Artificial intelligence in virtual standardized patients: Combining natural language understanding and rule based dialogue management to improve conversational fidelity.

INTRODUCTION: Advances in natural language understanding have facilitated the development of Virtual Standardized Patients (VSPs) that may soon rival human patients in conversational ability. We describe herein the development of an artificial intelligence (AI) system for VSPs enabling students to practice their history taking skills. METHODS: Our system consists of (1) Automated Speech Recognition (ASR), (2) hybrid AI for question identification, (3) classifier to choose between the two systems, and (4) automated speech generation. We analyzed the accuracy of the ASR, the two AI systems, the classifier, and student feedback with 620 first year medical students from 2018 to 2021. RESULTS: System accuracy improved from ∼75% in 2018 to ∼90% in 2021 as refinements in algorithms and additional training data were utilized. Student feedback was positive, and most students felt that practicing with the VSPs was a worthwhile experience. CONCLUSION: We have developed a novel hybrid dialogue system that enables artificially intelligent VSPs to correctly answer student questions at levels comparable with human SPs. This system allows trainees to practice and refine their history-taking skills before interacting with human patients.

Using virtual standardized patients to accurately assess information gathering skills in medical students.

Introduction: Practicing a medical history using standardized patients is an essential component of medical school curricula. Recent advances in technology now allow for newer approaches for practicing and assessing communication skills. We describe herein a virtual standardized patient (VSP) system that allows students to practice their history taking skills and receive immediate feedback. Methods: Our VSPs consist of artificially intelligent, emotionally responsive 3D characters which communicate with students using natural language. The system categorizes the input questions according to specific domains and summarizes the encounter. Automated assessment by the computer was compared to manual assessment by trained raters to assess accuracy of the grading system. Results: Twenty dialogs chosen randomly from 102 total encounters were analyzed by three human and one computer rater. Overall scores calculated by the computer were not different than those provided by the human raters, and overall accuracy of the computer system was 87%, compared with 90% for human raters. Inter-rater reliability was high across 19 of 21 categories. Conclusions: We have developed a virtual standardized patient system that can understand, respond, categorize, and assess student performance in gathering information during a typical medical history, thus enabling students to practice their history-taking skills and receive immediate feedback.

Effect of gonadotropin-releasing hormone antagonist on primordial follicle survival in the primate ovary.

OBJECTIVE: To examine the effects of gonadotropin-releasing hormone (GnRH) antagonist on primordial follicle reserve in the primate ovary. STUDY DESIGN: A prospective basic research study in which 10 juvenile cynomolgus monkeys (Macaca fascicularis) had 1 ovary surgically removed. Six animals were then treated with the GnRH antagonist antide (1.0 mg/kg/day) for 14 days, and 4 animals were treated with vehicle. After treatment the contralateral ovary was removed and both ovaries were prepared for assessment of primordial, primary, and secondary follicle numbers. RESULTS: Antide treatment resulted in a modest (13%) but significant decrease in primordial follicle number in juvenile macaques (p = 0.048, n = 6). Three animals demonstrated a marked reduction in primordial follicles (19%, 25%, 36%) and 3 animals had no (< 5%) change in primordial follicles after antide treatment. Control animals demonstrated no change in primordial follicle number following vehicle treatment. Antide had no effect on primary, secondary, or early antral follicle numbers and did not affect circulating estradiol concentrations. CONCLUSION: In contrast to mice, in which GnRH antagonist treatment markedly reduces primordial follicle reserve, the effect of antide in nonhuman primates was less dramatic and somewhat variable. These data suggest there may be a subset of animals susceptible to the adverse effects of GnRH antagonist on primordial follicle survival.

Using Virtual Reality Simulation Environments to Assess Competence for Emergency Medicine Learners.

Immersive learning environments that use virtual simulation (VS) technology are increasingly relevant as medical learners train in an environment of restricted clinical training hours and a heightened focus on patient safety. We conducted a consensus process with a breakout group of the 2017 Academic Emergency Medicine Consensus Conference "Catalyzing System Change Through Health Care Simulation: Systems, Competency, and Outcomes." This group examined the current uses of VS in training and assessment, including limitations and challenges in implementing VS into medical education curricula. We discuss the role of virtual environments in formative and summative assessment. Finally, we offer recommended areas of focus for future research examining VS technology for assessment, including high-stakes assessment in medical education. Specifically, we discuss needs for determination of areas of focus for VS training and assessment, development and exploration of virtual platforms, automated feedback within such platforms, and evaluation of effectiveness and validity of VS education.

Neutralization of endogenous vascular endothelial growth factor depletes primordial follicles in the mouse ovary.

The regulation of early follicular growth and development involves a complex interaction of autocrine, paracrine, and endocrine signals. The ability of these factors to regulate follicle growth may depend in part on the extent of vascular delivery to and perfusion of the ovary. Vascular endothelial growth factor A (VEGFA) is a major regulator of vascular physiology in the ovary. VEGFA is produced in numerous ovarian compartments and likely plays a role in the regulation of all phases of follicular growth, from preantral through preovulatory. The aim of the present study was to further evaluate the role of VEGF in early follicle growth by neutralization of endogenous VEGF or VEGF receptors. Adult mice were injected systemically and prepubertal mice were injected directly under the ovarian bursa with antibodies designed to neutralize VEGF or block interaction with its receptors in the ovary. Both systemic and intrabursal injections of VEGF antibody significantly reduced the number of primordial follicles within 1-3 days after administration without affecting primary or secondary follicle numbers. Primordial follicle numbers were not different from control levels by 30 days after VEGFA antibody administration. Administration of antibodies to the kinase domain receptor (KDR), but not the FMS-like tyrosine receptor (FLT1), for VEGF also resulted in a significant decrease in primordial follicles. These data suggest that VEGF plays a vital role in the maintenance and growth of the primordial follicle pool.

Inhibition of alkaline phosphatase activity of boar semen by pentoxifylline, caffeine, and theophylline.

Methyl xanthines have been used frequently as additives to sperm suspensions in order to improve sperm characteristics. The mechanism of action on spermatozoa is generally assumed to be inhibition of sperm phosphodiesterase activity, resulting in elevation of complementary adenosine monophosphate levels in spermatozoa. The present study was designed to examine the effect of methyl xanthines (pentoxifylline, caffeine, and theophylline) on another important enzyme system, alkaline phosphatase, in boar seminal plasma and spermatozoa. Inhibition of sperm alkaline phosphatase could be distinguished from that of seminal plasma by a paradoxical stimulation by pentoxifylline at lower pH values in spermatozoa. Among the three methyl xanthines, theophylline exhibited the most dramatic inhibition of alkaline phosphatase activity and substrate inhibition was observed with increasing concentrations. Each methyl xanthine had a different action on alkaline phosphatase activity at lower pH; theophylline showed the highest inhibition, caffeine inhibition was not related to pH, and pentoxifylline did not inhibit alkaline phosphatase of seminal plasma and, in fact, it stimulated its activity (or that of a phosphatase with lower pH optimum) in spermatozoa. These results indicate another possible mechanism of action of methyl xanthines on sperm and are in agreement with data indicating that methyl xanthines are not specific inhibitors of sperm phosphodiesterase, because clearly, they inhibit alkaline phosphatase activity as well.

Using second life virtual simulation environment for mock oral emergency medicine examination.

OBJECTIVES: Oral examination is a method used to evaluate emergency medicine (EM) residents and is a requirement for board certification of emergency physicians. Second Life (SL) is a virtual three-dimensional (3-D) immersive learning environment that has been used for medical education. In this study we explore the use of SL virtual simulation technology to administer mock oral examinations to EM residents. METHODS: This was a prospective observational study of EM residents who had previously completed mock oral examinations, participating in a similar mock oral examination case scenario conducted via SL. EM residents in this training program completed mock oral examinations in a traditional format, conducted face to face with a faculty examiner. All current residents were invited to participate in a similar case scenario conducted via SL for this study. The examinee managed the case while acting as the physician avatar and communicated via headset and microphone from a remote computer with a faculty examiner who acted as the patient avatar. Participants were surveyed regarding their experience with the traditional and virtual formats using a Likert scale. RESULTS: Twenty-seven EM residents participated in the virtual oral examination. None of the examinees had used SL previously. SL proved easy for examinees to log into (92.6%) and navigate (96.3%). All felt comfortable communicating with the examiner via remote computer. Most examinees thought the SL encounter was realistic (92.6%), and many found it more realistic than the traditional format (70.3%). All examinees felt that the virtual examination was fair, objective, and conducted efficiently. A majority preferred to take oral examinations via SL over the traditional format and expressed interest in using SL for other educational experiences (66.6 and 92.6%, respectively). CONCLUSIONS: Application of SL virtual simulation technology is a potential alternative to traditional mock oral examinations for EM residents.

Acute depletion of murine primordial follicle reserve by gonadotropin-releasing hormone antagonists.

OBJECTIVE: To examine the effects of GnRH antagonists on preantral follicle survival in vivo and to investigate whether GnRH antagonist use during cyclophosphamide treatment would protect the ovary and preserve primordial follicle survival in a murine model. DESIGN: Prospective basic research study. SETTING: Research laboratory in an academic medical center. ANIMAL(S): Adult C57Bl/6 mice (5 to 6 weeks old). INTERVENTION(S): Mice received either a single injection of GnRH agonist (leuprolide acetate) on study day -10 or injections of the GnRH antagonist (antide or cetrorelix) on study days -3 and 0. Some animals also received the chemotherapeutic agent cyclophosphamide on day 0. All animals were killed by CO2 asphyxiation on day 7. To examine direct vs. indirect effects, some mice received GnRH antagonist under the bursa of one ovary, with the contralateral ovary receiving vehicle. Ovaries were fixed in Kahle's solution; 7-mum tissue sections were stained with Lillie's allochrome, and preantral follicles were counted on every fifth section. MAIN OUTCOME MEASURE(S): Numbers of primordial, primary, and secondary follicles. RESULT(S): Systemic administration of both GnRH antagonists caused a significant destruction of primordial follicles compared with control mice. Similar results were obtained whether the antagonists were administered systemically or directly to the ovary. Gonadotropin-releasing hormone agonist had no effect on primordial follicle numbers by itself but reduced the follicular depletion caused by cyclophosphamide. CONCLUSION(S): In contrast to the effects of GnRH agonists to reduce chemotherapeutic destruction of primordial follicles, GnRH antagonists do not protect the ovary from the damaging effects of cyclophosphamide. More importantly, GnRH antagonists alone deplete primordial follicles in this murine model, likely through a direct effect on the ovary. Whether these observations apply to other species requires further study.

Vascular endothelial growth factor stimulates preantral follicle growth in the rat ovary.

The regulation of preantral follicle growth in mammals is poorly understood. The availability of an adequate vascular supply to provide endocrine and paracrine signals may be important during the early states of follicle growth as well as the later states of follicle selection and dominance. The objective of the present study was to investigate whether vascular endothelial growth factor (VEGF) plays a role in preantral follicular development in the rat ovary. Immature (age, 21 days) Sprague-Dawley rats were injected with 500 ng of VEGF in saline or 50 microg of diethylstilbestrol (DES) in oil under the bursa of one ovary. The contralateral ovary was injected with a corresponding volume of vehicle. Rats were killed 48 h later, and the ovaries were removed and analyzed histologically. Intrabursal administration of VEGF significantly increased the number of primary and small secondary, but not of large secondary, preantral follicles in the ovary, similar to the effect of DES (P < 0.05). The VEGF stimulated preantral follicle growth in a time- and dose-dependent manner. Subcutaneous DES administration increased the number of primary and secondary follicles, and both s.c. and intrabursal estrogen administration stimulated VEGF protein expression in the rat ovary. These data indicate that VEGF stimulates preantral follicular development in the rat ovary, is regulated by estrogen, and may be one of the factors that participate in the regulation of early follicle growth in the rat.