Pathogenesis and transmission of SARS-CoV-2 in golden hamsters.

Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), a novel coronavirus with high nucleotide identity to SARS-CoV and to SARS-related coronaviruses that have been detected in horseshoe bats, has spread across the world and had a global effect on healthcare systems and economies1,2. A suitable small animal model is needed to support the development of vaccines and therapies. Here we report the pathogenesis and transmissibility of SARS-CoV-2 in golden (Syrian) hamsters (Mesocricetus auratus). Immunohistochemistry assay demonstrated the presence of viral antigens in nasal mucosa, bronchial epithelial cells and areas of lung consolidation on days 2 and 5 after inoculation with SARS-CoV-2, followed by rapid viral clearance and pneumocyte hyperplasia at 7 days after inoculation. We also found viral antigens in epithelial cells of the duodenum, and detected viral RNA in faeces. Notably, SARS-CoV-2 was transmitted efficiently from inoculated hamsters to naive hamsters by direct contact and via aerosols. Transmission via fomites in soiled cages was not as efficient. Although viral RNA was continuously detected in the nasal washes of inoculated hamsters for 14 days, the communicable period was short and correlated with the detection of infectious virus but not viral RNA. Inoculated and naturally infected hamsters showed apparent weight loss on days 6-7 post-inoculation or post-contact; all hamsters returned to their original weight within 14 days and developed neutralizing antibodies. Our results suggest that features associated with SARS-CoV-2 infection in golden hamsters resemble those found in humans with mild SARS-CoV-2 infections.

A gut microbial metabolite of dietary polyphenols reverses obesity-driven hepatic steatosis.

The molecular mechanisms by which dietary fruits and vegetables confer cardiometabolic benefits remain poorly understood. Historically, these beneficial properties have been attributed to the antioxidant activity of flavonoids. Here, we reveal that the host metabolic benefits associated with flavonoid consumption hinge, in part, on gut microbial metabolism. Specifically, we show that a single gut microbial flavonoid catabolite, 4-hydroxyphenylacetic acid (4-HPAA), is sufficient to reduce diet-induced cardiometabolic disease (CMD) burden in mice. The addition of flavonoids to a high fat diet heightened the levels of 4-HPAA within the portal plasma and attenuated obesity, and continuous delivery of 4-HPAA was sufficient to reverse hepatic steatosis. The antisteatotic effect was shown to be associated with the activation of AMP-activated protein kinase α (AMPKα). In a large survey of healthy human gut metagenomes, just over one percent contained homologs of all four characterized bacterial genes required to catabolize flavonols into 4-HPAA. Our results demonstrate the gut microbial contribution to the metabolic benefits associated with flavonoid consumption and underscore the rarity of this process in human gut microbial communities.

Self-perception of fatigue in individuals diagnosed with head and neck cancer.

PURPOSE: Head and neck cancer (HNCa) presents numerous challenges secondary to treatment. While there is substantial clinical awareness to the range of challenges demonstrated in this population, information on the impact of post-treatment fatigue is limited. This study investigated the degree of perceived fatigue in those treated for HNCa. METHODS: The study was a cross-sectional, self-report, survey design. Adult participants (n = 47) completed a series of three questionnaires; two validated fatigue measures - the Fatigue Screening Inventory (FSI) and the Multidimensional Fatigue Inventory (MFI-20) and a general health-related quality of life measure the European Organisation of Research on the Treatment of Cancer - Quality of Life Questionnaire (EORTC-QLQC30) and the head and neck site specific module (QLQ - H&N 35) were administered. RESULTS: Of the 47 participants, more than half (55%) were identified as having clinically significant self-reported levels of fatigue. Correlational analysis revealed an inverse relationship between fatigue and overall health-related quality of life (HRQOL) implying that as fatigue increases, one's perceived HRQOL decreases. CONCLUSIONS: These data suggest that efforts to proactively screen for and index fatigue and seek anticipatory interventions may benefit both short- and long-term HRQOL outcomes in those diagnosed with HNCa. LEVEL OF EVIDENCE: IV.

Kaposiform haemangioendothelioma of the spine associated with fixed hyperlordotic deformity and Kasabach-Merritt Syndrome: a case report and literature review.

Kaposiform haemangioendothelioma (KHE) is a rare childhood disease classified by the International Society for the Study of Vascular Anomalies (ISSVA) as a locally aggressive vascular tumor. It has been reported to affect any site, with a predilection for the extremities and trunk. Although it typically manifests as an enlarging cutaneous or soft tissue lesion, less than 10% of cases have no skin involvement, with the retroperitoneum being the most frequently involved extracutaneous site. Approximately twenty cases of KHE with bony involvement have been reported in the literature to date, with only five of those cases involving the spine specifically.We present a, rare case of KHE who presented with progressive fixed hyperlordotic deformity, multiple non-specific spinal lesions, and abnormal blood tests, posing a clinical and radiological diagnostic challenge. Additionally, we conducted a thorough review of the literature to compare and contrast the various multimodality imaging manifestations of KHE involving the spine.

Postoperative Respiratory Failure After Elective Abdominal Surgery: A Case-Control Study.

INTRODUCTION: Postoperative respiratory failure (PRF) contributes significantly to morbidity and mortality. We sought to identify patient characteristics and perioperative risk factors associated with PRF in patients undergoing elective abdominal surgery to improve patient outcomes. METHODS: We retrospectively reviewed patients undergoing elective abdominal surgery from 2011 to 2016 at our institution. An experimental group consisting of adult patients with the Patient Safety Indicator 11 diagnosis of PRF was compared with a time-matched control group. RESULTS: Each group consisted of 233 patients. Comorbidities associated with PRF included ascites, coronary artery disease, chronic kidney disease, chronic obstructive pulmonary disease, diabetes mellitus type II, hypertension, and hypoalbuminemia (P < 0.05). American Society of Anesthesiologists score IV (20.2% versus 3.95%; P < 0.001), operative time (4.13 versus 2.55 h; P < 0.001), laparotomy with open operation (77.7% versus 45.5%; P < 0.001), and net intraoperative fluid balance (3635 versus 2410 mL; P < 0.001) were higher in patients with PRF. On multivariate analysis, age, American Society of Anesthesiologists score, chronic obstructive pulmonary disease, diabetes mellitus type II, laparotomy, and net intraoperative fluid balance maintained significance (P < 0.05). CONCLUSIONS: We identified contributing pre- and intra-operative risk factors for PRF undergoing elective abdominal surgery. These findings may help identify those at increased risk for respiratory failure and mitigate complications.

Lower-Limb Muscle Activity During Aquatic Treadmill Running in Individuals With Anterior Cruciate Ligament Reconstruction.

INTRODUCTION: While anterior cruciate ligament (ACL) tears are commonly managed with ACL reconstruction (ACL-R), 35% of ACL-R individuals fail to return to the preinjury elite sport level. Persistent neuromuscular deficits in the hamstrings and quadriceps have been observed. It has been proposed that aquatic therapy can be used to optimize neuromuscular control after ACL-R. OBJECTIVES: (1) To compare muscle activity in ACL-R individuals during aquatic treadmill (ATM) running at different water depths and (2) to compare muscle activity during ATM running between ACL-R and healthy individuals. METHODS: A total of 38 participants, including 18 ACL-R individuals (mean postoperative time [SD] = 25.8 [25.0] mo) and 20 healthy individuals were recruited. Muscle activity of biceps femoris (BF), rectus femoris (RF), tibialis anterior, and medial gastrocnemius during land treadmill and ATM running at mid-shin, mid-thigh, and waist levels were recorded using surface electromyography (sEMG).  The sEMG signals of the selected muscles were normalized and expressed in % Maximal Voluntary Contraction (%MVC). Muscle activity of the ACL-R, ACL-contralateral, and healthy control limbs at different water depths was compared. RESULTS: Among the 3 groups, the ACL-R group demonstrated the most prominent percentage increase of 101.97% (P = .001) at mid-shin level, 139.66% (P = .001) at mid-thigh level, and 141.97% (P < .001) at waist level, respectively, in %MVC when compared to land. In the ACL-R group, muscle activity of BF in the stance phase (BFSt) was significantly higher than the control group on land at all water depths. Muscle activity of RF in the swing phase (RFSw) in the ACL-R group significantly increased in all water depths immersion when compared to land, respectively. CONCLUSION: This study showed an increasing trend in muscle activity of BFSt and RFSw in ACL-R individuals during ATM running at increased water depths. ATM running could be implemented as neuromuscular training in rehabilitation after ACL-R.

Vocal-cord Only vs. Complete Laryngeal radiation (VOCAL): a randomized multicentric Bayesian phase II trial.

BACKGROUND: Radiotherapy, along with laser surgery, is considered a standard treatment option for patients with early glottic squamous cell cancer (SCC). Historically, patients have received complete larynx radiotherapy (CL-RT) due to fear of swallowing and respiratory laryngeal motion and this remains the standard approach in many academic institutions. Local control (LC) rates with CL-RT have been excellent, however this treatment can carry significant toxicities include adverse voice and swallowing outcomes, along with increased long-term risk of cerebrovascular morbidity. A recent retrospective study reported improved voice quality and similar local control outcomes with focused vocal cord radiotherapy (VC-RT) compared to CL-RT. There is currently no prospective evidence on the safety of VC-RT. The primary objective of this Bayesian Phase II trial is to compare the LC of VC-RT to that of CL-RT in patients with T1N0 glottic SCC. METHODS: One hundred and fifty-five patients with T1a-b N0 SCC of the true vocal cords that are n ot candidate or declined laser surgery, will be randomized in a 1:3 ratio the control arm (CL-RT) and the experimental arm (VC-RT). Randomisation will be stratified by tumor stage (T1a/T1b) and by site (each site will be allowed to select one preferred radiation dose regimen, to be used in both arms). CL-RT volumes will correspond to the conventional RT volumes, with the planning target volume extending from the top of thyroid cartilage lamina superiorly to the bottom of the cricoid inferiorly. VC-RT volumes will include the involved vocal cord(s) and a margin accounting for respiration and set-up uncertainty. The primary endpoint will be LC at 2-years, while secondary endpoints will include patient-reported outcomes (voice impairment, dysphagia and symptom burden), acute and late toxicity radiation-induced toxicity, overall survival, progression free survival, as well as an optional component of acoustic and objective measures of voice analysis using the Consensus Auditory-Perceptual Evaluation of Voice. DISCUSSION: This study would constitute the first prospective evidence on the efficacy and safety of VC-RT in early glottic cancer. If positive, this study would result in the adoption of VC-RT as standard approach in early glottic cancer. TRIAL REGISTRATION: ClinicalTrials.gov Identifier: NCT03759431 Registration date: November 30, 2018.

Resilience: an essential element in head and neck cancer survivorship and quality of life.

PURPOSE: Individuals with head and neck cancer (HNCa) face myriad biopsychosocial challenges. Even after treatment completion, these challenges may cause continued disablement and diminished quality of life (QoL). Resilience may serve to minimize the disabling impact of HNCa and, in turn, maximize QoL. The purpose of this study was to formally assess resilience in HNCa survivors and explore its relationship with QoL. METHODS: A cross-sectional descriptive study was conducted. Forty HNCa survivors completed three validated, self-report questionnaires pertaining to the collection of resilience and QoL data. Descriptive and correlational analyses were performed. RESULTS: Resilience was identified in HNCa survivors and a positive correlation was found between resilience and QoL. CONCLUSIONS: Data suggest that resilience may buffer the influence of HNCa on QoL. Thus, screening for reduced levels of resilience may proactively facilitate identification of those who are most vulnerable to the psychosocial impact of HNCa. Interventions that foster resilience may ameliorate the challenges of HNCa and maximize QoL.

Treatment de-escalation for HPV-associated oropharyngeal squamous cell carcinoma with radiotherapy vs. trans-oral surgery (ORATOR2): study protocol for a randomized phase II trial.

BACKGROUND: Patients with human papillomavirus-positive (HPV+) oropharyngeal squamous cell carcinoma (OPC) have substantially better treatment response and overall survival (OS) than patients with HPV-negative disease. Treatment options for HPV+ OPC can involve either a primary radiotherapy (RT) approach (± concomitant chemotherapy) or a primary surgical approach (± adjuvant radiation) with transoral surgery (TOS). These two treatment paradigms have different spectrums of toxicity. The goals of this study are to assess the OS of two de-escalation approaches (primary radiotherapy and primary TOS) compared to historical control, and to compare survival, toxicity and quality of life (QOL) profiles between the two approaches. METHODS: This is a multicenter phase II study randomizing one hundred and forty patients with T1-2 N0-2 HPV+ OPC in a 1:1 ratio between de-escalated primary radiotherapy (60 Gy) ± concomitant chemotherapy and TOS ± de-escalated adjuvant radiotherapy (50-60 Gy based on risk factors). Patients will be stratified based on smoking status (< 10 vs. ≥ 10 pack-years). The primary endpoint is OS of each arm compared to historical control; we hypothesize that a 2-year OS of 85% or greater will be achieved. Secondary endpoints include progression free survival, QOL and toxicity. DISCUSSION: This study will provide an assessment of two de-escalation approaches to the treatment of HPV+ OPC on oncologic outcomes, QOL and toxicity. Results will inform the design of future definitive phase III trials. TRIAL REGISTRATION: Clinicaltrials.gov identifier: NCT03210103. Date of registration: July 6, 2017, Current version: 1.3 on March 15, 2019.

The circles of care game © - using gaming to teach interprofessional teamwork in clerkship.

The aim of this study was to gain insight into how online gaming can teach medical students about interprofessional collaborative practice and promote their development of interprofessional competencies prior to clerkship. This prospective cohort study involved third year medical students from the Schulich School of Medicine and Dentistry in London, Ontario, Canada who participated in the 'Circles of Care'© online board game. A total of 97 student reflections were obtained and subjected to conventional qualitative descriptive content analysis. The transcribed data were analyzed question by question and line by line. Themes evolved from four questions: (1) What surprised you the most about teamwork from this learning activity, (2) What did you learn about collaborative teamwork, (3) What will you take away from this learning event to use in your practice, and (4) Please comment on the value of using a game such as this one to develop your collaborative team practice. A total of seven themes emerged including: "Gaining insights", "What worked and what did not", "Openness to learning", "Comfort in sharing with others", "Commitment and skepticism", "Being a seeker", and "Continuum of value to learning and practice". Analysis of the student reflections illustrated the potential of using an online-based game to effectively introduce and teach interprofessional competencies to medical students.

Radiotherapy versus transoral robotic surgery and neck dissection for oropharyngeal squamous cell carcinoma (ORATOR): an open-label, phase 2, randomised trial.

BACKGROUND: Transoral robotic surgery (TORS) with concurrent neck dissection has supplanted radiotherapy in the USA as the most common treatment for oropharyngeal squamous cell carcinoma (OPSCC), yet no randomised trials have compared these modalities. We aimed to evaluate differences in quality of life (QOL) 1 year after treatment. METHODS: The ORATOR trial was an investigator-initiated, multicentre, international, open-label, parallel-group, phase 2, randomised study. Patients were enrolled at six hospitals in Canada and Australia. We randomly assigned (1:1) patients aged 18 years or older, with Eastern Cooperative Oncology Group scores of 0-2, and with T1-T2, N0-2 (≤4 cm) OPSCC tumour types to radiotherapy (70 Gy, with chemotherapy if N1-2) or TORS plus neck dissection (with or without adjuvant chemoradiotherapy, based on pathology). Following stratification by p16 status, patients were randomly assigned using a computer-generated randomisation list with permuted blocks of four. The primary endpoint was swallowing-related QOL at 1 year as established using the MD Anderson Dysphagia Inventory (MDADI) score, powered to detect a 10-point improvement (a clinically meaningful change) in the TORS plus neck dissection group. All analyses were done by intention to treat. This study is registered with ClinicalTrials.gov (NCT01590355) and is active, but not currently recruiting. FINDINGS: 68 patients were randomly assigned (34 per group) between Aug 10, 2012, and June 9, 2017. Median follow-up was 25 months (IQR 20-33) for the radiotherapy group and 29 months (23-43) for the TORS plus neck dissection group. MDADI total scores at 1 year were mean 86·9 (SD 11·4) in the radiotherapy group versus 80·1 (13·0) in the TORS plus neck dissection group (p=0·042). There were more cases of neutropenia (six [18%] of 34 patients vs none of 34), hearing loss (13 [38%] vs five [15%]), and tinnitus (12 [35%] vs two [6%]) reported in the radiotherapy group than in the TORS plus neck dissection group, and more cases of trismus in the TORS plus neck dissection group (nine [26%] vs one [3%]). The most common adverse events in the radiotherapy group were dysphagia (n=6), hearing loss (n=6), and mucositis (n=4), all grade 3, and in the TORS plus neck dissection group, dysphagia (n=9, all grade 3) and there was one death caused by bleeding after TORS. INTERPRETATION: Patients treated with radiotherapy showed superior swallowing-related QOL scores 1 year after treatment, although the difference did not represent a clinically meaningful change. Toxicity patterns differed between the groups. Patients with OPSCC should be informed about both treatment options. FUNDING: Canadian Cancer Society Research Institute Grant (#701842), Ontario Institute for Cancer Research Clinician-Scientist research grant, and the Wolfe Surgical Research Professorship in the Biology of Head and Neck Cancers grant.

A controlled trial of HNSCC patient-derived xenografts reveals broad efficacy of PI3Kα inhibition in controlling tumor growth.

Head and neck squamous cell carcinomas (HNSCCs) frequently harbor alterations in the PI3K/AKT/mTOR signaling axis, particularly in the PIK3CA gene. PI3K-targeted agents have therefore gained considerable preclinical and clinical interest as emerging therapies for HNSCC. Identification of predictive biomarkers of response would advance the clinical application of PI3K-targeted drugs for patients, in order to achieve maximal benefit. To date, studies of drug biomarkers have largely focused on screening cell lines, with much more limited in vivo testing, usually only as validation. This approach has rarely enabled accurate predictions of clinical efficacy. Recently, clinical trials of PDX models (PDX clinical trials) have been introduced as a preclinical approach to interrogate interpatient response heterogeneity. Already, PDX clinical trial responses have been demonstrated to correlate closely with patient outcomes. Here, using both an HNSCC specific, 28-cell line panel and a PDX clinical trial of 80 xenografts derived from 20 unique HNSCC tumors, we systematically examine patterns of response to PI3K inhibition in HNSCC. We find EGFR, AKT1 and CSMD1 copy number aberrations, but not PIK3CA mutations, to be associated with responsiveness to PI3K-targeted drugs. Further, we reveal PI3Kα inhibition to be almost globally tumoristatic in HNSCC xenografts regardless of PIK3CA mutational status, emphasizing its potential as a stabilizing neoadjuvant therapy for HNSCC patients.

Predictors of plate extrusion in oromandibular free flap reconstruction.

OBJECTIVES: Plate extrusions after free tissue transfer for mandibular reconstruction can be problematic and generally require revision surgery. Our objective was to assess the predictors of plate extrusion and compare outcomes between fibular free flaps (FFF), lateral border scapular flaps (LBSF), and scapular tip free flaps (STFF). METHODS: Retrospective review of consecutive patients who underwent osseous free tissue reconstruction of the mandible (2008-2014) at Victoria Hospital, London, Ontario. Patient demographics and treatment-related information were collected. RESULTS: We identified 134 procedures and 27 (20.2%) plate extrusions (21/61 FFF, 3/49 STFF, and 3/24 LBSF). Freedom from extrusion after 2 years was significantly associated with the use of FFF (P = .003, HR 6.09 1.82-20.44), performing 1 osteotomy (P = .03, HR 2.61 1.08-6.31), and anterior mandibular defects (P = .01, HR 2.66 1.25-5.66) in the univariate model. FFF's were employed more frequently in younger patients, with 2.4 mm plates, more anterior defects, and with a greater number of osteotomies (P < .001). However, after controlling for these variables in multivariate analyses the use of a FFF was the only significant predictor of extrusion at 2 years (P = .006, HR 3.68 1.46-9.28). CONCLUSIONS: At our institution, use of the STFF predicts mandibular defects that are less prone to developing plate extrusion and FFF tended to be used more frequently in anterior defects with osteotomies. However, after controlling for these factors use of the FFF appeared to have higher rates of extrusion than scapular flaps. Further prospective studies controlling for defect variables are needed to elucidate the risk factors for plate extrusion.

Interprofessional education day - an evaluation of an introductory experience for first-year students.

Interprofessional health care teams have been shown to improve patient safety and reduce medical errors, among other benefits. Introducing interprofessional concepts to students in full day events is an established model that allows students to learn together. Our group developed an academic day for first-year students devoted to an introductory interprofessional education (IPE) experience, 'IPE Day'. In total, 438 students representing medicine, dentistry, pharmacy and optometry gathered together, along with 25 facilitators, for IPE Day. Following the day's program, students completed the evaluation consisting of the Interprofessional Collaborative Competencies Attainment Survey and open-ended questions. Narrative responses were analyzed for content and coded using the Canadian Interprofessional Health Collaborative competency domains. Three hundred and eight evaluations were completed. Students reported increased self-ratings of competency across all 20 items (p < 0.05). Their comments were organized into the six domains: interprofessional communication, collaborative leadership, role clarification, patient-centred care, conflict resolution, and team functioning. Based on these findings, we suggest that this IPE activity may be useful for improving learner perceptions about their interprofessional collaborative practice competence.

Primary care specialty career choice among Canadian medical students: Understanding the factors that influence their decisions.

OBJECTIVE: To identify which factors influence medical students' decision to choose a career in family medicine and pediatrics, and which factors influence their decision to choose careers in non-front-line specialties. DESIGN: Survey that was created based on a comprehensive literature review to determine which factors are considered important when choosing practice specialty. SETTING: Ontario medical school. PARTICIPANTS: An open cohort of medical students in the graduating classes of 2008 to 2011 (inclusive). MAIN OUTCOME MEASURES: The main factors that influenced participants' decision to choose a career in primary care or pediatrics, and the main factors that influenced participants' decision to choose a career in a non-front-line specialty. RESULTS: A total of 323 participants were included in this study. Factors that significantly influenced participants' career choice in family medicine or pediatrics involved work-life balance (acceptable hours of practice [P = .005], acceptable on-call demands [P = .012], and lifestyle flexibility [P = .006]); a robust physician-patient relationship (ability to promote individual health promotion [P = .014] and the opportunity to form long-term relationships [P < .001], provide comprehensive care [P = .001], and treat patients and their families [P = .006]); and duration of residency program (P = .001). The career-related factors that significantly influenced participants' decision to choose a non-front-line specialty were as follows: becoming an expert (P < .001), maintaining a focused scope of practice (P < .001), having a procedure-focused practice (P = .001), seeing immediate results from one's actions (P < .001), potentially earning a high income (P < .001), and having a perceived status among colleagues (P < .001). CONCLUSION: In this study, 8 factors were found to positively influence medical students' career choice in family medicine and pediatrics, and 6 factors influenced the decision to choose a career in a non-front-line specialty. Medical students can be encouraged to explore a career in family medicine or pediatrics by addressing misinformation, by encouraging realistic expectations of career outcomes in the various specialties, and by demonstrating the capacity of primary care fields to incorporate specific motivating factors.

Current state of interprofessional education in Canadian medical schools: Findings from a national survey.

Interprofessional education (IPE) is being increasingly recognised and prioritised in undergraduate medical education. While efforts are underway to integrate IPE into health professional curricula across Canada, the state of IPE in Canadian medical schools remains unclear. This study aims to assess the current practice of IPE in Canadian undergraduate medical curricula. An online survey was distributed to IPE directors (or designees) of all Canadian medical schools. The survey gathered details of the IPE experiences offered, curriculum structure, and perceived barriers to the programmes. The survey was completed by 12 of 17 Canadian medical schools and revealed that IPE is generally well represented in Canadian undergraduate medical education curricula. Reported barriers to IPE efforts included scheduling and funding limitations. By comparison, student interest was one of the least commonly cited issues. It would appear that students and faculty are interested in advancing the state of IPE in undergraduate medical education. The results of this study are crucial as IPE continues to evolve as a component of undergraduate medical curricula across the globe.

Isolated Horner Syndrome From an Elongated Styloid Process (Eagle Syndrome).

Eagle syndrome occurs when an elongated styloid process causes otolaryngological or neurological symptoms or signs. We report a patient who had an isolated asymptomatic Horner syndrome that resulted from a pinned internal carotid artery being dynamically injured by an elongated styloid process during chiropractic neck manipulation. There was no evidence of arterial dissection.

Vaccinia virus outperforms a panel of other poxviruses as a potent oncolytic agent for the control of head and neck squamous cell carcinoma cell lines.

BACKGROUND: Head and neck squamous cell carcinoma (HNSCC) is the fifth most common cancer worldwide. Existing therapies for advanced tumors have high failure rates and can have severe consequences in terms of pain, disfigurement, and poor speech and swallowing function. New treatment strategies are needed to improve outcomes for patients suffering with this disease and oncolytic viruses represent a promising approach. METHODS: We infected six well-characterized HNSCC cell lines (Cal27, Detroit562, FaDu, SCC4, SCC15, SCC25), with increasing doses of a panel of poxviruses (including myxoma, vaccinia, raccoonpox and tanapox viruses) modified to express green fluorescence protein to determine which virus was the most effective oncolytic agent in cell-based assays. RESULTS: While myxoma, raccoonpox and tanapox displayed differing efficacy in the panel of cell lines, vaccinia virus was the most potent of the tested poxviruses and was highly effective in controlling cell growth in all cell lines. CONCLUSION: Oncolytic poxviruses, particularly vaccinia virus, were effective in killing HNSCC in vitro and hold promise as potential treatments for patients with HNSCC.

Evaluating the impact of an integrated multidisciplinary head & neck competency-based anatomy & radiology teaching approach in radiation oncology: a prospective cohort study.

BACKGROUND: Modern radiation oncology demands a thorough understanding of gross and cross-sectional anatomy for diagnostic and therapeutic applications. Complex anatomic sites present challenges for learners and are not well-addressed in traditional postgraduate curricula. A multidisciplinary team (MDT) based head-and-neck gross and radiologic anatomy program for radiation oncology trainees was developed, piloted, and empirically assessed for efficacy and learning outcomes. METHODS: Four site-specific MDT head-and-neck seminars were implemented, each involving a MDT delivering didactic and case-based instruction, supplemented by cadaveric presentations. There was no dedicated contouring instruction. Pre- and post-testing were performed to assess knowledge, and ability to apply knowledge to the clinical setting as defined by accuracy of contouring. Paired analyses of knowledge pretests and posttests were performed by Wilcoxon matched-pair signed-rank test. RESULTS: Fifteen post-graduate trainees participated. A statistically significant (p < 0.001) mean absolute improvement of 4.6 points (17.03%) was observed between knowledge pretest and posttest scores. Contouring accuracy was analyzed quantitatively by comparing spatial overlap of participants' pretest and posttest contours with a gold standard through the dice similarity coefficient. A statistically significant improvement in contouring accuracy was observed for 3 out of 20 anatomical structures. Qualitative and quantitative feedback revealed that participants were more confident at contouring and were enthusiastic towards the seminars. CONCLUSIONS: MDT seminars were associated with improved knowledge scores and resident satisfaction; however, increased gross and cross-sectional anatomic knowledge did not translate into improvements in contouring accuracy. Further research should evaluate the impact of hands-on contouring sessions in addition to dedicated instructional sessions to develop competencies.

DinoKnot: Duplex Interaction of Nucleic Acids With PseudoKnots.

Interaction of nucleic acid molecules is essential for their functional roles in the cell and their applications in biotechnology. While simple duplex interactions have been studied before, the problem of efficiently predicting the minimum free energy structure of more complex interactions with possibly pseudoknotted structures remains a challenge. In this work, we introduce a novel and efficient algorithm for prediction of Duplex Interaction of Nucleic acids with pseudoKnots, DinoKnot follows the hierarchical folding hypothesis to predict the secondary structure of two interacting nucleic acid strands (both homo- and hetero-dimers). DinoKnot utilizes the structure of molecules before interaction as a guide to find their duplex structure allowing for possible base pair competitions. To showcase DinoKnots's capabilities we evaluated its predicted structures against (1) experimental results for SARS-CoV-2 genome and nine primer-probe sets, (2) a clinically verified example of a mutation affecting detection, and (3) a known nucleic acid interaction involving a pseudoknot. In addition, we compared our results against our closest competition, RNAcofold, further highlighting DinoKnot's strengths. We believe DinoKnot can be utilized for various applications including screening new variants for potential detection issues and supporting existing applications involving DNA/RNA interactions, adding structural considerations to the interaction to elicit functional information.