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Abstract Osteosarcoma (OS) is a heterogeneous, aggressive malignancy of the bone that disproportionally affects children and adolescents. Therapeutic interventions for OS are limited, which is in part due to the complex tumor microenvironment (TME). As such, we used single-cell RNA sequencing (scRNA-seq) to describe the cellular and molecular composition of the TME in 6 treatment-naïve dogs with spontaneously occurring primary OS. Through analysis of 35,310 cells, we identified 41 transcriptomically distinct cell types including the characterization of follicular helper T cells, mature regulatory dendritic cells (mregDCs), and 8 tumor-associated macrophage (TAM) populations. Cell-cell interaction analysis predicted that mregDCs and TAMs play key roles in modulating T cell mediated immunity. Furthermore, we completed cross-species cell type gene signature homology analysis and found a high degree of similarity between human and canine OS. The data presented here act as a roadmap of canine OS which can be applied to advance translational immuno-oncology research.

Abstract Introduction Survival from refractory out of hospital cardiac arrest (OHCA) without timely return of spontaneous circulation (ROSC) utilising conventional advanced cardiac life support (ACLS) therapies is dismal. CHEER3 was a safety and feasibility study of pre-hospital deployed extracorporeal membrane oxygenation (ECMO) during cardiopulmonary resuscitation (ECPR) for refractory OHCA in metropolitan Australia. Methods This was a single jurisdiction, single-arm feasibility study. Physicians, with pre-existing ECMO expertise, responded to witnessed OHCA, age

Objective: Venous thromboembolic event (VTE) after spine surgery is a rare but potentially devastating complication. With the advent of machine learning, an opportunity exists for more accurate prediction of such events to aid in prevention and treatment. Methods: Seven models were screened using 108 database variables and 62 preoperative variables. These models included deep neural network (DNN), DNN with synthetic minority oversampling technique (SMOTE), logistic regression, ridge regression, lasso regression, simple linear regression, and gradient boosting classifier. Relevant metrics were compared between each model. The top four models were selected based on area under the receiver operator curve; these models included DNN with SMOTE, linear regression, lasso regression, and ridge regression. Separate random sampling of each model was performed 1000 additional independent times using a randomly generated training/testing distribution. Variable weights and magnitudes were analyzed after sampling. Results: Using all patient-related variables, DNN using SMOTE was the top-performing model in predicting postoperative VTE after spinal surgery (area under the curve [AUC] =0.904), followed by lasso regression (AUC = 0.894), ridge regression (AUC = 0.873), and linear regression (AUC = 0.864). When analyzing a subset of only preoperative variables, the top-performing models were lasso regression (AUC = 0.865) and DNN with SMOTE (AUC = 0.864), both of which outperform any currently published models. Main model contributions relied heavily on variables associated with history of thromboembolic events, length of surgical/anesthetic time, and use of postoperative chemoprophylaxis. Conclusions: The current study provides promise toward machine learning methods geared toward predicting postoperative complications after spine surgery. Further study is needed in order to best quantify and model real-world risk for such events.

Background: When COVID-19 cases began rising in early 2020, many universities transitioned online. Purpose/Hypothesis: This mixed-methods study examined how students, staff, and faculty members in a college of engineering experienced the early stages of the pandemic. We hypothesized that our prior work to build community and capacity around teaching and learning among faculty would support an empowered transition to online learning. Design/Method: We collected 70 participant accounts from April 10 to May 28, 2020 (students = 45, staff = 2, and faculty = 24). We collected these data using the SenseMaker® online survey platform. They comprised short stories written by the participants and quantitative data resulting from participant responses to a series of questions about their experiences. We used inferential statistics to determine pivotal variables that correlated to the emotional tone of a story and differentiated faculty and student experiences. Using these pivotal variables for interpretation, we examined participant stories to identify underlying trends in faculty and student experiences. Results: The majority of faculty members rated their stories positively (62%) while the majority of students rated their stories negatively (53%). Compared to students, faculty members reported greater opportunities, fewer struggles, higher levels of willingness to experiment, better treatment by people in positions of power, and more experiences of putting the needs of others before their own. Qualitatively, we identified two themes – ability and empowerment (or lack thereof) – to characterize the key differences between faculty and student experiences. Ability and empowerment are key facets of capacity. Conclusions: These findings confirm our hypothesis that prior work to build community and capacity around teaching and learning among faculty in our college supported an empowered transition to online learning. A next step in the development of our programming is finding ways to ensure our efforts lead to increased capacity for students, too.

Translationally relevant animal models are essential for the successful translation of basic science findings into clinical medicine. While rodent models are widely accessible, there are numerous limitations that prevent the extrapolation of findings to human medicine. One approach to overcome these limitations is to use animal models that are genetically diverse and naturally develop disease. For example, pet dogs spontaneously develop diseases that recapitulate the natural progression seen in humans and live in similar environments alongside humans. Thus, dogs represent a useful animal model for many areas of research. Despite the value of the canine model, species specific reagent limitations have hampered in depth characterization of canine immune cells, which constrains the conclusions that can be drawn from canine immunotherapy studies. To address this need, we used single-cell RNA sequencing to characterize the heterogeneity of circulating leukocytes in healthy dogs (n = 7) and osteosarcoma (OS) affected dogs (n = 10). We present a cellular atlas of leukocytes in healthy dogs, then employ the dataset to investigate the impact of primary OS tumors on the transcriptome of circulating leukocytes. We identified 36 unique cell populations amongst dog circulating leukocytes, with a remarkable amount of heterogeneity in CD4 T cell subtypes. In our comparison of healthy dogs and dogs with OS, we identified relative increases in the abundances of polymorphonuclear (PMN-) and monocytic (M-) myeloid-derived suppressor cells (MDSCs), as well as aberrations in gene expression within myeloid cells. Overall, this study provides a detailed atlas of canine leukocytes and investigates how the presence of osteosarcoma alters the transcriptional profiles of circulating immune cells.

Background: Traumatic vertebral artery dissections (tVADs) occur in up to 20% of patients with head trauma, yet data on their presentation and associated sequelae are limited. Aims and Objectives: To characterize the tVAD population and identify factors associated with clinical outcomes. Materials and Methods: We retrospectively analyzed all cases of tVAD at our institution from January 2004 to December 2018 with respect to mechanism of injury, clinical presentation, anatomic factors, associated pathologies, and relevant outcomes. Results: Of the 123 patients with tVAD, the most common presenting symptoms were neck pain (n=76, 67.3%), headache (57.5%), and visual changes (29.6%). 101 cases (82.1%) were unilateral, and 22 cases (17.9%) were bilateral. V2 was the most involved anatomic segment (83 cases, 70.3). 30 cases (25.4%) led to stroke, and 39 cases (31.7%) had a concomitant cervical fracture. The anatomic segment and number of segments involved, and baseline clinical and demographic characteristics were not associated with risk of stroke. Patients with associated fractures were older (50.3 years v. 36.4 years, p=0.0233), had a higher comorbid disease burden (CCI 1 vs. CCI 1, p

Purpose: We report the case of a 66-year-old female who returned with a rare recurrence of iridociliary melanoma 180° from the original lesion. Observations: Upon initial presentation eleven years prior, a pigmented iris lesion suspicious for primary uveal melanoma was noted in the right eye at 9 o'clock. After one year of observation, inferior growth of the iris lesion prompted treatment via primary iridectomy with excisional biopsy and pupilloplasty. Postoperative biopsy confirmed spindle B type melanoma with epithelial foci, and adjuvant brachytherapy was performed to treat the reported positive anterior ciliary body involvement. Ten years after initial plaque brachytherapy treatment, the patient returned with a pigmented iris lesion in the right eye at 3:30–5 o'clock, which was treated with enucleation. On pathology, the new melanoma was predominantly epithelioid, consistent with a transformed recurrent iridociliary melanoma. The patient remains metastasis free 13 years after initial diagnosis. Conclusions and importance: This case describes a rare, late recurrence of an iridociliary melanoma 180° away eleven years after initial presentation, emphasizing the importance of lifelong follow-up for patients with iridociliary melanoma. This rare form of recurrence has not been previously reported in the literature. We hypothesize the original lesion contained radiotherapy resistant epithelioid cells which grew superficially on the posterior iris and anterior ciliary body, ultimately breaking back through the anterior iris 180° away.

AbstractPolyploidy is considered a driving force in plant evolution and domestication. Although in the genus ArachisArachis hypogaeaArachis ipaënsisArachis duranensis

Evaluation of potential immunity against the novel severe acute respiratory syndrome (SARS) coronavirus that emerged in 2019 (SARS-CoV-2) is essential for health, as well as social and economic recovery. Generation of antibody response to SARS-CoV-2 (seroconversion) may inform on acquired immunity from prior exposure, and antibodies against the SARS-CoV-2 spike protein receptor binding domain (S-RBD) are speculated to neutralize virus infection. Some serology assays rely solely on SARS-CoV-2 nucleocapsid protein (N-protein) as the antibody detection antigen; however, whether such immune responses correlate with S-RBD response and COVID-19 immunity remains unknown. Here, we generated a quantitative serological ELISA using recombinant S-RBD and N-protein for the detection of circulating antibodies in 138 serial serum samples from 30 reverse transcription PCR–confirmed, SARS-CoV-2–hospitalized patients, as well as 464 healthy and non–COVID-19 serum samples that were collected between June 2017 and June 2020. Quantitative detection of IgG antibodies against the 2 different viral proteins showed a moderate correlation. Antibodies against N-protein were detected at a rate of 3.6% in healthy and non–COVID-19 sera collected during the pandemic in 2020, whereas 1.9% of these sera were positive for S-RBD. Approximately 86% of individuals positive for S-RBD–binding antibodies exhibited neutralizing capacity, but only 74% of N-protein–positive individuals exhibited neutralizing capacity. Collectively, our studies show that detection of N-protein–binding antibodies does not always correlate with presence of S-RBD–neutralizing antibodies and caution against the extensive use of N-protein–based serology testing for determination of potential COVID-19 immunity.

Dermatomal maps are a mainstay of clinical practice and provide information on the spatial distribution of the cutaneous innervation of spinal nerves. Dermatomal deficits can help isolate the level of spinal nerve root involvement in spinal conditions and guide clinicians in diagnosis and treatment. Dermatomal maps, however, have limitations, and the spatial distribution of spinal cord sensory activity in humans remains to be quantitatively assessed. Here we used spinal cord functional MRI to map and quantitatively compare the spatial distribution of sensory spinal cord activity during tactile stimulation of the left and right lateral shoulders (i.e. C5 dermatome) and dorsal third digits of the hands (i.e., C7 dermatome) in healthy humans (n ​= ​24, age ​= ​36.8 ​± ​11.8 years). Based on the central sites for processing of innocuous tactile sensory information, we hypothesized that the activity would be localized more to the ipsilateral dorsal spinal cord with the lateral shoulder stimulation activity being localized more superiorly than the dorsal third digit. The findings demonstrate lateralization of the activity with the left- and right-sided stimuli having more activation in the ipsilateral hemicord. Contradictory to our hypotheses, the activity for both stimulation sites was spread across the dorsal and ventral hemicords and did not demonstrate a clear superior-inferior localization. Instead, the activity for both stimuli had a broader than expected distribution, extending across the C5, C6, and C7 spinal cord segments. We highlight the complexity of the human spinal cord neuroanatomy and several sources of variability that may explain the observed patterns of activity. While the findings were not completely consistent with our a priori hypotheses, this study provides a foundation for continued work and is an important step towards developing normative quantitative spinal cord measures of sensory function, which may become useful objective MRI-based biomarkers of neurological injury and improve the management of spinal disorders.

Abstract Objective - Seeking information is a key element of evidence based practice and successful healthcare delivery. Significant literature exists on both the information seeking behaviour of professional nurses and information literacy teaching methods, but scarce evidence connects nurses’ information behaviour and environments with their education. This study sought to use data from nursing alumni to answer the following research questions: What are the current information practices of professional bachelor’s-prepared nurses? How do recently-graduated nurses suggest that their education could have better prepared them to find and evaluate information in the workplace? Methods - The researchers conducted a descriptive study using a 59-item survey instrument with a variety of question formats including short-answer, multiple choice, Likert, and open response. The researchers distributed the survey to baccalaureate nursing alumni who graduated in 2012-2017 from four universities in the state of Utah in the United States. Results - Nurses seek practical information primarily to provide informed patient care, while also clarifying medical situations and expanding their health care knowledge. They frequently consult nursing colleagues and physicians when seeking information. The majority of nurses consult electronic health records daily. Respondents described time as the biggest barrier to accessing information. They requested authentic, clinically-focused scenarios, training on freely-accessible resources, and more explicit teaching of lifelong learning skills, such as critical thinking. Conclusion - Information literacy education should prepare student nurses for the fast-paced information environment they will face in the workplace. This means incorporating more patient-focused scenarios, freely available quality resources, and time-based activities in their education. The researchers suggest areas to prepare nurses for information seeking, including problem-based clinical scenarios, building guides with databases accessible for free or little cost, and added emphasis on critical thinking and self-motivated learning.

MethodsTwenty patients with CSM and 17 controls were recruited. Clinical scores of modified Japanese Orthopedic Association (mJOA) and Nurick were collected. MRI based compression grades such as cord distortion were assessed. Hand dysfunction was tested using a custom motorized apparatus. Subject's forearm was placed in a cast and positioned such that their metacarpophalangeal (MCP) joint was vertically aligned with the motor shaft. Surface electromyographic sensors were placed on flexor digitorum superficialis (FDS) and extensor digitorum communis muscles. Hyperreflexia was measured as the FDS muscle activation during reflex when the MCP joint was moved from flexion to extension at 300°/sec. Proprioception was quantified as the angle of detection in absence of visual or auditory cues (subjects were blindfolded and given noise-cancelling headphones). Strength was measured as the maximum isometric force at the MCP joint. 2-sample t-test (pResultsPatients reported higher Nurick (1.90±1.0 vs 0±0, pConclusionIn conclusion, hyperreflexia and decline in proprioception are the main drivers of hand disability in patients with CSM. Of multiple scales, only a select few MRI scales (such as compression ratio) were predictive of increased reflexes. The study describes a pre-clinical testing apparatus to quantitatively and objectively assess primary presenting symptoms in CSM. This pilot apparatus has the potential to evaluate treatment efficacy through repeated testing. Objective testing of hand dysfunction can help inform the design of clinically feasible devices, guide MRI biomarker analysis, and improve our understanding of the progression of neurological injury in this patient population.

Background: The effects of recombinant interleukin-1β (rIL-1β) have been described for the middle carpal joint (MCJ). However, we are unaware of any studies that have described the cytological response of the tibiotarsal joint (TTJ) to rIL-1β or compared the clinical and cytological responses of the MCJ to the TTJ following the administration of intra-articular rIL-1β. Such information is critical for researchers planning to use rIL-1β to create acute synovitis models in horses.Objectives: To compare the clinical and cytological responses of the MCJ to the TTJ following administration of intra-articular rIL-1β.Methods: Twelve horses were used for the study. Eight horses received 75 ng of rIL-1β into the MCJ and four horses received 75 ng of rIL-1β into the TTJ. Clinical and cytological outcome parameters including lameness, joint circumference, joint effusion score, total nucleated cell count, cellular differentials, C-reactive protein, and prostaglandin-E2 concentrations were determined at baseline and multiple post-treatment time points over a 336 h period (2 weeks).Results: Recombinant IL-1β administered into the TTJ resulted in a significantly greater respiratory rate at 24 h and heart rate at 12 h when compared to rIL-1β administered into the MCJ. In addition, the TTJ had a significantly greater increase in joint circumference at 24 post-injection hour (PIH) and subjective effusion grade at 24 PIH and 336 PIH. The MCJ had significantly higher total protein concentration at 6 PIH, and a significantly higher NCC at 24 and 72 PIH when compared to the TTJ. Conversely, the TTJ had significantly higher neutrophilic infiltration than the MCJ at 6 PIH and 168 PIH.Conclusions: This study establishes that the same intra-articular dose of rIL-1 β elicits significantly different clinical and cytological responses in the MCJ compared to the TTJ in the equine model of intra-articular synovitis. In addition, clinical and cytological evidence of synovitis may persist up to or >1 week following intra-articular administration of rIL-1 β.