Childhood adversities characterize the heterogeneity in the brain pattern of individuals during neurodevelopment.

BACKGROUND: Several factors shape the neurodevelopmental trajectory. A key area of focus in neurodevelopmental research is to estimate the factors that have maximal influence on the brain and can tip the balance from typical to atypical development. METHODS: Utilizing a dissimilarity maximization algorithm on the dynamic mode decomposition (DMD) of the resting state functional MRI data, we classified subjects from the cVEDA neurodevelopmental cohort (n = 987, aged 6-23 years) into homogeneously patterned DMD (representing typical development in 809 subjects) and heterogeneously patterned DMD (indicative of atypical development in 178 subjects). RESULTS: Significant DMD differences were primarily identified in the default mode network (DMN) regions across these groups (p < 0.05, Bonferroni corrected). While the groups were comparable in cognitive performance, the atypical group had more frequent exposure to adversities and faced higher abuses (p < 0.05, Bonferroni corrected). Upon evaluating brain-behavior correlations, we found that correlation patterns between adversity and DMN dynamic modes exhibited age-dependent variations for atypical subjects, hinting at differential utilization of the DMN due to chronic adversities. CONCLUSION: Adversities (particularly abuse) maximally influence the DMN during neurodevelopment and lead to the failure in the development of a coherent DMN system. While DMN's integrity is preserved in typical development, the age-dependent variability in atypically developing individuals is contrasting. The flexibility of DMN might be a compensatory mechanism to protect an individual in an abusive environment. However, such adaptability might deprive the neural system of the faculties of normal functioning and may incur long-term effects on the psyche.

Quantification of Hydrogen-Bond-Donating Ability of Biologically Relevant Compounds.

Hydrogen bonding is a key factor in the design of ligands for biological binding, including drug targets. Our group previously developed a method for experimentally assessing the hydrogen-bond-donating ability of an analyte using UV-vis titrations with a colorimetric sensor. Using this method, 79 new titrations were performed on weak hydrogen-bond donors, with a focus on heterocycles and pharmaceutically relevant motifs. The hydrogen-bond donating abilities of drug compounds and the substructures of drug compounds were also measured. These titrations will be used to build a database of hydrogen-bond donors.

Scarcity and intertemporal choice.

Scarcity often encourages decisions that favor the present over the future. While prevailing theories largely attribute these decisions to myopic, impulsive decision making, five studies find support for an alternative, less prevalent perspective. We introduce the time horizon of threatened needs as an important determinant of scarcity's effect on intertemporal choice, demonstrating that people's decisions under scarcity reflect attempts to address threatened needs. Data from the Federal Reserve Bank of Philadelphia (Study 1) and preregistered studies (N = 10,297) show that time horizon moderates intertemporal decisions under scarcity. Study 2 manipulates scarcity perceptions among people engaged to be married, leading to increased preferences for sooner outcomes when wedding dates have shorter time horizons and a significant reversal when wedding dates have longer time horizons. Study 3 demonstrates that time horizon predicts intertemporal choice only when the intertemporal choice can help address threatened needs. Study 4 holds expense salience constant and replicates the moderation by time horizon using a paradigm that manipulates both scarcity and time horizon. Study 5 introduces multiple needs that vary in time horizon and importance, finding that decisions under scarcity reflect consideration of both the importance and temporal proximity of needs. These findings align with the perspective that people facing scarcity attempt to make decisions that are contextually appropriate. This work underscores the importance of understanding contextual variation in experiences of scarcity, suggests that decision making under scarcity is less thoughtless than presumed by the impulsive, myopic account, and offers recommendations for interventions for changing behavior under scarcity. (PsycInfo Database Record (c) 2023 APA, all rights reserved).

Clinical improvement in schizophrenia during antipsychotic treatment in relation to changes in glucose parameters: A systematic review.

Antipsychotics (APs) are the cornerstone of treatment for schizophrenia (SCZ) spectrum disorders. Previous research suggests that there may be a positive association between AP-induced weight gain and/or dyslipidemia and improvement in psychiatric symptoms, often referred to as a "metabolic threshold". To determine whether a similar relationship exists for glucose parameters, we conducted a systematic search in six databases from inception to June 2022 for all longitudinal studies that directly examined the relationship between changes in glucose-related outcomes and changes in psychopathology among patients with SCZ treated with APs. We identified 10 relevant studies and one additional study that considered cognition. In most cases, we found that increased levels of fasting glucose and insulin following treatment were associated with clinical improvement. These findings contribute to existing literature that could suggest a common mechanism between AP action and metabolic side effects and support a need for additional work aimed at exploring the validity of a glucose-psychopathology relation in SCZ.

Neurocognitive Analysis of Low-level Arsenic Exposure and Executive Function Mediated by Brain Anomalies Among Children, Adolescents, and Young Adults in India.

Importance: Arsenic, a contaminant of groundwater and irrigated crops, is a global public health hazard. Exposure to low levels of arsenic through food extends well beyond the areas with high arsenic content in water. Objective: To identify cognitive impairments following commonly prevalent low-level arsenic exposure and characterize their underlying brain mechanisms. Design, Setting, and Participants: This multicenter population-based cohort study analyzed cross-sectional data of the Indian Consortium on Vulnerability to Externalizing Disorders and Addictions (cVEDA) cohort, recruited between November 4, 2016, and May 4, 2019. Participants aged 6 to 23 years were characterized using deep phenotyping measures of behavior, neuropsychology, psychopathology, brain neuroimaging, and exposure to developmental adversities and environmental neurotoxins. All analyses were performed between June 1, 2020, and December 31, 2021. Exposure: Arsenic levels were measured in urine as an index of exposure. Main Outcomes and Measures: Executive function measured using the cVEDA neuropsychological battery, gray matter volume (GMV) from T1-weighted magnetic resonance imaging, and functional network connectivity measures from resting state functional magnetic resonance imaging. Results: A total of 1014 participants aged 6 to 23 years (589 male [58.1%]; mean [SD] age, 14.86 [4.79] years) were included from 5 geographic locations. Sparse-partial least squares analysis was used to describe a negative association of arsenic exposure with executive function (r = -0.12 [P = 5.4 × 10-4]), brain structure (r = -0.20 [P = 1.8 × 10-8]), and functional connectivity (within network, r = -0.12 [P = 7.5 × 10-4]; between network, r = -0.23 [P = 1.8 × 10-10]). Alterations in executive function were partially mediated by GMV (b = -0.004 [95% CI, -0.007 to -0.002]) and within-network functional connectivity (b = -0.004 [95% CI, -0.008 to -0.002]). Socioeconomic status and body mass index moderated the association between arsenic and GMV, such that the association was strongest in participants with lower socioeconomic status and body mass index. Conclusions and Relevance: The findings of this cross-sectional study suggest that low-level arsenic exposure was associated with alterations in executive functioning and underlying brain correlates. These results indicate potential detrimental consequences of arsenic exposure that are below the currently recommended guidelines and may extend beyond endemic risk areas. Precision medicine approaches to study global mental health vulnerabilities highlight widespread but potentially modifiable risk factors and a mechanistic understanding of the impact of low-level arsenic exposure on brain development.

Growth trajectories for executive and social cognitive abilities in an Indian population sample: Impact of demographic and psychosocial determinants.

Cognitive abilities are markers of brain development and psychopathology. Abilities, across executive, and social domains need better characterization over development, including factors that influence developmental change. This study is based on the cVEDA [Consortium on Vulnerability to Externalizing Disorders and Addictions] study, an Indian population based developmental cohort. Verbal working memory, visuo-spatial working memory, response inhibition, set-shifting, and social cognition (faux pas recognition and emotion recognition) were cross-sectionally assessed in > 8000 individuals over the ages 6-23 years. There was adequate representation across sex, urban-rural background, psychosocial risk (psychopathology, childhood adversity and wealth index, i.e. socio-economic status). Quantile regression was used to model developmental change. Age-based trajectories were generated, along with examination of the impact of determinants (sex, childhood adversity, and wealth index). Development in both executive and social cognitive abilities continued into adulthood. Maturation and stabilization occurred in increasing order of complexity, from working memory to inhibitory control to cognitive flexibility. Age related change was more pronounced for low quantiles in response inhibition (ß∼4 versus  -1 versus -0.25 for lower quantiles). Wealth index had the largest influence on developmental change across cognitive abilities. Sex differences were prominent in response inhibition, set-shifting and emotion recognition. Childhood adversity had a negative influence on cognitive development. These findings add to the limited literature on patterns and determinants of cognitive development. They have implications for understanding developmental vulnerabilities in young persons, and the need for providing conducive socio-economic environments.

Federated Analysis in COINSTAC Reveals Functional Network Connectivity and Spectral Links to Smoking and Alcohol Consumption in Nearly 2,000 Adolescent Brains.

With the growth of decentralized/federated analysis approaches in neuroimaging, the opportunities to study brain disorders using data from multiple sites has grown multi-fold. One such initiative is the Neuromark, a fully automated spatially constrained independent component analysis (ICA) that is used to link brain network abnormalities among different datasets, studies, and disorders while leveraging subject-specific networks. In this study, we implement the neuromark pipeline in COINSTAC, an open-source neuroimaging framework for collaborative/decentralized analysis. Decentralized exploratory analysis of nearly 2000 resting-state functional magnetic resonance imaging datasets collected at different sites across two cohorts and co-located in different countries was performed to study the resting brain functional network connectivity changes in adolescents who smoke and consume alcohol. Results showed hypoconnectivity across the majority of networks including sensory, default mode, and subcortical domains, more for alcohol than smoking, and decreased low frequency power. These findings suggest that global reduced synchronization is associated with both tobacco and alcohol use. This proof-of-concept work demonstrates the utility and incentives associated with large-scale decentralized collaborations spanning multiple sites.

Risk clustering and psychopathology from a multi-center cohort of Indian children, adolescents, and young adults.

Developmental adversities early in life are associated with later psychopathology. Clustering may be a useful approach to group multiple diverse risks together and study their relation with psychopathology. To generate risk clusters of children, adolescents, and young adults, based on adverse environmental exposure and developmental characteristics, and to examine the association of risk clusters with manifest psychopathology. Participants (n = 8300) between 6 and 23 years were recruited from seven sites in India. We administered questionnaires to elicit history of previous exposure to adverse childhood environments, family history of psychiatric disorders in first-degree relatives, and a range of antenatal and postnatal adversities. We used these variables to generate risk clusters. Mini-International Neuropsychiatric Interview-5 was administered to evaluate manifest psychopathology. Two-step cluster analysis revealed two clusters designated as high-risk cluster (HRC) and low-risk cluster (LRC), comprising 4197 (50.5%) and 4103 (49.5%) participants, respectively. HRC had higher frequencies of family history of mental illness, antenatal and neonatal risk factors, developmental delays, history of migration, and exposure to adverse childhood experiences than LRC. There were significantly higher risks of any psychiatric disorder [Relative Risk (RR) = 2.0, 95% CI 1.8-2.3], externalizing (RR = 4.8, 95% CI 3.6-6.4) and internalizing disorders (RR = 2.6, 95% CI 2.2-2.9), and suicidality (2.3, 95% CI 1.8-2.8) in HRC. Social-environmental and developmental factors could classify Indian children, adolescents and young adults into homogeneous clusters at high or low risk of psychopathology. These biopsychosocial determinants of mental health may have practice, policy and research implications for people in low- and middle-income countries.

Temperature-dependent Small RNA Expression Depends on Wild Genetic Backgrounds of Caenorhabditis briggsae.

Geographically distinct populations can adapt to the temperature conditions of their local environment, leading to temperature-dependent fitness differences between populations. Consistent with local adaptation, phylogeographically distinct Caenorhabditis briggsae nematodes show distinct fitness responses to temperature. The genetic mechanisms underlying local adaptation, however, remain unresolved. To investigate the potential role of small noncoding RNAs in genotype-specific responses to temperature, we quantified small RNA expression using high-throughput sequencing of C. briggsae nematodes from tropical and temperate strain genotypes reared under three temperature conditions (14 °C, 20 °C, and 30 C). Strains representing both tropical and temperate regions showed significantly lower expression of PIWI-interacting RNAs (piRNAs) at high temperatures, primarily mapping to a large ∼7 Mb long piRNA cluster on chromosome IV. We also documented decreased expression of 22G-RNAs antisense to protein-coding genes and other genomic features at high rearing temperatures for the thermally-intolerant temperate strain genotype, but not for the tropical strain genotype. Reduced 22G-RNA expression was widespread along chromosomes and among feature types, indicative of a genome-wide response. Targets of the EGO-1/CSR-1 22G-RNA pathway were most strongly impacted compared with other 22G-RNA pathways, implicating the CSR-1 Argonaute and its RNA-dependent RNA polymerase EGO-1 in the genotype-dependent modulation of C. briggsae 22G-RNAs under chronic thermal stress. Our work suggests that gene regulation via small RNAs may be an important contributor to the evolution of local adaptations.

Metacognitions in Symptomatic and Remitted Patients with Obsessive Compulsive Disorder: Preliminary Evidence for Metacognitive State and Trait Markers.

Background: The phenomenon of metacognition is instrumental in the conceptualization and management of obsessive compulsive disorder (OCD). Studies on the comparison between metacognitions in OCD patients and healthy controls or those with other clinical conditions have been conducted. We aimed to compare metacognitions among currently symptomatic OCD (S-OCD) patients, currently remitted OCD patients (R-OCD), and healthy controls (HC). Method: This cross-sectional research was conducted in the Department of Psychiatry of a tertiary care hospital in North India. Purposive sampling method was used to recruit 40 OCD patients, including an equal number of R-OCD and S-OCD patients, and 20 HC matched for age and education. Meta-Cognition Questionnaire and Thought Control Questionnaire were used to assess metacognitive functions. Results: The findings showed a gradient of highest maladaptive metacognitions in the S-OCD group and lowest in HC. In the OCD subgroups, specific metacognitive beliefs (negative beliefs F = 65.52; need to control thoughts F = 61.03) and strategies (worry F = 83.55; low distraction F = 105.61) remained significantly different (P ≤ 0.001) between S-OCD and R-OCD patients. Certain other metacognitions remained consistently more or less stable between S-OCD and R-OCD patients, that is, metacognitive beliefs (cognitive confidence F = 11.43; cognitive self-consciousness F = 37.12) and strategies (punishment F = 17.45; low social control F = 12.89). This finding is further corroborated by positive correlations of severity of OCD with need to control thoughts (r = 0.66, P < 0.001), negative beliefs (r = 0.63, P < 0.001), and worry (r = 0.76, P < 0.001), and negative correlations with distraction (r = - 0.79, P < 0.001). Conclusion: The study provides preliminary evidence for specific metacognitions distinguished as potential state and trait markers for OCD, which needs to be established on a larger sample using a longitudinal study design.

Combinatorial optimization of mRNA structure, stability, and translation for RNA-based therapeutics.

Therapeutic mRNAs and vaccines are being developed for a broad range of human diseases, including COVID-19. However, their optimization is hindered by mRNA instability and inefficient protein expression. Here, we describe design principles that overcome these barriers. We develop an RNA sequencing-based platform called PERSIST-seq to systematically delineate in-cell mRNA stability, ribosome load, as well as in-solution stability of a library of diverse mRNAs. We find that, surprisingly, in-cell stability is a greater driver of protein output than high ribosome load. We further introduce a method called In-line-seq, applied to thousands of diverse RNAs, that reveals sequence and structure-based rules for mitigating hydrolytic degradation. Our findings show that highly structured "superfolder" mRNAs can be designed to improve both stability and expression with further enhancement through pseudouridine nucleoside modification. Together, our study demonstrates simultaneous improvement of mRNA stability and protein expression and provides a computational-experimental platform for the enhancement of mRNA medicines.

Comorbidities in Obsessive-Compulsive Disorder Across the Lifespan: A Systematic Review and Meta-Analysis.

Comorbidities are seen with obsessive-compulsive disorder (OCD) across the lifespan. Neurodevelopmental comorbidities are common in young children, followed by mood, anxiety, and obsessive-compulsive related disorders (OCRDs) in children, adolescents and adults, and neurological and degenerative disorders in the elderly. Understanding comorbidity prevalence and patterns has clinical and research implications. We conducted a systematic review and meta-analysis on comorbidities in OCD across the lifespan, with the objective to, first, estimate age-wise pattern and prevalence of comorbidities with OCD and, second, to examine associations of demographic (age at assessment, gender distribution) and clinical characteristics (age of onset, illness severity) with comorbidities. Four electronic databases (PubMed, EMBASE, SCOPUS, and PsycINFO) were searched using predefined search terms for articles published between 1979 and 2020. Eligible studies, across age, reported original findings on comorbidities and had an OCD sample size of ≥100. We excluded studies that did not use standardised diagnostic assessments, or that excluded patients on the basis of comorbidity. We adhered to the Preferred Reporting Items for Systematic Reviews and Meta-Analyses guidelines. The review protocol has been registered on the International Prospective Register of Systematic Reviews. A comorbidity rate of 69% was found in a pooled sample of more than 15,000 individuals. Mood disorders (major depressive disorder), anxiety disorders (generalised anxiety disorder), neurodevelopmental disorders (NDDs) and OCRDs were the commonest comorbidities. Anxiety disorders prevailed in children, mood disorders in adults, whereas NDDs were similarly prevalent. Higher comorbidity with any psychiatric illness, NDDs, and severe mental disorders was seen in males, vs. females. Illness severity was inversely associated with rates for panic disorder, tic disorders, OCRDs, obsessive compulsive personality disorder, and anorexia nervosa. This systematic review and meta-analysis provides base rates for comorbidities in OCD across the lifespan. This has implications for comprehensive clinical evaluation and management planning. The high variability in comorbidity rates suggests the need for quality, multi-centric, large studies, using prospective designs. Systematic Review Registration: Unique Identifier: CRD42020215904.

Project SUMS (scaling up of mental health in schools): design and methods for a pragmatic, cluster randomised waitlist-controlled trial on integrated school mental health intervention for adolescents.

BACKGROUND: There is an increasing need for Mental Health Promotion (MHP) among adolescents, especially in developing countries with limited resources and rapid socio-demographic transition. With the growing burden of mental health problems among adolescents (suicide, depression) and their preferences to seek help from their peers, improving Mental Health Literacy (MHL) and behaviours for First Aid in Mental Health (MH-FA) becomes crucial to promote their mental health. METHODS: Schools are ideal settings for reaching the vulnerable adolescents. The proposed study evaluates the effectiveness of a classroom-based teacher-led integrated school mental health intervention called SUMS (MHP + MHL + MH-FA). The study will involve a pragmatic, cluster-randomised waitlist-controlled design to evaluate the effectiveness of SUMS intervention using schools as unit-of-randomisation. The study will be conducted in Srinivaspura taluka (Sub-district) of Kolar district (administrative unit of health) of Karnataka in collaboration with a multi-disciplinary expert team from NIMHANS (National Institute of Mental Health And Neuro Sciences), Bangalore-India and Department of Education, Government of Karnataka, India. A total of 8 schools (400 students studying in 6-8 grade) from Srinivaspura taluka will be randomised into intervention and waitlist control group. The intervention group will receive SUMS intervention through 10-15 h of classroom sessions. The primary outcome is the improvement in positive mental health literacy, as measured by the Mental Health-Promoting Knowledge (MHPK-10) scale. Changes in MH-FA knowledge and intentions, Mental health stigma, help-seeking and resilience are assessed as secondary outcomes. Data will be collected at baseline, 6-weeks, 6-months and 12-months post-intervention. The waitlist-control schools will receive the interventions at the end of the 12-month follow-up assessment in intervention-schools. DISCUSSION: This is the first study to integrate Mental Health Literacy with Mental Health Promotion and behaviours for First Aid in Mental Health to promote mental health well-being among adolescent school children in India. With a need to build a more substantial evidence base on School Mental Health Promotion approaches in developing countries, the study findings will have implications for implementing and operationalising Health and Wellness Ambassador initiative in India. TRIAL REGISTRATION: Clinical Trials Registry - India, CTRI/2019/07/020394. Registered prospectively on 29 July 2019. ( ctri.nic.in/Clinicaltrials/pmaindet2.php?trialid=35724&EncHid=&userName=sums ).

Preschool-onset OCD: A review of literature and clinical experience.

Obsessive-compulsive disorder (OCD) has been described in preschool children as young as 2-3 years old. A preschool age onset of OCD has unique diagnostic and therapeutic challenges. In this article, the authors review published literature on preschool onset OCD and present data on preschool-onset OCD (age of onset ≤ 5 years) from clinical records at a tertiary care child and adolescent psychiatry center in India. Literature suggests that OCD that starts this early is phenomenologically similar to OCD in older individuals; however, it has very high rates of comorbidity and a family history of OCD. There is a paucity of data on course, treatment, and long-term outcome in this group. At their center, the authors found a 3% prevalence of preschool-onset OCD, with a male predominance (69%) and fairly high comorbidity rates (62%). Qualitative review highlighted delay in treatment seeking, poor follow-up rates, frequent use of pharmacological treatment, and a high remission rate in those treated adequately.

Obsessive belief and emotional appraisal correlates of symptom dimensions and impairment in obsessive-compulsive disorder.

BACKGROUND: Obsessive-compulsive disorder (OCD) is a heterogeneous and debilitating illness. Symptom dimensions of OCD lend homogeneous avenues for research. Variations in one's appraisal of thoughts and emotions can influence symptom dimensions and impairment. However, little is known about the combined influence of these appraisals in OCD. A clear understanding of these relationships has putative treatment implications. AIM: The aim of the study is to examine the associations among obsessive beliefs, emotional appraisals, and OCD symptom dimensions in adults. MATERIALS AND METHODS: We examined 50 drug-naïve/drug-free adults with active OCD. Symptom dimensions and impairment were assessed using the Dimensional Yale-Brown Obsessive-Compulsive Severity Scale. Obsessive beliefs and emotional appraisals were studied using the Obsessive Beliefs Questionnaire-44 and Perception of Threat from Emotion Questionnaire. RESULTS: Tobit regression analysis showed the differential association of obsessive beliefs and symptom dimensions - perfectionism/certainty associated with contamination and responsibility/threat estimation associated with aggressive obsessions. Impairment was associated with dimensional symptom severities and with the perception of threat from anger. This association remained even after controlling for depression severity and obsessive beliefs. CONCLUSIONS: OCD symptom dimensions are heterogeneous in underlying obsessive beliefs. Emotional appraisals contribute significantly to impairment alongside symptom severity. Emotion-focused interventions must be included in the psychotherapeutic interventions for OCD.

Prevalence of child maltreatment in India and its association with gender, urbanisation and policy: a rapid review and meta-analysis protocol.

INTRODUCTION: India is home to 20% of the world's children and yet, little is known on the magnitude and trends of child maltreatment nationwide. The aims of this review are to provide a prevalence of child maltreatment in India with considerations for any effects of gender; urbanisation (eg, urban vs rural) and legislation (Protection of Children from Sexual Offences (POCSO) Act 2012). METHODS AND ANALYSIS: A rapid review will be undertaken of all quantitative peer-reviewed studies on child maltreatment in India between 2005 and 2020. Four electronic databases will be systematically searched: PubMed, EMBASE, Cochrane and PsychInfo. The primary outcomes will include all aspects of child maltreatment: physical abuse, sexual abuse, emotional abuse, emotional neglect and physical neglect. Study participants will be between 0 and 18 years and will have reported maltreatment experiences using validated, reliable tools such as the Adverse Childhood Experiences Questionnaire as well as child self-reports and clinician reports. Study selection will follow the Preferred Reporting Items for Systematic Reviews and Meta-Analyses guidelines, and the methodological appraisal of the studies will be assessed by the Newcastle-Ottawa Quality assessment scale. A narrative synthesis will be conducted for all included studies. Also, if sufficient data are available, a meta-analysis will be conducted. Effect sizes will be determined from random-effects models stratified by gender, urbanisation and the pre-2012 and post-2012 POCSO Act cut-off. I2 statistics will be used to assess heterogeneity and identify their potential sources and τ2 statistics will indicate any between-study variance. ETHICS AND DISSEMINATION: As this is a rapid review, minimal ethical risks are expected. The protocol and level 1 self-audit checklist were submitted and approved by the Usher Research Ethics Group panel in the Usher Institute (School of Medicine and Veterinary Sciences) at the University of Edinburgh (Reference B126255). Findings from this review will be disseminated widely through peer-reviewed publications and in various media, for example, conferences, congresses or symposia. PROSPERO REGISTRATION NUMBER: CRD42019150403.

Psychological ownership interventions increase interest in claiming government benefits.

Each year, eligible individuals forgo billions of dollars in financial assistance in the form of government benefits. To address this participation gap, we identify psychological ownership of government benefits as a factor that significantly influences individuals' interest in applying for government benefits. Psychological ownership refers to how much an individual feels that a target is their own. We propose that the more individuals feel that government benefits are their own, the less likely they are to perceive applying for them as an aversive ask for help, and thus, the more likely they are to pursue them. Three large-scale field experiments among low-income individuals demonstrate that higher psychological ownership framing of government benefits significantly increases participants' pursuit of benefits and outperforms other common psychological interventions. An additional experiment shows that this effect occurs because greater psychological ownership reduces people's general aversion to asking for assistance. Relative to control messages, these psychological ownership interventions increased interest in claiming government benefits by 20% to 128%. These results suggest that psychological ownership framing is an effective tool in the portfolio of potential behavioral science interventions and a simple way to stimulate interest in claiming benefits.

Combinatorial optimization of mRNA structure, stability, and translation for RNA-based therapeutics.

Therapeutic mRNAs and vaccines are being developed for a broad range of human diseases, including COVID-19. However, their optimization is hindered by mRNA instability and inefficient protein expression. Here, we describe design principles that overcome these barriers. We develop a new RNA sequencing-based platform called PERSIST-seq to systematically delineate in-cell mRNA stability, ribosome load, as well as in-solution stability of a library of diverse mRNAs. We find that, surprisingly, in-cell stability is a greater driver of protein output than high ribosome load. We further introduce a method called In-line-seq, applied to thousands of diverse RNAs, that reveals sequence and structure-based rules for mitigating hydrolytic degradation. Our findings show that "superfolder" mRNAs can be designed to improve both stability and expression that are further enhanced through pseudouridine nucleoside modification. Together, our study demonstrates simultaneous improvement of mRNA stability and protein expression and provides a computational-experimental platform for the enhancement of mRNA medicines.

Association of insight, avoidance behavior, indecisiveness, and inflated responsibility with other clinical characteristics in children and adolescents with obsessive-compulsive disorder

Objectives: Although the Children's Yale-Brown Obsessive-Compulsive Scale (CY-BOCS) includes ancillary symptom dimensions - insight, avoidance, degree of indecisiveness, inflated sense of responsibility, pervasive slowness/disturbance of inertia, and pathological doubting -, we know little about their clinical/scientific utility. We examined these ancillary dimensions in childhood obsessive-compulsive disorder (OCD), and tested their associations with clinical characteristics. Methods: Treatment-seeking children and adolescents (n=173) with a DSM-5 OCD diagnosis were recruited from six centers in India and evaluated with a semi-structured proforma for sociodemographic/clinical details, the Structured Clinical Interview for DSM-5, the CY-BOCS, the Children's Depression Rating Scale, and the Family Interview for Genetic Studies. Regression analysis was used to study the associations between ancillary dimensions (independent variables) and clinical variables (dependent variables). Results: 87.9% of the sample reported at least a mild-moderate severity of ancillary dimensions, which were highly intercorrelated. Multiple ancillary dimensions were correlated with illness severity on the CY-BOCS. On regression analysis, only insight and avoidance retained significance. There were few differential associations between OCD symptom and ancillary dimensions. Conclusion: Ancillary dimensions are more a feature of illness severity than differentially associated with individual symptom dimensions in childhood OCD. Insight and avoidance should be considered for inclusion in the assessment of illness severity in childhood OCD.