Lineage regulators direct BMP and Wnt pathways to cell-specific programs during differentiation and regeneration.

BMP and Wnt signaling pathways control essential cellular responses through activation of the transcription factors SMAD (BMP) and TCF (Wnt). Here, we show that regeneration of hematopoietic lineages following acute injury depends on the activation of each of these signaling pathways to induce expression of key blood genes. Both SMAD1 and TCF7L2 co-occupy sites with master regulators adjacent to hematopoietic genes. In addition, both SMAD1 and TCF7L2 follow the binding of the predominant lineage regulator during differentiation from multipotent hematopoietic progenitor cells to erythroid cells. Furthermore, induction of the myeloid lineage regulator C/EBPα in erythroid cells shifts binding of SMAD1 to sites newly occupied by C/EBPα, whereas expression of the erythroid regulator GATA1 directs SMAD1 loss on nonerythroid targets. We conclude that the regenerative response mediated by BMP and Wnt signaling pathways is coupled with the lineage master regulators to control the gene programs defining cellular identity.

Densely interconnected transcriptional circuits control cell states in human hematopoiesis.

Though many individual transcription factors are known to regulate hematopoietic differentiation, major aspects of the global architecture of hematopoiesis remain unknown. Here, we profiled gene expression in 38 distinct purified populations of human hematopoietic cells and used probabilistic models of gene expression and analysis of cis-elements in gene promoters to decipher the general organization of their regulatory circuitry. We identified modules of highly coexpressed genes, some of which are restricted to a single lineage but most of which are expressed at variable levels across multiple lineages. We found densely interconnected cis-regulatory circuits and a large number of transcription factors that are differentially expressed across hematopoietic states. These findings suggest a more complex regulatory system for hematopoiesis than previously assumed.

ARID5B as a critical downstream target of the TAL1 complex that activates the oncogenic transcriptional program and promotes T-cell leukemogenesis.

The oncogenic transcription factor TAL1/SCL induces an aberrant transcriptional program in T-cell acute lymphoblastic leukemia (T-ALL) cells. However, the critical factors that are directly activated by TAL1 and contribute to T-ALL pathogenesis are largely unknown. Here, we identified AT-rich interactive domain 5B (ARID5B) as a collaborating oncogenic factor involved in the transcriptional program in T-ALL. ARID5B expression is down-regulated at the double-negative 2-4 stages in normal thymocytes, while it is induced by the TAL1 complex in human T-ALL cells. The enhancer located 135 kb upstream of the ARID5B gene locus is activated under a superenhancer in T-ALL cells but not in normal T cells. Notably, ARID5B-bound regions are associated predominantly with active transcription. ARID5B and TAL1 frequently co-occupy target genes and coordinately control their expression. ARID5B positively regulates the expression of TAL1 and its regulatory partners. ARID5B also activates the expression of the oncogene MYC Importantly, ARID5B is required for the survival and growth of T-ALL cells, and forced expression of ARID5B in immature thymocytes results in thymus retention, differentiation arrest, radioresistance, and tumor formation in zebrafish. Our results indicate that ARID5B reinforces the oncogenic transcriptional program by positively regulating the TAL1-induced regulatory circuit and MYC in T-ALL, thereby contributing to T-cell leukemogenesis.

Synapse-Enriched m6A-Modified Malat1 Interacts with the Novel m6A Reader, DPYSL2, and Is Required for Fear-Extinction Memory.

The RNA modification N6-methyladenosine (m6A) regulates the interaction between RNA and various RNA binding proteins within the nucleus and other subcellular compartments and has recently been shown to be involved in experience-dependent plasticity, learning, and memory. Using m6A RNA-sequencing, we have discovered a distinct population of learning-related m6A- modified RNAs at the synapse, which includes the long noncoding RNA metastasis-associated lung adenocarcinoma transcript 1 (Malat1). RNA immunoprecipitation and mass spectrometry revealed 12 new synapse-specific learning-induced m6A readers in the mPFC of male C57/BL6 mice, with m6A-modified Malat1 binding to a subset of these, including CYFIP2 and DPYSL2. In addition, a cell type- and synapse-specific, and state-dependent, reduction of m6A on Malat1 impairs fear-extinction memory; an effect that likely occurs through a disruption in the interaction between Malat1 and DPYSL2 and an associated decrease in dendritic spine formation. These findings highlight the critical role of m6A in regulating the functional state of RNA during the consolidation of fear-extinction memory, and expand the repertoire of experience-dependent m6A readers in the synaptic compartment.SIGNIFICANCE STATEMENT We have discovered that learning-induced m6A-modified RNA (including the long noncoding RNA, Malat1) accumulates in the synaptic compartment. We have identified several new m6A readers that are associated with fear extinction learning and demonstrate a causal relationship between m6A-modified Malat1 and the formation of fear-extinction memory. These findings highlight the role of m6A in regulating the functional state of an RNA during memory formation and expand the repertoire of experience-dependent m6A readers in the synaptic compartment.

Implementation of sonopartogram: multicenter feasibility study.

OBJECTIVES: Well-established clinical practice to assess progress in labor involves routine abdominal palpation and vaginal examination (VE). However, VE is subjective, poorly reproducible and painful for women. In this study, our aim is to evaluate the feasibility of systematically integrating transabdominal and transperineal ultrasound assessment of fetal position, psAOP, HPD and SCD to monitor labor progress in women undergoing induction of labor (IOL). We also aim at determining if ultrasound can reduce women's pain during examinations. METHODS: Women were recruited as they presented for IOL in three maternity units. Ultrasound assessments were performed in 100 women between 37+0 and 41+6 weeks' gestation. A baseline combined transabdominal and transperineal scan was performed, including the assessment of fetal biometry, umbilical artery and middle cerebral artery Dopplers, amniotic fluid index (AFI), fetal spine and occiput positions, psAOP, HPD, SCD, and cervical length. Intrapartum scans were performed instead of VEs according to protocol. Participants were asked to indicate their level of pain by verbally giving a pain score from 0 - 10 (with 0 representing no pain) during assessment. The repeated measures data were analyzed by mixed effect models to identify the significant factors that affected the relationship between psAOP, HPD, SCD and mode of delivery. RESULTS: 223 intrapartum ultrasound scans with a median of 2 scans per participant (interquartile range (IQR) = 1 - 3), and 151 VEs were performed with a median of 1 per participant (IQR = 0 - 2). There were no adverse fetal or maternal outcomes. After excluding those with epidural anesthesia during examination, median pain score for intrapartum scan was 0 (IQR = 0 - 1) and 3 for VE (IQR = 0 - 6). Cesarean delivery and epidural anesthesia were significantly associated with slower rate of change in psAOP, HPD and SCD. Maternal height, parity and neonatal birth weight did not affect ultrasound measurements of labor progress. CONCLUSIONS: Comprehensive transabdominal and transperineal ultrasound assessment can be successfully used to assess progress in labor and can reduce the level of pain experienced during examination. Ultrasound assessment may be able to replace some transabdominal and VE examinations during labor. This article is protected by copyright. All rights reserved.

Learning whom not to trust across early and middle adolescence: A longitudinal neuroimaging study to trusting behavior involving an uncooperative other.

Longitudinal changes in trusting behavior across adolescence and their neural correlates were examined. Neural regions of interest (ROIs) included the medial prefrontal cortex (mPFC), dorsal anterior cingulate cortex (dACC), left anterior insula (AI), bilateral ventral striatum (VS), and right dorsal striatum (DS). Participants (wave 1 age: M = 12.90) played the investor in a Trust Game with an uncooperative trustee three times (1-year interval). Analyses included 77 primarily Dutch participants (33 females). Participants decreased their investments with wave. Furthermore, activity was heightened in mPFC, dACC, and DS during investment and repayment, and in right VS (investment) and AI (repayment). Finally, DS activity during repayment increased with wave. These findings highlight early-middle adolescence as an important period for developing sensitivity to uncooperative behavior.

Heterosexual couples' initial role and outcome expectations as predictors of the therapeutic alliance and relationship satisfaction prior to the fourth session.

We sampled routinely collected measures of role and outcome expectations, the expanded therapeutic alliance, and relationship satisfaction completed by 253 heterosexual couples seen by 35 therapists in the Marriage and Family Research Practice Network (Johnson et al., 2017) and investigated these variables as interdependent dyadic processes using the latent congruence model (Cheung, 2009) and the mediated actor-partner interdependence model (Ledermann et al., 2011). Taken together, we found a direct association between a couple's mean role and outcome expectation scores at Session 1 and individual partners' alliance perceptions at Session 3. Further, men rated the alliance more favorably when their outcome expectations were higher and the partners' outcome expectations were less discrepant. In terms of role expectations, both men and women began therapy expecting to be more actively engaged in the process than their partner. Whereas women rated the alliance more favorably when they had high role expectations for their partner as well as themselves, men rated the alliance more favorably when they had high expectations for their female partner's engagement in the therapy. Notably, alliance at Session 3 did not mediate the association between initial expectations and Session 4 relationship satisfaction due to a strong association (r = 0.85) between relationship satisfaction rated prior to Sessions 1 and 4. In other words, although the best predictor of relationship status before the fourth session was how the relationship was perceived before couple therapy began, men's and women's initial role and outcome expectations were important contributors to the early alliance. (PsycInfo Database Record (c) 2024 APA, all rights reserved).

Lost in translation: Therapeutic Alliance as a mediator in the relationship between teletherapy and marital satisfaction.

The global impact of the SARS-COV-2 pandemic necessitated a rapid shift to online/teletherapy psychotherapy services. While research suggests the feasibility and efficacy of teletherapy, there is limited investigation into couple teletherapy's impact on satisfaction and therapeutic alliance. This study aimed to address this gap by examining changes in couple satisfaction during tele- and in-person therapy sessions over 12 sessions and exploring whether therapeutic alliance development mediates these changes. Using growth curve modeling in a sample of 416 couples, it found that teletherapy participants initially reported higher couple satisfaction, but improvement in this domain was slower than in-person therapy recipients. The development of the therapeutic alliance mediated this effect via two indirect paths. Implications include the need for focused attention on alliance development in teletherapy and more empirically-informed approaches in couple teletherapy.

Perceived change in age after functional upper blepharoplasty.

PURPOSE: To evaluate the perceived age of patients before and after functional upper blepharoplasty. METHODS: Retrospective chart review of patients who underwent upper blepharoplasty by a single surgeon at an academic center. The inclusion criterion was having external photographs before and after blepharoplasty. Exclusion criteria included any other concurrent eyelid or facial surgery. Primary endpoint: perceived change in age after surgery as judged by the American Society of Ophthalmic Plastic & Reconstructive Surgery (ASOPRS) surgeons. RESULTS: Sixty-seven patients (14 men, 53 women) were included. Mean pre-operative age was 66.9 years (range 37.8-89.4) and mean post-operative age was 67.4 years (range 38.6-89). The mean perceived age pre-operatively was 68.9 years, and the mean perceived age post-operatively was 67.1 years, a change of 1.8 years (p = 0.0001 by two-tailed paired T-test). Inter-rater reliability of the observers was measured by intraclass correlation coefficient of 0.77 for pre-operative and 0.75 for post-operative photos. The decreased perceived age was 1.9 years for women, 1.4 years for men, 0.3 years for Asians, 1.2 years for Hispanics, and 2.1 years for whites. DISCUSSION: Functional upper blepharoplasty by an experienced ASOPRS surgeon was shown to reduce the perceived age of a patient by an average of 1.8 years.

Glycosylated fibronectin improves first-trimester prediction of pre-eclampsia.

OBJECTIVE: To determine whether maternal serum glycosylated fibronectin (GlyFn) level in the first trimester increases the sensitivity of the Fetal Medicine Foundation (FMF) triple test, which incorporates mean arterial pressure, uterine artery pulsatility index and placental growth factor, when screening for pre-eclampsia (PE) in an Asian population. METHODS: This was a nested case-control study of Chinese women with a singleton pregnancy who were screened for PE at 11-13 weeks' gestation as part of a non-intervention study between December 2016 and June 2018. GlyFn levels were measured retrospectively in archived serum from 1685 pregnancies, including 101 with PE, using an enzyme-linked immunosorbent assay (ELISA), and from 448 pregnancies, including 101 with PE, using a point-of-care (POC) device. Concordance between ELISA and POC tests was assessed using Lin's correlation coefficient and Passing-Bablok and Bland-Altman analyses. GlyFn was transformed into multiples of the median (MoM) to adjust for maternal and pregnancy characteristics. GlyFn MoM was compared between PE and non-PE pregnancies, and the association between GlyFn MoM and gestational age at delivery with PE was assessed. Risk for developing PE was estimated using the FMF competing-risks model. Screening performance for preterm and any-onset PE using different biomarker combinations was quantified by area under the receiver-operating-characteristics curve (AUC) and detection rate (DR) at a 10% fixed false-positive rate (FPR). Differences in AUC between biomarker combinations were compared using the DeLong test. RESULTS: The concordance correlation coefficient between ELISA and POC measurements was 0.86 (95% CI, 0.83-0.88). Passing-Bablok analysis indicated proportional bias (slope, 1.08 (95% CI, 1.04-1.14)), with POC GlyFn being significantly higher compared with ELISA GlyFn. ELISA GlyFn in non-PE pregnancies was independent of gestational age at screening (P = 0.11), but significantly dependent on maternal age (P < 0.003), weight (P < 0.0002), height (P = 0.001), parity (P < 0.02) and smoking status (P = 0.002). Compared with non-PE pregnancies, median GlyFn MoM using ELISA and POC testing was elevated significantly in those with preterm PE (1.23 vs 1.00; P < 0.0001 and 1.18 vs 1.00; P < 0.0001, respectively) and those with term PE (1.26 vs 1.00; P < 0.0001 and 1.22 vs 1.00; P < 0.0001, respectively). GlyFn MoM was not correlated with gestational age at delivery with PE (P = 0.989). Adding GlyFn to the FMF triple test for preterm PE increased significantly the AUC from 0.859 to 0.896 (P = 0.012) and increased the DR at 10% FPR from 64.9% (95% CI, 48.7-81.1%) to 82.9% (95% CI, 66.4-93.4%). The corresponding DRs at 10% FPR for any-onset PE were 52.5% (95% CI, 42.3-62.5%) and 65.4% (95% CI, 55.2-74.5%), respectively. CONCLUSIONS: Adding GlyFn to the FMF triple test increased the screening sensitivity for both preterm and any-onset PE in an Asian population. Prospective non-intervention studies are needed to confirm these initial findings. © 2023 The Authors. Ultrasound in Obstetrics & Gynecology published by John Wiley & Sons Ltd on behalf of International Society of Ultrasound in Obstetrics and Gynecology.

The development of adolescent trust behavior.

Interpersonal trust shows developmental changes during adolescence. The current study used a longitudinal design to examine the development of trust behavior, the presence of gender differences in these developmental trajectories, and the association between individual differences in these developmental trajectories and perspective-taking abilities. The participants played a trust game with a hypothetical trustworthy partner and a trust game with a hypothetical untrustworthy partner in 3 consecutive years (Mage = 12.55 years, Mage = 13.54 years, and Mage = 14.54 years). Concerning the development of trust behavior, the results showed an age-related increase in initial trust behavior and indicated increasingly adaptive trust behavior with age during untrustworthy interactions, whereas no evidence was found for age-related changes in the adaptation of trust during trustworthy interactions. Gender differences were found for the development of initial trust behavior (with boys showing a stronger increase with age than girls), whereas no support was found for the presence of gender differences in the developmental trajectories of adaptive trust behavior during trustworthy and untrustworthy interactions. Furthermore, no evidence was found for perspective-taking abilities to explain individual differences in the development of initial trust behavior or in the development of adaptive trust behavior during trustworthy and untrustworthy interactions. The results provide evidence that, during adolescence initial trust behavior increased with age, more for boys than for girls, and that both boys and girls showed a stronger adaptive response to the untrustworthy partner but not to the trustworthy partner.

Confirmatory factor analysis of the BRIEF2 in a sample of youth with Down syndrome.

BACKGROUND: The factor structure of the Behavior Rating Inventory of Executive Function, second edition (BRIEF2) has been widely examined in both typically developing children and specific clinical samples. Despite the frequent use of the BRIEF2 for measuring executive functioning in individuals with Down syndrome, no study has investigated the factorial validity or dimensionality of the BRIEF2 in this population. This study aimed to address this notable gap in the literature. METHODS: Parents of 407 children and youth with Down syndrome aged 6-18 years completed the BRIEF2 as part of different studies led by six sites. Three competing models proposed by previous studies were analysed using Confirmatory Factor Analysis: the theoretical structure of the BRIEF2 where the scales were constrained to load on three factors labelled as Cognitive, Behavioral, and Emotional Regulation, a two-factor correlated model with the merged Behavioral and Emotional regulation, and a single-factor model. RESULTS: The three-factor model provided a better fit than the one- and two-factor models, yet a large correlation was observed between Behavioural and Emotional regulation factors. The results provide meaningful explanatory value for the theoretical structure of the BRIEF2. However, the Behavioral and Emotional regulation factors might be less differentiated and the two-factor structure of the BRIEF2 may also make theoretical and empirical sense. CONCLUSIONS: Although more studies are needed to further examine the factor structure of the BRIEF2 in youth with Down syndrome, this investigation provides preliminary support for the interpretation of the three executive function index scores provided by the BRIEF2: Cognitive, Behavioral, and Emotional Regulation.

A genome-scale in vivo loss-of-function screen identifies Phf6 as a lineage-specific regulator of leukemia cell growth.

We performed a genome-scale shRNA screen for modulators of B-cell leukemia progression in vivo. Results from this work revealed dramatic distinctions between the relative effects of shRNAs on the growth of tumor cells in culture versus in their native microenvironment. Specifically, we identified many "context-specific" regulators of leukemia development. These included the gene encoding the zinc finger protein Phf6. While inactivating mutations in PHF6 are commonly observed in human myeloid and T-cell malignancies, we found that Phf6 suppression in B-cell malignancies impairs tumor progression. Thus, Phf6 is a "lineage-specific" cancer gene that plays opposing roles in developmentally distinct hematopoietic malignancies.

Emotion dysregulation and couple relationship satisfaction of clinical couples: An actor-partner interdependence model.

Despite the pivotal role that emotion regulation is thought to occupy for individual and relational wellbeing, emotion regulation in couples has been surprisingly understudied. With a clinical sample consisting of 275 couples starting therapy from 2017 to 2022, this study sought to clarify the actor and partner effects of clinical couples' emotion dysregulation on relationship satisfaction. Our results showed that, for partners' emotion dysregulation dimensions, while impulse control difficulties, lack of emotional awareness, and limited emotion regulation strategies were negatively predictive of couple relationship satisfaction, nonacceptance of negative emotions had a positive association with relationship satisfaction. Further, compared with other dimensions of emotion dysregulation, female limited emotion regulation strategies were greater predictors of decreased female relationship satisfaction. We also found significant gender differences in partners' emotion dysregulation dimensions and relationship satisfaction. These results show the significance of addressing emotion dysregulation for both partners at intra- and inter-personal levels simultaneously in couple therapy. Notably, the 275 couples in our sample did not report a clinically distressed relationship, though they attended at least one couple therapy session. Clinical implications and directions for future study are discussed.

Call me maybe? In-person vs. teletherapy outcomes among married couples.

ABSTRACTObjective: The objective of this study was to investigate the effectiveness of teletherapy compared to in-person couple therapy in outcomes such as couple satisfaction, sexual satisfaction, and the therapeutic alliance.Method: Data from 1157 married clients seeking couple therapy were examined. Individual growth curve models were used to analyze changes in the aforementioned outcomes, with teletherapy as a predictor. The study also examined client age and clinic type as moderators.Results: The results indicated that overall, teletherapy is as effective as in-person therapy in improving outcomes. However, there were notable differences in the development of the therapeutic alliance. The alliance improved at twice the rate in in-person therapy as in teletherapy. Clinic type was also found to be a moderator of changes in sexual satisfaction. Clients in group and private practices reported improvements in sexual satisfaction; whereas clients seen in training clinics reported decreases in sexual satisfaction.Conclusion: The study concludes that although teletherapy may be a viable alternative to in-person couple therapy, there are nevertheless differences in the development of the therapeutic alliance that warrant care and further investigation. The setting of the therapy also plays a role in the effectiveness of therapy, although not specific to therapy modality.

Is there a role for endovascular stent implantation in the management of postoperative right ventricular outflow tract obstruction in the era of transcatheter valve implantation?

BACKGROUND: The optimal management pathway for the dysfunctional right ventricular outflow tract (RVOT) is uncertain. We evaluated the long-term outcomes and clinical impact of stent implantation for obstructed RVOTs in an era of rapidly progressing transcatheter pulmonary valve technology. METHODS: Retrospective review of 151 children with a biventricular repair who underwent stenting of obstructed RVOT between 1991 and 2017. RESULTS: RVOT stenting resulted in significant changes in peak right ventricle (RV)-to-pulmonary artery (PA) gradient (39.4 ± 17.1-14.9 ± 8.3; p < 0.001) and RV-to-aortic pressure ratio (0.78 ± 0.22-0.49 ± 0.13; p < 0.001). Subsequent percutaneous reinterventions in 51 children to palliate recurrent stenosis were similarly effective. Ninety-nine (66%) children reached the primary outcome of subsequent pulmonary valve replacement (PVR). Freedom from PVR from the time of stent implantation was 91%, 51%, and 23% at 1, 5, and 10 years, respectively. Small balloon diameters for stent deployment were associated with shorter freedom from PVR. When additional children without stent palliation (with RV-to-PA conduits) were added to the stent cohort (total 506 children), the multistate analysis showed the longest freedom from PVR in those with stent palliation and subsequent catheter reintervention. Pulmonary regurgitation was well-tolerated clinically. Indexed RV dimensions and function estimated by echocardiography remained stable at last follow up or before primary outcome. CONCLUSION: Prolongation of conduit longevity with stent implant remains an important strategy to allow for somatic growth to optimize the risk-benefit profile for subsequent surgical or transcatheter pulmonary valve replacement performed at an older age.

Increased salivary syndecan-1 level is associated with salivary gland function and inflammation in patients with Sjögren's syndrome.

OBJECTIVE: Syndecan-1 (SDC-1), a transmembrane heparin sulphate proteoglycan predominantly expressed on epithelial cells, also exists in a soluble form through ectodomain shedding. SDC-1 expression and shedding may be modulated in the inflammatory milieu of primary Sjögren's syndrome (SS). We investigated SDC-1 expression in minor salivary glands (MSGs) and analysed the association between salivary or plasma levels of SDC-1 and clinical parameters in SS. METHOD: We measured salivary and plasma SDC-1 levels via an enzyme-linked immunosorbent assay and assessed the salivary flow rates (SFRs) in 70 patients with SS and 35 healthy subjects. Disease activity indices, serological markers, salivary gland scintigraphy, and MSG biopsy were evaluated in patients with SS. RESULTS: SDC-1 expression was upregulated on ductal epithelial cells in inflamed salivary glands. Salivary SDC-1 levels in patients significantly exceeded those in healthy subjects [median (interquartile range) 49.0 (20.7-79.1) vs 3.7 (1.7-6.3) ng/mL, p < 0.001] and inversely correlated with SFRs (r = -0.358, p = 0.032) and ejection fractions of the parotid (r = -0.363, p = 0.027) and submandibular (r = -0.485, p = 0.002) glands in salivary gland scintigraphy. Plasma SDC-1 levels were significantly correlated with the EULAR Sjögren's Syndrome Disease Activity Index (r = 0.507, p < 0.001) and EULAR Sjögren's Syndrome Patient Reported Index (r = 0.267, p = 0.033). Focus scores were correlated with salivary SDC-1 levels (r = 0.551, p = 0.004). CONCLUSIONS: Salivary and plasma SDC-1 levels may constitute potential biomarkers for salivary gland function and disease activity, respectively, in SS.

Updated profiles of everyday executive function in youth with Down syndrome using the BRIEF-2.

BACKGROUND: Executive function difficulties in youth with Down syndrome (DS) are well recognised using informant-report measures. However, the profile of relative challenges and strengths has not yet been evaluated using the Behavior Rating Inventory of Executive Function, Second Edition (BRIEF-2), which includes a new internal factor structure. METHOD: Using the BRIEF-2, profiles of everyday parent-reported executive function (EF) were evaluated in youth with DS (n = 34) and compared with age-based and sex-based norms. EF profiles were also compared across raters (parent vs. teacher, n = 20) and relative to mental age-matched typically developing controls (ns = 19 in each group). RESULTS: Although within-group differences were not revealed on indexes, significant differences were found among BRIEF-2 scales. Across raters, teachers reported significantly more difficulties than parents. Compared with mental age-matched typically developing controls, the DS group was rated more poorly on some but not all BRIEF-2 scales. CONCLUSIONS: At the scale, but not the index level, the BRIEF-2 identifies a variegated EF profile in children with DS. For several of the scales, significant differences were noted relative to both chronological age expectations (using norms) and mental-age expectations (using a developmentally matched comparison group). At the scale level, the BRIEF-2 continues to be a sensitive tool for identifying executive function difficulties as well as profiles of relative strengths and weaknesses in children with DS.

Latent profiles of autism symptoms in children and adolescents with Down syndrome.

BACKGROUND: Down syndrome (DS) is associated with elevated rates of autism spectrum disorder (ASD) and autism symptomatology. To better characterise heterogeneity in ASD symptomatology in DS, profiles of caregiver-reported ASD symptoms were modelled for children and adolescents with DS. METHODS: Participants (n = 125) were recruited through several multi-site research studies on cognition and language in DS. Using the Social Responsiveness Scale-2 (SRS-2; Constantino and Gruber 2012), two latent profile analyses (LPA) were performed, one on the broad composite scores of social communication and interaction and restricted interests and repetitive behaviour, and a second on the four social dimensions of social communication, social motivation, social awareness, and social cognition. RESULTS: A three-profile model was the best fit for both analyses, with each analysis yielding a low ASD symptom profile, an elevated or mixed ASD symptom profile and a high ASD symptom profile. Associations were observed between profile probability scores and IQ, the number of co-occurring biomedical conditions reported, sex, and SRS-2 form. CONCLUSIONS: Characterising heterogeneity in ASD symptom profiles can inform more personalised supports in this population, and implications for potential therapeutic approaches for individuals with DS are discussed.

Geological-Geophysical and Oceanographic Research in the Sea of Japan, Tatar Strait, on Cruise 61 of the R/V Akademik Oparin.

The paper presents brief results of comprehensive studies of the water area of the Tatar Strait and Sea of Japan obtained on cruise 61 of the R/V "Akademik Oparin" in November-December 2020. The bottom relief and geophysical and gas-geochemical fields were refined, and new features of the geochemistry and mineralogy of bottom sediments were revealed.