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Theory and research indicate considerable changes in parental control across adolescence (e.g., declining behavioral control), but the developmental course and significance of psychological control remains largely unknown. This study examined trajectories of adolescents’ reports of mothers’ and fathers’ psychological control from ages 12 to 19, predictors of occupying distinct trajectories, and the developmental significance of these trajectories for adolescents’ development of depressive and anxiety symptoms. It used eight waves of survey data on 500 adolescents (Mage = 11.83, SD = 1.03; 52% female; 67% White, 12% African American) and their parents from the Pacific Northwest United States. Most adolescents (about 90%) reported low but increasing levels of parental psychological control over time, with a small but significant subset (about 10%) perceiving perpetually elevated levels. Mothers’ (but not fathers’) depressive symptoms, reported at the age 12 assessment, predicted adolescents’ membership in the elevated psychological control trajectory. Adolescents occupying these elevated trajectories showed more problematic growth in depressive and anxiety symptoms across adolescence. Taken together, the findings suggest that many adolescents experience increased parental psychological control as they age, and that variability in these trends indicates individual differences in their development of depressive and anxiety symptoms over time.

Wearing costumes is a common experience during early childhood and is often important to sociodramatic play. Costumes tend to be highly gendered for both girls and boys (such as princess and superhero costumes). However, there is very little research on the impact that wearing costumes has on gender-differentiated behavior, such as toy preference, prosocial behavior, or perseverance during early childhood. The current study included 223 U.S. children, aged between 3 and 5 years-old. Children were assigned to wear either a gendered, counter-gendered, or gender-neutral costume, and they then took part in three gender-related tasks. There was no impact of wearing costumes on any task for girls. However, boys preferred feminine toys significantly more when wearing a neutral costume when compared to a masculine-typed one. Additionally, boys were significantly less likely to help when wearing a masculine-typed costume compared to a feminine-typed costume. There are several implications of these findings that are discussed in the paper. Parents may wish to purchase a wide range of costumes for their child for sociodramatic play, particularly for boys. Therapists could also potentially use costumes during play therapy to discuss gender issues. Additionally, costume producers could consider marketing a wide range of costumes for children as opposed to largely focusing on gendered ones.

Suicide rates have increased over the past decade, and screen media (and social media in particular) are often blamed for this marked increase. However, there is little longitudinal research on this topic. The current study examined the link between various types of screen media use over a 10-year period (from adolescence to emerging adulthood) to suicide risk in emerging adulthood. Participants included 500 adolescents (51% female) who were first surveyed in 2009, when they were an average of 13.82 years old (range 12-15 years). For girls, a high level of social media or television use in early adolescence followed by a marked increase over time was most predictive of suicide risk in emerging adulthood. Additionally, video game use that increased over time was also associated with a higher risk for developing suicide risk for girls. A passive sensing measurement was also included at the final wave of data collection to obtain a more accurate and complete picture of phone use in particular. The use of entertainment apps was risky for girls while reading apps were risky for boys. Additionally, video game use (for boys) was associated with suicide risk when cyberbullying was also high. Identifying nonnormative patterns of media during adolescence may be instructive in terms of suicide prevention efforts.

Influenza A virus’s (IAV’s) frequent genetic changes challenge vaccine strategies and engender resistance to current drugs. We sought to identify conserved and essential RNA secondary structures within IAV’s genome that are predicted to have greater constraints on mutation in response to therapeutic targeting. We identified and genetically validated an RNA structure (packaging stem–loop 2 (PSL2)) that mediates in vitro packaging and in vivo disease and is conserved across all known IAV isolates. A PSL2-targeting locked nucleic acid (LNA), administered 3 d after, or 14 d before, a lethal IAV inoculum provided 100% survival in mice, led to the development of strong immunity to rechallenge with a tenfold lethal inoculum, evaded attempts to select for resistance and retained full potency against neuraminidase inhibitor-resistant virus. Use of an analogous approach to target SARS-CoV-2, prophylactic administration of LNAs specific for highly conserved RNA structures in the viral genome, protected hamsters from efficient transmission of the SARS-CoV-2 USA_WA1/2020 variant. These findings highlight the potential applicability of this approach to any virus of interest via a process we term ‘programmable antivirals’, with implications for antiviral prophylaxis and post-exposure therapy. Targeting conserved secondary structure of RNA viruses offers the potential for a customizable therapeutic approach to viral variants.

Up to one third of congenital brain malformations and neurodevelopmental disorders are attributable to single-gene pathogenic variants, and yet we have little understanding of the cellular pathophysiology in the nervous system that arises from these variants. To investigate cortical cell type-specific biases in gene expression associated with distinct neurodevelopmental phenotypes, we integrated phenotypic information from two cohorts of subjects with monogenic neurodevelopmental diagnoses with two human cortical single-nucleus RNA-sequencing (snRNAseq) datasets. Phenotype data was gathered from (1) a single-institution cohort of 84 neonates with pathogenic single-gene variants referred to Duke Pediatric Genetics, and (2) a cohort of 4,238 patients with neurodevelopmental disorders and pathogenic single-gene variants enrolled in the Deciphering Developmental Disorders study. Human cortical snRNAseq datasets were obtained from public repositories and included 86 samples from human cortex spanning the 2nd trimester of gestation to adulthood. We identified reproducible cell-specific expression biases for genes in which pathogenic variants are associated with speech/cognitive delay and seizures. Enriched expression of these genes in excitatory neurons or microglia highlights the unique role both cell types play in neurodevelopment. Moreover, this information illuminates distinct cortical cell types that are more likely to be impacted by pathogenic variants and may mediate their symptomatology.

Chemical analyses of organic residues in fragments of ceramic vessels from Pueblo Bonito in Chaco Canyon, New Mexico, reveal theobromine, a biomarker for cacao. With an estimated 800 rooms, Pueblo Bonito is the largest archaeological site in Chaco Canyon and was the center of a large number of interconnected towns and villages spread over northwestern New Mexico. The cacao residues come from pieces of vessels that are likely cylinder jars, special containers occurring almost solely at Pueblo Bonito and deposited in caches at the site. This first known use of cacao drinks north of the Mexican border indicates exchange with cacao cultivators in Mesoamerica in a time frame of about A.D. 1000-1125. The association of cylinder jars and cacao beverages suggests that the Chacoan ritual involving the drinking of cacao was tied to Mesoamerican rituals incorporating cylindrical vases and cacao. The importance of Pueblo Bonito within the Chacoan world likely lies in part with the integration of Mesoamerican ritual, including critical culinary ingredients.

The widespread significance of tobacco in Mesoamerica is documented in historical and ethnographic sources, yet recovery of the organic remains of this plant from archaeological contexts is rare. Here, the authors present evidence for the ritual use of tobacco at Cotzumalhuapa, Guatemala, during the Late Classic period (AD 650–950). Detection of nicotine in residue analysis of three cylindrical ceramic vases recovered from cache deposits near the El Baúl acropolis suggests that these vessels contained tobacco infusions or other liquid preparations. These results suggest an ancient ritual practice involving tobacco for which there was previously no physical evidence in Mesoamerica.

Diffuse intrinsic pontine glioma (DIPG) is a fatal central nervous system (CNS) tumor that confers a median survival of 11 months. As B7-H3 is expressed on pediatric CNS tumors, we conducted BrainChild-03, a single-center, dose-escalation phase 1 clinical trial of repetitive intracerebroventricular (ICV) dosing of B7-H3-targeting chimeric antigen receptor T cells (B7-H3 CAR T cells) for children with recurrent or refractory CNS tumors and DIPG. Here we report results from Arm C, restricted to patients with DIPG. The primary objectives were to assess feasibility and tolerability, which were both met. Secondary objectives included assessments of CAR T cell distribution and survival. A total of 23 patients with DIPG enrolled, and 21 were treated with repeated doses of ICV B7-H3 CAR T cells using intra-patient dose-escalation regimens without previous lymphodepletion. Concurrent tumor-directed therapy, including re-irradiation, was not allowed while on protocol therapy. We delivered a total of 253 ICV doses and established the highest planned dose regimen, DR4, which escalated up to 10 × 10 7 cells per dose, as the maximally tolerated dose regimen. Common adverse events included headache, fatigue and fever. There was one dose-limiting toxicity (intratumoral hemorrhage) during DR2. For all treated patients ( n  = 21), the median survival from their initial CAR T cell infusion was 10.7 months and the median survival from diagnosis was 19.8 months with 3 patients still alive at 44, 45 and 52 months from diagnosis. Ultimately, this completed first-in-human trial shows that repetitive ICV dosing of B7-H3 CAR T cells in pediatric and young adult patients with DIPG is tolerable, including multiyear repeated dosing, and may have clinical efficacy that warrants further investigation on a multisite phase 2 trial. ClinicalTrials.gov registration: NCT04185038 . In the final report of a phase 1 trial evaluating intracerebroventricular B7-H3-targeting CAR T cells in children and young adults with diffuse intrinsic pontine glioma, repeated intracranial infusions were feasible and well tolerated with a median overall survival of 19.8 months and 3 patients surviving over 40 months from diagnosis.

Obesity is associated with enhanced tumor growth and progression. Within the adipose tissue are adipose-derived stromal/stem cells (ASCs) that have been shown to convert into carcinoma-associated fibroblast (CAFs) in the presence of tumor-derived factors. However, the impact of obesity on the ASCs and on the conversion of ASCs into CAFs has not been demonstrated. In the current study, ASCs isolated from lean donors (BMI < 25; lnASCs) were compared with ASCs isolated from obese donors (BMI > 30, obASCs). The contribution of tumor-derived factors on the conversion of ASCs to CAFs was investigated. Following exposure to cancer cells, obASCs expressed higher levels of CAF markers, including NG2, alpha-SMA, VEGF, FAP, and FSP, compared to lnASCs. To investigate the crosstalk between ASCs and breast cancer cells, MCF7 cells were serially cocultured with lnASCs or obASCs. After coculture with lnASCs and obASCs, MCF7 cells demonstrated enhanced proliferation and expressed an invasive phenotype morphologically, with more pronounced effects following exposure to obASCs. Long-term exposure to obASCs also enhanced the expression of protumorgenic factors. Together, these results suggest that obesity alters ASCs to favor their rapid conversion into CAFs, which in turn enhances the proliferative rate, the phenotype, and gene expression profile of breast cancer cells.