Distribution theories for genetic line of least resistance and evolvability measures.

Quantitative genetic theory on multivariate character evolution predicts that a population's response to directional selection is biased toward the major axis of the genetic covariance matrix G-the so-called genetic line of least resistance. Inferences on the genetic constraints in this sense have traditionally been made by measuring the angle of deviation of evolutionary trajectories from the major axis, or more recently by calculating the amount of genetic variance-the Hansen-Houle evolvability-available along the trajectories. However, there have not been clear practical guidelines on how these quantities can be interpreted, especially in a high-dimensional space. This study summarizes pertinent distribution theories for relevant quantities, pointing out that they can be written as ratios of quadratic forms in evolutionary trajectory vectors by taking G as a parameter. For example, a beta distribution with appropriate parameters can be used as a null distribution for squared cosine of the angle of deviation from a major axis or subspace. More general cases can be handled with the probability distribution of ratios of quadratic forms in normal variables. Apart from its use in hypothesis-testing, this latter approach could potentially be used as a heuristic tool for looking into various selection scenarios like directional and/or correlated selection as parameterized with mean and covariance of selection gradients.

Prototype theory and the importance of literary form for moral imagination.

Prototype theory, which argues that categories have graded (and thus fuzzy) membership based on prototypes, has been used as cognitive evidence to support moral particularism because if categories (in moral rules) only have fuzzy conceptual boundaries, moral rules are not enough for moral judgment, as specific situations also need to be considered to determine how these fuzzy categories should be understood, which is what moral particularism believes. The importance of literature for ethics, especially for moral imagination, has also been extensively discussed because literature can provide vivid examples for us to imagine different moral dilemmas, the consequences of different moral choices, and the feelings of different people facing different situations. Martha Nussbaum specifically argues that the literary form is the only adequate form to imagine certain complex moral situations. By analyzing concrete literary examples as well as the related ethical discussions and empirical findings, this article argues that, building on Nussbaum's argument, prototype theory can serve as a cognitive basis for the importance of literary form for moral imagination, because the literary form's tolerance of ambiguity suits how we ambiguously categorize the world.

Increasing cadence with a metronome and running barefoot changes the sagittal kinematics of the lower limbs and trunk.

The purpose was to compare two non-laboratory based running retraining programs on lower limb and trunk kinematics in recreational runners. Seventy recreational runners (30 ± 7.3 years old, 40% female) were randomised to a barefoot running group (BAR), a group wearing a digital metronome with their basal cadence increased by 10% (CAD), and a control group (CON). BAR and CAD groups included intervals from 15 to 40 min over 10 weeks and 3 days/week. 3D sagittal kinematics of the ankle, knee, hip, pelvis, and trunk were measured before and after the retraining program, at comfortable and high speeds. A 3 × 2 mixed ANOVA revealed that BAR and CAD groups increased knee and hip flexion at footstrike, increased peak hip flexion during stance and flight phase, decreased peak hip extension during flight phase, and increased anterior pelvic tilt at both speeds after retraining. In addition, BAR increased ankle plantar flexion at footstrike and increased anterior trunk tilt. Both retraining programs demonstrated significant moderate to large effect size changes in parameters that could reduce the mechanical risks of injury associated with excessive knee stress, which is of interest to coaches, runners and those prescribing rehabilitation and injury prevention programs.

Elevated CO2 and ammonium nitrogen promoted the plasticity of two maple in great lakes region by adjusting photosynthetic adaptation.

Introduction: Climate change-related CO2 increases and different forms of nitrogen deposition are thought to affect the performance of plants, but their interactions have been poorly studied. Methods: This study investigated the responses of photosynthesis and growth in two invasive maple species, amur maple (Acer ginnala Maxim.) and boxelder maple (Acer negundo L.), to elevated CO2 (400 µmol mol-1 (aCO2) vs. 800 µmol mol-1 (eCO2) and different forms of nitrogen fertilization (100% nitrate, 100% ammonium, and an equal mix of the two) with pot experiment under controlled conditions. Results and discussion: The results showed that eCO2 significantly promoted photosynthesis, biomass, and stomatal conductance in both species. The biochemical limitation of photosynthesis was switched to RuBP regeneration (related to Jmax) under eCO2 from the Rubisco carboxylation limitation (related to Vcmax) under aCO2. Both species maximized carbon gain by lower specific leaf area and higher N concentration than control treatment, indicating robust morphological plasticity. Ammonium was not conducive to growth under aCO2, but it significantly promoted biomass and photosynthesis under eCO2. When nitrate was the sole nitrogen source, eCO2 significantly reduced N assimilation and growth. The total leaf N per tree was significantly higher in boxelder maple than in amur maple, while the carbon and nitrogen ratio was significantly lower in boxelder maple than in amur maple, suggesting that boxelder maple leaf litter may be more favorable for faster nutrient cycling. The results suggest that increases in ammonium under future elevated CO2 will enhance the plasticity and adaptation of the two maple species.

Dynamics of urban expansion and form changes impacting carbon emissions in the Guangdong-Hong Kong-Macao Greater Bay Area counties.

Cities are the main carriers of social and economic development, and they are also important sources of carbon emissions. Therefore, it is essential to explore the impact of urban expansion and form changes on carbon emissions. Here, we attempted to analyzes the relationship between urban expansion and carbon emissions at the county level in the Guangdong-Hong Kong-Macao Greater Bay Area (GBA) from 1997 to 2017. It further decomposes the driving effects of carbon emissions from multiple factors, and considers the spatial heterogeneity between different urban form changes and driving effects. The results show that: The relationship between urban expansion and carbon emissions in the GBA has gone through three stages from 1997 to 2017, with 2012 as a turning point. Optimization of economic development models and strict protection of the ecological environment can effectively control carbon emissions. After 2012, the economic development effect (GE) and population scale effect (PE) are the driving factors of carbon emissions, while the carbon emission intensity effect (CE) and urban land intensity effect (UE) are the inhibitory factors of carbon emissions. The contribution rate of UE to carbon emission reduction can reach 86 %. The impact of urban form changes on carbon emissions has spatial heterogeneity. The changes in urban form have a significant impact on the carbon emissions of counties in Dongguan and Shenzhen. The increase in fragmentation indirectly promotes carbon emissions. In 2007-2012, the increase in centrality significantly weakened the economic development effect, which is conducive to emission reduction. After 2007, the increase in compactness in counties in the eastern part of the GBA, including Zhongshan and Zhuhai, is not conducive to emission reduction.

Non-B-form DNA is associated with centromere stability in newly-formed polyploid wheat.

Non-B-form DNA differs from the classic B-DNA double helix structure and plays a crucial regulatory role in replication and transcription. However, the role of non-B-form DNA in centromeres, especially in polyploid wheat, remains elusive. Here, we systematically analyzed seven non-B-form DNA motif profiles (A-phased DNA repeat, direct repeat, G-quadruplex, inverted repeat, mirror repeat, short tandem repeat, and Z-DNA) in hexaploid wheat. We found that three of these non-B-form DNA motifs were enriched at centromeric regions, especially at the CENH3-binding sites, suggesting that non-B-form DNA may create a favorable loading environment for the CENH3 nucleosome. To investigate the dynamics of centromeric non-B form DNA during the alloploidization process, we analyzed DNA secondary structure using CENH3 ChIP-seq data from newly formed allotetraploid wheat and its two diploid ancestors. We found that newly formed allotetraploid wheat formed more non-B-form DNA in centromeric regions compared with their parents, suggesting that non-B-form DNA is related to the localization of the centromeric regions in newly formed wheat. Furthermore, non-B-form DNA enriched in the centromeric regions was found to preferentially form on young LTR retrotransposons, explaining CENH3's tendency to bind to younger LTR. Collectively, our study describes the landscape of non-B-form DNA in the wheat genome, and sheds light on its potential role in the evolution of polyploid centromeres.

Particulate bioaerogels for respiratory drug delivery.

The bioaerogel microparticles have been recently developed for respiratory drug delivery and attract fast increasing interests. These highly porous microparticles have ultralow density and hence possess much reduced aerodynamic diameter, which favour them with greatly enhanced dispersibility and improved aerosolisation behaviour. The adjustable particle geometric dimensions by varying preparation methods and controlling operation parameters make it possible to fabricate bioaerogel microparticles with accurate sizes for efficient delivery to the targeted regions of respiratory tract (i.e. intranasal and pulmonary). Additionally, the technical process can provide bioaerogel microparticles with the opportunities of accommodating polar, weak polar and non-polar drugs at sufficient amount to satisfy clinical needs, and the adsorbed drugs are primarily in the amorphous form that potentially can facilitate drug dissolution and improve bioavailability. Finally, the nature of biopolymers can further offer additional advantageous characteristics of improved mucoadhesion, sustained drug release and subsequently elongated time for continuous treatment on-site. These fascinating features strongly support bioaerogel microparticles to become a novel platform for effective delivery of a wide range of drugs to the targeted respiratory regions, with increased drug residence time on-site, sustained drug release, constant treatment for local and systemic diseases and anticipated better-quality of therapeutic effects.

Hopf bifurcation in an age-structured predator-prey system with Beddington-DeAngelis functional response and constant harvesting.

In this paper, an age-structured predator-prey system with Beddington-DeAngelis (B-D) type functional response, prey refuge and harvesting is investigated, where the predator fertility function f(a) and the maturation function ß ( a ) are assumed to be piecewise functions related to their maturation period τ . Firstly, we rewrite the original system as a non-densely defined abstract Cauchy problem and show the existence of solutions. In particular, we discuss the existence and uniqueness of a positive equilibrium of the system. Secondly, we consider the maturation period τ as a bifurcation parameter and show the existence of Hopf bifurcation at the positive equilibrium by applying the integrated semigroup theory and Hopf bifurcation theorem. Moreover, the direction of Hopf bifurcation and the stability of bifurcating periodic solutions are studied by applying the center manifold theorem and normal form theory. Finally, some numerical simulations are given to illustrate of the theoretical results and a brief discussion is presented.

MelastomaTRAITs 1.0: A database of functional traits in Melastomataceae, a large pantropical angiosperm family.

The recent availability of open-access repositories of functional traits has revolutionized trait-based approaches in ecology and evolution. Nevertheless, the underrepresentation of tropical regions and lineages remains a pervasive bias in plant functional trait databases, which constrains large-scale assessments of plant ecology, evolution, and biogeography. Here, we present MelastomaTRAITs 1.0, a comprehensive and updatable database of functional traits for the pantropical Melastomataceae, the ninth-largest angiosperm family with 177 genera and more than 5800 species. Melastomataceae encompass species with a wide diversity of growth forms (herbs, shrubs, trees, epiphytes, and woody climbers), habitats (including tropical forests, savannas, grasslands, and wetlands from sea level to montane areas above the treeline), ecological strategies (from pioneer, edge-adapted and invasive species to shade-tolerant understory species), geographic distribution (from microendemic to continental-wide distribution), reproductive, pollination, and seed dispersal systems. MelastomaTRAITs builds on 581 references, such as taxonomic monographs, ecological research, and unpublished data, and includes four whole-plant traits, six leaf traits, 11 flower traits, 18 fruit traits, and 27 seed traits for 2520 species distributed in 144 genera across all 21 tribes. Most data come from the Neotropics where the family is most species-rich. Miconieae (the largest tribe) contains the highest number of trait records (49.6%) and species (41.1%) records. The trait types with the most information in the database were whole-plant traits, flowers, and leaf traits. With the breadth of functional traits recorded, our database helps to fill a gap in information for tropical plants and will significantly improve our capacity for large-scale trait-based syntheses across levels of organization, plant-animal interactions, regeneration ecology, and thereby support conservation and restoration programs. There are no copyright restrictions on the dataset; please cite this data paper when reusing the data.

Tabletized Nanomedicine: From the Current Scenario to Developing Future Medicine.

The limitations of conventional therapeutic treatments prevailed in the development of nanotechnology-based medical formulations, termed nanomedicine. Nanomedicine is an advanced medicine that often consists of therapeutic agent(s) embedded in biodegradable or biocompatible nanomaterial-based formulations. Among nanomedicine approaches, tablet (oral) nanomedicine is still under development. In tabletized nanomedicine, the dynamic interplay between nanoformulations and the intricate milieu of the gastrointestinal tract simulates a pivotal role, particularly accentuating the influence exerted upon the luminal, mucosal, and epithelial cells. In this work, we document the perspectives and opportunities of nanoformulations toward the development of tabletized nanomedicine. This review also unveils the notion of integrating nanomedicine within a tablet formulation, which facilitates the controlled release of drugs, biomolecules, and agent(s) from the formulation to achieve a better therapeutic response. Finally, an attempt was made to explore current trends in nanomedicine technology such as bacteriophage, probiotic, and oligonucleotide tabletized nanomedicine and the combination of nanomedicine with imaging agents, i.e., nanotheranostics.

Seeding Atomic Silver into Internal Lattice Sites of Transition Metal Oxide for Advanced Electrocatalysis.

Transition metal oxides (TMOs) are widely studied for loading of various catalysts due to their low cost and high structure flexibility. However, the prevailing close-packed nature of most TMOs crystals has restricted the available loading sites to surface only, while their internal bulk lattice remains unactuated due to the inaccessible narrow space that blocks out most key reactants and/or particulate catalysts. Herein, using tunnel-structured MnO2, we demonstrate how TMO's internal lattice space can be activated as extra loading sites for atomic Ag in addition to the conventional surface-only loading, via which a dual-form Ag catalyst within MnO2 skeleton is established. In this design, not only faceted Ag nanoparticles are confined onto MnO2 surface by coherent lattice-sharing, Ag atomic strings are also seeded deep into the sub-nanoscale MnO2 tunnel lattice, enriching the catalytically active sites. Tested for electrochemical CO2 reduction reaction (eCO2RR), such dual-form catalyst exhibits a high Faradaic efficiency (94%), yield (67.3 mol/g/h) and durability (∼ 48 h) for CO production, exceeding commercial Ag nanoparticles and most Ag-based electrocatalysts. Theoretical calculations further reveal the concurrent effect of such dual-form catalyst featuring facet-dependent eCO2RR for Ag nanoparticles and lattice-confined eCO2RR for Ag atomic strings, inspiring the future design of catalyst-substrate configuration. This article is protected by copyright. All rights reserved.

Modeling of Styl'One Evolution Correction Factors for Multicomponent Mixtures Scaling-up to Roller Compaction.

Roll compaction (RC) is a cost-effective dry granulation method, widely implemented in the pharmaceutical industry. In early formulation development however, when the material availability is limited, being able to predict the most important parameters in RC, like gap width and specific compaction force (SCF), to obtain a target ribbon solid fraction (SF) would significantly improve the formulation development efficiency as it would avoid the need of performing experiments on the roller compactor itself. However, at the present state of things, experiments on RC mechanical simulators present an overestimation of the target SF, when compared to roller compactor SF values. Although numerous correction approaches have been developed to improve the predictive performance of different mathematical models applied to the simulation experimental results, no study has collected a database wide enough to demonstrate the validity of a correction factor that allows to accurately simulate the compaction behavior of multicomponent mixtures. Here, 25 different formulations at 40 % drug load are compacted at different SCFs, both on a RC mimicking device (Styl'One Evolution) and on an actual roller compactor (Gerteis Mini-Pactor): following a similar approach as Reimer et al. and implementing a simplified version of the Johanson's mathematical model, 4 different correction factors are calculated, depending on how their material properties and pressure dependencies are considered. In conclusion, one correction factor is identified as the optimal trade-off between the SF prediction accuracy on the Gerteis Mini-Pactor and its applicability to a wide range of formulations, as it is independent of the material properties. This finding is particularly relevant when applied to scale-up to this specific roller compactor or early development processes of new formulations that have not been mechanically characterized yet.

What Is "Key Information"? Consideration of the Reasons People Do or Do Not Take Part in Research.

We performed a qualitative review of 50 consent forms posted on Clinicaltrials.gov, examining the content of key information sections. We found that key information disclosures are typically focused on procedures, risks, potential benefits, and alternatives. Drawing upon reviews of the large literature examining the reasons people do or do not take part in research, we propose that these disclosures should be based more directly on what we know to be the real reasons why people choose to take part or refuse participation. We propose key information language for consideration by researchers and institutional review boards.

A Comprehensive Analysis of Biopharmaceutical Products Listed in the FDA's Purple Book.

Although biopharmaceuticals constitute around 10% of the drug landscape, eight of the ten top-selling products were biopharmaceuticals in 2023. This study did a comprehensive analysis of the FDA's Purple Book database. Firstly, our research uncovered market trends and provided insights into biologics distributions. According to the investigation, although biotechnology has advanced and legislative shifts have made the approval process faster, there are still challenges to overcome, such as molecular instability and formulation design. Moreover, our research comprehensively analyzed biological formulations, pointing out significant strategies regarding administration routes, dosage forms, product packaging, and excipients. In conjunction with biologics, the widespread integration of innovative delivery strategies will be implemented to confront the evolving challenges in healthcare and meet an expanding array of treatment needs.

3D printing processes in precise drug delivery for personalized medicine.

With the advent of personalized medicine, the drug delivery system will be changed significantly. The development of personalized medicine needs the support of many technologies, among which three-dimensional printing (3DP) technology is a novel formulation-preparing process that creates 3D objects by depositing printing materials layer-by-layer based on the computer-aided design method. Compared with traditional pharmaceutical processes, 3DP produces complex drug combinations, personalized dosage, and flexible shape and structure of dosage forms (DFs) on demand. In the future, personalized 3DP drugs may supplement and even replace their traditional counterpart. We systematically introduce the applications of 3DP technologies in the pharmaceutical industry and summarize the virtues and shortcomings of each technique. The release behaviors and control mechanisms of the pharmaceutical DFs with desired structures are also analyzed. Finally, the benefits, challenges, and prospects of 3DP technology to the pharmaceutical industry are discussed.

Patients' Preference for Pharmaceutical Dosage Forms: Does It Affect Medication Adherence? A Cross-Sectional Study in Community Pharmacies.

Background: Dosage forms (DF), which are primarily divided into solid, semisolid, liquid, and gaseous, are among the different factors that influence drug adherence. Thus, the purpose of this study was to evaluate how patients' preferences for pharmaceutical DF affected their adherence to medication in community pharmacies in Gondar town. Methods: A cross-sectional study on community pharmacies was carried out from June 25 to July 27, 2023. The statistical package for social sciences, version 26, was used for data analysis. Factors associated with patient medication discontinuation were found using both bivariate and multivariate logistic regressions. Results: According to our study, the majority of respondents (42.4%) preferred tablet DF. Most respondents (63.9%) DF preference was affected by the size of the medication, in which small-sized were most preferable (59.6%). The oral route of administration was the most preferable (71.2%). The majority of the respondents (59.9%) had a history of discontinuation of medicines. Being male (AOR=2.21, 95% CI: 1.29, 3.79), living in rural areas (AOR=1.98, 95% CI: 1.03, 3.83), types of DF (AOR=4.59, 95% CI: 1.28, 16.52), high frequency of administration (AOR=2.22, 95% CI: 1.08, 4.57), high cost of medication (AOR=3.09, 95% CI: 1.69, 5.68), getting some improvement from illness (AOR=3.29, 95% CI: 1.10, 9.87), and high number of drugs (AOR=3.29, 95% CI: 1.67, 13.85) were significantly associated with medication discontinuation. Conclusion: Our findings showed that tablet dosage forms, oral routes of administration, and once-daily taking of medicines were the most preferred by our respondents. Being male, living in rural areas, types of DF, high frequency of administration, high cost of medication, getting some improvement from illness, and high number of drugs were significantly associated with medication discontinuation. This provides an insight into what to consider when prescribing medicine to enhance patients' adherence and overall therapeutic outcomes.

Translation and Validation of the Premenstrual Assessment Form-Short Form Questionnaire in Hungarian.

Introduction: Premenstrual symptoms, including premenstrual syndrome and its more severe form premenstrual dysphoric disorder, are a set of somatic and psychological symptoms that occur during the luteal phase of the menstrual cycle. Our research aimed to adapt the Hungarian version of the Premenstrual Assessment Form-Short Form (PAF-SF), a questionnaire suitable for assessing premenstrual symptoms, and to examine its reliability, validity, and applicability. Methods: The questionnaire was validated according to Beaton's six-step guidelines. Our sample consisted of 198 menstruating women, 50 of whom completed the instrument for a second time to assess reliability. Descriptive statistics were calculated presenting mean (standard deviation), the internal consistency was measured by Cronbach's alpha value, the test-retest reliability using intraclass correlation coefficients, Spearman rank correlation was applied to test the criterion validity of the questionnaire, and discriminant validity was examined using the independent-sample t test using IBM SPSS 28.0 software. The structural validity was evaluated by confirmatory factor analysis (CFA) using IBM AMOS 29.0 software. The level of significance was set at p < 0.05. Results: Our sample (average age 25.37 ± 4.80 years) scored 28.08 ± 9.49 points out of the maximum 60 points when filling out the PAF-SF questionnaire. The result of Cronbach's alpha calculation, which supports the reliability of the questionnaire, was 0.845. During the CFA, the three-factor structure (Affect, Water Retention, and Pain) was supported (root mean-square error approximation [RMSEA] = 0.054; Tucker-Lewis Index = 0.965; Comparative Fit Index = 0.976; χ2 = 48.642; df = 31; p = 0.023; χ2/df = 1.569). Discussion: The PAF-SF questionnaire proved to be a reliable measuring tool for assessing premenstrual symptoms among women of reproductive age.

Effect of magnetized water irrigation on Cd subcellular allocation and chemical forms in leaves of Festuca arundinacea during phytoremediation.

The application of an external magnetic field has been shown to improve the Cd phytoremediation efficiency of F. arundinacea by leaf harvesting. However, the influencing mechanisms of the promoting effect have not yet been revealed. This study evaluated variations in the Cd subcellular allocation and fractions in various F. arundinacea leaves, with or without magnetized water irrigation. Over 50 % of the metal were sequestered within the cell wall in all tissues under all treatments, indicating that cell wall binding was a critical detoxification pathway for Cd. After magnetized water treatment, the metal stored in the cytoplasm of roots raised from 33.1 % to 45.3 %, and the quantity of soluble Cd in plant roots enhanced from 53.4 % to 59.0 %. The findings suggested that magnetized water mobilized Cd in the roots, and thus drove it into the leaves. In addition, the proportion of Cd in the organelles, and the concentration of ethanol-extracted Cd in emerging leaves, decreased by 13.0 % and 47.1 %, respectively, after magnetized water treatment. These results explained why an external field improved the phytoextraction effect of the plant through leaf harvesting.

Novel fast dissolving freeze dried sublingual baicalin tablets for enhanced hepatoprotective effect: in-vitro characterization, cell viability, and in-vivo evaluation.

Baicalin (BG), a natural product, has been used in the prevention and treatment of drug-induced liver injury (DILI); however, its poor solubility and extensive liver metabolism limit its pharmacological use. The aim of the present study was the formulation of fast-dissolving freeze-dried sublingual tablets (FFSTs) to increase BG dissolution, avoid first-pass metabolism, and overcome swallowing difficulties. FFSTs were prepared following a 23 factorial design. The effect of three independent variables namely matrix former, Maltodextrin, concentration (4%, and 6%), binder concentration (2%, and 3%), and binder type (Methocel E5, and Methocel E15) on the FFSTs' in-vitro disintegration time and percentage dissolution was studied along with other tablet characteristics. Differential scanning calorimetry, scanning electron microscopy, in-vitro HepG2 cell viability assay, and in-vivo characterization were also performed. F8 (6% Maltodextrin, 2% Mannitol, 2% Methocel E5), with desirability of 0.852, has been furtherly enhanced using 1%PEG (F10). F10 has achieved an in-vitro disintegration time of 41 secs, and 60.83% in-vitro dissolution after 2 min. Cell viability assay, in-vivo study in rats, and histopathological studies confirmed that pretreatment with F10 has achieved a significant hepatoprotective effect against acetaminophen-induced hepatotoxicity. The outcome of this study demonstrated that FFSTs may present a patient-friendly dosage form against DILI.

Health-Related Quality of Life of Adolescent and Young Adult-Aged Childhood Cancer Survivors in a South African Cohort: A Pilot Study Using the Minneapolis-Manchester Quality of Life Instrument.

Purpose: We investigated the health-related quality of life (HRQoL) of an adolescent and young adult (AYA)-aged South African childhood cancer survivor (CCS) cohort. Methods: Participants completed the Minneapolis-Manchester Quality of Life adolescent and adult forms. The overall Cronbach's alpha coefficients were 0.81 (adolescent form) and 0.92 (adult form). The scale-level content validity indexes were acceptable (0.88 and 0.89 for the adolescent and adult forms, respectively). The total domain and overall HRQoL scores were calculated. Results: Sixty-two survivors completed the adolescent form and 30 completed the adult form. The median age was 17.5 years (range 13-34 years), and the median time from diagnosis was 12 years (male:female ratio 1:1.2). Risk factors for poor physical functioning included age at study visit (p = 0.015), solid tumor diagnosis (p = 0.012), radiotherapy (p = 0.021), and surgery (p = 0.006). Six or more late effects impacted most domains negatively; severe late effects (p = 0.020) decreased physical functioning. Lower socioeconomic status was associated with poorer physical (p = 0.006) and cognitive (p = 0.047) functioning. The adult form cohort had poorer psychological (p = 0.014) and social functioning (p = 0.005) and body image (p = 0.016) than the adolescent form cohort. Conclusion: Older age, radiotherapy, surgery, solid tumor diagnosis, and the number and severity of late effects negatively influenced HRQoL in AYA-aged CCSs. A long-term follow-up (LTFU) risk stratification system should include HRQoL status to assist with holistic LTFU care.