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Thoracic radiation therapy (TRT) is commonly used for breast, lung, and lymphoid cancers. While its cardiotoxic effects, particularly coronary artery disease, are well recognized, less is known about its association with arrhythmia-related hospitalizations. A retrospective cohort study using the National Inpatient Sample (2016-2022) was conducted. Hospitalizations for atrial fibrillation or flutter were identified using ICD-10 codes. Documented prior thoracic irradiation was defined using a history of radiation therapy code in combination with thoracic malignancy codes. Propensity score matching followed by post-matching multivariable regression adjustment was used to evaluate outcomes. The primary endpoint was in-hospital mortality; secondary endpoints included length of stay (LOS) and total costs. Among 3,198,304 weighted admissions, 8,570 (0.27%) had prior TRT. After matching, TRT was associated with higher odds of in-hospital mortality (adjusted odds ratio [aOR] 1.97; 95% CI 1.17-3.32; p=0.010) and longer LOS (+0.30 days; 95% CI 0.05-0.55; p=0.019) without increased costs (p=0.202). Hospitalizations with documented prior thoracic irradiation also had higher odds of palliative consultation (aOR 2.60, p<0.001) and DNR status (aOR 1.97, p<0.001), but lower odds of acute kidney injury (aOR 0.66, p<0.001). Documented prior thoracic irradiation identified a clinically complex subgroup of atrial fibrillation or flutter hospitalizations with higher in-hospital mortality, slightly longer length of stay, and greater goals-of-care utilization.

The experiences foster caregivers have while providing care are linked to important outcomes including placement stability for the child and foster caregiver retention within the child welfare system. Understanding the expectations prospective caregivers have about fostering, and how this compares to their lived experience while fostering, is important for building realistic expectations and addressing unmet needs. The current study used a phenomenological approach through semi-structured qualitative interviews with 45 foster parents (71% female) to assess their recollections of what they had expected fostering to be like, and their thoughts about their fostering experiences to date. Inductive coding revealed positive, negative and neutral expectation and experience themes, as well as a "no expectations" theme, with several subcodes within each. Participants were mixed in terms of whether they agreed their experience had matched their expectations. While a subset of foster caregivers felt their expectations were in alignment with what their lived experience fostering has been, many felt that there were multiple experiences they had not expected, both positive and negative. The themes revealing unmet expectations as well as unforeseen negative experiences have implications for foster care licensing agencies, who can work to assess and develop appropriate expectations for prospective caregivers.

Systematic clinical phenotyping using Human Phenotype Ontology (HPO) is central to rare disease diagnosis. However, current disease prioritization (ranking candidate diseases from HPO for a patient) methods face key challenges: they often fail to account for the hierarchical structure of HPO terms, ignore dependencies among correlated terms, and do not adjust for batch effects arising from systematic differences in phenotype documentation across cohorts, institutions, or clinicians. We aim to develop a scalable and statistically principled framework to address these limitations for rare disease prediction and patient stratification. We developed PhenoSS, a Gaussian copula-based framework that models disease-specific marginal prevalence of HPO terms while capturing their joint dependencies through a multivariate normal distribution. Phenotype frequencies were estimated using external curated resources, including OARD (Open Annotations for Rare Diseases) and HPO annotations. PhenoSS supports both pair-wise phenotype similarity calculation for patient clustering and posterior odds estimation for patient-specific disease prioritization. A batch-effect correction module mitigates systematic phenotyping differences across datasets. Across diverse simulation scenarios, PhenoSS demonstrated robust disease-prediction performance and consistently improved accuracy after batch-effect correction. In real electronic health record data, PhenoSS identified clinically meaningful patient clusters and effectively distinguished patients with different rare diseases. In disease prioritization tasks, PhenoSS achieved competitive performance with existing methods, particularly for patients exhibiting sparse or noisy phenotype annotations. PhenoSS provides a statistically interpretable framework for modeling phenotypic heterogeneity in rare disease research and is adaptable to other structured clinical vocabularies such as SNOMED-CT and ICD codes.

BackgroundNon-tobacco nicotine dependence (NTND) products, such as vaping, nicotine patches/pouches, gum, and lozenges, have become increasingly prevalent. While the negative effects of cigarette smoking on bone healing are well established, the impact of NTND on surgical outcomes remain unclear, particularly in foot and ankle surgery. This study aimed to evaluate the effect of NTND on short- and long-term postoperative complications following midfoot arthrodesis, a procedure commonly performed for arthritis, trauma, and congenital deformities.MethodsThis retrospective cohort study was conducted utilizing the TriNetX database. Patients undergoing midfoot arthrodesis were identified and stratified into NTND (ICD-10: F17, excluding tobacco-specific codes) and nonsmoker cohorts. 1:1 propensity score matching was performed based on demographic and comorbid variables. Postoperative complications were assessed at both 90 days and 2 years utilizing risk ratios (RRs) and 95% confidence intervals (CIs).ResultsAfter matching, 1235 patients were included in each cohort. At 90 days, NTND patients had significantly higher rates of opioid prescriptions (RR 1.18, 95% CI: 1.11-1.26), emergency department visits (RR 1.52, 95% CI: 1.20-1.93), hospitalizations (RR 1.59, 95% CI: 1.28-1.99), postoperative infections (RR 1.95, 95% CI: 1.13-3.37), and wound complications (RR 1.72, 95% CI: 1.14-2.58) (all P < .05). At 2 years, NTND was associated with increased rates of pseudoarthrosis (RR 1.27, 95% CI: 1.06-1.51) and mechanical implant failure (RR 1.39, 95% CI: 1.11-1.75) (both P < .05).ConclusionNon-tobacco nicotine dependence is associated with significantly increased risk of both early and late postoperative complications following midfoot arthrodesis. These findings suggest that vaping may adversely affect bone healing and implant integrity. Surgeons should incorporate NTND screenings and cessation counseling into preoperative planning to optimize patient outcomes.Level of Evidence:III-Retrospective Comparative Study.

AI has become increasingly used in mental health care for applications such as diagnosis, monitoring, and treatment support. These include tools like clinician support systems, large language models, and conversational agents used to augment psychotherapy and clinical decision-making. While prior research suggests potential benefits of and concerns with AI, little is known within the domain of obsessive-compulsive disorder (OCD). Given the expanding role of AI in psychiatry, understanding these perspectives is essential to ensuring AI implementation aligns with patient priorities and values. This study aims to explore the perspectives of individuals with OCD on the use of AI in health care, including perceived benefits, risks, and its role in relation to human clinicians. We conducted semistructured interviews with 24 adults self-reporting OCD, recruited through online communities and advocacy networks. Eligible individuals (&#x2265;18 y with self-reported OCD) completed screening, provided informed consent, and participated in remote Health Insurance Portability and Accountability Act (HIPAA)-compliant Zoom (Zoom Communications, Inc) interviews (May-December 2024). Transcripts were deidentified, open-coded, and used to develop a codebook. Focused codes were applied using a thematic analysis framework in Dedoose (v9.2.22; Sociocultural Research Consultants, LLC). Each transcript was independently coded by 2 reviewers, with discrepancies resolved through consensus. Themes were developed through iterative interpretive analysis of code clusters. Participants' perspectives encompassed concerns and benefits of AI in mental health care. Participants expressed concerns about the accuracy and efficacy of information provided by AI, as well as a limited ability for clinical judgment in psychiatric care. Additionally, participants emphasized the importance of human connection, particularly therapeutic alliance, empathy, and reassurance provided by clinicians, which they felt AI could not replicate. Concerns about data privacy, security, and downstream use of information were also highlighted. Despite concerns, many endorsed the use of AI as an adjunct rather than a replacement for clinicians, noting potential benefits in symptom monitoring, preliminary information gathering, and support for administrative tasks, provided that human oversight is maintained. Individuals with OCD expressed nuanced views on AI in mental health care, balancing cautious optimism with several concerns. While AI may improve efficiency, standardization, and symptom monitoring, participants highlighted risks related to deindividualization, accuracy, and erosion of human connection. These findings underscore the importance of patient-centered, ethically guided AI integration that preserves the therapeutic alliance while leveraging technological benefits.

Vortex beams carrying orbital angular momentum enable high-capacity optical communication and imaging, yet multiple scattering in dynamic media such as biological tissues disrupts their wavefront. Brownian motion decorrelates the scattered field and invalidates conventional methods. To address this, we propose a high-fidelity deep-learning demodulation that integrates data-driven and physical priors. Specifically, we directly utilize experimentally acquired full-field speckle patterns from a dynamic aqueous milk scattering system as the training dataset. We introduce an improved quantum-limited-fidelity residual network, QLF-ResNet, that uses a forced L2 normalization layer at the output to hard-code energy conservation and applies rotation-based data augmentation for end-to-end training. Experiments achieve an average classification accuracy of [91.25]% &#xb1; [4.15]% for OAM modes l = 1-4. The model resolves complex coefficients, suppresses crosstalk, and analytically renders the donut intensity and helical phase. By hard-coding physical priors, our method avoids artifacts common in pure data-driven models and offers a robust, interpretable decoding scheme for complex time-varying scattering environments.

Student engagement in music classrooms is important because it reflects students' active participation in listening, performing, and creative activities and is associated with academic, social, and psychological outcomes. Although teacher support has been widely linked to student engagement, the indirect association between perceived teacher support, music learning motivation, and engagement in music education remains underexplored, especially in general school settings. This mixed-methods study examined associations among students' perceived teacher support, music learning motivation, and engagement in junior high school music classrooms. Survey data were collected from 568 junior high school students in urban and rural areas of Liaoning Province, Northeast China. Quantitative analyses examined associations among perceived teacher support, music learning motivation, and student engagement, and the SPSS PROCESS macro with 5,000 bootstrap samples was used to estimate the statistical indirect association. Semi-structured interviews with 15 students were analyzed through a three-level coding procedure to explain students' learning experiences. The results showed significant positive associations among perceived teacher support, music learning motivation, and student engagement. Music learning motivation was statistically associated with the link between perceived teacher support and student engagement, and the bootstrap confidence interval for the indirect association did not include zero. Qualitative findings indicated that encouragement, emotional care, clear explanation, interactive support, and content aligned with students' interests and abilities helped explain how students translated supportive classroom experiences into confidence, interest, and willingness to participate. Because the study used cross-sectional self-report data, the findings should be interpreted as associational rather than causal.

Endophyte Pseudomonas sp. Can09R was isolated from surface-sterilized roots of Chenopodium album L. DNA sequencing was performed using the Illumina platform, and the genome was assembled with SPAdes software. The final scaffolded assembly spans 6,036,228 bp, has a guanine-cytosine content of 60%, and contains 5,281 predicted protein-coding genes.

Throughout their youth, non-autistic siblings of autistic individuals may begin considering their involvement in their autistic sibling's life, which may affect their well-being. However, there is little research on how expectations for future involvement differ across cultures. Understanding why and how youth siblings' expectations manifest may inform the design of family interventions that are appropriate for culturally-diverse samples. The present analysis examines how Latino and non-Latino youth siblings perceive their future supportive roles in their autistic sibling's life. Semi-structured qualitative interviews were conducted in English with 12 Latino and 9 non-Latino youth siblings (N&#x202f;=&#x202f;21). Eligible families had at least one child diagnosed with autism and a non-autistic sibling between 8 and 17 years old. Audio-recorded interviews were transcribed verbatim and coded using a coding structure. Data were analyzed using applied thematic analysis and were both analyzed in aggregate and stratified by ethnic background. Two themes were identified: 1) expectations of evolving sibling roles and responsibilities into adulthood shape siblings' visions of their future involvement and 2) without family support, anxiety about the future pushes siblings into action or avoidance. Driven by a sense of duty, Latino siblings were more certain of a support role in their autistic sibling's life. Non-Latino siblings expressed more uncertainty and variability in their expectations for a future support role, feeling conflicted between prioritizing their autistic sibling or future family. These themes are consistent with literature emphasizing how cultural values, such as familism and individualism, shape caregiving attitudes and expectations. These findings may inform the design of culturally-responsive family interventions.

Protein structure characters have great potential for improving phylogenetic inference, especially for deep nodes where amino acid sequences are highly diverged. The combination of AlphaFold structure predictions and Foldseek's "3Di" structural alphabet makes it relatively easy to conduct model-based phylogenetic inference that includes a partition of slow-evolving 3Di characters. However, we show that even identical amino acid sequences can produce substantially different 3Di characters, depending on the source of structural model and whether inter-chain interactions are considered. We argue that such variability can be addressed with key concepts from traditional organism-based phylogenetic systematics: semaphoront, hypodigm, and character ascertainment method. To illustrate this, we develop an analogy between organismal development, taphonomy, and subsequent description and character coding by a systematist, and the process of protein synthesis, folding, and interaction and subsequent extraction, experimentation, and structural modeling by a biochemist. We conclude that differences in 3Di characters between semaphoronts are not intrinsically a problem, but they do require that the researcher uses the same replicable method on all proteins in the phylogenetic analysis. The guiding principle should be to maximize the chance that character differences in the data matrix are the results of underlying evolutionary changes, rather than artefacts due to differences in the methods used for obtaining semaphoronts and coding characters.

Infertility has long been a major health concern worldwide, with male infertility accounting for approximately half of all cases. In recent years, increasing evidence has shown that long non-coding RNAs (lncRNAs) are involved in the regulation of spermatogenesis. LncRNA AK015322 is a testis-specific lncRNA that is highly expressed in testicular tissue. Previous studies have demonstrated that lncRNA AK015322 promotes the proliferation of spermatogonial stem cells (C18-4) in vitro; however, its role in spermatogenesis in vivo remains unclear. To investigate the effects of lncRNA AK015322 gene knockout on spermatogenesis in male mice. LncRNA AK015322 knockout mice (C57BL/6J) were generated using CRISPR/Cas9 technology. Computer-aided sperm analysis was performed to evaluate sperm parameters in knockout mice. In addition, transcriptome sequencing was conducted to identify potential regulatory genes and signaling pathways associated with lncRNA AK015322. Compared with wild-type mice, lncRNA AK015322-deficient mice exhibited delayed epididymal development, increased sperm morphological abnormalities, and significantly reduced sperm motility. Transcriptome sequencing of testicular tissues identified 98 significantly upregulated genes and 109 significantly downregulated genes in knockout mice. Gene ontology, Kyoto Encyclopedia of Genes and Genomes, and gene set enrichment analyses indicated that lncRNA AK015322 may be involved in pathways such as the Hippo signaling pathway and androgen response. Differentially expressed genes were further validated by RT-qPCR. LncRNA AK015322 plays an important role in spermatogenesis, and its deletion leads to impaired sperm function and delayed epididymal development in mice.

Drug-induced liver injury (DILI) is a common complication of anti-tuberculosis therapy and frequently leads to treatment interruption or modification. In routine clinical practice, liver function abnormalities during tuberculosis treatment are often attributed to DILI. However, isolated indirect hyperbilirubinemia in the presence of persistently normal transaminase levels represents an atypical biochemical pattern that is inconsistent with classical hepatocellular injury and may indicate alternative underlying conditions, posing a diagnostic challenge in tuberculosis management. We report the case of a 22-year-old Han Chinese woman treated for smear-negative pulmonary tuberculosis who developed recurrent elevations in total and indirect bilirubin while alanine aminotransferase and aspartate aminotransferase levels remained persistently within normal ranges. These abnormalities were repeatedly misinterpreted as suspected DILI, resulting in multiple interruptions and modifications of anti-tuberculosis regimens. Bilirubin levels continued to fluctuate despite drug withdrawal, suggesting a non-hepatocellular etiology. Repeated treatment interruption contributed to a delay in effective tuberculosis management exceeding 1 year and was associated with radiological disease progression and cavity formation. Further evaluation, including UGT1A1 genetic testing, identified heterozygous promoter (c.-41_-40dupTA) and coding (c.211G>A, p.Gly71Arg) variants, confirming a diagnosis of Gilbert syndrome. Recognition of this underlying condition prevented further unnecessary cessation of anti-tuberculosis therapy. The patient subsequently resumed an individualized regimen guided by drug susceptibility testing and demonstrated radiological improvement during follow-up. This case highlights an important diagnostic pitfall during tuberculosis treatment. Persistent indirect hyperbilirubinemia with normal transaminases should prompt consideration of Gilbert syndrome rather than DILI. Early recognition and appropriate genetic testing may prevent unwarranted treatment interruption, reduce the risk of disease progression, and improve treatment continuity. To our knowledge, reports describing Gilbert syndrome masquerading as recurrent suspected DILI during tuberculosis treatment remain exceedingly rare.

Treatment Abroad (TA) programs are a key component of healthcare delivery for complex cases requiring highly specialized care. In Qatar, the International Medical Affairs Office (IMAO) manages over 11,000 TA requests annually through multidisciplinary committees and specialized subcommittees to support evidence-based decision-making. Despite advances in committee structures and the adoption of hybrid meeting models, challenges persist in optimizing efficiency, transparency, and committee member satisfaction, highlighting the need for systematic evaluation of committee processes and composition. To identify challenges affecting decision-making and operational effectiveness within IMAO Treatment Abroad committees, define characteristics of optimal committee composition, and develop a reproducible framework to enhance transparency, communication, and committee practices across the IMAO and similar healthcare organizations. Between July and December 2024, a cross-sectional survey was conducted among 162 CMs from main and specialized subcommittees using a home-developed instrument combining Likert-scale, yes/no, and open-ended questions; the tool was pilot-tested for reliability (Cronbach's &#x3b1; = 0.82). Quantitative data were analyzed using non-parametric tests, while qualitative data underwent dual-coded thematic analysis. A total of 87/162 committee members (CMs) responded (53.7%), predominantly male (72.4%) and highly experienced within HMC (&#x2265;9 years, 86.2%), while 50.6% had similar experience within the IMAO committee. Most preferred remote or hybrid meetings (67.8%) and email communication (51.7%), with high satisfaction reported for workflows (93.1%) and IMAO collaboration (65-69%). While 81.6% reported no external influence on decisions, 23% identified the absence of subcommittee input as a barrier, and 52.9% supported anonymized patient requests to enhance transparency. Greater organizational experience was associated with higher satisfaction and increased perception of subcommittee absence as a barrier (36.4% vs. 9.3%; p < 0.05), whereas committee-specific experience showed no significant effect. Key challenges included communication gaps with overseas facilities, interface usability, incomplete medical information, lack of financial compensation (95.4%), and exposure to patient reprisals. Medical committee effectiveness in Treatment Abroad programs is influenced by committee members' organizational experience and perceptions of decision-making processes. Findings underscore the need for structured multidisciplinary input, transparent governance, streamlined communication, and diverse committee representation across gender and experience levels to support equitable and consistent decision-making. The proposed hierarchical framework provides a practical model to standardize processes, enhance transparency, and optimize committee performance within IMAO and comparable healthcare settings.

Visit-to-visit blood pressure variability (BPV) may be associated with cognitive decline beyond mean blood pressure (BP), but its relevance across treatment contexts remains uncertain. We pooled individual-participant data from Action to Control Cardiovascular Risk in Diabetes Memory in Diabetes (ACCORD-MIND) and Systolic Blood Pressure Intervention Trial Memory and Cognition in Decreased Hypertension (SPRINT-MIND) (n&#xa0;=&#xa0;11,104). Participants had baseline and follow-up cognitive testing and &#x2265;3 BP measurements from 3 months onwards. The primary exposure was systolic BP variation independent of the mean (SBP-VIM). The primary outcome was annualized change in standardized Digit Symbol Substitution or Coding Test Z-scores. Each 10% increment in SBP-VIM was independently associated with faster annual cognitive decline (&#x3b2;&#xa0;=&#xa0;-0.008 per year; 95% confidence interval [CI]: -0.014 to -0.003) after adjustment including mean SBP. Associations were observed in the intensive but not standard BP treatment arms of both trials, although the pooled interaction was not statistically significant (p&#xa0;=&#xa0;0.054). Higher systolic BPV was associated with accelerated cognitive decline independently of mean BP. The exploratory treatment-context pattern warrants prospective confirmation.

Young people increasingly experience mental health challenges and often turn to the internet for support. Self-guided digital mental health promotion services have become widely used resources for youth seeking help and guidance. These platforms offer accessible, anonymous support, yet little is known about the concerns young people articulate when engaging with them. This study aims to examine inquiries submitted to the digital letter box of Mindhelper.dk, Denmark's most widely used digital mental health promotion service. Using qualitative analysis, the study aims to identify recurring themes in young people's mental health concerns, explore gender differences in engagement, and generate insights to inform the development of more relevant and targeted digital self-help interventions. Using an inductive thematic approach informed by a constructivist-grounded theory coding framework, this study analyzes 2523 inquiries submitted to the Mindhelper digital letter box between March 2016 and August 2023. The dataset provides unsolicited first-person accounts from young people in moments of emotional vulnerability, offering insights into how mental health concerns are articulated in naturalistic settings. The analysis identifies 17 recurring themes reflecting the mental health challenges young people seek help for. These were grouped into 3 overarching analytical categories: Social Relationships and Social Contexts, Emotional Life, and Body and Illness, with the first 2 dominating the material. Prominent themes included Sociality, Love Life, Unease, Self-doubt and Insecurity, and Seeking Support. Across genders, inquiries frequently focused on social relationships, particularly Sociality and Love Life. However, girls were markedly overrepresented among users, while only minor gender differences were observed in the distribution of themes. The findings suggest that young people's mental health concerns are closely tied to everyday developmental and relational challenges rather than severe psychopathology alone. Digital letter box services may capture early expressions of distress that might not otherwise reach formal support systems. This highlights the preventive potential of such services and the value of using self-initiated digital data to inform the development of relevant digital mental health support and better understand how young people articulate and act on emerging mental health concerns.

Supernumerary (B) chromosomes are widespread genomic elements that persist through non-Mendelian inheritance by exploiting host cellular mechanisms, yet the basis of their selective transmission and elimination remains poorly understood. This review integrates current knowledge on chromosome-specific behaviour, with particular emphasis on the centromere function, kinetochore assembly, epigenetic chromatin states, non-coding RNAs, and sequence composition. We examine how perturbations in these systems can skew chromosome segregation, or lead to chromosome elimination, and consider growing evidence that B chromosomes may themselves encode or modulate factors influencing these processes. Their repeat-rich architecture and enrichment in chromosome-specific satellite DNA are also discussed as contributors to their recognition by the cellular machinery. By unifying structural, epigenetic, and genetic perspectives, this review outlines a framework for understanding chromosome drive and elimination and highlights key directions for future research.

As robotic-assisted total knee arthroplasty (TKA) gains traction in revision procedures, the urgent need to investigate its effectiveness compared with manual methods becomes apparent. Data were retrospectively obtained from the TriNetX Collaborative Network. Revision TKA (rKA) cases were identified using CPT codes and categorized as manual or robotic assisted using ICD-10 procedure codes. Cohorts were balanced with 1:1 propensity score matching for demographics, comorbidities, and revision history. Complication rates were compared across follow-up using chi-square analysis. An initial query identified 19,088 manual and 2,709 robotic-assisted rKA cases. After 1:1 propensity matching, 2,010 patients remained in each group. Robotic rKA had significantly lower mechanical implant&#x2011;related complications at 3 and 6 months (OR 1.67 and 1.66; P < 0.001) and lower early VTE, while PJI, readmission, and revision rates were not significantly different. Manual rKA showed higher opioid use at 0 to 3 months (OR 1.40, 95% CI, 1.14 to 1.71, P < 0.001) and 3 to 6 months (OR 1.28, 95% CI, 1.12 to 1.47, P < 0.001) and throughout the 3 years of follow-up.Throughout the follow-up period, patellar dislocation, wound infection, non&#x2011;implant-related complications, and transfusion did not differ. At 1 year, manual rKA had higher instability (OR 1.59; P = 0.001) and higher hazard of mechanical implant&#x2011;related complications (HR 1.52, 95% CI, 1.32 to 1.75; P = 0.049). Instability, loosening, and periprosthetic fracture remained higher at 2 to 3 years, and revision was significantly more frequent at 3 years (13.5% vs. 11.4%; OR 1.22, 95% CI, 1.02 to 1.46; P = 0.03). Robotic-assisted rKA was associated with markedly lower mechanical implant&#x2011;related complications across early and midterm follow-up, including reduced rates of instability, aseptic loosening, periprosthetic fracture, VTE, and lower opioid requirements. Rates of PJI, readmission, and revision were largely comparable, although manual rKA demonstrated a markedly higher revision rate by 3 years. These findings suggest that robotic assistance may improve implant reliability and postoperative recovery, but prospective studies and cost-effectiveness analyses remain necessary.

ASCVD and stroke remain leading causes of death in the United States, sharing overlapping risk factors and clinical consequences. Long-term declines in vascular mortality have slowed while disparities persist. We evaluated national trends and disparities in mortality involving coexisting ASCVD- and stroke-related conditions among U.S. adults from 1999 to 2025. We performed a retrospective population-based study using the CDC WONDER Multiple Cause of Death database. Adults aged &#x2265;25 years were included. Deaths were identified when prespecified ASCVD-related and stroke-related ICD-10 codes were both documented on the same death certificate, whether as underlying or contributing causes. The outcome represents a death-certificate-defined mortality phenotype rather than clinically adjudicated concurrent disease. Age-adjusted mortality rates (AAMRs) per 100,000 were calculated using the 2000 U.S. standard population. Trends were assessed overall and by sex, age group, race/ethnicity, census region, urbanization, and state. Urbanization analyses were restricted to 1999-2020. Sensitivity analyses included restriction to atherosclerotic-specific codes (I25.x) and exclusion of provisional 2025 data. A total of 876,383 deaths were identified. Overall average AAMR was 15.01 per 100,000. Mortality declined from 26.82 in 1999 to 10.91 per 100,000 in 2025, with an AAPC of -3.53% (95% CI, -4.27 to -2.78; p&#x2009;<&#x2009;0.001). After sustained declines through 2018, AAMR showed a borderline significant increase during 2018-2021 (APC: 6.06%; 95% CI, 0.01-12.48; p&#x2009;=&#x2009;0.050), not replicated under stricter cause-of-death definitions, followed by renewed decline from 2021 to 2025 (APC: -2.85%; 95% CI, -4.58 to -1.09; p&#x2009;=&#x2009;0.004). Mortality burden remained higher among men, older adults, Black individuals, residents of the South, and non-metropolitan populations. Adults aged 25-44 years showed a significant increase after 2015, though absolute rates remain low and this finding warrants cautious interpretation. Although mortality involving coexisting ASCVD- and stroke-related conditions declined substantially from 1999 to 2025, this progress was interrupted by a borderline reversal in the pandemic period and remained marked by persistent disparities. These findings support the need for stronger and more equitable prevention strategies, particularly for younger adults and high-burden populations and regions.

&#x3b2;-catenin-coding gene CTNNB1 is a top-ranking risk gene for autism and intellectual disability. To better understand how CTNNB1 haploinsufficiency is involved in the pathophysiology of neurodevelopmental disorders, we generated a new mouse model that enables Ctnnb1 deletion in forebrain excitatory neurons starting at embryonic corticogenesis. Behavioural assays of the Ctnnb1 conditional knockout (cKO) mice revealed significant fear memory deficits, despite normal social preference, anxiety, spatial and recognition memory. Pyramidal neurons in prefrontal cortex (PFC) of Ctnnb1 cKO mice exhibited the significantly elevated intrinsic excitability but markedly decreased AMPA receptor-mediated synaptic response, while GABAA or NMDA receptor-mediated synaptic response was unchanged. Gene profiling revealed the significantly reduced mRNA level of Syp (encoding Synaptophysin) and Nlng2 (encoding Neuroligin-2) in PFC of Ctnnb1 cKO mice, while most of other screened genes were unchanged. These results suggest that &#x3b2;-catenin deficiency in forebrain excitatory neurons leads to fear conditioning impairment, which could be contributed by the diminished excitatory synaptic transmission in PFC resulting from disrupted synaptic gene expression.