Search

Abstract Background Lipid metabolic reprogramming in colon cancer shows a potential impact on tumor immune microenvironment and is associated with response to immunotherapy. Therefore, this study aimed to develop a lipid metabolism-related prognostic risk score (LMrisk) to provide new biomarkers and combination therapy strategies for colon cancer immunotherapy. Methods Differentially expressed lipid metabolism-related genes (LMGs) including cytochrome P450 (CYP) 19A1 were screened to construct LMrisk in TCGA colon cancer cohort. The LMrisk was then validated in three GEO datasets. The differences of immune cell infiltration and immunotherapy response between LMrisk subgroups were investigated via bioinformatic analysis. These results were comfirmed by in vitro coculture of colon cancer cells with peripheral blood mononuclear cells, human colon cancer tissue microarray analysis, multiplex immunofluorescence staining and mouse xenograft models of colon cancer. Results Six LMGs including CYP19A1, ALOXE3, FABP4, LRP2, SLCO1A2 and PPARGC1A were selected to establish the LMrisk. The LMrisk was positively correlated with the abundance of macrophages, carcinoma-associated fibroblasts (CAFs), endothelial cells and the levels of biomarkers for immunotherapeutic response including programmed cell death ligand 1 (PD-L1) expression, tumor mutation burden and microsatellite instability, but negatively correlated with CD8+ T cell infiltration levels. CYP19A1 protein expression was an independent prognostic factor, and positively correlated with PD-L1 expression in human colon cancer tissues. Multiplex immunofluorescence analyses revealed that CYP19A1 protein expression was negatively correlated with CD8+ T cell infiltration, but positively correlated with the levels of tumor-associated macrophages, CAFs and endothelial cells. Importantly, CYP19A1 inhibition downregulated PD-L1, IL-6 and TGF-β levels through GPR30-AKT signaling, thereby enhancing CD8+ T cell-mediated antitumor immune response in vitro co-culture studies. CYP19A1 inhibition by letrozole or siRNA strengthened the anti-tumor immune response of CD8+ T cells, induced normalization of tumor blood vessels, and enhanced the efficacy of anti-PD-1 therapy in orthotopic and subcutaneous mouse colon cancer models. Conclusion A risk model based on lipid metabolism-related genes may predict prognosis and immunotherapeutic response in colon cancer. CYP19A1-catalyzed estrogen biosynthesis promotes vascular abnormality and inhibits CD8+ T cell function through the upregulation of PD-L1, IL-6 and TGF-β via GPR30-AKT signaling. CYP19A1 inhibition combined with PD-1 blockade represents a promising therapeutic strategy for colon cancer immunotherapy.

This study aimed to investigate the effects of tea polyphenol (TP), epigallocatechin gallate (EGCG), and their palmitic acid-modified derivatives palmitoyl-TP (pTP) and palmitoyl-EGCG (pEGCG) on the accumulation of N-nitrosamine and biogenic amines (BAs), residual nitrites, and lipid oxidation in Chinese sausages. The microorganisms, color, and texture properties of sausages were evaluated. TP, EGCG, pTP, or pEGCG significantly inhibited the accumulation of N-nitrosodimethylamine (NDMA) and BAs, residual nitrites, and lipid oxidation, but enhanced the redness, hardness, and chewiness of sausages. The concentration of NDMA in sausages was reduced by 58.11%, 63.51%, 36.49%, and 44.59%, respectively, after treatment with TP, EGCG, pTP, and pEGCG. Both EGCG and pEGCG exhibited excellent inhibitory effects on the predominant BAs, including putrescine, tyramine, cadaverine, histamine, and 2-phenylethylamine. Palmitoyl-EGCG was found to be the strongest inhibitor of lipid oxidation. Besides, the four antioxidants weakly affected the population of total aerobic bacteria and lactic acid bacteria but totally suppressed the growth of undesirable Enterobacteriaceae. The principal component and correlation analyses proved that BAs, nitrites, lipid oxidation, and microbiota were responsible for the formation of NDMA. The results indicated that palmitic acid-modified TPs and similar derivatives might serve as potential preservatives to improve the safety and quality of fermented meat products.

We report the use of four-layer graphene (4LG) as a highly reliable transparent conductive electrode (TCE) for polymer-dispersed liquid crystal (PDLC)-based smart window devices. The adhesion between 4LG and the substrate was successfully improved through a water-induced interface-cleaning (WIIC) process. We compared the performance of a device with a WIIC-processed 4LG electrode with that of devices with a conventional indium tin oxide (ITO) electrode and a 4LG electrode without a WIIC. With the application of the WIIC process, the PDLC smart window with a 4LG electrode exhibited reduced turn-on voltage and haze compared to 4LG without the WIIC process and characteristics comparable to those of the ITO electrode. The WIIC-processed 4LG electrode demonstrated enhanced electrical properties and better optical performance, leading to improved device efficiency and reliability. Furthermore, our study revealed that the WIIC process not only improved the adhesion between 4LG and the substrate but also enhanced the compatibility and interfacial interactions, resulting in the superior performance of the smart window device. These findings suggest that 4LG with WIIC holds great promise as a transparent conductive electrode for flexible smart windows, offering a cost-effective and efficient alternative to conventional ITO electrodes.

A direct current magnetron sputtering (DCMS) system at room temperature was applied to deposit the Ti/TiN/TiCN films. In order to research the effect of the microstructure of the TiN/TiCN layer on the Ti/TiN/TiCN films, the deposition time ratio of the TiN/TiCN layer ranged from 28.57 to 200%, and the whole deposition time of the films and the deposition time of Ti layer were constant. In this work, the relationship between structure and mechanical properties of films were investigated. The research results showed that the composition and structure of the films only slightly changed, while the crystalline orientation of the TiCN layer was of significant variation with the deposition time of the TiN layer. It is shown that the adhesion strength and internal stresses were 18.6 ± 1.5 N and 140 MPa when the deposition time ratio was 50%. By adjusting the deposition time ratio, the films displayed significant improvement in tribological behaviors. The coefficients of friction (COF) for the films deposited under deposition time ratio of 50% were about only 0.139 when the value of COF was stabilized. This work can provide a good wear-resisting film prepared approach at room temperature.

Autohemotherapy is a commonly used treatment for recalcitrant chronic urticaria in some countries. Herein we report our experience using autologous serum therapy in eight patients with recalcitrant chronic spontaneous urticaria. Autologous serum therapy was initiated weekly for nine weeks followed by every fortnightly. Urticaria Activity Score (UAS) 7, Dermatology Life Quality Index (DLQI), and reduction of antihistamine usage were used to assess the treatment response. Eight patients (age range: 25–76 years old; four females and four males) had one to ten years of duration of recalcitrant chronic spontaneous urticaria. All failed to respond to high doses of second-generation antihistamines and five to immune-modulating agents. Three did not respond to omalizumab. At week nine, the reduction of UAS7 ranged from 76.2% to 100%. There was more than an 80% improvement in DLQI in all patients. The number of wheals seemed to be reduced first followed by pruritus. Three patients had stopped antihistamines by week eight of treatment. No adverse events were reported in all eight patients. Autologous serum therapy may serve as an alternative treatment for recalcitrant chronic spontaneous urticaria. Apart from the practicality, which requires frequent clinic visits, venipuncture, and centrifugation, it is cheap and effective with minimal adverse events.

This paper presents a comprehensive investigation of the optimal design of an interior permanent magnet synchronous motor (IPMSM) for electric vehicles (EVs), utilizing the hybrid artificial bee colony algorithm–support vector machine (HAS) algorithm. The performance of the drive motor is a crucial determinant of the overall vehicle performance, particularly in EVs that rely solely on a motor for propulsion. In this context, interior permanent magnet synchronous motors (IPMSMs) offer a compelling choice due to their high torque density, wide speed range, superior efficiency, and robustness. However, accurate analysis of the nonlinear characteristics of IPMSMs necessitates finite element analysis, which can be time-consuming. Therefore, research into methods for deriving an optimal model with minimal computation is of significant importance. The HAS is a powerful multimodal optimization technique that is capable of exploring several optimal solutions. It enhances the navigation capability by combining the artificial bee colony algorithm (ABC) with the kernel support vector machine (KSVM). Specifically, the algorithm improves the search ability by optimizing the movement of bees in each region generated by the KSVM. Furthermore, hybridization with the Nelder–Mead method ensures accurate and quick convergence at pointers discovered in the ABC. To demonstrate the effectiveness of the proposed algorithm, this study compared its performance with a conventional algorithm in two mathematical test functions, verifying its remarkable performance. Finally, the HAS algorithm was applied to the optimal design of the IPMSM for EVs. Overall, this paper provides a thorough investigation of the application of the HAS algorithm to the design of IPMSMs for electric vehicles, and its application is expected to benefit from the combination of machine-learning techniques with various other optimization algorithms. [ABSTRACT FROM AUTHOR]

Background Biological treatments are effective in the management of psoriasis. However, results in the real-world setting may differ from clinical trials. Objectives We aimed to evaluate the effectiveness of biological drugs among patients with psoriasis in Malaysia. Methods This was a retrospective review of adult patients on biologics who were notified to the Malaysian Psoriasis Registry between 2011 and 2019. Univariate and multivariate logistic regression was performed to identify factors associated with response to treatment in terms of the Psoriasis Area and Severity Index (PASI) 75, PASI 90, and Dermatology Life Quality Index (DLQI) 0/1. Results Of 130 patients, the most prescribed drug was ustekinumab (40.8%), followed by adalimumab (29.2%) and secukinumab (24.6%). Overall, the differences in the median PASI scores from baseline were −23.9 at 3–6 months, −25.8 at 12 months, and −27.8 at 3 years, while the difference in the median DLQI scores was −13.0 at 3–6 months. At 3–6 months, 57.6% achieved PASI-75, 32.9% achieved PASI-90, and 4.7% achieved PASI-100. These responses were sustained at 12 months and 3 years. Adalimumab was the most effective treatment with 88.9% achieving PASI-75, 77.8% PASI-90, and 22.2% PASI-100 at 3 years. However, secukinumab was more effective at achieving a PASI-100 response at 3–6 months (9.1%). Chinese or Indian ethnicity, concurrent use of systemic therapy or phototherapy, comorbidities, and a longer duration of psoriasis were associated with poorer response. Conclusion Biological treatments, particularly adalimumab and secukinumab, are effective in reducing disease severity and improving the quality of life of patients with psoriasis in Malaysia.

Aim: Buprenorphine is one of the strongest opioids used for the relief of cancer pain. This study aims to evaluate the real‐world clinical experiences of transdermal buprenorphine used in moderate to severe cancer pain in the Asian population. Methods: This is an open‐labeled, multicenter, 4‐week observational study. Stable cancer pain patients who decided to switch the previous opioid to transdermal buprenorphine will be enrolled in this study. The safety and effectiveness were observed and collected. Pain assessment was performed using a numerical rating scale by the investigators and the Brief Pain Inventory Short Form (BPI‐SF) by the patient. The safety profiles included concomitant medications and adverse events (AEs). Results: A total of 83 patients were enrolled in this study. The global pain scores in the BPI, as well as the four individual pain parameters (worst, least, average, and right now), showed a continued decrease (p <.05) from week 2 to week 4. Significant improvements were observed in normal work activities, relations with other people, sleep, enjoyment of life, and global BPI pain interference score on week 4. Pain assessments conducted by investigators demonstrated significant, continuous improvements during the study periods. In addition, transdermal buprenorphine demonstrated good safety/tolerability with limited drug‐related AEs in the Asian population with cancer pain. Conclusion: This study demonstrated that transdermal buprenorphine in the Asian population has good safety profiles and continued improvements in pain relief, sleep, and pain interferences. Transdermal buprenorphine can be an effective and convenient option as a transdermal opioid for patients with moderate to severe cancer pain in Taiwan. (NCT Number: NCT04315831) [ABSTRACT FROM AUTHOR]

The energy conversion units and energy storage equipment connected to the multi-energy system are becoming diversified, and the uncertain factors brought by distributed wind power and photovoltaic power generation make the system energy flow structure more complex, which brings great difficulties to the modeling and application of traditional energy hub modeling methods. This study deeply analyzes the multi-energy flow coupling structure and operation mechanism of multi-energy systems, and carries out the power flow calculation and analysis of multi-energy systems based on an energy hub, so as to ensure the safe and stable operation of regional energy. Based on the physical characteristics of energy systems such as power systems, thermal systems, and gas systems, this article studies the comprehensive power flow model including the electric-gas-thermal multi-energy coupling network and proposes the power flow decomposition of the energy supply subsystem and its applicable equation based on Newton–Raphson method. The effectiveness of the proposed method under different operation modes is verified by case studies. The calculation results show that under constant load, the energy hub running in fixing thermal by electricity (FEL) and fixing electricity by thermal (FTL) mode has little influence on the voltage of each node in the power sub-network. Within the constraint range, the natural gas flow obtained from the natural gas subsystem is coupled with the power subsystem to meet the load demand. The influence on the power flow at each node of the heat network is not obvious.

Abstract Background Non-small cell lung cancer (NSCLC) is the leading cause of morality among all malignant tumors. Smoking is one of the most important causes of NSCLC, which contributes not only to the initiation of NSCLC but also to its progression. The identification of specific biomarkers associated with smoking will promote diagnosis and treatment. Methods Data mining was used to identify the smoking associated gene SERPINB12. CCK8 assays, colony formation assays, a mouse xenograft model and transwell assays were performed to measure the biological functions of SERPINB12 in NSCLC. GSEA, luciferase reporter assays and immunofluorescence were conducted to explore the potential molecular mechanisms of SERPINB12 in NSCLC. Results In this study, by data mining the TCGA database, we found that SERPINB12 was greatly upregulated in NSCLC patients with cigarette consumption behavior, while the expression level was positively correlated with disease grade and poor prognosis. SERPINB12 is a kind of serpin peptidase inhibitor, but its function in malignant tumors remains largely unknown. Functionally, knockdown of SERPINB12 observably inhibited the proliferation and metastasis of NSCLC cells in vitro and in vivo. Moreover, downregulation of SERPINB12 attenuated Wnt signaling by inhibiting the nuclear translocation of β-catenin, which explained the molecular mechanism underlying tumor progression. Conclusions In conclusion, SERPINB12 functions as a tumorigenesis factor, which could be a promising biomarker for NSCLC patients with smoking behavior, as well as a therapeutic target.

In this paper, an electromagnetic analysis method is proposed to improve force characteristics by using spring permanent magnets (PMs) along the axial and circumferential directions of a linear oscillatory generator (LOG). For accurate electromagnetic analysis, a detailed analysis model of the LOG is developed, and the governing equations of each subdomain are derived based on Maxwell’s equations and electromagnetic theory. Analytical solutions of the magnetic vector potential in each subdomain are derived using boundary conditions. The reliability of the proposed method is verified through a comparison with the results of a two-dimensional finite element analysis (FEA). In particular, the force characteristics depending on the spring PM is effectively derived by considering the three-dimensional (3D) circumferential and axial end effects. The proposed analysis method is used to determine the thickness of spring PM that transforms the detent force of the LOG with the spring PM into restoring force. The reliability of the proposed analysis method is verified through comparison with the results of a 3D FEA.

This paper presents a comprehensive investigation of the optimal design of an interior permanent magnet synchronous motor (IPMSM) for electric vehicles (EVs), utilizing the hybrid artificial bee colony algorithm–support vector machine (HAS) algorithm. The performance of the drive motor is a crucial determinant of the overall vehicle performance, particularly in EVs that rely solely on a motor for propulsion. In this context, interior permanent magnet synchronous motors (IPMSMs) offer a compelling choice due to their high torque density, wide speed range, superior efficiency, and robustness. However, accurate analysis of the nonlinear characteristics of IPMSMs necessitates finite element analysis, which can be time-consuming. Therefore, research into methods for deriving an optimal model with minimal computation is of significant importance. The HAS is a powerful multimodal optimization technique that is capable of exploring several optimal solutions. It enhances the navigation capability by combining the artificial bee colony algorithm (ABC) with the kernel support vector machine (KSVM). Specifically, the algorithm improves the search ability by optimizing the movement of bees in each region generated by the KSVM. Furthermore, hybridization with the Nelder–Mead method ensures accurate and quick convergence at pointers discovered in the ABC. To demonstrate the effectiveness of the proposed algorithm, this study compared its performance with a conventional algorithm in two mathematical test functions, verifying its remarkable performance. Finally, the HAS algorithm was applied to the optimal design of the IPMSM for EVs. Overall, this paper provides a thorough investigation of the application of the HAS algorithm to the design of IPMSMs for electric vehicles, and its application is expected to benefit from the combination of machine-learning techniques with various other optimization algorithms.

Importance: Linking prenatal drug exposures to both infant behavior and adult cognitive outcomes may improve early interventions., Objective: To assess whether neonatal physical, neurobehavioral, and infant cognitive measures mediate the association between prenatal cocaine exposure (PCE) and adult perceptual reasoning IQ., Design, Setting, and Participants: This study used data from a longitudinal, prospective birth cohort study with follow-up from 1994 to 2018 until offspring were 21 years post partum. A total of 384 (196 PCE and 188 not exposed to cocaine [NCE]) infants and mothers were screened for cocaine or polydrug use. Structural equation modeling was performed from June to November 2023., Exposures: Prenatal exposures to cocaine, alcohol, marijuana, and tobacco assessed through urine and meconium analyses and maternal self-report., Main Outcomes and Measures: Head circumference, neurobehavioral assessment, Bayley Scales of Infant Development, Fagan Test of Infant Intelligence score, Wechsler Perceptual Reasoning IQ, Home Observation for Measurement of the Environment (HOME) score, and blood lead level., Results: Among the 384 mothers in the study, the mean (SD) age at delivery was 27.7 (5.3) years (range, 18-41 years), 375 of 383 received public assistance (97.9%) and 336 were unmarried (87.5%). Birth head circumference (standardized estimate for specific path association, -0.05, SE = 0.02; P = .02) and 1-year Bayley Mental Development Index (MDI) (standardized estimate for total of the specific path association, -0.05, SE = 0.02; P = .03) mediated the association of PCE with Wechsler Perceptual Reasoning IQ, controlling for HOME score and other substance exposures. Abnormal results on the neurobehavioral assessment were associated with birth head circumference (β = -0.20, SE = 0.08; P = .01). Bayley Psychomotor Index (β = 0.39, SE = 0.05; P < .001) and Fagan Test of Infant Intelligence score (β = 0.16, SE = 0.06; P = .01) at 6.5 months correlated with MDI at 12 months., Conclusions and Relevance: In this cohort study, a negative association of PCE with adult perceptual reasoning IQ was mediated by early physical and behavioral differences, after controlling for other drug and environmental factors. Development of infant behavioral assessments to identify sequelae of prenatal teratogens early in life may improve long-term outcomes and public health awareness.

Background: In a birth-cohort study, we followed offspring with prenatal cocaine exposure (PCE) to investigate longitudinal associations of PCE with self-reported behavioral adjustment from early adolescence to emerging adulthood (EA). Environmental pathways (family functioning, non-kinship care, maltreatment) were specified as potential mediators of PCE., Methods: Participants were 372 (190 PCE; 47% male), primarily Black, low socioeconomic status, enrolled at birth. Internalizing and externalizing behaviors were assessed using Youth Self-Report at ages 12 and 15 and Adult Self-Report at age 21. Extended random-intercept cross-lagged panel modeling was used to account for potential bidirectional relationships between internalizing and externalizing behaviors over time, examining potential mediators., Results: Adjusting for covariates, significant indirect effects were found for each mediator at different ages. For family functioning, these were both internalizing ( β = 0.83, p = 0.04) and externalizing behaviors ( β = 1.58, p = 0.02) at age 12 and externalizing behaviors at age 15 ( β = 0.51, p = 0.03); for non-kinship care, externalizing behaviors at ages 12 ( β = 0.63, p = 0.02) and 15 ( β = 0.20, p = 0.03); and for maltreatment, both internalizing and externalizing behaviors at ages 15 ( β = 0.64, p = 0.02 for internalizing; β = 0.50, p = 0.03 for externalizing) and 21 ( β = 1.39, p = 0.01 for internalizing; β = 1.11, p = 0.01 for externalizing). Direct associations of PCE with internalizing and externalizing behaviors were not observed, nor cross-lagged relationships between internalizing and externalizing behaviors., Conclusions: Negative associations of PCE with behavioral adjustment persist into EA via environmental pathways, specifying intervention points to disrupt adverse pathways toward healthy development.

Background: Although there is a well-established link between child maltreatment and adolescent substance use, it remains unclear if and how longitudinal patterns of maltreatment experiences are associated with substance use in adolescence., Objective: The purpose of the study was to examine how distinct patterns of longitudinal maltreatment experiences are associated with adolescent substance use., Participants and Setting: The participants were 899 adolescents from the Longitudinal Studies of Child Abuse and Neglect (LONGSCAN)., Methods: We conducted repeated measures latent class analysis (RMLCA) to identify patterns of physical abuse, sexual abuse, and neglect from birth to age 17 and their relations to tobacco, alcohol, and marijuana use at age 18., Results: RMLCA identified three physical abuse classes (Stable low physical abuse; School age peak physical abuse; Physical abuse primarily in infancy/toddlerhood), two sexual abuse classes (Stable no/low sexual abuse; School age peak sexual abuse), and three neglect classes (High neglect in childhood; Neglect primarily in infancy/toddlerhood; Neglect primarily at school age). Adolescents in the school age peak physical abuse class showed greater alcohol, cigarette, and marijuana use, compared to other physical abuse classes. Similarly, adolescents in the school age peak sexual abuse class showed greater substance use than those in the stable no/low sexual abuse class. Lastly, adolescents in the neglect primarily in infancy/toddlerhood class showed significantly less substance use than those in the other two neglect classes., Conclusions: Findings highlight the importance of early intervention and ongoing maltreatment prevention., Competing Interests: Declaration of competing interest This document includes data from the Consortium of Longitudinal Studies of Child Abuse and Neglect (LONGSCAN), which was funded by the Office on Child Abuse and Neglect (OCAN), Children's Bureau, Administration for Children and Families, Dept. of Health and Human Services, National Center on Child Abuse and Neglect (NCCAN). The data were made available by the National Data Archive on Child Abuse and Neglect (NDACAN), Cornell University, Ithaca, NY, and have been used with permission. The collector of the original data, the funder, NDACAN, Cornell University, and their agents or employees bear no responsibility for the analyses or interpretations presented here., (Copyright © 2023 Elsevier Ltd. All rights reserved.)

Aim: Buprenorphine is one of the strongest opioids used for the relief of cancer pain. This study aims to evaluate the real-world clinical experiences of transdermal buprenorphine used in moderate to severe cancer pain in the Asian population., Methods: This is an open-labeled, multicenter, 4-week observational study. Stable cancer pain patients who decided to switch the previous opioid to transdermal buprenorphine will be enrolled in this study. The safety and effectiveness were observed and collected. Pain assessment was performed using a numerical rating scale by the investigators and the Brief Pain Inventory Short Form (BPI-SF) by the patient. The safety profiles included concomitant medications and adverse events (AEs)., Results: A total of 83 patients were enrolled in this study. The global pain scores in the BPI, as well as the four individual pain parameters (worst, least, average, and right now), showed a continued decrease (p < .05) from week 2 to week 4. Significant improvements were observed in normal work activities, relations with other people, sleep, enjoyment of life, and global BPI pain interference score on week 4. Pain assessments conducted by investigators demonstrated significant, continuous improvements during the study periods. In addition, transdermal buprenorphine demonstrated good safety/tolerability with limited drug-related AEs in the Asian population with cancer pain., Conclusion: This study demonstrated that transdermal buprenorphine in the Asian population has good safety profiles and continued improvements in pain relief, sleep, and pain interferences. Transdermal buprenorphine can be an effective and convenient option as a transdermal opioid for patients with moderate to severe cancer pain in Taiwan. (NCT Number: NCT04315831)., (© 2022 John Wiley & Sons Australia, Ltd.)

Objective: Prenatal cocaine exposure (PCE) has been linked to specific cognitive deficits and behavioral outcomes through early adolescence but there is little information on adult outcomes nor on the relationship of environmental interventions, such as foster/adoptive care, to outcomes., Methods: At 21 years, data were available on 325 young adults, [163 PCE and 162 non-exposed (NCE)], primarily African-American, with low SES, who were followed from birth in a prospective longitudinal cohort study. Participants were administered the Wechsler Abbreviated Scale of Intelligence (WASI-II) and surveyed regarding high school completion, problematic substance use, and incarceration/probation history. In the PCE group, 32 remained in non-kinship foster/adoptive care (PCE/FA) from early in life (< 4 years) to 17 years. Group differences were examined through t-tests, MANOVA/ MANCOVA with post-hoc analyses, comparing outcomes and environmental correlates of young adults with PCE vs. NCE, as well as outcomes of PCE young adults in non-kinship foster/adoptive care (PCE/ FA) vs. PCE in birth/kinship care and NCE young adults., Results: At 21 years, young adults with PCE had lower mean Full Scale (83.7 ± 10.4 vs. 87.3 ± 12.5, p < .01) and Perceptual Reasoning IQs (87.3 ± 11.5 vs. 91.4 ± 13.9, (p < .02), lower high school completion rates (75% vs. 86%, p < .02), and were marginally more likely to have been on probation than NCE young adults, but did not differ in Verbal IQ, self-report of problematic substance use or incarceration. Young adults with PCE in F/A had similar lower IQ scores but had better verbal skills and high school graduation rates that did not differ from NCE young adults (80.6 vs 86.2%, p > .05). They had higher drug exposure at birth and more experiences of maltreatment (p's < 0.05) but their home environment quality was better and lead levels lower (p's < 0.05) than those of young adults with PCE in birth/kinship care., Conclusions: Young adults with PCE had lower Perceptual Reasoning and Full-Scale IQ scores, independent of caregiving placement, compared to non-exposed young adults. Young adults with PCE placed in non-kinship foster/adoptive care had lower lead levels, more stimulating home environments, better vocabulary skills and were more likely to graduate from high school than those in birth/kinship care,but were not different in their self-report of problematic substance use, or experiences of incarceration or probation. Our data suggest that some cognitive deficits observed in young adults with PCE may be biologically based, but that some functional outcomes can be modified through environmental interventions. Our data also reflect the complexity of disentangling the effects of teratologic exposures on long term outcomes across a variety of domains and the need for studies of children in the foster care system., Competing Interests: Declaration of Competing Interest Lynn Singer PhD reports financial support was provided by National Institutes of Health. author and co-authors are editors of journal LS, SM., (Copyright © 2023 Elsevier Inc. All rights reserved.)

Background: Prenatal cocaine exposure (PCE) has been associated with child and adolescent externalizing behaviors and early substance use, yet few studies investigated its association with substance use disorder (SUD) in emerging adults. The present study examined the association of PCE with SUD in emerging adulthood, and whether childhood externalizing behaviors and adolescent substance use mediated the relationship., Methods: Participants were 367 (187 PCE; 53% female) adults at age 21, primarily urban African American who were recruited at birth. PCE and exposure to alcohol, tobacco, and marijuana were determined using biologic assays for drug metabolites and/or maternal self-report at birth. Offspring externalizing problems were assessed using the Youth Self-Report at age 12, substance use and substance use-related problems via biologic assays and/or self-report at age 15, and SUD determined using DSM-5 diagnostic criteria at age 21., Results: About 32.3% of the emerging adults were determined to have marijuana use disorder, 30.3% tobacco use disorder, and 15.5% alcohol use disorder. PCE was related to greater externalizing behaviors at age 12 (β = 0.12, p = .042), which in turn was related to SUD (β = 0.22, p = .008). PCE was also related to substance use, mainly marijuana, at age 15 (β = 0.22, p = .011), which was related to SUD (β = 0.51, p < .001). Total indirect effects including these two pathways were significant (β = 0.19, p = .002)., Conclusions: PCE may increase risk for SUD in emerging adulthood through childhood externalizing behaviors and adolescent substance use., Competing Interests: Conflict of interest None., (Copyright © 2022 Elsevier B.V. All rights reserved.)

Objective: Prenatal cocaine exposure (PCE) has been associated with small but significant effects on language development in childhood and early adolescence. This study examined whether this association persists into later adolescence and what relationship language skills may have with reading proficiency in this population., Methods: Enrolled were 338 (167 with PCE, 171 with NCE or no cocaine exposure) 17-year-olds recruited at birth who, together with their current caregiver, were seen as part of a 17-year follow-up. Participants were given assessments of reading achievement (WIAT-III), receptive and expressive language (CELF-IV), and phonological processing (CTOPP). Relationships between PCE status and language outcomes were modeled using multiple linear regression controlling for environmental and caregiver factors, and other prenatal substance exposures., Results: Adolescents with PCE scored lower in areas of phonological processing and reading related skills compared to adolescents with NCE. PCE by sex interactions were identified on language, memory and spoken language comprehension, with lower scores for girls with PCE compared to girls with NCE., Conclusion: These findings suggest the persistence of PCE's relationship with phonological awareness well into adolescence. PCE was also associated with lower scores on measures of skills related to reading ability, which may be a manifestation of the observed deficits in phonological processing., Competing Interests: Declaration of Competing Interest The authors have no conflicts or competing interests to report., (Copyright © 2022 Elsevier Inc. All rights reserved.)

No known studies have investigated co-occurrence of psychopathology problems in adolescents with biologic and/or environmental susceptibility, including prenatal drug exposure. This study identified comorbidity patterns of psychopathology problems by utilizing data from urban, primarily African American, youth, majority of whom were at heightened risk for exposure to drugs in utero. The roles of Research Domain Criteria (RDoC)-informed behavioral constructs of the Negative Valence (irritability) and Social Process Systems (social disinhibition) as antecedents of the comorbidity patterns were further examined. Lastly, the predictive validity of the identified patterns was evaluated in relation to emerging adulthood outcomes. Participants were 358 urban adolescents, primarily African Americans, drawn from a 21-year prospective birth-cohort study of the effects of prenatal drug exposure. Psychopathology problems were assessed at age 15. Irritability and social disinhibition were self-reported at age 12. Emerging adulthood outcomes were measured at age 21. Latent class modeling indicated four patterns: Normative (57%), substance-use (SU; 24%), mental-health-problems-without-substance-use (MH; 11%), and substance-use-and-other-mental-health-problems (SUMH; 7%). Higher irritability increased the odds of developing the MH pattern, whereas higher social disinhibition increased the odds of developing the SU pattern. The odds of manifesting the SUMH pattern were higher for children with higher irritability. For children with higher social disinhibition, the odds of manifesting the SUMH pattern were higher at a trend level. Adolescent comorbidity patterns were differentially associated with problematic tobacco and marijuana use and clinically relevant mental health problems in emerging adulthood, and completion of high school education. Peri-pubertal identification of individual differences in irritability and social disinhibition may mitigate the emergence of adolescent psychopathology, which could influence emerging adulthood adjustment in this at-risk population., Competing Interests: Conflict of Interest/Competing Interests: June-Yung Kim, Sonia Minnes, and Meeyoung O. Min declare that they have no conflict of interest. Ty A. Ridenour’s spouse owns the intellectual property of the Assessment of Liability and EXposure to Substance use and Antisocial behavior (ALEXSA).

Objective: Adverse developmental effects of prenatal cocaine exposure (PCE) are hypothesized to extend into late adolescence, yet few studies have investigated the association between PCE and late adolescent mental health outcomes. We examined the associations between PCE and self-reported mental health symptoms at age 17, controlling for biologic and environmental confounders. We further explored the potential moderating role of sex and the mediating role of earlier drug use by age 15 in the associations., Method: 327 (162 PCE; 165 non-cocaine exposed, NCE) urban adolescents, primarily African Americans, of low socioeconomic status, were prospectively recruited at birth for a longitudinal study and participated in the current study. We administered the Computerized Diagnostic Interview Schedule for Children-IV to assess their mental health symptoms at age 17. Alcohol, tobacco, and marijuana use by age 15 were assessed using biologic samples and self-reports. Confounders included other prenatal drug exposures, caregiving environment, and childhood maltreatment., Results: Although no overall associations between PCE and mental health outcomes were observed, multivariate logistic regression models indicate girls with PCE were 3.60 times (95% CI = 1.45-8.96, p = .006) more likely to have symptoms of oppositional defiance disorder than girls with NCE. This relationship was partially mediated by marijuana use by age 15., Conclusion: Continued studies into emerging adulthood will further elucidate the long-term mental health outcomes associated with PCE., Competing Interests: Declaration of Competing Interest All authors declare that they have no conflict of interest., (Copyright © 2022 Elsevier Inc. All rights reserved.)

Objective: Establishing positive network resources and rebuilding drug free networks are key components of recovery process for women with substance use disorder (SUDs). Theory of planned behavior (TPB) posits that behaviors are determined by behavioral intentions, which are determined by three factors: attitude toward the behavior, perceived behavioral control, and subjective norms. The current study applied TPB to examine whether women's personal social network characteristics (as subjective norms) were related to intentions towards, and/or a substance use relapse using prospective research design., Methods: Longitudinal data from 300 American women with SUD who received treatment at three county-funded, women-only intensive treatment programs was utilized for the current study., Results: Bayesian estimation path analyses indicated that attitude and abstinence self-efficacy at intake were not related to intention at the 6-month follow-up, but abstinence self-efficacy was directly related to substance use relapse by 12 months. Personal social network characteristics, number of treatment related persons in personal social network and sobriety support were significantly associated with intention at 6 months. The interaction between the numbers of treatment related persons and density was found on intention, suggesting that density strengthens the relationship between treatment related persons in network and intention. Intention to use substance was associated with relapse to substance use behavior., Conclusion: Our findings support that personal social network characteristics can be considered as subjective norms in the TPB model. Personal social network interventions focusing on rebuilding consistent social norms against drug-using behaviors may decrease intention to use substance, which will lead to abstinence.

Introduction: To investigate patterns of divergence in adolescent adjustment, this study examined the co-occurring patterns of adolescents' individual assets (e.g., school engagement, values) and substance use, and whether the co-occurring patterns were associated with later functioning in emerging adulthood., Methods: Participants were 358 (54% females), predominantly African American, urban adolescents, recruited at birth for a prospective study on the effects of prenatal substance exposure in the Midwest United States. Individual assets, using the Developmental Assets Profile, substance use (alcohol, tobacco, marijuana), via biologic assays and self-report, and substance use-related problems were assessed at age 15 years. High-school completion, substance use disorder, mental health symptoms, and legal problems were assessed at age 21 years., Results: Latent class analysis identified five classes as follows: high assets with low substance use (C1, 10.2%); moderate assets with low substance use (C2, 28.7%); low assets with low substance use (C3, 32%); moderate assets with high substance use (C4, 9.4%); and low assets with high substance use (C5, 19.2%). Despite similar levels of assets, adolescents in C5 reported more life adversities (suboptimal caregiving environment, daily hassles, non-birth parents' care) than those in C3. C4 and C5 reported more substance use disorder at age 21 years than the three low substance use classes; adolescents in C5 were less likely to complete high school than those in C2. More females in C5 reported greater mental health symptoms than those in C1 and C3, and criminal justice involvement than those in C1., Conclusions: The current findings underscore the significance of substance use in adolescence in disrupting healthy transition to adulthood, especially among females in the context of low individual assets., (© 2022 The Foundation for Professionals in Services for Adolescents.)

Background: Elevated lead levels in children are a persistent public health problem, particularly in urban areas in the United States, yet few prospective studies have examined the association of childhood lead levels with substance use in adolescence., Objectives: To determine the association of early lead levels with adolescent substance use and whether childhood IQ, language skills, and externalizing (aggressive and disruptive) behavior mediate the association, controlling for confounding biological and environmental factors., Methods: The participants (N = 265) were a subsample of a prospective birth cohort study on the developmental effects of prenatal cocaine exposure in the Midwest United States. Blood lead levels (BLL) were assessed at age 4, IQ at age 11, language skills and externalizing behavior at age 12, and substance (alcohol, tobacco, marijuana) use and substance use-related problems at age 15. Biologic assays (hair, urine, bloodspots), along with self-report, were utilized to determine adolescent substance use. Path analyses were conducted to examine the direct and indirect associations of BLL with adolescent substance use., Results: The children's mean BLL at 4 years of age was 7.07 (SD = 4.12) μg/dL. Approximately 31% of adolescents used tobacco or marijuana, 40% used alcohol, and 23% reported experiencing substance use-related problems at age 15.7 (SD = 0.28). Elevated BLL was related to a higher likelihood of substance use. Childhood language skills fully mediated the relationship of BLL with substance use-related problems. IQ was related to neither substance use nor substance use-related problems., Discussion: Elevated BLL in preschool years is a risk factor for adolescent substance use and related problems. Early screening and intervention for language impairment may reduce substance use-related problems., (Copyright © 2021 Elsevier Inc. All rights reserved.)