University of Minnesota

Background In pediatric non-rhabdomyosarcoma soft tissue sarcoma (NRSTS), the frequency and prognostic impact of regional lymph node involvement (N1) are not clearly defined and may vary according to histological type. We therefore to analyze the rate of N1 at diagnosis, the pattern of nodal relapse, and the prognostic impact of N1 in pediatric patients with NRSTS. Methods Data were collected and analyzed through the International Soft Tissue SaRcoma ConsorTium (INSTRuCT). Patients aged 0–21 years with NRSTS prospectively enrolled in European and North American cooperative group trials from October 1, 1990 to October 1, 2018 were included. Descriptive statistics, logistic regressions, and Cox proportional hazards models were used to analyze the data and assess prognostic factors. Findings 1937 patients were eligible for inclusion. The main histotypes were synovial sarcoma (628 cases; 32%), undifferentiated/unclassified sarcoma (396 cases, 20%) and malignant peripheral nerve sheath tumor (275 cases, 14%). Distant metastases were present in 197 (10.2%) patients. N1 was present in 152 (7.8%) patients. With a median follow-up of 7.2 years (95% CI 7.0–7.4), 615 patients (31.7%) had local relapse or progression, 30 (1.5%) had nodal relapse (including four with initial N1), and 287 (14.8%) developed metastases. In multivariate analysis, node positive (N1) status was associated with high pathologic grade (p = 0.010) and distant metastasis (p < 0.0001), but not with tumor size, invasiveness, and histological subgroups (p = 0.36). For non-metastatic tumors (1740 cases), metastatic-free-survival differed between node negative N0 and N1 patients, but overall survival, event-free-survival and nodal relapse-free-interval did not. Interpretation N1 is rare in NRSTS during childhood (<8%) and mainly presents in a subset of histotypes. Regional nodal control at 5 years is adequate. However, N1 in NRSTS is a marker of aggressive disease. Funding 10.13039/100002002Cancer Research Foundation, Children's Research Foundation, Comer Development Board, KickCancer, 10.13039/501100006282King Baudouin Foundation, 10.13039/100003287Rally Foundation for Childhood Cancer Research, 10.13039/100018762Seattle Children's Foundation from Kat's Crew Guild through the 10.13039/100001845Scleroderma Research Foundation, 10.13039/100006058St. Baldrick's Foundation, The Andrew McDonough B+ Foundation, Maddie’s Promise, Summer’s Way Foundation, Friends of T.J. Foundation, Sebastian Strong, Children’s Oncology Group Foundation, and the Sarah Jane Adicoff Endowment for Research in Rhabdomyosarcoma through the 10.13039/100018762Seattle Children's Foundation.

Cell division commonly produces two daughter cells, but there are many exceptions where large cells produce multiple daughters. Multiple fission of some green algae and bacteria; cellularization during embryogenesis of plants and insects; and growth of Ichthyosporeans, Chytrids, and Apicomplexans all provide variations on this theme. In some yeast species, a large multinucleate mother cell grows multiple buds (daughters) simultaneously. Here, we address how mothers partition growth equally among their buds in the multi-budding yeast Aureobasidium pullulans. Bud growth is directed by actin cable networks that appear to be optimized for even partitioning despite complex cell geometries. Even partitioning does not rely on compensatory mechanisms to adjust bud volumes but rather stems directly from effective equalization of polarity sites. These results reveal how conserved cell polarity and cytoskeletal networks are adapted to build complex morphologies in fungi.

Veterinary medicine is centered on the animal patient, and similarly, human medicine is centered on the human patient. Yet animal health, human health, and the environment intersect in myriad ways. Despite this intersection, there are few resources that take a family-centered, collaborative approach to human, animal, and environmental health. To help address this gap, AAHA has brought together a task force of human and veterinary medical professionals with the goal of improving collaboration between professions to facilitate better outcomes for families with pets. These guidelines address common scenarios (e.g., zoonotic disease, disability, intimate partner violence) that intersect with human and animal health and provide strategies for greater communication and collaboration between the professions. The guidelines cover (1) terms and definitions to establish a common language between professions; (2) how to determine if a case requires a One Health approach; (3) how and when to reach out to other professionals for a case (e.g., social worker, physician, other medical professionals); and (4) how and when to follow up and close cases. These guidelines also offer case studies illustrating One Health scenarios that connect with human/family health, with supplemental materials available on the AAHA website at aaha.org/one-health.

Perennial flax ( Linum sp.) is a new horticultural crop with potential use as a cut flower (CF) and an herbaceous perennial (HP) because its blue flowers provide a rare color in ornamentals. Crop ideotypes for CF and HP perennial flax serve as guides for future testing and product development (e.g., stock plant, cutting, and liner production). The objectives of this research were to determine greenhouse parameters for vegetative cuttings and flowering stem production to provide guidelines for producers. Fifteen CF Linum ( Linum perenne , L. austriacum , L. lewisii , L. bienne ) genotypes (CF1–CF15) were tested for greenhouse production factors. In Expt. 1, cutting yield and rooting ability/stock plant were measured to determine the genotype, container size (8.9 cm or 16.5 cm), soft pinching (pinched or unpinched), number of plants per container (one, two, or three), vernalization (before or after), and plant growth regulator (0 or 200 ppm ethephon) for 22 weeks. In Expt. 2, we tested indoor production requirements for flowering stem production to inform selection, breeding, and production scheduling. We measured morphological, phenotypic, and phenological production traits/genotype using one plant per container (13.3 cm) for 27 weeks. Pinching and ethephon treatments (Expt. 1) did not increase cutting production for CF genotypes; both container sizes averaged 2 to 3 cuttings/plant/week, regardless of plant number. Genotypes differed in production, and those with significantly higher cutting quantity and percent rooting included CF8, CF10, CF12, and CF14. Growing 3 stock plants/16.5-cm container under long days (16 hours) for 6 months was a successful protocol for stock plant production. Most traits differed significantly by CF genotype in Expt. 2. Genotypes with the CF ideotype traits of early flowering, extended flowering period, higher number of flowering stems/plant, stem length, large flowers, and plant habit were CF4, CF13, and CF14. These three genotypes averaged 25 flowering stems/plant and produced the greatest technical stem lengths (42–60 cm). Of the 15 Linum genotypes tested, the best selections for cutting production were CF12 and CF14, while CF4 and CF13 had the highest flowering stem production. All four genotypes should advance in the CF flax breeding program based on alignment with the CF ideotype model and should be hybridized to combine maximum flowering stems, greatest technical stem length, and greatest flower longevity in new hybrids.

Early intervention has the potential to improve the outcomes of children with autism. As more evidence-based early intervention approaches become available, data generated from studies testing their efficacy provide the unique opportunity to examine whether specific interventions differentially benefit children based on their demographic and behavioral characteristics. In this study, we retrospectively applied a probability-of-intervention-benefit framework to data from a randomized controlled trial comparing the outcomes of children with autism receiving community intervention as usual to those receiving the Early Start Denver Model (ESDM) delivered by university-based clinicians. Data from 85 children, randomized to one of the two intervention groups were analyzed. The primary outcome was the Brief Observation of Social Communication Change, a video coded measure of autism related social communication and repetitive behaviors. Children were classified as making reliable change or not on this outcome based on their reliable change index. 73% of children in the ESDM group and 57% in the community group made reliable improvements over the 24 months of intervention. The probability of intervention benefit in the community group depended on children’s baseline characteristics. Those with more significant cognitive delays and greater autism severity were less likely to make reliable change in the community group, but not the ESDM group. Overall, the data highlight the variability of change that individual children make in early interventions, the role of various factors contributing to change, and finally, the importance of analyzing change at both the group and the individual levels.

Teleoperation can enable human intervention to help handle instances of failure in autonomy thus allowing for much safer deployment of autonomous vehicle technology. Successful teleoperation requires recreating the environment around the remote vehicle using camera data received over wireless communication channels. This paper develops a new predictive display system to tackle the significant time delays encountered in receiving camera data over wireless networks. First, a new high gain observer is developed for estimating the position and orientation of the ego vehicle. The novel observer is shown to perform accurate state estimation using only GNSS and gyroscope sensor readings. A vector field method which fuses the delayed camera and Lidar data is then presented. This method uses sparse 3D points obtained from Lidar and transforms them using the state estimates from the high gain observer to generate a sparse vector field for the camera image. Polynomial based interpolation is then performed to obtain the vector field for the complete image which is then remapped to synthesize images for accurate predictive display. The method is evaluated on real-world experimental data from the nuScenes and KITTI datasets. The performance of the high gain observer is also evaluated and compared with that of the EKF. The synthesized images using the vector field based predictive display are compared with ground truth images using various image metrics and offer vastly improved performance compared to delayed images.

Proactive work behavior is critical for sustaining organizational competitiveness and ensuring long‐term success. As such, it is essential to identify its antecedents in order to develop effective strategies to foster proactive work behavior. Grounded in Parker et al.'s Proactive Motivation Process Framework, this paper proposes and validates a model for the motivational state antecedents of proactive work behavior by conducting a meta‐analysis. Examining 298 articles comprising 308 independent studies (N = 107 084), this study fully supports the expected relationships between three categories of antecedents—“can do,” “reason to,” and “energized to”—and proactive work behavior. Additionally, we identify power distance and uncertainty avoidance as key moderators influencing the relationship between motivational states and proactive work behavior. Our study further explores which motivational states most effectively promote overall proactive work behavior and its specific forms (taking charge, voice, and individual innovation) and distinguishes their effects on proactive behavior versus job performance. Finally, we discuss the theoretical and practical implications, offering new research directions and guidance for managers to formulate effective strategies for encouraging proactive work behavior.

Skeletal muscle is integral to life and functions to produce movement and locomotion, postural control, respiratory activity, and heat production. Yet, injuries to skeletal muscles occur across the lifespan, and depending on the injury mechanism, nuances in physiology and severity, how and if recovery of muscle function is possible is varied. This chapter presents the current physiologic understanding of various traumatic skeletal muscle injuries with attention to landmark work that has built the foundation for our current understanding. Injuries ranging from those that leave the extracellular matrix (ECM) intact or completely lost will be discussed as well as the common eccentric contraction-induced and ischemia-reperfusion injuries.

Hyperacetylation of proteins represents a stress to aged organisms. Increased consumption and loss of NAD+ homeostasis underlie a major mechanism for the disturbed acetylation/deacetylation balance during aging. Nicotinamide adenine dinucleotide (NAD) is a versatile chemical compound serving as a coenzyme in metabolic pathways and as a substrate to support the enzymatic functions of sirtuins (SIRTs), poly (ADP-ribose) polymerase-1 (PARP-1), and cyclic ADP ribose hydrolase (CD38). Under normal physiological conditions, NAD+ consumption is matched by its synthesis primarily via the salvage pathway catalyzed by nicotinamide phosphoribosyltransferase (NAMPT). However, aging and muscular contraction enhance NAD+ utilization, whereas NAD+ replenishment is limited by cellular sources of NAD+ precursors and/or enzyme expression. This chapter will briefly review NAD+ metabolic functions, its roles in regulating cell signaling, mechanisms of its degradation and biosynthesis, and major challenges to maintain its cellular level in skeletal muscle. The effects of aging, physical exercise, and dietary supplementation on NAD+ homeostasis will be highlighted based on recent literature.

Background Metabolic dysfunction-associated steatotic liver disease (MASLD) is a global health challenge, with cardiovascular mortality. The cardiometabolic index (CMI), a biomarker derived by multiplying the waist-to-height ratio (WHtR) with the triglyceride-to-high-density lipoprotein cholesterol ratio (TG/HDL-C), shows promise as a predictive tool for MASLD. This study aims to systematically evaluate the association between CMI and MASLD. Methods A comprehensive search of PubMed, Scopus, Embase, and Web of Science was conducted up to January 2025. Studies reporting the association between CMI and MASLD in adults were included. For meta-analysis, odds ratios (OR) and standardized mean differences (SMD) were computed. Heterogeneity was assessed using I², and publication bias was evaluated via Egger’s test. Subgroup analyses and meta-regressions explored sources of heterogeneity. Results Ten studies with 51,037 participants were included. Individuals with MASLD had significantly higher CMI (SMD = 1.22, 95%CI: 0.99, 1.45; I² = 98.5%) compared to those without MASLD. Studies with higher smoking prevalence and elevated systolic and diastolic blood pressure showed a lower SMD of CMI in MASLD compared to non-MASLD patients, while meta-regression indicated that factors such as age, gender, body mass index, fasting blood glucose, lipid profile, and liver function tests were not significant sources of heterogeneity. Each 1-SD increase in CMI was associated with roughly 2-fold higher odds of MASLD (OR = 2.26, 95%CI: 1.75, 2.91; I² = 96.6%). Patients in the highest CMI quartile had substantially greater odds of MASLD compared to the lowest quartile (OR = 7.66, 95%CI: 4.84, 12.10; I² = 90.2%). The pooled area under the curve (AUC) for CMI in predicting MASLD was 0.81, 95%CI: 0.79–0.84. Conclusions CMI correlates strongly with MASLD, suggesting its potential as a non-invasive tool for early detection and risk stratification. Future research should investigate whether interventions that reduce CMI can slow disease progression and prevent complications such as cirrhosis or hepatocellular carcinoma. Future research should focus on refining CMI cut-off values and validating its applicability across diverse populations.

Central line‐associated bloodstream infections (CLABSI) are a significant cause of morbidity in children with intestinal failure (IF). Probiotic therapy is discouraged in patients with IF because of the increased risk of bacteremia with the probiotic organism. We report an unusual, previously undescribed, clinical presentation of a Lactobacillus‐species CLABSI linked to yogurt consumption in a toddler with IF secondary to Megacystis–microcolon–intestinal hypoperistalsis syndrome. Lactobacillus is abundant in fermented foods like yogurt and among the commensal constituents of the oral cavity microbiome and mucosal surfaces in the gastrointestinal tract. It is rarely implicated as the causative organism in CLABSI. At the time of presentation with fever, blood cultures were collected from the patient's central venous catheter (CVC), and peripherally. Both grew Lactobacillus species. Comparative genetic analysis predicted ~99% similarity between the CLABSI isolate and Lactobacillus isolates from the Greek yogurt the patient regularly consumed. Our patient's Lactobacillus CLABSI was linked to the consumption of Greek yogurt. We speculate that daily consumption of yogurt with live cultures posed a high cumulative exposure to Lactobacillus species either through external contamination of our patient's CVC or translocation of the ingested organisms from his gastrointestinal tract into the bloodstream. This is the first case report that links CLABSI in children with IF to yogurt consumption.

Network control theory (NCT) models human connectomes as high-dimensional input-state-output stable systems where the efficiency of neural connections can be addressed by energy cost (of state transitions) and controllability (from/to reachable states). Different options are available to extract NCT features: initial/final states, control time horizon, structural (vs. functional), and static (vs. dynamic) connectivity measure. Leveraging the minimum control paradigm, assuming the Schur stability for discrete systems, we investigate intra- and inter-individual variability of NCT features, across different settings and datasets, and assess their potential as useful connectome metrics in clinical studies. NCT was applied to structural and functional MRI (fMRI), in a cohort of 82 cognitively unimpaired elderly subjects with normal or (age-related) sensorineural condition (hearing loss), and in young adults from the Human Connectome Project database. Results demonstrated low intra-individual and moderate within-group inter-individual variability of NCT features. The energy cost was related to the time horizon of the system but did not discriminate groups. Controllability analyses revealed significant group effects and acceptable discrimination between normal and disease-affected connectomes, particularly for the default-mode network. We provide a systematic evaluation of different settings for fMRI-derived NCT features that may help guiding clinical applications toward capturing neurologically meaningful changes in the human connectome.

When a third layer of graphene is transferred on top of twisted bilayer graphene with a second twist, the atomic and electronic structure of the system can be significantly enriched. Generally, the two coexisting moiré superlattices give rise to a higher-order moiré-of-moiré (MoM) superlattice, with a plethora of new length scales and associated novel quantum phenomena. This article reviews the current theoretical understanding and experimental observations of twisted trilayer graphene MoM (or supermoiré) superlattices, and the theoretical predictions and ongoing experimental efforts for unraveling rich exotic quantum phenomena and underlying physics.

In this work, we explore the possibility of reconstructing microseismic events in a solid body, in terms of both event locations and respective seismic moment tensors, using full-waveform observations of acoustic pressure fluctuations generated in the surrounding fluid. Our developments are motivated by the prospect of locating and characterizing, via hydrophone measurements, reaction-driven cracking in (coastal or seabed) geologic formations underpinning mineralization-driven, permanent carbon storage in the subsurface. On representing the microseismic events as dipole and double-couple point sources in the solid, the prototype (two-dimensional) analysis is reduced to an inverse source problem that deploys (i) time-harmonic forward map for the solid–fluid system; (ii) combinatorial search over a prescribed grid spanning the source region; (iii) global and local grid refinements catering for the stability and veracity of source reconstruction, and (iv) multi-frequency components of the acoustic pressure traces observed in the surrounding fluid. Numerical simulations demonstrate the feasibility of reconstructing multiple (contemporaneous) microseismic events, in terms of both their locations and respective seismic moment tensors, using a modest number of acoustic pressure observations in the fluid. The simulations highlight the importance of observation aperture on the quality of source reconstruction, an item that features two modalities: (a) spatial—manifested via the number and location of pointwise sensors (hydrophones), and (b) temporal—synthesized via the number and linear independence of multi-frequency observations. The two aperture modalities are found via numerical simulations to work in unison in that the scarcity of one can, to a degree, be compensated by the abundance of another. In a physical setting, (a) is controlled by the sensing setup, while (b) hinges on the spectral bandwidth of microseismic events.