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Background: Time frees people from bereavement, but also fades childhood happiness, these dynamics can be understood through the framework of past temporal discounting (PTD), which refers to the gradual decrease in affect intensity elicited by recalling positive or negative events over time. Despite its importance, measuring PTD has been challenging, and its impact on real-life outcomes, such as mental health remains unknown. Method: Here, we employed a longitudinal tracking approach to measure PTD in healthy participants (N = 210) across eight time points. We recorded changes in affect intensity for positive and negative events and examined the impact of PTD on mental health outcomes, including general mental well-being, depression, stress sensitivity, and etc. Results: The results of Bayesian multilevel modeling indicated that the affect intensity for positive and negative events discounted over time at a gradually decelerating rate. Furthermore, we found that maintaining good mental health heavily depended on rapid PTD of negative events and slow PTD of positive events. Conclusions: These results provide a comprehensive characterization PTD and demonstrate its importance in maintaining mental health.

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INTRODUCTION: The shortfall in medical workers in rural and remote Australia has led to health discrepancies in these regions. The University of Wollongong's medical program was designed to encourage graduates to work in these regions to address this shortfall. OBJECTIVE: To compare rural and regional locations of work and choices of speciality between University of Wollongong's graduates and graduates from all Australian universities. DESIGN: We conducted a longitudinal analysis on data available from the Medical Schools Outcome database, with graduate exit surveys linked to registrations of location and speciality. Rural and remote locations were identified as MM2-7 regions using the Modified Monash Model. In total, 716 graduates from the University of Wollongong and 26 915 graduates from all Australian medical schools completed the MSOD exit survey in 2010-2021 and registered with the Australian Health Practitioner Regulation Agency in 2022. The main outcome was the relative likelihood (relative risk) of cohorts working in rural and regional areas and of cohorts choosing general practice as their speciality. FINDINGS: University of Wollongong's medical graduates were 1.51 times or 51% more likely to work in regional or rural areas (RR 1.51, 95% CI 1.34 to 1.71, p < 0.0001). Respondents who were 10 or more years post graduation were 1.57 times or 57% more likely to specialise in general practice than all other Australian medical graduates (RR 1.57 95% CI: 1.40 to 1.79, p < 0.0001). DISCUSSION: The University of Wollongong's medical school is producing graduates to meet Australia's rural health workforce needs. This may be due to a higher intake of rural students, and a higher percentage of students taking rural placements. CONCLUSIONS: Rural health workforce needs can be addressed through rural-focussed education strategies.

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Glioblastoma (GBM) has a poor survival rate even with aggressive surgery, concomitant radiation therapy (RT), and adjuvant chemotherapy. Standard-of-care RT involves irradiating a lower dose to the hyperintense lesion in T2-weighted fluid-attenuated inversion recovery MRI (T2w/FLAIR) and a higher dose to the enhancing tumor on contrast-enhanced, T1-weighted MRI (CE-T1w). While there have been several attempts to segment pre-surgical brain tumors, there have been minimal efforts to segment post-surgical tumors, which are complicated by a resection cavity and postoperative blood products, and tools are needed to assist physicians in generating treatment contours and assessing treated patients on follow up. This report is one of the first to train and test multiple deep learning models for the purpose of post-surgical brain tumor segmentation for RT planning and longitudinal tracking. Post-surgical FLAIR and CE-T1w MRIs, as well as their corresponding RT targets (GTV1 and GTV2, respectively) from 225 GBM patients treated with standard RT were trained on multiple deep learning models including: Unet, ResUnet, Swin-Unet, 3D Unet, and Swin-UNETR. These models were tested on an independent dataset of 30 GBM patients with the Dice metric used to evaluate segmentation accuracy. Finally, the best-performing segmentation model was integrated into our longitudinal tracking web application to assign automated structured reporting scores using change in percent cutoffs of lesion volume. The 3D Unet was our best-performing model with mean Dice scores of 0.72 for GTV1 and 0.73 for GTV2 with a standard deviation of 0.17 for both in the test dataset. We have successfully developed a lightweight post-surgical segmentation model for RT planning and longitudinal tracking.

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BACKGROUND AND OBJECTIVES: Advanced artificial intelligence and machine learning have great potential to redefine how skin lesions are detected, mapped, tracked and documented. Here, we propose a 3D whole-body imaging system known as 3DSkin-mapper to enable automated detection, evaluation and mapping of skin lesions. METHODS: A modular camera rig arranged in a cylindrical configuration was designed to automatically capture images of the entire skin surface of a subject synchronously from multiple angles. Based on the images, we developed algorithms for 3D model reconstruction, data processing and skin lesion detection and tracking based on deep convolutional neural networks. We also introduced a customised, user-friendly, and adaptable interface that enables individuals to interactively visualise, manipulate, and annotate the images. The interface includes built-in features such as mapping 2D skin lesions onto the corresponding 3D model. RESULTS: The proposed system is developed for skin lesion screening, the focus of this paper is to introduce the system instead of clinical study. Using synthetic and real images we demonstrate the effectiveness of the proposed system by providing multiple views of a target skin lesion, enabling further 3D geometry analysis and longitudinal tracking. Skin lesions are identified as outliers which deserve more attention from a skin cancer physician. Our detector leverages expert annotated labels to learn representations of skin lesions, while capturing the effects of anatomical variability. It takes only a few seconds to capture the entire skin surface, and about half an hour to process and analyse the images. CONCLUSIONS: Our experiments show that the proposed system allows fast and easy whole body 3D imaging. It can be used by dermatological clinics to conduct skin screening, detect and track skin lesions over time, identify suspicious lesions, and document pigmented lesions. The system can potentially save clinicians time and effort significantly. The 3D imaging and analysis has the potential to change the paradigm of whole body photography with many applications in skin diseases, including inflammatory and pigmentary disorders. With reduced time requirements for recording and documenting high-quality skin information, doctors could spend more time providing better-quality treatment based on more detailed and accurate information.

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The adaptive immune system is a diverse ecosystem that responds to pathogens by selecting cells with specific receptors. While clonal expansion in response to particular immune challenges has been extensively studied, we do not know the neutral dynamics that drive the immune system in the absence of strong stimuli. Here, we learn the parameters that underlie the clonal dynamics of the T cell repertoire in healthy individuals of different ages, by applying Bayesian inference to longitudinal immune repertoire sequencing (RepSeq) data. Quantifying the experimental noise accurately for a given RepSeq technique allows us to disentangle real changes in clonal frequencies from noise. We find that the data are consistent with clone sizes following a geometric Brownian motion and show that its predicted steady state is in quantitative agreement with the observed power-law behavior of the clone-size distribution. The inferred turnover time scale of the repertoire increases with patient age and depends on the clone size in some individuals.

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The underlying psychological mechanism of the effect of neuroticism on depressed emotion has been widely studied. However, the neural mechanism of this relationship remains unclear. Therefore, the present study aimed to apply voxel-based morphometry (VBM) to explore the neural mechanism of the relationship between depressed emotion and neuroticism in healthy and young participants through longitudinal tracking research. The behavioral results showed that neuroticism was positively related to depressed emotion at T1 and T2 (6 months later). The VBM analysis revealed that neuroticism positively associated with the gray matter volume (GMV) in the dorsal medial prefrontal cortex (dmPFC). Mediation analysis was conducted to investigate the neural basis of the association between depressed emotion and neuroticism. The mediation result revealed that GMV of the dmPFC partially mediates the relationship between neuroticism and depressed emotion at T1 but not T2. Together, these findings suggest that the gray matter volume of dmPFC could may affect the relationship between depressed emotion and neuroticism.

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Three-dimensional (3D) in vitro models of tumors are gaining interest as versatile platforms for treatment screening. In this context, heterocellular cultures in which various cell types are co-cultured are being explored to investigate whether partner cells can influence the treatment efficacies. However, when the cells are co-cultured, it is challenging to distinguish them and it becomes impossible to identify whether the treatment affects each cell line in a similar way or if there is a certain selectivity. Here, we propose a protocol in which different cell types are pre-labeled with fluorescent reporters prior to 3D culture initiation. Subsequently, the internal architecture of the 3D cancer models can be longitudinally monitored for model characterization, and to potentially detect architectural and treatment selectivity in response to therapy. This protocol employs quantum dots as non-photobleaching dyes and two-photon excited microscopy as a widely accessible imaging modality. In combination with an appropriate image analysis workflow, this protocol will help to investigate the architectural development of heterotypic microtumor/spheroid/organoid models and possibly identify treatment efficacies on individual cell populations represented within the models.

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Alzheimer's disease (AD) is a progressive neurodegenerative disorder affecting millions of people worldwide and is currently incurable. As the population ages, AD and related dementia are becoming the biggest epidemic in medical history: the number of people aged 65 and older with AD is projected to increase between two- and three-fold by 2050. Imaging and biomarker studies suggest that the pathophysiological processes of AD begin more than a decade before the diagnosis of dementia, opening the possibility of early, preemptive prediction. For accurate prediction, it is important although challenging to fully understand how multiple etiologies and age-related prodromal processes contribute to the onset of Alzheimer's continuum, across a long period comparable to the lifespan. Addressing this challenge was one of the overarching transformative concepts at the 2015 AD Research Summit, "to develop new programs on systems biology and integrative physiology to gain a deeper understanding of the complex biology of the disease." Among other factors, cerebral microvascular degeneration (CMD) may play a key role in the onset and development of Alzheimer's continuum, potentially prior to, along with, or independently of the beta-amyloid (Aß) accumulation. Despite its importance for early detection and as a therapeutic target for early intervention, it is unknown whether CMD is a causal factor for AD pathogenesis or an early consequence of multifactorial conditions that lead to AD at a later stage. Here, this Viewpoint suggests that we should fill two critical knowledge gaps: (1) Temporal relationships between various CMDs and other key factors before/during/after the onset of Alzheimer's continuum have not been established; (2) Little integrative study down to the capillary vessel level has been conducted on how individual defects in various microvascular structural and flow properties distinctly correlate with and/or contribute to neuronal degeneration. As the first step toward filling these gaps, I propose utilizing recent advances in microscopic imaging and image analysis techniques to longitudinally track a comprehensive set of CMDs over the lifespan in model animals, along with Aß, tau, neuronal degeneration, and cognitive impairment when possible.

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In the context of the Covid-19, the present study designed a longitudinal study to examine the relationship among interpersonal alienation, meaning in life and smartphone addiction. Meanwhile, with the development of the epidemic whether there would be changes in the three variables was also examined. A sample of 579 university students (baseline mean age = 20.59, SD = 2.20) finished the anonymous questionnaires about interpersonal alienation, meaning in life and smartphone addiction. Three repeated measurements were obtained in June, September and December 2020. The finding indicated that university students' interpersonal alienation and meaning in life significantly increased, and the risk of smartphone addiction significantly decreased with the epidemic under control. Besides, meaning in life in the middle mitigating period of the epidemic mediated the relationship between interpersonal alienation in the early severe period of the epidemic and smartphone addiction in the basic end period of the epidemic. The study contributes to our understanding of how low levels of interpersonal alienation may improve meaning in life and reduce the risk of smartphone addiction. What' s more, it provides scientific suggestions for the prevention and intervention of the adverse effects during public health emergencies.

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Multiphoton microscopy is one of several new technologies providing unprecedented insight into the activity dynamics and function of neural circuits. Unfortunately, some of these technologies require experimentation in head-restrained animals, limiting the behavioral repertoire that can be integrated and studied. This issue is especially evident in drug addiction research, as no laboratories have coupled multiphoton microscopy with simultaneous intravenous drug self-administration, a behavioral paradigm that has predictive validity for treatment outcomes and abuse liability. Here, we describe a new experimental assay wherein head-restrained mice will press an active lever, but not inactive lever, for intravenous delivery of heroin or cocaine. Similar to freely moving animals, we find that lever pressing is suppressed through daily extinction training and subsequently reinstated through the presentation of relapse-provoking triggers (drug-associative cues, the drug itself, and stressors). Finally, we show that head-restrained mice will show similar patterns of behavior for oral delivery of a sucrose reward, a common control used for drug self-administration experiments. Overall, these data demonstrate the feasibility of combining drug self-administration experiments with technologies that require head-restraint, such as multiphoton imaging. The assay described could be replicated by interested labs with readily available materials to aid in identifying the neural underpinnings of substance use disorder.

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The main objective of the present study was to provide seasonal variation data for inter-limb asymmetry in youth elite team-sport athletes. Fifty-nine players performed the single-leg countermovement jump (SLCMJ) and the one leg hop for distance (OLHT) tests during pre-season, mid-season and end-season. A repeated-measures analysis of variance was conducted to determine magnitude differences in asymmetry scores between time points. Kappa coefficients (κ) were calculated to determine the levels of agreement for the direction of asymmetry. When comparing inter-limb asymmetry magnitudes across the season, the SLCMJ test showed significantly higher asymmetries at mid-season in comparison with pre-season and end-season (p< 0.01, d= -1.03 for pre to mid; p< 0.01, d= 1.12 for pre to end). However, OLHT inter-limb asymmetry magnitude remained consistent throughout the season (ES range = -0.02 to -0.06). For the direction of asymmetry, levels of agreement ranged from poor to slight in the SLCMJ (k= -0.10 to 0.18) and in the OLHT (k= -0.21 to 0.18). No significant differences were found between mean asymmetry values at any time point or for either test when comparing males and females. In conclusion, jump height asymmetry during the SLCMJ was the only metric to show significant magnitude changes across the season.

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Microendoscopic calcium imaging with one-photon miniature microscopes enables unprecedented readout of neural circuit dynamics during active behavior in rodents. In this study, we describe successful application of this technology in the rhesus macaque, demonstrating plug-and-play, head-mounted recordings of cellular-resolution calcium dynamics from large populations of neurons simultaneously in bilateral dorsal premotor cortices during performance of a naturalistic motor reach task. Imaging is stable over several months, allowing us to longitudinally track individual neurons and monitor their relationship to motor behavior over time. We observe neuronal calcium dynamics selective for reach direction, which we could use to decode the animal's trial-by-trial motor behavior. This work establishes head-mounted microendoscopic calcium imaging in macaques as a powerful approach for studying the neural circuit mechanisms underlying complex and clinically relevant behaviors, and it promises to greatly advance our understanding of human brain function, as well as its dysfunction in neurological disease.

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Considerable concerns relating to the duration of protective immunity against severe acute respiratory syndrome-coronavirus-2 (SARS-CoV-2) exist, with evidence of antibody titers declining rapidly after infection and reports of reinfection. Here, we monitor the antibody responses against SARS-CoV-2 receptor-binding domain (RBD) for up to 6 months after infection. While antibody titers are maintained, ∼13% of the cohort's neutralizing responses return to background. However, encouragingly, in a selected subset of 13 participants, 12 have detectable RBD-specific memory B cells and these generally are increasing out to 6 months. Furthermore, we are able to generate monoclonal antibodies with SARS-CoV-2 neutralizing capacity from these memory B cells. Overall, our study suggests that the loss of neutralizing antibodies in plasma may be countered by the maintenance of neutralizing capacity in the memory B cell repertoire.

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Glioblastoma is a common and aggressive form of brain cancer affecting up to 20,000 new patients in the US annually. Despite rigorous therapies, current median survival is only 15-20 months. Patients who complete initial treatment undergo follow-up imaging at routine intervals to assess for tumor recurrence. Imaging is a central part of brain tumor management, but MRI findings in patients with brain tumor can be challenging to interpret and are further confounded by interpretation variability. Disease-specific structured reporting attempts to reduce variability in imaging results by implementing well-defined imaging criteria and standardized language. The Brain Tumor Reporting and Data System (BT-RADS) is one such framework streamlined for clinical workflows and includes quantitative criteria for more objective evaluation of follow-up imaging. To facilitate accurate and objective monitoring of patients during the follow-up period, we developed a cloud platform, the Brain Imaging Collaborative Suite's Longitudinal Imaging Tracker (BrICS-LIT). BrICS-LIT uses semiautomated tumor segmentation algorithms of both T2-weighted FLAIR and contrast-enhanced T1-weighted MRI to assist clinicians in quantitative assessment of brain tumors. The LIT platform can ultimately guide clinical decision-making for patients with glioblastoma by providing quantitative metrics for BT-RADS scoring. Further, this platform has the potential to increase objectivity when measuring efficacy of novel therapies for patients with brain tumor during their follow-up. Therefore, LIT will be used to track patients in a dose-escalated clinical trial, where spectroscopic MRI has been used to guide radiation therapy (Clinicaltrials.gov NCT03137888), and compare patients to a control group that received standard of care.

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BACKGROUND: A high level of physical fitness is associated with cardiovascular health in adolescents. We describe change in physical fitness levels assessed at two time points over 3 years. METHODS: The study presents a longitudinal design, with the first phase data collection at 8 years and the second phase carried out at 11 years. A total of 516 children (254 boys) aged to 7.7±0.4 years (in 2010) and 10.9±0.4 years (in 2010) and 10.9 ± 0.4 years (in 2013) participated to the study. Cardiorespiratory fitness, muscular strength, speed, and agility were assessed in this study. For each physical fitness test, determination of the situation (in terms of percentiles) of each child in 2010 and then in 2013 compared to national standards. The 2010 and 2013 percentiles are then compared using the Wilcoxon signed rank test. RESULTS: Muscular strength, agility and cardiorespiratory fitness decrease in both sex (p<0.01). A significant decrease was also found for all physical fitness components in normal weight children (p<0.05). For normal weight children in 2010 who became overweight or obese in 2013, there was a significant decrease in scores of cardiorespiratory fitness and agility tests (p<0.05). For overweight children in 2010 becoming from to normal weight status in 2013, only the agility test decreased significantly (p<0.05). Children being overweight or obese in 2010 and remaining in 2013, had a significant decrease in their physical fitness levels (p<0.05). CONCLUSIONS: Our results indicate that the physical fitness of French youth decrease between childhood and early adolescence. Developing and introducing a health promotion curriculum in the French schools is suggested to improve health and physical fitness.

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Long-term follow-up is needed to evaluate the impact of short-term cancer research programs on the career trajectories of medical and graduate students. Participation in these programs may be crucial in fostering the next generation of cancer research scientists. This report presents the career outcomes and research productivity of 77 medical and public health students with 25 years of tracking data following their participation in a summer cancer research training program at the University of Alabama at Birmingham (UAB) in 1990-1998. Of 64 summer trainees with contact information, complete survey responses were received from 55 (86.0%) individuals. Over half reported clinical care of cancer patients and 18.2% stated that they were engaged in cancer research. Literature searches confirmed that 23.4% (18/77) of trainees have published cancer research papers. Future studies should explore the optimal timing of short-term post-baccalaureate academic cancer training experiences to identify participant characteristics and institutional factors that influence career choices and determine research productivity.

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A key outcome measure of cancer research training programs is the number of cancer-related peer-reviewed publications after training. Because program graduates do not routinely report their publications, staff must periodically conduct electronic literature searches on each graduate. The purpose of this study is to compare findings of an innovative computer-based automated search program versus repeated manual literature searches to identify post-training peer-reviewed publications. In late 2014, manual searches for publications by former R25 students identified 232 cancer-related articles published by 112 of 543 program graduates. In 2016, a research assistant was instructed in performing Scopus literature searches for comparison with individual PubMed searches on our 543 program graduates. Through 2014, Scopus found 304 cancer publications, 220 of that had been retrieved manually plus an additional 84 papers. However, Scopus missed 12 publications found manually. Together, both methods found 316 publications. The automated method found 96.2 % of the 316 publications while individual searches found only 73.4 %. An automated search method such as using the Scopus database is a key tool for conducting comprehensive literature searches, but it must be supplemented with periodic manual searches to find the initial publications of program graduates. A time-saving feature of Scopus is the periodic automatic alerts of new publications. Although a training period is needed and initial costs can be high, an automated search method is worthwhile due to its high sensitivity and efficiency in the long term.

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Most studies on new cancer drugs are based on population-derived data, where the absence of response of a small population may pass unnoticed. Thus, individual longitudinal tracking of cells is important for the future development of efficient cancer treatments. We have used digital holographic microscopy to track individual JIMT-1 human breast cancer cells and L929 mouse fibroblast cultivated in normoxia or hypoxia. In addition, JIMT-1 cells were treated with salinomycin, a cancer stem cell targeting compound. Three-day time-lapse movies were captured and individual cells were analysed with respect to cell division (cell cycle length) and cell movement. Comparing population-doubling time derived from population-based growth curves and individual cell cycle time data from time-lapse movies show that the former hide a sub-population of dividing cells. Salinomycin treatment increased the motility of cells, however, this motility did not result in an increased distant migration i.e. the cells increased their local movement. MCF-7 breast cancer cells showed similar motility behaviour as salinomycin-treated JIMT-1 cells. We suggest that combining features, such as motility and migration, can be used to distinguish cancer cells with mesenchymal (JIMT-1) and epithelial (MCF-7) features. The data clearly emphasize the importance of longitudinal cell tracking to understand the biology of individual cells under different conditions.

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The stable presence of fluorophores within the biocompatible and biodegradable elastomer poly(glycerol-co-sebacate) acrylate (PGSA) is critical for monitoring the transplantation, performance, and degradation of the polymers in vivo. However, current methods such as physically entrapping the fluorophores in the polymer matrix or providing a fluorescent coating suffer from rapid leakage of fluorophores. Covalent conjugation of fluorophores with the polymers and the subsequent core-cross-linking are proposed here to address this challenge. Taking rhodamine as the model dye and PGSA nanoparticles (NPs) as the model platform, we successfully showed that the synthesized rhodamine-conjugated PGSA (PGSAR) NPs only released less than 30% rhodamine at day 28, whereas complete release of dye occurred for rhodamine-encapsulated PGSA (PGSA-p-R) NPs at day 7 and 57.49% rhodamine was released out for the un-cross-linked PGSAR NPs at day 28. More excitingly, PGSAR NPs showed a strong quantum yield enhancement (26.24-fold) of the fluorophores, which was due to the hydrophobic environment within PGSAR NPs and the restricted rotation of (6-diethylamino-3H-xanthen-3-ylidene) diethyl group in rhodamine after the conjugation and core-cross-linking. The stable presence of dye in the NPs and enhanced fluorescence allowed a longitudinal tracking of stem cells both in vitro and in vivo for at least 28 days.

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BACKGROUND: In Australia, 61.5 % of children aged 3-4 attend Early Childhood Education and Care (ECEC) programs. Children's experiences within these programs vary widely and impact directly on educational wellbeing and social development. Research has shown that higher quality programs enhance children's learning and developmental outcomes, foster social participation and have long-lasting effects on their productivity as adults. Quality matters, yet we do not know what components of ECEC result in a quality program. Effective Early Educational Experiences (E4Kids) is a 5-year longitudinal study designed to identify and assess the impact of mainstream ECEC programs and program components on children's learning, development, social inclusion and well-being. E4Kids sets out to measure quality ECEC; identify components that add value and positively impact children's outcomes; evaluate the effects of child, family, community and environment characteristics on programs; and provide evidence on how best to invest in ECEC. METHODS/DESIGN: E4Kids follows a sample of 2,494 children who have experienced a variety of approved care programs (long day care, kindergarten, family day care and occasional care), as well as 157 children who have not accessed such programs. Children are tracked to the first point of National Assessment Program - Literacy and Numeracy (NAPLAN) testing at Year 3. The study presents a multi-level design in which ECEC programs were sampled from two states - Queensland and Victoria - then randomly sampled from two greater metropolitan regions and two regional and remote locations. Parents, centre directors, educators and carers complete questionnaires to provide information on demographics and children's progress. Data collected also include the make-up and organisation of ECEC programs and schools children attended. The quality of adult-child interactions is directly assessed using the Classroom Assessment Scoring System (CLASS) and direct testing of children's cognitive abilities and achievements is undertaken over 3 years and linked with NAPLAN scores. DISCUSSION: Findings from the E4Kids study have the potential to influence the quality of ECEC available in Australia by providing up-to-date evidence on the impact of ECEC programs and program components to inform future policy decisions and research.

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