Can ChatGPT help patients answer their otolaryngology questions?

Background: Over the past year, the world has been captivated by the potential of artificial intelligence (AI). The appetite for AI in science, specifically healthcare is huge. It is imperative to understand the credibility of large language models in assisting the public in medical queries. Objective: To evaluate the ability of ChatGPT to provide reasonably accurate answers to public queries within the domain of Otolaryngology. Methods: Two board-certified otolaryngologists (HZ, RS) inputted 30 text-based patient queries into the ChatGPT-3.5 model. ChatGPT responses were rated by physicians on a scale (accurate, partially accurate, incorrect), while a similar 3-point scale involving confidence was given to layperson reviewers. Demographic data involving gender and education level was recorded for the public reviewers. Inter-rater agreement percentage was based on binomial distribution for calculating the 95% confidence intervals and performing significance tests. Statistical significance was defined as p < .05 for two-sided tests. Results: In testing patient queries, both Otolaryngology physicians found that ChatGPT answered 98.3% of questions correctly, but only 79.8% (range 51.7%-100%) of patients were confident that the AI model was accurate in its responses (corrected agreement = 0.682; p < .001). Among the layperson responses, the corrected coefficient was of moderate agreement (0.571; p < .001). No correlation was noted among age, gender, or education level for the layperson responses. Conclusion: ChatGPT is highly accurate in responding to questions posed by the public with regards to Otolaryngology from a physician standpoint. Public reviewers were not fully confident in believing the AI model, with subjective concerns related to less trust in AI answers compared to physician explanation. Larger evaluations with a representative public sample and broader medical questions should immediately be conducted by appropriate organizations, governing bodies, and/or governmental agencies to instill public confidence in AI and ChatGPT as a medical resource. Level of Evidence: 4.

Members of the high mobility group B protein family are dynamically expressed in embryonic neural stem cells.

Neural Stem Cells (NSCs) are a distinct group of cells present in the embryonic and adult mammalian central nervous system (CNS) that are able to differentiate into neurons, astrocytes and oligodendrocytes. As NSC proliferation declines with age, factors that regulate this process need to be defined. To search for NSC regulatory factors, we performed a quantitative shotgun proteomics study that revealed that members of the High Mobility Group B (HMGB) family are highly expressed in NSCs. Using a neurosphere assay, we report the differential expression of HMGB 1, 2, 3, and 4 mRNAs in proliferating NSCs isolated from various time points during embryonic development, as well as the dynamic expression of HMGB1 and B2 mRNAs and proteins in differentiating embryonic NSCs. Expression of HMGB2 underwent the most dramatic changes during the developmental ages examined; as a result, we assessed its role in NSC proliferation and differentiation. We report the predominance of small diameter HMGB2-/- neurospheres in comparison to wild-type, which correlated with increased proliferation in these smaller HMGB2-/- neurospheres. Our data suggest that HMGB2 plays a regulatory role in NSC cell proliferation and maintenance pathways.

Neurogenic to Gliogenic Fate Transition Perturbed by Loss of HMGB2.

Mouse cortical development relies heavily on a delicate balance between neurogenesis and gliogenesis. The lateral ventricular zone produces different classes of excitatory pyramidal cells until just before birth, when the production of astroglia begins to prevail. Epigenetic control of this fate shift is of critical importance and chromatin regulatory elements driving neuronal or astroglial development play an vital role. Different classes of chromatin binding proteins orchestrate the transcriptional repression of neuronal-specific genes, while allowing for the activation of astrocyte-specific genes. Through proteomic analysis of embryonic neural progenitor cells (NPCs) our group had previously identified high mobility group B2 (HMGB2), a chromatin protein dynamically expressed throughout embryonic development. In the current study using cultures of perinatal NPCs from HMGB2+/+ and HMGB2-/- mice we discovered that vital elements of the polycomb group (PcG) epigenetic complexes polycomb repressive complexes 1 and 2 (PRC1/2) were downregulated during the differentiation process of HMGB2-null NPCs. These epigenetic changes led to downstream changes in specific histone modification levels, specifically the trimethylation of H3K27, and a subsequent shift in the perinatal neurogenesis to gliogenesis fate transition. Collectively these results demonstrate that chromatin binding proteins, such as HMGB2, can have significant effects on the epigenetic landscape of perinatal neural stem/progenitor cells.

The Role of Necroptosis in Burn Injury Progression in a Rat Comb Burn Model.

OBJECTIVES: Progression of cell death after burn injury may occur by one of three mechanisms: passive necrosis, apoptosis, and programmed necroptosis that requires the receptor-interacting protein kinase-3 (RIP-3). The hypothesis was that RIP-3 is present in normal and burned skin; that necroptosis plays a role in burn injury progression; and that treatment with necrostatin-1, an inhibitor of necroptosis, would reduce burn progression. METHODS: Skin specimens from rats were examined for the presence of RIP-3. Using a 150-g brass comb preheated to 100°C, we created two comb burns (one on each side) consisting of four rectangular burns, separated by three unburned interspaces, on both sides of the backs of anesthetized male Sprague-Dawley rats (240 to 300 g). The interspaces represent the ischemic zones surrounding the central necrotic core. Left untreated, these areas undergo necrosis. In the first experiment, 10 rats each were randomized to 1.65 mg/kg necrostatin-1 or control given by intraperitoneal injection 1 hour after injury. In the second experiment, 10 rats each were randomized to two intravenous injections of 1.65 mg/kg necrostatin-1 or its vehicle at 1 and 4 hours after injury. The primary outcome was the percentage of interspaces undergoing necrosis within 7 days of injury. Binary data were compared with chi-square or Fishers' exact tests. RESULTS: All normal and burned skin specimens from rats stained positive for RIP-3. In the first experiment, nearly all unburned interspaces in both the experimental and the control rats underwent necrosis (47 of 48, 97.9% vs. 48 of 48, 100%; p = not significant [NS]). Similarly, in the second experiment, there was no difference in the percentage of unburned interspaces undergoing necrosis within 7 days of injury in rats treated with two doses of necrostatin-1 or the control vehicle (46 of 48, 95.8% vs. 48 of 48, 100%; p = NS). There were no wound infections noted in rats injected with necrostatin-1. CONCLUSIONS: The skin of rats contains RIP-3 necessary for necroptosis. Injection of rats with either a single intraperitoneal dose or two intravenous doses of necrostatin-1 failed to reduce burn injury progression in a rat comb burn model. This may be due to inactivity of necrostatin-1 or the lack of a role of necroptosis in burn injury progression in the rat comb burn model.

Aberrant neural stem cell proliferation and increased adult neurogenesis in mice lacking chromatin protein HMGB2.

Neural stem and progenitor cells (NSCs/NPCs) are distinct groups of cells found in the mammalian central nervous system (CNS). Previously we determined that members of the High Mobility Group (HMG) B family of chromatin structural proteins modulate NSC proliferation and self-renewal. Among them HMGB2 was found to be dynamically expressed in proliferating and differentiating NSCs, suggesting that it may regulate NSC maintenance. We report now that Hmgb2(-/-) mice exhibit SVZ hyperproliferation, increased numbers of SVZ NSCs, and a trend towards aberrant increases in newly born neurons in the olfactory bulb (OB) granule cell layer. Increases in the levels of the transcription factor p21 and the Neural cell adhesion molecule (NCAM), along with down-regulation of the transcription/pluripotency factor Oct4 in the Hmgb2-/- SVZ point to a possible pathway for this increased proliferation/differentiation. Our findings suggest that HMGB2 functions as a modulator of neurogenesis in young adult mice through regulation of NSC proliferation, and identify a potential target via which CNS repair could be amplified following trauma or disease-based neuronal degeneration.