CTNNB1 and APC Mutations in Sinonasal Myxoma : Expanding the Spectrum of Tumors Driven By WNT/ß-catenin Pathway.

Sinonasal myxoma (SNM) is a rare, benign mesenchymal neoplasm with distinct clinicopathologic features and aberrant nuclear localization of ß-catenin by immunohistochemistry. The molecular underpinnings have been linked to that of a "myxoid variant" of desmoid fibromatosis. Herein, we describe a series of 8 cases of SNM and propose clinical and biologic differences compared with desmoid fibromatosis. Our patient cohort is comprised of 5 males and 3 females (age range: 10 mo to 12 y), 6 of whom are aged less than or equal to 24 months. All presented with facial swelling, reflecting lesions involving the maxillary bone, and all underwent resection. All tumors were variably cellular and comprised of bland spindled to stellate cells in a profusely myxoid background with diffuse nuclear ß-catenin expression. All cases of SNM were analyzed by next-generation sequencing using the Oncopanel assay. Three cases failed sequencing, 2 of 5 successful cases exhibited exon 3 CTNNB1 alterations involving the ubiquitin recognition motif, and 3 had adenomatous polyposis coli ( APC ) deletions. One patient had APC germline testing which was negative. No germline testing was available for the remaining 7 patients. Follow-up data over a range of 1 month to 23 years was available for 7 of the 8 SNMs. One case patient had local recurrence, and all were alive without evidence of disease. This is in contrast to the high recurrence rate typically seen in desmoid fibromatosis, particularly after resection. Our findings expand the spectrum of tumors with underlying WNT/ß-catenin pathway and highlight the histologic, clinical, and genetic differences of SNM compared with desmoid fibromatosis. APC deletion raises the possibility of underlying germline alteration and familial adenomatous polyposis.

Reward motivation more consistently modulates memory for younger compared to older adults in a directed forgetting task.

Remembering and forgetting are both important processes of a healthy memory system, but both processes can show age-related decline. Reward anticipation is effective at improving remembering in both younger and older adults, but little is known about the effects of incentives on forgetting. In four online experiments, we examined whether reward motivation modulates intentional remembering and forgetting in younger and older adults, and systematically varied the presentation of reward cues during encoding to test whether the temporal dynamics of reward anticipation are important for directed forgetting performance. Both age groups showed directed forgetting effects such that participants remembered more items they were instructed to remember than instructed to forget, but across experiments, we found no evidence that reward incentives improved forgetting in either age group. Younger adults consistently exhibited reward-modulated memory across experiments and varying the timing of the reward cue had little impact on performance. Older adults displayed inconsistent effects of reward on memory, only when reward anticipation was elicited closer to the middle of the experimental trial did it enhance memory in this task. Overall, the findings from the current set of experiments indicate that reward anticipation improved memory, but not forgetting, and most consistently for younger adults, compared to older adults. Further, older adults' cognitive performance may be more sensitive to the placement and timing of reward anticipation in the experimental trial perhaps due to the time course of reward anticipation and interactions with the hippocampus that may show age-related change. (PsycInfo Database Record (c) 2023 APA, all rights reserved).

Behavioral and fMRI evidence that arousal enhances bottom-up selectivity in young but not older adults.

The locus coeruleus-noradrenergic system integrates signals about arousal states throughout the brain and helps coordinate cognitive selectivity. However, age-related changes in this system may impact how arousal coordinates selectivity in older adults. To examine this, we compared how increases in emotional arousal modulates cognitive selectivity for images differing in perceptual salience in young and older adults. Using functional magnetic resonance imaging, we found that relative to older adults, hearing an arousing sound enhanced young adults' bottom-up processing and incidental memory for high versus low salience category-selective body images. We also examined how arousing sounds impacted a top-down goal to detect dot-probes that appeared immediately after high or low salience images. We found that young adults were slower to detect probes appearing after high salience body images on arousing trials, whereas older adults showed this pattern on non-arousing trials. Taken together, our findings show that arousal's effect on selectivity changes with age and differs across bottom-up and top-down processing.

An integration engineering framework for machine learning in healthcare.

Background and Objectives: Machine Learning offers opportunities to improve patient outcomes, team performance, and reduce healthcare costs. Yet only a small fraction of all Machine Learning models for health care have been successfully integrated into the clinical space. There are no current guidelines for clinical model integration, leading to waste, unnecessary costs, patient harm, and decreases in efficiency when improperly implemented. Systems engineering is widely used in industry to achieve an integrated system of systems through an interprofessional collaborative approach to system design, development, and integration. We propose a framework based on systems engineering to guide the development and integration of Machine Learning models in healthcare. Methods: Applied systems engineering, software engineering and health care Machine Learning software development practices were reviewed and critically appraised to establish an understanding of limitations and challenges within these domains. Principles of systems engineering were used to develop solutions to address the identified problems. The framework was then harmonized with the Machine Learning software development process to create a systems engineering-based Machine Learning software development approach in the healthcare domain. Results: We present an integration framework for healthcare Artificial Intelligence that considers the entirety of this system of systems. Our proposed framework utilizes a combined software and integration engineering approach and consists of four phases: (1) Inception, (2) Preparation, (3) Development, and (4) Integration. During each phase, we present specific elements for consideration in each of the three domains of integration: The Human, The Technical System, and The Environment. There are also elements that are considered in the interactions between these domains. Conclusion: Clinical models are technical systems that need to be integrated into the existing system of systems in health care. A systems engineering approach to integration ensures appropriate elements are considered at each stage of model design to facilitate model integration. Our proposed framework is based on principles of systems engineering and can serve as a guide for model development, increasing the likelihood of successful Machine Learning translation and integration.

Retracted: The Effect of Bilingualism on Older Adults' Inhibitory Control: A Meta-Analysis.

BACKGROUND AND OBJECTIVES: The effect bilingualism has on older adults' inhibitory control has been extensively investigated, yet there is continued controversy regarding whether older adult bilinguals show superior inhibitory control compared with monolinguals. The objective of the current meta-analysis was to examine the reliability and magnitude of the bilingualism effect on older adults' inhibitory control as measured by the Simon and Stroop tasks. In addition, we examined whether individual characteristics moderate the bilingual advantage in inhibition, including age (young-old vs old-old), age of second language acquisition, immigrant status, language proficiency, and frequency of language use. RESEARCH DESIGN AND METHODS: A total of 22 samples for the Simon task and 14 samples for the Stroop task were derived from 28 published and unpublished articles (32 independent samples, with 4 of these samples using more than 1 task) and were analyzed in 2 separate meta-analyses. RESULTS: Analyses revealed a reliable effect of bilingualism on older adults' performance on the Simon (g = 0.60) and Stroop (g = 0.27) tasks. Interestingly, individual characteristics did not moderate the association between bilingualism and older adults' inhibitory control. DISCUSSION AND IMPLICATIONS: The results suggest there is a bilingual advantage in inhibitory control for older bilinguals compared with older monolinguals, regardless of the individual characteristics previously thought to moderate this effect. Based on these findings, bilingualism may protect inhibitory control from normal cognitive decline with age.

Adverse events in pediatric cochlear implant patients undergoing magnetic resonance imaging.

OBJECTIVE: To investigate the prevalence and nature of adverse events in magnetic resonance imaging (MRI) of pediatric cochlear implant (CI) patients. METHODS: Retrospective chart review at a tertiary pediatric hospital. CI patients who underwent MRI from 2004 through 2019 were identified via our internal radiology database. Comorbidities, CI model, age at MRI, number of MRIs, type of MRIs, indication for MRIs, precautions taken for MRIs, quality of MRIs, anesthesia during MRIs, patient language abilities, and adverse events were recorded from the electronic medical record. The literature was reviewed, and our results were compared to those of previous similar series. RESULTS: From 2004 to 2019, 12 pediatric patients (17 ears) with CIs underwent 22 MRIs. 12 MRIs were performed in CI patients with retained internal magnet. 4/22 MRIs resulted in morbidity; 2 patients experienced pain requiring MRI abortion, 1 experienced magnet rotation requiring surgical replacement, and 1 underwent operative removal of the magnet prior to the scan with surgical replacement thereafter. 19/22 MRIs were performed to evaluate the brain; 17/22 of the radiologic reports noted limitation of evaluation due to artifact. 18/22 MRIs required the administration of anesthesia. 9 of the 22 MRI events involved 2 patients whose CIs had been without internal magnet in anticipation of future MRI requirement. CONCLUSIONS: Adverse events affecting pediatric patients with CI can occur as a result of MRI, despite appropriate precautions. Safety requires consideration of factors unique to a pediatric hearing-impaired population. Clinicians must remain informed on best practices and manufacturer recommendations.

Contemporary Management of Vascular Anomalies of the Head and Neck-Part 1: Vascular Malformations: A Review.

Importance: Vascular anomalies of the head and neck are relatively rare lesions. Management is challenging because of the high likelihood of involvement of functionally critical structures. Multiple modalities of treatment exist for vascular anomalies of the head and neck, including medical therapies, sclerotherapy and embolization procedures, and surgery. This review focuses on the accurate diagnosis and the relative roles of the various therapeutic options. Observations: Vascular anomalies are classified by the International Society for the Study of Vascular Anomalies into 2 major groups: vascular tumors and vascular malformations. Vascular tumors encompass proliferative lesions ranging from infantile and congenital hemangiomas to kaposiform hemangioendothelioma. Alternatively, vascular malformations are embryologic errors in vasculogenesis. This article focuses on the management of vascular malformations. The 3 primary vascular malformation subclassifications are lymphatic, venous, and arteriovenous. The burden of disease, diagnosis, and current management options are discussed in detail for each subtype. Conclusions and Relevance: Most vascular malformations of the head and neck require a multidisciplinary approach. Available medical, interventional radiologic, and surgical interventions are constantly evolving. Optimization of function and cosmesis must be balanced with minimization of treatment-associated morbidity. Otolaryngologists-head and neck surgeons must remain up to date regarding options for diagnosis and management of these lesions.

Cognitive and Psychosocial Outcomes of Self-Guided Executive Function Training and Low-Intensity Aerobic Exercise in Healthy Older Adults.

OBJECTIVES: Prior work has demonstrated that executive function training or physical exercise can improve older adults' cognition. The current study takes an exploratory approach to compare the feasibility and efficacy of online executive function training and low-intensity aerobic exercise for improving cognitive and psychosocial functioning in healthy older adults. METHOD: Following a standard pretest-training-posttest protocol, 40 older adults (aged 65 and above) were randomly assigned to an executive function or a physical training group. A battery of cognitive and psychosocial outcome measures were administered before and after training. During the 10 weeks of self-guided training at home (25-30 min/day, 4 days/week), the executive function training group practiced a set of adaptive online executive function tasks designed by Lumos Labs, whereas the physical training group completed an adaptive Digital Video Disc (DVD)-based low-intensity aerobic exercise program. RESULTS: Training transfer effects were limited. Relative to low-intensity aerobic exercise, executive function training yielded cognitive improvement on the 64-card Wisconsin Card Sorting Task (WCST-64), a general executive function measure. Depression and stress levels dropped following both training programs, but this could be driven by decreased stress or excitement in performing the tasks over time. DISCUSSION: The results revealed limited cognitive benefits of the online executive function training program, specifically to a near transfer test of general executive control. Importantly, the current study supports the feasibility of home-based self-guided executive function and low-intensity physical training with healthy older adults.

Influence of Reward Motivation on Directed Forgetting in Younger and Older Adults.

An important feature of the memory system is the ability to forget, but aging is associated with declines in the ability to intentionally forget potentially due to declines in cognitive control. Despite cognitive deficits, older adults are sensitive to affective manipulations, such as reward motivation, and reward anticipation can improve older adults' memory performance. The goal of the current studies was to examine the effect of reward motivation on directed remembering and forgetting. Participants were healthy CloudResearch/Turk Prime workers aged 18-35 and 60-85. In Experiment 1, we conducted a typical item-method directed forgetting task using neutral words presented one at a time followed by a to-be-remembered (TBR) or to-be-forgotten (TBF) cue. A recognition memory test followed that included all words from the encoding task, as well as new words. We replicated prior findings of better memory for TBR compared to TBF items, but not typical age-related differences in recognition of TBF items. In Experiments 2-4, we repeated this paradigm except that in the second block of trials, each word was presented with a high ($0.75) or low ($0.01) reward cue indicating the value that could be earned if the item was successfully Remembered or Forgotten (depending on cue). During recognition, correct responses to target items (both TBR and TBF) resulted in the associated reward, but incorrect "old" responses resulted in a loss of $0.50. In three experiments, high rewards led to better memory for younger and older adults compared to low rewards, regardless of the directed cue to remember or forget the word. In Experiments 3 and 4, older adults showed typical deficits in directed forgetting, but this was across reward conditions. For older adults, there was no evidence that including reward motivation improved cognitive control abilities as high value reward anticipation did not improve directed forgetting. Instead, in line with hypotheses, high compared to low value reward anticipation leads to engagement of processes that result in better memory regardless of the TBR or TBF cue, and reward anticipation bolsters memory in a relatively automatic, rather than strategic, fashion that overrides one's ability to cognitively control encoding processes.

Age differences in vulnerability to distraction under arousal.

Aging affects brain circuitry involved in both inhibition and arousal. In this study, we tested whether older adults are more or less prone to distraction from emotionally arousing events than young adults. To do so, we examined how arousing taboo distractor words affected concurrent 1-back task performance and subsequent memory for distractors. Our second goal was to examine how the arousal level of 1 item can modulate processing of preceding neutral distractors (taboo-minus-1 distractors). During the task, participants first made 1-back judgments about target pictures that were superimposed with to-be-ignored neutral or taboo distractors. Relative to young adults, older adults were more distracted by taboo than neutral words on the 1-back task and remembered more of the taboo distractors on a later incidental recognition task. Furthermore, young adults showed better suppression of taboo-minus-1 distractors than neutral distractors, whereas in older adults, arousal did not facilitate suppression of taboo-minus-1 distractors. This effect appeared to require attentional control as adding an unrelated attentional load during the 1-back task eliminated the beneficial effect of arousal for young adults' suppression of taboo-minus-1 distractors. Finally, when top-down attentional guidance was provided by increasing the goal relevance of target pictures, both groups showed enhanced suppression of taboo-minus-1 distractors versus other neutral distractors. Together, these findings imply that the effect of arousal on distractibility in aging may arise from an interaction between top-down and bottom-up processes. (PsycInfo Database Record (c) 2020 APA, all rights reserved).

The effect of emotional distraction on hyper-binding in young and older adults.

Our cognitive system implicitly binds relevant stimulus features into a coherent episodic event. According to past research, relative to young adults, older adults are more likely to hyper-bind extraneous co-occurrences and tend to prioritise positive over negative information. However, the interaction of these cognitive and emotional processes is unknown. The current study thus examined the influence of emotion on age-related hyper-binding. Participants completed a 1-back task for neutral target pictures paired with positive, negative, or neutral distractor words. After a delay, participants completed a paired-associate learning task for pairs that were either preserved or disrupted from the 1-back task, followed by a cued-recall test for those pairs. Compared to young adults, older adults showed better recall of preserved neutral pairs relative to disrupted neutral pairs, replicating the age-related hyper-binding effect. Interestingly, whereas older adults did not hyper-bind emotional pairs, young adults showed hyper-binding of negative pairs, but not positive or neutral. This implies that young adults may also implicitly bind irrelevant co-occurrences when they include negative information. Consistent with a negativity bias in youth, negative words may have captured young adults' attention, facilitating binding of pairs. These findings highlight the need to consider emotional effects on age differences in cognitive processing.

Age differences in cue utilization during prospective and retrospective memory monitoring.

Memory monitoring is an inferential process that we use to evaluate and make judgments about the contents of our memory. Prior work has shown age-related similarity in prospective monitoring of ongoing memory processes, but age-related deficits when retrospectively monitoring the source of memories. In the current study, we examined how extrinsic and intrinsic cues influence age differences in these 2 forms of memory monitoring. Two experiments were conducted in which young and older adults made prospective judgments of learning (JOLs) to monitor ongoing memory processes as well as retrospective source judgments during retrieval. The emotional valence of words (positive, negative, and neutral) served as an intrinsic cue across experiments. Extrinsic importance cues were manipulated via item-based directed forgetting cues (to-be-remembered versus to-be-forgotten cues) in Experiment 1 and value-based cues (+10 versus -10 cues) in Experiment 2. Results provide novel evidence for age-related similarity in use of extrinsic and intrinsic cues during prospective memory monitoring via JOLs. By contrast, during retrospective source monitoring, older but not young adults showed a bias to attribute positive items to extrinsic cues with higher importance, even when those attributions were inaccurate. These findings suggest that the age-related tendency to favor positive information may lead to systematic errors in retrospective monitoring, which has implications for the credibility of older adults' source judgments when monitoring memory for emotional events. (PsycINFO Database Record (c) 2019 APA, all rights reserved).

Comparison of Skull Radiograph and Computed Tomography Measurements of Cochlear Implant Insertion Angles.

BACKGROUND: Measurement of the angular depth of insertion (aDOI) of cochlear implant electrode arrays has numerous clinical and research applications. Plain-film radiographs are easily obtained intraoperatively and have been described as a means to calculate aDOI. CT imaging with 3D reformatting can also be used for this measurement, but is less conveniently obtained and requires higher radiation doses, a particular concern in pediatrics. The extent to which plain-film and 3D CT image-based measurements are representative of the true position of the electrode within the cochlea is unknown. METHODS: Cochlear implantation was performed on 10 cadaveric temporal bones. Five bones were implanted with perimodiolar electrodes (Contour Advance TM, Cochlear, Sydney, Australia) and five were implanted with lateral wall electrodes (Slim Straight, Cochlear). The insertion depths of the electrodes were varied. Each bone was imaged with a radiograph and CT. aDOI was measured for each bone in each imaging modality by a neurotologist and a neuroradiologist. To obtain a 'gold standard' estimate of aDOI, the implanted temporal bones were embedded in an epoxy resin and methodically sectioned at 100 µm intervals; histologic images were captured at each interval. A 3D stack of the images was compounded, and a MATLAB script used to calculate aDOI of the most apical electrode. Measurements in the three modalities (radiograph, CT, and histology) were then compared. RESULTS: The average aDOI across all bones was similar for all modalities: 423° for radiographs, 425° for CT scans, and 427° for histology, indicating that neither imaging modality resulted in large systematic errors. Using the histology-measured angles as a reference, the average error for CT-based measures (regardless of whether the error was in the positive or negative direction) was 12°, and that for radiograph-based measures was 15°. This small difference (12 vs 15° error) was not statistically significant. CONCLUSION: Based on this cadaveric temporal bone model, both radiographs and CTs can provide reasonably accurate aDOI measurements. In this small sample, and as expected, the CT-based estimates were more accurate than the radiograph-based measurements. However, the difference was small and not statistically significant. Thus, the use of plain radiographs to calculate aDOI seems judicious whenever it is desired to prevent unnecessary radiation exposure and expense.

Age differences in the neural correlates underlying control of emotional memory: An event-related potential study.

The ability to selectively remember important information and forget irrelevant details is fundamental to successful memory. Research has shown that both younger and older adults can intentionally remember and forget information varying in emotional valence; however, whether the neural correlates of these processes change with age is unknown. In this event-related potential (ERP) study, we sought to fill this knowledge gap using the item-directed forgetting (DF) task. Younger and older adults encoded positive, negative, or neutral words that were cued as either to-be-remembered (TBR) or to-be-forgotten (TBF), while brain activity was recorded with electroencephalography (EEG). Behaviorally, both age groups showed DF effects, although the magnitude of DF was reduced in older adults. Moreover, DF was not influenced by the emotional valence of words in either age group. In the brain, age differences emerged across both word- and cue-related ERPs. Whereas the late positive potential (LPP) was greater for negative than positive words in younger adults, older adults showed a reduced LPP for negative versus positive items. In response to memory cues, younger adults' ERPs showed enhanced parietal and frontal positivity following TBR and TBF cues, respectively. In contrast, older adults displayed greater frontal activity while encoding TBR items than younger adults but age invariance in parietal ERPs following TBR cues. Together, these findings suggest that both younger and older adults are able to intentionally forget information that varies in emotional valence but that the neural mechanisms underlying these processes may change with age.

Validity of the Hum Test, a Simple and Reliable Alternative to the Weber Test.

OBJECTIVES: To compare the diagnostic performance of the Hum Test against the Weber Test using pure tone audiometry (PTA) as the "gold standard" comparator. METHODS: 29 participants with normal hearing of ages 18 to 35 without any history of hearing abnormalities or otologic conditions were enrolled. Subjects underwent three tests (Hum Test, Weber Test, and PTA) across two conditions: with an ear plug in one ear (side randomized) and without ear plugs. RESULTS: When examining the ability of the Hum Test to detect simulated conductive hearing loss (CHL), the test had a sensitivity of 89.7% and specificity of 100% with high pitched humming and 93.1% and 100%, respectively, with low pitched humming. The Weber Test had a sensitivity and specificity of 96.6% and 100%, respectively. McNemar's test demonstrated agreement between the Hum Test, performed with either high pitched ( P = .32) or low pitched ( P = .56) humming, and the Weber Test. Receiver operating characteristic (ROC) curves for the Hum Test (both high and low pitched) and Weber test were compared and demonstrated no statistically significant difference. CONCLUSION: The Hum Test is comparable to the Weber Test with regards to its sensitivity, specificity, and diagnostic accuracy in assessing new onset unilateral CHL in previously normal hearing subjects.