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IntroductionWhile abnormal responses to threat, including overgeneralization to conditioned fear, have been postulated to play a critical role in pathological anxiety, the relevance of previous findings to social anxiety disorder (SAD) is unclear. We investigated conditioned and generalized fear responses in patients with SAD using socially relevant stimuli.MethodsA total of 26 patients with SAD and 25 healthy controls participated in a fear conditioning and generalization paradigm consisting of two neutral faces as conditioned stimuli (CS+ or CS−) and an angry face with contemptuous comments as unconditioned stimuli. Eight morphed faces of two conditioned stimuli in each continuum were given to test generalization. Behavioral data and physiological responses were acquired.ResultsSuccessful conditioning was observed in the risk ratings for both groups, while only a marginal indication of conditioning was noted in physiological measures. During the generalization phase, patients rated the risk higher than CS− when the stimuli close to CS− contained a portion of CS+ features. Larger skin conductance responses to this stimulus were linked to higher fear of negative evaluation. In addition, patients spent a longer time evaluating safe and ambiguous stimuli than healthy controls and exhibited consistently high levels of subjective arousal.DiscussionTaken together, our findings suggest that SAD patients may exhibit a tendency towards overgeneralization of fear responses and show distinct patterns in processing generalized threat stimuli compared to healthy controls. Even though overgeneralization was not evident in physiological measures, it is necessary to consider this behavioral characteristic in the clinical management of patients with SAD.

Background Fludarabine in combination with cyclophosphamide (FC) is the standard lymphodepletion regimen for CAR T-cell therapy (CAR T). A national fludarabine shortage in 2022 necessitated the exploration of alternative regimens with many centers employing single-agent bendamustine as lymphodepletion despite a lack of clinical safety and efficacy data. To fill this gap in the literature, we evaluated the safety, efficacy, and expansion kinetics of bendamustine as lymphodepletion prior to axicabtagene ciloleucel (axi-cel) therapy.Methods 84 consecutive patients with relapsed or refractory large B-cell lymphoma treated with axi-cel and managed with a uniform toxicity management plan at Stanford University were studied. 27 patients received alternative lymphodepletion with bendamustine while 57 received FC.Results Best complete response rates were similar (73.7% for FC and 74% for bendamustine, p=0.28) and there was no significant difference in 12-month progression-free survival or overall survival estimates (p=0.17 and p=0.62, respectively). The frequency of high-grade cytokine release syndrome and immune effector cell-associated neurotoxicity syndrome was similar in both the cohorts. Bendamustine cohort experienced lower proportions of hematological toxicities and antibiotic use for neutropenic fever. Immune reconstitution, as measured by quantitative assessment of cellular immunity, was better in bendamustine cohort as compared with FC cohort. CAR T expansion as measured by peak expansion and area under the curve for expansion was comparable between cohorts.Conclusions Bendamustine is a safe and effective alternative lymphodepletion conditioning for axi-cel with lower early hematological toxicity and favorable immune reconstitution.

Abstract Chronic disseminated candidiasis (CDC) is a severe but rarely seen fungal infection presenting in patients with hematologic malignancies after a prolonged duration of neutropenia. A high index of suspicion is required to diagnose CDC as standard culture workup is often negative. While tissue biopsy is the gold standard of diagnosis, it is frequently avoided in patients with profound cytopenias and increased bleeding risks. A presumptive diagnosis can be made in patients with recent neutropenia, persistent fevers unresponsive to antibiotics, imaging findings of hypoechoic, non-rim enhancing target-like lesions in the spleen and liver, and mycologic evidence. Here, we describe the case of an 18-year-old woman with relapsed B-cell acute lymphoblastic leukemia treated with re-induction chemotherapy who subsequently developed CDC with multi-organ involvement. The diagnosis was made based on clinical and radiologic features with positive tissue culture from a skin nodule and hepatic lesion. The patient was treated for a total course of 11 months with anti-fungal therapy, most notably amphotericin B and micafungin, and splenectomy. After initial diagnosis, the patient was monitored with monthly CT abdomen imaging that showed disease control after 5 months of anti-fungal therapy and splenectomy. The diagnosis, treatment, and common challenges of CDC are outlined here to assist with better understanding, diagnosis, and treatment of this rare condition.

Abstract Background Neuropsychiatric symptoms and delusions are highly prevalent among people with dementia. However, multiple roots of neurobiological bases and shared neural basis of delusion and cognitive function remain to be characterized. By utilizing a fine-grained multivariable approach, we investigated distinct neuroanatomical correlates of delusion symptoms across a large population of dementing illnesses. Methods In this study, 750 older adults with mild cognitive impairment and Alzheimer’s disease completed brain structural imaging and neuropsychological assessment. We utilized principal component analysis followed by varimax rotation to identify the distinct multivariate correlates of cortical thinning patterns. Five of the cognitive domains were assessed whether the general cognitive abilities mediate the association between cortical thickness and delusion. Results The result showed that distributed thickness patterns of temporal and ventral insular cortex (component 2), inferior and lateral prefrontal cortex (component 1), and somatosensory-visual cortex (component 5) showed negative correlations with delusions. Subsequent mediation analysis showed that component 1 and 2, which comprises inferior frontal, anterior insula, and superior temporal regional thickness accounted for delusion largely through lower cognitive functions. Specifically, executive control function assessed with the Trail Making Test mediated the relationship between two cortical thickness patterns and delusions. Discussion Our findings suggest that multiple distinct subsets of brain regions underlie the delusions among older adults with cognitive impairment. Moreover, a neural loss may affect the occurrence of delusion in dementia largely due to impaired general cognitive abilities.

Abstract The safety and efficacy of CAR T‐cell therapy are unknown in pediatric and adolescent patients with relapsed or refractory primary mediastinal large B‐cell lymphoma (R/R PMBCL) which is associated with dismal prognosis. Here, we present a case report of a 16‐year‐old patient with R/R PMBCL treated with lisocabtagene maraleucel including correlative studies. Patient achieved complete response at 6 months without cytokine release syndrome and immune effector cell‐associated neurotoxicity syndrome. She only experienced mild cytopenias, requiring filgrastim once. This report highlights the safety and efficacy of lisocabtagene maraleucel in this population, warranting prospective studies to improve clinical outcomes.

Abstract The potential use of gelatin materials in the liquid composite molding manufacturing (LCM) process was investigated, with specific focus on the reinforcement deformation phenomenon. The adoptability of gelatin as a binder in a composite material with glass fiber for application in the LCM process was evaluated by analyzing the permeability and microscopic structure of the gelatin-coated glass fiber. To assess the tow deformation, the permeability of the non-crimped unidirectional glass fiber mat was evaluated at different flow rates that could be applied in the LCM process. Hysteresis of the permeability was observed as the flow rate increased and decreased, indicative of tow deformation. The permeability of the gelatin-treated glass fiber mat exhibited a relatively smaller variation than that of the untreated glass fiber at the same flow rate. Tow deformation in the untreated and gelatin-treated non-crimped glass fiber mats at different flow rates was evaluated by microscopic analysis and quantified using the tow thickness index. Relatively smaller variations in the permeability and minimal changes in the tow thickness of the gelatin-treated glass fiber mat were observed via microscopic analysis, indicating that gelatin effectively maintained the binding structure of the glass fiber mat.

Abstract Introduction Handedness is a conspicuous characteristic in human behavior, with a worldwide proportion of approximately 90% of people preferring to use the right hand for many tasks. In the Korean population, the proportion of left‐handedness is relatively low at approximately 7%–10%, similar to that in other East‐Asian cultures in which the use of the left hand for writing and other public activities has historically been oppressed. Methods In this study, we conducted two genome‐wide association studies (GWASs) between right‐handedness and left‐handedness, and between right‐handedness and ambidexterity using logistic regression analyses using a Korean community‐based cohort. We also performed association analyses with previously reported variants and our findings. Results A total of 8806 participants were included for analysis, and the results identified 28 left‐handedness‐associated and 15 ambidexterity‐associated loci; of these, two left‐handedness loci (NEIL3 [rs11726465] and SVOPL [rs117495448]) and one ambidexterity locus (PDE8B/WDR41 [rs118077080]) showed near genome‐wide significance. Association analyses with previously reported variants replicated ANKS1B (rs7132513) in left‐handedness and ANKIB1 (rs2040498) in ambidexterity. Conclusion The variants and positional candidate genes identified and replicated in this study were largely associated with brain development, cerebral asymmetry, neurological processes, and neuropsychiatric diseases in line with previous findings. As the first East‐Asian GWAS related to handedness, these results may provide an intriguing reference for further human neurologic research in the future.

Abstract One dimension of the emerging politics of connected and automated vehicles (CAVs) is the development of public concerns over their societal implications and associated policy issues. This study uses original survey data from the United States to contribute to the anticipation of future policy and political issues for CAVs. Several studies have surveyed the public regarding CAVs; however, there are few studies that highlight the multidimensional public concerns that CAVs will most likely bring. The study breaks down the concept of “public” by showing that the demographic variables of gender, age, race, ethnicity, income, location (rural, suburban, urban), and political ideology (conservative, moderate, liberal) are significantly associated with three of the most salient public concerns to date (safety, privacy, and data security). Furthermore, the effects of demographic variables also vary across the type of policy issue. For example, women tend to be more concerned about safety than their male counterparts, and Hispanics (Latinx) tend to be more concerned about privacy than non-Hispanics. The research shows how the social scientific analysis of the “politics” of CAVs will require attention to the variegated connections between different types of public concern and different demographic variables.

Treprostinil is a prostacyclin approved for the treatment of pulmonary arterial hypertension. Commercial data sets indicate that approximately 20–25% of patients are prescribed a higher dose than the maximum recommended dosage of nine breaths per treatment session (bps) (54 μg), four times a day (QID) and numerous studies have demonstrated the safety of doses >9 bps QID. This phase 4, retrospective analysis of specialty pharmacy records assessed the effects of inhaled treprostinil at doses >9 bps QID. Patients receiving inhaled treprostinil between September 2009 and June 2018 were included, and a random sampling of 5000 patients was selected for further analysis. Subjects were grouped based on the highest dose reached for ≥2 months within a rolling six‐month window and were followed for up to three years. Of the total of 5000 patients analyzed, 28.5% received >9 bps QID. Survival rates were significantly higher in the >9 bps QID dosing group for years one, two, and three (P 9 bps (17.5 months) compared to doses ≤9 bps (9.5 moths; P 9 bps at years 1, 2, and 3 (P 9 bps QID had a higher rate of survival and drug persistence over a three‐year period, suggesting that higher doses may provide clinically relevant benefits while remaining tolerable.

IntroductionWe have demonstrated that intensive cognitive training can produce sustained improvements in cognitive performance in adolescents. Few studies, however, have investigated the neural basis of these training effects, leaving the underlying mechanism of cognitive plasticity during this period unexplained.MethodsIn this study, we trained 51 typically developing adolescents on cognitive control tasks and examined how their intrinsic brain networks changed by applying graph theoretical analysis. We hypothesized that the training would accelerate the process of network integration, which is a key feature of network development throughout adolescence.ResultsWe found that the cognitive control training enhanced the integration of functional networks, particularly the cross-network integration of the cingulo-opercular network. Moreover, the analysis of additional data from older adolescents revealed that the cingulo-opercular network was more integrated with other networks in older adolescents than in young adolescents.DiscussionThese findings are consistent with the hypothesis that cognitive control training may speed up network development, such that brain networks exhibit more mature patterns after training.

The common dolphin (Delphinus delphis) is the second-most bycaught species in Korean waters. To provide key information about their habitat boundaries and hotspots for spatial conservation and management, the spatial use of this species was examined using data obtained from sighting and bycatch surveys of cetaceans in the past 20 years. The 95% minimum convex polygon and 95% density contour of fixed-kernel analysis suggested that the boundary of the home range of common dolphins is limited to the coastal region (Busan–Sokcho) of the East Sea/Sea of Japan. From 50% density contours drawn by kernel density estimation, it was suggested that their hotspots are around the coast of Ulsan–Pohang, Doghae, and Sokcho within the home range. Common dolphins were not observed in the Yellow Sea. Hence, shallow waters in the geographic area of the coastal region of the Yellow Sea are likely not a suitable habitat for common dolphins in this region.

Background: The non-saponin fraction of Korean Red Ginseng has been reported to have many biological activities. However, the effect of this fraction on anti-diabetic activity has not been elucidated in detail. In this study, we investigated the effects of KGC05P0, a non-saponin fraction of Korean Red Ginseng, on anti-diabetic activity in vitro and in vivo. Methods: We measured the inhibition of commercially obtained α-glucosidase and α-amylase activities in vitro and measured the glucose uptake and transport rate in Caco-2 cells. C57BL/6J mice and C57BLKS/Jdb/db (diabetic) mice were fed diets with or without KGC05P0 for eight weeks. To perform the experiments, the groups were divided as follows: normal control (C57BL/6J mice), db/db control (C57BLKS/Jdb/db mice), positive control (inulin 400 mg/kg b.w.), low (KGC05P0 100 mg/kg b.w.), medium (KGC05P0 200 mg/kg b.w.), and high (KGC05P0 400 mg/kg b.w.). Results: KGC05P0 inhibited α-glucosidase and α-amylase activities in vitro, and decreased glucose uptake and transport rate in Caco-2 cells. In addition, KGC05P0 regulated fasting glucose level, glucose tolerance, insulin, HbA1c, carbonyl contents, and proinflammatory cytokines in blood from diabetic mice and significantly reduced urinary glucose excretion levels. Moreover, we found that KGC05P0 regulated glucose production by down-regulation of the PI3K/AKT pathway, which inhibited gluconeogenesis. Conclusion: Our study thereby demonstrated that KGC05P0 exerted anti-diabetic effects through inhibition of glucose absorption and the PI3K/AKT pathway in in vitro and in vivo models of diabetes. Our results suggest that KGC05P0 could be developed as a complementary food to help prevent T2DM and its complications. Keywords: Diabetes mellitus, Korean Red Ginseng, Non-saponin fraction, Glucose regulation

Abstract Real‐world dosing and titration of parenteral (subcutaneous, SC; intravenous, IV) prostacyclin, a mainstay of pulmonary arterial hypertension (PAH) treatment, is not always consistent with prescribing information or randomized trials and has yet to be adequately characterized. The current study describes real‐world outpatient dosing and titration patterns over time, in PAH patients initiated on SC or IV treprostinil. A longitudinal, cross‐sectional analysis of medication shipment records from US specialty pharmacy services between 2009 and 2018 was conducted to determine dosing and titration patterns of SC or IV treprostinil in the outpatient setting beginning with the patient's first shipment. The sample for analysis included shipment records for 2647 patients (IV = 1040, SC = 1607). Although more patients were started on SC treprostinil than IV, median initial outpatient IV treprostinil dose (11 ng/kg/min at month on therapy one [MOT1]) was consistently and statistically significantly higher than initial outpatient SC dose (7.5 ng/kg/min at MOT1; p

Bacillus cereus (B. cereus) is a known cause of a food poisoning in the general population. However, it can cause life-threatening sepsis and shock in severely immunocompromised patients with hematologic malignancies, which frequently lead to central nervous system (CNS) infections associated with high mortality and morbidity. In this case report, we describe a patient with a newly diagnosed acute myeloid leukemia that underwent induction chemotherapy and developed B. cereus infection that was associated with septic shock and brain abscesses. Definitive diagnosis of multiple brain abscesses was not manifested with routine microbiological investigation but required the use of 16S ribosomal (rRNA) gene polymerase chain reaction (PCR) sequencing of the resected brain lesion. The patient was eventually treated with 8-week course of intravenous vancomycin and high-dose ciprofloxacin which led to a full recovery. This report highlights the significant risk posed by B. cereus infection in neutropenic patients, the use of 16S rRNA PCR sequencing test for definitive diagnosis and use of combination therapy for successful treatment of B. Cereus CNS infection.

Community involvement and citizenship have been crucial drivers in energy transitions worldwide. To deepen our understanding of the energy transition and to further promote energy citizenship, we leverage Bourdieu’s concept of cultural capital to shed light on the inequities in community-centered energy transition processes. More specifically, this study demonstrates that cultural capital is an important indicator of an individual’s willingness to participate in renewable energy-related behavior and social movements. Using survey data in the Netherlands as a case study, it finds that depending on the type of energy citizenship, i.e., material participation (investments) or communicative participation (protest), different types of cultural capital are in play. The results of this study imply that a nuanced approach towards both concepts, namely energy citizenship and cultural capital, is needed. The scholarly and practical implications of this study are discussed, and the study concludes with pathways for more comprehensive community engagement.

PurposeFibromyalgia (FM) and complex regional pain syndrome (CRPS) share many pathological mechanisms related to chronic pain and neuroinflammation, which may contribute to the multifactorial pathological mechanisms in both FM and CRPS. The aim of this study was to assess neuroinflammation in FM patients compared with that in patients with CRPS and healthy controls.MethodsNeuroinflammation was measured as the distribution volume ratio (DVR) of [11C]-(R)-PK11195 positron emission tomography (PET) in 12 FM patients, 11 patients with CRPS and 15 healthy controls.ResultsNeuroinflammation in FM patients was significantly higher in the left pre (primary motor cortex) and post (primary somatosensory cortex) central gyri (p < 0.001), right postcentral gyrus (p < 0.005), left superior parietal and superior frontal gyri (p < 0.005), left precuneus (p < 0.01), and left medial frontal gyrus (p = 0.036) compared with healthy controls. Furthermore, the DVR of [11C]-(R)-PK11195 in FM patients demonstrated decreased neuroinflammation in the medulla (p < 0.005), left superior temporal gyrus (p < 0.005), and left amygdala (p = 0.020) compared with healthy controls.ConclusionsTo the authors' knowledge, this report is the first to describe abnormal neuroinflammation levels in the brains of FM patients compared with that in patients with CRPS using [11C]-(R)-PK11195 PET. The results suggested that abnormal neuroinflammation can be an important pathological factor in FM. In addition, the identification of common and different critical regions related to abnormal neuroinflammation in FM, compared with patients with CRPS and healthy controls, may contribute to improved diagnosis and the development of effective medical treatment for patients with FM.

Peripheral T-cell lymphoma (PTCL) is a rare, heterogenous group of mature T-cell neoplasms that comprise 10–15% of non-Hodgkin lymphoma cases in the United States. All subtypes of PTCL, except for ALK+ anaplastic T-cell lymphoma, are associated with poor prognosis, with median overall survival (OS) rates of 1–3 years. The diagnosis of PTCL is mainly based on clinical presentation, morphologic features, and immunophenotypes. Recent advances in genome sequencing and gene expression profiling have given new insights into the pathogenesis and molecular biology of PTCL. An enhanced understanding of its genomic landscape holds the promise of refining the diagnosis, prognosis, and management of PTCL. In this review, we examine recently discovered genetic abnormalities identified by molecular profiling in 3 of the most common types of PTCL: RHOAG17V and epigenetic regulator mutations in angioimmunoblastic T-cell lymphoma, ALK expression and JAK/STAT3 pathway mutations in anaplastic T-cell lymphoma, and T-follicular helper phenotype and GATA3/TBX21 expression in PTCL-not otherwise specified. We also discuss the implications of these abnormalities for clinical practice, new/potential targeted therapies, and the role of personalized medicine in the management of PTCL.

The Japanese sea lion (Z. japonicus) has been regarded as an extinct species since the last report on Dokdo in 1951. Not much ecological information on the Z. japonicus on Dokdo (hereafter Dokdo sea lion) is currently available. Using a discrete time stage-structured population model, we reconstructed the Dokdo sea lion population to explore the effect of human hunting pressure on them. This study provides the first estimate for the Dokdo sea lion population from 1900 to 1951. The reconstructed capture numbers of the Dokdo sea lion and the parameters estimated in this study were well matched with the recorded numbers and ecological parameters reported previously for the Californian sea lion. Based on the reconstructed population, their number rapidly declined after hunting started and it took less than 10 years for a 70% decline of the initial population, which would be considered to be an extinction risk. Since some caveats exist in this study, some caution about our results is necessary. However, this study demonstrates how rapidly human over-hunting can cause the extermination of a large local population. This study will be helpful to raise people’s awareness about endangered marine animals such as local finless porpoises in Korea.

Adolescence is a unique period in which higher cognition develops to adult-level, while plasticity of neuron and behavior is at one of its peak. Notably, cognitive training studies for adolescents has been sparse and neural correlates of the training effects yet to be established. This study investigated the effects of multi-component training of cognitive control (MTCC) in order to examine whether the training enhanced adolescents’ cognitive control ability and if the effects were generalizable to other cognitive domains. Cognitive control refers to the ability to adjust a series of thoughts and behaviors in correspondence to an internal goal, and involves inhibition, working memory, shifting, and dual tasking as subcomponents. The participants were middle school students (aged 11–14) and randomly assigned to either a training group or an active control group. The training group performed 30 min of MTCC per day for 6 weeks. To identify the training effects, we examined the cognitive performance, regional gray matter, and their relationship. The training group showed modest improvement in a visuospatial fluid intelligence test (Block Design) after MTCC, which was not significant after correcting for multiple comparisons. In addition, the training effect on the gray matter volume (time × group interaction) was observed in the right inferior cortex (rIFC). While the control group showed a typical reduction in the rIFC volume, the training group showed a relative increase in the homologous region. The relative change in rIFC volume was associated with the change in Stroop performance. These results imply that MTCC may affect brain structure relevant to inhibitory control process.

Hepatocellular carcinoma (HCC) is the most common malignancy of the liver, which can progress rapidly and has a poor prognosis. Glypican-3 (GPC3) has been proposed to be an important diagnostic biomarker and therapeutic target for HCC. Aptamers have emerged as promising drug delivery vehicles because of their high binding affinity for target molecules. Herein, we developed G12msi, a gemcitabine-incorporated DNA aptamer, targeting GPC3, and evaluated its binding specificity and anti-tumor efficacy in GPC3-overexpressing HCC cell lines and murine xenograft models. GPC3-targeted aptamers were selected by using the SELEX process and the chemotherapy drug gemcitabine was internally incorporated into the aptamer. To determine the binding affinity and internalization of the G12msi, flow cytometry and confocal microscopy were performed on GPC3-positive HepG2, Hep3B, and Huh7 cells, as well as a GPC3-negative A431 cell. The anti-tumor activities of G12msi were evaluated with in vitro and in vivo models. We found that G12msi binds to GPC3-overexpressing HCC tumor cells with high specificity and is effectively internalized. Moreover, G12msi treatment inhibited the cell proliferation of GPC3-positive HCC cell lines with minimal cytotoxicity in control A431 cells. In vivo systemic administration of G12msi significantly inhibited tumor growth of HCC HepG2 cells in xenograft models without causing toxicity. These results suggest that gemcitabine-incorporated GPC3 aptamer-based drug delivery may be a promising strategy for the treatment of HCC.

EGFR is a key player in cell proliferation and survival signaling, and its sorting into MVBs for eventual lysosomal degradation is controlled by the coordination of multiple ESCRT complexes on the endosomal membrane. HD-PTP is a cytosolic protein tyrosine phosphatase, and is associated with EGFR trafficking by interacting with the ESCRT-0 protein STAM2 and the ESCRT-III protein CHMP4B via its N-terminal Bro1 domain. Intriguingly, the homologous domain of two other human Bro1 domain-containing proteins, Alix and Brox, binds CHMP4B but not STAM2, despite their high structural similarity. To elucidate this binding specificity, we determined the complex structure of the HD-PTP Bro1 domain bound to the STAM2 core region. STAM2 binds to the hydrophobic concave pocket of the HD-PTP Bro1 domain, as CHMP4B does to the pocket of Alix, Brox, or HD-PTP but in the opposite direction. Critically, Thr145 of HD-PTP, corresponding to Lys151 of Alix and Arg145 of Brox, is revealed to be a determinant residue enabling this protein to bind STAM2, as the Alix- or Brox-mimicking mutations of this residue blocks the intermolecular interaction. This work therefore provides the structural basis for how HD-PTP recognizes the ESCRT-0 component to control EGFR sorting.

Early cochlear development is marked by an exuberant outgrowth of neurites that innervate multiple targets. The establishment of mature cochlear neural circuits is, however, dependent on the pruning of inappropriate axons and synaptic connections. Such refinement also occurs in the central nervous system (CNS), and recently, genes ordinarily associated with immune and inflammatory processes have been shown to play roles in synaptic pruning in the brain. These molecules include the major histocompatibility complex class I (MHCI) genes, H2-K(b) and H2-D(b), and the complement cascade gene, C1qa. Since the mechanisms involved in synaptic refinement in the cochlea are not well understood, we investigated whether these immune system genes may be involved in this process and whether they are required for normal hearing function. Here we report that these genes are not necessary for normal synapse formation and refinement in the mouse cochlea. We further demonstrate that C1qa expression is not necessary for normal hearing in mice but the lack of expression of H2-K(b) and H2-D(b) causes hearing impairment. These data underscore the importance of the highly polymorphic family of MHCI genes in hearing in mice and also suggest that factors and mechanisms regulating synaptic refinement in the cochlea may be distinct from those in the CNS.