Concurrent Changes Research Articles

Abstract 4137636: Cardiac radiation dose and changes in physical activity and quality of life in patients with locally advanced lung cancer

Background: Physical activity is associated with prognosis in cancer. However, in non-small cell lung cancer (NSCLC), a high cardiovascular (CV) population, the relationships between RT dose, physical activity, and CV patient-reported outcomes remain unclear. We determined the associations between cardiac radiation dose-volume metrics and changes in physical activity and quality-of-life (QoL) in patients treated with definitive chemoradiation. Methods: NSCLC participants treated with chemoradiation were enrolled in a multi-center longitudinal cohort study. Self-reported physical activity via Godin–Shephard Leisure-Time Physical Activity Questionnaire (Godin) and QoL via Functional Assessment of Chronic Illness Therapy (FACIT) Fatigue and Dyspnea Scales were collected at baseline, end of RT, 6, and 12 months post-RT. Changes in Godin and FACIT scores over time were examined using linear mixed-effects models. Multivariable linear regression via generalized estimating equations assessed the associations between: 1) mean heart dose (MHD) and longitudinal changes in physical activity and QoL, and 2) concurrent changes in physical activity and FACIT scores. Results: Across 101 participants, the mean age was 66 years, with 57% male, 66% White, and 25% Black. The median (Q1, Q3) MHD was 10.8 Gy (6.1,16.3). Very low physical activity [9 (0, 25)], high dyspnea [4 (1, 9)], and low fatigue [39 (31,46)] were reported at baseline. With chemoRT, there was a significant worsening of physical activity ( P = 0.03), fatigue ( P < 0.001), and dyspnea ( P < 0.001). Each 1-Gy increase in MHD was associated with a modest decline in physical activity (-0.28; 95% CI -0.53, -0.02, P = 0.03), and higher physical activity was associated with a concurrent decrease in fatigue ( P < 0.001) and dyspnea ( P = 0.007) (Table). Conclusions: In locally advanced NSCLC, physical activity levels prior to RT were very low, and higher cardiac radiation dose was associated with a further decline in physical activity. Increased physical activity was associated with concurrent decreases in fatigue and dyspnea. Strategies to promote physical activity may result in improved QoL in this high CV group.

Effect duration of a self-applied talocrural joint mobilization on restricted dorsiflexion: a repeated measures design

ABSTRACT Objectives We aimed to determine the effect duration of a talocrural mobilization on individuals with restricted dorsiflexion during a static weight bearing lunge test (WBLT) and dynamic 3D motion capture-based peak ankle dorsiflexion during a forward step down (FSD) task. Secondarily, we aimed to correlate any immediate changes in ankle mobility with concurrent changes in proximal joint kinematics during the FSD post-mobilization. Methods Seventy-six individuals were screened for dorsiflexion restriction, of which 26 (15 females, 22.3 ± 2.2 years old, body mass index 25.2 ± 2.9 kg/m2) qualified with a WBLT of ≤ 35° on at least one limb. A baseline WBLT measure and 3D motion capture of 5 consecutive FSD repetitions on a 6-inch box were obtained. Participants then viewed an instructional video of a talocrural joint self-mobilization using a resistance band. WBLT and FSD were collected again immediately post-mobilization and at 5-min intervals for 60 min or until the WBLT returned to baseline for 2 consecutive measures. Results WBLT dorsiflexion showed a mean increase of 6.5 degrees (p < 0.001) post-mobilization. The effect faded over time and no longer differed from baseline 25 min post-mobilization (p = 0.964). Dynamic peak ankle dorsiflexion did not change post-mobilization at any time point (p ≥ 0.546). No 3D kinematic time-course changes were observed at the hip or knee. However, immediate raw alterations in dorsiflexion correlated with alterations for hip and knee flexion. Discussion/Conclusion A talocrural joint mobilization increased static dorsiflexion per the WBLT for a 20–25-min period with regression to baseline. However, increased dynamic ankle dorsiflexion was not observed during the FSD task. Improved mobility alone does not appear to change movement patterns. Clinicians should be aware of both effect duration and the potential need for task-specific training to better facilitate dynamic utilization of increased mobility.

Sugar beet root susceptibility to storage rots and downregulation of plant defense genes increases with time in storage

Storage rots are a significant cause of postharvest losses for the sugar beet crop, however, intrinsic physiological and genetic factors that determine the susceptibility of roots to pathogen infection and disease development are unknown. Research, therefore, was carried out to evaluate the disease development in sugar beet roots caused by two common storage pathogens as a function of storage duration and storage temperature, and to identify changes in the expression of defense genes that may be influencing the root susceptibility to disease. To evaluate root susceptibility to disease, freshly harvested roots were inoculated with Botrytis cinerea or Penicillium vulpinum on the day of harvest or after 12, 40, or 120 d storage at 5 or 12 °C and the weight of rotted tissue present in the roots after incubation for 35 d after inoculation were determined. Disease susceptibility and progression to B. cinerea and P. vulpinum increased with storage duration with elevations in susceptibility occurring more rapidly to B. cinerea than P. vulpinum. Also, B. cinerea was more aggressive than P. vulpinum and caused greater rotting and tissue damage in postharvest sugar beet roots. Storage temperature had minimal effect on root susceptibility to these rot-causing pathogens. Changes in defense gene expression were determined by sequencing mRNA isolated from uninoculated roots that were similarly stored for 12, 40 or 120 d at 5 or 12 °C. As susceptibility to rot increased during storage, concurrent changes in defense-related gene expression were identified, including the differential expression of 425 pathogen receptor and 275 phytohormone signal transduction pathway-related genes. Furthermore, plant resistance and hormonal signaling genes that were significantly altered in expression coincident with the change in root susceptibility to storage rots were identified. Further investigation into the function of these genes may ultimately elucidate methods by which storage rot resistance in sugar beet roots may be improved in the future.

Historical increases of maize leaf area index in the US Corn Belt due primarily to plant density increases

ContextLeaf area index (LAI) and leaf area distribution within the maize plant are important traits used to explain and predict light interception and thus crop productivity. ObjectivesHere we investigate breeding and plant density effects of leaf area traits. Our objectives are to 1) quantify maize breeding impacts on leaf area distribution and determine bell-shape coefficients used in crop modeling, 2) dissect the contribution of breeding from plant density, and 3) explore the relationship between LAI and crop yields. MethodsWe studied 18 hybrids released between 1983 and 2017 at two density treatments: current (8.5 pl m-2) and historical increasing density (from 4.6 to 8.5 pl m-2) in Iowa, USA. ResultsResults indicated that concurrent changes in hybrids and increases in plant density have increased LAI from 3.4 (in 1983) to 5.9 m2 m-2 (in 2017), with the highest LAI increases (>50%) to be realized in the middle canopy. At historical increasing in plant density treatment, the LAI increased by 1.6% year-1, but the individual plant leaf area decreased by 0.33% year-1 from 1983 to 2017. This trade-off indicates that new hybrids are more tolerant to higher plant populations than old hybrids. At current plant density treatment, the year of hybrid release did not affect LAI or individual plant leaf area. New hybrids had 5% narrower leaf area distributions, 23% higher optimum LAI values (5.2 vs 4.2 m2 m-2) and 19% higher grain yields compared to old hybrids. ConclusionsThe main reason for the increase in maize LAI in the US Corn Belt is plant density. However, an increase in LAI does not necessarily translate to higher grain yields as new hybrids had significantly higher grain yields than older hybrids at similar LAI values. Present results contribute to our understanding of maize canopy architecture and allow us to better calibrate crop models to accurately estimate LAI and grain yield.

Characterisation of the stellar wind in Cyg X-1 via modelling of colour-colour diagrams

Context. Cygnus X-1 (Cyg X-1) is a high-mass X-ray binary where accretion onto the black hole (BH) is mediated by the stellar wind from the blue supergiant companion star HDE 226868. Due to its inclination, the system is a perfect laboratory to study the not yet well-understood stellar wind structure. In fact, depending on the position of the BH along the orbit, X-ray observations can probe different layers of the stellar wind. Deeper wind layers can be investigated at superior conjunction (i.e. null orbital phases). Aims. We aim to characterise the stellar wind in the Cyg X-1/HDE 226868 system, analysing one passage at superior conjunction covered by XMM-Newton during the ‘Cyg X-1 Hard state Observations of a Complete Binary Orbit in X-rays’ (CHOCBOX) campaign. Methods. To analyse the properties of the stellar wind, we computed colour-colour diagrams. Since X-ray absorption is energy-dependent, colour indices provide information on the parameters of the stellar wind, such as the column density, NH, w, and the covering factor, fc. We fitted colour-colour diagrams with models that include both a continuum and a stellar wind component. We used the kernel density estimation method to infer the unknown probability distribution of the data points in the colour-colour diagram, and selected the model corresponding to the highest likelihood. In order to study the temporal evolution of the wind around superior conjunction, we extracted and fitted time-resolved colour-colour diagrams. Results. We found that the model that best describes the shape of the colour-colour diagram of Cyg X-1 at superior conjunction requires the wind to be partially ionised. The shape of the colour-colour diagram strongly varies during the analysed observation, due to concurrent changes of the mean NH, w and the fc of the wind. Our results suggest the existence of a linear scaling between the rapid variability amplitude of NH, w (on timescales between 10 s and 11 ks) and its long-term variations (on timescales &gt; 11 ks). Using the inferred best-fit values, we estimated the stellar mass loss rate to be ∼7 × 10−6 M⊙ yr−1 and the clumps to have a characteristic mass of ∼1017 g.

Intolerance of Uncertainty as a Central Influence on Social Media Use: A School-Based Program for Adolescents.

This study evaluated a classroom program to address Intolerance of uncertainty (IU) in secondary school students in Australia. IU is a transdiagnostic vulnerability factor for a range of psychological difficulties. A universal classroom program aimed to increase student understanding of feelings of uncertainty and explored socioemotional factors that could influence behaviors when facing uncertainty. Classroom teachers in two high schools were trained to deliver an 18-lesson program under naturalistic classroom conditions. Relative to the control group, the intervention lowered IU at post-test, but not at a later follow-up. The only socioemotional outcome measure to demonstrate a concurrent change was social media use. Limitations of the study were associated with the naturalistic classroom intervention, including the high level of attrition. Future studies may need to address broader factors in the students' context that could influence intolerance of uncertainty.

Experimental demonstration on the proactive detection of fiber tapping in optical chaos communication.

Optical chaos communication has a physical-layer security advantage but defends passively against a malicious attack. Here, we conduct a proof-of-concept experiment of detecting the attack proactively by observing performance degradation in optical chaos communication tapped with fiber bending. Influences of the curvature radius of the bent fiber on a chaos synchronization coefficient and bit error rate are investigated. Results show that the synchronization coefficient decreases from 0.958 to 0.904 and the bit error rate increases from 1.31 × 10-4 to 1.73 × 10-3 under a curvature radius of 10 mm, revealing the attack. Bending fiber to this extent leads to a power loss of 1.81%, which is difficult to detect by the optical time-domain reflectometer but causes significant interference to chaos communication due to the concurrent change in the light polarization, jointly decreasing the effective optical injection strength for yielding chaos synchronization.

Direct Evidence for Microbial Regulation of the Temperature Sensitivity of Soil Carbon Decomposition.

Soil physicochemical protection, substrates, and microorganisms are thought to modulate the temperature sensitivity of soil carbon decomposition (Q10), but their regulatory roles have yet to be distinguished because of the confounding effects of concurrent changes of them. Here, we sought to differentiate these effects through microorganism reciprocal transplant and aggregate disruption experiments using soils collected from seven sites along a 5000-km latitudinal transect encompassing a wide range of climatic conditions and from a 4-year laboratory incubation experiment. We found direct microbial regulation of Q10, with a higher Q10 being associated with greater fungal:bacterial ratios. However, no significant direct effects of physicochemical protection and substrate were observed on the variation in Q10 along the latitudinal transect or among different incubation time points. These findings highlight that we should move forward from physicochemical protection and substrate to microbial mechanisms regulating soil carbon decomposition temperature sensitivity to understand and better predict soil carbon-climate feedback.

Divergent apparent temperature sensitivity of forest-floor respiration across a managed boreal forest landscape

Understanding the apparent temperature sensitivity (Q10) of forest floor respiration (Q10Rff) and its plant autotrophic (Q10Ra) and soil heterotrophic (Q10Rh) components is critical for determining the strength and direction of forest carbon cycle-climate feedbacks. However, the spatial variability of Q10Rff and its controlling factors across the spatially heterogeneous boreal forest landscape remains poorly understood. In this study, we used chamber-based respiration measurements conducted on paired natural and trenching plots over three growing seasons (2016–2018) to determine Q10Rff, Q10Rh and Q10Ra to soil temperature across 50 diverse forest stands (ranging 5–211 years old) in a managed landscape in northern Sweden. Additionally, we estimated ecosystem- and landscape-scale Q10 based on conventional and tall tower eddy covariance measurements, respectively, conducted over the same landscape. Our results suggest manifold variations (i.e., 10th to 90th percentiles) of Q10Rff (1.7 to 6.6), with Q10Ra (0.9 to 7.4) showing a greater range than Q10Rh (1.6 to 5.3). Forest-floor understory biomass was the main control of variations in Q10Ra, whereas soil properties explained best those of Q10Rh. Furthermore, a seasonal hysteresis of Q10Rff was observed, with higher values mostly occurring during the late growing season. The magnitude of this hysteresis scaled with stand age in response to concurrent changes in net primary production. The Q10Rff to air temperature declined with increasing stand age, which was attributed to the increased decoupling of air and soil temperatures with canopy development. Despite the considerable stand-level variations, when averaged over the 50 forest stands, Q10Rff to air temperature converged with that of both ecosystem- and landscape-scale respiration. In conclusion, our study highlights the complexity of Q10Rff, which needs to be considered in predictions of the interactions of climate change and management with the carbon cycle of managed boreal forests.

Attention to social threat predicts diurnal cortisol dynamics during the high school transition

Adolescence is a developmental period marked by significant social shifts accompanied by concurrent changes across biological, cognitive, and emotional domains. Within adolescence, the high school transition is a pivotal time for youth that is ripe with opportunities yet has the potential to disrupt functioning. An increasingly sophisticated understanding of health and developmental biology indicates that the hypothalamic-pituitary-adrenal (HPA) axis plays an important role in transducing social experiences into physiological changes that have long-term impacts on health and wellbeing. There is reason to believe that attentional biases to social threat could impact cortisol, a steroid hormone indexing activity of the HPA axis, during the high school transition. The present study examined associations between attentional biases to socially threatening stimuli, measured using the Affective Posner paradigm, and components of the diurnal cortisol rhythm among youth across the first two days of high school. Participants included 67 youth (N = 504 saliva samples) with a mean age of 12.86 years and a relatively equal split with regard to both sex assigned at birth and gender identity (54% male; 54% boys). Findings build upon and extend previous work by demonstrating that greater attentional engagement bias to socially threatening stimuli is associated with a pattern of greater diurnal HPA axis reactivity across the first two days of the high school transition, as evidenced by a steeper cortisol awakening response and a steeper diurnal cortisol slope. This work extends our understanding of the mechanisms through which stress relates to wellbeing in youth by embedding biological development in the life course. Clinically, this work has the potential to inform interventions to protect youth against the biological embedding of stress by identifying a theoretically driven, socio-contextually relevant risk factor to be attenuated – namely, attentional bias to threat.

Does insecurity lead to Envy? The longitudinal interplay between dispositional envy and Self-Esteem

Despite evidence of a close, cross-sectional association between dispositional envy and low self-esteem, there is no research on the mutual development of these two constructs across time. The aim of the present research was to systematically investigate correlated change and prospective effects between dispositional envy and self-esteem at the global level and within comparison domains. In two preregistered longitudinal studies across 6 years (Ntotal > 7,000 adult participants), change in dispositional envy was negatively correlated with concurrent self-esteem change at the global level and within domains. Moreover, we found preliminary evidence that self-esteem predicted later change in dispositional envy but not vice versa. Our findings illustrate that the development of dispositional envy is closely intertwined with self-esteem development.

CoMPers: A configurable conflict management framework for personalized collaborative modeling

Context:Modeling is an activity in the software development life cycle where experts and stakeholders collaborate as a team. In collaborative modeling, adhering to the optimistic versioning paradigm allows users to make concurrent changes to the same model, but conflicts may arise. To achieve an integrated and consistent merged model, conflicts must be resolved. Objective:The primary objective of this study was to provide a customizable and extensible framework for conflict management in personalized change propagation during collaborative modeling. Methods:We propose CoMPers, a customizable and extensible conflict management framework designed to address various conflicts encountered in collaborative modeling. We present the duel algorithm for automatically detecting and resolving conflicts according to user preferences. The framework utilizes personalized change propagation to customize collaboration and supports the conflict management process by executing the duel algorithm based on user preferences. As a proof-of-concept, we have implemented the CoMPers framework and extended the EMF.cloud modeling framework to demonstrate its applicability. Results:We have constructed a proof-of-concept implementation and conducted a real-world case study, a benchmark experiment, and a user experience evaluation. Our findings demonstrate that: (1) CoMPers enables collaborators to configure propagation strategies according to their habits; (2) CoMPers successfully identifies all anticipated conflicts and achieves a 100% accuracy in conflict handling; (3) The majority of participants agreed that CoMPers is user-friendly for collaborative modeling. Conclusion:This paper presents the CoMPers framework, which is based on personalized change propagation, and helps collaborators customize conflict management activities. The results confirm the feasibility and advantages of consistent and concurrent modeling within the collaborative CoMPers platform, with an acceptable functionality for approximately ten collaborators.

Genome-wide characterization of dynamic DNA 5-hydroxymethylcytosine and TET2-related DNA demethylation during breast tumorigenesis

BackgroundBreast tumorigenesis is a complex and multistep process accompanied by both genetic and epigenetic dysregulation. In contrast to the extensive studies on DNA epigenetic modifications 5-hydroxymethylcytosine (5hmC) and 5-methylcytosine (5mC) in malignant breast tumors, their roles in the early phases of breast tumorigenesis remain ambiguous.ResultsDNA 5hmC and 5mC exhibited a consistent and significant decrease from usual ductal hyperplasia to atypical ductal hyperplasia and subsequently to ductal carcinoma in situ (DCIS). However, 5hmC showed a modest increase in invasive ductal breast cancer compared to DCIS. Genomic analyses showed that the changes in 5hmC and 5mC levels occurred around the transcription start sites (TSSs), and the modification levels were strongly correlated with gene expression levels. Meanwhile, it was found that differentially hydroxymethylated regions (DhMRs) and differentially methylated regions (DMRs) were overlapped in the early phases and accompanied by the enrichment of active histone marks. In addition, TET2-related DNA demethylation was found to be involved in breast tumorigenesis, and four transcription factor binding sites (TFs: ESR1, FOXA1, GATA3, FOS) were enriched in TET2-related DhMRs/DMRs. Intriguingly, we also identified a certain number of common DhMRs between tumor samples and cell-free DNA (cfDNA).ConclusionsOur study reveals that dynamic changes in DNA 5hmC and 5mC play a vital role in propelling breast tumorigenesis. Both TFs and active histone marks are involved in TET2-related DNA demethylation. Concurrent changes in 5hmC signals in primary breast tumors and cfDNA may play a promising role in breast cancer screening.

Label free, capillary-scale blood flow mapping in vivo reveals that low intensity focused ultrasound evokes persistent dilation in cortical microvasculature.

Non-invasive, low intensity focused ultrasound (FUS) is an emerging neuromodulation technique that offers the potential for precision, personalized therapy. An increasing body of research has identified mechanosensitive ion channels that can be modulated by FUS and support acute electrical activity in neurons. However, neuromodulatory effects that persist from hours to days have also been reported. The brain's ability to provide targeted blood flow to electrically active regions involve a multitude of non-neuronal cell types and signaling pathways in the cerebral vasculature; an open question is whether persistent effects can be attributed, at least partly, to vascular mechanisms. Using a novel in vivo optical approach, we found that microvascular responses, unlike larger vessels which prior investigations have explored, exhibit persistent dilation following sonication without the use of microbubbles. This finding and approach offers a heretofore unseen aspect of the effects of FUS in vivo and indicate that concurrent changes in neurovascular function may partially underly persistent neuromodulatory effects.

Nitrogen nutrition effects on δ13C of plant respired CO2 are mostly caused by concurrent changes in organic acid utilisation and remobilisation.

Nitrogen (N) nutrition impacts on primary carbon metabolism and can lead to changes in δ13C of respired CO2. However, uncertainty remains as to whether (1) the effect of N nutrition is observed in all species, (2) N source also impacts on respired CO2 in roots and (3) a metabolic model can be constructed to predict δ13C of respired CO2 under different N sources. Here, we carried out isotopic measurements of respired CO2 and various metabolites using two species (spinach, French bean) grown under different NH4 +:NO3 - ratios. Both species showed a similar pattern, with a progressive 13C-depletion in leaf-respired CO2 as the ammonium proportion increased, while δ13C in root-respired CO2 showed little change. Supervised multivariate analysis showed that δ13C of respired CO2 was mostly determined by organic acid (malate, citrate) metabolism, in both leaves and roots. We then took advantage of nonstationary, two-pool modelling that explained 73% of variance in δ13C in respired CO2. It demonstrates the critical role of the balance between the utilisation of respiratory intermediates and the remobilisation of stored organic acids, regardless of anaplerotic bicarbonate fixation by phosphoenolpyruvate carboxylase and the organ considered.

Negative Poisson's ratio can enhance stability of layered composite structures

Composite laminates with negative Posson's ratios (i.e., auxetic composite laminates) were experimentally found to demonstrate a three-fold increase in buckling strength under uniaxial compression in comparison with the equivalent non-auxetic ones. To investigate whether the enhancement is genuinely due to the negative Poisson's ratio (i.e., the auxeticity) or merely caused by the concurrent change in the bending stiffness matrix as the composite layup changes, a novel monoclinic plate-based composite laminate approach is proposed, which for the first time, allows to isolate the auxeticity effect from the concurrent change of the stiffness matrix. Results provided theoretical proof that the auxeticity plays an active role in enhancing the critical buckling strength of layered composite structure. However, such a role is dynamically sensitive to elements in the bending stiffness matrix, especially the bending-twisting ratio and the anisotropy of the bending stiffness between the longitudinal and lateral directions. Insights are expected to provide guidance in exploiting negative Poisson's ratio for improving the stability of layered composite structures.

Electrochemical Behaviour of Nickel(II)-Rhenium(VII) And Electrodeposition of Nickel-Rhenium Alloy from Choline Chloride - Urea Deep Eutectic Solvent

The electrochemical behaviour of nickel(II)-rhenium(VII) and the electrodeposition of nickel-rhenium alloy using choline chloride: 2 Urea deep eutectic solvent (Reline DES) is reported. Speciation of nickel(II)-rhenium(VII) in Reline DES was studied using UV -Visible spectroscopy. Cyclic voltammetry of Ni2+-ReO4 − in Reline indicates the simultaneous reduction of two metal ions at glassy carbon electrode controlled by non-reversible diffusion process. Chronoamperograms obtained for the reduction of Ni2+-ReO4 − suggests nucleation and three-dimensional growth of bimetallic phase on electrode surface followed progressive nucleation. Electrodeposition of nickel—rhenium alloy was carried out on copper substrates under galvanostatic and potentiostatic conditions. Smooth and uniform deposits were obtained by galvanostatic deposition. X-ray diffraction analysis of the deposit confirmed it to be nickel-rhenium alloy (at −1.2 V) in amorphous form which upon annealing at 1000 °C crystallizes into hexagonal phase with concurrent morphology change from spherical particles to irregular polygons.

CDK4 gene copy number increase and concurrent genetic changes in acral melanoma of a Chinese cohort

Acral melanoma (AM) is the most common subtype of melanoma in Asian population. Abnormalities in the p16-cyclin D1-CDK4 signalling pathway play a crucial role in the development and progression of AM. However, the alterations of CDK4 gene copy number in AM are underreported. In this study, we investigated CDK4 gene copy number and concurrent molecular changes in a Chinese cohort with AM, in aim of exploring CDK4 gene alterations and its significance in AM. We examined copy number alterations of CDK4 with fluorescence in situ hybridisation (FISH) in 31 patients with AM. Six patients with CDK4 high-level copy number increase were examined by next-generation sequencing to detect concurrent molecular changes. Using FISH, 12 (12/31, 38.7%) cases showed CDK4 copy number increase, with 6 (6/31, 19.4%) low-level copy number increase and 6 (6/31, 19.4%) high-level copy number increase. Five of six CDK4 low-level copy number increase cases were accompanied by polysomy of chromosome 12, while one case was not. Two of six CDK4 high-level copy number increase cases were accompanied by polysomy of chromosome 12, while four cases were not. CDK4 copy number increase was significantly correlated with younger patient age. In six CDK4 high-level copy number increase cases, one case was found to be accompanied by NRAS mutation, one case was accompanied by HER2 mutation, one case was accompanied by BCL2L11 mutation ​and one case was accompanied by BRAF, HER2 and BCL2L11 mutations. Our study confirmed the presence of CDK4 copy number increase in AM cases. Detecting CDK4 copy number increase by FISH can be reliable in the diagnosis of AM. Some CDK4 copy number increases are the results of polysomy of chromosome 12. CDK4 high-level copy number increase coexists with other pathogenic mutations in AM. CDK4 appears to be a promising target for AM treatment and is expected to be combined with other targeted therapies.

Unexpected hydrologic response to ecosystem state change in tallgrass prairie

In grasslands around the world, climate change is occurring in tandem with woody encroachment (the spread of woody vegetation in grass-dominated ecosystems). State transitions from grassland to shrub/woodland have been identified aboveground via changes in species cover and composition, but the hydrological impact of these transitions is not well understood. Shifts from grass- to woody-dominance have the potential to impact evapotranspiration, soil moisture dynamics, and groundwater recharge. Therefore, it is possible that the consequences of aboveground vegetation change may be observable in the hydrological system. We leveraged long-term hydrological records from a tallgrass prairie site in northeastern Kansas, USA, to examine how concurrent changes in climate and land-cover have altered hydrological dynamics over the last century. Stream discharge has declined in recent decades despite > 100 years of climate wetting. The relationship between incoming precipitation and streamflow has weakened over the last 40 years, suggesting that shifts in the physical landscape are altering patterns of hydrological connectivity. Long-term isotope records show a divergence in the isotopic composition of precipitation (no change in δ18O) and stream/groundwater (decreasing δ18O) over the last decade. These results suggest that woody encroachment is accelerating the hydrological cycle, potentially by decreasing groundwater recharge (via increased evapotranspiration) and/or increasing infiltration rates (via creation of macropores). Holistically, these changes illustrate the interdependence of above- and below-ground processes in the local hydrological cycle, and the cascading long-term consequences (decades to centuries) for critical zone function once woody encroachment has occurred.

Lagged effects of childhood depressive symptoms on adult epigenetic aging.

Cross-sectional studies have identified health risks associated with epigenetic aging. However, it is unclear whether these risks make epigenetic clocks 'tick faster' (i.e. accelerate biological aging). The current study examines concurrent and lagged within-person changes of a variety of health risks associated with epigenetic aging. Individuals from the Great Smoky Mountains Study were followed from age 9 to 35 years. DNA methylation profiles were assessed from blood, at multiple timepoints (i.e. waves) for each individual. Health risks were psychiatric, lifestyle, and adversity factors. Concurrent (N = 539 individuals; 1029 assessments) and lagged (N = 380 individuals; 760 assessments) analyses were used to determine the link between health risks and epigenetic aging. Concurrent models showed that BMI (r = 0.15, PFDR < 0.01) was significantly correlated to epigenetic aging at the subject-level but not wave-level. Lagged models demonstrated that depressive symptoms (b = 1.67 months per symptom, PFDR = 0.02) in adolescence accelerated epigenetic aging in adulthood, also when models were fully adjusted for BMI, smoking, and cannabis and alcohol use. Within-persons, changes in health risks were unaccompanied by concurrent changes in epigenetic aging, suggesting that it is unlikely for risks to immediately 'accelerate' epigenetic aging. However, time lagged analyses indicated that depressive symptoms in childhood/adolescence predicted epigenetic aging in adulthood. Together, findings suggest that age-related biological embedding of depressive symptoms is not instant but provides prognostic opportunities. Repeated measurements and longer follow-up times are needed to examine stable and dynamic contributions of childhood experiences to epigenetic aging across the lifespan.