Bimodal Group Research Articles

Recidivism risk factors among Mississippi justice-involved youth: latent class analysis of the SAVRY

ABSTRACT The Structured Assessment of Violence Risk in Youth (SAVRY) instrument is a popular risk-need-responsivity tool for justice-involved youth. This study conducted a multi-group (based on sex) latent class analysis model of the SAVRY items to explore heterogeneity in risk/needs among youths involved in the juvenile court in Mississippi between 2017 and 2021. Results indicated a three-class solution best with the data, with Very Low, Low, and Bimodal classes. Generally, these groups were similar across sex, though the Bimodal subgroup was proportionally larger for females than males. Subsequent analyses indicated the Bimodal group was significantly younger and more involved in future one-year recidivism. These findings suggest subgroups of risk exist and should be examined further to assess future recidivism and other risks.

Effectiveness of bimodal stimulation of the auditory-somatosensory system in the treatment of tonal tinnitus

Background and objectivesThe dorsal cochlear nucleus (DCN) is the interaction site of auditory and somatosensory system inputs. According to the stochastic resonance theory, hearing loss increases the neural activity of the somatosensory system in the DCN and causes tinnitus. it is possible to modulate this neural hyperactivity by applying random noise through the auditory and somatosensory systems (bimodal stimulation). Therefore, this study aimed to investigate the effectiveness of the bimodal intervention based on the theory of stochastic resonance. MethodsThe study divided 34 participants into unimodal and bimodal groups with 17 subjects in each. The bimodal group received customized acoustic stimulation along with transcutaneous auricular vagus nerve stimulation (tAVNS) and the unimodal group received customized acoustic stimulation along with tAVNS as a sham. The treatment sessions in both groups were 6 sessions and each session lasted for 20 min. The participants were evaluated before, immediately after, and one month after the completion of the intervention sessions, using the Tinnitus Handicap Inventory (THI) questionnaire and the mismatch negativity (MMN) test. ResultsAfter the intervention sessions, the results indicated a statistically significant decrease in THI scores and a significant increase in the MMN amplitude in the bimodal group compared to the unimodal group. No significant changes in MMN latency were observed between the two groups. These changes were stable in the one-month follow-up visit. ConclusionsOur study showed that bimodal stimulation is a better intervention option compared to unimodal stimulation. Bimodal stimulation may be an effective intervention method for some subjects with tinnitus, especially people with hearing loss who have tonal tinnitus.

Lexical tone recognition in multi-talker babbles and steady-state noise by Mandarin-speaking children with unilateral cochlear implants or bimodal hearing

Background and objectivesLexical tone presents challenges to cochlear implant (CI) users especially in noise conditions. Bimodal hearing utilizes residual acoustic hearing in the contralateral side and may offer benefits for tone recognition in noise. The purpose of the present study was to evaluate tone recognition in both steady-state noise and multi-talker babbles by the prelingually-deafened, Mandarin-speaking children with unilateral CIs or bimodal hearing. MethodsFifty-three prelingually-deafened, Mandarin-speaking children who received CIs participated in this study. Twenty-two of them were unilateral CI users and 31 wore a hearing aid (HA) in the contralateral ear (i.e., bimodal hearing). All subjects were tested for Mandarin tone recognition in quiet and in two types of maskers: speech-spectrum-shaped noise (SSN) and two-talker babbles (TTB) at four signal-to-noise ratios (−6, 0, +6, and +12 dB). ResultsWhile no differences existed in tone recognition in quiet between the two groups, the Bimodal group outperformed the Unilateral CI group under noise conditions. The differences between the two groups were significant at SNRs of 0, +6, and +12 dB in the SSN conditions (all p < 0.05), and at SNRs of +6 and +12 dB of TTB conditions (both p < 0.01), but not significant at other conditions (p > 0.05). The TTB exerted a greater masking effect than the SSN for tone recognition in the Unilateral CI group as well as in the Bimodal group at all SNRs tested (all p < 0.05). Among demographic or audiometric variables, only age at implantation showed a weak but significant correlation with the mean tone recognition performance under the SSN conditions (r = −0.276, p = 0.045). However, when Bonferroni correction was applied to the correlation analysis results, the weak correlation became not significant. ConclusionPrelingually-deafened children with CIs face challenges in tone perception in noisy environments, especially when the noise is fluctuating in amplitude such as the multi-talker babbles. Wearing a HA on the contralateral side when residual hearing permits is beneficial for tone recognition in noise.

Distributional learning of non-native tone contrasts by older adults after training and overnight consolidation

Despite decline in psychoacoustic and statistical learning (SL) abilities, older adults demonstrate remarkably intact perceptual learning in both L2 (tone-word learning) and L1 settings (perceptual adaptation to accented/noise-vocoded speech) but show limited transfer of learning to untrained stimuli. This study tests whether perceptual learning is maintained in an implicit statistical learning task where older adults learn L2 tonal contrasts through exposure to probability distributions of tonal tokens, which may pose higher requirements on both psychoacoustic and SL abilities, and whether sleep-dependent consolidation helps the generalization of perceptual knowledge. L1-Cantonese older adults learned to discriminate a perceptually difficult level-falling tone contrast following a pre-test, training, post- training overnight interval. Training stimuli were synthesized by interpolating naturally produced Mandarin level and high-falling tones into six equidistant steps. Participants either heard a bimodal (two-peak resembling level-falling categories) or unimodal distribution (single-peak) consisting of 256 tokens. ABX discrimination task was administered for testing, with tokens by two genders and on two pseudo-syllables to test generalization. Pilot data of 14 participants showed a trend of group effect with the bimodal group outperforming the unimodal group after training and sleep-dependent consolidation, showing that perceptual learning is maintained in a paradigm that relies heavily on psychoacoustic and SL abilities.

Incidental vocabulary acquisition through watching movies with bimodal and standard subtitles: The case of L2 Swahili learners

This study aimed to identify the level of vocabulary that can be acquired by L2 Swahili learners after watching a single Swahili movie with either Swahili or English subtitles. 30 University of Ghana L2 Swahili students, ranging in age from 18-30 were divided into two groups. The groups watched the same movie in Swahili with either bimodal (BM) or standard (STD) subtitling. Those in the bimodal group watched the movie with Swahili subtitles and those in the standard group watched the movie with English subtitles. English is the medium of instruction at the University of Ghana and the official language of Ghana. Participants were tested on vocabulary taken from the movie both before and after watching the movie. They took a pre-test before watching the movie, and a post-test right after watching it, and data were analyzed using MS Excel. Results from the post-tests showed an increase in all participants’ vocabulary levels after watching the movie, with those in the standard group making statistically significant gains. The study suggests that watching a movie in L2 and visually seeing the subtitles in L1 has a greater effect on vocabulary acquisition than watching and seeing the subtitles in L2.

Effects of different input modes on blended EFL speaking instruction: a quasi-experimental study

While blended learning has received scholarly attention in EFL contexts, little empirical research has investigated the effects of online input modes on learning achievement and attitudes. This study thus examined the effects of bimodal and multimodal online input on blended speaking instruction in a Chinese university. A quasi-experimental, between-subjects design over 20 wk involved two groups of participants. A bimodal group (BG, N = 30) learnt with online text-and-audio materials, while a multimodal group (MG, N = 30) learnt with online videos. In order to examine their learning achievement and attitudes, two speaking tests, one questionnaire and semi-structured interviews were administered in the study. The quantitative results revealed that learners’ speaking skills and learning attitudes improved through both bimodal and multimodal blended learning. However, no significant differences were found between the two groups in terms of both speaking performance and learning attitudes. The qualitative results for learning experience showed that students in both groups generally expressed a positive attitude towards engaging in blended learning to enhance their comprehensive speaking skills. The study aligned with the literature while allowing an empirical discussion of the effects of different input modes on blended course design and explicit speaking instruction.

Unimodal versus bimodal auditory stimulation in inner ear malformations: Cognitive, language, and motor performance.

New perspectives on rehabilitation options for inner ear malformations have still been studied in the literature. This study investigated the cognitive, language, and motor skills of auditory brainstem implant (ABI) users in unimodal and bimodal groups. The motor competency of the participants was assessed with Bruininks-Oseretsky Motor Proficiency Test-2 Short Form (BOT2 SF). Language performance was evaluated by the test of Early Language Development-3 and Speech Intelligibility Rating. Word identification, sentence recognition tests, and Categories of Auditory Performance were used to assess auditory perception skills. To examine the cognitive performance, Cancellation Test and Gesell Copy Form were administered. All the tests were conducted in a quiet environment without any distractions. The participants were divided into two groups: (1) 17 children in the unimodal group and (2) 11 children in the bimodal (who used a cochlear implant on one side and ABI on the other side) group. There were significant correlations between the chronological age of participants and BOT2 SF total score, cancellation tests, auditory perception tests, and language performance. Similarly, there were significant correlations between the duration of ABI use and auditory perception tests, language performance, cancellation test, and some BOT2 SF subtests (r = -0.47 to -0.60, p < .001). There was no significant difference between the unimodal and bimodal groups in any task (p > .05). However, there were moderate-to-strong correlations among the auditory perception tests, cancellation test, language test, and BOT2 SF total score and subtests (r = 0.40 to 0.55, p < .05). Although there were no significant differences between bimodal and unimodal groups, a holistic approach, which indicates that hearing and balance issues can have broader impacts on a person's physical, emotional, social, and psychological aspects, should be used in the assessment process. Level 4.

Haplotype Disequilibrium in the TLR Genes of Czech Red Pied Cattle

Hybrid resequencing of the antibacterial innate immune genes coding for toll-like receptors, namely TLR1, TLR2, TLR4, TLR5, and TLR6, using HiSeq and PacBio technologies of pooled population samples of Czech Simmental (Czech Red) cattle allowed us to determine haplotypes formed by the polymorphisms present. Directly determined haplotypes within the range of the large proximal amplicon in TLR2 formed two clusters in the network tree graph. The distribution of the statistically reconstructed haplotypes based on individual genotyping of the present SNPs was consistent. Similarly, the statistically reconstructed haplotypes in TLR5 and TLR6 formed two clusters. The trend of bimodal distribution was also observed in TLR4, while the limited diversity of TLR1 did not allow for any conclusion. The observed bimodal distribution is consistent with earlier reports for cattle populations worldwide. The stability of this phenomenon cannot be ascribed to historical origin but rather to a long-term effect of balancing selection. The equilibrium might be based on two different essential functions performed by the TLR genes or their products. The formation of two kinds of heterodimers by the TLR2 product, namely, TLR2/TLR1 and TLR2/TLR6 with different ligand specificities, is considered to be a particular case. On the other hand, the better expression of the bimodal groups in the 5′-proximal SNPs supports the localization of the selection targets in the upstream regulatory regions or the functional interactions in the proximal part of the transcripts.

Contralateral hearing aid use in adult cochlear implant recipients: retrospective analysis of auditory outcomes

Objective To investigate retrospectively the frequency of usage of bimodal stimulation among cochlear implant (CI) users, as well its clinical benefit relative to unilateral use. Design All subjects had been monitored with the clinical Minimal Outcome Measurements test battery. Study samples 103 adults with bilateral postlingual profound sensorineural hearing loss and unilateral CI use were extracted from the local database. These were divided into two groups: those who only used a CI and those who used bimodal stimulation. Results The preoperative contralateral residual hearing in the bimodal group was significantly better than that of the CI-only group. In both groups, speech perception in quiet and in noise improved after CI, with no significant difference between postoperative unimodal conditions. For the bimodal group, an additional significant improvement was found for the bimodal condition compared to the unimodal. Conclusion Given the observed auditory benefit of bimodal stimulation in comparison to unimodal stimulation and given the finding that degree of residual hearing is not correlated with bimodal benefits, it is recommended to encourage CI recipients to continue contralateral HA use after CI. As a result of expanding CI criteria worldwide, the population of bimodal users is expected to grow in the near future.

Effect of cochlear implantation on speech recognition under different listening modes in children

Objective:To investigate speech recognition among children with a unilateral cochlear implant（CI）, bilateral CI, and bimodal hearing and identify the benefits of binaural hearing. Methods:A total of 67 children with severe sensorineural hearing loss who received bilateral CI, bimodal hearing, and unilateral CI from 2012 to 2021 were recruited, including 23 cases with unilateral CI, 25 cases of bimodal hearing, and 19 cases of bilateral CI. The aided hearing threshold at 250-4000 Hz and speech recognition performance of two-syllable words and short sentences in quiet and noisy environments were tested, respectively. Results:There was no significant difference in the hearing threshold results of the bilateral CI group, the bimodal hearing group, and the unilateral CI group by ANOVA（P>0.05）. According to the paired t-test within the group, the speech recognition of disyllabic words and short sentences in quiet and noisy environments were significantly different among the three groups（P<0.05）. There was no significant difference in the speech recognition rates of disyllabic words and short sentences among the three groups in a quiet environment（P>0.05）, but there was a statistically significant difference in a noisy environment（P<0.05）. Additional multiple linear regression analysis showed no significant difference in the recognition rates of disyllabic words and short sentences between the bimodal group and the bilateral CI group in quiet and noisy environments（β=-0.567, P>0.05; β=-0.643, P>0.05）. There was a statistically significant difference in speech recognition of disyllabic words and short sentences between the bimodal group and the unilateral CI group in the noise environment（β=-0.124, P<0.05）, but the difference was not statistically significant in a quiet environment（β=-0.671, P>0.05）; there was a statistically significant difference in the recognition rate of disyllabic words and short sentences between the bilateral CI group and the unilateral CI group in the noise environment（β=-0.226, P<0.05）, but the difference was not statistically significant in a quiet environment（β=-0.341, P>0.05）. Conclusion:Clinicians and guardians are encouraged to provide the most comprehensive audiological evaluation for children with hearing loss. Bilateral CI and bimodal hearing have demonstrated enormous advantages over unilateral CI regarding speech recognition in noise. Bimodal hearing deems a strong recommendation if the contralateral ear has sufficient speech recognition capability. Bilateral CI should be warranted if hearing aids deemed to be ineffective.

Production of Tone 2 in disyllabic words in Mandarin Chinese speaking children aged 3-5 with a cochlear implant and a contralateral hearing aid

ABSTRACT To investigate Mandarin Tone 2 production of disyllabic words of prelingually deafened children with a cochlear implant (CI) and a contralateral hearing aid (HA) and to evaluate the relationship between their demographic variables and tone-production ability. Thirty prelingually Mandarin-speaking preschoolers with CI+HA and 30 age-matched normal-hearing (NH) children participated in the study. Fourteen disyllabic words were recorded from each child. A total of 840 tokens (14 × 60) were then used in tone-perception tests in which four speech therapists participated. The production of T2-related disyllabic words of the bimodal group was significantly worse than that of the NH group, as reflected in the overall accuracy (88.57% ± 16.31% vs 99.29% ± 21.79%, p < 0.05), the accuracy of T1+T2 (93.33% vs 100%), the accuracy of T2+T1 (66.67 ± 37.91% vs 98.33 ± 9.13%), and the accuracy of T2+T4 (78.33 ± 33.95% vs 100%). In addition, the bimodal group showed significantly inferior production accuracy of T2+T1 than T2+T2 and T3+T2, p < 0.05. Both bimodal age and implantation age were significantly negatively correlated with the overall production accuracy, p < 0.05. For the error patterns, bimodal participants experienced more errors when T2 was in the first position of the tone combination, and T2 was most likely to be mispronounced as T1 and T3. Bimodal patients aged 3–5 have T2-related disyllabic lexical tone production defects, and their performances are related to tone combination, implantation age, and bimodal age.

Increasing density and mechanical performance of binder jetting processing through bimodal particle size distribution

Binder jetting is an additive manufacturing (AM) technology that has gained popularity and attention in recent years for production applications in tooling, biomedical, energy, and defense sectors. When compared to other powder bed fusion-based AM methods, binder jetting processes powder feedstock without the need of an energy source during printing. This avoids defects associated with melting, residual stresses, and rapid solidification within the parts. However, one of the challenges of this process is the relatively lower densities which impacts part density, and subsequently, sintering and mechanical properties. In this study, we investigated the influence of bimodal powder size distributions (a mixture of coarse to fine particles) as a method for increasing part density and mechanical strength, and used stainless steel (SS) 316L bimodal mixtures in this case. Four unimodal and two bimodal groups were evaluated under similar AM processing conditions for sintered density measurements and flexural strengths. Our results demonstrated that bimodal size distributions showed a statistically significant increase in density by 20% and ultimate flexural strength by 170% when compared to the highest performing unimodal group. In addition to experimental findings, reactive molecular dynamics simulations showed that the presence of finer powders along with coarser particles in the bimodal particle mixture contribute to additional bonds that are stronger across the particle interfaces. Findings from this study can be used to design bimodal particle size distributions to achieve higher density and better mechanical properties in binder jetting AM process.

Acoustic analysis of tone production in Mandarin-speaking bimodal cochlear implant users

The benefit of using a hearing aid with a cochlear implant (bimodal hearing) has been demonstrated for tone perception under certain conditions. The present study evaluated bimodal effects for tone production by comparing performance between a bimodal and a unimodal implant group. Results showed that acoustic differentiation of tones produced by the bimodal group was better than the unimodal implant group, and performance was dependent on the subject's acoustic thresholds but not related to implant experience or age at implantation. The findings support the use of amplified acoustic hearing in conjunction with the implant for better development of pitch production.

Effects of the Configuration of Hearing Loss on Consonant Perception between Simulated Bimodal and Electric Acoustic Stimulation Hearing.

Cochlear implant technology allows for acoustic and electric stimulations to be combined across ears (bimodal) and within the same ear (electric acoustic stimulation [EAS]). Mechanisms used to integrate speech acoustics may be different between the bimodal and EAS hearing, and the configurations of hearing loss might be an important factor for the integration. Thus, differentiating the effects of different configurations of hearing loss on bimodal or EAS benefit in speech perception (differences in performance with combined acoustic and electric stimulations from a better stimulation alone) is important. Using acoustic simulation, we determined how consonant recognition was affected by different configurations of hearing loss in bimodal and EAS hearing. A mixed design was used with one between-subject variable (simulated bimodal group vs. simulated EAS group) and one within-subject variable (acoustic stimulation alone, electric stimulation alone, and combined acoustic and electric stimulations). Twenty adult subjects (10 for each group) with normal hearing were recruited. Consonant perception was unilaterally or bilaterally measured in quiet. For the acoustic stimulation, four different simulations of hearing loss were created by band-pass filtering consonants with a fixed lower cutoff frequency of 100 Hz and each of the four upper cutoff frequencies of 250, 500, 750, and 1,000 Hz. For the electric stimulation, an eight-channel noise vocoder was used to generate a typical spectral mismatch by using fixed input (200-7,000 Hz) and output (1,000-7,000 Hz) frequency ranges. The effects of simulated hearing loss on consonant recognition were compared between the two groups. Significant bimodal and EAS benefits occurred regardless of the configurations of hearing loss and hearing technology (bimodal vs. EAS). Place information was better transmitted in EAS hearing than in bimodal hearing. These results suggest that configurations of hearing loss are not a significant factor for integrating consonant information between acoustic and electric stimulations. The results also suggest that mechanisms used to integrate consonant information may be similar between bimodal and EAS hearing.

Prevalence and functional implications of Soleus and Tibialis anterior activation strategies during cycling

ABSTRACT Key areas of sports science research investigate the functional role of muscle activations within human movement. Even within relatively constrained movements like cycling, significant variability is observed in muscle activation strategies. Particular attention has been given to particular muscles, despite Soleus and Tibialis anterior muscles presenting a potentially functionally relevant split between monomodal and bimodal activation strategies. The current study (N = 54) investigated the prevalence and functional implications of these different strategies and identified, in addition to monomodal [Soleus: N = 24, Tibialis anterior: N = 7] and bimodal [Soleus: N = 12, Tibialis anterior: N = 31] strategies, a third group switching between strategies [Soleus: N = 16, Tibialis anterior: N = 13]. The combined Soleus group showed significantly higher Index of Force Effectiveness, lower negative work and lower radial forces than the bimodal group. Furthermore, bimodal Soleus strategies produced a period of significantly greater plantar flexion during the upstroke. No differences were found between the Tibialis anterior groups. These data show an identifiable group of cyclists utilising a combination of monomodal and bimodal strategies potentially benefiting mechanical effectiveness. Awareness of such functional implications can aid researchers and practitioners when interpreting cycling biomechanics data or intervention responses. Further research should investigate the factors that mediate transitions between activation strategies within the combined groups.

Differences in perceptual assimilation following training.

Learning to perceive non-native speech sounds is difficult for adults. One method to improve perception of non-native contrasts is through a distributional learning paradigm. Three groups of native-English listeners completed a perceptual assimilation task in which they mapped French vowels onto English vowel categories: Two groups (bimodal, unimodal distribution) completed a perceptual learning task for the French /œ/-/o/ contrast and a third completed no training. Both trained groups differed from the untrained group, but participants in the bimodal group showed a different perceptual mapping for the targeted /œ/ vowel, suggesting that the bimodal condition may maximize perception of non-native contrasts.

Cochlear Implant and Hearing Aid: Objective Measures of Binaural Benefit.

Cochlear implants (CI) improve hearing for the severely hearing impaired. With an extension of implantation candidacy, today many CI listeners use a hearing aid on their contralateral ear, referred to as bimodal listening. It is uncertain, however, whether the brains of bimodal listeners can combine the electrical and acoustical sound information and how much CI experience is needed to achieve an improved performance with bimodal listening. Patients with bilateral sensorineural hearing loss undergoing implant surgery were tested in their ability to understand speech in quiet and in noise, before and again 3 and 6 months after provision of a CI. Results of these bimodal listeners were compared to age-matched, normal hearing controls (NH). The benefit of adding a contralateral hearing aid was calculated in terms of head shadow, binaural summation, binaural squelch, and spatial release from masking from the results of a sentence recognition test. Beyond that, bimodal benefit was estimated from the difference in amplitudes and latencies of the N1, P2, and N2 potentials of the brains’ auditory evoked response (AEP) toward speech. Data of fifteen participants contributed to the results. CI provision resulted in significant improvement of speech recognition with the CI ear, and in taking advantage of the head shadow effect for understanding speech in noise. Some amount of binaural processing was suggested by a positive binaural summation effect 6 month post-implantation that correlated significantly with symmetry of pure tone thresholds. Moreover, a significant negative correlation existed between binaural summation and latency of the P2 potential. With CI experience, morphology of the N1 and P2 potentials in the AEP response approximated that of NH, whereas, N2 remained different. Significant AEP differences between monaural and binaural processing were shown for NH and for bimodal listeners 6 month post-implantation. Although the grand-averaged difference in N1 amplitude between monaural and binaural listening was similar for NH and the bimodal group, source localization showed group-dependent differences in auditory and speech-relevant cortex, suggesting different processing in the bimodal listeners.

Self-assessment of unilateral and bimodal cochlear implant experiences in daily life.

The subjective experiences were assessed of cochlear implant (CI) users either wearing or not wearing a hearing aid (HA) at the contralateral ear. Unilateral CI-recipients were asked to fill out a set of daily-life questionnaires on bimodal HA use, hearing disability, hearing handicap and general quality of life. Twenty-six CI-recipients who regularly use a contralateral HA (bimodal group) and twenty-two CI-recipients who do not use a HA in the contralateral ear (unilateral group). Comparisons between both groups (bimodal versus unilateral) showed no difference in self-rated disability, hearing handicap or general quality of life. However within the group of bimodal listeners, participants did report a benefit of bimodal hearing ability in various daily life listening situations. Bimodal benefit in daily life can consistently be experienced and reported within the group of bimodal users.

Reading Fluency in Young Elementary School Age Deaf and Hard-of-Hearing Children.

The Center on Literacy and Deafness examined the language and reading progress of 336 young deaf and hard-of-hearing children in kindergarten, first and second grades on a series of tests of language, reading, and spoken and fingerspelled phonological awareness in the fall and spring of the school year. Children were divided into groups based on their auditory access and classroom communication: a spoken-only group (n = 101), a sign-only group (n = 131), and a bimodal group (n = 104). Previous work reports the overall data (Antia, S., Lederberg, A., Schick, B., Branum-Martin, L., Connor, C. M., & Webb, M. (2020a). Language and reading progress of young DHH children. Journal of Deaf Studies and Deaf Education, (3), 25; Lederberg, A. R., Branum-Martin, L., Webb, M. L., Schick, B., Antia, S., Easterbrooks, S. R., & Connor, C. M. (2019). Modality and interrelations among language, reading, spoken phonological awareness, and fingerspelling. Journal of Deaf Studies and Deaf Education, 24(4), 408-423). This report presents an in-depth look at the reading fluency of the participants measured along multiple dimensions. In general, 43% of the participants were unable to read fluently and an additional 23% were unable to read fluently at grade level. Rate and accuracy, rate of growth, miscue analysis, and self-corrections differed by communication modality. Most notably, children demonstrated limited strategies for self-correction during reading fluency tasks.

Abstract 4449: Plinabulin, a microtubule destabilizing agent, improves tumor control by enhancing dendritic cell maturation and CD8 T cell infiltration in combination with immunoradiotherapy

Abstract There are theoretical benefits of combining immune checkpoint blockade with radiotherapy, however, there are few indications that such combinations have translated to significant clinical benefit to patients. There is an unmet need to further enhance the effectiveness of these “immunoradiotherapy” combinations. We hypothesize that enhancing antigen presentation through augmenting dendritic cell (DC) activation could potentially improve the effectiveness of immunoradiotherapy. Towards this end, we have investigated the potential for combining the microtubule destabilizing first-in-class agent Plinabulin as the candidate DC activator, with radiotherapy and anti-PD1 immunotherapy (αPD1). First, we investigated how DCs could be affected by Plinabulin and irradiation in in vitro assays. We irradiated SP37A3 and XS106 DC lines with 10Gy and added Plinabulin to those cells. With the addition of Plinabulin, the phosphorylation of JNK and NFκB was upregulated and DC maturation was promoted with high MHC-II, CD86, CD80 and CD40 surface expressions (p&amp;lt;0.05, Dunnett's test). Combining Plinabulin and radiotherapy further augmented the response, particularly in sequence with plinabulin but not in combination. In in vivo models. TSA syngeneic breast cancer cells were implanted to the flank of BALB/c mice, irradiated with 24Gy/3fr, and treated with αPD1 and Plinabulin. There were no anti-tumoral effects with αPD1 alone, Plinabulin alone, and αPD1+Plinabulin groups. However, triple therapy showed much stronger tumor regression than the double therapy of irradiation and αPD1. Tumors were collected from the mice at 2.5-3 weeks after the irradiation and dissociated tumor cells were analyzed for DC activation and immune repertoire using flow cytometry. The percentage of CD8 T cells and CD86+ DCs in the tumor were significantly increased in the triple therapy group that were not seen for the monotherapy or bimodal therapy groups (p&amp;lt;0.05, Dunnett's test). Our findings may serve as a rationale for establishing clinical trial designs of synergistic combinational approaches to enhance immunoradiotherapy. Citation Format: Shinya Neri. Plinabulin, a microtubule destabilizing agent, improves tumor control by enhancing dendritic cell maturation and CD8 T cell infiltration in combination with immunoradiotherapy [abstract]. In: Proceedings of the Annual Meeting of the American Association for Cancer Research 2020; 2020 Apr 27-28 and Jun 22-24. Philadelphia (PA): AACR; Cancer Res 2020;80(16 Suppl):Abstract nr 4449.