Exploring the structure of relative age effects research using citation network analysis.

Since the 1980s, research on relative age effects (RAEs) consistently shows that relatively older individuals are advantaged in sport and other contexts. With the recent proliferation of studies on RAEs, periodic knowledge synthesis becomes imperative. Our purpose was to conduct a cross-disciplinary citation network analysis of RAEs literature to enhance our knowledge of RAEs citation structures and the interconnectivity of RAEs studies. We analysed 484 RAEs articles found in Web of Science that were published before 2022. Descriptive results revealed a 12.6% annual growth rate for total RAEs articles published since 1980. The articles appeared in 151 journals, had 1,180 unique authors, and averaged 23.9 citations received. Three theoretical/review papers had the most substantial influence on the field. For the conceptual structure of the field, it was apparent that RAEs research focused mainly on sport performance, maturity, and competition. Regarding intellectual structure, three distinct clusters of articles were cited together, and 13 authorship clusters were detected with few between-cluster connections. The results describe a field with productivity but little interconnectivity among authors and papers. We offer insights into this trend and the role that influential authors/articles have in the field.

The Internet of Things in assisted reproduction.

The Internet of Things (IoT) is a network connecting physical objects with sensors, software and internet connectivity for data exchange. Integrating the IoT with medical devices shows promise in healthcare, particularly in IVF laboratories. By leveraging telecommunications, cybersecurity, data management and intelligent systems, the IoT can enable a data-driven laboratory with automation, improved conditions, personalized treatment and efficient workflows. The integration of 5G technology ensures fast and reliable connectivity for real-time data transmission, while blockchain technology secures patient data. Fog computing reduces latency and enables real-time analytics. Microelectromechanical systems enable wearable IoT and miniaturized monitoring devices for tracking IVF processes. However, challenges such as security risks and network issues must be addressed through cybersecurity measures and networking advancements. Clinical embryologists should maintain their expertise and knowledge for safety and oversight, even with IoT in the IVF laboratory.

A Road to Microbiology Literacy (and More): an Opportunity for a Paradigm Change in Teaching.

Microbial activities pervasively impact the wellbeing of all organisms, including humans, and the functioning of the planet itself. In order for society to form informed opinions and take effective actions related to its welfare, it must be able to understand the causes of issues of importance and to appreciate the range of possible responses and their likely effectiveness. Society must become microbiology literate. The International Microbiology Literacy Initiative is creating a comprehensive range of teaching resources that will constitute a child-centric school curriculum of societally relevant microbiology. The core of the teaching resources, the lessons, are somewhat unusual in that each one is designed to be essentially stand-alone, so courses can be individually structured by teachers according to their perception of what is interesting and important for their charges. Moreover, the lessons deal not only with societally pertinent microbial activities, but also discuss and propose discussion of their relevance to sustainable development, of their impact on policies and decisions (personal, community, and national), and of issues of stewardship and stakeholder responsibilities. The class lessons are complemented by other child-centric teaching resources whose functions are to add value, to stimulate pupil imagination and excitement in discovery, to engage pupil interest and enthusiasm for topics like sustainability, climate change, international cooperation, citizen science, etc., and to empower pupils as stakeholders in their microbiology education and as educators and multiplicators.

Population structure and genetic connectivity of Plasmodium falciparum in pre-elimination settings of Southern Africa.

To accelerate malaria elimination in the Southern African region by 2030, it is essential to prevent cross-border malaria transmission. However, countries within the region are highly interconnected due to human migration that aids in the movement of the parasite across geographical borders. It is therefore important to better understand Plasmodium falciparum transmission dynamics in the region, and identify major parasite source and sink populations, as well as cross-border blocks of high parasite connectivity. We performed a meta-analysis using collated parasite allelic data generated by microsatellite genotyping of malaria parasites from Namibia, Eswatini, South Africa, and Mozambique (N = 5,314). The overall number of unique alleles was significantly higher (P ≤ 0.01) in Namibia (mean A = 17.3 ± 1.46) compared to South Africa (mean A = 12.2 ± 1.22) and Eswatini (mean A = 13.3 ± 1.27, P ≤ 0.05), whilst the level of heterozygosity was not significantly different between countries. The proportion of polyclonal infections was highest for Namibia (77%), and lowest for Mozambique (64%). A was significant population structure was detected between parasites from the four countries, and patterns of gene flow showed that Mozambique was the major source area and Eswatini the major sink area of parasites between the countries. This study showed strong signals of parasite population structure and genetic connectivity between malaria parasite populations across national borders. This calls for strengthening the harmonization of malaria control and elimination efforts between countries in the southern African region. This data also proves its potential utility as an additional surveillance tool for malaria surveillance on both a national and regional level for the identification of imported cases and/or outbreaks, as well as monitoring for the potential spread of anti-malarial drug resistance as countries work towards malaria elimination.

Macroporous dextran hydrogels for controlled growth factor capture and delivery using coiled-coil interactions.

Macroporous hydrogels possess a vast potential for various applications in the biomedical field. However, due to their large pore size allowing for unrestricted diffusion in the macropore network, macroporous hydrogels alone are not able to efficiently capture and release biomolecules in a controlled manner. There is thus a need for biofunctionalized, affinity-based gels that can efficiently load and release biomolecules in a sustained and controlled manner. For this purpose, we report here the use of a E/K coiled-coil affinity pair for the controlled capture and delivery of growth factors from highly interconnected, macroporous dextran hydrogels. By conjugating the Kcoil peptide to the dextran backbone, we achieved controlled loading and release of Ecoil-tagged Epidermal and Vascular Endothelial Growth Factors. To finely tune the behavior of the gels, we propose four control parameters: (i) macropore size, (ii) Kcoil grafting density, (iii) Ecoil valency and (iv) E/K affinity. We demonstrate that Kcoil grafting can produce a 20-fold increase in passive growth factor capture by macroporous dextran gels. Furthermore, we demonstrate that our gels can release as little as 20% of the loaded growth factors over one week, while retaining bioactivity. Altogether, we propose a versatile, highly tunable platform for the controlled delivery of growth factors in biomedical applications. STATEMENT OF SIGNIFICANCE: This work presents a highly tunable platform for growth factor capture and sustained delivery using affinity peptides in macroporous, fully interconnected dextran hydrogels. It addresses several ongoing challenges by presenting: (i) a versatile platform for the delivery of a wide range of stable, bioactive molecules, (ii) a passive, affinity-based loading of growth factors in the platform, paving the way for in situ (re)loading of the device and (iii) four different control parameters to finely tune growth factor capture and release. Altogether, our macroporous dextran hydrogels have a vast potential for applications in controlled delivery, tissue engineering and regenerative medicine.

Post-COVID-19 performance evaluation of urban metro transit system in Delhi and influence on access mode.

The impact of the COVID-19 pandemic has been observed to affect the travel patterns, routes and traffic in public transportation systems across the world. It is important to evaluate the performance of the Delhi Metro (DM) post-COVID-19 pandemic for its successful operation. In this study, the BLUE line of DM with the longest route and highest number of metro stations has been examined for performance evaluation. The performance is evaluated based on travel time components (access, egress, transfer, waiting and main haul time) to calculate various performance indicators i.e., Level of Service (LOS), Service Time Ratio (STR), Passengers Waiting Index (PWI), Total Travel Ratio (TTR) and Interconnectivity Ratio (IR). The post-COVID-19 LOS evaluation indicates that the users are spending 72.6 % to 84.4 % of their main haul time on their access-egress trips. The STR shows that the users are spending 10.9 % to 12.6 % of their total travel time in waiting and transferring only during the main haul trip. The mean PWI, RI and TTR are noted as 1.008, 0.794 and 2.069 respectively. The IR is observed as 0.312 for the given route. The median and average main haul distances across all access modes are observed to be (12-21) Km. and (19.69 ± 11.19) Km. respectively. It is revealed that the observed mean value of LOS is (0.775 ± 0.575). It is further revealed that the metro fare per trip and the access-egress trip cost per day are significant factors for access mode choice in the case of walking and auto-rickshaw whereas LOS, RI and PWI are other significant operator's performance indicators influencing the access mode choice. The study reveals that post-COVID-19 the performance indicators exhibit the unsatisfactory performance of DM and there is further scope to improve the UMTS performance.

Effects of pore interconnectivity on bone regeneration in carbonate apatite blocks.

Porous architecture in bone substitutes, notably the interconnectivity of pores, is a critical factor for bone ingrowth. However, controlling the pore interconnectivity while maintaining the microarchitecture has not yet been achieved using conventional methods, such as sintering. Herein, we fabricated a porous block using the crystal growth of calcium sulfate dihydrate, and controlled the pore interconnectivity by limiting the region of crystal growth. The calcium sulfate dihydrate blocks were transformed to bone apatite, carbonate apatite (CO3Ap) through dissolution-precipitation reactions. Thus, CO3Ap blocks with 15% and 30% interconnected pore volumes were obtained while maintaining the microarchitecture: they were designated as CO3Ap-15 and CO3Ap-30, respectively. At 4 weeks after implantation in a rabbit femur defect, new bone formed throughout CO3Ap-30, whereas little bone was formed in the center region of CO3Ap-15. At 12 weeks after implantation, a large portion of CO3Ap-30 was replaced with new bone and the boundary with the host bone became blurred. In contrast, CO3Ap-15 remained in the defect and the boundary with the host bone was still clear. Thus, the interconnected pores promote bone ingrowth, followed by replacement of the material with new bone. These findings provide a useful guide for designing bone substitutes for rapid bone regeneration.

The ultrastructure of cartilage tissue and its swelling response in relation to matrix health.

This multi-length scale anatomical study explores the influence of mild cartilage structural degeneration on the tissue swelling response. While the swelling response of cartilage has been studied extensively, this is the first study to reveal and correlate tissue microstructure and ultrastructure, with the swelling induced cartilage tissue strains. Cartilage sample strips (n = 30) were obtained from the distal-lateral quadrant of thirty mildly degenerate bovine patellae and, following excision from the bone, the cartilage strips were allowed to swell freely for 2 h in solutions of physiological saline and distilled water successively. The swelling response of this group of samples were compared with that of healthy cartilage, with (n = 20) and without the surface layer (n = 20). The subsequent curling response of cartilage showed that in healthy tissue it was highly variable, and with the surface removed some samples curved in the opposite direction, while in the mildly degenerate tissue group, virtually all tissue strips curved in a consistent upward manner. A significant difference in strain was observed between healthy samples with surface layer removed and mildly degenerate samples, illustrating how excision of the surface zone from pristine cartilage is insufficient to model the swelling response of tissue which has undergone natural degenerative changes. On average, total tissue thickness increased from 940 µm (healthy) to 1079 µm (mildly degenerate), however, looking at the zonal strata, surface and transition zone thicknesses both decreased while deep zone thickness increased from healthy to mildly degenerate tissue. Morphologically, changes to the surface zone integrity were correlated with a diminished surface layer which, at the ultrastructural scale, correlated with a decreased fibrillar density. Similarly, fibrosity of the general matrix visible at the microscale was associated with a loss of later interconnectivity resulting in large, aggregated fibril bundles. The microstructural and ultrastructural investigation revealed that the key differences influencing the tissue swelling strain response was (1) the thickness and extent of disruption to the surface layer and (2) the amount of fibrillar network destructuring, highlighting the importance of the collagen and tissue matrix structure in restraining cartilage swelling.

Highly Elastic Interconnected Porous Hydrogels through Self-Assembled Templating for Solar Water Purification.

Interfacial evaporation using porous hydrogels has demonstrated highly effective solar evaporation performance under natural sunlight to ensure an affordable clean water supply. However, it remains challenging to realize scalable and ready-to-use hydrogel materials with durable mechanical properties. Here, self-assembled templating (SAT) is developed as a simple yet effective method to fabricate large-scale elastic hydrogel evaporators with excellent desalination performance. The highly interconnected porous structure of the hydrogels with low tortuosity and tunable pore size enables high level of tunability on the water transport rate. With superior elasticity, the porous hydrogels are easy to process with a rapid shape recovery after being rolled, folded, and twisted over hundred times, and exhibit highly effective and stable evaporation with an evaporation rate of ≈2.8 kg m-2 h-1 and ≈90 % solar-to-vapor efficiency. It is anticipated that this SAT strategy, without the typical need for freeze-drying, will accelerate the industrialization of hydrogel solar evaporators for practical applications.

STUDENTS' HEALTH STATUS AND THEIR ABILITY TO ADAPT TO A MULTINATIONAL UNIVERSITY ENVIRONMENT.

OBJECTIVE: The aim: Development of practical recommendations to further improve students' adaptation to a multicultural university environment as a factor in ensuring their health. PATIENTS AND METHODS: Materials and methods: The publication is based on the results of a comprehensive multi-purpose randomized epidemiological study using a standardized questionnaire. Questionnaire results (n = 355) were tested for paired correlations of all considered factors. RESULTS: Results: 93,8 % of respondents positively assessed their overall health with a mode of 3 (satisfactory health). In general, students' health was not particularly sensitive to the effects of temporal and natural factors. Recommendations have been developed to improve students' adaptation to the university's multinational environment, including by preventing stressful situations. It is important that students are sufficiently informed, financially secure, and mentally prepared for student life. CONCLUSION: Conclusions: The key to safeguarding students' health is developing their skills in adapting to a multinational university environment.

Entropy in Heart Rate Dynamics Reflects How HRV-Biofeedback Training Improves Neurovisceral Complexity during Stress-Cognition Interactions.

Despite considerable appeal, the growing appreciation of biosignals complexity reflects that system complexity needs additional support. A dynamically coordinated network of neurovisceral integration has been described that links prefrontal-subcortical inhibitory circuits to vagally-mediated heart rate variability. Chronic stress is known to alter network interactions by impairing amygdala functional connectivity. HRV-biofeedback training can counteract stress defects. We hypothesized the great value of an entropy-based approach of beat-to-beat biosignals to illustrate how HRVB training restores neurovisceral complexity, which should be reflected in signal complexity. In thirteen moderately-stressed participants, we obtained vagal tone markers and psychological indexes (state anxiety, cognitive workload, and Perceived Stress Scale) before and after five-weeks of daily HRVB training, at rest and during stressful cognitive tasking. Refined Composite Multiscale Entropy (RCMSE) was computed over short time scales as a marker of signal complexity. Heightened vagal tone at rest and during stressful tasking illustrates training benefits in the brain-to-heart circuitry. The entropy index reached the highest significance levels in both variance and ROC curves analyses. Restored vagal activity at rest correlated with gain in entropy. We conclude that HRVB training is efficient in restoring healthy neurovisceral complexity and stress defense, which is reflected in HRV signal complexity. The very mechanisms that are involved in system complexity remain to be elucidated, despite abundant literature existing on the role played by amygdala in brain interconnections.

Basic Principles of Emulsion Templating and Its Use as an Emerging Manufacturing Method of Tissue Engineering Scaffolds.

Tissue engineering (TE) aims to regenerate critical size defects, which cannot heal naturally, by using highly porous matrices called TE scaffolds made of biocompatible and biodegradable materials. There are various manufacturing techniques commonly used to fabricate TE scaffolds. However, in most cases, they do not provide materials with a highly interconnected pore design. Thus, emulsion templating is a promising and convenient route for the fabrication of matrices with up to 99% porosity and high interconnectivity. These matrices have been used for various application areas for decades. Although this polymer structuring technique is older than TE itself, the use of polymerised internal phase emulsions (PolyHIPEs) in TE is relatively new compared to other scaffold manufacturing techniques. It is likely because it requires a multidisciplinary background including materials science, chemistry and TE although producing emulsion templated scaffolds is practically simple. To date, a number of excellent reviews on emulsion templating have been published by the pioneers in this field in order to explain the chemistry behind this technique and potential areas of use of the emulsion templated structures. This particular review focusses on the key points of how emulsion templated scaffolds can be fabricated for different TE applications. Accordingly, we first explain the basics of emulsion templating and characteristics of PolyHIPE scaffolds. Then, we discuss the role of each ingredient in the emulsion and the impact of the compositional changes and process conditions on the characteristics of PolyHIPEs. Afterward, current fabrication methods of biocompatible PolyHIPE scaffolds and polymerisation routes are detailed, and the functionalisation strategies that can be used to improve the biological activity of PolyHIPE scaffolds are discussed. Finally, the applications of PolyHIPEs on soft and hard TE as well as in vitro models and drug delivery in the literature are summarised.

Metabolic and functional specialisations of the pancreatic beta cell: gene disallowance, mitochondrial metabolism and intercellular connectivity.

All forms of diabetes mellitus involve the loss or dysfunction of pancreatic beta cells, with the former predominating in type 1 diabetes and the latter in type 2 diabetes. Deeper understanding of the coupling mechanisms that link glucose metabolism in these cells to the control of insulin secretion is therefore likely to be essential to develop new therapies. Beta cells display a remarkable metabolic specialisation, expressing high levels of metabolic sensing enzymes, including the glucose transporter GLUT2 (encoded by SLC2A2) and glucokinase (encoded by GCK). Genetic evidence flowing from both monogenic forms of diabetes and genome-wide association studies for the more common type 2 diabetes, supports the importance for normal glucose-stimulated insulin secretion of metabolic signalling via altered ATP generation, while also highlighting unsuspected roles for Zn2+ storage, intracellular lipid transfer and other processes. Intriguingly, genes involved in non-oxidative metabolic fates of the sugar, such as those for lactate dehydrogenase (LDHA) and monocarboxylate transporter-1 ([MCT-1] SLC16A1), as well as the acyl-CoA thioesterase (ACOT7) and others, are selectively repressed ('disallowed') in beta cells. Furthermore, mutations in genes critical for mitochondrial oxidative metabolism, such as TRL-CAG1-7 encoding tRNALeu, are linked to maternally inherited forms of diabetes. Correspondingly, impaired Ca2+ uptake into mitochondria, or collapse of a normally interconnected mitochondrial network, are associated with defective insulin secretion. Here, we suggest that altered mitochondrial metabolism may also impair beta cell-beta cell communication. Thus, we argue that defective oxidative glucose metabolism is central to beta cell failure in diabetes, acting both at the level of single beta cells and potentially across the whole islet to impair insulin secretion. Graphical abstract.

Insights into the microstructure and interconnectivity of porosity in porous starch by hyperpolarized 129Xe NMR.

For the first time, hyperpolarized (HP) 129Xe NMR measurements are utilized to explore porous structures of porous starch (PS) successfully. Some micropores resided inside the mesopore walls of PS were detected by variable temperature (VT) HP 129Xe NMR, and the pore sizes of micropores were also estimated using the empirical relationship. Furthermore, the interconnectivity of pores was investigated in detail by two-dimensional (2D) exchange spectroscopy (EXSY). The exchange process of xenon from microporosity within pore walls to the free gas space was occurred at the mixing time of ≥12 ms at 173 K, which indicated the well interconnectivity between micropores and mesopores. This study not only exhibits a new approach for investigation of pores and hollows of PS, but also provides a better understanding of porous structures for rational design in adsorbing functional compounds.

3D high spatial resolution visualisation and quantification of interconnectivity in polymer films.

A porous network acts as transport paths for drugs through films for controlled drug release. The interconnectivity of the network strongly influences the transport properties. It is therefore important to quantify the interconnectivity and correlate it to transport properties for control and design of new films. This work presents a novel method for 3D visualisation and analysis of interconnectivity. High spatial resolution 3D data on porous polymer films for controlled drug release has been acquired using a focused ion beam (FIB) combined with a scanning electron microscope (SEM). The data analysis method enables visualisation of pore paths starting at a chosen inlet pore, dividing them into groups by length, enabling a more detailed quantification and visualisation. The method also enables identification of central features of the porous network by quantification of channels where pore paths coincide. The method was applied to FIB-SEM data of three leached ethyl cellulose (EC)/hydroxypropyl cellulose (HPC) films with different weight percentages. The results from the analysis were consistent with the experimentally measured release properties of the films. The interconnectivity and porosity increase with increasing amount of HPC. The bottleneck effect was strong in the leached film with lowest porosity.

Changing Spatial Interconnectivity during the "Great American Migration Slowdown": A Decomposition of Intercounty Migration Rates, 1990-2010.

Prior research on the "Great American Migration Slowdown," or the declining rate of U.S. internal migration in recent decades, is dominated by two research foci. The first is concerned with the determinants of the migration slowdown. The second is concerned with spatial heterogeneity in the migration slowdown in and across places. With respect to the aim of this paper, many studies of spatial heterogeneity in the migration slowdown have implicitly raised questions about whether and to what extent places are connected to one another by migration flows, or the spatial interconnectivity of migration. The spatial interconnectivity of migration is a concrete manifestation of underlying spatial interdependence among places, and, as such, deserves to be explicitly unpacked to further our understanding of the migration slowdown. Using county-to-county migration flow data from the Internal Revenue Service and a novel application of Das Gupta's demographic standardization and decomposition procedures, we document changes in the spatial interconnectivity of migration during the migration slowdown between 1990 and 2010. We show that counties became more connected to one another by migration over time, and that the increasing spatial interconnectivity of migration helped to keep the migration slowdown from slowing further. We also document changes in the spatial interconnectivity of migration for four types of migration flows: metro-to-metro, nonmetro-to-metro, metro-to-nonmetro, and nonmetro-to-nonmetro. Our work further elucidates the characteristics of the migration slowdown by describing changes in the spatial interconnectivity of migration. It also raises new questions for future research about the determinants and consequences of these changes.

Recent advances in signal integration mechanisms in the unfolded protein response.

Since its discovery more than 25 years ago, great progress has been made in our understanding of the unfolded protein response (UPR), a homeostatic mechanism that adjusts endoplasmic reticulum (ER) function to satisfy the physiological demands of the cell. However, if ER homeostasis is unattainable, the UPR switches to drive cell death to remove defective cells in an effort to protect the health of the organism. This functional dichotomy places the UPR at the crossroads of the adaptation versus apoptosis decision. Here, we focus on new developments in UPR signaling mechanisms, in the interconnectivity among the signaling pathways that make up the UPR in higher eukaryotes, and in the coordination between the UPR and other fundamental cellular processes.

Bruno's Score.

Many of our experiences in hospice and palliative care medicine are challenging. We support dying patients and their families as they struggle with the transition from life to death and continue to support those in mourning. Many times, in America, it is difficult to even appreciate a glimmer of spiritual grace as our patients die. We easily remain stuck in the material and distance ourselves from the spiritual. Some exits are quite graceful, however. I present the case of an exceptional person, who enjoyed an exceptional life and had an exceptionally graceful dying process and death, in hopes that his story may encourage other healers as much as he inspired me. Bruno was a composer and cognitive musicologist, whose art forms of light and music simultaneously move and challenge virtually all the people and other artists he interfaced with and taught, including his talented wife and family, his friends, his acquaintances, his students, his colleagues, and his deans. He embodied theories as diverse as mathematical strange loops, continually paradoxical/recursive illusory art, contrapuntal fugues, and artificial intelligence. Bruno's spirituality was uncommonly profound. It spanned and interconnected many eclectic faith traditions, theologies, and philosophies, including Taoism, Greek mythology, distributed cognition, mathematics, and Tibetan Buddhism. It resonated strongly with Zen and Christian mysticism. Some of Bruno's being and transformation to nonbeing was obvious; some of it was inscrutable.

Pretherapeutic resting-state fMRI profiles are associated with MR signature volumes after stereotactic radiosurgical thalamotomy for essential tremor.

OBJECTIVEEssential tremor (ET) is the most common movement disorder. Drug-resistant ET can benefit from standard stereotactic deep brain stimulation or radiofrequency thalamotomy or, alternatively, minimally invasive techniques, including stereotactic radiosurgery (SRS) and high-intensity focused ultrasound, at the level of the ventral intermediate nucleus (Vim). The aim of the present study was to evaluate potential correlations between pretherapeutic interconnectivity (IC), as depicted on resting-state functional MRI (rs-fMRI), and MR signature volume at 1 year after Vim SRS for tremor, to be able to potentially identify hypo- and hyperresponders based only on pretherapeutic neuroimaging data.METHODSSeventeen consecutive patients with ET were included, who benefitted from left unilateral SRS thalamotomy (SRS-T) between September 2014 and August 2015. Standard tremor assessment and rs-fMRI were acquired pretherapeutically and 1 year after SRS-T. A healthy control group was also included (n = 12). Group-level independent component analysis (ICA; only n = 17 for pretherapeutic rs-fMRI) was applied. The mean MR signature volume was 0.125 ml (median 0.063 ml, range 0.002-0.600 ml). The authors correlated baseline IC with 1-year MR signatures within all networks. A 2-sample t-test at the level of each component was first performed in two groups: group 1 (n = 8, volume < 0.063 ml) and group 2 (n = 9, volume ≥ 0.063 ml). These groups did not statistically differ by age, duration of symptoms, baseline ADL score, ADL point decrease at 1 year, time to tremor arrest, or baseline tremor score on the treated hand (TSTH; p > 0.05). An ANOVA was then performed on each component, using individual subject-level maps and continuous values of 1-year MR signatures, correlated with pretherapeutic IC.RESULTSUsing 2-sample t-tests, two networks were found to be statistically significant: network 3, including the brainstem, motor cerebellum, bilateral thalamus, and left supplementary motor area (SMA) (pFWE = 0.004, cluster size = 94), interconnected with the red nucleus (MNI -2, -22, -32); and network 9, including the brainstem, posterior insula, bilateral thalamus, and left SMA (pFWE = 0.002, cluster size = 106), interconnected with the left SMA (MNI 24, -28, 44). Higher pretherapeutic IC was associated with higher MR volumes, in a network including the anterior default-mode network and bilateral thalamus (ANOVA, pFWE = 0.004, cluster size = 73), interconnected with cerebellar lobule V (MNI -12, -70, -22). Moreover, in the same network, radiological hyporesponders presented with negative IC values.CONCLUSIONSThese findings have clinical implications for predicting MR signature volumes after SRS-T. Here, using pretherapeutic MRI and data processing without prior hypothesis, the authors showed that pretherapeutic network interconnectivity strength predicts 1-year MR signature volumes following SRS-T.

Structurally graduated collagen scaffolds applied to the ex vivo generation of platelets from human pluripotent stem cell-derived megakaryocytes: Enhancing production and purity.

Platelet transfusions are a key treatment option for a range of life threatening conditions including cancer, chemotherapy and surgery. Efficient ex vivo systems to generate donor independent platelets in clinically relevant numbers could provide a useful substitute. Large quantities of megakaryocytes (MKs) can be produced from human pluripotent stem cells, but in 2D culture the ratio of platelets harvested from MK cells has been limited and restricts production rate. The development of biomaterial cell supports that replicate vital hematopoietic micro-environment cues are one strategy that may increase in vitro platelet production rates from iPS derived Megakaryocyte cells. In this paper, we present the results obtained generating, simulating and using a novel structurally-graded collagen scaffold within a flow bioreactor system seeded with programmed stem cells. Theoretical analysis of porosity using micro-computed tomography analysis and synthetic micro-particle filtration provided a predictive tool to tailor cell distribution throughout the material. When used with MK programmed stem cells the graded scaffolds influenced cell location while maintaining the ability to continuously release metabolically active CD41 + CD42 + functional platelets. This scaffold design and novel fabrication technique offers a significant advance in understanding the influence of scaffold architectures on cell seeding, retention and platelet production.