Identification, structural, and biophysical characterization of a positive modulator of human Kv3.1 channels.

Voltage-gated potassium channels (Kv) are tetrameric membrane proteins that provide a highly selective pathway for potassium ions (K+) to diffuse across a hydrophobic cell membrane. These unique voltage-gated cation channels detect changes in membrane potential and, upon activation, help to return the depolarized cell to a resting state during the repolarization stage of each action potential. The Kv3 family of potassium channels is characterized by a high activation potential and rapid kinetics, which play a crucial role for the fast-spiking neuronal phenotype. Mutations in the Kv3.1 channel have been shown to have implications in various neurological diseases like epilepsy and Alzheimer's disease. Moreover, disruptions in neuronal circuitry involving Kv3.1 have been correlated with negative symptoms of schizophrenia. Here, we report the discovery of a novel positive modulator of Kv3.1, investigate its biophysical properties, and determine the cryo-EM structure of the compound in complex with Kv3.1. Structural analysis reveals the molecular determinants of positive modulation in Kv3.1 channels by this class of compounds and provides additional opportunities for rational drug design for the treatment of associated neurological disorders.

Gastroesophageal reflux disease and head and neck cancers: A systematic review and meta-analysis.

PURPOSE: Gastroesophageal reflux disease (GERD) has been associated with head and neck cancer (HNC), including laryngeal and pharyngeal anatomical sites. A systematic review and meta-analysis was performed to examine these associations. METHODS: Articles were retrieved from the Medline, Web of Science, Scopus, and Embase databases using keywords "gastroesophageal reflux disease", "laryngopharyngeal reflux", "head and neck cancer", and associated variants. Inclusion criteria were English language publications, human subjects, and controlled studies with described development of head and neck cancer among individuals with GERD. 13 studies with a total of 39,824 patients were included. RESULTS: Overall, presence of GERD was associated with an increased risk of developing HNC (OR = 1.86, 95% Confidence Interval [CI] = 1.27-2.74). This association remained significant with laryngeal cancers (OR = 1.95, 95% CI = 1.33-2.86), but not pharyngeal cancers (OR = 1.56, 95% CI = 0.86-2.83). Subgroup analyses of hypopharyngeal (OR = 2.26, 95% CI = 0.67-7.68) and oropharyngeal subsites (OR = 1.39, 95% CI = 0.51-3.84) were not statistically significant. Meta-analysis of studies that objectively assessed reflux, such as pH monitor placement, showed statistical significance (OR = 2.81, 95% CI = 1.36-5.81), while studies that used subjective reporting or chart review of GERD were not significant (OR = 1.46, 95% CI = 0.89-2.40). Association between H. pylori infection and head and neck cancers was not statistically significant (OR = 2.66, 95% CI = 0.59-11.97). CONCLUSION: A diagnosis of GERD is associated with a later diagnosis of HNC, but this association is not significant for pharyngeal cancers. Associations of GERD with HNC may be specific to laryngeal cancers. LEVEL OF EVIDENCE: Systematic review and meta-analysis of case control studies (3a).

Nonpharmacological Relaxation Technology for Office-Based Rhinologic Procedures.

BACKGROUND: Office-based rhinologic procedures are increasingly performed to control costs and enhance patient convenience. Adequate management of pain and anxiety is essential for the technical performance of these procedures, in addition to ensuring patient comfort. Pharmacologic agents are often used to manage anxiety and pain. Nonpharmacological adjuncts may be useful for achieving these effects without oral opioids and benzodiazepines. METHODS: Charts of patients who underwent office-based rhinologic procedures with the NuCalm system (Solace Lifesciences, Inc., Wilmonton, DE, USA) in combination with local anesthesia were reviewed. NuCalm is a proprietary system that combines cranial electrotherapy stimulation, neuroacoustic software, light-blocking lenses, and topical γ--aminobutyric acid. Patients rated their pain and anxiety before, during, and after the procedure. RESULTS: Twenty-five patients underwent office procedures using the NuCalm system. Preoperative anxiety (2.00) was significantly higher than postoperative anxiety (1.25) according to patient reporting on a 5-point scale (p = 0.005). Preoperative pain (1.83) was not significantly different from intraoperative (2.54) and postoperative pain (2.04, p = 0.054). CONCLUSIONS: A variety of office-based rhinologic procedures are technically feasible and can be performed with adequate patient comfort without the use of oral drugs. Adjuncts to pharmacologic agents may enhance pain control and anxiety management and improve patient tolerance of these procedures.

Anesthetic Implications of Ebola Patient Management: A Review of the Literature and Policies.

As of mid-October 2014, the ongoing Ebola epidemic in Western Africa has affected approximately 10,000 patients, approached a 50% mortality rate, and crossed political and geographic borders without precedent. The disease has spread throughout Liberia, Guinea, and Sierra Leone. Isolated cases have arrived in urban centers in Europe and North America. The exponential growth, currently unabated, highlights the urgent need for effective and immediate management protocols for the various health care subspecialties that may care for Ebola virus disease patients. We conducted a comprehensive review of the literature to identify key areas of anesthetic care affected by this disease. The serious potential for "high-risk exposure" and "direct contact" (as defined by the Centers for Disease Control and Prevention) of anesthesiologists caring for Ebola patients prompted this urgent investigation. A search was conducted using MEDLINE/PubMed, MeSH, Cochrane Review, and Google Scholar. Key words included "anesthesia" and/or "ebola" combined with "surgery," "intubation," "laryngoscopy," "bronchoscopy," "stethoscope," "ventilation," "ventilator," "phlebotomy," "venous cannulation," "operating room," "personal protection," "equipment," "aerosol," "respiratory failure," or "needle stick." No language or date limits were applied. We also included secondary-source data from government organizations and scientific societies such as the Centers for Disease Control and Prevention, World Health Organization, American Society of Anesthesiologists, and American College of Surgeons. Articles were reviewed for primary-source data related to inpatient management of Ebola cases as well as evidence-based management guidelines and protocols for the care of Ebola patients in the operative room, infection control, and health care worker personal protection. Two hundred thirty-six articles were identified using the aforementioned terminology in the scientific database search engines. Twenty articles met search criteria for information related to inpatient Ebola virus disease management or animal virology studies as primary or secondary sources. In addition, 9 articles met search criteria as tertiary sources, representing published guidelines. The recommendations developed in this article are based on these 29 source documents. Anesthesia-specific literature regarding the care of Ebola patients is very limited. Secondary-source guidelines and policies represent the majority of available information. Data from controlled animal experiments and tuberculosis patient research provide some evidence for the existing recommendations and identify future guideline considerations.

Validated Symptom Outcomes Following Septal Perforation Repair: Application of the NOSE-Perf Scale.

OBJECTIVE: The Nasal Obstruction Symptom Evaluation (NOSE)-Perf scale was developed and validated to measure symptoms associated with nasal septal perforations. This study reports the application of the NOSE-Perf scale to evaluate symptom change following septal perforation repair. METHODS: Patients with NOSE-Perf evaluations ≥6 months following attempted perforation closure from July 2018 to December 2021 utilizing bilateral nasal mucosal flaps with an interposition graft were eligible for study inclusion. Change in NOSE-Perf scores were noted. Patient demographics, perforation size, and concurrent functional procedures were analyzed for impact on symptom outcomes. RESULTS: One-hundred and seventeen patients met the study criteria. Seventy-nine (67.5%) of the patients were female and the mean (range) age at surgery was 47.3 (14-78) years. Repair failure was noted in 7 (6.0%) patients. Mean (SD) preoperative NOSE-Perf score was 25.3 (95% CI, 23.5-27.1) and postoperative score was 7.9 (95% CI, 6.5-9.3). Minimal clinically important difference (MCID) was estimated and greater than 91% of patients had improvement above this threshold. Patient age, perforation size, or concurrent functional procedures did not impact outcomes. Postoperative scores at short (2-4 months), intermediate (5-8 months), and long-term (≥9 months) time periods showed significant improvement (all p < 0.001) compared to preoperative NOSE-Perf scores. CONCLUSION: Significant reduction in nasal symptoms as measured by the NOSE-Perf scale is noted following bilateral mucosal flap repair. Although the nose does not completely normalize following repair, clinically important improvement was noted in at least 91% of patients. The NOSE-Perf scale is positioned to play a role in the standardization of septal perforation evaluation and outcomes assessment. LEVEL OF EVIDENCE: 4 Laryngoscope, 134:3067-3072, 2024.

Combined endoscopic sinus surgery and endonasal septal perforation repair: Symptom outcomes and perforation closure rates.

KEY POINTS: Combined endoscopic sinus surgery and nasal septal perforation repair is technically feasible. NOSE-Perf is a recently developed patient-reported outcome measure for nasal septal perforation. The decision to perform combined ESS and NSP repair should be made on a case-by-case basis.

Autologous Interposition Grafts for Mucosal Flap Septal Perforation Repair.

Background: Nasal septal perforation repair is commonly attempted utilizing bilateral nasal mucosal flaps supported with an interposition graft. Objectives: To compare the failure rates for bilateral flap repairs utilizing four different autologous interposition grafts. Methods: This is a retrospective review of a single surgeon's bilateral flap perforation repairs supported with an autologous interposition graft. Study inclusion over the 18-year review period required at least one examination 1 month after surgery. Repair failure rates were calculated and compared for each graft type, and logistic regression was performed for multivariate analysis. Results: For the 356 study patients, median (range) age was 51 years (14-81) and 63.0% were women. Mean (range) perforation length was 13.9 mm (1-45). Median (range) at last follow-up was 11.2 months (1-192). Graft types used (percentage of patients and failure rate) were temporalis fascia (58.7/4.4), septal cartilage (23.3/7.3), auricular perichondrium (13.8/4.1), and septal bone (4.2/6.7) (p > 0.05). Conclusion: There was no significant difference in bilateral mucosal flap perforation repair failure rate when either a temporalis fascia, septal cartilage, auricular perichondrium, or septal bone interposition graft was used.

Assessment of a Novel Tool for the Clinical Grading of Nasal Septal Perforation.

BACKGROUND: Nasal septal perforations (NSP) can have a heterogeneous appearance on endoscopic examination with varying degrees of crusting, inflammatory change, and associated septal deviation. The clinical applicability of these findings as contributors to patient symptoms may be enhanced by use of a standardized assessment. METHODS: Video nasal endoscopy recordings were obtained from 40 patients with NSP. Five raters with varied levels of training ranging from a senior resident to an experienced septal perforation surgeon independently reviewed the videos for the following exam findings: crusting, scarring, granulation tissue, septal deviation, and edema. Scoring for each item was reported on a 3-point (0-2) scale, and each reviewer repeated scoring at a 14-day interval. Interrater and intrarater agreement were calculated using Fleiss kappa for each item and the total scores. Additionally, endoscopy scores were correlated with patient-reported NOSE-Perf symptom scores. RESULTS: Interrater agreement for the overall instrument was in the "fair-to-moderate" range with the following interrater agreement for each item: crusting (0.458-0.575), scarring (0.286-0.308), granulation (0.403-0.406), deviation (0.487-0.494), and edema (0.253-0.406). Intrarater agreement was generally "substantial" for individual items as well as the overall instrument (0.688). The NSP endoscopy scores were moderately correlated with NOSE-Perf scores (r = 0.44, p = 0.008). CONCLUSIONS: An endoscopic evaluation of NSP comprising five exam findings has acceptable interrater and intrarater reliability and correlates with patient-reported outcomes. NSP endoscopy may be applied to future clinical studies for characterization of NSP and assessment of treatment outcomes. LEVEL OF EVIDENCE: 3 Laryngoscope, 134:3049-3053, 2024.

Nasal Septal Perforation Dimensional Analysis.

OBJECTIVE: To describe and illustrate septal perforation shape through the documentation and analysis of length and height measurements. A secondary objective is to correlate perforation size to surgical and nonsurgical etiologies. STUY DESIGN: Retrospective case series. SETTING: Tertiary academic medical center. METHODS: Length and height of consecutively treated perforations over a 3-year period were measured directly or through computed tomography. Mean differences in length and height measurements were compared and regression analysis used to determine perforation shape and the effect of etiology on perforation size. Perforations were classified by length into small (1-5 mm), medium (6-15 mm), and large (>15 mm) and correlated to shape and etiology. RESULTS: One hundred twenty-four patients (mean age 50.4 years, 60.5% female) met study inclusion criteria. Height was less than length in 93% of perforations 5 mm or greater in length. Mean perforation height was significantly less than length for medium and large perforations (P < .001). Mean length and height measurements of nonsurgical perforations were greater than those for surgical perforations (P < .001). CONCLUSION: Height is less than length in over 90% of septal perforations. Most perforations assume an elliptical shape as they enlarge. Accurate measurement and presentation of length and height is relevant information to perforation management decisions and for the evaluation of treatment outcomes.

Translation, cultural adaptation, and validation of the NOSE-Perf scale to Brazilian Portuguese.

OBJECTIVE: To perform the translation, cultural adaptation, and validation of the NOSE-Perf Scale to Brazilian Portuguese. METHODS: This study was divided into two stages. In the first stage, the questionnaire was submitted for translation and cultural adaptation, following the guidelines recommended by the ISPOR Task Force (International Society for Pharmacoeconomics and Outcomes Research). Then, the Brazilian Portuguese version of the NOSE-Perf scale was applied to a group with septal perforation and a control group. The group with perforation answered the questionnaire again after one month. Internal consistency, test-retest reliability, and discriminant validity were assessed. RESULTS: The Brazilian Portuguese version of the NOSE-Perf scale was applied to 32 participants, 16 from the group with septal perforations and 16 controls. The instrument obtained high internal consistency, with Cronbach's alpha scores of 0.986. High reliability was also obtained, with Spearman's correlation coefficient of 0.996 (p < 0.001) and the intraclass correlation coefficient of 0.965 with a 95% Confidence Interval (95% CI) of 0.886‒0.988. The NSP group obtained a mean total score of 13.8 ±â€¯12.6 and the control group a score of 2.3 ±â€¯1.8, with a statistical difference between the groups (p < 0.001), demonstrating good discriminant validity. CONCLUSION: The Brazilian Portuguese version of the NOSE-Perf scale is a reliable and valid instrument for measuring symptoms in patients with nasal septum perforations. LEVEL OF EVIDENCE: Level 2-Oxford Centre for Evidence-Based Medicine 2011 Levels of Evidence.

The clinical presentation of PIT1 positive pituitary neuroendocrine tumor immunonegative for growth hormone, prolactin, and thyroid stimulating hormone with analysis of clinical and immunostaining dissociation.

BACKGROUND: PIT1 is a pituitary transcription factor that is associated with either growth hormone (GH), prolactin (PRL), or thyroid-stimulating hormone (TSH) production. However, PIT1-positive pituitary neuroendocrine tumors (PitNETs) are occasionally immunonegative for GH, PRL, and TSH. This paper describes the clinical presentation of PIT1 positive however immunonegative PitNETs. METHODS: We conducted a retrospective analysis, identifying 228 PIT1-positive PitNET patients between 2017 and 2022. Out of these, ten (4%) tested negative for GH, PRL, and TSH. Functioning PitNETs were defined as those causing hormonal excess symptoms or hormonal overproduction. RESULTS: As for 10 patients immunonegative for all three hormones however PIT1-positive, the mean ( ± standard deviation) age was 46 ± 13 years with 70% women. Six patients exhibited signs of excess GH or PRL, and three had visual problems. Additionally, one patient had secondary hypothyroidism and adrenal insufficiency resulting from the mass effect. All tumors were macroadenoma, with a median volume of 2.1 cm3 (range, 0.8-17.5 cm3). Gross total resection was attained in six patients by trans-sphenoidal surgery. Postoperatively, eight patients experienced clinical improvement: three in vision, two in amenorrhea, two in headache, and one in acromegaly symptoms. Biochemical improvement was observed in six patients, with all experiencing remission in hormonal excess and one showing improvement in secondary hypothyroidism. Stereotactic radiosurgery was performed in three patients. CONCLUSIONS: Patients with functioning PitNETs may exhibit PIT1 staining without GH, PRL, or TSH staining. Hormonally active tumors exist in this patient population; therefore, close endocrine follow-up is necessary despite the lack of staining for GH, PRL, and TSH.

Features of Importance in Nasal Endoscopy: Deriving a Meaningful Framework.

OBJECTIVE: Critical components of the nasal endoscopic examination have not been definitively established for either the normal examination or for clinical disorders. This study aimed to identify concordance among rhinologists regarding the importance of examination findings for various nasal pathologies. STUDY DESIGN: A consortium of 19 expert rhinologists across the United States was asked to rank the importance of findings on nasal endoscopy for 5 different sinonasal symptom presentations. SETTING: An online questionnaire was distributed in July 2023. METHODS: The questionnaire utilized JotForm® software and featured 5 cases with a set of 4 identical questions per case, each covering a common indication for nasal endoscopy. Rankings were synthesized into Normalized Attention Scores (NASs) and Weighted Normalized Attention Scores (W-NASs) to represent the perceived importance of each feature, scaled from 0 to 1. RESULTS: General concordance was found for examination findings on nasal endoscopy within each case. The perceived features of importance differed between cases based on clinical presentation. For instance, in evaluating postnasal drip, the middle meatus was selected as the most important structure to examine (NAS, 0.73), with mucus selected as the most important abnormal finding (W-NAS, 0.66). The primary feature of interest for mucus was whether it was purulent or not (W-NAS, 0.67). Similar analyses were performed for features in each case. CONCLUSION: The implicit framework existing among rhinologists may help standardize examinations and improve diagnostic accuracy, augment the instruction of trainees, and inform the development of artificially intelligent algorithms to enhance clinical decision-making during nasal endoscopy.

Unified Airway Disease: Future Directions.

Unified airway disease describes the shared epidemiologic and pathophysiologic relationship among the chronic inflammatory diseases of the upper and lower airways including allergic rhinitis, chronic rhinosinusitis, asthma, and chronic otitis media. This concept proposes that these diseases are manifestations of a single inflammatory process and require an integrated diagnostic and therapeutic approach to achieve global disease control. Future directions to further establish this entity should focus on pathophysiology, diagnostic markers, flora microbes with particular emphasis on fungi, the role of type 3 inflammation, and targeted therapeutics including biologics, JAK inhibitors, and synthetic peptides.

Unified Airway Disease: Genetics and Epigenetics.

Although unified airway disease (UAD) may have heritable components, genetic changes involving coexistent chronic rhinosinusitis (CRS) are not well understood. Genetic predisposition is stronger in patients with CRS with nasal polyps compared with those without nasal polyps (CRSsNP). Genetic factors account for 25% to 80% of asthma risk and 90% of allergic rhinitis risk but risk contributions are not well described for CRS. Susceptibility genes identified in coexistent CRS-asthma relate to innate and adaptive immunity, cytokine signaling, tissue remodeling, arachidonic acid metabolism, and other proinflammatory pathways. Non-type 2 UAD such as CRS-bronchitis/bronchiectasis and CRSsNP are currently inadequately characterized.

Presenting Symptomatology for Patients With Nasal Septal Perforation: Application of the NOSE-Perf Scale.

OBJECTIVE: To objectively identify and quantitate presenting nasal symptoms in patients with a septal perforation using the validated NOSE-Perf scale. STUDY DESIGN: Case series retrospective review. METHODS: The medical records from August 2018 through January 2022 of patients at a tertiary care academic center with a septal perforation, and who completed the NOSE-Perf questionnaire, were reviewed. Perforation symptoms were identified and quantified using the 12-item NOSE-Perf scale (score range 0-48). NOSE-Perf findings were correlated to patient demographics, perforation etiology, and perforation length. NOSE-Perf scores of patients who pursued treatment were compared with those who did not. RESULTS: NOSE-Perf data were collected from 202 patients. Nasal crusting was noted in 94.1% of patients and was the most severe symptom reported (mean 2.9 of 4.0). Nasal congestion, difficulty breathing, and nasal obstruction followed in prevalence and severity. The mean total NOSE-Perf score was 23.7. Linear regression analysis demonstrated a weakly negative association of NOSE-Perf score with patient age and weakly positive association with increasing perforation length. NOSE-Perf scores were significantly higher in women and in patients pursuing treatment. CONCLUSION: This is the first study to use the validated NOSE-Perf scale to objectively characterize and establish baseline septal perforation symptomatology. The NOSE-Perf scale can play a role in the standardization of perforation evaluation and treatment outcomes assessment. Laryngoscope, 133:1315-1320, 2023.

Septal Perforation Repair Quality of Life Outcomes Using the Revised 15-item Glasgow Benefit Inventory.

BACKGROUND: The 18-item Glasgow Benefit Inventory (GBI) has been widely used to measure patient general health response to otorhinolaryngologic and facial plastic interventions. The GBI was recently reorganized into 15 questions with 5 sub-scale factors (GBI-5F) to improve its utility. Application of the GBI-5F to septal perforation treatments may improve our understanding of quality of life outcomes. METHODOLOGY/PRINCIPAL: The GBI was given to patients seen from August 2018 through October 2021 who were at least 6 months postoperative attempted perforation surgical closure using bilateral nasal mucosal flaps with an interposition graft. Original GBI and GBI-5F scores were computed and subgroup analysis performed in this retrospective medical record review. RESULTS: Of the 98 patients (mean age 45.5 years) who met study criteria, 65 were female. Mean perforation length was 12.9, and height 9.7 mm. The mean postoperative time to GBI completion was 12.7 months. Highest GBI-5F scores were noted in the Quality of Life factor, followed by Self-confidence and Social Involvement. Females reported significantly higher scores than men. Total GBI scores were similar to those recorded for other rhinologic procedures. CONCLUSIONS: The GBI-5F provides measurable insight into patient quality of life benefit following septal perforation repair.

Outcomes of Frontal Sinus Stenting With Steroid Impregnated Microsponge Versus Steroid-Eluting Implant.

BACKGROUND: Mometasone-eluting poly-L-lactide-coglycolide (MPLG) is available commercially for frontal sinus ostium (FSO) stenting. An alternative chitosan polymer-based drug delivery microsponge is also available at a lower cost per unit. OBJECTIVE: To compare the outcomes of MPLG stents versus triamcinolone-impregnated chitosan polymer (TICP) microsponge in frontal sinus surgery. METHODS: Patients who underwent endoscopic sinus surgery from December 2018 to February 2022 were reviewed to identify those with the intraoperative placement of TICP microsponge or MPLG stent in the FSO. FSO patency was evaluated by endoscopy at follow-up. Twenty-two-item sinonasal outcome test (SNOT-22) was also recorded, and complications were noted. RESULTS: A total of 68 subjects and 96 FSOs were treated. TICP was first used in August 2021 and MPLG in December 2018. MPLG placement in a Draf 3 cavity was excluded since TICP had not been used during Draf 3 procedure. Both cohorts (TICP 20 subjects, 35 FSOs; MPLG 26 subjects, 39 FSOs) had similar clinical characteristics. At a mean total follow-up of 249.2 days for TICP and 490.4 days for MPLG, FSO patency was 82.9% and 87.1%, respectively (P = .265). At an equivalent follow-up of 130.6 days in TICP and 154.0 days in MPLG, patency was 94.3% and 89.7%, respectively (P = .475). Both groups showed significant reductions in SNOT-22 (P < .001). MPLG demonstrated crusting within the FSO at 1 month (none in TICP). CONCLUSION: FSO patency for both stents was similar, although TICP had significantly lower costs per unit. Additional comparative trials may be helpful for guiding clinicians on the appropriate clinical situations for the use of these devices.

Genome-wide Epigenetic Study of Chronic Rhinosinusitis Tissues Reveals Dysregulated Inflammatory, Immunologic and Remodeling Pathways.

BACKGROUND: Epigenetics studies mechanisms such as DNA methylation, histone modifications, non-coding RNAs, and alternative polyadenylation that can modify gene activity without changing the underlying DNA nucleotide base-pair structure. Because these changes are reversible, they have potential in developing novel therapeutics. Currently, seven pharmaceutical agents targeting epigenetic changes are FDA approved and commercially available for treatment of certain cancers. However, studies investigating epigenetics in chronic rhinosinusitis (CRS) have not been undertaken previously in the United States. OBJECTIVES: The goal of this study was to investigate sinonasal DNA methylation patterns in CRS versus controls, to discern environmentally-induced epigenetic changes impacting CRS subjects. METHODS AND RESULTS: Ethmoidal samples from CRS and inferior turbinate mucosal tissue samples from controls without CRS were studied. DNA methylation was studied by Reduced Representation Bisulfite Sequencing. RADMeth® biostatistical package was used to identify differentially methylated regions (DMRs) between CRS and controls. Ingenuity Pathway analysis of DMRs was performed to identify top upstream regulators and canonical pathways. Ninety-three samples from 64 CRS subjects (36 CRSwNP; 28 CRSsNP) and 29 controls were studied. CRS and control samples differed in 13 662 CpGs sites and 1381 DMRs. Top upstream regulators identified included: 1. CRS versus controls: TGFB1, TNF, TP53, DGCR8, and beta-estradiol. 2. CRSwNP versus controls: TGFB1, CTNNB1, lipopolysaccharide, ID2, and TCF7L2. 3. CRSsNP versus controls: MYOD1, acetone, ID2, ST8SIA4, and LEPR. CONCLUSIONS: Differential patterns of methylation were identified between controls and CRS, CRSwNP, and CRSsNP. Epigenetic, environmentally-induced changes related to novel, inflammatory, immunologic, and remodeling pathways appear to affect epithelial integrity, cell proliferation, homeostasis, vascular permeability, and other yet uncharacterized pathways and genes.

Avoiding bias in artificial intelligence.

Artificial intelligence (AI) is ubiquitous and expanding, and the healthcare industry has rapidly adopted AI and machine learning for numerous applications. It is essential to understand that AI is not immune to the biases that impact our clinical and academic work, and in fact may inadvertently amplify rather than reduce them. As we harness the power of AI, it is our obligation to our patients to ensure that we address these concerns. We must take responsibility for proactive stewardship to protect against bias, not only for new AI algorithms, but also for our research studies that may one day provide data for those algorithms.