CARDIAN: a novel computational approach for real-time end-diastolic frame detection in intravascular ultrasound using bidirectional attention networks.

Introduction: Changes in coronary artery luminal dimensions during the cardiac cycle can impact the accurate quantification of volumetric analyses in intravascular ultrasound (IVUS) image studies. Accurate ED-frame detection is pivotal for guiding interventional decisions, optimizing therapeutic interventions, and ensuring standardized volumetric analysis in research studies. Images acquired at different phases of the cardiac cycle may also lead to inaccurate quantification of atheroma volume due to the longitudinal motion of the catheter in relation to the vessel. As IVUS images are acquired throughout the cardiac cycle, end-diastolic frames are typically identified retrospectively by human analysts to minimize motion artefacts and enable more accurate and reproducible volumetric analysis. Methods: In this paper, a novel neural network-based approach for accurate end-diastolic frame detection in IVUS sequences is proposed, trained using electrocardiogram (ECG) signals acquired synchronously during IVUS acquisition. The framework integrates dedicated motion encoders and a bidirectional attention recurrent network (BARNet) with a temporal difference encoder to extract frame-by-frame motion features corresponding to the phases of the cardiac cycle. In addition, a spatiotemporal rotation encoder is included to capture the IVUS catheter's rotational movement with respect to the coronary artery. Results: With a prediction tolerance range of 66.7 ms, the proposed approach was able to find 71.9%, 67.8%, and 69.9% of end-diastolic frames in the left anterior descending, left circumflex and right coronary arteries, respectively, when tested against ECG estimations. When the result was compared with two expert analysts' estimation, the approach achieved a superior performance. Discussion: These findings indicate that the developed methodology is accurate and fully reproducible and therefore it should be preferred over experts for end-diastolic frame detection in IVUS sequences.

Observing and Quantifying Fluorescent Reporters.

Genetically encoded fluorescent reporters take advantage of C. elegans' transparency to allow non-invasive, in vivo observation, and recording of physiological processes in intact animals. Here, we discuss the basic microscope components required to observe, image, and measure fluorescent proteins in live animals for students and researchers who work with C. elegans but have limited experience with fluorescence imaging and analysis.

Machine learning for atherosclerotic tissue component classification in combined near-infrared spectroscopy intravascular ultrasound imaging: Validation against histology.

BACKGROUND AND AIMS: Accurate classification of plaque composition is essential for treatment planning. Intravascular ultrasound (IVUS) has limited efficacy in assessing tissue types, while near-infrared spectroscopy (NIRS) provides complementary information to IVUS but lacks depth information. The aim of this study is to train and assess the efficacy of a machine learning classifier for plaque component classification that relies on IVUS echogenicity and NIRS-signal, using histology as reference standard. METHODS: Matched NIRS-IVUS and histology images from 15 cadaveric human coronary arteries were analyzed (10 vessels were used for training and 5 for testing). Fibrous/pathological intimal thickening (F-PIT), early necrotic core (ENC), late necrotic core (LNC), and calcific tissue regions-of-interest were detected on histology and superimposed onto IVUS frames. The pixel intensities of these tissue types from the training set were used to train a J48 classifier for plaque characterization (ECHO-classification). To aid differentiation of F-PIT from necrotic cores, the NIRS-signal was used to classify non-calcific pixels outside yellow-spot regions as F-PIT (ECHO-NIRS classification). The performance of ECHO and ECHO-NIRS classifications were validated against histology. RESULTS: 262 matched frames were included in the analysis (162 constituted the training set and 100 the test set). The pixel intensities of F-PIT and ENC were similar and thus these two tissues could not be differentiated by echogenicity. With ENC and LNC as a single class, ECHO-classification showed good agreement with histology for detecting calcific and F-PIT tissues but had poor efficacy for necrotic cores (recall 0.59 and precision 0.29). Similar results were found when F-PIT and ENC were treated as a single class (recall and precision for LNC 0.78 and 0.33, respectively). ECHO-NIRS classification improved necrotic core and LNC detection, resulting in an increase of the overall accuracy of both models, from 81.4% to 91.8%, and from 87.9% to 94.7%, respectively. Comparable performance of the two models was seen in the test set where the overall accuracy of ECHO-NIRS classification was 95.0% and 95.5%, respectively. CONCLUSIONS: The combination of echogenicity with NIRS-signal appears capable of overcoming limitations of echogenicity, enabling more accurate characterization of plaque components.

Three-Dimensional Fruit Tissue Habitats for Culturing Caenorhabditis elegans.

Environmental factors influence many traits of biological interest, but reproducing an animal's natural habitat in a controlled laboratory environment is challenging. Environmental enrichment-adding complexity to the usually simplistic conditions under which laboratory animals are raised-offers a potential tool for better understanding biological traits while maintaining controlled laboratory conditions. For the model nematode Caenorhabditis elegans, the contrast between the natural environment and the laboratory conditions in which they are raised is enormous. Although several methods have been developed in an effort to complexify C. elegans laboratory conditions, there is still a need for an enriched controlled laboratory habitat in which C. elegans can be raised over several generations, the bacterial food availability is similar to that in traditional agar plates, and the animals are crawling as opposed to swimming or burrowing. To this end, we describe here a standardized protocol for creating controlled, reproducible, three-dimensional environments for multigenerational maintenance of C. elegans in the laboratory. These environments are derived from decellularized apple hypanthium tissue and have bacterial food uniformly distributed throughout. We also describe how traditional C. elegans methods of collecting synchronized eggs, cleaning contaminated stocks, and collecting animal populations are adapted to our scaffold environment. These methods can be adapted to host different bacteria or bacterial populations, and the resulting scaffolds can be used in a range of experimental designs for behavioral and phenotypical studies in C. elegans and other nematodes. © 2021 The Authors. Current Protocols published by Wiley Periodicals LLC. Basic Protocol 1: Decellularization and storage of apple tissue Basic Protocol 2: Preparation of plates from decellularized apple scaffolds Basic Protocol 3: Synchronization of eggs or animals and cleaning contaminated stocks from scaffold plates Alternate Protocol: Collection of non-synchronized larvae and adults from scaffold plates.

C. elegans does a spit take.

Eating can turn into spitting because individual parts of a muscle cell are able to contract in different ways.

A three-dimensional habitat for C. elegans environmental enrichment.

As we learn more about the importance of gene-environment interactions and the effects of environmental enrichment, it becomes evident that minimalistic laboratory conditions can affect gene expression patterns and behaviors of model organisms. In the laboratory, Caenorhabditis elegans is generally cultured on two-dimensional, homogeneous agar plates abundantly covered with axenic bacteria culture as a food source. However, in the wild, this nematode thrives in rotting fruits and plant stems feeding on bacteria and small eukaryotes. This contrast in habitat complexity suggests that studying C. elegans in enriched laboratory conditions can deepen our understanding of its fundamental traits and behaviors. Here, we developed a protocol to create three-dimensional habitable scaffolds for trans-generational culture of C. elegans in the laboratory. Using decellularization and sterilization of fruit tissue, we created an axenic environment that can be navigated throughout and where the microbial environment can be strictly controlled. C. elegans were maintained over generations on this habitat, and showed a clear behavioral bias for the enriched environment. As an initial assessment of behavioral variations, we found that dauer populations in scaffolds exhibit high-frequency, complex nictation behavior including group towering and jumping behavior.

Lead Toxicity in Children: An Unremitting Public Health Problem.

BACKGROUND: Lead is a pervasive environmental contaminant. Lead accumulates in the body, impairing a molecular level various cellular processes. Lead exposure during childhood causes adverse and permanent neurodevelopmental consequences, sometimes even with "low" blood lead levels. Symptoms are frequently silent, making lead exposure an often unrecognized and underestimated threat for pervasive neurocognitive disorders. METHODS: We identified articles focusing on childhood exposure to lead and neurodevelopment via a search of the electronic database PubMed (National Library of Medicine), including journal articles published from 2007 to 2019. These articles were used to evaluate the effect of environmental lead exposure and analyze whether control efforts over the past decades have altered the prevalence of exposed children. CONCLUSIONS: Children are still being exposed to lead despite evidence of the adverse impact of exposure, even for children with blood lead levels below the currently recognized threshold for intervention. Legislative and educational efforts have reduced lead exposure but are not being followed universally. Primary prevention and identification of high-risk populations are the best cost-benefit interventions to fight this public health problem.

Environmental Programming of Adult Foraging Behavior in C. elegans.

Foraging strategies should be tuned to the expected distribution of resources in the environment. Tuning can occur over generations and lead to genetic differences in innate foraging behavior or over shorter timescales within an individual's lifespan. Both genetically encoded and experience-based strategies are implemented by neural circuits that respond to environmental cues and track internal states. Caenorhabditis elegans exhibit both between-strain genetic differences and within-strain plasticity in foraging. In individuals, changes in foraging are usually short term and based on recent experience. Here, we tested whether developmental experience could permanently alter foraging. We found that, in most wild strains, early-life starvation led to "cautious" foraging strategies, in which exploration is reduced, and these behavioral changes are associated with altered dynamics in a locomotory circuit. Possessing either the derived (domestication-associated) or ancestral allele of the neuroglobin glb-5 determines foraging plasticity. Overall, we show that C. elegans exhibit adaptive developmental plasticity that affects multiple aspects of foraging behavior and leads to changes in a core navigation circuit and that innate foraging traits and plasticity in those traits are genetically separable. VIDEO ABSTRACT.

Gender differences in spatial navigation: Characterizing wayfinding behaviors.

Men show a consistent spatial navigation advantage over women, which is often attributed to their increased use of survey spatial strategies. But what about men's navigation gives them an advantage? One possibility is that the way in which men explore environments is fundamentally different, leading to better navigational performance. To test this possibility, this study investigated whether there are gender differences in wayfinding behaviors during navigation that relate to navigational success in a real-world, large-scale, unconstrained navigation task. West Point cadets were given a masked GPS tracker and sent into a large-scale, natural environment to locate targets indicated on maps. We assessed how they explored the environment by computing three measures from the GPS tracks and related these measures to their ability to find the assigned target locations. We also tested whether their self-reported spatial ability related to navigational success. Results showed that males performed better than females, which replicates prior work. Further, traveling longer distances without changing course, pausing less, and fewer returns to previously visited locations were significantly related to the ability to locate the correct target. Consistent with full mediation, the significant relationship between gender and navigational success is fully accounted for by men and women producing different wayfinding behaviors, which in turn predict differences in navigational success. Further, there was no unique relationship between self-reported spatial skills and navigational success. This study is a first step toward showing the relationship between gender, wayfinding behaviors, and navigational success in a natural, real-world navigation task.

Neuronal Small RNAs Control Behavior Transgenerationally.

It is unknown whether the activity of the nervous system can be inherited. In Caenorhabditis elegans nematodes, parental responses can transmit heritable small RNAs that regulate gene expression transgenerationally. In this study, we show that a neuronal process can impact the next generations. Neurons-specific synthesis of RDE-4-dependent small RNAs regulates germline amplified endogenous small interfering RNAs (siRNAs) and germline gene expression for multiple generations. Further, the production of small RNAs in neurons controls the chemotaxis behavior of the progeny for at least three generations via the germline Argonaute HRDE-1. Among the targets of these small RNAs, we identified the conserved gene saeg-2, which is transgenerationally downregulated in the germline. Silencing of saeg-2 following neuronal small RNA biogenesis is required for chemotaxis under stress. Thus, we propose a small-RNA-based mechanism for communication of neuronal processes transgenerationally.

Are gender gaps due to evaluations of the applicant or the science? A natural experiment at a national funding agency.

BACKGROUND: Across countries and disciplines, studies show male researchers receive more research funding than their female peers. Because most studies have been observational, it is unclear whether imbalances stem from evaluations of female research investigators or of their proposed research. In 2014, the Canadian Institutes of Health Research created a natural experiment by dividing investigator-initiated funding applications into two new grant programmes: one with and one without an explicit review focus on the calibre of the principal investigator. METHODS: We analysed application success among 23 918 grant applications from 7093 principal investigators in all investigator-initiated Canadian Institutes of Health Research grant programmes between 2011 and 2016. We used generalised estimating equations to account for multiple applications by the same applicant and compared differences in application success between male and female principal investigators under different review criteria. FINDINGS: Overall application success across competitions was 15·8%. After adjusting for age and research domain, the predicted probability of success in traditional programmes was 0·9 percentage points lower for female applicants than male applicants (95% CI 2·0 lower-0·2 higher; odds ratio 0·934, 95% CI 0·854-1·022). In the new programme, in which review focused on the proposed science, the gap remained 0·9 percentage points (3·2 lower-1·4 higher; 0·998, 0·794-1·229). In the new programme with an explicit review focus on the calibre of the principal investigator, the gap was 4·0 percentage points (6·7 lower-1·3 lower; 0·705, 0·519-0·960). INTERPRETATION: Gender gaps in grant funding are attributable to less favourable assessments of women as principal investigators, not of the quality of their proposed research. We discuss reasons less favourable assessments might occur and strategies to foster fair and rigorous peer review. FUNDING: None.

A Gate-and-Switch Model for Head Orientation Behaviors in Caenorhabditis elegans.

The nervous system seamlessly integrates perception and action. This ability is essential for stable representation of and appropriate responses to the external environment. How the sensorimotor integration underlying this ability occurs at the level of individual neurons is of keen interest. In Caenorhabditis elegans, RIA interneurons receive input from sensory pathways and have reciprocal connections with head motor neurons. RIA simultaneously encodes both head orientation and sensory stimuli, which may allow it to integrate these two signals to detect the spatial distribution of stimuli across head sweeps and generate directional head responses. Here, we show that blocking synaptic release from RIA disrupts head orientation behaviors in response to unilaterally presented stimuli. We found that sensory encoding in RIA is gated according to head orientation. This dependence on head orientation is independent of motor encoding in RIA, suggesting a second, posture-dependent pathway upstream of RIA. This gating mechanism may allow RIA to selectively attend to stimuli that are asymmetric across head sweeps. Attractive odor removal during head bends triggers rapid head withdrawal in the opposite direction. Unlike sensory encoding, this directional response is dependent on motor inputs to and synaptic output from RIA. Together, these results suggest that RIA is part of a sensorimotor pathway that is dynamically regulated according to head orientation at two levels: the first is a gate that filters sensory representations in RIA, and the second is a switch that routes RIA synaptic output to dorsal or ventral head motor neurons.

Where do children die and what are the causes? Under-5 deaths in the Metro West geographical service area of the Western Cape, South Africa, 2011.

BACKGROUND: Accurate child mortality data are essential to plan health interventions to reduce child deaths. OBJECTIVES: To review the deaths of children aged <5 years during 2011 in the Metro West geographical service area (GSA) of the Western Cape Province (WC), South Africa, from routine data sources. METHODS: A retrospective study of under-5 deaths in the Metro West GSA was done using the WC Local Mortality Surveillance System (LMSS), the Child Healthcare Problem Identification Programme (Child PIP) and the Perinatal Problem Identification Programme (PPIP), and linking where possible. RESULTS: The LMSS reported 700 under-5 deaths, Child PIP 99 and PPIP 252, with an under-5 mortality rate of 18 deaths per 1 000 live births. The leading causes of death were pneumonia (25%), gastroenteritis (10%), prematurity (9%) and injuries (9%). There were 316 in-hospital deaths (45%) and 384 out-of-hospital deaths (55%). Among children aged <1 year, there were significantly more pneumonia deaths out of hospital than in hospital (144 (49%) v. 16 (6%); p<0.001). Among children aged 1 - 4 years there were significantly more injury-related deaths out of hospital than in hospital (43 (47%) v. 4 (9%); p<0.001). In 56 (15%) of the cases of out-of-hospital death the child had visited a public healthcare facility within 1 week of death. Thirty-six (64%) of these children had died of pneumonia or gastroenteritis. CONCLUSIONS: Health interventions targeted at reducing under-5 deaths from pneumonia, gastroenteritis, prematurity and injuries need to be implemented across the service delivery platform in the Metro West GSA. It is important to consider all routine data sources in the evaluation of child mortality.

A role for attention during wilderness navigation: Comparing effects of BDNF, KIBRA, and CHRNA4.

OBJECTIVE: To better understand what influences interindividual differences in ability to navigate in the wilderness, we hypothesized that better performance would be seen in (a) BDNF (rs6265) Val/Val homozygotes increased use of a spatial strategy, (b) KIBRA rs17070145 T/T homozygotes superior episodic memory, (c) CHRNA4 (rs1044396) T allele carriers better ability to focus visuospatial attention. METHOD: Military cadets (n = 382) genotyped for BDNF, KIBRA, and CHRNA4 SNPs used a map and compass to navigate in unmarked woods. Participants completed a morning course within 3.0 km and an afternoon course within 7.0 km. RESULTS: Success or failure in finding each point was analyzed in a logistic regression model with KIBRA, BDNF, and CHRNA4 genotypes as fixed effects. For the morning course, the adjusted odds ratio for the effect of KIBRA T/T over KIBRA C/C was 2.58 (95% CI of 1.31, 5.06) demonstrating a statistical benefit of the KIBRA T/T genotype over individuals with KIBRA C/C genotype. BDNF did not have an independent association with navigational success. For the afternoon course, the adjusted odds ratio for the effect of CHRNA4 C/T over C/C was 1.67 (95% CI of 1.24, 2.25) demonstrating a statistical benefit of CHRNA4 T allele carriers over the C/C genotype. CONCLUSIONS: Ability to navigate in the wilderness benefits less from sense of direction (BDNF and Santa Barbara Sense of Direction) and more from episodic memory (KIBRA) in the first course and heightened ability to focus attention (CHRNA4) after experience in the 2nd course. (PsycINFO Database Record

Large lipid-rich coronary plaques detected by near-infrared spectroscopy at non-stented sites in the target artery identify patients likely to experience future major adverse cardiovascular events.

AIMS: A recent study demonstrated that intracoronary near-infrared spectroscopy (NIRS) findings in non-target vessels are associated with major adverse cardiovascular and cerebrovascular events (MACCE). It is unknown whether NIRS findings at non-stented sites in target vessels are similarly associated with future MACCE. This study evaluated the association between large lipid-rich plaques (LRP) detected by NIRS at non-stented sites in a target artery and subsequent MACCE. METHODS AND RESULTS: This study evaluated 121 consecutive registry patients undergoing NIRS imaging in a target artery. After excluding stented segments, target arteries were evaluated for a large LRP, defined as a maximum lipid core burden index in 4 mm (maxLCBI4 mm) ≥400. Excluding events in stented segments, Cox regression analysis was performed to evaluate for an association between a maxLCBI4 mm ≥400 and future MACCE, defined as all-cause mortality, non-fatal acute coronary syndrome, and cerebrovascular events. NIRS detected a maxLCBI4 mm ≥400 in a non-stented segment of the target artery in 17.4% of patients. The only baseline clinical variable marginally associated with MACCE was ejection fraction (HR 0.96, 95% CI 0.93-1.00, P = 0.054). A maxLCBI4 mm ≥400 in a non-stented segment at baseline was significantly associated with MACCE during follow-up (HR 10.2, 95% CI 3.4-30.6, P < 0.001). CONCLUSION: Detection of large LRP by NIRS at non-stented sites in a target artery was associated with an increased risk of future MACCE. These findings support ongoing prospective studies to further evaluate the ability of NIRS to identify vulnerable patients.

Observing and Quantifying Fluorescent Reporters.

Genetically encoded fluorescent reporters take advantage of C. elegans' transparency to allow noninvasive, in vivo observation and recording of physiological processes in intact animals. Here, I discuss the basic microscope components required to observe, image, and measure fluorescent proteins in live animals for students and researchers who work with C. elegans but have limited experience with fluorescence imaging and analysis.

Neuroecology: tuning foraging strategies to environmental variability.

Caenorhabditis elegans has been shown to measure variability in environmental food density, using the information to fine-tune foraging strategies; a compact neural circuit has been identified that responds to large fluctuations in food-related cues and uses dopamine to encode the amount of recently encountered variability.