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Infantile perianal pyramidal protrusion is characterized by a light pink to skin-colored soft tissue protrusion that is often midline and anterior [A1]to the anus. It most commonly occurs in young females and is relatively asymptomatic. Although biopsies are not routinely done, histopathology is relatively nonspecific and can appear similar to an acrochordon. The differential diagnosis is broad and clinical misdiagnosis as condyloma can lead to unnecessary accusations of child abuse. We report a case of perianal pyramidal protrusion that was originally biopsied owing to concern of condyloma acuminatum or molluscum. This case raises awareness of this diagnosis to help avoid unnecessary procedures and prevent emotional distress that could come for families with an inaccurate diagnosis of condyloma in young children.

Over the past two decades Biomedical Engineering has emerged as a major discipline that bridges societal needs of human health care with the development of novel technologies. Every medical institution is now equipped at varying degrees of sophistication with the ability to monitor human health in both non-invasive and invasive modes. The multiple scales at which human physiology can be interrogated provide a profound perspective on health and disease. We are at the nexus of creating avatars (herein defined as an extension of digital twins) of human patho/physiology to serve as paradigms for interrogation and potential intervention. Motivated by the emergence of these new capabilities, the IEEE Engineering in Medicine and Biology Society, the Departments of Biomedical Engineering at Johns Hopkins University and Bioengineering at University of California at San Diego sponsored an interdisciplinary workshop to define the grand challenges that face biomedical engineering and the mechanisms to address these challenges. The Workshop identified five grand challenges with cross-cutting themes and provided a roadmap for new technologies, identified new training needs, and defined the types of interdisciplinary teams needed for addressing these challenges. The themes presented in this paper include: 1) accumedicine through creation of avatars of cells, tissues, organs and whole human; 2) development of smart and responsive devices for human function augmentation; 3) exocortical technologies to understand brain function and treat neuropathologies; 4) the development of approaches to harness the human immune system for health and wellness; and 5) new strategies to engineer genomes and cells.

Abstract Atrial fibrillation (AF) is the most common sustained arrhythmia in humans, yet the molecular basis of AF remains incompletely understood. To determine the cell type-specific transcriptional changes underlying AF, we perform single-nucleus RNA-seq (snRNA-seq) on left atrial (LA) samples from patients with AF and controls. From more than 175,000 nuclei we find that only cardiomyocytes (CMs) and macrophages (MΦs) have a significant number of differentially expressed genes in patients with AF. Attractin Like 1 (ATRNL1) was overexpressed in CMs among patients with AF and localized to the intercalated disks. Further, in both knockdown and overexpression experiments we identify a potent role for ATRNL1 in cell stress response, and in the modulation of the cardiac action potential. Finally, we detect an unexpected expression pattern for a leading AF candidate gene, KCNN3. In sum, we uncover a role for ATRNL1 which may serve as potential therapeutic target for this common arrhythmia.

Abstract Introduction The delineation of organs-at-risk and lymph node areas is a crucial step in radiotherapy, but it is time-consuming and associated with substantial user-dependent variability in contouring. Artificial intelligence (AI) appears to be the solution to facilitate and standardize this work. The objective of this study is to compare eight available AI software programs in terms of technical aspects and accuracy for contouring organs-at-risk and lymph node areas with current international contouring recommendations. Material and methods From January–July 2023, we performed a blinded study of the contour scoring of the organs-at-risk and lymph node areas by eight self-contouring AI programs by 20 radiation oncologists. It was a single-center study conducted in radiation department at the Lorraine Cancer Institute. A qualitative analysis of technical characteristics of the different AI programs was also performed. Three adults (two women and one man) and three children (one girl and two boys) provided six whole-body anonymized CT scans, along with two other adult brain MRI scans. Using a scoring scale from 1 to 3 (best score), radiation oncologists blindly assessed the quality of contouring of organs-at-risk and lymph node areas of all scans and MRI data by the eight AI programs. We have chosen to define the threshold of an average score equal to or greater than 2 to characterize a high-performing AI software, meaning an AI with minimal to moderate corrections but usable in clinical routine. Results For adults CT scans: There were two AI programs for which the overall average quality score (that is, all areas tested for OARs and lymph nodes) was higher than 2.0: Limbus (overall average score = 2.03 (0.16)) and MVision (overall average score = 2.13 (0.19)). If we only consider OARs for adults, only Limbus, Therapanacea, MVision and Radformation have an average score above 2. For children CT scan, MVision was the only program to have a average score higher than 2 with overall average score = 2.07 (0.19). If we only consider OARs for children, only Limbus and MVision have an average score above 2. For brain MRIs: TheraPanacea was the only program with an average score over 2, for both brain delineation (2.75 (0.35)) and OARs (2.09 (0.19)). The comparative analysis of the technical aspects highlights the similarities and differences between the software. There is no difference in between senior radiation oncologist and residents for OARs contouring. Conclusion For adult CT-scan, two AI programs on the market, MVision and Limbus, delineate most OARs and lymph nodes areas that are useful in clinical routine. For children CT-scan, only one IA, MVision, program is efficient. For adult brain MRI, Therapancea,only one AI program is efficient. Trial registration: CNIL-MR0004 Number HDH434.

Abstract Human cognition supports complex behaviour across a range of situations, and traits (e.g. personality) influence how we react in these different contexts. Although viewing traits as situationally grounded is common in social sciences, often studies attempting to link brain activity to human traits examine brain-trait associations in a single task, or, under passive conditions like wakeful rest. These studies, often referred to as brain wide association studies (BWAS) have recently become the subject of controversy because results are often unreliable even with large sample sizes. Although there are important statistical reasons why BWAS yield inconsistent results, we hypothesised that the situation in which brain activity is measured will impact the power in detecting a reliable link to specific traits. We performed a state-space analysis where tasks from the Human Connectome Project (HCP) were organized into a low-dimensional space based on how they activated different large-scale neural systems. We examined how individuals’ observed brain activity across these different contexts related to their personality. We found that for multiple personality traits, stronger associations with brain activity emerge in some tasks than others. These data highlight the importance of context-bound views for understanding how brain activity links to trait variation in human behaviour.

Abstract Brain connectome analysis suffers from the high dimensionality of connectivity data, often forcing a reduced representation of the brain at a lower spatial resolution or parcellation. This is particularly true for graph-based representations, which are increasingly used to characterize connectivity gradients, capturing patterns of systematic spatial variation in the functional connectivity structure. However, maintaining a high spatial resolution is crucial for enabling fine-grained topographical analysis and preserving subtle individual differences that might otherwise be lost. Here we introduce a computationally efficient approach to establish spatially fine-grained connectivity gradients. At its core, it leverages a set of landmarks to approximate the underlying connectivity structure at the full spatial resolution without requiring a full-scale vertex-by-vertex connectivity matrix. We show that this approach reduces computational time and memory usage while preserving informative individual features and demonstrate its application in improving brain-behavior predictions. Overall, its efficiency can remove computational barriers and enable the widespread application of connectivity gradients to capture spatial signatures of the connectome. Importantly, maintaining a spatially fine-grained resolution facilitates to characterize the spatial transitions inherent in the core concept of gradients of brain organization.

AbstractThe American Institute for Medical and Biological Engineering (AIMBE) hosted a virtual symposium titled “Diversifying Paths to Academic Leadership” on January 27 and 28, 2022. The symposium sought to educate the community on the opportunities for and impact of leadership by biomedical engineering faculty, to encourage and invite women faculty, especially women of color, to consider and prepare to pursue leadership roles, to educate faculty on the expectations and duties of these roles, and to highlight experiences and paths to leadership of women engineering leaders. Here we review the main outcomes of the symposium to provide perspective on (1) personal visioning and positioning for leadership, (2) negotiating for success in leadership positions, and (3) leadership strategies for success specific to women faculty and where applicable, faculty of color.

Complex macro-scale patterns of brain activity that emerge during periods of wakeful rest provide insight into the organisation of neural function, how these differentiate individuals based on their traits, and the neural basis of different types of self-generated thoughts. Although brain activity during wakeful rest is valuable for understanding important features of human cognition, its unconstrained nature makes it difficult to disentangle neural features related to personality traits from those related to the thoughts occurring at rest. Our study builds on recent perspectives from work on ongoing conscious thought that highlight the interactions between three brain networks – ventral and dorsal attention networks, as well as the default mode network. We combined measures of personality with state-of-the-art indices of ongoing thoughts at rest and brain imaging analysis and explored whether this ‘tri-partite’ view can provide a framework within which to understand the contribution of states and traits to observed patterns of neural activity at rest. To capture macro-scale relationships between different brain systems, we calculated cortical gradients to describe brain organisation in a low-dimensional space. Our analysis established that for more introverted individuals, regions of the ventral attention network were functionally more aligned to regions of the somatomotor system and the default mode network. At the same time, a pattern of detailed self-generated thought was associated with a decoupling of regions of dorsal attention from regions in the default mode network. Our study, therefore, establishes that interactions between attention systems and the default mode network are important influences on ongoing thought at rest and highlights the value of integrating contemporary perspectives on conscious experience when understanding patterns of brain activity at rest.

Background: Short mindfulness-based interventions have gained traction in research due to their positive impact on well-being, cognition, and clinical symptoms across various settings. However, these short-term trainings are viewed as preliminary steps within a more extensive transformative path, presumably leading to long-lasting trait changes. Despite this, little is still known about the brain correlates of these meditation traits. Methods: To address this gap, we investigated the neural correlates of meditation expertise in long-term Buddhist practitioners, comparing the large-scale brain functional connectivity of 28 expert meditators with 47 matched novices. Our hypothesis posited that meditation expertise would be associated with specific and enduring patterns of functional connectivity present during both meditative (open monitoring/open presence and loving-kindness and compassion meditations) and nonmeditative resting states, as measured by connectivity gradients. Results: Applying a support vector classifier to states not included in training, we successfully decoded expertise as a trait, demonstrating its non–state-dependent nature. The signature of expertise was further characterized by an increased integration of large-scale brain networks, including the dorsal and ventral attention, limbic, frontoparietal, and somatomotor networks. The latter correlated with a higher ability to create psychological distance from thoughts and emotions. Conclusions: Such heightened integration of bodily maps with affective and attentional networks in meditation experts could point toward a signature of the embodied cognition cultivated in these contemplative practices.

This work focuses on molecules that are encoded by the major histocompatibility complex (MHC) and that bind self-, foreign- or tumor-derived peptides and display these at the cell surface for recognition by receptors on T lymphocytes (T cell receptors, TCR) and natural killer (NK) cells. The past few decades have accumulated a vast knowledge base of the structures of MHC molecules and the complexes of MHC/TCR with specificity for many different peptides. In recent years, the structures of MHC-I molecules complexed with chaperones that assist in peptide loading have been revealed by X-ray crystallography and cryogenic electron microscopy. These structures have been further studied using mutagenesis, molecular dynamics and NMR approaches. This review summarizes the current structures and dynamic principles that govern peptide exchange as these relate to the process of antigen presentation.

Abstract Exogenous attention, the process that makes external salient stimuli pop-out of a visual scene, is essential for survival. How attention-capturing events modulate human brain processing remains unclear. Here we show how the psychological construct of exogenous attention gradually emerges over large-scale gradients in the human cortex, by analyzing activity from 1,403 intracortical contacts implanted in 28 individuals, while they performed an exogenous attention task. The timing, location and task-relevance of attentional events defined a spatiotemporal gradient of three neural clusters, which mapped onto cortical gradients and presented a hierarchy of timescales. Visual attributes modulated neural activity at one end of the gradient, while at the other end it reflected the upcoming response timing, with attentional effects occurring at the intersection of visual and response signals. These findings challenge multi-step models of attention, and suggest that frontoparietal networks, which process sequential stimuli as separate events sharing the same location, drive exogenous attention phenomena such as inhibition of return.

Pharmacologic activation of branched-chain amino acid (BCAA) catabolism is protective in models of heart failure (HF). How protection occurs remains unclear, although a causative block in cardiac BCAA oxidation is widely assumed. Here, we use in vivo isotope infusions to show that cardiac BCAA oxidation in fact increases, rather than decreases, in HF. Moreover, cardiac-specific activation of BCAA oxidation does not protect from HF even though systemic activation does. Lowering plasma and cardiac BCAAs also fails to confer significant protection, suggesting alternative mechanisms of protection. Surprisingly, activation of BCAA catabolism lowers blood pressure (BP), a known cardioprotective mechanism. BP lowering occurred independently of nitric oxide and reflected vascular resistance to adrenergic constriction. Mendelian randomization studies revealed that elevated plasma BCAAs portend higher BP in humans. Together, these data indicate that BCAA oxidation lowers vascular resistance, perhaps in part explaining cardioprotection in HF that is not mediated directly in cardiomyocytes.

COVID-19 stay-at-home (SAH) orders were impactful on adolescence, when social interactions affect development. This has the potential to change adolescent trauma. A post-hoc multicenter retrospective analysis of adolescent (13-17 years-old) trauma patients (ATPs) at 11 trauma centers was performed. Patients were divided into 3 groups based on injury date: historical control (CONTROL:3/19/2019-6/30/2019, before SAH (PRE:1/1/2020-3/18/2020), and after SAH (POST:3/19/2020-6/30/2020). The POST group was compared to both PRE and CONTROL groups in separate analyses. 726 ATPs were identified across the 3 time periods. POST had a similar penetrating trauma rate compared to both PRE (15.8% vs 13.8%, P = .56) and CONTROL (15.8% vs 14.5%, P = .69). POST also had a similar rate of suicide attempts compared to both PRE (1.2% vs 1.5%, P = .83) and CONTROL (1.2% vs 2.1%, P = .43). However, POST had a higher rate of drug positivity compared to CONTROL (28.6% vs 20.6%, P = .032), but was similar in all other comparisons of alcohol and drugs to PRE and POST periods (all P > .05). Hence ATPs were affected differently than adults and children, as they had a similar rate of penetrating trauma, suicide attempts, and alcohol positivity after SAH orders. However, they had increased drug positivity compared to the CONTROL, but not PRE group.

Heart failure (HF) is a leading cause of mortality. Failing hearts undergo profound metabolic changes, but a comprehensive evaluation in humans is lacking. We integrate plasma and cardiac tissue metabolomics of 678 metabolites, genome-wide RNA-sequencing, and proteomic studies to examine metabolic status in 87 explanted human hearts from 39 patients with end-stage HF compared with 48 nonfailing donors. We confirm bioenergetic defects in human HF and reveal selective depletion of adenylate purines required for maintaining ATP levels. We observe substantial reductions in fatty acids and acylcarnitines in failing tissue, despite plasma elevations, suggesting defective import of fatty acids into cardiomyocytes. Glucose levels, in contrast, are elevated. Pyruvate dehydrogenase, which gates carbohydrate oxidation, is de-repressed, allowing increased lactate and pyruvate burning. Tricarboxylic acid cycle intermediates are significantly reduced. Finally, bioactive lipids are profoundly reprogrammed, with marked reductions in ceramides and elevations in lysoglycerophospholipids. These data unveil profound metabolic abnormalities in human failing hearts.

Heart disease is associated with re-expression of key transcription factors normally active only during prenatal development of the heart. However, the impact of this reactivation on the regulatory landscape in heart disease is unclear. Here, we use RNA-seq and ChIP-seq targeting a histone modification associated with active transcriptional enhancers to generate genome-wide enhancer maps from left ventricle tissue from up to 26 healthy controls, 18 individuals with idiopathic dilated cardiomyopathy (DCM), and five fetal hearts. Healthy individuals have a highly reproducible epigenomic landscape, consisting of more than 33,000 predicted heart enhancers. In contrast, we observe reproducible disease-associated changes in activity at 6,850 predicted heart enhancers. Combined analysis of adult and fetal samples reveals that the heart disease epigenome and transcriptome both acquire fetal-like characteristics, with 3,400 individual enhancers sharing fetal regulatory properties. We also provide a comprehensive data resource (http://heart.lbl.gov) for the mechanistic exploration of DCM etiology.

We designed and tested a system for real-time control of a user interface by extracting surface electromyographic (sEMG) activity from eight electrodes in a wristband configuration. sEMG data were streamed into a machine-learning algorithm that classified hand gestures in real-time. After an initial model calibration, participants were presented with one of three types of feedback during a human-learning stage: veridical feedback, in which predicted probabilities from the gesture classification algorithm were displayed without alteration; modified feedback, in which we applied a hidden augmentation of error to these probabilities; and no feedback. User performance was then evaluated in a series of minigames, in which subjects were required to use eight gestures to manipulate their game avatar to complete a task. Experimental results indicated that relative to the baseline, the modified feedback condition led to significantly improved accuracy. Class separation also improved, though this trend was not significant. These findings suggest that real-time feedback in a gamified user interface with manipulation of feedback may enable intuitive, rapid, and accurate task acquisition for sEMG-based gesture recognition applications.

Over the past two decades Biomedical Engineering has emerged as a major discipline that bridges societal needs of human health care with the development of novel technologies. Every medical institution is now equipped at varying degrees of sophistication with the ability to monitor human health in both non-invasive and invasive modes. The multiple scales at which human physiology can be interrogated provide a profound perspective on health and disease. We are at the nexus of creating “avatars” (herein defined as an extension of “digital twins”) of human patho/physiology to serve as paradigms for interrogation and potential intervention. Motivated by the emergence of these new capabilities, the IEEE Engineering in Medicine and Biology Society, the Departments of Biomedical Engineering at Johns Hopkins University and Bioengineering at University of California at San Diego sponsored an interdisciplinary workshop to define the grand challenges that face biomedical engineering and the mechanisms to address these challenges. The Workshop identified five grand challenges with cross-cutting themes and provided a roadmap for new technologies, identified new training needs, and defined the types of interdisciplinary teams needed for addressing these challenges. The themes presented in this paper include: 1) accumedicine through creation of avatars of cells, tissues, organs and whole human; 2) development of smart and responsive devices for human function augmentation; 3) exocortical technologies to understand brain function and treat neuropathologies; 4) the development of approaches to harness the human immune system for health and wellness; and 5) new strategies to engineer genomes and cells.

Abstract Cognitive neuroscience has gained insight into covert states using experience sampling. Traditionally, this approach has focused on off-task states. However, task-relevant states are also maintained via covert processes. Our study examined whether experience sampling can also provide insights into covert goal-relevant states that support task performance. To address this question, we developed a neural state space, using dimensions of brain function variation, that allows neural correlates of overt and covert states to be examined in a common analytic space. We use this to describe brain activity during task performance, its relation to covert states identified via experience sampling, and links between individual variation in overt and covert states and task performance. Our study established deliberate task focus was linked to faster target detection, and brain states underlying this experience—and target detection—were associated with activity patterns emphasizing the fronto-parietal network. In contrast, brain states underlying off-task experiences—and vigilance periods—were linked to activity patterns emphasizing the default mode network. Our study shows experience sampling can not only describe covert states that are unrelated to the task at hand, but can also be used to highlight the role fronto-parietal regions play in the maintenance of covert task-relevant states.

Background/Objectives: Sports-related concussions are a main cause of cognitive dysfunction and somatic complaints, particularly in youth. While the majority of concussion symptoms resolve within one week, cognitive effects may persist. In this study, we sought to study changes to cognition within this acute time frame. Methods: In this current study, we use an established swine model of traumatic brain injury (TBI) to study the effects of single and repeated head rotations on resting-state electroencephalography (rs-EEG) in awake piglets in the acute (within 7 days) time period after injury. We studied both healthy and experimental groups to (1) establish healthy reference ranges (RRs; N = 23) for one-minute rs-EEG in awake piglets, (2) compare the effects of single (N = 12) and repeated head rotations (N = 13) on rs-EEG, and (3) examine the acute time course (pre-injury and days 1, 4, and 7 post-injury) in animals administered single and repeated head rotations. EEG data were Fourier transformed, and total (1–30 Hz) and relative power in the alpha (8–12 Hz), beta (16.5–25 Hz), delta (1–4 Hz), and theta (4–7.5 Hz) bands were analyzed. Results: Total power and relative alpha, beta, delta, and theta power were consistent measures across days in healthy animals. We found a significant and transient increase in relative alpha power after repeated injury on day 1 in all regions and a rise above the healthy RR in the frontal and left temporal regions. Conclusions: Future studies will expand the study duration to investigate and inform clinical prognoses from acute measurements of rs-EEG.