Mapping Youth Awareness of Sports Betting Advertising During the 2022 FIFA World Cup.

Young people are known to be highly engaged in sports betting and therefore may be particularly susceptible to the effects of gambling-related advertising. The purpose of the present study was to examine young people's recall of sports betting advertising during the 2022 FIFA World Cup. The sample consisted of 190 UK residents aged 18-24 who had watched at least one 2022 World Cup match. A cross-sectional survey was conducted to collect data on participants' recall of sports betting advertisements across several media types and for different bets and betting offers, as well as their problem gambling scores. The findings indicated that young people were able to recall a high amount of advertising for various types of bets (95.6%) and betting inducements (89.5%). A high proportion of young people recalled advertising for risky bet types and promotions, such as 64.2% for in-play betting and 68.1% for sign-up offers. Overall, higher-risk gamblers recalled encountering more advertising than lower-risk gamblers. Participants recalled encountering sports betting advertisements on social media the most (10-14 ads per week), then on internet banners and television (5-9 ads per week, respectively). Less than half (46.3%) of respondents were aware of advertising for responsible gambling tools. This study underscores the need for policy measures that limit young people's exposure to gambling advertising, particularly for products that may contribute to gambling-related harm, and that increase the promotion of responsible gambling tools.

Organic Reactivity Made Easy and Accurate with Automated Multireference Calculations.

In organic reactivity studies, quantum chemical calculations play a pivotal role as the foundation of understanding and machine learning model development. While prevalent black-box methods like density functional theory (DFT) and coupled-cluster theory (e.g., CCSD(T)) have significantly advanced our understanding of chemical reactivity, they frequently fall short in describing multiconfigurational transition states and intermediates. Achieving a more accurate description necessitates the use of multireference methods. However, these methods have not been used at scale due to their often-faulty predictions without expert input. Here, we overcome this deficiency with automated multiconfigurational pair-density functional theory (MC-PDFT) calculations. We apply this method to 908 automatically generated organic reactions. We find 68% of these reactions present significant multiconfigurational character in which the automated multiconfigurational approach often provides a more accurate and/or efficient description than DFT and CCSD(T). This work presents the first high-throughput application of automated multiconfigurational methods to reactivity, enabled by automated active space selection algorithms and the computation of electronic correlation with MC-PDFT on-top functionals. This approach can be used in a black-box fashion, avoiding significant active space inconsistency error in both single- and multireference cases and providing accurate multiconfigurational descriptions when needed.

The Scalable Variant Call Representation: Enabling Genetic Analysis Beyond One Million Genomes.

The Variant Call Format (VCF) is widely used in genome sequencing but scales poorly. For instance, we estimate a 150,000 genome VCF would occupy 900 TiB, making it both costly and complicated to produce and analyze. The issue stems from VCF's requirement to densely represent both reference-genotypes and allele-indexed arrays. These requirements lead to unnecessary data duplication and, ultimately, very large files. To address these challenges, we introduce the Scalable Variant Call Representation (SVCR). This representation reduces file sizes by ensuring they scale linearly with samples. SVCR achieves this by adopting reference blocks from the Genomic Variant Call Format (GVCF) and employing local allele indices. SVCR is also lossless and mergeable, allowing for N+1 and N+K incremental joint-calling. We present two implementations of SVCR: SVCR-VCF, which encodes SVCR in VCF format, and VDS, which uses Hail's native format. Our experiments confirm the linear scalability of SVCR-VCF and VDS, in contrast to the super-linear growth seen with standard VCF files. We also discuss the VDS Combiner, a scalable, open-source tool for producing a VDS from GVCFs and unique features of VDS which enable rapid data analysis. SVCR, and VDS in particular, ensure the scientific community can generate, analyze, and disseminate genetics datasets with millions of samples.

The role of stigma in cannabis use disclosure: an exploratory study.

BACKGROUND: Although cannabis use incidence, societal acceptance, and legislation all trend positively, cannabis remains federally illegal in the USA. Prior studies have revealed that patients are reluctant to disclose their cannabis use history in the healthcare system, which can negatively impact patient care. This study reports the frequency of cannabis use disclosure with special considerations for stigmatization. To better understand the limitations, providers face in providing collaborative, comprehensive, and informed care, this study evaluated four domains of stigma: perceived, anticipated, enacted, and internalized. METHODS: This study used a descriptive exploratory design. Data collection occurred using an anonymous, online national survey with a convenience sample in the USA. Recruitment relied on electronic media and occurred between July and December 2022. Participants were adults older than 21 years and self-identified as having used cannabis and accessed the healthcare system within the last five years. The survey measured demographic characteristics, cannabis use, and disclosure patterns. Stigma was measured using the Stigma Use Stigma Mechanism Scale (SU-SMS) and Substance Abuse Use Self-Stigma Scale (SASSS) with language modifications for cannabis. Ordinal logistic regression models were performed to evaluate associations between the frequency of cannabis use disclosure patterns and each stigma category. Associations were assessed using Chi-squared or Fisher's exact tests. RESULTS: Data were available for 249 respondents. Most participants (57.1%) reported initiating a conversation about cannabis with their healthcare provider; 27.8% of the time, cannabis is never discussed, and healthcare providers initiate only 15.1% of related discussions. Anticipated stigma [95% CI 1.045-1.164] and total stigma [95% CI 1.001-1.039] had statistically significant associations with nondisclosure. Annual household income (p = .04), chronicity of cannabis use (p = .03), frequency of cannabis use (p = .02), and a known amount of CBD in products consumed (p = .01) had statistically significant associations with the frequency of cannabis use disclosure. CONCLUSIONS: Patients who use cannabis experience stigmatization in the healthcare setting that may limit disclosure of cannabis use history. Future studies would be well served to explore anticipated stigma more deeply. Healthcare providers should be knowledgeable to lead such conversations relating to cannabis while maintaining an unbiased perspective.

Divergent Bimetallic Mechanisms in Copper(II)-Mediated C-C, N-N, and O-O Oxidative Coupling Reactions.

Copper-catalyzed aerobic oxidative coupling of diaryl imines provides a route for conversion of ammonia to hydrazine. The present study uses experimental and density functional theory computational methods to investigate the mechanism of N-N bond formation, and the data support a mechanism involving bimolecular coupling of Cu-coordinated iminyl radicals. Computational analysis is extended to CuII-mediated C-C, N-N, and O-O coupling reactions involved in the formation of cyanogen (NC-CN) from HCN, 1,3-butadiyne from ethyne (i.e., Glaser coupling), hydrazine from ammonia, and hydrogen peroxide from water. The results reveal two different mechanistic pathways. Heteroatom ligands with an uncoordinated lone pair (iminyl, NH2, OH) undergo charge transfer to CuII, generating ligand-centered radicals that undergo facile bimolecular radical-radical coupling. Ligands lacking a lone pair (CN and CCH) form bridged binuclear diamond-core structures that undergo C-C coupling. This mechanistic bifurcation is rationalized by analysis of spin densities in key intermediates and transition states, as well as multiconfigurational calculations. Radical-radical coupling is especially favorable for N-N coupling owing to energetically favorable charge transfer in the intermediate and thermodynamically favorable product formation.

Red box, green box: A self-report behavioral frequency measurement approach for behavioral addictions research.

Behavior frequency measures in behavioral addictions research fail to account for how engagement in the activity relates to each respondent's personal circumstances. We propose a "Red Box, Green Box" method, an alternative to conventional self-report behavior questions. Participants report two distinct time-based values: (1) Green box: time spent engaged in the activity during 'free' time, and (2) Red box: engagement in the activity at times when the respondent should be doing something else (e.g., studying, working, sleeping, exercising, etc.). Some practical examples of the 'red box, green box' method are provided. This method may help to calibrate behavioral frequency for each respondent and yield clearer insights into displacement effects and risks associated with frequency of use. We suggest some future research directions to test the feasibility and utility of this approach in different implementations.

The longitudinal associations between internet addiction and ADHD symptoms among adolescents.

Background and aims: Internet addiction has been linked to ADHD-related symptoms. However, the direction of the relationship and its potential for reciprocal relations is not well understood. This study examined the potential reciprocal relations between the three components of ADHD and Internet addiction, as well as the moderating effects of gender on these relations. Methods: Using a longitudinal design, we collected data of 865 Chinese adolescents across three waves (Mage = 13.78, SD = 1.56 in wave 1), with a time interval of 6 months. Results: Cross-lagged analyses revealed bidirectional associations between hyperactivity, inattention, impulsivity, and Internet addiction over time. Multi-group analyses did not yield any significant gender differences in these relationships. Discussion and conclusions: These findings enhance our understanding of the complex link between ADHD components and Internet addiction and have implications for interventions aimed at reducing the prevalence of Internet addiction and ADHD.

Distinct Hodgkin lymphoma subtypes defined by noninvasive genomic profiling.

The scarcity of malignant Hodgkin and Reed-Sternberg cells hampers tissue-based comprehensive genomic profiling of classic Hodgkin lymphoma (cHL). By contrast, liquid biopsies show promise for molecular profiling of cHL due to relatively high circulating tumour DNA (ctDNA) levels1-4. Here we show that the plasma representation of mutations exceeds the bulk tumour representation in most cases, making cHL particularly amenable to noninvasive profiling. Leveraging single-cell transcriptional profiles of cHL tumours, we demonstrate Hodgkin and Reed-Sternberg ctDNA shedding to be shaped by DNASE1L3, whose increased tumour microenvironment-derived expression drives high ctDNA concentrations. Using this insight, we comprehensively profile 366 patients, revealing two distinct cHL genomic subtypes with characteristic clinical and prognostic correlates, as well as distinct transcriptional and immunological profiles. Furthermore, we identify a novel class of truncating IL4R mutations that are dependent on IL-13 signalling and therapeutically targetable with IL-4Rα-blocking antibodies. Finally, using PhasED-seq5, we demonstrate the clinical value of pretreatment and on-treatment ctDNA levels for longitudinally refining cHL risk prediction and for detection of radiographically occult minimal residual disease. Collectively, these results support the utility of noninvasive strategies for genotyping and dynamic monitoring of cHL, as well as capturing molecularly distinct subtypes with diagnostic, prognostic and therapeutic potential.

Palliative Medicine and End of Life Care Between Races in an Academic Intensive Care Unit.

Background: Although palliative medicine (PM) is more commonly being integrated into the intensive care unit (ICU), research on racial disparities in this area is lacking. Our objectives were to (a) identify racial disparities in utilization of PM consultation for patients who received ICU care and (b) determine if there were differences in the use of code status or PM consultation over time based on race. Materials and Methods: Retrospective analysis of 571 patients, 18 years and above, at a tertiary care institution who received ICU care and died during their hospital stay. We analyzed two timeframes, 2008-2009 and 2018-2019. Univariate analysis was utilized to evaluate baseline characteristics. A multivariate logistic regression model and interaction P values were employed to assess for differential use of PM consultation, do not resuscitate (DNR) orders, and comfort care (CC) orders between races in aggregate and for changes over time. Results: There was a notable increase in Black/African-American (AA) (54% to 61%) and Hispanic/Latino (2% to 3%) patients over time in our population. Compared to White patients, we found no differences between PM consultation and CC orders. There was a lower probability of DNR orders for Black/AA (adjusted odds ratio [aOR] 0.569; P = .049; confidence interval [CI]: 0.324-0.997) and other/unknown/multiracial patients (aOR: 0.389; P = .273; CI: 0.169-0.900). Comparing our earlier time period to the later time period, we found an increased usage of PM for all patients. Interaction P values suggest there were no differences between races regarding PM, DNR, and CC orders. Conclusions: PM use has increased over time at our institution. Contrary to the previous literature, there were no differences in the frequency of utilization of PM consultation between races. Further analysis to evaluate the usage of PM in the ICU setting in varying populations and geographic locations is warranted.

Impaired control and gaming-related harm in relation to gaming Disorder.

The concept of impaired control (IC) over gaming is an important element of assessment and interventions for problem gaming and gaming-related harm. Past studies have reported that gaming disorder (GD) is associated with various negative consequences, but there is limited research on the relationship between IC over gaming and negative outcomes. To address this gap, the study investigated the relationship between impaired control and gaming-related harm among individuals with self-identified gaming disorder. It was hypothesized that IC would be positively associated with gaming-related harm and harm severity. In addition, it was predicted that IC would be a significant predictor of harm when controlling for age, gender, psychological distress, and gaming urges. The current study recruited 513 participants through an online survey platform. The Impaired Control Over Gaming Scale (ICOGS) was used to measure IC, and modified items from Browne et al.'s taxonomy of gambling harms were used to assess gaming harm severity. The logistic regression results showed that IC was positively related to all forms of harm, after controlling for other variables. The predictive value of IC was similar across financial, psychological, relationship, social and work/school domains. These results supported the importance of IC as a mechanism that contributes to the experience of gaming-related harm, and the need to target IC in interventions for GD.

Reconsidering item response categories in gaming disorder symptoms measurement.

Gaming disorder (GD) screening often involves self-report survey measures to detect the presence of symptoms. Studies have shown that gamers' responses vary greatly across survey items. Some symptoms, such as preoccupation and tolerance, are frequently reported by highly engaged but non-problematic gamers, and therefore these symptoms are thought to lack specificity and are suggested to be less important in classification decisions. We argue that the influence of response categories (e.g., dichotomous responses, such as 'yes' or 'no'; or frequency categories, such as 'rarely' and 'often') on item responses has been relatively underexplored despite potentially contributing significantly to the psychometric performance of items and scales. In short, the type of item response may be just as important to symptom reporting as the content of survey questions. We propose some practical alternatives to currently used item categories across GD tools. Research should examine the performance of different response categories, including whether certain response categories aid respondents' comprehension and insight, and better capture pathological behaviours and harms.

Social chatbot use (e.g., ChatGPT) among individuals with social deficits: Risks and opportunities.

Social chatbots powered by artificial intelligence (AI) may be particularly appealing to individuals with social deficits or conditions that affect their social functioning. In this letter, we discuss some of the noteworthy characteristics of social chatbots and how they may influence adaptive and maladaptive behaviors, including the potential for 'dependency' on chatbots. We call for more independent studies to evaluate the potential developmental and therapeutic effects of this increasingly popular technology.

CHARR efficiently estimates contamination from DNA sequencing data.

DNA sample contamination is a major issue in clinical and research applications of whole-genome and -exome sequencing. Even modest levels of contamination can substantially affect the overall quality of variant calls and lead to widespread genotyping errors. Currently, popular tools for estimating the contamination level use short-read data (BAM/CRAM files), which are expensive to store and manipulate and often not retained or shared widely. We propose a metric to estimate DNA sample contamination from variant-level whole-genome and -exome sequence data called CHARR, contamination from homozygous alternate reference reads, which leverages the infiltration of reference reads within homozygous alternate variant calls. CHARR uses a small proportion of variant-level genotype information and thus can be computed from single-sample gVCFs or callsets in VCF or BCF formats, as well as efficiently stored variant calls in Hail VariantDataset format. Our results demonstrate that CHARR accurately recapitulates results from existing tools with substantially reduced costs, improving the accuracy and efficiency of downstream analyses of ultra-large whole-genome and exome sequencing datasets.

Variational Active Space Selection with Multiconfiguration Pair-Density Functional Theory.

The selection of an adequate set of active orbitals for modeling strongly correlated electronic states is difficult to automate because it is highly dependent on the states and molecule of interest. Although many approaches have shown some success, no single approach has worked well in all cases. In light of this, we present the "discrete variational selection" (DVS) approach to active space selection, in which one generates multiple trial wave functions from a diverse set of systematically constructed active spaces and then selects between these wave functions variationally. We apply this DVS approach to 207 vertical excitations of small-to-medium-sized organic and inorganic molecules (with 3 to 18 atoms) in the QUESTDB database by (i) constructing various sets of active space orbitals through diagonalization of parametrized operators and (ii) choosing the result with the lowest average energy among the states of interest. This approach proves ineffective when variationally selecting between wave functions using the density matrix renormalization group (DMRG) or complete active space self-consistent field (CASSCF) energy but is able to provide good results when variationally selecting between wave functions using the energy of the translated PBE (tPBE) functional from multiconfiguration pair-density functional theory (MC-PDFT). Applying this DVS-tPBE approach to selection among state-averaged DMRG wave functions, we obtain a mean unsigned error of only 0.17 eV using hybrid MC-PDFT. This result matches that of our previous benchmark without the need to filter out poor active spaces and with no further orbital optimization following active space selection of the SA-DMRG wave functions. Furthermore, we find that DVS-tPBE is able to robustly and effectively select between the new SA-DMRG wave functions and our previous SA-CASSCF results.

Linearized Pair-Density Functional Theory for Vertical Excitation Energies.

Multiconfiguration pair-density functional theory (MC-PDFT) is a computationally efficient method that computes the energies of electronic states in a state specific or state average framework via an on-top functional. However, MC-PDFT does not include state interaction among these states since the final energies do not come from the diagonalization of an effective model-space Hamiltonian. Recently, multistate extensions such as linearized PDFT (L-PDFT) have been developed to accurately model the potentials near conical intersections and avoided crossings. However, there has not been any systematic study evaluating their performance for predicting vertical excitations at the equilibrium geometry of a molecule, when the excited states are generally well separated. In this paper, we report the performance of L-PDFT on the extensive QUESTDB data set of vertical excitations using a database of automatically selected active spaces. We show that L-PDFT performs well on all these excitations and successfully reproduces the performance of MC-PDFT. These results further demonstrate the potential of L-PDFT, as its scaling is constant with the number of states included in the state-average manifold, whereas MC-PDFT scales linearly in this regard.

Validation of the Ten-Item Internet Gaming Disorder Test (IGDT-10) and Its Association with Functional Impairment in Brazilian Gamers.

INTRODUCTION: Despite the growing recognition of gaming disorder as a mental disorder, there is still debate about how it should be best screened for. This is especially relevant in countries where prevalence studies that could support evidence-based policymaking are still to be conducted. This study aims to evaluate the psychometric properties of the Brazilian Portuguese version of the Ten-Item Internet Gaming Disorder Test (IGDT-10) and to explore its association with functional impairment. METHODS: An online convenience sample of 805 Brazilian adults who reported playing games completed the adapted version of IGDT-10 and World Health Organization Disability Assessment Schedule 2.0, as well as the Problematic Internet Use Questionnaire, the Center for Epidemiologic Studies-Depression Scale, the Rosenberg Self Esteem Scale and socio-demographic questions. RESULTS: The Brazilian Portuguese version of IGDT-10 demonstrated a unidimensional structure in both confirmatory and exploratory factor analysis, with satisfactory internal consistency and adequate temporal stability. Participants who scored five or more on IGDT-10 presented higher levels of functional impairment compared to those who scored positive for four symptoms or less. The difference between the two groups was statistically significant and showed a moderate effect size. Network analysis showed a direct connection between IGDT-10 and functional impairment, and identified "negative consequences" as the most relevant item connecting these variables. CONCLUSION: The IGDT-10 is a brief, easy-to-understand, valid, and reliable instrument, proving to be a suitable candidate for screening gaming disorder in future epidemiological studies.

Plasma cells in human pancreatic ductal adenocarcinoma secrete antibodies against self-antigens.

Intratumoral B cell responses are associated with more favorable clinical outcomes in human pancreatic ductal adenocarcinoma (PDAC). However, the antigens driving these B cell responses are largely unknown. We sought to discover these antigens by using single-cell RNA sequencing (scRNA-Seq) and immunoglobulin (Ig) sequencing of tumor-infiltrating immune cells from 7 primary PDAC samples. We identified activated T and B cell responses and evidence of germinal center reactions. Ig sequencing identified plasma cell (PC) clones expressing isotype-switched and hypermutated Igs, suggesting the occurrence of T cell-dependent B cell responses. We assessed the reactivity of 41 recombinant antibodies that represented the products of 235 PCs and 12 B cells toward multiple cell lines and PDAC tissues and observed frequent staining of intracellular self-antigens. Three of these antigens were identified: the filamentous actin (F-actin), the nucleic protein RuvB like AAA ATPase 2 (RUVBL2), and the mitochondrial protein heat shock protein family D (Hsp60) member 1 (HSPD1). Antibody titers against F-actin and HSPD1 were substantially elevated in the plasma of patients with PDAC compared with healthy donors. Thus, PCs in PDAC produce autoantibodies reacting with intracellular self-antigens, which may result from promotion of preexisting, autoreactive B cell responses. These observations indicate the chronic inflammatory microenvironment of PDAC can support the adaptive immune response.

Predicting 'Brainage' in late childhood to adolescence (6-17yrs) using structural MRI, morphometric similarity, and machine learning.

Brain development is regularly studied using structural MRI. Recently, studies have used a combination of statistical learning and large-scale imaging databases of healthy children to predict an individual's age from structural MRI. This data-driven, predicted 'Brainage' typically differs from the subjects chronological age, with this difference a potential measure of individual difference. Few studies have leveraged higher-order or connectomic representations of structural MRI data for this Brainage approach. We leveraged morphometric similarity as a network-level approach to structural MRI to generate predictive models of age. We benchmarked these novel Brainage approaches using morphometric similarity against more typical, single feature (i.e., cortical thickness) approaches. We showed that these novel methods did not outperform cortical thickness or cortical volume measures. All models were significantly biased by age, but robust to motion confounds. The main results show that, whilst morphometric similarity mapping may be a novel way to leverage additional information from a T1-weighted structural MRI beyond individual features, in the context of a Brainage framework, morphometric similarity does not provide more accurate predictions of age. Morphometric similarity as a network-level approach to structural MRI may be poorly positioned to study individual differences in brain development in healthy participants in this way.

The relationship between parenting styles and adolescent problematic Internet use: A three-level meta-analysis.

Background and aims: Problematic Internet use (PIU) has become a global public health problem. It has been suggested that parenting style is associated with adolescent PIU. However, the evidence in favor of this view is mixed. Based on the PRISMA method, the present study employed three-level meta-analysis approach to investigate the relationship between these two variables and further explore potential moderators. Methods: After a systematic search for published articles, 35 studies were included, reporting 171 effect sizes (N = 40,587). Results: The results showed that positive parenting styles were significantly negatively related to PIU. This association was moderated by gender, age, publication year, and measurements of PIU, but was not by culture and measurements of parenting styles. Negative parenting styles were significantly positively related to PIU, which was moderated by publication year, culture, and sub-types of negative parenting, but not by gender, age, and measurements of both parenting styles and PIU. In addition, the correlation of PIU with negative parenting styles was stronger than that with positive parenting styles. Discussion and Conclusions: The present results demonstrated that parenting styles, especially punitive parenting styles, should be attached to more important when treating adolescent PIU.