed four broad themes related to both success and failure: Performance, Content, Preparation, and Attitude. Although there were common themes in how students defined success and failure overall, individual students often (65%) described success or failure in relation to different standards. We also found some definitions of success and failure were predicted by grades. These results highlight the complexity of building self-efficacy in introductory biology and suggest the need for greater awareness and acknowledgment of the different standards students use to judge their success and failure.

Maternal social environment shapes yolk testosterone allocation and embryonic neural gene expression in tree swallows.

Offspring from females breeding in competitive social environments are often exposed to more testosterone (T) during embryonic development, which can affect traits from growth to behavior in potentially adaptive ways. Despite the important role of maternally derived steroids in shaping offspring development, the molecular mechanisms driving these processes are currently unclear. Here, we use tree swallows (Tachycineta bicolor) to explore the effects of the maternal social environment on yolk T concentrations and genome-wide patterns of neural gene expression in embryos. We measured aggressive interactions among females breeding at variable densities and collected their eggs at two timepoints, including the day laid to measure yolk T concentrations and on embryonic day 11 to measure gene expression in whole brain samples. We found that females breeding in high-density sites experienced elevated rates of physical aggression and their eggs had higher yolk T concentrations. A differential gene expression and weighted gene co-expression network analysis indicated that embryos from high-density sites experienced an upregulation of genes involved in hormone, circulatory, and immune processes, and these gene expression patterns were correlated with yolk T levels and aggression. Genes implicated in neural development were additionally downregulated in embryos from high-density sites. These data highlight how early neurogenomic processes may be affected by the maternal social environment, giving rise to phenotypic plasticity in offspring.

Federated Learning Survival Model and Potential Radiotherapy Decision Support Impact Assessment for Non-small Cell Lung Cancer Using Real-World Data.

AIMS: The objective of this study was to develop a two-year overall survival model for inoperable stage I-III non-small cell lung cancer (NSCLC) patients using routine radiation oncology data over a federated (distributed) learning network and evaluate the potential of decision support for curative versus palliative radiotherapy. METHODS: A federated infrastructure of data extraction, de-identification, standardisation, image analysis, and modelling was installed for seven clinics to obtain clinical and imaging features and survival information for patients treated in 2011-2019. A logistic regression model was trained for the 2011-2016 curative patient cohort and validated for the 2017-2019 cohort. Features were selected with univariate and model-based analysis and optimised using bootstrapping. System performance was assessed by the receiver operating characteristic (ROC) and corresponding area under curve (AUC), C-index, calibration metrics and Kaplan-Meier survival curves, with risk groups defined by model probability quartiles. Decision support was evaluated using a case-control analysis using propensity matching between treatment groups. RESULTS: 1655 patient datasets were included. The overall model AUC was 0.68. Fifty-eight percent of patients treated with palliative radiotherapy had a low-to-moderate risk prediction according to the model, with survival times not significantly different (p = 0.87 and 0.061) from patients treated with curative radiotherapy classified as high-risk by the model. When survival was simulated by risk group and model-indicated treatment, there was an estimated 11% increase in survival rate at two years (p < 0.01). CONCLUSION: Federated learning over multiple institution data can be used to develop and validate decision support systems for lung cancer while quantifying the potential impact of their use in practice. This paves the way for personalised medicine, where decisions can be based more closely on individual patient details from routine care.

Performance evaluation of different albumin assays for the detection of analbuminemia.

Analbuminemia is characterized by the near absence of albumin in the plasma. Different methods are available for measuring albumin levels, but they do not necessarily agree with one another. It is a concern that analbuminemic samples could be falsely characterized due to the incorrect estimation of albumin. The objective of the work was to evaluate the performance of different assays in detecting analbuminemia. Albumin knockout (Alb-/-) mouse plasma was used to test the suitability of different albumin assays for their ability to properly characterize extreme albumin deficiency. Bromocresol green (BCG), bromocresol purple (BCP), enzyme-linked immunosorbent assay (ELISA), liquid chromatography-tandem mass spectrometry (LC-MS/MS), and gel electrophoresis were tested. The LC-MS/MS assay exhibited broad coverage of the amino acid sequence of albumin and indicated 8,400-fold lower (P<0.0001) albumin expression in Alb-/- than wildtype (WT), demonstrating its suitability for identifying extreme albumin deficiency. ELISA estimated albumin at 1.5±0.1 g/dL in WT and was below the detection limit in all Alb-/- samples. Gel electrophoresis yielded consistent results with LC-MS/MS and ELISA. The BCG assay overestimated albumin with apparently appreciable albumin concentrations in Alb-/- mice, yet the assay still indicated a significant difference between genotypes (Alb-/-, 1.2±0.05 g/dL, WT, 3.7±0.1 g/dL, P<0.0001). BCP drastically overestimated albumin and could not successfully identify the known analbuminemic phenotype of Alb-/- mice. By using Alb-/- plasma as a reference material and LC-MS/MS as a reference method, ELISA and gel electrophoresis appear appropriate for identifying analbuminemia, while BCG and BCP are not suitable. It is concluded that dye-binding assays should be avoided when extreme hypoalbuminemia or analbuminemia is suspected.

A 3D-MICROPRINTED COAXIAL NOZZLE FOR FABRICATING LONG, FLEXIBLE MICROFLUIDIC TUBING.

A variety of emerging applications, particularly those in medical and soft robotics fields, are predicated on the ability to fabricate long, flexible meso/microfluidic tubing with high customization. To address this need, here we present a hybrid additive manufacturing (or "three-dimensional (3D) printing") strategy that involves three key steps: (i) using the "Vat Photopolymerization (VPP) technique, "Liquid-Crystal Display (LCD)" 3D printing to print a bulk microfluidic device with three inlets and three concentric outlets; (ii) using "Two-Photon Direct Laser Writing (DLW)" to 3D microprint a coaxial nozzle directly atop the concentric outlets of the bulk microdevice, and then (iii) extruding paraffin oil and a liquid-phase photocurable resin through the coaxial nozzle and into a polydimethylsiloxane (PDMS) channel for UV exposure, ultimately producing the desired tubing. In addition to fabricating the resulting tubing-composed of polymerized photomaterial-at arbitrary lengths (e.g., > 10 cm), the distinct input pressures can be adjusted to tune the inner diameter (ID) and outer diameter (OD) of the fabricated tubing. For example, experimental results revealed that increasing the driving pressure of the liquid-phase photomaterial from 50 kPa to 100 kPa led to fluidic tubing with IDs and ODs of 291±99 µm and 546±76 µm up to 741±31 µm and 888±39 µm, respectively. Furthermore, preliminary results for DLW-printing a microfluidic "M" structure directly atop the tubing suggest that the tubing could be used for "ex situ DLW (esDLW)" fabrication, which would further enhance the utility of the tubing.

Elucidating the pathogenesis behind arteriovenous malformations of the central nervous system: a bibliometric analysis.

Arteriovenous malformations (AVMs) are vascular malformations of the central nervous system (CNS) with potential for significant consequences. The exact pathophysiologic mechanism of AVM formation is not fully understood. This study aims to evaluate bibliometric parameters and citations of the literature of AVMs to provide an overview of how the field has evolved. We performed an electronic search on Web of Science to identify the top 100 published and indexed articles with the highest number of citations discussing the pathogenesis of AVMs. This study yielded 1863 articles, of which the top 100 were selected based on the highest total citation count. These articles included 24% basic science, 46% clinical, and 30% review articles. The most-cited article was a clinical article from 2003, and the most recent was published in 2022. The median number of authors was 6, with the highest being 46 for a clinical article. The top 5 journals were identified, with the highest impact factor being 20.1. 13 countries were identified, with the US contributing the most articles (approximately 70%). Regarding genes of investigation, VEGF was one of the early genes investigated, while more interested in RAS/MAPK has been garnered since 2015. There is a growing interest in AVM genomics and pathogenesis research. While progress has been made in understanding clinical aspects and risk factors, the exact pathophysiological mechanisms and genetic basis of AVM formation remain incompletely understood. Further investigation of key genes in AVM pathogenesis can allow identification of potential therapeutic targets.

FABRICATION OF MULTILUMEN MICROFLUIDIC TUBING FOR EX SITU DIRECT LASER WRITING.

Among the numerous additive manufacturing or "three-dimensional (3D) printing" techniques, two-photon Direct Laser Writing (DLW) is distinctively suited for applications that demand high geometric versatility with micron-to-submicron-scale feature resolutions. Recently, "ex situ DLW (esDLW)" has emerged as a powerful approach for printing 3D microfluidic structures directly atop meso/macroscale fluidic tubing that can be manipulated by hand; however, difficulties in creating custom esDLW-compatible multilumen tubing at such scales has hindered progress. To address this impediment, here we introduce a novel methodology for fabricating submillimeter multilumen tubing for esDLW 3D printing. Preliminary fabrication results demonstrate the utility of the presented strategy for resolving 743 µm-in-diameter tubing with three lumens-each with an inner diameter (ID) of 80 µm. Experimental results not only revealed independent flow of discrete fluorescently labelled fluids through each of the three lumens, but also effective esDLW-printing of a demonstrative 3D "MEMS" microstructure atop the tubing. These results suggest that the presented approach could offer a promising pathway to enable geometrically sophisticated microfluidic systems to be 3D printed with input and/or output ports fully sealed to multiple, distinct lumens of fluidic tubing for emerging applications in fields ranging from drug delivery and medical diagnostics to soft surgical robotics.

Influence of body mass normalization on the correlations between muscle cross-sectional area and physical performance outcomes in older women.

AIMS: Normalization is a method used to account for body mass in clinical practice and research. It is unclear if this method will improve the correlation between muscle cross-sectional area (CSA) and physical performance. We examined the correlations between quadriceps muscle morphology parameters and physical performance outcomes in older women. Material and methods: Twenty older women participated in this study. Ultrasound imaging was used to measure quadriceps muscle CSA and echo intensity. Muscle CSA was expressed as an absolute value (cm2) and as a relative value normalized to body mass (cm2/kg). Physical performance was assessed from timed up-and-go and 6-min walk tests. RESULTS: Relative CSA was significantly related to timed up-and-go scores (r=-0.489, p=0.029) and 6-min walking speed (r=0.606, p=0.005), whereas absolute CSA was not significantly associated with these performances (r=-0.231, p=0.327 and r=0.373, p=0.105). There was a significant correlation between absolute CSA and body mass (r=0.456, p=0.043). There were also significant correlations between echo intensity and timed up-and-go scores (r=0.556, p=0.011) and 6-min walking speed (r=-0.484, p=0.031). CONCLUSIONS:  Our study showed that relative CSA correlated better than absolute CSA with physical performance. These findings support the need to normalize measurements of muscle CSA to body mass in older adults.

Multicultural Considerations for the Psychometrics of the Brief Pornography Screen.

Problematic pornography use (PPU) is a burgeoning area of clinical interest. The Brief Pornography Screen (BPS) is a new PPU measure. The BPS has not been psychometrically studied within specific race/cultural groups. We sought to broaden the PPU literature by examining the confirmatory factor analysis (CFA) fit, measurement invariance, and structural invariance of the BPS across eight identity groups. Participants came from a survey administered at three U.S. universities. In total, n = 2,475 participants were analyzed, with the following identity group breakdowns: Asian American/Pacific Islander (AAPI) male = 268, AAPI female = 303, Black male = 101, Black female = 189, Latin male = 208, Latin female = 372, White male = 432, and White female = 602. BPS CFA fit was good across all groups. Measurement invariance analyses suggested metric, but not scalar invariance across all groups. We then split participants by sex assignment, full residual invariance was evident across groups for male participants and partial residual invariance was evident for female participants. Structural invariance analyses indicated anxiety as a weak positive BPS correlate in AAPI, Latin, and White male participants (ß's = 0.25-0.27), but not meaningfully related in the other groups. Pornography viewing frequency was positively correlated with BPS scores across most groups with a wide range (ß's = 0.29-0.52), except for Black male participants (ß = 0.15). Our results suggest that the BPS is an appropriate PPU measure across the tested identity groups. While between-group measurement is relatively accurate within sex assignment groups, correlates differed in strength, meaning different variables likely predict PPU for different groups of people.

A hybrid transistor with transcriptionally controlled computation and plasticity.

Organic electrochemical transistors (OECTs) are ideal devices for translating biological signals into electrical readouts and have applications in bioelectronics, biosensing, and neuromorphic computing. Despite their potential, developing programmable and modular methods for living systems to interface with OECTs has proven challenging. Here we describe hybrid OECTs containing the model electroactive bacterium Shewanella oneidensis that enable the transduction of biological computations to electrical responses. Specifically, we fabricated planar p-type OECTs and demonstrated that channel de-doping is driven by extracellular electron transfer (EET) from S. oneidensis. Leveraging this mechanistic understanding and our ability to control EET flux via transcriptional regulation, we used plasmid-based Boolean logic gates to translate biological computation into current changes within the OECT. Finally, we demonstrated EET-driven changes to OECT synaptic plasticity. This work enables fundamental EET studies and OECT-based biosensing and biocomputing systems with genetically controllable and modular design elements.

Mechanisms of DNA Methylation Regulatory Function and Crosstalk with Histone Lysine Methylation.

DNA methylation is a well-studied epigenetic modification that has key roles in regulating gene expression, maintaining genome integrity, and determining cell fate. Precisely how DNA methylation patterns are established and maintained in specific cell types at key developmental stages is still being elucidated. However, research over the last two decades has contributed to our understanding of DNA methylation regulation by other epigenetic processes. Specifically, lysine methylation on key residues of histone proteins has been shown to contribute to the allosteric regulation of DNA methyltransferase (DNMT) activities. In this review, we discuss the dynamic interplay between DNA methylation and histone lysine methylation as epigenetic regulators of genome function by synthesizing key recent studies in the field. With a focus on DNMT3 enzymes, we discuss mechanisms of DNA methylation and histone lysine methylation crosstalk in the regulation of gene expression and the maintenance of genome integrity. Further, we discuss how alterations to the balance of various sites of histone lysine methylation and DNA methylation contribute to human developmental disorders and cancers. Finally, we provide perspectives on the current direction of the field and highlight areas for continued research and development.

ERK hyperactivation serves as a unified mechanism of escape in intrinsic and acquired CDK4/6 inhibitor resistance in acral lentiginous melanoma.

Patients with metastatic acral lentiginous melanoma (ALM) suffer worse outcomes relative to patients with other forms of cutaneous melanoma (CM), and do not benefit as well to approved melanoma therapies. Identification of cyclin-dependent kinase 4 and 6 (CDK4/6) pathway gene alterations in >60% of ALMs has led to clinical trials of the CDK4/6 inhibitor (CDK4i/6i) palbociclib for ALM; however, median progression free survival with CDK4i/6i treatment was only 2.2 months, suggesting existence of resistance mechanisms. Therapy resistance in ALM remains poorly understood; here we report hyperactivation of MAPK signaling and elevated cyclin D1 expression serve as a mechanism of intrinsic early/adaptive CDK4i/6i resistance. ALM cells that have acquired CDK4i/6i resistance following chronic treatment exposure also exhibit hyperactivation of the MAPK pathway. MEK and/or ERK inhibition increases CDK4i/6i efficacy against therapy naïve and CDK4i/6i-resistant AM cells in xenograft and patient-derived xenograft (PDX) models and promotes a defective DNA repair, cell cycle arrested and apoptotic program. Notably, gene alterations poorly correlate with protein expression of cell cycle proteins in ALM or efficacy of CDK4i/6i, urging additional strategies when stratifying patients for CDK4i/6i trial inclusion. Concurrent targeting of the MAPK pathway and CDK4/6 represents a new approach for patients with metastatic ALM to improve outcomes.

Development of a job-exposure matrix-like exposure assessment method for the US general population based on Occupational Information Network (O*NET) job tasks.

BACKGROUND: Job-exposure matrices (JEMs) are often used for exposure assessment in occupational exposure and epidemiology studies. However, general population JEMs are difficult to find and access for workers in the United States of America. OBJECTIVE: We aimed to use publicly available information to develop a JEM-like exposure assessment method to determine exposure to a wide range of occupational agents in a wide range of occupations for US general population studies. METHODS: We used information from the US Department of Labor's Occupational Information Network database (O*NET) for 19,636 job tasks and 974 civilian occupations. We used automated keyword searches to identify 1,804 job tasks that involved exposure to 50 occupational agents. We had 2 reviewers determine whether each identified job task actually involved exposure to the 50 occupational agents. We had a third reviewer, a certified industrial hygienist, assess any job task and exposure for which the first 2 reviewers disagreed. For each U.S. Census 2010 occupation code, we used this information to derive 3 exposure variables for each occupational agent: ever exposure, number of job tasks of exposure, and frequency of exposure. RESULTS: Our keyword searches identified a median of 10 (interquartile range [IQR]: 43.75) job tasks for each occupational agent, and the maximum was 308. We determined job tasks actually involved exposure to 45 occupational agents, including solvents, air pollution, pesticides, radiation, metals, etc. We derived the 3 exposure variables for these 45 occupational agents for 516 U.S. Census 2010 occupation codes. The median percentage for ever exposure to individual occupational agents was 1.16% (IQR: 1.74%), and the maximum was 11.43%. CONCLUSIONS: Our JEM-like exposure assessment method based on O*NET information can be used to determine exposure to a wide range of occupational agents in a wide range of occupations for the US general population.

A quantitative framework for patient-specific collision detection in proton therapy.

BACKGROUND: Beam modifying accessories for proton therapy often need to be placed in close proximity of the patient for optimal dosimetry. However, proton treatment units are larger in size and as a result the planned treatment geometry may not be achievable due to collisions with the patient. A framework that can accurately simulate proton treatment geometry is desired. PURPOSE: A quantitative framework was developed to model patient-specific proton treatment geometry, minimize air gap, and avoid collisions. METHODS: The patient's external contour is converted into the International Electrotechnique Commission (IEC) gantry coordinates following the patient's orientation and each beam's gantry and table angles. All snout components are modeled by three-dimensional (3D) geometric shapes such as columns, cuboids, and frustums. Beam-specific parameters such as isocenter coordinates, snout type and extension are used to determine if any point on the external contour protrudes into the various snout components. A 3D graphical user interface is also provided to the planner to visualize the treatment geometry. In case of a collision, the framework's analytic algorithm quantifies the maximum protrusion of the external contour into the snout components. Without a collision, the framework quantifies the minimum distance of the external contour from the snout components and renders a warning if such distance is less than 5 cm. RESULTS: Three different snout designs are modeled. Examples of potential collision and its aversion by snout retraction are demonstrated. Different patient orientations, including a sitting treatment position, as well as treatment plans with multiple isocenters, are successfully modeled in the framework. Finally, the dosimetric advantage of reduced air gap enabled by this framework is demonstrated by comparing plans with standard and reduced air gaps. CONCLUSION: Implementation of this framework reduces incidence of collisions in the treatment room. In addition, it enables the planners to minimize the air gap and achieve better plan dosimetry.

A Descriptive Analysis of Blood Products Utilized by a Forward Deployed Surgical Team in Syria.

INTRODUCTION: Traumatically injured combat casualties urgently need both blood and surgery. Forward Surgical Teams (FSTs) or Role 2 (R2) surgical teams were created to minimize the time-space distance from point of injury to damage control surgery. Our goal is to describe the use of blood products from a Split FST deployed to Green Village from July 2018 to April 2019. MATERIALS AND METHODS: A retrospective review of a collection of patients treated by a single R2 was conducted following institutional regulatory approval. De-identified data were input into the study database and were then retrospectively reviewed for patients who presented to and received treatment at the R2 facility. RESULTS: Of the 470 total patients treated in 10 months: 226 (48%) received blood products and 132 (28%) underwent operative procedures. The patients were 98% male; 74% Host Nationals (HN), 24% North American Treaty Organization members. Mechanism of injury was 75% explosive and 98% penetrating. Documented Injury Severity Scores (n = 214) were: <9 (n = 57/27%), 9 to 15 (n = 34/16%), 16 to 25 (n = 64/30%), and >25 (n = 59/28%). In total 1,052 units of blood products were administered: whole blood (n = 495), red blood cells (n = 200), fresh frozen plasma (n = 109), and liquid plasma (n = 248). HN whole blood used was 337/495 (68%) units for 78 patients; walking blood bank was mobilized six times for HN patients. Of the patients seen, >99% who arrived with a pulse survived to be discharged to a higher level of care. CONCLUSIONS: This analysis describes blood usage associated with one high volume forward deployed operative team and demonstrates the vital importance of the R2 split FST to provide coalition forces with surgical care in proximity to the point of injury. Over time, the supply chain has improved with more component therapy available at R2s; however, the need for walking blood bank and innovative solutions to care for all casualties must be part of small team capabilities. Liquid plasma use should be expanded as soon as it is feasible.

Clostridioides difficile utilizes siderophores as an iron source and FhuDBGC contributes to ferrichrome uptake.

IMPORTANCE: This study is the first example of C. difficile growing with siderophores as the sole iron source and describes the characterization of the ferric hydroxamate uptake ABC transporter (FhuDBGC). This transporter shows specificity to the siderophore ferrichrome. While not required for pathogenesis, this transporter highlights the redundancy in iron acquisition mechanisms that C. difficile uses to compete for iron during an infection.

VENUM (Vascular Education iN Undergraduate Medicine): a multicentre evaluation of undergraduate vascular education in the UK.

INTRODUCTION: Vascular surgery is a recognised surgical subspecialty covering an array of circulatory conditions predominately affecting geriatric and diabetic patients. As such, a wide breadth of clinicians will see patients with vascular pathologies, but it is unclear how detailed their knowledge base is. Key to this is the education of medical students, which has been poorly documented during undergraduate training in the UK. VENUM aimed to establish students' perceptions of vascular surgery and their confidence in performing vascular objective structured clinical examination (OCSE) skills. METHODS: During the academic year of 2022/2023, final-year medical students were invited to complete a JISC survey (collaborative authorship). Seventy-seven research leads were recruited to disseminate the survey. Quantitative and thematic analysis was used to assess the data. RESULTS: In total, 240 final-year medical students completed the survey (54% female; 26 medical schools represented). Forty-five per cent of students reported never having had a vascular placement, 24% had never completed a vascular-focused clinical examination and 26% reported low confidence in performing ankle brachial pressure index measurement. An assessment of peripheral arterial disease morbidity was answered correctly in 17% of respondents compared with 92% for angina (chi-square test p<0.001). Students perceived the specialty to be non-inclusive and that early exposure to vascular surgery was required for better engagement with the specialty. CONCLUSION: Students have experienced little exposure to vascular surgery. This may affect future recruitment to vascular surgery and overall knowledge of vascular conditions in UK-trained doctors, which may affect long-term patient management.

Building Authentic Science Experiences: Students' Perceptions of Sequential Course-Based Undergraduate Research.

Course-based Undergraduate Research Experiences (CUREs) are attractive solutions for scaling undergraduate research experiences at primarily undergraduate teaching institutions, where resources for faculty research activities can be limited. The Sustainable Interdisciplinary Research to Inspire Undergraduate Success (SIRIUS) project is a unique program that integrates CUREs, coordinated around a local real-world problem, throughout a biology department's curricula. The CUREs are scaffolded to provide all biology majors with multiple opportunities to engage in scientific investigations as they advance through introductory, intermediate, and advanced courses. In this mixed methods, cross-sectional study, we explore students' perceptions of the authenticity of their experiences as they progress through the SIRIUS CUREs. Triangulated data collected from two instruments indicated that students in advanced courses recognized more involvement in research activities and perceived greater authenticity in the science they were performing compared with introductory and intermediate students. Intermediate and advanced students perceived more opportunities for independence; however, experiences with failure and the influence these experiences had on the perceptions of authenticity was primarily observed with advanced students. This study contributes to the growing literature on CUREs with a focus on students from a primarily undergraduate institution with multiple minority-serving designations.

Origins of slow growth on the crocodilian stem lineage.

Crocodilians grow slowly and have low metabolic rates similar to other living reptiles, but palaeohistology indicates that they evolved from an ancestor with higher growth rates.1,2,3,4,5 It remains unclear when slow growth appeared in the clade due to the sparse data on key divergences among early Mesozoic members of their stem lineage. We present new osteohistological data from a broad sample of early crocodylomorphs, evaluated in a phylogenetic context alongside other pseudosuchians. We find that the transition to slow-growing bone types during mid-late ontogeny occurred around the origin of Crocodylomorpha during the Late Triassic. Earlier-diverging pseudosuchians had high maximum growth rates, as indicated by the presence of woven bone during middle and (sometimes) late ontogeny.6,7,8,9 Large-bodied pseudosuchians in particular exhibit some of the fastest-growing bone types, giving evidence for prolonged, rapid growth. By contrast, early-branching crocodylomorphs, including a new large-bodied taxon, had slow maximum rates of bone deposition, as evidenced by the presence of predominantly parallel-fibered or lamellar bone tissue during middle-late ontogeny. Late Triassic crocodylomorphs show skeletal anatomy consistent with "active" terrestrial habits,10,11,12 and their slow growth rates reject hypotheses linking this transition with sedentary, semiaquatic lifestyles or sprawling posture. Faster-growing pseudosuchian lineages go extinct in the Triassic, whereas slow-growing crocodylomorphs do not. This contrasts with the Jurassic radiation of fast-growing dinosaurs on the bird-stem lineage,13 suggesting that the End-Triassic mass extinction initiated a divergent distribution of growth strategies that persist in present-day archosaurs.