Faculty Bibliography

While motor cortical circuits contain information related to specific movement parameters¹, long-range inputs also have a critical role in action execution^2,3. Thalamic projections can shape premotor activity^2-6 and have been suggested⁷ to mediate the selection of short, stereotyped actions comprising more complex behaviours⁸. However, the mechanisms by which thalamus interacts with motor cortical circuits to execute such movement sequences remain unknown. Here we find that thalamic drive engages a specific subpopulation of premotor neurons within the zebra finch song nucleus HVC (proper name) and that these inputs are critical for the progression between vocal motor elements (that is, 'syllables'). In vivo two-photon imaging of thalamic axons in HVC showed robust song-related activity, and online perturbations of thalamic function caused song to be truncated at syllable boundaries. We used thalamic stimulation to identify a sparse set of thalamically driven neurons within HVC, representing ~15% of the premotor neurons within that network. Unexpectedly, this population of putative thalamorecipient neurons is robustly active immediately preceding syllable onset, leading to the possibility that thalamic input can initiate individual song components through selectively targeting these 'starter cells'. Our findings highlight the motor thalamus as a director of cortical dynamics in the context of an ethologically relevant behavioural sequence.

PURPOSE/UNASSIGNED:Fertility discussions are an integral part of comprehensive care for pediatric, adolescent, and young adult patients newly diagnosed with cancer and are supported by national guidelines. Current institutional practices are poorly understood. METHODS/UNASSIGNED:A cross-sectional survey was distributed to 220 Children's Oncology Group member institutions regarding fertility discussion practices. Descriptive statistics were calculated for all variables. The association between specific practices and selected outcomes on the basis of sex was examined via multivariable logistic regression. RESULTS/UNASSIGNED:< .001). Program characteristics associated with fertility discussions included reproductive endocrinology and infertility on site (females odds ratio [OR], 2.1; 95% CI, 1.0 to 4.3), discussion documentation mandate (females OR, 2.3; 95% CI, 1.0 to 5.5; males OR, 3.5; 95% CI, 1.4 to 8.7), and cumulative institution-based FP infrastructure (which included [1] routine practice of documentation, [2] template for documentation, [3] mandate for documentation, and [4] availability of FP navigation; females OR, 1.6; 95% CI, 1.1 to 2.3; males OR, 2.3; 95% CI, 1.6 to 3.4). Utilization of practices unsupported by guidelines included offering sperm banking after treatment initiation (39/135 programs; 28.9%), gonadotropin-releasing hormone analogs for ovarian suppression/FP (75/144 programs; 52.1%), ovarian tissue cryopreservation at diagnosis for patients with leukemia (19/64 programs; 29.7%), and testicular tissue cryopreservation (23/138 programs; 16.7%) not part of a clinical trial. CONCLUSION/UNASSIGNED:Despite recommended guidelines, fertility discussions with patients/families before treatment initiation are not routine at Children's Oncology Group institutions. Standard criteria to determine which options should be offered to patients are more common for males than females.

OBJECTIVES/OBJECTIVE:To examine the effects of short-term and long-term engagement with structured choral singing on vocal function and quality of life outcomes in older adults. METHODS:Two groups of older adult singers over 55 years, one with fewer than 4 semesters and one with 4 or more semesters singing in a chorale, were assessed at 3 time points: baseline, after 1 semester of singing, and either after 1 semester of rest or after 1 semester of rest and 1 semester more of singing. Acoustic and aerodynamic measures, voice-related quality of life ratings, and measures of singing accuracy were obtained. Percent change between time points were calculated to determine three outcomes: improvement, lack of change, or worsening of measures across time. RESULTS:Long-term average spectrum (LTAS), difference in first and second harmonics and estimated subglottic pressure were significantly more likely to improve after a semester of singing with less experience singers, and LTAS continued to improve after a semester of rest. Flow was significantly more likely to improve with more singing experience after a semester of singing. Aerodynamic variables consistently changed in more experienced singers and improvement was maintained over the three visits. No significant changes occurred over time for singing accuracy for any singer type. Self-perception of singing voice continued to improve with more singing experience. CONCLUSIONS:This study demonstrated that for older adults in good health, regular singing provided a mechanism for maintaining speaking voice over time.

OBJECTIVES/OBJECTIVE:Hearing loss (HL) is associated with imbalance and increased fall risk. The mechanism underlying this relationship and differences across types of hearing loss remains unclear. Head mounted displays (HMD) can shed light on postural control mechanisms via an analysis of head sway. PURPOSE/OBJECTIVE:The purpose of this study was to evaluate head sway in response to sensory perturbations in individuals with bilateral (BHL) or unilateral hearing loss (UHL) and compare them to controls. MATERIALS AND METHODS/METHODS:We recruited 36 controls, 23 individuals with UHL and 14 with BHL. An HMD (HTC Vive) measured head sway while participants stood on the floor, hips-width apart. Stimuli included two levels of visuals and sound. Root Mean Square Velocity (RMSV) and Power Spectral Density (PSD) were used to quantify head sway. RESULTS:Adjusting for age, individuals with BHL had significantly higher anterior-posterior and medio-lateral RMSV than controls and individuals with UHL. Individuals with UHL demonstrated significantly lower response to visual perturbations in RMSV AP and in all 3 frequency segments of PSD compared to controls. Individuals with UHL showed significantly lower movements at high frequencies compared to controls. Sounds or severity of HL did not impact head sway. CONCLUSIONS:Individuals with BHL demonstrated increased sway with visual perturbations and should be clinically assessed for balance performance and fall risk. Individuals with UHL exhibited reduced responses to visual stimuli compared with controls, which may reflect conscious movement processing. Additional studies are needed to further understand the mechanistic relationship between hearing loss and imbalance.

OBJECTIVES/UNASSIGNED:To present a patient with the first case of NTM (nontuberculous mycobacteria) infection of the larynx extending to cervical trachea, and the first case of subglottic stenosis associated with an NTM infection. METHODS/UNASSIGNED:Case report and review of the literature. RESULTS/UNASSIGNED:laser incision, balloon dilation, and steroid injection of the subglottic stenosis. Patient remains disease free without further subglottic stenosis. CONCLUSION/UNASSIGNED:Laryngeal NTM infections are exceedingly rare. Failure to consider NTM infection in the differential diagnosis when presented with an ulcerative, exophytic mass in patients with increased risk factors (structural lung disease, Pseudomonas colonization, chronic steroid use, prior NTM positivity) may result in insufficient tissue evaluation, delayed diagnosis, and disease progression.

Epidemiological evidence suggests that kava (Piper methysticum Forst) drinks may reduce the risk of cancer in South Pacific Island smokers. However, little is known about the anti-carcinogenic effects of kava on tobacco smoking-related bladder cancer and its underlying mechanisms. Here we show that dietary feeding of kawain (a major active component in kava root extracts) to mice either before or after hydroxy butyl(butyl) nitrosamine (OH-BBN) carcinogen exposure slows down urinary bladder carcinogenesis and prolongs the survival of the OH-BBN-exposed mice. OH-BBN-induced bladder tumors exhibit significantly increased expression of lysine-specific demethylase 1 (LSD1), accompanied by decreased levels of H3K4 mono-methylation compared to normal bladder epithelium, whereas dietary kawain reverses the effects of OH-BBN on H3K4 mono-methylation. Human bladder cancer tumor tissues at different pathological grades also show significantly increased expression of LSD1 and decreased levels of H3K4 mono-methylation compared to normal urothelium. In addition, kava root extracts and the kavalactones kawain and methysticin all increase the levels of H3K4 mono- and di-methylation, leading to inhibitory effects on cell migration. Taken together, our results suggest that modification of histone lysine methylation may represent a new approach to bladder cancer prevention and treatment and that kavalactones may be promising agents for bladder cancer interception in both current and former smokers.

Background: Racial/ethnic (R/E) minorities with head and neck squamous cell carcinoma (HNSCC) have worse survival outcomes compared to White patients. While disparities in patient outcomes for R/E minorities have been well documented, the specific drivers of the inferior outcomes remain poorly understood. Patients and Methods: This was a population-based retrospective cohort study that analyzed HNSCC patients using the National Cancer Database (NCDB) from 2000"“2016. Patient outcomes were stratified by R/E groups including White, Black, Hispanic, Native American/Other, and Asian. The main outcome in this study was overall survival (OS). Univariate time-to-event survival analyses were performed using the Kaplan"“Meier product limit estimates and the log-rank test to evaluate the differences between strata. Results: There were 304,138 patients with HNSCC identified in this study, of which 262,762 (86.3%) were White, 32,528 (10.6%) were Black, 6191 were Asian (2.0%), and 2657 were Native American/Other (0.9%). Black R/E minorities were more likely to be uninsured (9% vs. 5%, p < 0.0001), have Medicaid insurance (22% vs. 8%, p < 0.0001), be in a lower income quartile (<30,000, 42% vs. 13%, p < 0.0001), have metastatic disease (5% vs. 2%, p < 0.001), and have a total treatment time 6 days longer than White patients (median 107 vs. 101 days, p < 0.001). The 5-year OS for White, Black, Native American/Other, and Asian patients was 50.8%, 38.6%, 51.1%, and 55.8%, respectively. Among the oropharynx HNSCC patients, the 5-year OS rates in p16+ White, Black, and Asian patients were 65.7%, 39.4%%, and 55%, respectively. After a multivariate analysis, Black race was still associated with an inferior OS (HR:1.09, 95% CI: 1.03"“1.15, p = 0.002). Conclusions: This large cohort study of HNSCC patients demonstrates that Black race is independently associated with worse OS, in part due to socioeconomic, clinical, and treatment-related factors.

OBJECTIVE:Dysphagia is the most commonly reported complication of annterior cervical discectomy and fusion (ACDF) surgery. However, the incidence of dysphagia post-ACDF varies widely-partly attributable to differing outcome measures used to capture dysphagia. Our objective was to conduct a scoping review of the literature to quantify which dysphagia outcome measures have been employed post-ACDF and examine trends by study design, year, and location. METHODS:After removing duplicates, 2396 abstracts were screened for inclusion. A total of 480 studies were eligible for full-text review. After applying exclusion criteria, data was extracted from 280 studies. We extracted the dysphagia outcome measure(s), study design (prospective vs retrospective), year, and location (country). Approximately 10% of studies were repeated for intra-rater agreement. RESULTS:In total, 317 dysphagia outcome measures were reported in 280 studies (primarily retrospective-63%). The largest proportion of outcome measures were categorized as "unvalidated patient-reported outcome measures" (46%), largely driven by use of the popular Bazaz scale. The next most common categories were "insufficient detail" and "validated patient-reported outcome measures" (both 16%) followed by "chart review/database" (13%) and instrumental assessment (7%). Studies examining dysphagia post-ACDF steadily increased over the years and the use of validated measures increased in the past 10 years. CONCLUSIONS:This scoping review of the literature highlights that nearly half of the ACDF dysphagia literature relies on unvalidated patient-reported outcome measures. The current understanding of the mechanism, timeline, and presentation of dysphagia post-ACDF are likely limited due to the metrics that are most commonly reported in the literature.

BACKGROUND:A recent survey of pediatric hematology oncology (PHO) physicians identified that a majority believe fellows are struggling to find jobs that align with their goals. Career development for trainees has historically been home institution-specific, limiting fellows' exposures to career path possibilities. The "virtual-Symposium of Pediatric Hematology/Oncology of New York (v-SYMPHONY)" instituted a tristate Career Development Series for PHO trainees to better address their needs and increase awareness of the variety of PHO career opportunities. PROCEDURE/METHODS:The v-SYMPHONY Career Development Series incorporated three sessions: (a) institutional perspective, (b) individual perspectives, and (c) nuts and bolts of job search. Pre- and post-series surveys were administered to participants to measure impact. RESULTS:Forty-one fellows registered for the series and completed a pre-survey. Over half (54%) were in their third or later year of fellowship. Careers with a clinical focus were the most commonly desired career path (59%). Most had received career development advice only from faculty within their institutions (90%). Post-surveys were completed by 11 PHO fellows. Overall, 100% of respondents reported benefiting from the career sessions and recommended the series should be repeated annually. Over 90% learned new information to prepare for the job search. CONCLUSIONS:The v-SYMPHONY Career Development Series for PHO fellows across multiple institutions was established and was extremely well received by its participants. PHO fellows agreed that these sessions were beneficial in helping prepare them for the job search process. An annual regional Career Development Series is feasible and is strongly suggested to support PHO fellows.