Predictors of middle school students' perceptions of automated writing evaluation.

This study examined middle school students' perceptions of an automated writing evaluation (AWE) system, MI Write. We summarize students' perceptions of MI Write's usability, usefulness, and desirability both quantitatively and qualitatively. We then estimate hierarchical entry regression models that account for district context, classroom climate, demographic factors (i.e., gender, special education status, limited English proficiency status, socioeconomic status, grade), students' writing-related beliefs and affect, and students' writing proficiency as predictors of students' perceptions. Controlling for districts, students reporting more optimal classroom climate also reported higher usability, usefulness, and desirability for MI Write. Also, model results revealed that eighth graders, students with limited English proficiency, and students of lower socioeconomic status perceived MI Write relatively more useable; students with lower socioeconomic status also perceived MI Write relatively more useful and desirable. Students who liked writing more and more strongly believed that writing is a recursive process viewed MI Write as more useable, useful, and desirable. Students with greater writing proficiency viewed MI Write as less useable and useful; writing proficiency was not related to desirability perceptions. We conclude with a discussion of implications and future directions.

Experiencing violence and other predictors of within-person same-day use of multiple substances in youth: a longitudinal study in emergency settings.

Background: Although experiencing violence is a risk factor for substance use among youth, its association with same-day use of multiple substances (a form of polysubstance use) and mitigating factors is less well understood.Objectives: To identify whether prosocial factors modified the effect of experiencing violence on the frequency of same-day use, and examine gender-specific risk/protective factors for same-day use.Methods: We analyzed longitudinal data from a cohort of youth who use drugs aged 14-24 (n = 599; 58% male) presenting to an urban emergency department between 2009-2011 and assessed biannually for two years. Using Poisson-generalized linear models with person-level fixed effects, we estimated within-person associations between self-reported experiencing violence and same-day use and analyzed gender and peer/parent support as effect modifiers. We adjusted for negative peer influence, parental drug and alcohol use, family conflict, anxiety and depression, and age.Results: Overall, positive parental support corresponded to lower rates of same-day use (rate ratio [RR]:0.93, 95% CI:0.87-0.99) and experiencing violence was associated with higher rates of same-day use (RR:1.25, 95% CI:1.10-1.41). Violence exposure was a risk factor among males (RR:1.42, 95% CI:1.21-1.66), while negative peer influences and parental substance use were risk factors among females (RR:1.63, 95% CI:1.36-1.97 and RR:1.58, 95% CI:1.35-1.83, respectively). Positive peer support reduced the association between violence exposure and same-day use among males (RR:0.69, 95% CI:0.57-0.84, p < .05).Conclusions: Tailored interventions may address gender differences in coping with experiencing violence - including interventions that promote parental support among males and reduce influence from parental substance use among females.

Where Do Adults in the United States Obtain Cannabis? A Nationally Representative Study Examining the Relationships Between Sociodemographic Factors, Cannabis Use Characteristics and Sources of Cannabis.

OBJECTIVE: Characterization of population subgroups based on where they acquire cannabis is unexplored. We examine relationships between sociodemographic characteristics, cannabis use modality, risky cannabis use, and source of cannabis. METHOD: Analyzing a representative sample (unweighted n = 8,089) of U.S. adults living in medical cannabis-permitting states with past-year cannabis use from the 2021 National Survey on Drug Use and Health, we determined source of last cannabis used. Outcome groups were purchased from a dispensary, purchased from another source, or nonpurchased source. Incorporating the complex survey design, descriptive statistics and adjusted multinomial logistic regressions evaluated associations between sociodemographic, individual cannabis use characteristics, and source of cannabis. Secondary analyses described cannabis purchasing characteristics among the subsample who last purchased cannabis. RESULTS: Purchasing from a dispensary was the most common source of cannabis (42.5%). Significant relationships between sociodemographic characteristics, cannabis use modality, risky cannabis use, and source of cannabis were found. Recent cannabis initiates and those with cannabis vaporizer use had an increased likelihood of purchasing cannabis from a dispensary. Purchasing from a nondispensary source was most likely among those with daily cannabis use, past-month blunt use, past-year driving under the influence, cannabis use disorder, and cannabis and alcohol co-use. Among those purchasing cannabis, joints and other forms of cannabis were more likely to be purchased from a dispensary than purchased from other sources. CONCLUSIONS: We identified key sociodemographic and cannabis use characteristics that may influence where individuals obtain cannabis, which are important for cannabis behavior surveillance and cannabis use prevention and intervention strategies to consider.

Discovering useful genetic variation in the seed parent gene pool for sorghum improvement.

Multi-parent populations contain valuable genetic material for dissecting complex, quantitative traits and provide a unique opportunity to capture multi-allelic variation compared to the biparental populations. A multi-parent advanced generation inter-cross (MAGIC) B-line (MBL) population composed of 708 F6 recombinant inbred lines (RILs), was recently developed from four diverse founders. These selected founders strategically represented the four most prevalent botanical races (kafir, guinea, durra, and caudatum) to capture a significant source of genetic variation to study the quantitative traits in grain sorghum [Sorghum bicolor (L.) Moench]. MBL was phenotyped at two field locations for seven yield-influencing traits: panicle type (PT), days to anthesis (DTA), plant height (PH), grain yield (GY), 1000-grain weight (TGW), tiller number per meter (TN) and yield per panicle (YPP). High phenotypic variation was observed for all the quantitative traits, with broad-sense heritabilities ranging from 0.34 (TN) to 0.84 (PH). The entire population was genotyped using Diversity Arrays Technology (DArTseq), and 8,800 single nucleotide polymorphisms (SNPs) were generated. A set of polymorphic, quality-filtered markers (3,751 SNPs) and phenotypic data were used for genome-wide association studies (GWAS). We identified 52 marker-trait associations (MTAs) for the seven traits using BLUPs generated from replicated plots in two locations. We also identified desirable allelic combinations based on the plant height loci (Dw1, Dw2, and Dw3), which influences yield related traits. Additionally, two novel MTAs were identified each on Chr1 and Chr7 for yield traits independent of dwarfing genes. We further performed a multi-variate adaptive shrinkage analysis and 15 MTAs with pleiotropic effect were identified. The five best performing MBL progenies were selected carrying desirable allelic combinations. Since the MBL population was designed to capture significant diversity for maintainer line (B-line) accessions, these progenies can serve as valuable resources to develop superior sorghum hybrids after validation of their general combining abilities via crossing with elite pollinators. Further, newly identified desirable allelic combinations can be used to enrich the maintainer germplasm lines through marker-assisted backcross breeding.

Comparison of homemade mask designs based on calculated infection risk, using actual COVID-19 infection scenarios.

During pandemics such as COVID-19, shortages of approved respirators necessitate the use of alternative masks, including homemade designs. The effectiveness of the masks is often quantified in terms of the ability to filter particles. However, to formulate public policy the efficacy of the mask in reducing the risk of infection for a given population is considerably more useful than its filtration efficiency (FE). The effect of the mask on the infection profile is complicated to estimate as it depends strongly upon the behavior of the affected population. A recently introduced tool known as the dynamic-spread model is well suited for performing population-specific risk assessment. The dynamic-spread model was used to simulate the performance of a variety of mask designs (all used for source control only) in different COVID-19 scenarios. The efficacy of different masks was found to be highly scenario dependent. Switching from a cotton T-shirt of 8% FE to a 3-layer cotton-gauze-cotton mask of 44% FE resulted in a decrease in number of new infections of about 30% in the New York State scenario and 60% in the Harris County, Texas scenario. The results are valuable to policy makers for quantifying the impact upon the infection rate for different intervention strategies, e.g., investing resources to provide the community with higher-filtration masks.

HATCHet2: clone- and haplotype-specific copy number inference from bulk tumor sequencing data.

Multi-region DNA sequencing of primary tumors and metastases from individual patients helps identify somatic aberrations driving cancer development. However, most methods to infer copy-number aberrations (CNAs) analyze individual samples. We introduce HATCHet2 to identify haplotype- and clone-specific CNAs simultaneously from multiple bulk samples. HATCHet2 introduces a novel statistic, the mirrored haplotype B-allele frequency (mhBAF), to identify mirrored-subclonal CNAs having different numbers of copies of parental haplotypes in different tumor clones. HATCHet2 also has high accuracy in identifying focal CNAs and extends the earlier HATCHet method in several directions. We demonstrate HATCHet2's improved accuracy using simulations and a single-cell sequencing dataset. HATCHet2 analysis of 50 prostate cancer samples from 10 patients reveals previously-unreported mirrored-subclonal CNAs affecting cancer genes.

Writing motivation and ability profiles and transition during a technology-based writing intervention.

Students exhibit heterogeneity in writing motivation and ability. Profiles based on measures of motivation and ability might help to describe this heterogeneity and better understand the effects of interventions aimed at improving students' writing outcomes. We aimed to identify writing motivation and ability profiles in U.S. middle-school students participating in an automated writing evaluation (AWE) intervention using MI Write, and to identify transition paths between profiles as a result of the intervention. We identified profiles and transition paths of 2,487 students using latent profile and latent transition analysis. Four motivation and ability profiles emerged from a latent transition analysis with self-reported writing self-efficacy, attitudes toward writing, and a measure of writing writing: Low, Low/Mid, Mid/High, and High. Most students started the school year in the Low/Mid (38%) and Mid/High (30%) profiles. Only 11% of students started the school year in the High profile. Between 50 and 70% of students maintained the same profile in the Spring. Approximately 30% of students were likely to move one profile higher in the Spring. Fewer than 1% of students exhibited steeper transitions (e.g., from High to Low profile). Random assignment to treatment did not significantly influence transition paths. Likewise, gender, being a member of a priority population, or receiving special education services did not significantly influence transition paths. Results provide a promising profiling strategy focused on students' attitudes, motivations, and ability and show students' likeliness to belong to each profile based on their demographic characteristics. Finally, despite previous research indicating positive effects of AWE on writing motivation, results indicate that simply providing access to AWE in schools serving priority populations is insufficient to produce meaningful changes in students' writing motivation profiles or writing outcomes. Therefore, interventions targeting writing motivation, in conjunction with AWE, could improve results.

Assessing the diagnostic utility of the Cannabis Use Disorder Identification Test - Revised (CUDIT-R) among veterans with medical and non-medical cannabis use.

BACKGROUND: Few studies examine the utility of the Cannabis Use Disorder Identification Test - Revised (CUDIT-R) in relation to the Diagnostic and Statistical Manual of Mental Disorders, Fifth Edition, (DSM-5) criteria for cannabis use disorder (CUD). This study assesses the performance of the CUDIT-R among a sample of Veterans with and without medical cannabis use. METHODS: We approached and consented primary care patients presenting to one of three Department of Veterans Affairs (VA) Medical Centers. Veterans with at least monthly cannabis use and complete CUD data at baseline were included in this analysis (n=234). CUDIT-R scores were compared against Alcohol Use Disorder and Associated Disabilities Interview Schedule-5 (DSM-5) CUD as the standard to calculate measures of validity (sensitivity, specificity), identify optimal CUDIT-R cutoff values, and assess the diagnostic proficiency of the CUDIT-R using receiver operating characteristic (ROC) curves. We further stratified analyses by active medical cannabis card holder status and DSM-5 CUD severity (any, moderate, and severe). RESULTS: Among the entire sample, 38.9% qualified for any DSM-5 CUD, with 10.7% and 3.0% meeting criteria for moderate and severe CUD, respectively. We identified optimal CUDIT-R scores at 10 for any DSM-5 CUD (sensitivity=0.58; specificity=0.80), at 12 for moderate CUD (sensitivity=0.72; specificity=0.82), and at 14 for severe CUD (sensitivity=0.71; specificity=0.87). ROC curves showed higher CUDIT-R validity among non-card holders compared with medical cannabis card holders. CONCLUSION: The present study identified optimal CUDIT-R cutoff scores for Veterans who use cannabis. Varying DSM-5 validity measures inform the need for population-specific CUDIT-R cutoff values.

Firearms Availability Among High-School Age Youth With Recent Depression or Suicidality.

BACKGROUND AND OBJECTIVES: Limiting firearm access is essential to decreasing teen suicide. Previous efforts have focused on household firearms; however, less is known about firearm access and possession among teens at increased suicide risk. Our objective was to estimate prevalence of firearm possession and access among high school-aged teens with recent depression and/or lifetime history of suicidality (DLHS). METHODS: We conducted a probability-based, cross-sectional Web survey of 1914 parent-teen dyads between June 24, 2020, and July 22, 2020, with data weighted to generate a nationally representative sample of US teenagers (aged 14-18). Logistic regression analyses examined the difference between teens with and without DLHS for: (1) personal firearm possession, (2) perceived firearm access, and (3) method of firearm attainment. RESULTS: Among high school-aged teens, 22.6% (95% confidence interval [CI], 19.4-25.8) reported DLHS, 11.5% (95% CI, 8.7-14.3) reported personal firearm possession, and 44.2% (95% CI, 40.2-48.2) endorsed firearm access. Teens experiencing DLHS had increased perceived access (adjusted odds ratio, 1.56; 95% CI, 1.07-2.28) compared with non-DLHS peers. There was no association between DLHS and personal firearm possession (adjusted odds ratio, 0.97; 95% CI, 0.47-2.00). Among teens reporting firearm possession, those with DLHS were more likely to have acquired it by buying/trading for it (odds ratio, 5.66; 95% CI, 1.17-27.37) and less likely receiving it as a gift (odds ratio, 0.06; 95% CI, 0.01-0.36). CONCLUSIONS: High school-aged teens experiencing DLHS have higher perceived firearm access compared with lower-risk peers. Providers should speak directly to high school-aged teens at increased suicide risk about firearm access, in addition to counseling parents.

Development and characterization of a sorghum multi-parent advanced generation intercross (MAGIC) population for capturing diversity among seed parent gene pool.

Multiparent advanced eneration inter-cross (MAGIC) populations improve the precision of quantitative trait loci (QTL) mapping over biparental populations by incorporating increased diversity and opportunities to reduce linkage disequilibrium among variants. Here, we describe the development of a MAGIC B-Line (MBL) population from an inter-cross among 4 diverse founders of grain sorghum [Sorghum bicolor (L.) Moench] across different races (kafir, guinea, durra, and caudatum). These founders were selected based on genetic uniqueness and several distinct qualitative features including panicle architecture, plant color, seed color, endosperm texture, and awns. A whole set of MBL (708 F6) recombinant inbred lines along with their founders were genotyped using Diversity Arrays Technology (DArTseq) and 5,683 single-nucleotide polymorphisms (SNPs) were generated. A genetic linkage map was constructed using a set of polymorphic, quality-filtered markers (2,728 SNPs) for QTL interval-mapping. For population validation, 3 traits (seed color, plant color, and awns) were used for QTL mapping and genome-wide association study (GWAS). QTL mapping and GWAS identified 4 major genomic regions located across 3 chromosomes (Chr1, Chr3, and Chr6) that correspond to known genetic loci for the targeted traits. Founders of this population consist of the fertility maintainer (A/B line) gene pool and derived MBL lines could serve as female/seed parents in the cytoplasmic male sterility breeding system. The MBL population will serve as a unique genetic and genomic resource to better characterize the genetics of complex traits and potentially identify superior alleles for crop improvement efforts to enrich the seed parent gene pool.

Driving under the influence of cannabis, alcohol, and illicit drugs among adults in the United States from 2016 to 2020.

OBJECTIVE: Driving under the influence (DUI) of substances increases motor vehicle crash risk. Understanding current national trends of driving under the influence of alcohol (DUIA), cannabis (DUIC), and drugs other than cannabis (DUID) can inform public health efforts. Herein, we provide updated trends among United States (US) adults regarding DUIA, DUIC, DUID, and DUI of any substance. METHOD: We used nationally-representative National Survey on Drug Use and Health (2016-2020) data to derive prevalence estimates of past-year DUIC, DUIA, DUID, and DUI of any substance among non-institutionalized US adults and among those reporting respective past-year  substance use. Prevalence estimates and adjusted logistic regressions characterized temporal trends of these behaviors among US adults, among those with respective past-year substance use, and among stratified demographic subpopulations. RESULTS: Over 1 in 10 US adults reported DUI of any substance annually from 2016 to 2020.DUIA was most prevalent among all US adults (8.7% in 2017); however, this behavior is decreasing (AOR:0.96; 95%CI:0.94,0.98). No change in DUIC among the US adult population was found, but a decrease was found among those with past-year cannabis use (AOR:0.95; 95%CI:0.93,0.98), which coincided with a 29.1% increase in past-year cannabis use. There were no significant changes in overall DUID; however, females, those ages 26-34 and 65 or older with past-year use displayed increasing trends. DUI of any substance decreased among the US adult population. CONCLUSIONS: DUI remains a salient public health concern in the US and results indicate population subgroups who may benefit from impaired driving prevention interventions.

Vessel Rupture Thresholds for Vessel-Bubble Interactions Using an Earthworm Vasculature Model.

OBJECTIVE: Intravenous microbubble oscillation in the presence of ultrasound has the potential to yield a wide range of therapeutic benefits. However, the likelihood of vessel damage caused by mechanical effects has not been quantified as a function of the numerous important parameters in therapeutic ultrasound procedures. In this study, we examined the effects of microbubbles injected into the vasculature of the earthworm. It was found that the elastic properties of earthworm blood vessels are similar to those of arteries in older humans, and that earthworms are well suited to the large number of experiments necessary to investigate safety of procedures involving microbubble oscillation in sonicated vessels. METHODS: Microbubbles were infused into earthworm vessels, and the rupture time during sonication was recorded as a function of ultrasound frequency, pulse repetition frequency and acoustic pressure. DISCUSSION: A modified mechanical index (MMI) was defined that successfully captured the trends in rupture probability and rupture time for the different parameter values, creating a database of vessel rupture thresholds. In the absence of bubbles, the product of MMI squared and rupture time was approximately constant, indicating a possible radiation-force effect. CONCLUSION: The MMI was an effective correlating parameter in the presence of bubbles, though the mathematical dependence is not yet apparent. The results of the study are expected to be valuable in designing more refined studies in vertebrate models, as well as informing computational models.

Genomic prediction of hybrid performance for agronomic traits in sorghum.

Hybrid breeding in sorghum [Sorghum bicolor (L.) Moench] utilizes the cytoplasmic-nuclear male sterility (CMS) system for seed production and subsequently harnesses heterosis. Since the cost of developing and evaluating inbred and hybrid lines in the CMS system is costly and time-consuming, genomic prediction of parental lines and hybrids is based on genetic data genotype. We generated 602 hybrids by crossing two female (A) lines with 301 diverse and elite male (R) lines from the sorghum association panel and collected phenotypic data for agronomic traits over two years. We genotyped the inbred parents using whole genome resequencing and used 2,687,342 high quality (minor allele frequency > 2%) single nucleotide polymorphisms for genomic prediction. For grain yield, the experimental hybrids exhibited an average mid-parent heterosis of 40%. Genomic best linear unbiased prediction (GBLUP) for hybrid performance yielded an average prediction accuracy of 0.76-0.93 under the prediction scenario where both parental lines in validation sets were included in the training sets (T2). However, when only female tester was shared between training and validation sets (T1F), prediction accuracies declined by 12-90%, with plant height showing the greatest decline. Mean accuracies for predicting the general combining ability of male parents ranged from 0.33 to 0.62 for all traits. Our results showed hybrid performance for agronomic traits can be predicted with high accuracy, and optimizing genomic relationship is essential for optimal training population design for genomic selection in sorghum breeding.

Characterization of aerosols generated by high-power electronic nicotine delivery systems (ENDS): Influence of atomizer, temperature and PG:VG ratios.

The aerosol characteristics of electronic nicotine delivery systems (ENDS) are important parameters in predicting health outcomes since parameters such as aerosol particle size correlate strongly to aerosol delivery and deposition efficiency. However, many studies to date do not account for aerosol aging, which may affect the measurement of ultra-fine particles that typically coagulate or agglomerate during puff development. To reduce aerosol aging, we herein present a unique instrumentation method that combines a) positive pressure ENDS activation and sample collection, b) minimization of both sample tubing length and dilution factors, and c) a high-resolution, electrical low-pressure impactor. This novel approach was applied to systematically investigate the effects of coil design, coil temperature, and propylene glycol to vegetable glycerol ratios on aerosol characteristics including aerosol mass generation, aerosol count generation, and the mass and count size distributions for a high-powered ENDS. Aerosol count measurements revealed high concentrations of ultra-fine particles compared to fine and coarse particles at 200°C, while aerosol mass measurements showed an increase in the overall aerosol mass of fine and coarse particles with increases in temperature and decreases in propylene glycol content. These results provide a better understanding on how various ENDS design parameters affect aerosol characteristics and highlight the need for further research to identify the design parameters that most impact ultra-fine particle generation.

Firearm safety counseling among caregivers of high-school age teens: Results from a National Survey.

Firearms are the leading cause of death for high-school age teens. To inform prevention efforts, we characterize the prevalence of healthcare provider (HCP) counseling of caregivers of teens around firearm safety, safety conversation elements, and caregiver receptivity towards counseling. A cross-sectional web survey (6/24/2020-7/22/2020) was conducted among caregivers (n = 2924) of teens (age:14-18). Weights were applied to generate nationally representative estimates. Bivariate analyses and multivariate regressions were examined. Among respondents, 56.0% were women, 75.1% were non-Hispanic White, and mean (SD) age was 47.4. Firearm safety was the least discussed topic among caregivers reporting their teen received HCP preventative counseling (14.9%). For caregivers receiving counseling, the most common issues discussed were household firearms screening (75.7%); storing firearms locked (66.8%); and storing firearms unloaded (53.0%). Only 24.6% of caregivers indicated firearm safety was an important issue for teen HCPs to discuss and only 21.9% trusted teen HCPs to counsel about firearm safety. Female caregivers (aOR = 1.86;95%CI = 1.25-2.78), those trusting their teen's HCP to counsel on firearm safety (aOR = 9.63;95%CI = 6.37-14.56), and those who received teen HCP firearm safety counseling (aOR = 5.14;95%CI = 3.02-8.72) were more likely to favor firearm safety counseling. Caregivers of teens with prior firearm safety training (aOR = 0.50;95%CI = 0.31-0.80) were less likely to agree that firearm safety was an important preventative health topic. In conclusion, few caregivers receive preventive counseling on firearm safety from their teen's HCP, with trust a key barrier to effective intervention delivery. Future research, in addition to understanding barriers and establishing effective strategies to increase safety practices, should focus on increasing provider counseling competency.

Comparison of effectiveness of enhanced infection countermeasures in different scenarios, using a dynamic-spread-function model.

When formulating countermeasures to epidemics such as those generated by COVID-19, estimates of the benefits of a given intervention for a specific population are highly beneficial to policy makers. A recently introduced tool, known as the "dynamic-spread" SIR model, can perform population-specific risk assessment. Behavior is quantified by the dynamic-spread function, which includes the mechanisms of droplet reduction using facemasks and transmission control due to social distancing. The spread function is calibrated using infection data from a previous wave of the infection, or other data felt to accurately represent the population behaviors. The model then computes the rate of spread of the infection for different hypothesized interventions, over the time window for the calibration data. The dynamic-spread model was used to assess the benefit of three enhanced intervention strategies - increased mask filtration efficiency, higher mask compliance, and elevated social distancing - in four COVID-19 scenarios occurring in 2020: the first wave (i.e. until the first peak in numbers of new infections) in New York City; the first wave in New York State; the spread aboard the Diamond Princess Cruise Liner; and the peak occurring after re-opening in Harris County, Texas. Differences in the efficacy of the same intervention in the different scenarios were estimated. As an example, when the average outward filtration efficiency for facemasks worn in New York City was increased from an assumed baseline of 67% to a hypothesized 90%, the calculated peak number of new infections per day decreased by 40%. For the same baseline and hypothesized filtration efficiencies aboard the Diamond Princess Cruise liner, the calculated peak number of new infections per day decreased by about 15%. An important factor contributing to the difference between the two scenarios is the lower mask compliance (derivable from the spread function) aboard the Diamond Princess.

Dissecting the Genetic Architecture of Carbon Partitioning in Sorghum Using Multiscale Phenotypes.

Carbon partitioning in plants may be viewed as a dynamic process composed of the many interactions between sources and sinks. The accumulation and distribution of fixed carbon is not dictated simply by the sink strength and number but is dependent upon the source, pathways, and interactions of the system. As such, the study of carbon partitioning through perturbations to the system or through focus on individual traits may fail to produce actionable developments or a comprehensive understanding of the mechanisms underlying this complex process. Using the recently published sorghum carbon-partitioning panel, we collected both macroscale phenotypic characteristics such as plant height, above-ground biomass, and dry weight along with microscale compositional traits to deconvolute the carbon-partitioning pathways in this multipurpose crop. Multivariate analyses of traits resulted in the identification of numerous loci associated with several distinct carbon-partitioning traits, which putatively regulate sugar content, manganese homeostasis, and nitrate transportation. Using a multivariate adaptive shrinkage approach, we identified several loci associated with multiple traits suggesting that pleiotropic and/or interactive effects may positively influence multiple carbon-partitioning traits, or these overlaps may represent molecular switches mediating basal carbon allocating or partitioning networks. Conversely, we also identify a carbon tradeoff where reduced lignin content is associated with increased sugar content. The results presented here support previous studies demonstrating the convoluted nature of carbon partitioning in sorghum and emphasize the importance of taking a holistic approach to the study of carbon partitioning by utilizing multiscale phenotypes.

Convergent evolution and multi-wave clonal invasion in H3 K27-altered diffuse midline gliomas treated with a PDGFR inhibitor.

The majority of diffuse midline gliomas, H3 K27-altered (DMG-H3 K27-a), are infiltrating pediatric brain tumors that arise in the pons with no effective treatment. To understand how clonal evolution contributes to the tumor's invasive spread, we performed exome sequencing and SNP array profiling on 49 multi-region autopsy samples from 11 patients with pontine DMG-H3 K27-a enrolled in a phase I clinical trial of PDGFR inhibitor crenolanib. For each patient, a phylogenetic tree was constructed by testing multiple possible clonal evolution models to select the one consistent with somatic mutations and copy number variations across all tumor regions. The tree was then used to deconvolute subclonal composition and prevalence at each tumor region to study convergent evolution and invasion patterns. Somatic variants in the PI3K pathway, a late event, are enriched in our cohort, affecting 70% of patients. Convergent evolution of PI3K at distinct phylogenetic branches was detected in 40% of the patients. 24 (~ 50%) of tumor regions were occupied by subclones of mixed lineages with varying molecular ages, indicating multiple waves of invasion across the pons and extrapontine. Subclones harboring a PDGFRA amplicon, including one that amplified a PDGRFAY849C mutant allele, were detected in four patients; their presence in extrapontine tumor and normal brain samples imply their involvement in extrapontine invasion. Our study expands the current knowledge on tumor invasion patterns in DMG-H3 K27-a, which may inform the design of future clinical trials.