A-SOiD, an active-learning platform for expert-guided, data-efficient discovery of behavior.

To identify and extract naturalistic behavior, two methods have become popular: supervised and unsupervised. Each approach carries its own strengths and weaknesses (for example, user bias, training cost, complexity and action discovery), which the user must consider in their decision. Here, an active-learning platform, A-SOiD, blends these strengths, and in doing so, overcomes several of their inherent drawbacks. A-SOiD iteratively learns user-defined groups with a fraction of the usual training data, while attaining expansive classification through directed unsupervised classification. In socially interacting mice, A-SOiD outperformed standard methods despite requiring 85% less training data. Additionally, it isolated ethologically distinct mouse interactions via unsupervised classification. We observed similar performance and efficiency using nonhuman primate and human three-dimensional pose data. In both cases, the transparency in A-SOiD's cluster definitions revealed the defining features of the supervised classification through a game-theoretic approach. To facilitate use, A-SOiD comes as an intuitive, open-source interface for efficient segmentation of user-defined behaviors and discovered sub-actions.

B-SOiD, an open-source unsupervised algorithm for identification and fast prediction of behaviors.

Studying naturalistic animal behavior remains a difficult objective. Recent machine learning advances have enabled limb localization; however, extracting behaviors requires ascertaining the spatiotemporal patterns of these positions. To provide a link from poses to actions and their kinematics, we developed B-SOiD - an open-source, unsupervised algorithm that identifies behavior without user bias. By training a machine classifier on pose pattern statistics clustered using new methods, our approach achieves greatly improved processing speed and the ability to generalize across subjects or labs. Using a frameshift alignment paradigm, B-SOiD overcomes previous temporal resolution barriers. Using only a single, off-the-shelf camera, B-SOiD provides categories of sub-action for trained behaviors and kinematic measures of individual limb trajectories in any animal model. These behavioral and kinematic measures are difficult but critical to obtain, particularly in the study of rodent and other models of pain, OCD, and movement disorders.

A comprehensive analysis of authorship trends in Skeletal Radiology since inception from 1976 to 2020.

OBJECTIVE: The purpose of this study is to explore authorship trends within the musculoskeletal radiology subspecialty-focused journal, Skeletal Radiology, from inception to 2020. MATERIALS AND METHODS: Skeletal Radiology articles published in 1976, 1986, 1996, 2006, 2016, and 2020 were reviewed. For each article, the number of authors, the number of distinct institutions, the names of first and last authors, the country of the first author, the article length, and the number of article references were recorded. RESULTS: A total of 885 articles passed the exclusion criteria to be included in the study. Since inception, there has been a significant increase in the number of SR articles published (P = 0.02), the mean number of authors per article (P < 0.01), the mean number of references per article (P < 0.01), the mean number of distinct institutions per article (P = 0.02), and the mean number of pages per article (P < 0.01). The proportion of female first and last authors significantly increased (P = 0.02, P = 0.02). There was a significant increase in the proportion of articles published from Asia (P = 0.04). However, no significant changes in the proportion of articles published from other regions were observed. CONCLUSION: Similar to authorship trends in other medical journals, Skeletal Radiology demonstrated upward trends in authorship count, distinct institutional count, and article length. A rise in first and last female authorship was observed. Finally, an increase in the proportion of authors from Asia was observed while no significant changes in the proportion of authors from other regions were demonstrated.

Smart Self-Assembly Amphiphilic Cyclopeptide-Dye for Near-Infrared Window-II Imaging.

Development of novel nanomaterials for disease theranostics represents an important direction in chemistry and precision medicine. Fluorescent molecular probes in the second near-infrared window (NIR-II, 1000-1700 nm) show high promise because of their exceptional high detection sensitivity, resolution, and deep imaging depth. Here, a sharp pH-sensitive self-assembling cyclopeptide-dye, SIMM1000, as a smart nanoprobe for NIR-II imaging of diseases in living animals, is reported. This small molecule assembled nanoprobe exhibits smart properties by responding to a sharp decrease of pH in the tumor microenvironment (pH 7.0 to 6.8), aggregating from small nanoprobe (80 nm at pH 7.0) into large nanoparticles (>500 nm at pH 6.8) with ≈20-30 times enhanced fluorescence compared with the non-self-assembled CH-4T. It yields micrometer-scale resolution in blood vessel imaging and high contrast and resolution in bone and tumor imaging in mice. Because of its self-aggregation in acidic tumor microenvironments in situ, SIMM1000 exhibits high tumor accumulation and extremely long tumor retention (>19 days), while being excretable from normal tissues and safe. This smart self-assembling small molecule strategy can shift the paradigm of designing new nanomaterials for molecular imaging and drug development.

MD and DO: Differing Medical Degrees and the Associated Perceptions.

PURPOSE: To highlight perspectives about differing medical degrees and graduate medical education amongst current allopathic (MD) and osteopathic (DO) radiology residents. MATERIALS AND METHOD: Two hundred sixty-eight radiology residents were interviewed using an approved Association of Program Coordinators in Radiology (APCR) survey designed to evaluate perceptions of allopathic and osteopathic radiology residents regarding type of medical degree and their career development. The surveys were kept anonymous with no identifiable information. Residents in their first through fourth years of training replied with an approximate equal distribution amongst the different years. RESULTS: Based on the 268 respondents, DOs' more so than MDs', reported that their degree type altered their medical careers (P < 0.0001) and that they were advised to not pursue a radiology residency based on degree type (P< 0.0001). In addition, a large majority of both DOs' and MDs' felt that residency selection is favored towards the allopathic degree (P= 0.0451). CONCLUSION: This survey-based study does reveal perceived differences in the residency recruitment process based on degree type. Future discussions to bridge this perceived gap will be important, especially in light of the recent ACGME merger between the 2 educational pathways.

Evaluating Neuroradiology Fellowship Program Websites: A Critical Analysis of all 84 Programs in the United States.

PURPOSE: To investigate the accessibility and content of neuroradiology fellowship program websites (NRFW). METHODS: A list of neuroradiology fellowship programs were obtained from the official Accreditation Council for Graduate Medical Education (ACGME) website. A google search was used to identify each NRFW of individual programs. Each NRFW was evaluated for the availability of content under recruitment and education domains. RESULTS: At the time of the study, there were 84 ACGME accredited neuroradiology fellowship websites available for analysis. In the recruitment domain, evaluators found program description (98.8%), contact address (94.1%), and searchable on google (97.7%) most readily available while, interview day itinerary (3.5%), meal allowance (16.5%), and parking (21.2%) were least readily available. In the education domain, research (91.8%), facility description (89.4%), and faculty listing (82.4%) were most readily available, while postfellowship placement (10.6%), alumni education history (17.7%), and responsibility progression (25.9%) were least readily available. CONCLUSIONS: NRFW vary greatly in the amount of information they display. Programs display their descriptions and contact information most frequently while interview day itinerary was the least likely to be found. There were no statistically significant differences between the amount of recruitment and educational content listed when programs were stratified by rank (top ten vs below top ten), region (west, midwest, northeast, and south), and program size (>3 fellows vs 1-3 fellows). Website content development is relatively low cost and our findings suggest that there is room for improvement in website comprehensiveness.

A drug-inducible sex-separation technique for insects.

Here, we describe a drug-inducible genetic system for insect sex-separation that demonstrates proof-of-principle for positive sex selection in D. melanogaster. The system exploits the toxicity of commonly used broad-spectrum antibiotics geneticin and puromycin to kill the non-rescued sex. Sex-specific rescue is achieved by inserting sex-specific introns into the coding sequences of antibiotic-resistance genes. When raised on geneticin-supplemented food, the sex-sorter line establishes 100% positive selection for female progeny, while the food supplemented with puromycin positively selects 100% male progeny. Since the described system exploits conserved sex-specific splicing mechanisms and reagents, it has the potential to be adaptable to other insect species of medical and agricultural importance.

Time cells might be optimized for predictive capacity, not redundancy reduction or memory capacity.

Recently, researchers have found time cells in the hippocampus that appear to contain information about the timing of past events. Some researchers have argued that time cells are taking a Laplace transform of their input in order to reconstruct the past stimulus. We argue that stimulus prediction, not stimulus reconstruction or redundancy reduction, is in better agreement with observed responses of time cells. In the process, we introduce new analyses of nonlinear, continuous-time reservoirs that model these time cells.

Infective Aortic Valve Endocarditis Causing Embolic Consecutive ST-Elevation Myocardial Infarctions.

ST-elevation myocardial infarction (STEMI) is a rare and potentially fatal complication of infective endocarditis. We report the ninth case of embolic native aortic valve infective endocarditis causing STEMI and the first case to describe consecutive embolisms leading to infarctions of separate coronary territories. Through examination of this case in the context of the previous eight similar documented cases in the past, we find that infective endocarditis of the aortic valve can and frequently affect more than a single myocardial territory and can occur consecutively. Further, current treatment modalities for embolic infective endocarditis causing acute myocardial infarction are limited and unproven. This index case illustrates the potential severity of complications and the challenges in developing standardized management for such patients.

Exploring a Third Confirmed Case of Hemoperitoneum following Open Inguinal Hernia Repair Caused by Sampson Artery Hemorrhage.

Hemoperitoneum is a rare complication of open inguinal hernia repair. This is the third reported case of this complication attributed to the same bleeding source: Sampson's artery. Sampson's artery courses along the round ligament of the uterus in the inguinal canal of females, originating from the arcade formed between the uterine and ovarian arteries. Usually obliterated in postembryonic development, this artery can persist in some adult female patients. Disruption of Sampson's artery can lead to hemoperitoneum following ligation of the uterine round ligament during open inguinal hernia repair in females. This case report describes a third confirmed case of hemoperitoneum complicating an open inguinal hernia repair. We review all three reported cases to date and discuss the recurring signs, symptoms, epidemiologic factors, and diagnostic findings associated. Our review suggests that females of childbearing age, particularly those in the peripartum period, are most at risk of developing this rare complication.

Comparative ultrastructural features of excitatory synapses in the visual and frontal cortices of the adult mouse and monkey.

The excitatory glutamatergic synapse is the principal site of communication between cortical pyramidal neurons and their targets, a key locus of action of many drugs, and highly vulnerable to dysfunction and loss in neurodegenerative disease. A detailed knowledge of the structure of these synapses in distinct cortical areas and across species is a prerequisite for understanding the anatomical underpinnings of cortical specialization and, potentially, selective vulnerability in neurological disorders. We used serial electron microscopy to assess the ultrastructural features of excitatory (asymmetric) synapses in the layers 2-3 (L2-3) neuropil of visual (V1) and frontal (FC) cortices of the adult mouse and compared findings to those in the rhesus monkey (V1 and lateral prefrontal cortex [LPFC]). Analyses of multiple ultrastructural variables revealed four organizational features. First, the density of asymmetric synapses does not differ between frontal and visual cortices in either species, but is significantly higher in mouse than in monkey. Second, the structural properties of asymmetric synapses in mouse V1 and FC are nearly identical, by stark contrast to the significant differences seen between monkey V1 and LPFC. Third, while the structural features of postsynaptic entities in mouse and monkey V1 do not differ, the size of presynaptic boutons are significantly larger in monkey V1. Fourth, both presynaptic and postsynaptic entities are significantly smaller in the mouse FC than in the monkey LPFC. The diversity of synaptic ultrastructural features demonstrated here have broad implications for the nature and efficacy of glutamatergic signaling in distinct cortical areas within and across species.

Is the effect of surface modifying molecules on antibacterial activity universal for a given material?

Antibacterial activity of nanomaterials is strongly dependent on their properties, and their stability and toxicity can be varied using surface coatings. We investigated the effect of different surface modifying molecules on the antibacterial properties of two ZnO nanoparticle samples. We found that the starting surface properties of the nanoparticles have significant effects on the attachment of the surface modifying molecules and consequent antibacterial activity. Two out of five investigated surface modifying molecules not only had a significant difference in the magnitude of their effect on different nanoparticles, but also resulted in the opposite effects on two ZnO nanoparticle samples (an enhancement of antibacterial activity for one and a reduction of antibacterial activity for the other ZnO sample). This indicates that no general rule on the effect of a specific molecule on the toxicity of a metal oxide nanoparticle can be derived without knowing the nanoparticle properties, due to the fact that surface modifier attachment onto the surface is affected by the initial surface properties.

Clavulanic acid reduces rewarding, hyperthermic and locomotor-sensitizing effects of morphine in rats: a new indication for an old drug?

BACKGROUND: Despite the efficacy of ceftriaxone (CTX) in animal models of CNS diseases, including drug addiction, its utility as a CNS-active therapeutic may be limited by poor brain penetrability and cumbersome parenteral administration. An alternative is the ß-lactamase inhibitor clavulanic acid (CA), a constituent of Augmentin that prevents antibiotic degradation. CA possesses the ß-lactam core necessary for CNS activity but, relative to CTX, possesses: (1) oral activity; (2) 2.5-fold greater brain penetrability; and (3) negligible antibiotic activity. METHODS: To compare the effectiveness of CA (10mg/kg) and CTX (200mg/kg) against centrally-mediated endpoints, we investigated their effects against morphine's rewarding, hyperthermic, and locomotor-sensitizing actions. Endpoints were based on prior evidence that CTX attenuates morphine-induced physical dependence, tolerance, and hyperthermia. RESULTS: As expected, rats treated with morphine (4 mg/kg) displayed hyperthermia and conditioned place preference (CPP). Co-treatment with CTX or CA inhibited development of morphine-induced CPP by approximately 70%. Morphine's hyperthermic effect was also suppressed, with CTX and CA producing 57% and 47% inhibition, respectively. Locomotor sensitization induced by repeated morphine exposures was inhibited by CA but not CTX. CONCLUSIONS: The present findings are the first to suggest that CA disrupts the in vivo actions of morphine and point toward further studying CA as a potential therapy for drug addiction. Further, its ability to disrupt morphine's rewarding effects at 20-fold lower doses than CTX identifies CA as an existing, orally-active alternative to direct CTX therapy for CNS diseases.

Curation-free biomodules mechanisms in prostate cancer predict recurrent disease.

MOTIVATION: Gene expression-based prostate cancer gene signatures of poor prognosis are hampered by lack of gene feature reproducibility and a lack of understandability of their function. Molecular pathway-level mechanisms are intrinsically more stable and more robust than an individual gene. The Functional Analysis of Individual Microarray Expression (FAIME) we developed allows distinctive sample-level pathway measurements with utility for correlation with continuous phenotypes (e.g. survival). Further, we and others have previously demonstrated that pathway-level classifiers can be as accurate as gene-level classifiers using curated genesets that may implicitly comprise ascertainment biases (e.g. KEGG, GO). Here, we hypothesized that transformation of individual prostate cancer patient gene expression to pathway-level mechanisms derived from automated high throughput analyses of genomic datasets may also permit personalized pathway analysis and improve prognosis of recurrent disease. RESULTS: Via FAIME, three independent prostate gene expression arrays with both normal and tumor samples were transformed into two distinct types of molecular pathway mechanisms: (i) the curated Gene Ontology (GO) and (ii) dynamic expression activity networks of cancer (Cancer Modules). FAIME-derived mechanisms for tumorigenesis were then identified and compared. Curated GO and computationally generated "Cancer Module" mechanisms overlap significantly and are enriched for known oncogenic deregulations and highlight potential areas of investigation. We further show in two independent datasets that these pathway-level tumorigenesis mechanisms can identify men who are more likely to develop recurrent prostate cancer (log-rank_p = 0.019). CONCLUSION: Curation-free biomodules classification derived from congruent gene expression activation breaks from the paradigm of recapitulating the known curated pathway mechanism universe.