MRI Scoring Systems for Predicting Isocitrate Dehydrogenase Mutation and Chromosome 1p/19q Codeletion in Adult-type Diffuse Glioma Lacking Contrast Enhancement.

Background According to 2021 World Health Organization criteria, adult-type diffuse gliomas include glioblastoma, isocitrate dehydrogenase (IDH)-wildtype; oligodendroglioma, IDH-mutant and 1p/19q-codeleted; and astrocytoma, IDH-mutant, even when contrast enhancement is lacking. Purpose To develop and validate simple scoring systems for predicting IDH and subsequent 1p/19q codeletion status in gliomas without contrast enhancement using standard clinical MRI sequences. Materials and Methods This retrospective study included adult-type diffuse gliomas lacking contrast at contrast-enhanced MRI from two tertiary referral hospitals between January 2012 and April 2022 with diagnoses confirmed at pathology. IDH status was predicted primarily by using T2-fluid-attenuated inversion recovery (FLAIR) mismatch sign, followed by 1p/19q codeletion prediction. A visual rating of MRI features, apparent diffusion coefficient (ADC) ratio, and relative cerebral blood volume was measured. Scoring systems were developed through univariable and multivariable logistic regressions and underwent calibration and discrimination, including internal and external validation. Results For the internal validation cohort, 237 patients were included (mean age, 44.4 years ± 14.4 [SD]; 136 male patients; 193 patients in IDH prediction and 163 patients in 1p/19q prediction). For the external validation cohort, 35 patients were included (46.1 years ± 15.3; 20 male patients; 28 patients in IDH prediction and 24 patients in 1p/19q prediction). The T2-FLAIR mismatch sign demonstrated 100% specificity and 100% positive predictive value for IDH mutation. IDH status prediction scoring system for tumors without mismatch sign included age, ADC ratio, and morphologic characteristics, whereas 1p/19q codeletion prediction for IDH-mutant gliomas included ADC ratio, cortical involvement, and mismatch sign. For IDH status and 1p/19q codeletion prediction, bootstrap-corrected areas under the receiver operating characteristic curve were 0.86 (95% CI: 0.81, 0.90) and 0.73 (95% CI: 0.65, 0.81), respectively, whereas at external validation they were 0.99 (95% CI: 0.98, 1.0) and 0.88 (95% CI: 0.63, 1.0). Conclusion The T2-FLAIR mismatch sign and scoring systems using standard clinical MRI predicted IDH and 1p/19q codeletion status in gliomas lacking contrast enhancement. © RSNA, 2024 Supplemental material is available for this article. See also the editorial by Badve and Hodges in this issue.

Interpersonal sensitivity predicts slower change and less change in anxiety symptoms in cognitive behavioural therapy.

OBJECTIVES: Patients in cognitive behavioural therapy (CBT) who are high in interpersonal sensitivity may have difficulty fully engaging in treatment because therapy sessions require intimate interpersonal interactions that are especially uncomfortable for these individuals. The current study tests the hypotheses that patients who are high in interpersonal sensitivity benefit less from CBT for symptoms of depression and anxiety, show a slower rate of change in those symptoms, and are more likely to drop out of treatment. METHODS: Participants were 832 outpatients who received naturalistic CBT. We assessed interpersonal sensitivity before treatment began and depression and anxiety symptoms at every therapy session. We assessed early, premature, and uncollaborative termination after treatment ended. We constructed multilevel linear regression models and logistic regression models to assess the effects of baseline interpersonal sensitivity on the treatment outcome, the slope of change in depression and anxiety symptoms, and each type of dropout. RESULTS: Higher baseline interpersonal sensitivity was associated with a slower rate of change and less overall change in anxiety but not depressive symptoms. Baseline interpersonal sensitivity was not a predictor of dropout. CONCLUSIONS: Interpersonal sensitivity at baseline predicts less change and a slower rate of change in anxiety symptoms. Early detection of elevated interpersonal sensitivity can help therapists take action to address these barriers to successful treatment and help scientists build decision support tools that accurately predict the trajectory of change in anxiety symptoms for these patients.

HER3 overexpression: a predictive marker for poor prognosis in advanced ALK-positive non-small cell lung cancer treated with ALK inhibitors.

Background: Anaplastic lymphoma kinase (ALK)-targeted tyrosine kinase inhibitors (TKIs) improve patient survival; however, some patients develop ALK-TKI resistance with unidentified mechanisms. We investigated ErbB family and c-MET expression in patients with ALK-positive non-small cell lung cancer (NSCLC) to understand their roles in the ALK-TKI response. Methods: We studied 72 patients with advanced ALK-positive NSCLC with EML4-ALK fusion variant subtyping and immunostaining for c-MET, EGFR, HER2, and HER3 on tissue specimens both pre- (primary) and post-treatment (secondary) with ALK-TKI. We investigated the association of their expression with survival outcomes and assessed the effectiveness of combining ALK and EGFR inhibitors in ALK-positive NSCLC cell lines stimulated with the HER3-specific ligand HRG1. Results: High expression of c-MET, EGFR, HER2, and HER3 was observed in 4.9%, 18.0%, 1.6%, and 25.8% of primary tumors, respectively, and 18.5%, 37.0%, 10.7%, and 35.7% of secondary tumors, respectively. HER3 overexpression in primary tumors showed inferior survival (P=0.132). In the subgroup with EML4-ALK variant 1/2 (V1/V2), HER3 overexpression was significantly associated with inferior survival in both primary and secondary tumors (P=0.022 and P=0.004, respectively). Combination treatment with lorlatinib and erlotinib significantly reduced HRG1-induced activation of RTK signaling in ALK-positive NSCLC cells. Conclusions: HER3 overexpression has potential as a prognostic marker in ALK-positive NSCLCs, including ALK-TKI naïve and treated cases, especially those with EML4-ALK V1/V2. Assessing HER3 expression may be crucial for treatment planning and outcome prediction in these patients.

Understanding organotropism in cancer metastasis using microphysiological systems.

Cancer metastasis, the leading cause of cancer-related deaths, remains a complex challenge in medical science. Stephen Paget's "seed and soil theory" introduced the concept of organotropism, suggesting that metastatic success depends on specific organ microenvironments. Understanding organotropism not only offers potential for curbing metastasis but also novel treatment strategies. Microphysiological systems (MPS), especially organ-on-a-chip models, have emerged as transformative tools in this quest. These systems, blending microfluidics, biology, and engineering, grant precise control over cell interactions within organ-specific microenvironments. MPS enable real-time monitoring, morphological analysis, and protein quantification, enhancing our comprehension of cancer dynamics, including tumor migration, vascularization, and pre-metastatic niches. In this review, we explore innovative applications of MPS in investigating cancer metastasis, particularly focusing on organotropism. This interdisciplinary approach converges the field of science, engineering, and medicine, thereby illuminating a path toward groundbreaking discoveries in cancer research.

c-MET-positive circulating tumor cells and cell-free DNA as independent prognostic factors in hormone receptor-positive/HER2-negative metastatic breast cancer.

BACKGROUND: Endocrine therapy resistance in hormone receptor-positive/HER2-negative (HR+/HER2-) breast cancer (BC) is a significant clinical challenge that poses several unmet needs in the management of the disease. This study aimed to investigate the prognostic value of c-MET-positive circulating tumor cells (cMET+ CTCs), ESR1/PIK3CA mutations, and cell-free DNA (cfDNA) concentrations in patients with hormone receptor-positive (HR+) metastatic breast cancer (mBC). METHODS: Ninety-seven patients with HR+ mBC were prospectively enrolled during standard treatment at Samsung Medical Center. CTCs were isolated from blood using GenoCTC® and EpCAM or c-MET CTC isolation kits. PIK3CA and ESR1 hotspot mutations were analyzed using droplet digital PCR. CfDNA concentrations were calculated using internal control copies from the ESR1 mutation test. Immunocytochemistry was performed to compare c-MET overexpression between primary and metastatic sites. RESULTS: The proportion of c-MET overexpression was significantly higher in metastatic sites than in primary sites (p = 0.00002). Survival analysis showed that c-MET+ CTC, cfDNA concentration, and ESR1 mutations were significantly associated with poor prognosis (p = 0.0026, 0.0021, and 0.0064, respectively) in HR+/HER2- mBC. By contrast, EpCAM-positive CTC (EpCAM+ CTC) and PIK3CA mutations were not associated with progression-free survival (PFS) in HR+/HER2- mBC. Multivariate analyses revealed that c-MET+ CTCs and cfDNA concentration were independent predictors of PFS in HR+/HER2- mBC. CONCLUSIONS: Monitoring c-MET+ CTC, rather than assessing c-MET expression in the primary BC site, could provide valuable information for predicting disease progression, as c-MET expression can change during treatment. The c-MET+ CTC count and cfDNA concentration could provide complementary information on disease progression in HR+ /HER2- mBC, highlighting the importance of integrated liquid biopsy.

Development of polysaccharide-complexed nano-sized rice protein dispersion.

The objective of this study was to improve water solubility of the rice protein (RP) by forming complexes with anionic polysaccharides, such as sodium alginate (SA) and xanthan gum (XG). In addition, utilization of the RP complexes as an emulsifier was evaluated. The prepared RP-SA or RP-XG complexes were analyzed by measuring their particle size, ζ-potential, and water solubility as well as by confocal laser scanning microscopy. The formation of a complex between RP-SA and RP-XG improved the water solubility and dispersibility of RP over a wide range of pH values (3, 5, 7, and 9). Confocal fluorescence images showed that the aggregation of RP molecules was prevented by the formation of complexes between RP and polysaccharides. When soybean oil-in-water emulsions were prepared with complexes, RP-SA (ratio 4:1) and RP-XG(ratio 4:1) complex-stabilized emulsions were stable for 4 weeks of storage.

Patient-Derived Microphysiological Systems for Precision Medicine.

Patient-derived microphysiological systems (P-MPS) have emerged as powerful tools in precision medicine that provide valuable insight into individual patient characteristics. This review discusses the development of P-MPS as an integration of patient-derived samples, including patient-derived cells, organoids, and induced pluripotent stem cells, into well-defined MPSs. Emphasizing the necessity of P-MPS development, its significance as a nonclinical assessment approach that bridges the gap between traditional in vitro models and clinical outcomes is highlighted. Additionally, guidance is provided for engineering approaches to develop microfluidic devices and high-content analysis for P-MPSs, enabling high biological relevance and high-throughput experimentation. The practical implications of the P-MPS are further examined by exploring the clinically relevant outcomes obtained from various types of patient-derived samples. The construction and analysis of these diverse samples within the P-MPS have resulted in physiologically relevant data, paving the way for the development of personalized treatment strategies. This study describes the significance of the P-MPS in precision medicine, as well as its unique capacity to offer valuable insights into individual patient characteristics.

Bedtime regularity predicts positive affect among veterans with posttraumatic stress disorder: an ecological momentary assessment study.

BACKGROUND: Regularizing bedtime and out-of-bed times is a core component of behavioral treatments for sleep disturbances common among patients with posttraumatic stress disorder (PTSD). Although improvements in subjective sleep complaints often accompany improvements in PTSD symptoms, the underlying mechanism for this relationship remains unclear. Given that night-to-night sleep variability is a predictor of physical and mental well-being, the present study sought to evaluate the effects of bedtime and out-of-bed time variability on daytime affect and explore the optimal window lengths of over which variability is calculated. METHODS: For about 30 days, male U.S. military veterans with PTSD (N = 64) in a residential treatment program provided ecological momentary assessment data on their affect and slept on beds equipped with mattress actigraphy. We computed bedtime and out-of-bed time variability indices with varying windows of days. We then constructed multilevel models to account for the nested structure of our data and evaluate the impact of bedtime and out-of-bed time variability on daytime affect. RESULTS: More regular bedtime across 6-9 days was associated with greater subsequent positive affect. No similar effects were observed between out-of-bed time variability and affect. CONCLUSIONS: Multiple facets of sleep have been shown to differently predict daily affect, and bedtime regularity might represent one of such indices associated with positive, but not negative, affect. A better understanding of such differential effects of facets of sleep on affect will help further elucidate the complex and intertwined relationship between sleep and psychopathology. TRIAL REGISTRATION: The trial retrospectively was registered on the Defense Technical Information Center website: Award # W81XWH-15-2-0005.

Color-Tuning Mechanism of the Lit Form of Orange Carotenoid Protein.

Orange carotenoid protein (OCP) of photosynthetic cyanobacteria binds to ketocarotenoids noncovalently and absorbs excess light to protect the host organism from light-induced oxidative damage. Herein, we found that mutating valine 40 in the α3 helix of Gloeocapsa sp. PCC 7513 (GlOCP1) resulted in blue- or red-shifts of 6-20 nm in the absorption maxima of the lit forms. We analyzed the origins of absorption maxima shifts by integrating X-ray crystallography, homology modeling, molecular dynamics simulations, and hybrid quantum mechanics/molecular mechanics calculations. Our analysis suggested that the single residue mutations alter the polar environment surrounding the bound canthaxanthin, thereby modulating the degree of charge transfer in the photoexcited state of the chromophore. Our integrated investigations reveal the mechanism of color adaptation specific to OCPs and suggest a design principle for color-specific photoswitches.

Awareness and related factors of depressive symptoms in breastfeeding people in South Korea: a survey-based cross-sectional study.

OBJECTIVES: This study identifies depressive symptoms and the factors that could explain its presence in breastfeeding people. DESIGN: This study is a cross-sectional study from national survey data. SETTING AND PARTICIPANTS: Data were derived from the 2019 Korean Community Health Survey. The study subjects were breastfeeding people under the age of 50. PRIMARY OUTCOME MEASURES: Depressive symptoms in breastfeeding people were classified according to the Patient Health Questionnaire-9 (PHQ-9) score. Physical and health behaviours were considered as factors related to depressive symptoms. A multilevel logistic regression analysis was used. RESULTS: Among 497 participants, 19.4% (n=97) of breastfeeding people were depressed. We found that depressive symptoms were associated with age (31-35, OR: 0.79, 95% CI: 0.67 to 0.94; 35-49, OR: 0.42, 95% CI: 0.32 to 0.56), rural setting (OR: 0.62, 95% CI: 0.51 to 0.76), economic activity (OR: 0.75, 95% CI: 0.61 to 0.91) and physical health (diabetus mellitus or hypertension, OR: 5.17, 95% CI: 3.78 to 7.06). CONCLUSIONS: This study implies that socioeconomic factors, physical health and health behaviours may influence depressive symptoms in breastfeeding people. These findings should be used as descriptive data to support the development of education programmes to help breastfeeding people.

Sleep Quality Moderates the Relationship Between Daily Mean Levels and Variability of Positive Affect.

Despite the well-established bidirectional association between sleep and daytime affect, most studies examining this relationship have focused on mean levels of affect. However, research solely focusing on mean levels of affect inherently neglects variability in affect, which has been shown to predict both psychological and physical well-being beyond mean levels. The present study assessed sleep quality and daytime affect using ecological momentary assessment in a combined sample of individuals (N = 80; 8,881 observations) with and without anxiety and mood disorders. Results from the present study partially replicated extant work on the negative association between negative affect (NA) variability and subsequent sleep quality. Furthermore, less satisfying sleep amplified the positive relationship between daily mean levels and variability of positive affect (PA). The results did not differ by clinical status. The present study offers novel evidence suggesting that previous night's sleep quality influences the stability of varying daily levels of PA. Uncovering the dynamics of sleep and affect beyond mean levels will help further elucidate mechanisms linking sleep and subsequent affective experiences.

Comparing Message-Based Psychotherapy to Once-Weekly, Video-Based Psychotherapy for Moderate Depression: Randomized Controlled Trial.

BACKGROUND: Despite the high prevalence of major depressive disorder and the related societal burden, access to effective traditional face-to-face or video-based psychotherapy is a challenge. An alternative that offers mental health care in a flexible setting is asynchronous messaging therapy. To date, no study has evaluated its efficacy and acceptability in a randomized controlled trial for depression. OBJECTIVE: The aim of this study was to compare the efficacy and acceptability of message-based psychotherapy for depression to once-weekly video-based psychotherapy. METHODS: In this 2-armed randomized controlled trial, individuals (N=83) with depressive symptomatology (Patient Health Questionnaire-9 ≥10) were recruited on the internet and randomly assigned to either a message-based intervention group (n=46) or a once-weekly video-based intervention group (n=37). Patients in the message-based treatment condition exchanged asynchronous messages with their therapist following an agreed-upon schedule. Patients in the video-based treatment condition met with their therapist once each week for a 45-minute video teletherapy session. Self-report data for depression, anxiety, and functional impairment were collected at pretreatment, weekly during treatment, at posttreatment, and at a 6-month follow-up. Self-reported treatment expectancy and credibility for the assigned intervention were assessed at pretreatment and therapeutic alliance at posttreatment. RESULTS: Findings from multilevel modeling indicated significant, medium-to-large improvements in depression (d=1.04; 95% CI 0.60-1.46), anxiety (d=0.61; 95% CI 0.22-0.99), and functional impairment (d=0.66; 95% CI 0.27-1.05) for patients in the message-based treatment condition. Changes in depression (d=0.11; 95% CI -0.43 to 0.66), anxiety (d=-0.01; 95% CI -0.56 to 0.53), and functional impairment (d=0.25; 95% CI -0.30 to 0.80) in the message-based treatment condition were noninferior to those in the video-based treatment condition. There were no significant differences in treatment credibility (d=-0.09; 95% CI -0.64 to 0.45), therapeutic alliance (d=-0.15; 95% CI -0.75 to 0.44), or engagement (d=0.24; 95% CI -0.20 to 0.67) between the 2 treatment conditions. CONCLUSIONS: Message-based psychotherapy could present an effective and accessible alternative treatment modality for patients who might not be able to engage in traditional scheduled services such as face-to-face or video-based psychotherapy. TRIAL REGISTRATION: ClinicalTrials.gov NCT05467787; https://www.clinicaltrials.gov/ct2/show/NCT05467787.

Methods of Visualizing the Results of an Artificial-Intelligence-Based Computer-Aided Detection System for Chest Radiographs: Effect on the Diagnostic Performance of Radiologists.

It is unclear whether the visualization methods for artificial-intelligence-based computer-aided detection (AI-CAD) of chest radiographs influence the accuracy of readers' interpretation. We aimed to evaluate the accuracy of radiologists' interpretations of chest radiographs using different visualization methods for the same AI-CAD. Initial chest radiographs of patients with acute respiratory symptoms were retrospectively collected. A commercialized AI-CAD using three different methods of visualizing was applied: (a) closed-line method, (b) heat map method, and (c) combined method. A reader test was conducted with five trainee radiologists over three interpretation sessions. In each session, the chest radiographs were interpreted using AI-CAD with one of the three visualization methods in random order. Examination-level sensitivity and accuracy, and lesion-level detection rates for clinically significant abnormalities were evaluated for the three visualization methods. The sensitivity (p = 0.007) and accuracy (p = 0.037) of the combined method are significantly higher than that of the closed-line method. Detection rates using the heat map method (p = 0.043) and the combined method (p = 0.004) are significantly higher than those using the closed-line method. The methods for visualizing AI-CAD results for chest radiographs influenced the performance of radiologists' interpretations. Combining the closed-line and heat map methods for visualizing AI-CAD results led to the highest sensitivity and accuracy of radiologists.

Overexpression of the NEK9-EG5 axis is a novel metastatic marker in pathologic stage T3 colon cancer.

NEK9 is a key player in the NEK9-EG5 axis for microtubule polymerization, chromosome alignment, and mitosis. In present study, we investigated the altered expression of the NEK9, EG5 and acetyl-α-tubulin as well as common epithelial-mesenchymal transition (EMT) markers (E-cadherin, vimentin, claudin-1, and ß-catenin) through the immunohistochemistry analysis of 138 patients with pathologic T3 (pT3) stage colon cancers, and evaluated their metastatic potential. NEK9 expression showed an association with distant metastasis (P = 0.032) and was an independent predictive factor for distant metastasis (HR = 3.365, P < 0.001) by multivariate analysis, which was more significant than either the regional nodal metastasis (HR = 2.496, P = 0.007) or lymphovascular invasion (HR = 2.090, P = 0.153). Positive correlations were observed between NEK9 and EG5 or acetyl-α-tubulin (r = 0.236 and P = 0.007; r = 0.181 and P = 0.038, respectively) and concordant overexpression of the NEK9-EG5 axis was further confirmed in colon cancer cell lines. These findings collectively suggest that the overexpression of the NEK9-EG5 axis is present and associated with distant metastasis in colon cancer. These biomarkers might be useful for predicting metastatic potential among the patients with pT3 colon cancers.

Cancer-Specific Sequences in the Diagnosis and Treatment of NUT Carcinoma.

PURPOSE: NUT carcinoma (NC) is a solid tumor caused by the rearrangement of NUTM1 that usually develops in midline structures, such as the thorax. No standard treatment has been established despite high lethality. Thus, we investigated whether targeting the junction region of NUTM1 fusion breakpoints could serve as a potential treatment option for NC. Materials and Methods: We designed and evaluated a series of small interfering RNAs (siRNAs) targeting the junction region of BRD4-NUTM1 fusion (B4N), the most common form of NUTM1 fusion. Droplet digital polymerase chain reaction using the blood of patients was also tested to evaluate the treatment responses by the junction sequence of the B4N fusion transcripts. RESULTS: As expected, the majority of NC fusion types were B4N (12 of 18, 67%). B4N fusion-specific siRNA treatment on NC cells showed specific inhibitory effects on the B4N fusion transcript and fusion protein without affecting the endogenous expression of the parent genes, resulting in decreased relative cell growth and attenuation of tumor size. In addition, the fusion transcript levels in platelet-rich-plasma samples of the NC patients with systemic metastasis showed a negative correlation with therapeutic effect, suggesting its potential as a measure of treatment responsiveness. CONCLUSION: This study suggests that tumor-specific sequences could be used to treat patients with fusion genes as part of precision medicine for a rare but deadly disease.

Analysis of PIK3CA Mutation Concordance and Frequency in Primary and Different Distant Metastatic Sites in Breast Cancer.

PURPOSE: The purpose of this study was to investigate the concordance rate of PIK3CA mutations between primary and matched distant metastatic sites in patients with breast cancer and to verify whether there are differences in the frequency of PIK3CA hotspot mutations depending on the metastatic sites involved. MATERIALS AND METHODS: Archived formalin-fixed paraffin-embedded (FFPE) specimens of primary breast and matched distant metastatic tumors were retrospectively obtained for 49 patients. Additionally, 40 archived FFPE specimens were independently collected from different breast cancer metastatic sites, which were limited to three common sites: the liver, brain, and lung. PIK3CA mutations were analyzed using droplet digital PCR, including hotspots involving exons 9 and 20. RESULTS: After analysis of 49 breast tumors with matched metastasis sites, 87.8% showed concordance in PIK3CA mutation status. According to PIK3CA hotspot mutation testing in 89 cases of breast cancer metastatic sites, the proportion of PIK3CA mutations at sites of metastasis involving the liver, brain, and lung was 37.5%, 28.6%, and 42.9%, respectively, which did not result in statistical significance. CONCLUSION: The high concordance of PIK3CA mutation status between primary and matched metastasis sites suggests that metastatic sites, regardless of the metastatic organ, could be considered sample sources for PIK3CA mutation testing for improved therapeutic strategies in patients with metastatic breast cancer.

Examining the Concurrent and Predictive Validity of Single Items in Ecological Momentary Assessments.

Although single items can save time and burden in psychology research, concerns about their reliability have made the use of multiple-item measures the default standard practice. Although single items cannot demonstrate internal reliability, their criterion validity can be compared with multiple-item measures. Using ecological momentary assessment data, we evaluated repeated measures correlations and constructed multilevel cross-lagged models to assess concurrent and predictive validity of single- and multiple-item measures. Correlations between the single- and multiple-item measures ranged from .24 to .61. In 27 of 29 unique single-item predictor models, single items demonstrated significant predictive validity, and in one of eight sets of comparisons, a single-item predictor exhibited a larger effect size than its multiple-item counterpart. Although multiple-item measures generally performed better than single items, the added benefit of multiple items was modest in most cases. The present data provide support for the use of single-item measures in intensive longitudinal designs.

Brain organoid-on-a-chip: A next-generation human brain avatar for recapitulating human brain physiology and pathology.

Neurodegenerative diseases and neurodevelopmental disorders have become increasingly prevalent; however, the development of new pharmaceuticals to treat these diseases has lagged. Animal models have been extensively utilized to identify underlying mechanisms and to validate drug efficacies, but they possess inherent limitations including genetic heterogeneity with humans. To overcome these limitations, human cell-based in vitro brain models including brain-on-a-chip and brain organoids have been developed. Each technique has distinct advantages and disadvantages in terms of the mimicry of structure and microenvironment, but each technique could not fully mimic the structure and functional aspects of the brain tissue. Recently, a brain organoid-on-a-chip (BOoC) platform has emerged, which merges brain-on-a-chip and brain organoids. BOoC can potentially reflect the detailed structure of the brain tissue, vascular structure, and circulation of fluid. Hence, we summarize recent advances in BOoC as a human brain avatar and discuss future perspectives. BOoC platform can pave the way for mechanistic studies and the development of pharmaceuticals to treat brain diseases in future.

A pilot randomized effectiveness trial of the unified protocol in trauma-exposed veterans.

BACKGROUND: The unified protocol (UP) is a promising transdisgnostic treatment for emotional disorders; limited data exists with trauma-exposed populations. This study compared effectiveness of the UP, presented centered therapy (PCT), and treatment as usual (TAU) in trauma-exposed veterans presenting to routine care. METHOD: Trauma-exposed veterans with one or more emotional disorder diagnoses participated in a pilot hybrid-1 effectiveness/preimplementation study. Thirty-seven male and female veterans were randomized to one of three conditions. RESULTS: Multilevel growth curve modeling demonstrated improvement over time across conditions with large effect sizes (range: -2.15 to -3.32), with the UP demonstrating the greatest change. The between group effect sizes for reductions in number of comorbid diagnoses were medium to small and statistically significant (TAU and UP, d = 0.49, p = .056; TAU and PCT d = 0.18, p = .166, UP and PCT d = 0.31, p = .229). Only the UP led to a decrease in the number of comorbid diagnoses (d = -0.71). Psychosocial functioning varied by group, with slight increases in impairment in PCT and TAU, and medium effect size reduction in the UP. Only the UP exhibited significant decreases in self-reported anxiety and depression. Between group differences for UP and PCT were medium to large and statistically significant for depression across two measures (d = -0.72 to d = -1.40). CONCLUSIONS: This represents the first trial examining effectiveness of the UP, PCT, and TAU in trauma-exposed veterans. Despite a small sample, large effect size differences demonstrated promising advantages for the UP. Trial Registration Number: NCT02944994.

Cancellation of dolphin sonar clicks in a communication signal based on adaptive time reversal processing.

In long-range underwater communication, conventional time reversal processing (CTRP) is used to mitigate the distortion caused by multipath and temporal spreading. However, signals produced by marine animals can contaminate communication signals. Impulsive signals, such as dolphin sonar clicks, have wide bandwidths and short pulse durations, making it difficult to isolate the communication signal. This letter proposes a method to cancel these sounds by estimating the Green's function of marine animal clicks and applying adaptive time reversal processing (ATRP). The effectiveness of the click nulling was verified by comparing the performances of CTRP and ATRP with seagoing experimental data.