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BACKGROUND: Kidneys are at risk from drug-induced toxicity, with a significant proportion of acute kidney injury (AKI) linked to medications, particularly cisplatin. Existing cytoprotective drugs for cisplatin-AKI carry side effects, prompting a search for better biological therapies. Mesenchymal Stem Cells (MSCs) are under consideration given their regenerative properties, yet their clinical application has not achieved their full potential, mainly due to variability in the source of MSC tested. In addition, translating treatments from rodent models to humans remains challenging due to a lack of standardized dosing and understanding potential differential responses to cisplatin between animal strains. METHOD: In the current study, we performed a time-course analysis of the effect of cisplatin across different mouse strains and evaluated gender related differences to create a robust preclinical model that could then be used to explore the therapeutic efficacy of different sources of MSCs for their ability to reverse AKI. RESULT: Our data indicated that different mouse strains produce differential responses to the same cisplatin dosing regimen. Despite this, we did not observe any gender-related bias towards cisplatin nephrotoxicity. Furthermore, our time-course analysis identified that cisplatin-induced inflammation was driven by a strong CXCL1 response, which was used as a putative biomarker to evaluate the comparative therapeutic efficacy of different MSC sources in reversing AKI. Our data indicates that UC-MSCs have a stronger anti-inflammatory effect compared to BM-MSCs and AD-MSCs, which helped to ameliorate cisplatin-AKI. CONCLUSION: Overall, our data underscores the importance of using an optimized preclinical model of cisplatin-AKI to test different therapies. We identified CXCL1 as a potential biomarker of cisplatin-AKI and identified the superior efficacy of UC-MSCs in mitigating cisplatin-AKI.

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OBJECTIVE: To investigate interview and match outcomes of medical students who received pass/fail USMLE reporting vs medical students with numeric scoring during the same period. DESIGN: Retrospective analysis of a cross-sectional survey-based study. SETTING: United States 2023 residency match. PARTICIPANTS: Medical student applicants in the 2023 residency match cycle who responded to the Texas Seeking Transparency in Application to Residency (STAR) survey. RESULTS: Among 6756 applicants for the 2023 match, 496 (7.3%) took USMLE Step 1 with pass/fail reporting. Pass/fail reporting was associated with lower USMLE Step 2-CK scores (245.9 vs 250.7), fewer honored clerkships (2.4 vs 3.1), and lower Alpha Omega Alpha membership (12.5% vs 25.2%) (all p < 0.001). Applicants with numeric USMLE Step 1 scores received more interview offers after adjusting for academic performance (beta coefficient 1.04 (95% CI 0.28-1.79); p = 0.007). Numeric USMLE Step 1 scoring was associated with more interview offers in nonsurgical specialties (beta coefficient 1.64 [95% CI 0.74-2.53]; p < 0.001), but not in general surgery (beta coefficient 3.01 [95% CI -0.82 to 6.84]; p = 0.123) or surgical subspecialties (beta coefficient 1.92 [95% CI -0.78 to 4.62]; p = 0.163). Numeric USMLE Step 1 scoring was not associated with match outcome. CONCLUSIONS: Applicants with numeric USMLE Step 1 scoring had stronger academic profiles than those with pass/fail scoring; however, adjusted analyses found only weak associations with interview or match outcomes. Further research is warranted to assess longitudinal outcomes.

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OBJECTIVE: To investigate whether a gap year for either research or a master's degree is associated with interview offers or match outcomes among otolaryngology applicants. METHODS: Using the Texas Seeking Transparency in Application to Residency (Texas STAR) database, we conducted a cross-sectional analysis of otolaryngology applicants from 2018 to 2022. Applicants were stratified based on the presence and type of gap year during medical school. Applicant characteristics, signaling, research productivity, and application costs were analyzed, with primary outcomes including number of interview offers and match status. RESULTS: Among 564 otolaryngology applicant respondents to the Texas STAR survey, 160 (28%) reported a gap year, including 64 (40%) applicants participating in a research year, 65 (41%) completing a Master of Public Health or Science (MPH and MSc), and 31 (19%) completing a Master of Business Administration, Education, or other degree (MBA and MEd). Gap-year applicants who completed a research year or MPH/MSc degree received more interview offers (P < .01) than MBA, MEd applicants, or those without a gap year. Applicants with a research year had the most publications, oral presentations, abstracts, posters, and research experiences (all P < .01). When controlling for USMLE scores, clerkship honors, and applications submitted, applicants completing a research year or an MPH/MSc-degree received increased interview offers (P < .01). No significant differences were seen in expenditures or match rates. CONCLUSIONS: Research and MPH/MSc gap years were associated with increased residency interview offers but not increased match success. Further longitudinal studies are needed to assess how yearlong experiences affect long-term career outcomes.

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BACKGROUND: Neoadjuvant chemotherapy for induction selection of definitive treatment (IS) protocols have shown excellent outcomes for organ preservation and survival in patients with T3 laryngeal squamous cell carcinoma (LSCC). We seek to evaluate survival and organ preservation outcomes in T4 LSCC patients treated with IS protocols. METHODS: Retrospective cohort of advanced T3 and T4 LSCC patients who underwent IS protocols based upon potential for preserving a functional larynx. Patients received one neoadjuvant cycle of platinum-based chemotherapy with either 5-fluorouracil or docetaxel or with two cycles of platinum-based chemotherapy with docetaxel and a Bcl-2 inhibitor. Patients who achieved ≥ 50 % response as determined by radiographic review and/or endoscopic evaluation received definitive chemoradiation. Patients who had < 50 % response after IS underwent total laryngectomy (TL) followed by post-operative radiation +/- chemotherapy. RESULTS: Amongst T4 patients, 114 met inclusion criteria including 89 who underwent IS protocols and 25 who received an upfront TL. In total, 76.0 % of T3 patients and 71.9 % of T4 patients responded to IS and underwent definitive chemoradiation. There was no significant difference in hazard of death between T4 IS and T4 TL patients (HR: 0.9, p = 0.86). Among responders, there was no significant difference in 5-year laryngectomy-free survival (T3 - 59.6 %, T4 44.3 %, p = 0.15) or laryngeal preservation by T stage (T3 - 72.8 %, T4 - 73.0 %, p = 0.84). CONCLUSIONS: Select T4 patients may benefit from organ preservation using IS protocols with similar response rates to patients with T3 tumors, without compromising survival when compared to upfront TL.

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OBJECTIVES: To compare otolaryngology interview and match outcomes between applicants with and without home residency programs. METHODS: Otolaryngology applicants from US allopathic medical schools during the 2019-2023 cycles who responded to the Texas Seeking Transparency in Application to Residency (STAR) survey were identified. Students were stratified based upon whether their medical school had an affiliated otolaryngology residency program. The primary outcomes were number of interviews and match rate. Wilcoxon-rank sum and χ2 testing was used to assess associations between home program status and interview and match outcomes. RESULTS: Of the 633 fourth-year medical students applying to otolaryngology during the 2019-2023 application cycles, 89 had no home program (NHP) and 544 had a home program (HP). Applicants with NHP completed significantly more away rotations than applicants with a HP (2.2 vs. 1.5; p < 0.01). There was no difference in mean number of applications submitted between applicants with NHP and applicants with a HP. However, applicants with a HP received a significantly greater number of interviews (14.7 vs. 11.8; p < 0.01), attended more interviews (12.4 vs. 11.3; p = 0.02), attended a lower percentage of their offered interviews (84.4% vs. 95.8%), and had a higher match rate (81.8% vs. 70.8%; p = 0.02) than applicants with NHP. Applicants with NHP interviewed at (1.9 vs. 1.3; p < 0.01) and matched at (33.7% vs. 23.9%; p = 0.048) significantly more away rotation institutions than applicants with a HP. CONCLUSION: Applicants with NHP received fewer interviews and had lower match rates. Away rotations may be especially important for applicants with NHP. LEVEL OF EVIDENCE: NA Laryngoscope, 2024.

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OBJECTIVE: Multiple studies suggest routine post-operative intensive care unit (ICU) stays after endovascular treatment (EVT) of unruptured intracranial aneurysms (UIAs) is unnecessary, though rates of ICU utilization nationwide are unknown. We aim to evaluate rates and characteristics of ICU utilization in patients undergoing elective endovascular repair of UIAs. METHODS: This is a retrospective cohort study utilizing a nationwide private-payer database in the United States to evaluate the ICU utilization in patients undergoing elective endovascular repair of UIAs between 2005 and 2019. Demographics and pre-operative comorbidities as well as post-procedural complications and discharge status were compared. An analysis of charges and costs was also performed. RESULTS: Among 6218 patients who underwent elective EVT of a UIA, 4890 (78.6%) were admitted to the ICU post-operatively. There were no differences in age, sex, or Charlson comorbidity scores in patients admitted to the ICU post-operatively compared to those admitted elsewhere. ICU utilization was more common in urban locations compared to rural. 12.7% of patients had ICU-specific needs sufficient to be billed by a critical care provider. Total provider costs were significantly higher in patients utilizing the ICU post-operatively, even among uncomplicated patients with routine discharges. CONCLUSION: Most patients undergoing elective endovascular UIA repair in the United States are admitted to the ICU postoperatively. Only 12.7% have ICU needs, and these patients are predictable from pre-operative characteristics or peri-operative complications. Reducing ICU use in this subgroup of patients may be an important target to improve healthcare value in this patient population.

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Infertility is becoming increasingly common, affecting one in six people globally. Half of these cases can be attributed to male factors, many driven by abnormalities in the process of sperm development. Emerging evidence from genome-wide association studies, genetic screening of patient cohorts, and animal models highlights an important genetic contribution to spermatogenic defects, but comprehensive identification and characterization of the genes critical for male fertility remain lacking. High divergence of gene regulation in spermatogenic cells across species poses challenges for delineating the genetic pathways required for human spermatogenesis using common model organisms. In this study, we leveraged post-translational histone modification and gene transcription data for 15,491 genes in four mammalian species (human, rhesus macaque, mouse, and opossum), to identify human-specific patterns of gene regulation during spermatogenesis. We combined H3K27me3 ChIP-seq, H3K4me3 ChIP-seq, and RNA-seq data to define epigenetic states for each gene at two stages of spermatogenesis, pachytene spermatocytes and round spermatids, in each species. We identified 239 genes that are uniquely active, poised, or dynamically regulated in human spermatogenic cells distinct from the other three species. While some of these genes have been implicated in reproductive functions, many more have not yet been associated with human infertility and may be candidates for further molecular and epidemiologic studies. Our analysis offers an example of the opportunities provided by evolutionary and epigenomic data for broadly screening candidate genes implicated in reproduction, which might lead to discoveries of novel genetic targets for diagnosis and management of male infertility and male contraception.

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OBJECTIVE: To assess whether the geographic region where medical students complete an away rotation predicts the same site, region-specific, or overall interview offers and match success in otolaryngology. STUDY DESIGN: Cross-sectional. SETTING: US medical schools. METHODS: We queried the Texas Seeking Transparency in Application to Residency database to analyze outcomes of otolaryngology applicants during the 2018 to 2020 and 2022 match cycles. Outcomes included a number of interviews offered, geographic location of interviews, and match results, including region-specific and overall match success rate. RESULTS: Of 455 otolaryngology applicants, 402 (90.3%) completed an away rotation. Among these, 368 (91.8%) were offered an interview and 124 (30.9%) matched to the program where they completed an away rotation. Applicants who completed away rotations outside their home region received more interview offers from that region than those who did not (Northeast: 4.2 vs 2.9; South: 4.3 vs 3.0; Central: 4.8 vs 3.0; West: 3.8 vs 1.6, P < .01 for all). Completing a remote away rotation increased the odds of receiving an interview from and matching within that region. After excluding programs where an away rotation was completed, a remote away rotation increased the odds of receiving an interview in the central and western regions (Central: odds ratio [OR]: 1.2 [1.1, 1.5]); West OR: 1.9 [1.7, 2.2]; and the odds of matching in the western region (OR: 2.9 [1.2, 7.4], all P < .01). CONCLUSION: Away rotations are associated with increased odds of interviewing and matching at that away program, with possible associations across the region, most evident for the West coast.

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PURPOSE: To assess the impact of applicant and residency program characteristics on preference signaling outcomes in the Match during the first 2 years of implementation across 6 specialties. METHOD: Data were obtained from the Texas Seeking Transparency in Application to Residency survey for applicants applying into otolaryngology during the 2020-2021 and 2021-2022 application cycles and into dermatology, internal medicine (categorical and preliminary year), general surgery, and urology during the 2021-2022 application cycle. The primary outcome was signal yield, defined as the number of interviews at signaled programs divided by the total number of signals sent. Associations with applicant-reported characteristics and geographic connections to residency programs were assessed using Wilcoxon rank sum testing, Spearman's rank correlation testing, and ordinary least squares regression. RESULTS: 1,749 applicants with preference signaling data were included from internal medicine (n = 884), general surgery (n = 291), otolaryngology (n = 217), dermatology (n = 147), urology (n = 124), and internal medicine preliminary year (n = 86). On average 60.9% (standard deviation 32.3%) of signals resulted in an interview (signal yield). There was a stepwise increase in signal yield with the percentage of signals sent to programs with a geographic connection (57.3% for no signals vs. 68.9% for 5 signals, P < .01). Signal yield was positively associated with applicant characteristics, such as United States Medical Licensing Exam Step 1 and 2 scores, honors society membership, and number of publications ( P < .01). Applicants reporting a lower class rank quartile were significantly more likely to have a higher percentage of their interviews come from signaled programs ( P < .01). CONCLUSIONS: Signal yield is significantly associated with geographic connections to residency programs and applicant competitiveness based on traditional metrics. These findings can inform applicants, programs, and specialties as preference signaling grows.

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BACKGROUND: The American Association of Medical Colleges trialed residency application initiatives including geographic preferences and preference signals in 2022. OBJECTIVE: To assess the impact of geographic preferences on application outcomes during the 2022 residency match year. DESIGN: Cross-sectional. PARTICIPANTS: Applicants to categorical and preliminary internal medicine during the 2022 application cycle who completed the Texas Seeking Transparency in Applications to Residency survey. MAIN MEASURES: The primary outcome was interview rate (interview offers/total applications) and whether an application resulted in a match. The key dependent variables were geographic preferences and program-specific preference signals. We also assessed differences in utilization of geographic preferences between specialties. KEY RESULTS: A total of 970 applicants into categorical (n = 884) and preliminary (n = 86) internal medicine were included in our study. A total of 704 (72.6%) applicants submitted at least one geographic preference and 424 (43.7%) submitted three preferences. On average, applicants who submitted a geographic preference had a higher interview rate than those who did not (46.0% vs. 41.8%). Applications submitted with both a preference signal and geographic preference were significantly more likely to receive an interview offer (OR: 3.2, p < 0.01) and match (OR: 6.4, p < 0.01) than applications with neither a preference signal nor a geographic preference. Geographic preferences were associated with an increase in the odds of an application receiving an interview offer, even in the setting of a preference signal (OR: 1.4, p < 0.01). CONCLUSIONS: Both preference signals and geographic preferences have significant associations with odds of an application receiving an interview and matching for both categorical and preliminary internal medicine applicants. This study can be used to inform applicants, advisors, and programs how novel application strategies can affect important application outcomes for US medical school graduates. As more specialties pilot alternative processes, it will be important to study all application outcomes among varying applicant populations.

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PURPOSE: Tracheostomy care is supply- and resource-intensive, and airway-related adverse events in community settings have high rates of readmission and mortality. Devices are often implicated in harm, but little is known about insurance coverage, gaps, and barriers to obtaining tracheostomy-related medically necessary durable medical equipment. We aimed to identify barriers patients may encounter in procuring tracheostomy-related durable medical equipment through insurance plan coverage. MATERIALS AND METHODS: Tracheostomy-related durable medical equipment provisions were evaluated across insurers, extracting data via structured telephone interviews and web-based searches. Each insurance company was contacted four times and queried iteratively regarding the range of coverage and co-pay policies. Outcome measures include call duration, consistency of explanation of benefits, and the number of transfers and disconnects. We also identified six qualitative themes from patient interviews. RESULTS: Tracheostomy-related durable medical equipment coverage was offered in some form by 98.1 % (53/54) of plans across 11 insurers studied. Co-pays or deductibles were required in 42.6 % (23/54). There was significant variability in out-of-pocket expenditures. Fixed co-pays ranged from $0-30, and floating co-pays ranged from 0 to 40 %. During phone interviews, mean call duration was 19 ± 10 min, with an average of 2 ± 1 transfers between agents. Repeated calls revealed high information variability (mean score 2.4 ± 1.5). Insurance sites proved challenging to navigate, scoring poorly on usability, literacy, and information quality. CONCLUSIONS: Several factors may limit access to potentially life-saving durable medical equipment for patients with tracheostomy. Barriers include out-of-pocket expenditures, lack of transparency on coverage, and low-quality information. Further research is necessary to evaluate patient outcomes.

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Objective: Auricular/periauricular cutaneous malignancies can be challenging to manage surgically due to the complex anatomy of the region. Otologists/neurotologists have unique skillsets that are well-suited to surgically treat these patients. We aim to highlight the role of otologists and neurotologists in providing surgical care of patients with auricular and periauricular malignancies by describing the experience of a single fellowship-trained neurotologist over a 10-year period. Methods: Retrospective chart review of 387 patients with auricular and periauricular malignancy treated by a single neurotologist between 2012 and 2022 was completed. Tumor histology and procedures performed for each patient were extracted. Additional data was collected for a subset of 84 patients with complex cases requiring selective neck dissection, parotidectomy, lateral temporal bone resection, regional advancement or rotational flap reconstruction, and/or free tissue transfer reconstruction. Results: Within the series of 387 patients, squamous cell carcinoma was the most common histology (42.6%, n = 165), followed by basal cell carcinoma (40.8%, n = 158), and melanoma (9.8%, n = 38). Common surgical procedures included wide local excision (61.8%, n = 239), partial/sub-total auriculectomy 18.3% (n = 71), or total auriculectomy 5.2% (n = 20). Within the 84-patient subset, median age at diagnosis was 71.9 years. Dermatologists provided most patient referrals (50.0%, n = 42). Most common tumor locations included: auricular (58.3%, n = 49), pre-auricular (21.4%, n = 18), and parotid (27.4%, n = 23). Revision surgery occurred in 22.6% of cases (n = 19), of which 26.3% (n = 5) for positive margins and 31.6% (n = 6) for recurrence. Mean follow-up was 22.8 months. Disease-specific 5-year survival was 91%. Conclusions: We demonstrate the feasibility of an otologist/neurotologist incorporating the surgical management of auricular and periauricular malignancies into their practice. Level of Evidence: 4.

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Objective: To examine how virtual away rotations might influence interview and match outcomes in otolaryngology. Study Design: Cross-sectional retrospective analysis of survey-based study. Setting: United States medical students applying to otolaryngology residency in the 2020 to 2021 cycle. Methods: The Texas Seeking Transparency in Application to Residency database was queried to identify otolaryngology applicants during the 2020 to 2021 cycle. The primary outcome was mean number of interview offers. χ 2 tests, 2-sided t tests, logistic regression models, and ordinary least squares regression models were used to examine associations with virtual away rotations. Results: Among 115 otolaryngology applicants identified, 35 (30.4%) applicants reported completing 1 or more virtual away rotations. Applicants who completed at least 1 virtual away rotation received significantly more interview offers than their counterparts who did not participate in virtual away rotations (mean [SD], 14.9 [8.2] vs 11.6 [7.9]; P < .03). Each virtual away rotation completed was associated with an incremental increase of 2 additional interview offers (ß coefficient: 2.29 [95% confidence interval, CI: 0.8-3.7; P < .01]). Applicants who completed a virtual away rotation were more likely to receive an interview from that program (62.7% vs 16.8%, P < .01) and to match there (odds ratio 7.7 [95% CI: 2.7-21.7]; P < .01) when compared to applicants who had not done the away rotation. Participation in virtual away rotations was not associated with significant improvement in match success (82.9% vs 67.5%; P = .09). Conclusion: Virtual away rotations were associated with improved program-specific interview and match outcomes, as well as a higher overall number of interview offers.

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The mammalian epidermis undergoes constant renewal, replenished by a pool of stem cells and terminal differentiation of their progeny. This is accompanied by changes in gene expression and morphology that are orchestrated, in part, by epigenetic modifiers. Here, we define the role of the histone acetyltransferase KAT2A in epidermal homeostasis and provide a comparative analysis that reveals key functional divergence with its paralog KAT2B. In contrast to the reported function of KAT2B in epidermal differentiation, KAT2A supports the undifferentiated state in keratinocytes. RNA-seq analysis of KAT2A- and KAT2B- depleted keratinocytes revealed dysregulated epidermal differentiation. Depletion of KAT2A led to premature expression of epidermal differentiation genes in the absence of inductive signals, whereas loss of KAT2B delayed differentiation. KAT2A acetyltransferase activity was indispensable in regulating epidermal differentiation gene expression. The metazoan-specific N terminus of KAT2A was also required to support its function in keratinocytes. We further showed that the interplay between KAT2A- and KAT2B-mediated regulation was important for normal cutaneous wound healing in vivo. Overall, these findings reveal a distinct mechanism in which keratinocytes use a pair of highly homologous histone acetyltransferases to support divergent functions in self-renewal and differentiation processes.

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The impact of the oral microbiome on head and neck cancer pathogenesis and outcomes requires further study. 16s rRNA was isolated and amplified from pre-treatment oral wash samples for 52 cases and 102 controls. The sequences were binned into operational taxonomic units (OTUs) at the genus level. Diversity metrics and significant associations between OTUs and case status were assessed. The samples were binned into community types using Dirichlet multinomial models, and survival outcomes were assessed by community type. Twelve OTUs from the phyla Firmicutes, Proteobacteria, and Acinetobacter were found to differ significantly between the cases and the controls. Beta-diversity was significantly higher between the cases than between the controls (p < 0.01). Two community types were identified based on the predominant sets of OTUs within our study population. The community type with a higher abundance of periodontitis-associated bacteria was more likely to be present in the cases (p < 0.01), in older patients (p < 0.01), and in smokers (p < 0.01). Significant differences between the cases and the controls in community type, beta-diversity, and OTUs indicate that the oral microbiome may play a role in HNSCC.

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Objectives: To assess the impact of applicant and program characteristics on preference signaling outcomes during the 2021 and 2022 application cycles in otolaryngology. Methods: The Texas Seeking Transparency in Applications to Residency survey was used for otolaryngology applicants during the 2021 and 2022 match years. The primary outcome of interest was signal yield, defined as the number of interviews at signaled programs divided by the total number of signals sent. Associations with applicant-reported characteristics, geographic connections to programs, and program reputation were assessed. Results: On average 59.5% of signals resulted in an interview (signal yield). There was a positive correlation between the number of signals sent to a program with a reported geographic connection and signal yield, with each additional signal resulting in a 3.4% increase in signal yield (p = .03). Signal yield was positively associated with number of publications (p < .001); number of abstracts, posters, and presentations (p = .04); and whether the applicant took a research year (p = .003). Applicants with higher USMLE Step 1 (p = .01) and Step 2 (p = .003) scores, publications (p = .03), volunteer (p = .008) and leadership (p = .001) experiences received a lower percentage of their total interviews from signaled programs whereas applicants from the 3rd (p < .001) and 4th (p = .03) cumulative class ranked quartiles received a higher percentage of their total interviews from signaled programs. Conclusions: Signal yield appears to have a significant association with geographic connections to programs and applicant competitiveness. This study may help applicants, advisors, and programs maximize the benefit of the preference signaling system.Levels of evidence: Level 4.

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BACKGROUND: The impact of monoclonal antibody therapy (mAB) for advanced head and neck cancer on end-of-life health care utilization and costs has yet to be adequately studied. METHODS: Retrospective cohort study of patients aged 65 and over with a diagnosis of head and neck cancer between 2007 and 2017 within the SEER-Medicare registry assessing the impact of mAB therapy (i.e., cetuximab, nivolumab, or pembrolizumab) on end-of-life health care utilization (ED visits, inpatient admissions, ICU admissions, and hospice claims) and costs. RESULTS: Of 12 544 patients with HNC, 270 (2.2%) utilized mAB therapy at the end-of-life period. On multivariable analyses adjusting for demographic and clinicopathologic characteristics, there was a significant association between mAB therapy and emergency department visits (OR: 1.38, 95% CI: 1.1-1.8, p = 0.01) and healthcare costs (ß: $9760, 95% CI: 5062-14 458, p < 0.01). CONCLUSIONS: mAB use is associated with higher emergency department utilization and health care costs potentially due to infusion-related and drug toxicity expenses.

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We report an immunocompromised patient in Alabama, USA, 75 years of age, with relapsing fevers and pancytopenia who had spirochetemia after a tick bite. We identified Borrelia lonestari by using PCR, sequencing, and phylogenetic analysis. Increasing clinical availability of molecular diagnostics might identify B. lonestari as an emerging tickborne pathogen.

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Argonaute 2 (AGO2) is a ubiquitously expressed protein critical for regulation of mRNA translation and vital to animal development. AGO2 protein is found in both cytoplasmic and nuclear compartments, and although its cytoplasmic role is well studied, the biological relevance of nuclear AGO2 is unclear. Here, we address this problem in vivo using spermatogenic cells as a model. We find that AGO2 transiently binds both chromatin and nucleus-specific mRNA transcripts of hundreds of genes required for sperm production during male meiosis in mice, and that germline conditional knockout (cKO) of Ago2 causes depletion of the encoded proteins. Correspondingly, Ago2 cKO males show abnormal sperm head morphology and reduced sperm count, along with reduced postnatal viability of offspring. Together, our data reveal an unexpected nuclear role for AGO2 in enhancing expression of developmentally important genes during mammalian male reproduction.

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Objective: This study aims to assess trends in applicant-reported costs of the otolaryngology residency application process between 2019 and 2021 and evaluate the impact of application costs on number of interview offers. Study Design: Cross-sectional study. Setting: US allopathic and osteopathic medical schools. Methods: Survey data from applicants were obtained from the Texas STAR database (Seeking Transparency in Application to Residency) for the years 2019 to 2021. Outcomes included total cost, interview cost, other costs, application fees, and number of interview offers. Simple and multivariable linear regression was used to identify novel predictors of cost and assess the correlation between cost and interview offers. Results: Among 363 otolaryngology applicants, there was a 74% reduction in total costs and a 97% reduction in interview costs in the 2021 cycle vs the 2020 cycle. Significant predictors of total cost among otolaryngology applicants included the number of away rotations (P < .01), the number of research experiences (P = .04), and couples matching (P < .01). During the 2019 and 2020 application cycles, there was a significant association between applicant-reported total spending and number of otolaryngology interview offers (P < .01), which was not present during the 2021 cycle (P = .35). Conclusion: Number of otolaryngology interview offers appears to be directly correlated with applicant-reported total costs regardless of number of applications or interviews attended, which may be a source of inequality in the application process. There was a drastic reduction in total costs, interview costs, and other costs during the COVID-19 pandemic, which was likely driven by virtual interviewing and the absence of away rotations.